Streptococcus pneumoniae serotype prevalence and antibiotic resistance among young children with invasive pneumococcal disease: experience from a tertiary care center in South India

PubMed Central

Nagaraj, Savitha; Kalal, Bhuvanesh Sukhlal; Manoharan, Anand; Shet, Anita

2017-01-01

Introduction We performed a study to describe the clinical profile, antimicrobial susceptibility and prevalent serotypes of pneumococcal isolates from children with suspected invasive pneumococcal disease (IPD) admitted to a tertiary care hospital in South India. Methods Hospitalized children, ≤ 5 years with fever (>38 °C); increased respiratory rate or neurological symptoms were recruited, (as part of the Alliance for Surveillance of Invasive Pneumococci – ASIP – project) from January 2011 to March 2013. Identification of pneumococcal isolates from blood or cerebrospinal fluid samples was done by routine culture methods. Isolates were analyzed for antimicrobial susceptibility, and confirmed by serotyping (using Quellung’s test) and multiplex PCR. Results Out of the 171 samples received in the lab, 17 grew pneumococci identified by standard methods. Fourteen of them were confirmed by multiplex PCR. Maximum recruitment was observed during the months of January and February (36.4%, 28.6%). The average age of affected subjects was 21 months. The common clinical presentation was pneumonia (42.8%). Two isolates belonging to the 19F and 19B serotypes were resistant to penicillin (on Etest). The observed serotype distribution was 6B and 19F (2 each), and 1, 2, 6A, 9V, 10A, 14, 15A, 19B, 21, 35F (1 each). The overall fatality rate was 14.3% (n=2); the S. pneumoniae isolates from these two patients belonged to the non-vaccine serotype 19B and vaccine serotype 19F and demonstrated in vitro resistance to penicillin and erythromycin. Conclusion Our study demonstrates the presence of invasive pneumococcal disease among under-5-year-old children in India caused by serotypes that are in large part covered by available pneumococcal vaccines. PMID:28626738

Nasopharyngeal bacterial load as a marker for rapid and easy diagnosis of invasive pneumococcal disease in children from Mozambique

PubMed Central

Lanaspa, Miguel; Henares, Desiree; Perez-Arguello, Amaresh; Madrid, Lola; Balcells, Reyes; Acacio, Sozinho; Andres-Franch, Maria; Marcos, Maria Angeles; Valero-Rello, Ana

2017-01-01

Background Current diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children. Methods Matched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction. Results Thirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log10 copies/mL in cases vs. 5.8 log10 copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log10 copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%). Conclusion Use of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in children. PMID:28910402

SEPAR-ALAT Consensus Document on Antipneumoccal Vaccination in Smokers.

PubMed

Jiménez Ruiz, Carlos A; Buljubasich, Daniel; Sansores, Raúl; Riesco Miranda, Juan Antonio; Guerreros Benavides, Alfredo; Luhning, Susana; Chatkin, José Miguel; Zabert, Gustavo; de Granda Orive, José Ignacio; Solano Reina, Segismundo; Casas Herrera, Alejandro; de Lucas Ramos, Pilar

2015-07-01

Streptococcus pneumoniae is responsible for several clinical syndromes, such as community-acquired pneumonia, sinusitis, otitis media, and others. The most severe clinical entity caused by this bacteria is undoubtedly invasive pneumococcal disease. Certain factors are known to increase the risk of presenting invasive pneumococcal disease, the most important being smoking habit and underlying concomitant diseases. This article comprises a consensus document on antipneumococcal vaccination in smokers, drawn up by a Smoking Expert Group from the Spanish Society of Pulmonology and Thoracic Surgery and the Latin American Chest Association. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Serotype 5 pneumococci causing invasive pneumococcal disease outbreaks in Barcelona, Spain (1997 to 2011).

PubMed

Rolo, Dora; Fenoll, Asunción; Fontanals, Dionísia; Larrosa, Nieves; Giménez, Montserrat; Grau, Immaculada; Pallarés, Román; Liñares, Josefina; Ardanuy, Carmen

2013-11-01

In this study, we analyzed the clinical and molecular epidemiology of invasive serotype 5 (Ser5) pneumococcal isolates in four teaching hospitals in the Barcelona, Spain, area (from 1997 to 2011). Among 5,093 invasive pneumococcal isolates collected, 134 (2.6%) Ser5 isolates were detected. Although the overall incidence of Ser5-related invasive pneumococcal disease (IPD) was low (0.25 cases/100,000 inhabitants), three incidence peaks were detected: 0.63/100,000 in 1999, 1.15/100,000 in 2005, and 0.37/100,000 in 2009. The rates of Ser5 IPD were higher among young adults (18 to 64 years old) and older adults (>64 years old) in the first two peaks, whereas they were higher among children in 2009. The majority (88.8%) of the patients presented with pneumonia. Comorbid conditions were present in young adults (47.6%) and older adults (78.7%), the most common comorbid conditions being chronic obstructive pulmonary disease (20.6% and 38.3%, respectively) and cardiovascular diseases (11.1% and 38.3%, respectively). The mortality rates were higher among older adults (8.5%). All Ser5 pneumococci tested were fully susceptible to penicillin, cefotaxime, erythromycin, and ciprofloxacin. The resistance rates were 48.5% for co-trimoxazole, 6.7% for chloramphenicol, and 6% for tetracycline. Two major related sequence types (STs), ST1223 (n = 65) and ST289 (n = 61), were detected. The Colombia(5)-ST289 clone was responsible for all the cases in the Ser5 outbreak in 1999, whereas the ST1223 clone accounted for 73.8% and 61.5% of the isolates in 2005 and 2009, respectively. Ser5 pneumococci are a frequent cause of IPD outbreaks in the community and involve children and adults with or without comorbidities. The implementation of the new pneumococcal conjugated vaccines (PCV10 and PCV13) might prevent such outbreaks.

Population Structure of Invasive Streptococcus pneumoniae in the Netherlands in the Pre-Vaccination Era Assessed by MLVA and Capsular Sequence Typing

PubMed Central

Elberse, Karin E. M.; van de Pol, Ingrid; Witteveen, Sandra; van der Heide, Han G. J.; Schot, Corrie S.; van Dijk, Anita; van der Ende, Arie; Schouls, Leo M.

2011-01-01

The introduction of nationwide pneumococcal vaccination may lead to serotype replacement and the emergence of new variants that have expanded their genetic repertoire through recombination. To monitor alterations in the pneumococcal population structure, we have developed and utilized Capsular Sequence Typing (CST) in addition to Multiple-Locus Variable number tandem repeat Analysis (MLVA). To assess the serotype of each isolate CST was used. Based on the determination of the partial sequence of the capsular wzh gene, this method assigns a capsular type of an isolate within a single PCR reaction using multiple primersets. The genetic background of pneumococcal isolates was assessed by MLVA. MLVA and CST were used to create a snapshot of the Dutch pneumococcal population causing invasive disease before the introduction of the 7-valent pneumococcal conjugate vaccine in the Netherlands in 2006. A total of 1154 clinical isolates collected and serotyped by the Netherlands Reference Laboratory for Bacterial Meningitis were included in the snapshot. The CST was successful in discriminating most serotypes present in our collection. MLVA demonstrated that isolates belonging to some serotypes had a relatively high genetic diversity whilst other serotypes had a very homogeneous genetic background. MLVA and CST appear to be valuable tools to determine the population structure of pneumococcal isolates and are useful in monitoring the effects of pneumococcal vaccination. PMID:21637810

Effectiveness of pneumococcal vaccination for elderly people in Catalonia, Spain: a case-control study.

PubMed

Dominguez, Angela; Salleras, Lluis; Fedson, David S; Izquierdo, Conchita; Ruiz, Laura; Ciruela, Pilar; Fenoll, Asuncion; Casal, Julio

2005-05-01

Observational studies offer an approach to evaluating the effectiveness of vaccination programs. We evaluated the effectiveness of a 23-valent pneumococcal vaccination program for elderly people in Catalonia, Spain, in a matched-set case-control study. We identified 149 cases of invasive pneumococcal disease among patients aged > or =65 years who were hospitalized in 12 large hospitals in Catalonia during the period of 1 January 2001 through 31 March 2002. We selected 2 hospital control patients and 1 outpatient control subject for each case patient, matching on the basis of age and underlying medical conditions. We obtained their pneumococcal vaccination histories and used conditional logistic regression to determine effectiveness of vaccination. Among all 149 cases of invasive pneumococcal disease, 131 (87.9%) were caused by vaccine or vaccine-related serotypes. In the adjusted analysis, overall effectiveness of vaccination against infections due to all serotypes was 70% (95% confidence interval [CI], 48%-82%). Among immunocompetent subjects with or without high-risk conditions, effectiveness of vaccination was 76% (95% CI, 51%-88%), but among immunocompromised subjects it was 50% (95% CI, -44% to 82%). Among subjects with infections due to vaccine or vaccine-related serotypes, effectiveness of vaccination was 72% (95% CI, 50%-85%) overall and 78% (95% CI, 50%-90%) in those who were immunocompetent, but it was only 46% (95% CI, -54% to 81%) in those who were immunocompromised. Overall effectiveness of vaccination was 65% (95% CI, 35%-81%) during the noninfluenza period. Pneumococcal vaccination was effective in preventing invasive pneumococcal disease among all elderly persons in Catalonia. Effectiveness was greater in immunocompetent persons, most of whom had underlying high-risk conditions. The number of subjects was too small to determine whether vaccination was effective in those who were immunocompromised.

The economic burden of childhood invasive pneumococcal diseases and pneumonia in Taiwan: Implications for a pneumococcal vaccination program

PubMed Central

Ho, Yi-Chien; Lee, Pei-Lun; Wang, Yu-Chiao; Chen, Shiou-Chien; Chen, Kow-Tong

2015-01-01

Invasive pneumococcal disease (IPD) and pneumonia are the major causes of morbidity and deaths in children in the world. The management of IPD and pneumonia is an important economic burden on healthcare systems and families. The aim of this study was to assess the economic burden of IPD and pneumonia among younger children in Taiwan. We used a cost-illness approach to identify the cost categories for analysis in this study according to various perspectives. We obtained data of admission, outpatient, and emergency department visit data from the National Health Insurance Research (NHIR) database for children <5 y of age between January 2008 and December 2008. A prospective survey was administered to the families of patients to obtain detailed personal costs. All costs are presented in US dollars and were estimated by extrapolating 2008 cost data to 2013 price levels. We estimated the number of pneumococcal disease cases that were averted if the PCV-13 vaccine had been available in 2008. The total annual social and hospital costs for IPD were US $4.3 million and US $926,000, respectively. The total annual social and hospital costs for pneumonia were US $150 million and US $17 million, respectively. On average, families spent US $653 or US $218 when their child was diagnosed with IPD or pneumonia, respectively. This cost is approximately 27%–81% of the monthly salary of an unskilled worker. In conclusion, a safe and effective pediatric pneumococcal vaccine is needed to reduce the economic burden caused by pneumococcal infection. PMID:25874476

[Pharmaco-economic aspects of vaccination against invasive pneumococcal infections in persons over 65 years of age; review of the literature on cost effectiveness analysis].

PubMed

Postma, M J; Heijnen, M L A; Beutels, Ph; Jager, J C

2002-05-04

To assess the cost-effectiveness of vaccination to prevent invasive pneumococcal disease in the elderly. Review of the literature. Articles in Dutch or English reporting studies into the cost-effectiveness of vaccination for the prevention of invasive pneumococcal infection in persons over 65 years of age were retrieved from Medline (1980-2000; search terms: 'pneumococcal' and 'vaccine' in combination with 'costs' or 'economics') and on the basis of the reference lists in the articles found. The following aspects of the selected studies were assessed: the net costs per year of life gained, the incidence of invasive pneumococcal disease in the elderly, the mortality due to invasive pneumococcal infections, the effectiveness of the vaccine in the prevention of invasive pneumococcal infections, and the costs of the vaccine and its administration. Attention was also given to specific age categories and to the effects of varying certain crucial assumptions. We retrieved a total of five studies: one each for the USA, Canada, the Netherlands and Spain and a multinational study for five European countries. The cost-effectiveness of vaccination of the elderly against invasive pneumococcal infections varied from cost savings to [symbol: see text] 33,000,-per life-year gained. The Dutch study estimated the cost-effectiveness at [symbol: see text] 10,100,-per life-year gained (price level 1995). Almost all the studies selected based their estimate of the effectiveness of vaccination on the same case-control study from the USA. The potential effects on cost-effectiveness of more extensive influenza vaccination and of the inclusion of re-vaccination against pneumococci were not included in the analyses. The cost-effectiveness of vaccination against invasive pneumococcal infections in persons over 65 years of age (in the Netherlands as well as in several other countries) was below the previously accepted threshold of [symbol: see text] 20,000,-.

Other age groups than children need to be considered as carriers of Streptococcal pneumoniae serotypes.

PubMed

Slotved, Hans-Christian

2016-10-02

We need to raise the issue that focus on children as the only carriage group for pneumococci is not optimal; we need to consider that other age groups might also be carriers of pneumococcal serotypes causing invasive pneumococcal diseases (IPD) in unvaccinated age groups. The pneumococcal conjugate vaccines (PCV) have successfully removed IPD from vaccinated children. Studies have shown an effect of PCV reducing the pneumococcal carriage of PCV serotypes in children. The status for several countries having used PCV for many years is that they do not see PCV serotypes neither carried nor as a cause of IPD in children. PCV vaccination of children has shown a herd protection effect in unvaccinated groups as a reduction in IPD cases caused by PCV serotypes. However, not all PCV serotypes have disappeared as the cause of IPD in the unvaccinated age groups. The author therefore believes that if we are to see PCV serotypes disappear as a cause of IPD in unvaccinated age groups, we need to perform further carriage studies to examine carriage in other age groups. Alternatively, all age groups should be vaccinated against pneumococci to eliminate IPD caused by PCV serotypes from possible hidden carriers.

Pneumococcal surface protein A (PspA) is effective at eliciting T cell-mediated responses during invasive pneumococcal disease in adults

PubMed Central

Baril, L; Dietemann, J; Essevaz-Roulet, M; Béniguel, L; Coan, P; Briles, D E; Guy, B; Cozon, G

2006-01-01

Humoral immune response is essential for protection against invasive pneumococcal disease and this property is the basis of the polysaccharide-based anti-pneumococcal vaccines. Pneumococcal surface protein A (PspA), a cell-wall-associated surface protein, is a promising component for the next generation of pneumococcal vaccines. This PspA antigen has been shown to stimulate an antibody-based immunity. In the present study, we evaluated the capacity of PspA to stimulate CD4+ T cells which are needed for the correct development of a B cell based immune response in humans. Cellular immunity to PspA was evaluated by whole-blood culture with different pneumococcal antigens, followed by flow cytometric detection of activated CD4+CD25+ T cells. T cell-mediated immune responses to recombinant PspA proteins were assessed in acute-phase and convalescent blood from adults with invasive pneumococcal disease and in blood from healthy subjects. All cases had detectable antibodies against PspA on admission. We found that invasive pneumococcal disease induced transient T cell depletion but adaptive immune responses strengthened markedly during convalescence. The increased production of both interleukin (IL)-10 and interferon (IFN)-γ during convalescence suggests that these cytokines may be involved in modulating antibody-based immunity to pneumococcal disease. We demonstrated that PspA is efficient at eliciting T cell immune responses and antibodies to PspA. This study broadens the applicability of recombinant PspA as potent pneumococcal antigen for vaccination against S. pneumoniae. PMID:16879247

Pneumococcal conjugate vaccines: proceedings from an interactive symposium at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy.

PubMed

Pelton, Stephen I; Dagan, Ron; Gaines, Beverly M; Klugman, Keith P; Laufer, Dagna; O'Brien, Katherine; Schmitt, Heinz J

2003-04-02

Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children. The emergence of antibiotic-resistant strains has increased interest in prevention through immunization. Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7. This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines. The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.

Effectiveness of 7-valent pneumococcal conjugate vaccine in the prevention of invasive pneumococcal disease in children aged 7-59 months. A matched case-control study.

PubMed

Domínguez, Angela; Ciruela, Pilar; García-García, Juan José; Moraga, Fernando; de Sevilla, Mariona F; Selva, Laura; Coll, Francis; Muñoz-Almagro, Carmen; Planes, Ana María; Codina, Gemma; Jordán, Iolanda; Esteva, Cristina; Hernández, Sergi; Soldevila, Núria; Cardeñosa, Neus; Batalla, Joan; Salleras, Luis

2011-11-08

The aim of this study was to evaluate the effectiveness of the administration of the 7-valent pneumococcal conjugate vaccine in a region with an intermediate vaccination coverage. A matched case-control study was carried out in children aged 7-59 months with invasive pneumococcal disease (IPD) admitted to two university hospitals in Catalonia. Three controls matched for hospital, age, sex, date of hospitalization and underlying disease were selected for each case. Information on the vaccination status of cases and controls was obtained from the vaccination card, the child's health card, the hospital medical record or the vaccination register of the primary healthcare center where the child was attended for non-severe conditions. A conditional logistic regression analysis was made to control for the effect of possible confounding variables. The adjusted vaccination effectiveness of the complete vaccination schedule (3 doses at 2, 4 and 6 months and a fourth dose at 15 months, 2 doses at least two months apart in children aged 12-23 months or a single dose in children aged >24 months) in preventing IPD caused by vaccine serotypes was 93.7% (95% CI 51.8-99.2). It was not effective in preventing cases caused by non-vaccine serotypes. The results of this study carried out in a population with intermediate vaccination coverage confirm those of other observational studies showing high levels of effectiveness of routine 7-valent pneumococcal conjugate vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bayesian Model Averaging with Change Points to Assess the Impact of Vaccination and Public Health Interventions

PubMed Central

Warren, Joshua L.; Schuck-Paim, Cynthia; Lustig, Roger; Lewnard, Joseph A.; Fuentes, Rodrigo; Bruhn, Christian A. W.; Taylor, Robert J.; Simonsen, Lone; Weinberger, Daniel M.

2017-01-01

Background: Pneumococcal conjugate vaccines (PCVs) prevent invasive pneumococcal disease and pneumonia. However, some low-and middle-income countries have yet to introduce PCV into their immunization programs due, in part, to lack of certainty about the potential impact. Assessing PCV benefits is challenging because specific data on pneumococcal disease are often lacking, and it can be difficult to separate the effects of factors other than the vaccine that could also affect pneumococcal disease rates. Methods: We assess PCV impact by combining Bayesian model averaging with change-point models to estimate the timing and magnitude of vaccine-associated changes, while controlling for seasonality and other covariates. We applied our approach to monthly time series of age-stratified hospitalizations related to pneumococcal infection in children younger 5 years of age in the United States, Brazil, and Chile. Results: Our method accurately detected changes in data in which we knew true and noteworthy changes occurred, i.e., in simulated data and for invasive pneumococcal disease. Moreover, 24 months after the vaccine introduction, we detected reductions of 14%, 9%, and 9% in the United States, Brazil, and Chile, respectively, in all-cause pneumonia (ACP) hospitalizations for age group 0 to <1 years of age. Conclusions: Our approach provides a flexible and sensitive method to detect changes in disease incidence that occur after the introduction of a vaccine or other intervention, while avoiding biases that exist in current approaches to time-trend analyses. PMID:28767518

Pneumolysin plays a key role at the initial step of establishing pneumococcal nasal colonization.

PubMed

Hotomi, Muneki; Yuasa, Jun; Briles, David E; Yamanaka, Noboru

2016-09-01

Nasopharyngeal colonization by Streptococcus pneumoniae is an important initial step for the subsequent development of pneumococcal infections. Pneumococci have many virulence factors that play a role in colonization. Pneumolysin (PLY), a pivotal pneumococcal virulence factor for invasive disease, causes severe tissue damage and inflammation with disruption of epithelial tight junctions. In this study, we evaluated the role of PLY in nasal colonization of S. pneumoniae using a mouse colonization model. A reduction of numbers of PLY-deficient pneumococci recovered from nasal tissue, as well as nasal wash, was observed at days 1 and 2 post-intranasal challenges, but not later. The findings strongly support an important role for PLY in the initial establishment nasal colonization. PLY-dependent invasion of local nasal mucosa may be required to establish nasal colonization with S. pneumoniae. The data help provide a rationale to explain why an organism that exists as an asymptomatic colonizer has evolved virulence factors that enable it to occasionally invade and kill its hosts. Thus, the same pneumococcal virulence factor, PLY that can contribute to killing the host, may also play a role early in the establishment of nasopharynx carriage.

Antibody persistence after pneumococcal conjugate vaccination in patients with chronic lymphocytic leukemia.

PubMed

Lindström, Vesa; Aittoniemi, Janne; Salmenniemi, Urpu; Käyhty, Helena; Huhtala, Heini; Itälä-Remes, Maija; Sinisalo, Marjatta

2018-02-08

Patients with chronic lymphocytic leukemia (CLL) are at a high risk for infections caused by Streptococcus pneumoniae. A pneumococcal conjugate vaccine (PCV) can induce a significant antibody response for some CLL patients. In this study we investigated antibody persistence after PCV7 in patients with CLL. The study material comprised 24 patients with CLL and 8 immunocompetent controls. The median antibody concentrations five years after PCV7 were lower for six pneumococcal serotypes in patients with CLL compared to controls, but the difference was not statistically significant. Depending on the serotype, the percentage of the CLL patients with antibody levels suggested to provide protection against invasive pneumococcal disease (IPD) varied from 29 to 71% five years after vaccination. This data suggests that PCV could result in antibody persistence at least five years in CLL patients.

Burden of vaccine-preventable pneumococcal disease in hospitalized adults: A Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) network study.

PubMed

LeBlanc, Jason J; ElSherif, May; Ye, Lingyun; MacKinnon-Cameron, Donna; Li, Li; Ambrose, Ardith; Hatchette, Todd F; Lang, Amanda L; Gillis, Hayley; Martin, Irene; Andrew, Melissa K; Boivin, Guy; Bowie, William; Green, Karen; Johnstone, Jennie; Loeb, Mark; McCarthy, Anne; McGeer, Allison; Moraca, Sanela; Semret, Makeda; Stiver, Grant; Trottier, Sylvie; Valiquette, Louis; Webster, Duncan; McNeil, Shelly A

2017-06-22

Pneumococcal community acquired pneumonia (CAP Spn ) and invasive pneumococcal disease (IPD) cause significant morbidity and mortality worldwide. Although childhood immunization programs have reduced the overall burden of pneumococcal disease, there is insufficient data in Canada to inform immunization policy in immunocompetent adults. This study aimed to describe clinical outcomes of pneumococcal disease in hospitalized Canadian adults, and determine the proportion of cases caused by vaccine-preventable serotypes. Active surveillance for CAP Spn and IPD in hospitalized adults was performed in hospitals across five Canadian provinces from December 2010 to 2013. CAP Spn were identified using sputum culture, blood culture, a commercial pan-pneumococcal urine antigen detection (UAD), or a serotype-specific UAD. The serotype distribution was characterized using Quellung reaction, and PCR-based serotyping on cultured isolates, or using a 13-valent pneumococcal conjugate vaccine (PCV13) serotype-specific UAD assay. In total, 4769 all-cause CAP cases and 81 cases of IPD (non-CAP) were identified. Of the 4769 all-cause CAP cases, a laboratory test for S. pneumoniae was performed in 3851, identifying 14.3% as CAP Spn . Of CAP cases among whom all four diagnostic test were performed, S. pneumoniae was identified in 23.2% (144/621). CAP Spn cases increased with age and the disease burden of illness was evident in terms of requirement for mechanical ventilation, intensive care unit admission, and 30-day mortality. Of serotypeable CAP Spn or IPD results, predominance for serotypes 3, 7F, 19A, and 22F was observed. The proportion of hospitalized CAP cases caused by a PCV13-type S. pneumoniae ranged between 7.0% and 14.8% among cases with at least one test for S. pneumoniae performed or in whom all four diagnostic tests were performed, respectively. Overall, vaccine-preventable pneumococcal CAP and IPD were shown to be significant causes of morbidity and mortality in hospitalized Canadian adults in the three years following infant PCV13 immunization programs in Canada. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study.

PubMed

Domínguez, Ángela; Ciruela, Pilar; Hernández, Sergi; García-García, Juan José; Soldevila, Núria; Izquierdo, Conchita; Moraga-Llop, Fernando; Díaz, Alvaro; F de Sevilla, Mariona; González-Peris, Sebastià; Campins, Magda; Uriona, Sonia; Martínez-Osorio, Johanna; Solé-Ribalta, Anna; Codina, Gemma; Esteva, Cristina; Planes, Ana María; Muñoz-Almagro, Carmen; Salleras, Luis

2017-01-01

The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7-59 months in a population with suboptimal vaccination coverage of 55%. The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1-87.2) and 90% (95% CI, 63.9-97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7-97.9) against serotype 1 and 86.0% (95% CI, 51.2-99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7-59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually.

Cost-effectiveness of the introduction of the pneumococcal polysaccharide vaccine in elderly Colombian population.

PubMed

Castañeda-Orjuela, Carlos; Alvis-Guzmán, Nelson; Paternina, Angel José; De la Hoz-Restrepo, Fernando

2011-10-13

Streptococcus pneumoniae causes community-acquired pneumonia, otitis media and meningitis, with higher incidences at the extremes of life. PPV-23 vaccine is widely used in prevention of pneumonia and invasive pneumococcal disease in older adults in developed countries. We developed an evaluation of cost-effectiveness of implementing PPV-23 in Colombian population over 60 years. The number of cases of pneumonia and meningitis in patients over 60 years and the proportion by S. pneumoniae was estimated based on a review of literature. A decision tree model with a 5-year time horizon was built to evaluate the cost-effectiveness of the implementation of the PPV-23 in this population. Direct health care costs of out- and in-patients were calculated based on expenditure records from the Bogota public health system. Incremental cost-effectiveness ratios per life saved and per year of life gained were estimated based on the decision tree model. Deterministic and probabilistic sensitivity analyses were performed. Without vaccination 4460 (range 2384-8162) bacteremic pneumococcal pneumonias and 141 (range 73-183) pneumococcal meningitis would occur among people over 60 years old in Colombia. In the first year, vaccination with PPV-23 at US$8/dose would save 480 (range 100-1753) deaths due to Invasive and non-invasive pneumococcal disease. Vaccination would results in US$3400/deaths averted (range US$1028-10,862) and US$1514/life years gained (range US$408-5404). Vaccination with PPV-23 in over 60 years is a highly cost-effective public health measure in Colombia. Despite some limitations, the results are robust, and may help developing countries to perform informed decisions about the introduction of the vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

An outbreak of pneumonia associated with S. pneumoniae at a military training facility in Finland in 2006.

PubMed

Vainio, Anni; Lyytikäinen, Outi; Sihvonen, Reetta; Kaijalainen, Tarja; Teirilä, Laura; Rantala, Merja; Lehtinen, Pirkko; Ruuska, Pekka; Virolainen, Anni

2009-07-01

Streptococcus pneumoniae is a well-known cause of community-acquired bacterial pneumonia. The purpose of this study was to assess the cause and extent of the outbreak of pneumonia which occurred among military recruits following a 1-week hard encampment in Finland. We also assessed the carriage rate and molecular characteristics of the S. pneumoniae isolates. All pneumococcal isolates were studied for antibiotic susceptibility, serotyped, genotyped by multilocus sequence typing (MLST), and the presence of pneumococcal rlrA pilus islet was detected. The genotype results defined by MLST corresponded with the serotype results. S. pneumoniae serotype 7F, ST2331, seemed to be associated with an outbreak of pneumonia and nasopharyngeal carriage among 43 military recruits. Of the 43 military recruits, five (12%) were hospitalized with pneumonia and two (40%) of them were positive for S. pneumoniae serotype 7F, ST2331 by blood culture. Eighteen (42%) of the 43 men were found to be positive for S. pneumoniae by nasopharyngeal culture, and nine (50%) of them carried pneumococcal serotype 7F, ST2331. The outbreak strain covered 55% of all the pneumococcal findings. Outbreaks of invasive pneumococcal disease seem to occur in a crowded environment such as a military training facility even among previously healthy young men.

[Bacteremic pneumococcal pneumonia].

PubMed

Pineda Solas, V; Pérez Benito, A; Domingo Puiggros, M; Larramona Carrera, H; Segura Porta, F; Fontanals Aymerich, D

2002-11-01

Streptococcus pneumonia is the most common bacterial cause of community-acquired pneumonia in children. The reference standard for etiological diagnosis is isolation of S. pneumoniae from blood Since the advent of conjugate vaccines, disease caused by this organism can now be prevented. Many studies have been performed of the global incidence of invasive pneumococcal infections and of pneumococcal meningitis but few studies investigated bacteremic pneumococcal pneumonia and its complications in children. To determine the incidence, patient characteristics, clinical signs, laboratory data, percentage and days of hospitalization, response to antibiotic treatment, antibiotic resistance, complications and causal serogroups of bacteremic pneumococcal pneumonia in our environment in order to estimate requirements for systematic vaccination programs. From January 1990 to May 2001, data on all pediatric cases of invasive pneumococcal infections diagnosed in our hospital were collected. Several characteristics of patients with bacteremic pneumococcal pneumonia were analyzed. Bacteremic pneumococcal pneumonia was diagnosed in patients with positive blood or pleural fluid cultures for S. pneumoniae and radiographically evident pulmonary infiltrate. The incidence of both types of pneumonia were determined according to population census data. All S. pneumonia strains were sent to the Pneumococci Reference Laboratory of the Instituto Carlos III in Madrid for serotyping. We estimated the serotype coverage of the pneumococcal 7-valent conjugate vaccine according to the serotypes included in this vaccine and their distribution. Forty cases of bacteremic pneumococcal pneumonia were diagnosed, yielding an incidence of 17,10 and 5 cases per 10(5) children aged less than 2, 4 and 15 years old respectively. The mean age was 50 months and 43% were aged less than 4 years. Peaks occurred in January, March, April and May. A total of 77.5% of the patients were admitted to hospital and the mean length of stay was 9.2 days. The mean duration of fever was 2 days and was 4.2 days in patients with pleural empyema. All patients presented fever and its mean duration before admission was 4 days. Fifty-eight percent of the patients had cough. Thirty-nine percent appeared generally unwell, vomiting was present in 47% and abdominal pain in 28%. Respiratory auscultation detected rales in 30% of the patients, hypophonesis in 28% and polypnea or dyspnea in 35%. Most patients showed alveolar bilateral infiltrations and 20% had pleural empyema. Seventy-eight percent had WBC counts > 15,000 and 93% showed neutrophilia of > 60%. Erythrocyte sedimentation rate and C-reactive protein were elevated in 77% and 85% of the patients, respectively. Overall, 40% of the isolates showed intermediate susceptibility to penicillin and 5% were resistant. Eighteen percent showed intermediate susceptibility to cefotaxime and 18% were resistant to erythromycin. Thirty-four strains were resistant to erythromycin. Thirty-four strains were serogroups and in children < or = 59 months, 34% of the serogroups were included in the pneumococcal 7-valent pneumococcal conjugate vaccine. The significant morbidity of bacteremic pneumococcal pneumonia and the implicated serogroups supports the use of the new heptavalent vaccine in the pediatric age group.

Invasive pneumococcal disease in Catalonian elderly people, 2002-2009: serotype coverage for different anti-pneumococcal vaccine formulations at the beginning of the new conjugate vaccines era.

PubMed

Vila-Corcoles, Angel; Ochoa-Gondar, Olga; Gomez-Bertomeu, Frederic; Raga-Luria, Xavier

2011-10-06

Population-based surveillance study conducted among persons 65 years or older from the region of Tarragona (Southern Catalonia, Spain) during 2002-2009. All cases with isolation of pneumococcus from normally sterile bodily fluids were included. Incidence rates of invasive pneumococcal disease (IPD) and prevalence of infections caused by serotypes included in different pneumococcal conjugate vaccines (PCVs) and the 23-valent pneumococcal polysaccharide vaccine (PPV-23) were calculated. Overall, 176 IPD cases were observed, which means an incidence of 48 episodes per 100,000 person-year throughout the study period. The most dominant serotypes were 7F (10.1%), 14 (9.4%), 19A (9.4%), 3 (8.6%), 6A (7.9%) and 1 (7.2%). IPD cases due to PCV-7 types (from 37.2% to 14.6%; p=0.003) and PCV-10 types (from 60.5% to 32.3%; p=0.002) considerably decreased between 2002-2005 and 2006-2009 periods. Percentage of cases due to PCV-13 types (76.7% vs 62.5%; p=0.099) and PPV-23 types (81.4% vs 68.8%; p=0.122) did not significantly change between both periods. As main conclusion, in our setting, the PCV-13 has almost similar serotype coverage to the PPV-23 in preventing IPD among the elderly population, which suggests a possible future use of the conjugate vaccine in all age groups. Copyright © 2011 Elsevier Ltd. All rights reserved.

Serotypes and Clonal Diversity of Streptococcus pneumoniae Causing Invasive Disease in the Era of PCV13 in Catalonia, Spain

PubMed Central

del Amo, Eva; Esteva, Cristina; Hernandez-Bou, Susanna; Galles, Carmen; Navarro, Marian; Sauca, Goretti; Diaz, Alvaro; Gassiot, Paula; Marti, Carmina; Larrosa, Nieves; Ciruela, Pilar; Jane, Mireia; Sá-Leão, Raquel; Muñoz-Almagro, Carmen

2016-01-01

The aim of this study was to study the serotypes and clonal diversity of pneumococci causing invasive pneumococcal disease in Catalonia, Spain, in the era of 13-valent pneumococcal conjugate vaccine (PCV13). In our region, this vaccine is only available in the private market and it is estimated a PCV13 vaccine coverage around 55% in children. A total of 1551 pneumococcal invasive isolates received between 2010 and 2013 in the Molecular Microbiology Department at Hospital Sant Joan de Déu, Barcelona, were included. Fifty-two serotypes and 249 clonal types—defined by MLST—were identified. The most common serotypes were serotype 1 (n = 182; 11.7%), 3 (n = 145; 9.3%), 19A (n = 137; 8.8%) and 7F (n = 122; 7.9%). Serotype 14 was the third most frequent serotype in children < 2 years (15 of 159 isolates). PCV7 serotypes maintained their proportion along the period of study, 16.6% in 2010 to 13.4% in 2013, whereas there was a significant proportional decrease in PCV13 serotypes, 65.3% in 2010 to 48.9% in 2013 (p<0.01). This decrease was mainly attributable to serotypes 19A and 7F. Serotype 12F achieved the third position in 2013 (n = 22, 6.4%). The most frequent clonal types found were ST306 (n = 154, 9.9%), ST191 (n = 111, 7.2%), ST989 (n = 85, 5.5%) and ST180 (n = 80, 5.2%). Despite their decrease, PCV13 serotypes continue to be a major cause of disease in Spain. These results emphasize the need for complete PCV13 vaccination. PMID:26953887

A protein chimera including PspA in fusion with PotD is protective against invasive pneumococcal infection and reduces nasopharyngeal colonization in mice.

PubMed

Converso, T R; Goulart, C; Darrieux, M; Leite, L C C

2017-09-12

Despite the success of the available polysaccharide-based vaccines against Streptococcus pneumoniae in preventing invasive diseases, this bacterium remains a major cause of death in many parts of the world. New vaccine strategies are needed in order to increase protection. Thus, the utilization of fusion proteins is being investigated as an alternative to the current formulations. In the present work, we demonstrate that a chimeric protein, composed of PspA and PotD in fusion is able to maintain the protective characteristics of both parental proteins, providing protection against systemic infection while reducing nasal colonization. The hybrid was not able to improve the response against invasive disease elicited by PspA alone, but the inclusion of PotD was able to reduce colonization, an effect never observed using subcutaneous immunization with PspA. The mechanisms underlying the protective efficacy of the rPspA-PotD hybrid protein were investigated, revealing the production of antibodies with an increased binding capacity to pneumococcal strains of diverse serotypes and genetic backgrounds, enhanced opsonophagocytosis, and secretion of IL-17 by splenocytes. These findings reinforce the use of chimeric proteins based on surface antigens as an effective strategy against pneumococcal infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pneumococcal vaccines for children: a global public health priority.

PubMed

Pittet, L F; Posfay-Barbe, K M

2012-10-01

Pneumococcal conjugated vaccines have been recommended in children for over a decade in many countries worldwide. Here we review the development of pneumococcal vaccines with a focus on the two types currently available for children and their safety record. We discuss also the effect of vaccines, including the 13-valent pneumococcal conjugate vaccine, on invasive pneumococcal diseases in children, particularly bacteraemia, pneumonia and meningitis, as well as on mucosal disease and carriage. In regions where immunization was implemented in young children, the number of invasive pneumococcal diseases decreased significantly, not only in the target age group, but also in younger and much older subjects. Challenges and future perspectives regarding the development of new 'universal' vaccines, which could bypass the current problem of serotype-specific protection in a context of serotype replacement, are also discussed. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.

Pneumococcal serotypes in adult non-invasive and invasive pneumonia in relation to child contact and child vaccination status.

PubMed

Rodrigo, Chamira; Bewick, Thomas; Sheppard, Carmen; Greenwood, Sonia; Macgregor, Vanessa; Trotter, Caroline; Slack, Mary; George, Robert; Lim, Wei Shen

2014-02-01

On a population level, pneumococcal conjugate vaccination in children has reduced the incidence of vaccine-type disease in all age groups, including older adults. Few individual level studies have been performed describing the pneumococcal serotypes associated with adult community acquired pneumonia (CAP) and quantifying associations with child contact and child vaccination status. Pneumococcal serotypes were determined using a validated multiplex immunoassay (Bio-Plex) in a large prospective cohort of adults hospitalised with CAP. Child (<16 years old) contact history and child pneumococcal vaccination status were obtained from patients and public health records, respectively. Of 1130 participants, 329 (29.1%) reported child contact, and pneumococcal infection was identified in 410 (36.3%). Pneumococcal CAP was commoner in adults with child contact (148/329 (45.0%) vs 262/801 (32.7%); adjusted OR 1.63, CI 1.25 to 2.14; p<0.001). A serotype was determined in 263 of 410 (64.1%) adults with pneumococcal CAP; 112 (42.6%) reported child contact, 38 (33.9%) with a vaccinated child. Adults in contact with a vaccinated child were significantly less likely to have vaccine-type CAP compared with adults in contact with an unvaccinated child (6 of 38 (15.8%) vs 25 of 74 (33.8%), respectively; OR 0.37, 95% CI 0.14 to 0.99; p=0.044). Pneumococcal aetiology in adult CAP is independently associated with child contact and implicated serotypes are influenced by child vaccination status. This is the first study to demonstrate these associations at an individual rather than population level; it affirms that 'herd protection' from childhood vaccination extends beyond adult invasive disease to pneumococcal CAP.

Carriage and invasive isolates of Streptococcus pneumoniae in Caracas, Venezuela: the relative invasiveness of serotypes and vaccine coverage.

PubMed

Rivera-Olivero, I A; del Nogal, B; Sisco, M C; Bogaert, D; Hermans, P W M; de Waard, J H

2011-12-01

The introduction of a pneumococcal conjugate vaccine in Venezuela needs previous studies to assess vaccine efficiency. We conducted a survey of nasopharyngeal pneumococcal carriage in urban children in Caracas and studied the distribution of serotypes. We compared these data with survey data available for invasive strains isolated in the same area and in the same time period. An overall pneumococcal carriage rate of 27% was observed. The most predominant capsular serotypes among carriage isolates were 6B (29%), 19A (13.8%), 23F (10%), 14 (8.3%), 6A (8.3%) and 15B/C (3.3%) and among invasive isolates 6B (25%), 14 (15%), and 19A, 6A, 7F, and 18 (7.5% each). The serotypes/groups 1, 5, 7F and 18, jointly covering 30% of the invasive strains, represented less than 0.7% of the carrier strains. The theoretical coverage of the pneumococcal conjugate vaccine PCV13 for carriage and invasive strains was calculated to be 74% and 90%, respectively. Our study demonstrates important differences for the serotype distribution in disease and carriage isolates and provides a key baseline for future studies addressing the prevalence and replacement of invasive and carriage serotypes after the introduction of the PCV 13 vaccine in Venezuela in the year 2010.

Effect of the different 13-valent pneumococcal conjugate vaccination uptakes on the invasive pneumococcal disease in children: Analysis of a hospital-based and population-based surveillance study in Madrid, Spain, 2007-2015

PubMed Central

Picazo, Juan; Ruiz-Contreras, Jesús; Casado-Flores, Juan; Negreira, Sagrario; Baquero, Fernando; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina

2017-01-01

In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding. Vaccine uptakes reached 95% in periods with public-funded pneumococcal vaccination, but fell to 67% in the private funding period. Overall, IR of IPD decreased by 68% (p<0.001) in 2014–15, due to 93% reduction in the IR of PCV13-type IPD (p<0.001) without significant changes in non-PCV13-type IPD. A fully government-funded PCV13 vaccination program lead to high vaccine uptake and dramatic reductions in both overall and PCV13-type IPD IR. When this program was switched to private PCV13 vaccination, there was a fall in vaccine coverage and stagnation in the decline of PCV13-type IPD with data suggesting a weakening of herd immunity. PMID:28207888

Cost-Effectiveness of Healthcare Worker Pneumococcal Polysaccharide Vaccination During Pandemic Influenza

PubMed Central

Smith, Kenneth J.; Raymund, Mahlon; Nowalk, Mary Patricia; Roberts, Mark S.; Zimmerman, Richard K.

2010-01-01

Objective In prior influenza pandemics, pneumococcal complications of influenza have caused substantial morbidity and mortality. The usefulness and cost-effectiveness of pneumococcal vaccination for healthcare workers during an influenza pandemic is unknown. Study Design Markov modeling was used to estimate the cost-effectiveness of pneumococcal polysaccharide vaccination (PPV) in previously unvaccinated healthcare workers during an influenza pandemic. Methods Invasive pneumococcal disease (IPD) incidence rates were incorporated into the model, assuming that IPD events occurred at twice the usual rate during the year of pandemic influenza. Both societal and hospital perspectives were examined. Assumptions were that: pneumococcal disease transmission from healthcare worker to patient did not occur, heightened IPD risk occurred for only 1 year, and PPV did not prevent noninvasive pneumonia, all of which potentially bias against vaccination. Results From a societal standpoint, pneumococcal vaccination of healthcare workers during an influenza pandemic is economically reasonable, costing $2,935 per quality adjusted life year gained; results were robust to variation in multiple sensitivity analyses. However, from the hospital perspective vaccinating healthcare workers was expensive, costing $1,676 per employee absence day avoided, given an IPD risk that, though increased, would still remain <1%. Conclusion Vaccinating all healthcare workers to protect against pneumococcal disease during a pandemic influenza outbreak is likely to be economically reasonable from the societal standpoint. However, pneumococcal vaccination is expensive from the hospital perspective, which might prevent implementation of a PPV program unless it is externally subsidized. PMID:20225915

Pediatric Invasive Pneumococcal Disease in Guatemala City: Importance of Serotype 2.

PubMed

Gaensbauer, James T; Asturias, Edwin J; Soto, Monica; Holt, Elizabeth; Olson, Daniel; Halsey, Neal A

2016-05-01

To inform estimations of the potential impact of recently introduced pneumococcal conjugate vaccine (PCV), we report results of 11 years of pre-PCV surveillance for invasive pneumococcal disease (IPD) among children in Guatemala City. Cases of IPD in children younger than 5 years were identified by active surveillance at 3 referral hospitals in Guatemala City from October 1996 through 2007. Clinical and demographic data were obtained, and isolates of Streptococcus pneumoniae from normally sterile sites were serotyped using latex agglutination and confirmed by Quellung reaction. Four hundred fifty-two cases of IPD were identified with a case fatality rate of 21%. Meningitis was the most common cause of death (77% of all deaths) and occurred more often in infancy (median age 5 months) than other clinical syndromes. Of the 137 isolates serotyped, type 1 (26 cases, 17%), type 2 (25 cases, 16%) and type 5 (18 cases, 12%) were the most common. Serotype 2 was associated with a higher case fatality rate (28%), higher rate of meningitis (68%) and occurred in younger infants (median age, 3.5 months) than other common serotypes. Recently introduced PCV13 includes 73% of observed serotypes in the study. Infants with IPD presented at a young age. Serotype 2, rarely reported as a significant cause of IPD and not included in available PCVs, was a common cause of disease in this population. PCV13 introduction in Guatemala, begun in 2013, may not have as great an impact in disease reduction as has been observed in other countries.

Pneumonia research in Papua New Guinea: 1967-1986.

PubMed

Riley, Ian D

2010-01-01

Between 1967 and 1985 research on pneumonia in Papua New Guinea (PNG) was fundamental not only to standard treatments of disease in PNG, but also to the establishment of the World Health Organization's global Program for Control of Acute Respiratory Infections. Pneumonia was the leading cause of death in both population-based and hospital studies. Research that began in 1967 revealed a pattern of disease in adults reminiscent of that seen in industrialized countries in the early 20th century. Streptococcus pneumoniae (pneumococcus) was the predominant causative organism. Pneumococci were commensals of the upper respiratory tract that invaded first the lungs and then the blood stream. Some serotypes were more invasive than others and case fatality increased with deeper levels of invasion. The pandemic of Hong Kong (H3N2) influenza spread to the Southern Highlands in 1969 resulting in 2000 deaths. The conclusion that pneumococcal pneumonia had been the principal cause of death led to the establishment of a pneumonia research unit in Tari. A field trial of pneumococcal polysaccharide vaccine showed the vaccine to be most effective in preventing invasive disease. Vaccination reduced pneumonia mortality by 44% in previously healthy adults. The epidemiological situation was more complex in children than in adults because many different species and serotypes of bacteria could be isolated from lung aspirate. Although many of these organisms would normally have been regarded as non-pathogenic, S. pneumoniae and Haemophilus influenzae, recognized pathogens, were the principal causes of severe morbidity and mortality. The same principles of carriage of and invasion by upper respiratory commensals applied as much to children as they did to adults, and the rank order of invasive serotypes of S. pneumoniae and H. influenzae was the same in different age groups. Slow maturation of a child's immune system meant, however, that children could be susceptible to invasion by particular serotypes. Infants were frequently colonized by pathogenic bacteria within days of birth. Nasal discharge, which was extremely common, was most probably a result of domestic smoke pollution and low standards of hygiene. Aspiration of infected secretions was a likely explanation for the variety of organisms isolated from lung aspirate. A trial of pneumococcal polysaccharide vaccine showed the vaccine to be effective in preventing death from pneumonia in children 6-9 months of age provided pneumonia was not associated with other causes of death; this result was shown to be consistent with the principles of infection and invasion described above. Principles of antibiotic therapy for child pneumonia were also established at this time.

Cost Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccination Program in Chronic Obstructive Pulmonary Disease Patients Aged 50+ Years in Spain.

PubMed

Rodríguez González-Moro, Jose Miguel; Menéndez, Rosario; Campins, Magda; Lwoff, Nadia; Oyagüez, Itziar; Echave, María; Rejas, Javier; Antoñanzas, Fernando

2016-01-01

Patients with chronic obstructive pulmonary disease (COPD) are at elevated risk of pneumococcal infection. A 13-valent pneumococcal conjugate vaccine (PCV13) was approved for protection against invasive disease and pneumonia caused by Streptococcus pneumoniae in adults. This study estimated the incremental cost-effectiveness ratio (ICER) of vaccinating COPD patients ≥50 years old with PCV13 compared with current vaccination policy (CVP) with 23-valent pneumococcal polysaccharide vaccine. A Markov model accounting for the risks and costs for all-cause non-bacteremic pneumonia (NBP) and invasive pneumococcal disease (IPD) was developed. All parameters, such as disease incidence and costs (€; 2015 values), were based on published data. The perspective of the analysis was that of the Spanish National Healthcare System, and the horizon of evaluation was lifetime in the base case. Vaccine effectiveness considered waning effect over time. Outcomes and costs were both discounted by 3% annually. Over a lifetime horizon and for a 629,747 COPD total population, PCV13 would prevent 2224 cases of inpatient NBP, 3134 cases of outpatient NBP, and 210 IPD extra cases in comparison with CVP. Additionally, 398 related deaths would be averted. The ICER was €1518 per quality-adjusted life-year (QALY) gained for PCV13 versus CVP. PCV13 was found to be cost effective versus CVP from a 5-year modelling horizon (1302 inpatient NBP and 1835 outpatient NBP cases together with 182 deaths would be prevented [ICER €25,573/QALY]). Univariate and probabilistic sensitivity analyses confirmed the robustness of the model. At the commonly accepted willingness-to-pay threshold of €30,000/QALY gained, PCV13 vaccination in COPD patients aged ≥50 years was a cost-effective strategy compared with CVP from 5 years to lifetime horizon in Spain.

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study

PubMed Central

Ciruela, Pilar; Hernández, Sergi; García-García, Juan José; Soldevila, Núria; Izquierdo, Conchita; Moraga-Llop, Fernando; Díaz, Alvaro; F. de Sevilla, Mariona; González-Peris, Sebastià; Campins, Magda; Uriona, Sonia; Martínez-Osorio, Johanna; Solé-Ribalta, Anna; Codina, Gemma; Esteva, Cristina; Planes, Ana María; Muñoz-Almagro, Carmen; Salleras, Luis

2017-01-01

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7–59 months in a population with suboptimal vaccination coverage of 55%. Methods The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). Results 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1–87.2) and 90% (95% CI, 63.9–97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7–97.9) against serotype 1 and 86.0% (95% CI, 51.2–99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). Conclusions The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7–59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually. PMID:28806737

Impact of 13-Valent Pneumococcal Conjugate Vaccine Used in Children on Invasive Pneumococcal Disease in Children and Adults in the United States: Analysis of Multisite, Population-based Surveillance

PubMed Central

Moore, Matthew R.; Link-Gelles, Ruth; Schaffner, William; Lynfield, Ruth; Lexau, Catherine; Bennett, Nancy M.; Petit, Susan; Zansky, Shelley M.; Harrison, Lee H.; Reingold, Arthur; Miller, Lisa; Scherzinger, Karen; Thomas, Ann; Farley, Monica M.; Zell, Elizabeth R.; Taylor, Thomas H.; Pondo, Tracy; Rodgers, Loren; McGee, Lesley; Beall, Bernard; Jorgensen, James H.; Whitney, Cynthia G.

2016-01-01

SUMMARY Background In 2000, 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the U.S. and resulted in dramatic reductions in invasive pneumococcal disease (IPD) and modest increases in non-PCV7-type IPD. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the U.S. immunization schedule. We evaluated the effect of PCV13 use in children on IPD in children and adults in the U.S. Methods We used laboratory- and population-based data on incidence of IPD from CDC’s Emerging Infections Program / Active Bacterial Core surveillance in a time-series model to estimate the impact of vaccination. Cases of IPD during July 2004–June 2013 were classified as being caused by the PCV13 serotypes against which PCV7 has no effect (PCV13/nonPCV7). Findings Compared with incidence expected among children <5 years old if PCV7 alone had been continued, incidence of IPD overall and IPD caused by PCV13/nonPCV7 serotypes declined by 64% (95% interval estimate [IE] 59–68 %) and 93% (95%IE 91–94), respectively, by July 2012–June 2013. Among adults, incidence of IPD overall and PCV13/nonPCV7-type IPD also declined by 12–32% and 58–72%, respectively, depending on age. In all age groups, reductions were driven principally by changes in incidence of serotypes 19A and 7F. We estimate that over 30,000 cases of IPD and 3,000 deaths were averted in the first 3 years following PCV13 introduction. Interpretation PCV13 has reduced IPD among all ages when used routinely in children in the U.S. Serotypes 19A and 7F, which emerged after PCV7 introduction, have been effectively controlled. PMID:25656600

Outbreak of invasive pneumococcal disease at a Belfast shipyard in men exposed to welding fumes, Northern Ireland, April-May 2015: preliminary report.

PubMed

Patterson, L; Irvine, N; Wilson, A; Doherty, L; Loughrey, A; Jessop, L

2015-05-28

We report an outbreak of four confirmed cases of invasive pneumococcal disease (IPD) in individuals occupationally exposed to welding fumes, at a Belfast shipyard (Northern Ireland). All cases were hospitalised. A high-risk sub-group of 679 workers has been targeted for antibiotic prophylaxis and pneumococcal vaccination. Physicians and public health institutions outside Northern Ireland should be alert to individuals presenting with pneumonia or IPD and recent links to the shipyard, to facilitate early assessment and treatment.

Whole-Genome Sequence Analysis of Streptococcus pneumoniae Strains That Cause Hospital-Acquired Pneumonia Infections.

PubMed

Chang, Bin; Morita, Masatomo; Lee, Ken-Ichi; Ohnishi, Makoto

2018-05-01

Streptococcus pneumoniae colonizes the nasopharyngeal mucus in healthy individuals and can cause otitis media, pneumonia, and invasive pneumococcal diseases. In this study, we analyzed S. pneumoniae strains that caused 19 pneumonia episodes in long-term inpatients with severe underlying disease in a hospital during a period of 14 months (from January 2014 to February 2015). Serotyping and whole-genome sequencing analyses revealed that 18 of the 19 pneumonia cases were caused by S. pneumoniae strains belonging to 3 genetically distinct groups: clonal complex 9999 (CC9999), sequence type 282 (ST282), and ST166. The CC9999 and ST282 strains appeared to have emerged separately by a capsule switch from the pandemic PMEN 1 strain (Spain 23F -ST81). After all the long-term inpatients were inoculated with the 23-valent pneumococcal polysaccharide vaccine, no other nosocomial pneumonia infections occurred until March 2016. Copyright © 2018 American Society for Microbiology.

The Saudi Thoracic Society pneumococcal vaccination guidelines-2016

PubMed Central

Alharbi, N. S.; Al-Barrak, A. M.; Al-Moamary, M. S.; Zeitouni, M. O.; Idrees, M. M.; Al-Ghobain, M. O.; Al-Shimemeri, A. A.; Al-Hajjaj, Mohamed S.

2016-01-01

Streptococcus pneumoniae (pneumococcus) is the leading cause of morbidity and mortality worldwide. Saudi Arabia is a host to millions of pilgrims who travel annually from all over the world for Umrah and the Hajj pilgrimages and are at risk of developing pneumococcal pneumonia or invasive pneumococcal disease (IPD). There is also the risk of transmission of S. pneumoniae including antibiotic resistant strains between pilgrims and their potential global spread upon their return. The country also has unique challenges posed by susceptible population to IPD due to people with hemoglobinopathies, younger age groups with chronic conditions, and growing problem of antibiotic resistance. Since the epidemiology of pneumococcal disease is constantly changing, with an increase in nonvaccine pneumococcal serotypes, vaccination policies on the effectiveness and usefulness of vaccines require regular revision. As part of the Saudi Thoracic Society (STS) commitment to promote the best practices in the field of respiratory diseases, we conducted a review of S. pneumoniae infections and the best evidence base available in the literature. The aim of the present study is to develop the STS pneumococcal vaccination guidelines for healthcare workers in Saudi Arabia. We recommend vaccination against pneumococcal infections for all children <5 years old, adults ≥50 years old, and people ≥6 years old with certain risk factors. These recommendations are based on the presence of a large number of comorbidities in Saudi Arabia population <50 years of age, many of whom have risk factors for contracting pneumococcal infections. A section for pneumococcal vaccination before the Umrah and Hajj pilgrimages is included as well. PMID:27168856

Influenza A Virus Infection Predisposes Hosts to Secondary Infection with Different Streptococcus pneumoniae Serotypes with Similar Outcome but Serotype-Specific Manifestation.

PubMed

Sharma-Chawla, Niharika; Sender, Vicky; Kershaw, Olivia; Gruber, Achim D; Volckmar, Julia; Henriques-Normark, Birgitta; Stegemann-Koniszewski, Sabine; Bruder, Dunja

2016-12-01

Influenza A virus (IAV) and Streptococcus pneumoniae are major causes of respiratory tract infections, particularly during coinfection. The synergism between these two pathogens is characterized by a complex network of dysregulated immune responses, some of which last until recovery following IAV infection. Despite the high serotype diversity of S. pneumoniae and the serotype replacement observed since the introduction of conjugate vaccines, little is known about pneumococcal strain dependency in the enhanced susceptibility to severe secondary S. pneumoniae infection following IAV infection. Thus, we studied how preinfection with IAV alters host susceptibility to different S. pneumoniae strains with various degrees of invasiveness using a highly invasive serotype 4 strain, an invasive serotype 7F strain, and a carrier serotype 19F strain. A murine model of pneumococcal coinfection during the acute phase of IAV infection showed a significantly increased degree of pneumonia and mortality for all tested pneumococcal strains at otherwise sublethal doses. The incidence and kinetics of systemic dissemination, however, remained bacterial strain dependent. Furthermore, we observed strain-specific alterations in the pulmonary levels of alveolar macrophages, neutrophils, and inflammatory mediators ultimately affecting immunopathology. During the recovery phase following IAV infection, bacterial growth in the lungs and systemic dissemination were enhanced in a strain-dependent manner. Altogether, this study shows that acute IAV infection predisposes the host to lethal S. pneumoniae infection irrespective of the pneumococcal serotype, while the long-lasting synergism between IAV and S. pneumoniae is bacterial strain dependent. These results hold implications for developing tailored therapeutic treatment regimens for dual infections during future IAV outbreaks. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Medical microbiology: laboratory diagnosis of invasive pneumococcal disease.

PubMed

Werno, Anja M; Murdoch, David R

2008-03-15

The laboratory diagnosis of invasive pneumococcal disease (IPD) continues to rely on culture-based methods that have been used for many decades. The most significant recent developments have occurred with antigen detection assays, whereas the role of nucleic acid amplification tests has yet to be fully clarified. Despite developments in laboratory diagnostics, a microbiological diagnosis is still not made in most cases of IPD, particularly for pneumococcal pneumonia. The limitations of existing diagnostic tests impact the ability to obtain accurate IPD burden data and to assess the effectiveness of control measures, such as vaccination, in addition to the ability to diagnose IPD in individual patients. There is an urgent need for improved diagnostic tests for pneumococcal disease--especially tests that are suitable for use in underresourced countries.

New trends in the prevention and management of community-acquired pneumonia.

PubMed

Postma, D F; van Werkhoven, C H; Huijts, S M; Bolkenbaas, M; Oosterheert, J J; Bonten, M J M

2012-10-01

Community-acquired pneumonia (CAP) is an important cause of morbidity and mortality worldwide. This review summarises current trends and knowledge gaps in CAP management and prevention. Although Streptococcus pneumoniae is the most frequent cause of CAP, identification of the microbial cause of infection remains unsuccessful in most episodes, and little is known about the aetiology of CAP in immunocompromised patients. Urinary antigen testing has become standard care for diagnosing Legionella infection, and pneumococcal urinary antigen testing is now recommended in the Dutch guidelines to streamline antibiotic therapy in patients hospitalised with CAP. In primary care C-reactive protein determination is recommended to improve antibiotic prescription for lower respiratory tract infections. In patients hospitalised with CAP, three strategies are considered equally effective for choosing empirical antibiotic treatment. Yet, more (and better designed) studies are needed to determine the best strategy, as well as to determine optimal (which usually means the minimum) duration of antibiotic therapy and the role of adjuvant treatment with corticosteroids. The effectiveness of the 23-valent pneumococcal polysaccharide vaccine in preventing invasive pneumococcal disease and pneumococcal CAP remains debated, and whether the newer conjugate vaccines are more effective remains to be determined. Many of these questions are currently being addressed in large-scaled trials in the Netherlands, and their results may allow evidence-based decisions in CAP management and prevention.

Estimating the Burden of Pneumococcal Pneumonia among Adults: A Systematic Review and Meta-Analysis of Diagnostic Techniques

PubMed Central

Said, Maria A.; Johnson, Hope L.; Nonyane, Bareng A. S.; Deloria-Knoll, Maria; O′Brien, Katherine L.

2013-01-01

Background Pneumococcal pneumonia causes significant morbidity and mortality among adults. Given limitations of diagnostic tests for non-bacteremic pneumococcal pneumonia, most studies report the incidence of bacteremic or invasive pneumococcal disease (IPD), and thus, grossly underestimate the pneumococcal pneumonia burden. We aimed to develop a conceptual and quantitative strategy to estimate the non-bacteremic disease burden among adults with community-acquired pneumonia (CAP) using systematic study methods and the availability of a urine antigen assay. Methods and Findings We performed a systematic literature review of studies providing information on the relative yield of various diagnostic assays (BinaxNOW® S. pneumoniae urine antigen test (UAT) with blood and/or sputum culture) in diagnosing pneumococcal pneumonia. We estimated the proportion of pneumococcal pneumonia that is bacteremic, the proportion of CAP attributable to pneumococcus, and the additional contribution of the Binax UAT beyond conventional diagnostic techniques, using random effects meta-analytic methods and bootstrapping. We included 35 studies in the analysis, predominantly from developed countries. The estimated proportion of pneumococcal pneumonia that is bacteremic was 24.8% (95% CI: 21.3%, 28.9%). The estimated proportion of CAP attributable to pneumococcus was 27.3% (95% CI: 23.9%, 31.1%). The Binax UAT diagnosed an additional 11.4% (95% CI: 9.6, 13.6%) of CAP beyond conventional techniques. We were limited by the fact that not all patients underwent all diagnostic tests and by the sensitivity and specificity of the diagnostic tests themselves. We address these resulting biases and provide a range of plausible values in order to estimate the burden of pneumococcal pneumonia among adults. Conclusions Estimating the adult burden of pneumococcal disease from bacteremic pneumococcal pneumonia data alone significantly underestimates the true burden of disease in adults. For every case of bacteremic pneumococcal pneumonia, we estimate that there are at least 3 additional cases of non-bacteremic pneumococcal pneumonia. PMID:23565216

Invasive Pneumococcal Disease After Implementation of 13-Valent Conjugate Vaccine

PubMed Central

Madoff, Lawrence C.; Coombes, Brandon; Pelton, Stephen I.

2014-01-01

OBJECTIVE: To examine whether there is a different clinical profile and severity of invasive pneumococcal disease (IPD) in children caused by nonvaccine types in the era of 13-valent pneumococcal conjugate vaccine (PCV13). METHODS: Observational study of childhood IPD in Massachusetts based on state public health surveillance data comparing pre-PCV13 (2007–2009) and post-PCV13 (2010–2012) eras. RESULTS: There were 168 pre-PCV13 cases of IPD and 85 post-PCV13 cases of IPD in Massachusetts children ≤5 years of age. PCV13 serotypes declined by 18% in the first 2 years after PCV13 use (P = .011). In the post-PCV13 phase, a higher proportion of children were hospitalized (57.6% vs 50.6%), and a higher proportion of children had comorbidity (23.5% vs 19.6%). Neither difference was statistically significant, nor were comparisons of IPD caused by vaccine and nonvaccine types. Children with comorbidities had higher rates of IPD caused by a nonvaccine type (27.6% vs 17.2%; P = .085), were more likely to be hospitalized (80.4% vs 50%; P < .0001), and were more likely to have a longer hospital stay (median of 3 days vs 0.5 days; P = .0001). CONCLUSIONS: Initial data suggest that nonvaccine serotypes are more common in children with underlying conditions, who have greater morbidity from disease. In the post-PCV13 era, a larger proportion of patients are hospitalized, but mortality rates are unchanged. Routine vaccination with PCV13 may not be enough to reduce the risk in patients with comorbidity. PMID:25002663

Analysis of invasive pneumonia-causing strains of Streptococcus pneumoniae: serotypes and antimicrobial susceptibility.

PubMed

Yoshioka, Cristina R M; Martinez, Marina B; Brandileone, Maria C C; Ragazzi, Selma B; Guerra, Maria L L S; Santos, Silvia R; Shieh, Huei H; Gilio, Alfredo E

2011-01-01

To identify the most common pneumococcal serotypes in children hospitalized with invasive pneumonia, correlate isolated serotypes with those included in conjugate vaccines, and ascertain the sensitivity of the isolated pneumococcal strains to penicillin and other antibiotics. From January 2003 to October 2008, a retrospective study of hospitalized children with a diagnosis of Streptococcus pneumoniae pneumonia was conducted at the university hospital of Universidade de São Paulo. Criteria for inclusion were: age greater than 29 days and less than 15 years, radiological and clinical diagnosis of pneumonia, and isolation of Streptococcus pneumoniae in blood cultures and/or pleural effusion. The study included 107 children. The most common serotypes were 14 (36.5%), 1 (16%), 5 (14.6%), 6B (6.3%) and 3 (4.2%). The proportion of identified serotypes contained in the heptavalent, 10-valent and 13-valent conjugate vaccines was 53.1, 86.5, and 96.9%, respectively. Pneumococcal strains were sensitive to penicillin (minimum inhibitory concentration, MIC ≤ 2 µg/mL) in 100 cases (93.5%) and displayed intermediate resistance (MIC = 4 µg/mL) in 7 cases (6.5%). No strains were penicillin-resistant (MIC ≥ 8 µg/mL) according to the Clinical and Laboratory Standards Institute 2008 standards. Tested isolates were highly sensitive to vancomycin, rifampicin, ceftriaxone, clindamycin, erythromycin, and chloramphenicol. Our results confirm a significant potential impact of conjugate vaccines, mainly 10-valent and 13-valent, on invasive pneumonia. Furthermore, susceptibility testing results show that penicillin is still the treatment of choice for invasive pneumonia in our setting.

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

PubMed Central

Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

2011-01-01

Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

Dominance of multidrug-resistant Denmark(14)-32 (ST230) clone among Streptococcus pneumoniae serotype 19A isolates causing pneumococcal disease in Bulgaria from 1992 to 2013.

PubMed

Setchanova, Lena Petrova; Alexandrova, Alexandra; Dacheva, Daniela; Mitov, Ivan; Kaneva, Radka; Mitev, Vanio

2015-02-01

A pneumococcal conjugate vaccine (PCV10) was introduced in Bulgarian national immunization program since April 2010. Clonal composition based on pulsed-field gel electrophoresis and multilocus sequence typing genotyping of 52 serotype 19A Streptococcus pneumoniae isolates was analyzed. These were invasive and respiratory isolates collected between 1992 and 2013 from both children (78.8% <5 years) and adults with pneumococcal infections. Multidrug resistance was found in 82.7% of all 19A isolates. The most prevalent genotype (63.5%) among serotype 19A pneumococcal strains was the multidrug-resistant clonal complex CC230, which is a capsular switched variant of the Denmark(14)-32 (ST230) global clone. The most frequent sequence type (ST) was ST230 (48.1%) and together with four other closely related STs (15.4%), belonging to ST1611, ST276, ST7466, and ST2013, which were single- and double-locus variants; they were included in the main CC230. The disappearance of highly drug-resistant ST663 clone and emergence of new clones as CC320 and CC199 was also observed among the rest 19A isolates. A comparison of clonal composition between invasive and noninvasive isolates did not show a great genetic diversity among both kinds of isolates. Continuous surveillance of serotype 19A population following the introduction of PCV10 is essential to evaluate the impact of the vaccine on the epidemiology of this serotype.

Global Distribution of Invasive Serotype 35D Streptococcus pneumoniae Isolates following Introduction of 13-Valent Pneumococcal Conjugate Vaccine.

PubMed

Lo, Stephanie W; Gladstone, Rebecca A; van Tonder, Andries J; Hawkins, Paulina A; Kwambana-Adams, Brenda; Cornick, Jennifer E; Madhi, Shabir A; Nzenze, Susan A; du Plessis, Mignon; Kandasamy, Rama; Carter, Philip E; Eser, Özgen Köseoglu; Ho, Pak Leung; Elmdaghri, Naima; Shakoor, Sadia; Clarke, Stuart C; Antonio, Martin; Everett, Dean B; von Gottberg, Anne; Klugman, Keith P; McGee, Lesley; Breiman, Robert F; Bentley, Stephen D

2018-07-01

A newly recognized pneumococcal serotype, 35D, which differs from the 35B polysaccharide in structure and serology by not binding to factor serum 35a, was recently reported. The genetic basis for this distinctive serology is due to the presence of an inactivating mutation in wciG , which encodes an O-acetyltransferase responsible for O-acetylation of a galactofuranose. Here, we assessed the genomic data of a worldwide pneumococcal collection to identify serotype 35D isolates and understand their geographical distribution, genetic background, and invasiveness potential. Of 21,980 pneumococcal isolates, 444 were originally typed as serotype 35B by PneumoCaT. Analysis of the wciG gene revealed 23 isolates from carriage ( n = 4) and disease ( n = 19) with partial or complete loss-of-function mutations, including mutations resulting in premature stop codons ( n = 22) and an in-frame mutation ( n = 1). These were selected for further analysis. The putative 35D isolates were geographically widespread, and 65.2% (15/23) of them was recovered after the introduction of pneumococcal conjugate vaccine 13 (PCV13). Compared with serotype 35B isolates, putative serotype 35D isolates have higher invasive disease potentials based on odds ratios (OR) (11.58; 95% confidence interval[CI], 1.42 to 94.19 versus 0.61; 95% CI, 0.40 to 0.92) and a higher prevalence of macrolide resistance mediated by mefA (26.1% versus 7.6%; P = 0.009). Using the Quellung reaction, 50% (10/20) of viable isolates were identified as serotype 35D, 25% (5/20) as serotype 35B, and 25% (5/20) as a mixture of 35B/35D. The discrepancy between phenotype and genotype requires further investigation. These findings illustrated a global distribution of an invasive serotype, 35D, among young children post-PCV13 introduction and underlined the invasive potential conferred by the loss of O-acetylation in the pneumococcal capsule. Copyright © 2018 Lo et al.

Forecasting invasive pneumococcal disease trends after the introduction of 13-valent pneumococcal conjugate vaccine in the United States, 2010-2020.

PubMed

Link-Gelles, Ruth; Taylor, Thomas; Moore, Matthew R

2013-05-24

Pneumococcal vaccines are highly effective at preventing invasive pneumococcal disease (IPD), a leading cause of global morbidity. Because pneumococcal vaccines can be expensive, it is useful to estimate what impact might be expected from their introduction. Our objective was to develop a statistical model that could predict rates of IPD following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in the U.S. We used active surveillance data to design and validate a Poisson model forecasting the reductions in IPD observed after U.S. introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. We used this model to forecast rates of IPD from 2010 to 2020 in the presence of PCV13. Because increases in non-PCV7-type IPD were evident following PCV7 introduction, we evaluated varying levels of increase in non-PCV13-type IPD ("serotype replacement") by sensitivity analyses. A total of 43,507 cases of IPD were identified during 1998-2009; cases from this period were used to develop the model, which accurately predicted indirect effects of PCV7 in adults, as well as serotype replacement. Assuming that PCV13 provides similar protection against PCV13 serotypes as PCV7 did against PCV7 serotypes, the base-case model predicted approximately 168,000 cases of IPD prevented from 2011 to 2020. When serotype replacement was varied in sensitivity analyses from 0 to levels comparable to that seen with serotype 19A (the most common replacement serotype since PCV7 was introduced), the model predicted 167,000-170,000 cases prevented. The base-case model predicted rates of IPD in children under five years of age decreasing from 21.9 to 9.3 cases per 100,000 population. This model provides a "benchmark" for assessing progress in the prevention of IPD in the years after PCV13 introduction. The amount of serotype replacement is unlikely to greatly affect the overall number of cases prevented by PCV13. Published by Elsevier Ltd.

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

PubMed Central

Kim, Lindsay; McGee, Lesley; Tomczyk, Sara

2016-01-01

SUMMARY Streptococcus pneumoniae inflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand. PMID:27076637

Impact of the introduction of the pneumococcal conjugate vaccine in the Brazilian routine childhood national immunization program.

PubMed

Moreira, Marta; Cintra, Otavio; Harriague, Julie; Hausdorff, William P; Hoet, Bernard

2016-05-27

Brazil introduced the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™, GSK Vaccines) in the routine childhood immunization program in 2010 with a 3+1 schedule (with catch-up for children <2 years-old). This review represents the first analysis of the overall impact of a second-generation pneumococcal conjugate vaccine on nasopharyngeal carriage and all the major pneumococcal disease manifestations in a single, pneumococcal conjugate vaccine-naïve, developing country. A total of 15 published articles and 13 congress abstracts were included in the analysis. In children <5 years-old, studies showed a positive impact of PHiD-CV on the incidence of vaccine-type and any-type invasive pneumococcal disease (including decreases in pneumococcal meningitis morbidity and mortality), on pneumonia incidence and mortality, and on otitis media. Nasopharyngeal carriage of vaccine-type and any-type pneumococci decreased after the primary doses, with no early signs of replacement with other pathogens. Finally, herd protection against vaccine-type invasive pneumococcal disease and pneumonia in unvaccinated subjects was shown in some studies for some age groups. In conclusion, pneumococcal disease decreased after the introduction of PHiD-CV into the Brazilian national immunization program. Further follow-up is needed to evaluate the long-term overall impact of PHiD-CV in the Brazilian population. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Estimated severe pneumococcal disease cases and deaths before and after pneumococcal conjugate vaccine introduction in children younger than 5 years of age in South Africa.

PubMed

von Mollendorf, Claire; Tempia, Stefano; von Gottberg, Anne; Meiring, Susan; Quan, Vanessa; Feldman, Charles; Cloete, Jeane; Madhi, Shabir A; O'Brien, Katherine L; Klugman, Keith P; Whitney, Cynthia G; Cohen, Cheryl

2017-01-01

Streptococcus pneumoniae is a leading cause of severe bacterial infections globally. A full understanding of the impact of pneumococcal conjugate vaccine (PCV) on pneumococcal disease burden, following its introduction in 2009 in South Africa, can support national policy on PCV use and assist with policy decisions elsewhere. We developed a model to estimate the national burden of severe pneumococcal disease, i.e. disease requiring hospitalisation, pre- (2005-2008) and post-PCV introduction (2012-2013) in children aged 0-59 months in South Africa. We estimated case numbers for invasive pneumococcal disease using data from the national laboratory-based surveillance, adjusted for specimen-taking practices. We estimated non-bacteraemic pneumococcal pneumonia case numbers using vaccine probe study data. To estimate pneumococcal deaths, we applied observed case fatality ratios to estimated case numbers. Estimates were stratified by HIV status to account for the impact of PCV and HIV-related interventions. We assessed how different assumptions affected estimates using a sensitivity analysis. Bootstrapping created confidence intervals. In the pre-vaccine era, a total of approximately 107,600 (95% confidence interval [CI] 83,000-140,000) cases of severe hospitalised pneumococcal disease were estimated to have occurred annually. Following PCV introduction and the improvement in HIV interventions, 41,800 (95% CI 28,000-50,000) severe pneumococcal disease cases were estimated in 2012-2013, a rate reduction of 1,277 cases per 100,000 child-years. Approximately 5000 (95% CI 3000-6000) pneumococcal-related annual deaths were estimated in the pre-vaccine period and 1,900 (95% CI 1000-2500) in 2012-2013, a mortality rate difference of 61 per 100,000 child-years. While a large number of hospitalisations and deaths due to pneumococcal disease still occur among children 0-59 months in South Africa, we found a large reduction in this estimate that is temporally associated with PCV introduction. In HIV-infected individuals the scale-up of other interventions, such as improvements in HIV care, may have also contributed to the declines in pneumococcal burden.

Streptococcus pneumoniae Carriage Prevalence in Nepal: Evaluation of a Method for Delayed Transport of Samples from Remote Regions and Implications for Vaccine Implementation

PubMed Central

Hanieh, Sarah; Hamaluba, Mainga; Kelly, Dominic F.; Metz, Jane A.; Wyres, Kelly L.; Fisher, Roberta; Pradhan, Rahul; Shakya, Disuja; Shrestha, Lochan; Shrestha, Amrita; Joshi, Anip; Habens, Jocelyn; Maharjan, Bishnu D.; Thorson, Stephen; Bohler, Erik; Yu, Ly-Mee; Kelly, Sarah; Plested, Emma; John, Tessa; Werno, Anja M.; Adhikari, Neelam; Murdoch, David R.; Brueggemann, Angela B.; Pollard, Andrew J.

2014-01-01

Background Pneumococcal disease is a significant cause of morbidity and mortality in young children in Nepal, and currently available pneumococcal conjugate vaccines offer moderate coverage of invasive disease isolates. Methods A prevalence study of children aged 1.5 to 24 months in urban and rural Nepal was conducted. In the urban group, nasopharyngeal swabs (NPS) were transported using silica desiccant packages (SDP) with delayed processing (2 weeks), or skim-milk-tryptone-glucose-glycerin (STGG) with immediate processing (within 8 hours). Pneumococcal nasopharyngeal carriage prevalence, serogroup/type distribution and isolate genotypes (as defined by multilocus sequence typing) were determined. Results 1101 children were enrolled into the study: 574 in the urban group and 527 in the rural group. Overall carriage prevalence based on culture from specimens transported and stored in STGG was 58.7% (337/574), compared to 40.9% (235/574) in SDP. There was concordance of detection of pneumococcus in 67% of samples. Using the SDP method, pneumococcal carriage prevalence was higher in the rural population (69.2%; 364/526) compared to the urban population (40.9%; 235/574). Serogroup/type distribution varied with geographical location. Over half of the genotypes identified in both the urban and rural pneumococcal populations were novel. Conclusion The combination of delayed culture and transport using SDP underestimates the prevalence of pneumococcal carriage; however, in remote areas, this method could still provide a useful estimate of carriage prevalence and serogroup/type distribution. Vaccine impact is unpredictable in a setting with novel genotypes and limited serotype coverage as described here. Consequently, continued surveillance of pneumococcal isolates from carriage and disease in Nepali children following the planned introduction of pneumococcal conjugate vaccines introduction will be essential. PMID:24905574

Economic evaluation of second generation pneumococcal conjugate vaccines in Norway.

PubMed

Robberstad, Bjarne; Frostad, Carl R; Akselsen, Per E; Kværner, Kari J; Berstad, Aud K H

2011-11-03

A seven valent pneumococcal conjugate vaccine (PCV7) was introduced in the Norwegian childhood immunization programme in 2006, and since then the incidence of invasive pneumococcal disease has declined substantially. Recently, two new second generation pneumococcal conjugate vaccines have become available, and an update of the economic evidence is needed. The aim of this study was to estimate incremental costs, health effects and cost-effectiveness of the pneumococcal conjugate vaccines PCV7, PCV13 and PHiD-CV in Norway. We used a Markov model to estimate costs and epidemiological burden of pneumococcal- and NTHi-related diseases (invasive pneumococcal disease (IPD), Community Acquired Pneumonia (CAP) and acute otitis media (AOM)) for a specific birth cohort. Using the most relevant evidence and assumptions for a Norwegian setting, we calculated incremental costs, health effects and cost-effectiveness for different vaccination strategies. In addition we performed sensitivity analyses for key parameters, tested key assumptions in scenario analyses and explored overall model uncertainty using probabilistic sensitivity analysis. The model predicts that both PCV13 and PHiD-CV provide more health gains at a lower cost than PCV7. Differences in health gains between the two second generation vaccines are small for invasive pneumococcal disease but larger for acute otitis media and myringotomy procedures. Consequently, PHiD-CV saves more disease treatment costs and indirect costs than PCV13. This study predicts that, compared to PVC13, PHiD-CV entails lower costs and greater benefits if the latter is measured in terms of quality adjusted life years. PVC13 entails more life years gained than PHiD-CV, but those come at a cost of NOK 3.1 million (∼€0.4 million) per life year. The results indicate that PHiD-CV is cost-effective compared to PCV13 in the Norwegian setting. Copyright © 2011 Elsevier Ltd. All rights reserved.

Immunization with the 7-valent conjugate pneumococcal vaccine: impact evaluation, continuing surveillance and future perspectives.

PubMed

Bechini, Angela; Boccalini, Sara; Bonanni, Paolo

2009-05-26

The 7-valent Pneumococcal Conjugate Vaccine (PCV) showed high efficacy against invasive pneumococcal diseases caused by vaccine serotypes in children less than 2 years-old. Its effectiveness was confirmed under routine use in the US, Canada and several European countries. Disease surveillance and several studies showed that population indirect protection outweighs direct protection of immunized subjects. A substantial impact was also confirmed on pneumonia and acute otitis media. A limited increase in IPD caused by non-vaccine serotypes was registered to date, but far below the magnitude of the beneficial reduction in IPD due to vaccine serotypes. This fact underpins the need for ongoing improved surveillance. New tests based on PCR for the identification and typing of pneumococci represent a very interesting alternative to traditional cultural tests that should be evaluated in the near future. The World Health Organization has recognized the priority to introduce PCV into the routine infant immunization schedule in all countries, due to the extremely high yearly mortality toll for pneumococcal diseases in the world (1.6 million deaths estimated). Conjugate vaccines with additional serotypes are in advanced stage of development or under evaluation. These new products need to be compared with the existing vaccine, following WHO recommendations regarding correlates of protection, in order to show their possibility to substitute the current vaccine obtaining the same impressive level of efficacy and effectiveness.

[Paediatric Invasive Pneumococcal Disease Before Universal Vaccination: 1995 - 2015].

PubMed

Ferreira, Muriel; Oliveira, Henrique; Silva, Nuno Costa; Januário, Luís; Rodrigues, Fernanda

2017-06-30

Pneumococcal conjugate vaccine was introduced in the private market in Portugal in 2001, reaching over the years a moderately high coverage. In July 2015, it was included in the National Immunisation Program. The aim of this study was to characterize invasive pneumococcal disease in a pediatric hospital before universal use of the vaccine. Retrospective analysis of medical records of all children with Streptococcus pneumoniae identified by culture and/or molecular biology (available since 2008), in products obtained from sterile sites, from January 1995 to June 2015. We evaluated demographic, clinical and microbiological data. Serotype results are available since 2004. Over those 20 years, 112 invasive pneumococcal disease cases were identified, with a median age of 15 months (1 month - 15 years). The median number of cases /year was 4, the highest between 2001 - 2002 (8/year) and 2007 - 2012 (7 - 11/year). The identification occurred mostly in blood culture (72), cerebrospinal fluid (24), pleural fluid (11) an others (5). The most frequent diagnoses were pneumonia (38%), occult bacteraemia (34%) and meningitis (21%). Over the period under review, there was an increase of pneumonia and slight increase of OB, with meningitis cases remaining relatively unchanged. In the last two decades, there was no reduction in the number of cases of invasive pneumococcal disease. There was an increase in isolates from pneumonia and occult bacteraemia that might be due to the introduction of molecular biological methods for Streptococcus pneumoniae detection. Vaccine serotypes were predominant. This retrospective analysis before universal vaccination will contribute to evaluate the impact of vaccination in the Portuguese pediatric population.

Serotype 3 is a common serotype causing invasive pneumococcal disease in children less than 5 years old, as identified by real-time PCR.

PubMed

Selva, L; Ciruela, P; Esteva, C; de Sevilla, M F; Codina, G; Hernandez, S; Moraga, F; García-García, J J; Planes, A; Coll, F; Jordan, I; Cardeñosa, N; Batalla, J; Salleras, L; Dominguez, A; Muñoz-Almagro, C

2012-07-01

Serotype 3 is one of the most often detected pneumococcal serotypes in adults and it is associated with serious disease. In contrast, the isolation of serotype 3 by bacterial culture is unusual in children with invasive pneumococcal disease (IPD). The purpose of this study was to learn the serotype distribution of IPD, including culture-negative episodes, by using molecular methods in normal sterile samples. We studied all children<5 years of age with IPD admitted to two paediatric hospitals in Catalonia, Spain, from 2007 to 2009. A sequential real-time polymerase chain reaction (PCR) approach was added to routine methods for the detection and serotyping of pneumococcal infection. Among 257 episodes (219 pneumonia, 27 meningitis, six bacteraemia and five others), 33.5% were identified by culture and the rest, 66.5%, were detected exclusively by real-time PCR. The most common serotypes detected by culture were serotypes 1 (26.7%) and 19A (25.6%), and by real-time PCR, serotypes 1 (19.8%) and 3 (18.1%). Theoretical coverage rates by the PCV7, PCV10 and PCV13 vaccines were 10.5, 52.3 and 87.2%, respectively, for those episodes identified by culture, compared to 5.3, 31.6 and 60.2% for those identified only by real-time PCR. Multiplex real-time PCR has been shown to be useful for surveillance studies of IPD. Serotype 3 is underdiagnosed by culture and is important in paediatric IPD.

Molecular Typing of Pneumococci for Investigation of Linked Cases of Invasive Pneumococcal Disease ▿

PubMed Central

Pichon, Bruno; Moyce, Laura; Sheppard, Carmen; Slack, Mary; Turbitt, Deborah; Pebody, Richard; Spencer, David A.; Edwards, Justin; Krahé, Daniel; George, Robert

2010-01-01

In winter 2007-2008, an outbreak of pediatric pneumonia caused by serotype 5 pneumococci was identified in a northeast London suburb. Variable number of tandem repeat analyses clustered these pneumococci from the other serotype 5 pneumococci in the United Kingdom, highlighting the importance of this discriminative typing method in supporting epidemiological investigations. PMID:20164267

Pneumococcal vaccination programs and the burden of invasive pneumococcal disease in Ontario, Canada, 1995-2011.

PubMed

Rudnick, Wallis; Liu, Zhong; Shigayeva, Altynay; Low, Donald E; Green, Karen; Plevneshi, Agron; Devlin, Roslyn; Downey, James; Katz, Kevin; Kitai, Ian; Krajden, Sigmund; Ostrowska, Krystyna; Richardson, David; Richardson, Susan; Sarabia, Alicia; Silverman, Michael; Simor, Andrew E; Tyrrell, Gregory; McGeer, Allison

2013-12-02

In 1995, a publicly funded pneumococcal vaccination program for 23-valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). From 1995-2011, active, population-based surveillance for invasive pneumococcal disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada. 6404 IPD cases were included. After PPV23 program implementation in 1995, IPD due to PPV23 strains decreased 49% in older adults prior to PCV7 introduction. Estimated PPV23 efficacy in vaccine eligible adults was 42.2% (95% CI; 28.6-53.2%). IPD incidence due to PCV7 serotypes in children <5 years decreased significantly after PCV7 authorization and before introduction of a publicly funded PCV7 program. Seven years after PCV7 program implementation, the incidence of IPD due to PCV7 serotypes decreased to zero in children and by 88% in adults, however, overall IPD incidence remained unchanged in adults. In 2011, the incidence of IPD was 4.5 per 100,000 in adults aged 15-64 and 19.9 per 100,000 in adults aged over 65 years, with 45 serotypes causing disease. Between 1995 and 2011, the case fatality rate of IPD in adults decreased 2% per year (95% CI, -0.9% to -3.2%). In multivariable analysis, predictors of mortality included older age, chronic conditions, nursing home residence, current smoking, bacteraemia, and illness due to serotypes 3,11A, 19A, and 19F. While vaccination programs resulted in substantial public health benefits, herd immunity benefits of PCV7 were seen at low pediatric vaccination rates, and the case fatality rate of IPD has decreased, IPD will continue to be a cause of considerable morbidity and mortality in adults. Copyright © 2013. Published by Elsevier Ltd.

Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and Differences in Contribution to Complement Evasion.

PubMed

van der Maten, Erika; van den Broek, Bryan; de Jonge, Marien I; Rensen, Kim J W; Eleveld, Marc J; Zomer, Aldert L; Cremers, Amelieke J H; Ferwerda, Gerben; de Groot, Ronald; Langereis, Jeroen D; van der Flier, Michiel

2018-04-01

The pneumococcal capsular serotype is an important determinant of complement resistance and invasive disease potential, but other virulence factors have also been found to contribute. Pneumococcal surface protein C (PspC), a highly variable virulence protein that binds complement factor H to evade C3 opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG-anchored subgroup II. The prevalence of different PspC subgroups in invasive pneumococcal disease (IPD) and functional differences in complement evasion are unknown. The prevalence of PspC subgroups in IPD isolates was determined in a collection of 349 sequenced strains of Streptococcus pneumoniae isolated from adult patients. pspC deletion mutants and isogenic pspC switch mutants were constructed to study differences in factor H binding and complement evasion in relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD isolates than subgroup II pspC The presence of capsule was associated with a greater ability of bound factor H to reduce complement opsonization. Pneumococcal subgroup I PspC bound significantly more factor H and showed more effective complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We conclude that variation in the PspC subgroups, independent of capsule serotypes, affects pneumococcal factor H binding and its ability to evade complement deposition. Copyright © 2018 American Society for Microbiology.

Cost-Effectiveness of a Program to Eliminate Disparities in Pneumococcal Vaccination Rates in Elderly Minority Populations: An Exploratory Analysis

PubMed Central

Michaelidis, Constantinos I.; Zimmerman, Richard K.; Nowalk, Mary Patricia; Smith, Kenneth J.

2013-01-01

Objective Invasive pneumococcal disease is a major cause of preventable morbidity and mortality in the United States, particularly among the elderly (>65 years). There are large racial disparities in pneumococcal vaccination rates in this population. Here, we estimate the cost-effectiveness of a hypothetical national vaccination intervention program designed to eliminate racial disparities in pneumococcal vaccination in the elderly. Methods In an exploratory analysis, a Markov decision-analysis model was developed, taking a societal perspective and assuming a 1-year cycle length, 10-year vaccination program duration, and lifetime time horizon. In the base-case analysis, it was conservatively assumed that vaccination program promotion costs were $10 per targeted minority elder per year, regardless of prior vaccination status and resulted in the elderly African American and Hispanic pneumococcal vaccination rate matching the elderly Caucasian vaccination rate (65%) in year 10 of the program. Results The incremental cost-effectiveness of the vaccination program relative to no program was $45,161 per quality-adjusted life-year gained in the base-case analysis. In probabilistic sensitivity analyses, the likelihood of the vaccination program being cost-effective at willingness-to-pay thresholds of $50,000 and $100,000 per quality-adjusted life-year gained was 64% and 100%, respectively. Conclusions In a conservative analysis biased against the vaccination program, a national vaccination intervention program to ameliorate racial disparities in pneumococcal vaccination would be cost-effective. PMID:23538183

Burden of clinical infections due to S. pneumoniae during Hajj: A systematic review.

PubMed

Alqahtani, Amani S; Tashani, Mohamed; Ridda, Iman; Gamil, Amgad; Booy, Robert; Rashid, Harunor

2018-06-20

The burden of pneumococcal disease at Hajj has not been precisely evaluated through a systematic review. To this end we have conducted a systematic review on the burden of clinical infections due to Streptococcus pneumoniae among Hajj pilgrims. Major electronic databases including OVID Medline, Web of Science, OVID Embase, Social Sciences Citation Index, Google Scholar and relevant websites (e.g., online Saudi Epidemiology Bulletin) were searched by using MeSH terms and text words containing but not limited to 'Hajj', pneumonia and S. pneumoniae. This was buttressed by hand searching of reference lists of identified studies. Of 21 full text papers reviewed, nine articles were included in this review. Seven studies reported the burden of pneumococcal pneumonia and the other two reported the burden of invasive pneumococcal diseases including meningitis and sepsis. The proportion of pneumonia that was pneumococcal ranged from 1% to 54% of bacteriologically confirmed pneumonias. The pneumococcus accounted for 2/3rd of bacteriologically diagnosed meningitis cases, and 1/3rd of confirmed cases of sepsis. Case fatality rate of pneumococcal pneumonia was recorded in only two studies: 33.3% and 50%. Only one study provided data on antimicrobial susceptibility of S. pneumoniae isolates, reporting 33.3% to be penicillin resistant. None of the included studies provided data on serotype distribution of S. pneumoniae. This systematic review highlights the significance of pneumococcal disease during Hajj, and demonstrates paucity of data on its burden particularly on disease-causing serotype. Copyright © 2018. Published by Elsevier Ltd.

Combat pneumococcal infections: adhesins as candidates for protein-based vaccine development.

PubMed

Gamez, Gustavo; Hammerschmidt, Sven

2012-03-01

Streptococcus pneumoniae (pneumococcus) is an asymptomatic colonizer of the upper respiratory tract in humans. However, these apparently harmless bacteria have also a high virulence potential and are known as the etiologic agent of respiratory and life-threatening invasive diseases. Dissemination of pneumococci from the nasopharynx into the lungs or bloodstream leads to community-acquired pneumonia, septicaemia and meningitis. Traditionally, pneumococcal diseases are treated with antibiotics and prevented with polysaccharide-based vaccines. However, due to the dramatic increase in antibiotic resistance and limitations of the current available vaccines, the burden of diseases remains high. Thus, combating pneumococcal transmission and infections has emphasized the need for a new generation of protein-based vaccines. Interactions of pneumococci with soluble host proteins or cellular receptors are crucial for adherence, colonization, transmigration of host barriers and immune evasion. Therefore, surface-exposed proteins involved in these pathogenic processes and virtually expressed by all pneumococcal strains and serotypes are the prime potential targets for an immunogenic and highly protective pneumococcal-derived carrier protein of a vaccine. In this review, we will address the state of the art in deciphering, i). the conservation, distribution and pathogenic role of recently discovered pneumococcal adhesins in colonization and invasive diseases, ii). the interactions of these virulence factors with host-proteins and receptors, iii). the subversion of the host immune and cellular responses, and iv). the potential of pneumococcal adhesins as vaccine candidates.

An infant with concurrent serotype 6C invasive pneumococcal disease and infectious mononucleosis.

PubMed

Nishikawa-Nakamura, Naoko; Okada, Takafumi; Nishimura, Keiko; Iwai, Tsuyako; Ubukata, Kimiko; Iwata, Satoshi; Iwai, Asayuki

2017-11-01

Streptococcus pneumoniae is a main causative agent of serious invasive bacterial infections. However, concurrent infection with invasive pneumococcal disease (IPD) and viral infectious mononucleosis (IM) is rare. We report an infant with serotype 6C infection causing IPD occurring simultaneously with IM. A previously healthy 11-month-old girl referred to our hospital because of fever, leukopenia, and elevated C-reactive protein presented to us with disturbance of consciousness, tachycardia, tachypnea and agranulocytosis. Other findings included tonsillitis with purulent exudates and white spots, bilateral cervical adenopathy, and hepatosplenomegaly. We diagnosed her illness as sepsis and administered a broad-spectrum antibiotic, an antiviral agent, and granulocyte transfusions. After treatment was initiated, fever gradually decreased and general condition improved. IPD was diagnosed based upon isolation of S. pneumoniae of serotype 6C from blood cultures obtained on admission. Concurrently the girl had IM, based upon quantitation of Epstein-Barr viral DNA copies in blood and fluctuating serum antibody titers. Although simultaneous IPD and IM is a rare occurrence, this possibility is important to keep in mind. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Distribution of capsular types and antimicrobial susceptibility of invasive isolates of Streptococcus pneumoniae in Colombian children. Pneumococcal Study Group in Colombia.

PubMed

Castañeda, E; Leal, A L; Castillo, O; De La Hoz, F; Vela, M C; Arango, M; Trujillo, H; Levy, A; Gama, M E; Calle, M; Valencia, M L; Parra, W; Agudelo, N; Mejía, G I; Jaramillo, S; Montoya, F; Porras, H; Sánchez, A; Saa, D; Di Fabio, J L; Homma, A

1997-01-01

Streptococcus pneumoniae is the leading bacterial cause of childhood pneumonia in the developing world. This study describes the type distribution and antimicrobial susceptibility of invasive pneumococcal isolates from Colombian children and is part of the Sistema Regional de Vacunas (SIREVA), a PAHO regional initiative designed to determine the ideal serotype composition of a protein polysaccharide pneumococcal conjugate vaccine for use in children less than 5 years old in Latin America. In Colombia, during the study period, centres in Bogota, Medellin, and Cali collected 324 S. pneumoniae isolates from invasive diseases, 238 (73.5%) from children under the age of 2. Pneumonia was the clinical diagnosis in 41.3% cases, meningitis in 41%, and sepsis in 11.2%. The seven most frequent types included 14(21.9%), 5(10.5%), 23F(9.6%), 1(9%), 6B(9%), 19F(7.1%), and 6A(6.2%). The frequency of diminished susceptibility to penicillin (DSP) was 12%, with 8.9% of isolates showing intermediate level resistance and 3.1% showing high level resistance. Among DSP isolates, 23% were also resistant to cefotaxime, 33.3% to erythromycin, 48.7% to chloramphenicol, and 74.3% to trimethoprim/sulfamethoxazole. Multiple resistance was detected in 59% of the isolates that have DSP. Penicillin resistance was associated with types 23F (53.8%) and 14 (25.6%). These data provides information on capsular types prevalent in Colombia that will not only allow the formulation of an ideal vaccine for the region but also reinforce the need for ongoing regional surveillance.

Acute bacterial meningitis in infants and children: epidemiology and management.

PubMed

Agrawal, Shruti; Nadel, Simon

2011-12-01

Acute bacterial meningitis (ABM) continues to be associated with high mortality and morbidity, despite advances in antimicrobial therapy. The causative organism varies with age, immune function, immunization status, and geographic region, and empiric therapy for meningitis is based on these factors. Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis cause the majority of cases of ABM. Disease epidemiology is changing rapidly due to immunization practices and changing bacterial resistance patterns. Hib was the leading cause of meningitis in children prior to the introduction of an effective vaccination. In those countries where Hib vaccine is a part of the routine infant immunization schedule, Hib has now been virtually eradicated as a cause of childhood meningitis. Vaccines have also been introduced for pneumococcal and meningococcal diseases, which have significantly changed the disease profile. Where routine pneumococcal immunization has been introduced there has been a reported increase in invasive pneumococcal disease due to non-vaccine serotypes. In those parts of the world that have introduced conjugate meningococcal vaccines, there has been a significant change in the epidemiology of meningococcal meningitis. As a part of the United Nations Millennium Development Goal 4, the WHO has introduced a new vaccine policy to improve vaccine availability in resource poor countries. In addition, antibiotic resistance is an increasing problem, especially with pneumococcal infection. Effective treatment focuses on early recognition and use of effective antibiotics. This review will attempt to focus on the changing epidemiology of ABM in pediatric patients due to vaccination, the changing patterns of infecting bacterial serotypes due to vaccination, and on antibiotic resistance and its impact on current management strategies.

Pneumococcal meningitis and endocarditis in an infant: possible improved survival with factor V Leiden mutation.

PubMed

Mohapatra, Sitikant; Doulah, Assaf; Brown, Elspeth

2017-10-01

Streptococcus pneumoniae infections continue to remain associated with high morbidity and mortality. Although the incidence of invasive meningeal and/or lung disease are not uncommon, Streptococcus pneumoniae endocarditis is rare especially in healthy pediatric population. New studies have suggested a strong association between factor V leiden (FVL) mutation and favorable outcomes in critically ill children. A healthy 10 month old presented with sepsis and meningeal signs, was later confirmed to have Streptococcus pneumoniae meningitis and endocarditis. She was found to have factor V leiden mutation and made a complete recovery despite initial complications. Presence of factor V leiden mutation in critically ill children with severe septicaemia possibly contributes to better outcomes. What is known: • Mortality and morbidity remain high with invasive pneumococcal disease. • Pneumococcal endocarditis is rare in healthy pediatric population and results in significant morbidity and mortality What is new: • New studies have suggested a strong association between factor V leiden (FVL) mutation and favorable outcomes in critically ill children. • The presence of factor V mutation in children with extensive invasive pneumococcal disease possibly contributes to a better outcome.

Epidemiological burden of invasive pneumococcal disease in children and adolescents with predisposing risk factors.

PubMed

Falleiros-Arlant, Luiza Helena; Berezin, Eitan Naaman; Avila-Aguero, Maria Luisa; Pirez, Maria Catalina; Gentile, Angela; Richardson, Vesta; Brea, Jose; Mariño, Cristina

2015-09-01

Some medical conditions constitute important risk factors for the development of invasive pneumococcal diseases in children and adolescents aged from 5 to 19 years. Conjugate vaccines have potential efficacy in this scenario, but are not available in many Latin American public healthcare systems for this age group. This study aimed to estimate the preventable fraction of invasive pneumococcal diseases among individuals aged from 5 to 19 years with associated risk factors for its development. Data regarding the Latin America population, risk factors prevalence and conjugate vaccines efficacy were obtained from the literature. Total population at risk ranged from 17.3 to 64.6 million of individuals and asthma was the most impacting risk factor. According to SIREVA, PCV13 provided a 62.9% serotypes coverage in individuals from 5 to 29 years in 2012, potentially increasing the covered population from [8,338,457-31,057,620] with PCV10 to [10,906,356-40,622,078] with PCV13. To date, according to available efficacy data, the hypothetically immunized population ranged from 11.4 to 42.4 million, representing 7.0% to 26.0% of the total population in this age group. Vaccination in risk groups should be encouraged, as it potentially contributes to the reduction in the number of cases of invasive pneumococcal disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Health Economic Impact of Universal Infant Vaccination with the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as Compared with 13-Valent Pneumococcal Conjugate Vaccine in Hong Kong.

PubMed

Lee, Kenneth K C; Chia Wu, David Bin; Topachevskyi, Oleksandr; Delgleize, Emmanuelle; DeAntonio, Rodrigo

2013-05-01

Pneumococcal universal vaccination in Hong Kong was introduced in 2009. We assessed the health and economic impact of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PCV-10) compared with the current 13-valent pneumococcal conjugate vaccine (PCV-13) recommended for Hong Kong in 2011, providing new elements to be considered by public health authorities in the future decision-making process for pneumococcal vaccines in this country. An analytical model was used to estimate the annual economic and health outcomes of invasive pneumococcal disease (IPD), community-acquired pneumonia, and acute otitis media (AOM), including nontypeable H. influenzae-related AOM, for a birth cohort in Hong Kong from the payer perspective with a 10-year horizon. Clinical impact including morbidity-mortality, quality-adjusted life-years (QALYs), incremental costs, and cost-effectiveness comparing PCV-10 and PCV-13 were estimated. Probabilistic sensitivity analyses by using alternate scenarios were performed. Model projections indicate that PCV-13 and PCV-10 have approximately equivalent impact on the prevention of deaths caused by IPD and pneumonia. PCV-13 is projected to prevent 6 additional cases of IPD, whereas PCV-10 is projected to prevent 13,229 additional AOM cases and 101 additional QALYs. For the base case, PCV-10 vaccination is estimated to save 44.6 million Hong Kong dollars (34.1 million Hong Kong dollars discounted). Sensitivity analysis indicated that PCV-10 would generate more QALYs and save costs as compared with PCV-13. Universal infant vaccination with new available pneumococcal vaccines is expected to generate a significant additional impact on reducing the burden of pneumococcal diseases in Hong Kong. PCV-10 vaccination would be potentially a cost-saving strategy compared with PCV-13 vaccination, generating better cost offsets and higher QALY gains. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Risk factors for invasive pneumococcal disease among children less than 5 years of age in a high HIV prevalence setting, South Africa, 2010 to 2012.

PubMed

von Mollendorf, Claire; Cohen, Cheryl; de Gouveia, Linda; Naidoo, Nireshni; Meiring, Susan; Quan, Vanessa; Lindani, Sonwabo; Moore, David P; Reubenson, Gary; Moshe, Mamokgethi; Eley, Brian; Hallbauer, Ute M; Finlayson, Heather; Madhi, Shabir A; Conklin, Laura; Zell, Elizabeth R; Klugman, Keith P; Whitney, Cynthia G; von Gottberg, Anne

2015-01-01

Invasive pneumococcal disease (IPD) causes significant disease burden, especially in developing countries, even in the era of pneumococcal conjugate vaccine and maternal-to-child HIV transmission prevention programs. We evaluated factors that might increase IPD risk in young children in a high HIV prevalence setting. We conducted a case-control study using IPD cases identified at 24 Group for Enteric, Respiratory and Meningeal disease Surveillance-South Africa program sites (2010-2012). At least 4 controls were matched by age, HIV status and hospital to each case. Potential risk factors were evaluated using multivariable conditional logistic regression. In total, 486 age-eligible cases were enrolled. Factors associated with IPD in HIV-uninfected children (237 cases, 928 controls) included siblings <5 years [adjusted odds ratio (aOR) = 1.68, 95% confidence interval (CI): 1.16-2.46], underlying medical conditions (aOR = 1.99, CI 1.22-3.22), preceding upper respiratory tract infection (aOR = 1.79, CI 1.19-2.69), day-care attendance (aOR = 1.58, CI 1.01-2.47), perinatal HIV exposure (aOR = 1.62, CI 1.10-2.37), household car ownership (aOR = 0.45, CI 0.25-0.83) and ≥2 7-valent pneumococcal conjugate vaccine doses (aOR = 0.67, CI 0.46-0.99). Among HIV-infected children (124 cases, 394 controls), IPD-associated factors included malnutrition (aOR = 2.68, CI 1.40-5.14), upper respiratory tract infection (aOR = 3.49, CI 1.73-7.03), tuberculosis in the last 3 months (aOR = 5.12, CI 1.69-15.50) and current antiretroviral treatment (aOR = 0.13, CI 0.05-0.38). Previously identified factors related to poverty, poor health and intense exposure continue to be risk factors for IPD in children. Ensuring delivery of pneumococcal conjugate vaccine and antiretroviral treatment are important for improving disease prevention.

Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria.

PubMed

Setchanova, Lena; Murdjeva, Marianna; Stancheva, Iglika; Alexandrova, Alexandra; Sredkova, Maria; Stoeva, Temenuga; Yoneva, Magda; Kurchatova, Anna; Mitov, Ivan

The 10-valent pneumococcal conjugate vaccine (PCV10) has been included in Bulgarian Childhood Immunization Program since 2010. This study aimed to assess serotype distribution and antimicrobial resistance of 198 invasive and non-invasive Streptococcus pneumoniae strains that had been isolated in Bulgaria during 2011-2016 from patients with invasive (IPD) and non-invasive (NIPD) pneumococcal diseases. The most common invasive serotypes were 3 (10.1%), 19F (4.0%), and 7F (3.0%). A significant decrease in the proportion of invasive vaccine types (VTs) from 64.2% to 35.2% was found in comparison with pre-vaccine era. The most common serotypes among middle ear fluids were 3, 19A and 19F (5.6% each), and VTs fell down from 66.4% to 40.0% in post-PCV10 period. Among respiratory isolates, the most prevalent serotypes were some emergent serotypes such as 15A/B/C (5.0%), 19A, and 6C (4.0% each). VTs decreased significantly (16.3%) among vaccinated children compared to unvaccinated children and adults (44.0%). Two non-VTs (19A and 6C) have increased significantly more (p<0.05) in vaccinated children than in unvaccinated patients. The rates of antibiotic nonsusceptible S. pneumoniae in Bulgaria remained high in post-PCV10 era. Among all source of isolates, antimicrobial nonsusceptibility rates were: oral penicillin - 46.5%, trimethoprim-sulfamethoxazole - 45.4%, erythromycin - 43.9%, tetracycline - 37.4%, and multidrug-resistance (MDR) was 44%. The most common MDR serotypes were 19F, 19A, 6A/C, 15A/B/C and 23A. Our results proved that PCV10 vaccination substantially reduced VTs pneumococcal IPD and NIPD. There has been a shift in the distribution of S. pneumoniae serotypes mostly in vaccinated children but also in the whole population and strong serotype-specific antibiotic resistance was observed after vaccine implementation. Therefore, it is important to continue monitoring serotype changes and pneumococcal resistance among all patient ages in addition to aid in determining the long-term effectiveness of PCV10 interventions. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Prevalence of pneumococcal disease, serotype distribution, and antimicrobial susceptibility in Mexican children younger than 5 years of age.

PubMed

Bautista-Márquez, Aurora; Richardson, Vesta; Ortiz-Orozco, Oscar; Luna-Cruz, Maria Edilia; Carnalla-Barajas, M Noemí; Echaniz-Avilés, Gabriela; Bobadilla-del Valle, Miriam; Martínez-Medina, Lucila; Montalvo-Vázquez, Ana María; de la Re-Montaño, Norma; Anchondo-Martínez, Ivette; Tinoco-Favila, Juan Carlos; Martínez-Aguilar, Gerardo; Yberri-Zárate, Israel; Girón-Hernández, José Antonio; Sifuentes-Osornio, José; Guerrero, M Lourdes; Ruiz-Palacios, Guillermo M

2013-02-01

Streptococcus pneumoniae constitutes one of the main causes of sepsis, bacteremia and meningitis (pneumococcal invasive disease - PID), and pneumonia in infants and small children. Antipneumococcal vaccination in Mexico is expected to be a useful strategy to reduce morbimortality due to this cause. We undertook this study to determine the prevalence of PID and pneumonia and the PCV vaccination status of affected children as well as serotype distribution and antimicrobial susceptibility of pneumococcal strains responsible for PID in infants and small children in Mexico. From March 2010-June 2011, a prospective multicenter study was carried out in four states in Mexico to determine the prevalence of bacteremia, meningitis, septic arthritis and pneumonia due to S. pneumoniae and other microorganisms in children from 28 days-59 months of age. Isolated pneumococcal strains were serotyped and their antimicrobial resistance determined. During the study period, 545 children were diagnosed with bacteremia, meningitis, septic arthritis or pneumonia; 46.7% of these clinical entities occurred among children <12 months of age. Community-acquired pneumonia was the most prevalent disease. It was possible to identify a causal microorganism in 55 cases, from which 80% were S. pneumoniae. Fifteen percent of patients with PID died. The most prevalent pneumococcal serotypes were 19A, 35B, 19F and 6A. 10.2% of nonmeningeal strains were resistant to meropenem and 82% were resistant to TMP/SMX. This study shows that pneumococcus was the most common bacteria isolated in the studied population, although epidemiological and laboratory-based surveillance still needs improvement. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Choline Binding Proteins from Streptococcus pneumoniae: A Dual Role as Enzybiotics and Targets for the Design of New Antimicrobials

PubMed Central

Maestro, Beatriz; Sanz, Jesús M.

2016-01-01

Streptococcus pneumoniae (pneumococcus) is an important pathogen responsible for acute invasive and non-invasive infections such as meningitis, sepsis and otitis media, being the major cause of community-acquired pneumonia. The fight against pneumococcus is currently hampered both by insufficient vaccine coverage and by rising antimicrobial resistances to traditional antibiotics, making necessary the research on novel targets. Choline binding proteins (CBPs) are a family of polypeptides found in pneumococcus and related species, as well as in some of their associated bacteriophages. They are characterized by a structural organization in two modules: a functional module (FM), and a choline-binding module (CBM) that anchors the protein to the choline residues present in the cell wall through non-covalent interactions. Pneumococcal CBPs include cell wall hydrolases, adhesins and other virulence factors, all playing relevant physiological roles for bacterial viability and virulence. Moreover, many pneumococcal phages also make use of hydrolytic CBPs to fulfill their infectivity cycle. Consequently, CBPs may play a dual role for the development of novel antipneumococcal drugs, both as targets for inhibitors of their binding to the cell wall and as active cell lytic agents (enzybiotics). In this article, we review the current state of knowledge about host- and phage-encoded pneumococcal CBPs, with a special focus on structural issues, together with their perspectives for effective anti-infectious treatments. PMID:27314398

Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection.

PubMed

Alhamdi, Yasir; Neill, Daniel R; Abrams, Simon T; Malak, Hesham A; Yahya, Reham; Barrett-Jolley, Richard; Wang, Guozheng; Kadioglu, Aras; Toh, Cheng-Hock

2015-05-01

Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections.

Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

PubMed Central

Alhamdi, Yasir; Neill, Daniel R.; Abrams, Simon T.; Malak, Hesham A.; Yahya, Reham; Barrett-Jolley, Richard; Wang, Guozheng; Kadioglu, Aras; Toh, Cheng-Hock

2015-01-01

Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections. PMID:25973949

Diversity of Pneumolysin and Pneumococcal Histidine Triad Protein D of Streptococcus pneumoniae Isolated from Invasive Diseases in Korean Children.

PubMed

Yun, Ki Wook; Lee, Hyunju; Choi, Eun Hwa; Lee, Hoan Jong

2015-01-01

Pneumolysin (Ply) and pneumococcal histidine triad protein D (PhtD) are candidate proteins for a next-generation pneumococcal vaccine. We aimed to analyze the genetic diversity and antigenic heterogeneity of Ply and PhtD for 173 pneumococci isolated from invasive diseases in Korean children. Allele was designated based on the variation of amino acid sequence. Antigenicity was predicted by the amino acid hydrophobicity of the region. There were seven and 39 allele types for the ply and phtD genes, respectively. The nucleotide sequence identity was 97.2%-99.9% for ply and 91.4%-98.0% for phtD gene. Only minor variations in hydrophobicity were noted among the antigenicity plots of Ply and PhtD. Overall, the allele types of the ply and phtD genes were remarkably homogeneous, and the antigenic diversity of the corresponding proteins was very limited. The Ply and PhtD could be useful antigens for universal pneumococcal vaccines.

Serotype distribution of Streptococcus pneumoniae in children with invasive diseases in Turkey: 2008-2014.

PubMed

Ceyhan, Mehmet; Ozsurekci, Yasemin; Gürler, Nezahat; Öksüz, Lütfiye; Aydemir, Sohret; Ozkan, Sengul; Yuksekkaya, Serife; Keser Emiroglu, Melike; Gültekin, Meral; Yaman, Akgün; Kiremitci, Abdurrahman; Yanık, Keramettin; Karli, Arzu; Ozcinar, Hatice; Aydin, Faruk; Bayramoglu, Gulcin; Zer, Yasemin; Gulay, Zeynep; Gayyurhan, Efgan Dogan; Gül, Mustafa; Özakın, Cüneyt; Güdücüoğlu, Hüseyin; Perçin, Duygu; Akpolat, Nezahat; Ozturk, Candan; Camcıoğlu, Yıldız; Karadağ Öncel, Eda; Çelik, Melda; Şanal, Laser; Uslu, Hakan

2016-01-01

Successful vaccination policies for protection from invasive pneumococcal diseases (IPD) dependent on determination of the exact serotype distribution in each country. We aimed to identify serotypes of pneumococcal strains causing IPD in children in Turkey and emphasize the change in the serotypes before and after vaccination with 7-valent pneumococcal conjugate vaccine (PCV-7) was included and PCV-13 was newly changed in Turkish National Immunization Program. Streptococcus pneumoniae strains were isolated at 22 different hospitals of Turkey, which provide healthcare services to approximately 65% of the Turkish population. Of the 335 diagnosed cases with S. pneumoniae over the whole period of 2008-2014, the most common vaccine serotypes were 19F (15.8%), 6B (5.9%), 14 (5.9%), and 3 (5.9%). During the first 5 y of age, which is the target population for vaccination, the potential serotype coverage ranged from 57.5 % to 36.8%, from 65.0% to 44.7%, and from 77.4% to 60.5% for PCV-7, PCV-10, and PCV-13 in 2008-2014, respectively. The ratio of non-vaccine serotypes was 27.2% in 2008-2010 whereas was 37.6% in 2011-2014 (p=0.045). S. penumoniae serotypes was less non-susceptible to penicillin as compared to our previous results (33.7 vs 16.5 %, p=0.001). The reduction of those serotype coverage in years may be attributed to increasing vaccinated children in Turkey and the increasing non-vaccine serotype may be explained by serotype replacement. Our ongoing IPD surveillance is a significant source of information for the decision-making processes on pneumococcal vaccination.

Acquisition of Pneumococci Specific Effector and Regulatory Cd4+ T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue

PubMed Central

Pido-Lopez, Jeffrey; Kwok, William W.; Mitchell, Timothy J.; Heyderman, Robert S.; Williams, Neil A.

2011-01-01

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4+ T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25hi T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4+ T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines. PMID:22144893

[Pneumococcal vaccine recommendations in chronic respiratory diseases].

PubMed

Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A

2014-09-01

Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Invasive pneumococcal disease in infants younger than 90 days before and after introduction of PCV7.

PubMed

Olarte, Liset; Ampofo, Krow; Stockmann, Chris; Mason, Edward O; Daly, Judy A; Pavia, Andrew T; Byington, Carrie L

2013-07-01

Introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) changed the epidemiology of invasive pneumococcal disease (IPD). We evaluated the changes that occurred after PCV7 introduction among Utah infants aged 1 to 90 days, too young to be fully immunized. We identified children <18 years with culture-confirmed IPD from 1997-2010. We analyzed demographic, clinical, and serotype data for infants aged 1-90 days. The pre- and post-vaccine introduction periods spanned 1997-2000 and 2001-2010, respectively. Of 513 children with IPD, 36 were 1 to 90 days and accounted for 7% of IPD cases in both the pre- and post-vaccine introduction period. The pre-vaccine IPD incidence rate was 5.0 per 100 000 live births, and was unchanged in the post-vaccine introduction period. IPD caused by PCV7 serotypes decreased by 74% (from 2.2 to 0.58 per 100 000), whereas non-vaccine serotype IPD increased by 57% (from 2.8 to 4.4 per 100 000). Sixteen infants (44%) required intensive care, and 3 (8%) died. Bacteremia without focus (56%) and meningitis (44%) were the predominant syndromes in the pre- and post-vaccine introduction periods, respectively. In the post-vaccine introduction period, serotype 7F was the most common serotype among infants and was responsible for 50% of meningitis. The incidence of IPD in Utah infants aged 1 to 90 days caused by PCV7 serotypes decreased after PCV7 introduction, but overall incidence was unchanged. In the post-vaccine introduction period, serotype 7F predominated in this age group and was associated with meningitis.

Risk factors for invasive pneumococcal disease in a community with a high proportion of non vaccine serotypes.

PubMed

Ciruela, Pilar; Soldevila, Núria; Hernández, Sergi; Selva, Laura; de Sevilla, Mariona F; García-García, Juan José; Moraga, Fernando; Planes, Ana María; Muñoz-Almagro, Carmen; Domínguez, Angela

2013-01-30

The aim of this study was to investigate factors associated with vaccination with 7-pneumococcal conjugate vaccine (PCV7) and risk factors for invasive pneumococcal disease (IPD) and for penicillin-nonsusceptible strains in a community with intermediate vaccination coverage. We conducted a prospective, matched case-control study in children aged 3-59 months with IPD admitted to two hospitals in Catalonia. Three controls matched by hospital, age, sex, date of hospitalization and risk medical conditions were selected for each case. We calculated odds ratios for potential risk factors using logistic regression. Of the 1075 children included, 46.6% were considered fully vaccinated by age. 91.1% of cases were caused by non-PCV7 serotypes. Vaccination with PCV7 was positively associated with attending day care or school and negatively associated with age 24-59 months, >4 cohabitants and low social class. Attending day care or school and >4 cohabitants were risk factors for IPD. Previous antibiotic treatment in children aged 24-59 months was a protective factor for IPD; however, antibiotic use in the previous month and age <24 months were associated with penicillin-nonsusceptible IPD. In a community where IPD in children aged <5 years is caused mainly by non-PCV7 Streptococcus pneumoniae serotypes and where vaccine coverage is only intermediate, attending day care or school, age <24 months, >4 cohabitants and social class were associated with vaccination. Attending day care or school was a strong risk factor for IPD, while vaccination was protective in children aged <24 months. Age and antibiotic use in the previous month were associated with penicillin-nonsusceptible IPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Population-based incidence of invasive haemophilus influenzae and pneumococcal diseases before the introduction of vaccines in Japan.

PubMed

Nakamura, Riko; Togashi, Takehiro

2013-12-01

Before the introduction of vaccines, the incidence of bacterial meningitis among children aged 28 days to 5 years was 8.48, Haemophilus influenzae type-b meningitis was 5.65 and Streptococcus pneumoniae meningitis was 1.85 per 100,000 person-years in Hokkaido, Japan. The incidence of bacteremia caused by S. pneumoniae was 60.15 and H. influenzae was 18.80.

Serotype changes in adult invasive pneumococcal infections in Portugal did not reduce the high fraction of potentially vaccine preventable infections.

PubMed

Horácio, Andreia N; Diamantino-Miranda, Jorge; Aguiar, Sandra I; Ramirez, Mário; Melo-Cristino, José

2012-01-05

We determined the serotype and antimicrobial susceptibility of 1100 isolates responsible for adult invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes 3 (13%), 1 (12%), 7F (11%), 19A (10%) and 14 (7%) were the most frequent causes of IPD and the two later serotypes accounted for the majority of erythromycin and penicillin nonsusceptible isolates. Serotype 1 was associated with younger adults whereas serotype 3 was associated with older adults. Despite the availability of the 23-valent polysaccharide vaccine (PPV23) in Portugal since 1996, the proportion of PPV23 preventable IPD remained stable and above 80%. Comparing with previous data from Portugal, we showed a continued decline of the serotypes included in the 7-valent conjugate vaccine (PCV7) in adult IPD and a rise of serotypes included in the 13-valent conjugate vaccine, increasing its potential coverage of adult IPD to 70% in 2008. Penicillin non-susceptibility remained stable (17%) whereas erythromycin resistance (18%) has continued to rise in the post-PCV7 years. Copyright © 2011 Elsevier Ltd. All rights reserved.

Genetic diversity of pneumococcal surface protein A in invasive pneumococcal isolates from Korean children, 1991-2016.

PubMed

Yun, Ki Wook; Choi, Eun Hwa; Lee, Hoan Jong

2017-01-01

Pneumococcal surface protein A (PspA) is an important virulence factor of pneumococci and has been investigated as a primary component of a capsular serotype-independent pneumococcal vaccine. Thus, we sought to determine the genetic diversity of PspA to explore its potential as a vaccine candidate. Among the 190 invasive pneumococcal isolates collected from Korean children between 1991 and 2016, two (1.1%) isolates were found to have no pspA by multiple polymerase chain reactions. The full length pspA genes from 185 pneumococcal isolates were sequenced. The length of pspA varied, ranging from 1,719 to 2,301 base pairs with 55.7-100% nucleotide identity. Based on the sequences of the clade-defining regions, 68.7% and 49.7% were in PspA family 2 and clade 3/family 2, respectively. PspA clade types were correlated with genotypes using multilocus sequence typing and divided into several subclades based on diversity analysis of the N-terminal α-helical regions, which showed nucleotide sequence identities of 45.7-100% and amino acid sequence identities of 23.1-100%. Putative antigenicity plots were also diverse among individual clades and subclades. The differences in antigenicity patterns were concentrated within the N-terminal 120 amino acids. In conclusion, the N-terminal α-helical domain, which is known to be the major immunogenic portion of PspA, is genetically variable and should be further evaluated for antigenic differences and cross-reactivity between various PspA types from pneumococcal isolates.

Potential Impact of Conjugate Vaccine on the Incidence of Invasive Pneumococcal Disease among Children in Scotland

PubMed Central

Clarke, Stuart C.; Jefferies, Johanna M.; Smith, Andrew J.; McMenamin, Jim; Mitchell, Timothy J.; Edwards, Giles F. S.

2006-01-01

We sought to determine the potential impact of seven-valent pneumococcal conjugate vaccine on the incidence of invasive pneumococcal disease (IPD) among children in Scotland. Invasive pneumococci from blood and cerebrospinal fluid, isolated between 2000 and 2004 from all children aged less than 5 years in Scotland, were characterized by serotyping. Using reported efficacy data of the seven-valent pneumococcal conjugate vaccine (PCV7) along with likely coverage rates, we made an estimation of the potential impact on the incidence of IPD among children in Scotland. A total of 217 pneumococci were characterized into 22 different serogroups/types, the most common, in rank order, being 14, 19F, 6B, 18C, 23F, 9V, 4, 1, 19A, and 6A. Estimated serotype coverage for PCV7 was 76.5% in those aged less than 5 years of age but increased to 88.9% for those aged 1 year. By using serotype coverage and estimates of vaccine efficacy and uptake, the potential impact of the vaccine for those greater than 2 months of age, but less than 5 years, was estimated as 67.3%, leading to an average of 29 preventable cases per year. The introduction of PCV7 into the childhood immunization schedule would reduce the burden of pneumococcal disease in children, and the incidence would be particularly reduced in those children aged 1 year. Additional benefits may be gained in adults through herd protection. Continued surveillance of IPD is required before, during, and after the introduction of PCV7. PMID:16597842

Hospitalizations for pneumonia, invasive diseases and otitis in Tuscany (Italy), 2002-2014: Which was the impact of universal pneumococcal pediatric vaccination?

PubMed

Boccalini, Sara; Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bonanni, Paolo; Bechini, Angela

2017-02-01

Streptococcus pneumoniae is the main causative organism of acute media otitis in children and meningitis and bacterial pneumonia in the community. Since 2008 in Tuscany, central Italy, the pneumococcal conjugate vaccine (7-valent vaccine, switched to 13-valent vaccine in 2010) was actively offered free of charge to all newborns. Aim of the study is to evaluate the impact of pneumococcal pediatric vaccination in the Tuscan population on hospitalizations potentially caused by S. pneumoniae, during pre-vaccination (PVP, 2002-2007) and vaccination period (VP, 2009-2014). We analyzed hospital discharge records (HDRs) of all hospitals in Tuscany from 2002 to 2014. Hospitalizations potentially due to pneumococcal diseases were 347, 221. The general hospitalization rate was 716/100,000 inhabitants during PVP and 753/100,000 in VP, with a decrease of 29.1% in the age-group 0-9 y ("target" of the vaccination program) and an increase of 75.7% in subjects >64 y of age. During VP, admission days and hospitalization costs increased (6.2% and 24.2%, respectively), especially in patients >64 y (12.9% and 33.8%, respectively); in children <10 y decreased by 21.2% and 12.8%, respectively. The pneumococcal pediatric vaccination resulted in the decrease of hospitalizations in younger but the expected indirect effect in the elderly was not reported, justifying the Tuscan recommendation to extend the vaccination to subjects > 64 y.

[Anti-pneumococcal vaccine coverage for hospitalized risk patients: Assessment and suggestions for improvements].

PubMed

Richard, C; Le Garlantezec, P; Lamand, V; Rasamijao, V; Rapp, C

2016-05-01

Streptococcus pneumoniae can cause invasive infections. Incidence and severity are linked to patients' risk factors. Due to the resistance to leading antibiotics, the anti-pneumococcal vaccination has become a major public health issue. The purpose of this survey was to evaluate the anti-pneumococcal vaccine coverage in a population of adults with risk factors. This was a prospective study that included patients with at least one recommendation for pneumococcal vaccination as indicated by the Weekly Epidemiological Bulletin (BEH), to which three further US recommendations were added (diabetes, obesity and age>65years). One hundred and thirty-four patients with an average age of 70 years were included. The physician could only confirm 68 % of the patients' vaccination status. Vaccination coverage as recommended by the BEH board was 30 % (n=54). All HIV patients were vaccinated (n=2) and the vaccination coverage was 75 % (n=8) for patients treated for autoimmune diseases and only 10 % (n=20) for patients treated with chemotherapy. Patients with no vaccination didn't know the existence of the vaccine or didn't know that vaccination was recommended to them. This study has highlighted a deficit in pneumococcal vaccination coverage and a high level of ignorance of the existence of recommended vaccination. In addition to awareness campaign for patients and caregiver training, the expansion of the vaccine e-book utilization could improve the vaccination status. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Community-acquired pneumonia among smokers.

PubMed

Almirall, Jordi; Blanquer, José; Bello, Salvador

2014-06-01

Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Rapid reduction in invasive pneumococcal disease after introduction of PCV7 into the National Immunization Plan in Israel.

PubMed

Ben-Shimol, S; Greenberg, D; Givon-Lavi, N; Elias, N; Glikman, D; Rubinstein, U; Dagan, R

2012-10-12

The 7-valent conjugated vaccine (PCV7) was introduced into the Israeli National Immunization Program (NIP) in July 2009 (2, 4, 12 months schedule; 2 dose catch-up in second year of life). Nationwide active prospective surveillance on invasive pneumococcal disease (IPD) has been conducted in children since 1989. In the current study, IPD epidemiology in children <5 years during the 20 years before and 18 months after PCV7 NIP initiation, is reported. All 27 centers performing blood/cerebrospinal fluid (CSF) cultures in children reported monthly IPD cases. Capture-recapture approach was used for completeness. During 1989-2010, 6022 IPD cases were reported in children <5 years; PCV7 serotypes (7VST) caused ∼50% of all episodes. In 2009 and 2010, 7VST IPD incidences <5 years of age (per 100,000) were 15.9 and 5.4, respectively (a 43% and 81% decrease, respectively) compared to 2003-2007 (mean incidence 27.8). Serotype 6A dynamics resembled those of 7VST. The respective overall IPD incidence decreases were 23% and 42%. The incidence dynamics of serotypes 1, 3, 5, 7F and 19A IPD were characterized by considerable fluctuations over the study period without any upwards or downwards trend in any of the age groups. The overall incidence of serotypes not included in the 13-valent pneumococcal conjugate vaccine (PCV13) did not vary significantly during the study period. By the end of 2010, 72% of the remaining IPD was caused by pneumococcal serotypes included in PCV13. An active prospective long-term surveillance, showed a rapid and sharp decline in IPD in children <5 years following initiation of NIP with PCV7. No serotype replacement has been observed so far. The transition from PCV7 to PCV13 initiated in October 2010 may lead to a further substantial decrease in IPD. Follow-up is needed to better determine the long-term PCV effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

Childhood pneumococcal disease in Africa - A systematic review and meta-analysis of incidence, serotype distribution, and antimicrobial susceptibility.

PubMed

Iroh Tam, Pui-Ying; Thielen, Beth K; Obaro, Stephen K; Brearley, Ann M; Kaizer, Alexander M; Chu, Haitao; Janoff, Edward N

2017-04-04

Determining the incidence, disease-associated serotypes and antimicrobial susceptibility of invasive pneumococcal disease (IPD) among children in Africa is essential in order to monitor the impact of these infections prior to widespread introduction of the pneumococcal conjugate vaccine (PCV). To provide updated estimates of the incidence, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae causing disease in Africa, we performed a systematic review of articles published from 2000 to 2015 using Ovid Medline and Embase. We included prospective and surveillance studies that applied predefined diagnostic criteria. Meta-analysis for all pooled analyses was based on random-effects models. We included 38 studies consisting of 386,880 participants in 21 countries over a total of 350,613 person-years. The pooled incidence of IPD was 62.6 (95% CI 16.9, 226.5) per 100,000 person-years, including meningitis which had a pooled incidence of 24.7 (95% CI 11.9, 51.6) per 100,000 person-years. The pooled prevalence of penicillin susceptibility was 78.1% (95% CI 61.9, 89.2). Cumulatively, PCV10 and PCV13 included 66.9% (95% CI 55.9, 76.7) and 80.6% (95% CI 66.3, 90.5) of IPD serotypes, respectively. Our study provides an integrated and robust summary of incidence data, serotype distribution and antimicrobial susceptibility for S. pneumoniae in children ≤5years of age in Africa prior to widespread introduction of PCV on the continent. The heterogeneity of studies and wide range of incidence rates across the continent indicate that surveillance efforts should be intensified in all regions of Africa to improve the integrity of epidemiologic data, vaccine impact and cost benefit. Although the incidence of IPD in young children in Africa is substantial, currently available conjugate vaccines are estimated to cover the majority of invasive disease-causing pneumococcal serotypes. These data provide a reliable baseline from which to monitor the impact of the broad introduction of PCV. Copyright © 2017 Elsevier Ltd. All rights reserved.

Streptococcus pneumoniae Translocates into the Myocardium and Forms Unique Microlesions That Disrupt Cardiac Function

PubMed Central

Brown, Armand O.; Mann, Beth; Gao, Geli; Hankins, Jane S.; Humann, Jessica; Giardina, Jonathan; Faverio, Paola; Restrepo, Marcos I.; Halade, Ganesh V.; Mortensen, Eric M.; Lindsey, Merry L.; Hanes, Martha; Happel, Kyle I.; Nelson, Steve; Bagby, Gregory J.; Lorent, Jose A.; Cardinal, Pablo; Granados, Rosario; Esteban, Andres; LeSaux, Claude J.; Tuomanen, Elaine I.; Orihuela, Carlos J.

2014-01-01

Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD. PMID:25232870

Retrospective economic evaluation of childhood 7-valent pneumococcal conjugate vaccination in Australia: Uncertain herd impact on pneumonia critical.

PubMed

Newall, A T; Reyes, J F; McIntyre, P; Menzies, R; Beutels, P; Wood, J G

2016-01-12

Retrospective cost-effectiveness analyses of vaccination programs using routinely collected post-implementation data are sparse by comparison with pre-program analyses. We performed a retrospective economic evaluation of the childhood 7-valent pneumococcal conjugate vaccine (PCV7) program in Australia. We developed a deterministic multi-compartment model that describes health states related to invasive and non-invasive pneumococcal disease. Costs (Australian dollars, A$) and health effects (quality-adjusted life years, QALYs) were attached to model states. The perspective for costs was that of the healthcare system and government. Where possible, we used observed changes in the disease rates from national surveillance and healthcare databases to estimate the impact of the PCV7 program (2005-2010). We stratified our cost-effectiveness results into alternative scenarios which differed by the outcome states included. Parameter uncertainty was explored using probabilistic sensitivity analysis. The PCV7 program was estimated to have prevented ∼5900 hospitalisations and ∼160 deaths from invasive pneumococcal disease (IPD). Approximately half of these were prevented in adults via herd protection. The incremental cost-effectiveness ratio was ∼A$161,000 per QALY gained when including only IPD-related outcomes. The cost-effectiveness of PCV7 remained in the range A$88,000-$122,000 when changes in various non-invasive disease states were included. The inclusion of observed changes in adult non-invasive pneumonia deaths substantially improved cost-effectiveness (∼A$9000 per QALY gained). Using the initial vaccine price negotiated for Australia, the PCV7 program was unlikely to have been cost-effective (at conventional thresholds) unless observed reductions in non-invasive pneumonia deaths in the elderly are attributed to it. Further analyses are required to explore this finding, which has significant implications for the incremental benefit achievable by adult PCV programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Redistribution of Streptococcus pneumoniae Serotypes After Nationwide 13-valent Pneumococcal Conjugate Vaccine Program in Children in Northern Taiwan.

PubMed

Cho, Ying-Chun; Chiu, Nan-Chang; Lu, Chun-Yi; Huang, Daniel Tsung-Ning; Huang, Fu-Yuan; Chang, Luan-Yin; Huang, Li-Min; Chi, Hsin

2017-12-01

After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy. S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities. Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P < 0.0001) but nonvaccine serotypes increased from 8.8% to 51.5% (P < 0.0001). The step-by-step PCV13 national immunization program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.

Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza and Streptococcus pneumoniae

PubMed Central

Shrestha, Sourya; Foxman, Betsy; Dawid, Suzanne; Aiello, Allison E.; Davis, Brian M.; Berus, Joshua; Rohani, Pejman

2013-01-01

A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immune-mediated model of the viral–bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4–6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness. PMID:23825111

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a systematic review and meta-analysis, 1990–2010

PubMed Central

2012-01-01

Background Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region. Methods We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated. Results We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospital-based/sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin. Conclusions Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease. PMID:22639955

Drug treatment of pneumococcal pneumonia in the elderly.

PubMed

Neralla, Sridhar; Meyer, Keith C

2004-01-01

Streptococcus pneumoniae has been recognised as a major cause of pneumonia since the time of Sir William Osler. Drug-resistant S. pneumoniae (DRSP), which have gradually become resistant to penicillins as well as more recently developed macrolides and fluoroquinolones, have emerged as a consequence of indiscriminate use of antibacterials coupled with the ability of the pneumococcus to adapt to a changing antibacterial milieu. Pneumococci use cell wall choline components to bind platelet-activating factor receptors, colonise mucosal surfaces and evade innate immune defenses. Numerous virulence factors that include hyaluronidase, neuraminidase, iron-binding proteins, pneumolysin and autolysin then facilitate cytolysis of host cells and allow tissue invasion and bloodstream dissemination. Changes in pneumococcal cell wall penicillin-binding proteins account for resistance to penicillins, mutations in the ermB gene cause high-level macrolide resistance and mutations in topoisomerase IV genes coupled with GyrA gene mutations alter DNA gyrase and lead to high-level fluoroquinolone resistance. Risk factors for lower respiratory tract infections in the elderly include age-associated changes in oral clearance, mucociliary clearance and immune function. Other risks for developing pneumonia include poor nutrition, hypoalbuminaemia, bedridden status, aspiration, recent viral infection, the presence of chronic organ dysfunction syndromes including parenchymal lung disease and recent antibacterial therapy. Although the incidence of infections caused by DRSP is rising, the effect of an increase in the prevalence of resistant pneumococci on mortality is not clear. When respiratory infections occur, rapid diagnosis and prompt, empirical administration of appropriate antibacterial therapy that ensures adequate coverage of DRSP is likely to increase the probability of a successful outcome when treating community-acquired pneumonia in elderly patients, particularly those with multiple risk factors for DRSP. A chest x-ray is recommended for all patients, but other testing such as obtaining a sputum Gram's smear is not necessary and should not prolong the time gap between clinical suspicion of pneumonia and antibacterial administration. The selection of antibacterials should be based upon local resistance patterns of suspected organisms and the bactericidal efficacy of the chosen drugs. If time-dependent agents are chosen and DRSP are possible pathogens, dosing should keep drug concentrations above the minimal inhibitory concentration that is effective for DRSP. Treatment guidelines and recent studies suggest that combination therapy with a beta-lactam and macrolide may be associated with a better outcome in hospitalised patients, and overuse of fluoroquinolones as a single agent may promote quinolone resistance. The ketolides represent a new class of macrolide-like antibacterials that are highly effective in vitro against macrolide- and azalide-resistant pneumococci. Pneumococcal vaccination with the currently available polysaccharide vaccine is thought to confer some preventive benefit (preventing invasive pneumococcal disease), but more effective vaccines, such as nonconjugate protein vaccines, need to be developed that provide broad protection against pneumococcal infection.

Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany.

PubMed

Kuhlmann, Alexander; von der Schulenburg, J-Matthias Graf

2017-04-01

In 2009, the European Medicines Agency granted approval for two higher-valent pneumococcal conjugate vaccines. This study aims to evaluate the cost-effectiveness of universal infant (<2 years old) vaccination with a 13-valent pneumococcal conjugate vaccine (PCV13) in comparison with a 10-valent pneumococcal conjugate vaccine (PCV10) for the prevention of pneumococcal disease in Germany. A population-based Markov model was developed to estimate the impact of PCV13 and PCV10 on invasive pneumococcal disease (IPD), non-invasive pneumonia (PNE), and acute otitis media (AOM) over a time horizon of 50 years. The model included the effects of the historical vaccination scheme in infants as well as indirect herd effects and replacement disease. We used German epidemiological data to calculate episodes of IPD, PNE, and AOM, as well as direct and indirect effects of the vaccination. Parameter uncertainty was tested in univariate and probabilistic sensitivity analyses. In the base-case analysis, the ICER of PCV13 versus PCV10 infant vaccination was EUR 9826 per quality-adjusted life-year (QALY) gained or EUR 5490 per life-year (LY) gained from the societal perspective and EUR 3368 per QALY gained or EUR 1882 per LY gained from the perspective of the German statutory health insurance. The results were particularly sensitive to the magnitude of indirect effects of both vaccines. Universal infant vaccination with PCV13 is likely to be a cost-effective intervention compared with PCV10 within the German health care system, if additional net indirect effects of PCV13 vaccination are significant.

Cost effectiveness of pneumococcal conjugate vaccination against acute otitis media in children: a review.

PubMed

Boonacker, Chantal W B; Broos, Pieter H; Sanders, Elisabeth A M; Schilder, Anne G M; Rovers, Maroeska M

2011-03-01

While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the relationship between the costs and benefits of available vaccines remains a controversial topic. Our objective is to systematically review the literature on the cost effectiveness of pneumococcal conjugate vaccination against AOM in children. We searched PubMed, Cochrane and the Centre for Reviews and Dissemination databases (Database of Abstracts of Reviews of Effects [DARE], NHS Economic Evaluation Database [NHS EED] and Health Technology Assessment database [HTA]) from inception until 18 February 2010. We used the following keywords with their synonyms: 'otitis media', 'children', 'cost-effectiveness', 'costs' and 'vaccine'. Costs per AOM episode averted were calculated based on the information in this literature. A total of 21 studies evaluating the cost effectiveness of pneumococcal conjugate vaccines were included. The quality of the included studies was moderate to good. The cost per AOM episode averted varied from &U20AC;168 to &U20AC;4214, and assumed incidence rates varied from 20,952 to 118,000 per 100,000 children aged 0-10 years. Assumptions regarding direct and indirect costs varied between studies. The assumed vaccine efficacy of the 7-valent pneumococcal CRM197-conjugate vaccine was mainly adopted from two trials, which reported 6-8% efficacy. However, some studies assumed additional effects such as herd immunity or only took into account AOM episodes caused by serotypes included in the vaccine, which resulted in efficacy rates varying from 12% to 57%. Costs per AOM episode averted were inversely related to the assumed incidence rates of AOM and to the estimated costs per AOM episode. The median costs per AOM episode averted tended to be lower in industry-sponsored studies. Key assumptions regarding the incidence and costs of AOM episodes have major implications for the estimated cost effectiveness of pneumococcal conjugate vaccination against AOM. Uniform methods for estimating direct and indirect costs of AOM should be agreed upon to reliably compare the cost effectiveness of available and future pneumococcal vaccines against AOM.

Trends in incidence of pneumococcal disease before introduction of conjugate vaccine: South West England, 1996–2005

PubMed Central

IHEKWEAZU, C. A.; DANCE, D. A. B.; PEBODY, R.; GEORGE, R. C.; SMITH, M. D.; WAIGHT, P.; CHRISTENSEN, H.; CARTWRIGHT, K. A. V.; STUART, J. M.

2008-01-01

SUMMARY Introduction of pneumococcal conjugate and polysaccharide vaccines into the United Kingdom's routine immunization programmes is expected to change the epidemiology of invasive pneumococcal disease (IPD). We have documented the epidemiology of IPD in an English region (South West) with high-quality surveillance data before these programmes were established. We analysed data on isolates of Streptococcus pneumoniae from blood and CSF between 1996 and 2005 from microbiology laboratories in the South West that were reported and/or referred for serotyping to the Health Protection Agency Centre for Infections. The mean annual incidence of IPD increased from 11·2/100 000 in 1996 to 13·6/100 000 in 2005 (P<0·04). After adjusting for annual blood-culture sampling rates in hospitals serving the same catchment populations, an increase in annual incidence of IPD was no longer observed (P=1·0). Variation in overall incidence between laboratories could also be explained by variation in blood culture rates. The proportion of disease caused by serotypes 6B, 9V and 14 decreased significantly (P=0·001, P=0·007, and P=0·027 respectively) whereas that caused by serotype 4, 7F and 1 increased (P=0·001, P=0·003, and P<0·001 respectively) between 2000 and 2005. The level of penicillin non-susceptibility and resistance to erythromycin remained stable (2% and 12% respectively). This study provides an important baseline to assess the impact of changing vaccination programmes on the epidemiology of IPD, thus informing future use of pneumococcal vaccines. PMID:17961282

Decreasing incidence and changes in serotype distribution of invasive pneumococcal disease in persons aged under 18 years since introduction of 10-valent and 13-valent conjugate vaccines in Portugal, July 2008 to June 2012.

PubMed

Aguiar, S I; Brito, M J; Horacio, A N; Lopes, J P; Ramirez, M; Melo-Cristino, J

2014-03-27

The 10-valent pneumococcal conjugate vaccine (PCV10) became available in Portugal in mid-2009 and the 13-valent vaccine (PCV13) in early 2010. The incidence of invasive pneumococcal disease (IPD) in patients aged under 18 years decreased from 8.19 cases per 100,000 in 2008–09 to 4.52/100,000 in 2011–12. However, IPD incidence due to the serotypes included in the 7-valent conjugate vaccine (PCV7) in children aged under two years remained constant. This fall resulted from significant decreases in the number of cases due to: (i) the additional serotypes included in PCV10 and PCV13 (1, 5, 7F; from 37.6% to 20.6%), particularly serotype 1 in older children; and (ii) the additional serotypes included in PCV13 (3, 6A, 19A; from 31.6% to 16.2%), particularly serotype 19A in younger children. The decrease in serotype 19A before vaccination indicates that it was not triggered by PCV13 administration. The decrease of serotype 1 in all groups, concomitant with the introduction of PCV10, is also unlikely to have been triggered by vaccination, although PCVs may have intensified and supported these trends. PCV13 serotypes remain major causes of IPD, accounting for 63.2% of isolates recovered in Portugal in 2011–12, highlighting the potential role of enhanced vaccination in reducing paediatric IPD in Portugal.

The potential cost-effectiveness of infant pneumococcal vaccines in Australia.

PubMed

Newall, Anthony T; Creighton, Prudence; Philp, David J; Wood, James G; MacIntyre, C Raina

2011-10-19

Over the last decade infant pneumococcal vaccination has been adopted as part of routine immunisation schedules in many developed countries. Although highly successful in many settings such as Australia and the United States, rapid serotype replacement has occurred in some European countries. Recently two pneumococcal conjugate vaccines (PCVs) with extended serotype coverage have been licensed for use, a 10-valent (PHiD-CV) and a 13-valent (PCV-13) vaccine, and offer potential replacements for the existing vaccine (PCV-7) in Australia. To evaluate the cost-effectiveness of PCV programs we developed a static, deterministic state-transition model. The perspective for costs included those to the government and healthcare system. When compared to current practice (PCV-7) both vaccines offered potential benefits, with those estimated for PHiD-CV due primarily to prevention of otitis media and PCV-13 due to a further reduction in invasive disease in Australia. At equivalent total cost to vaccinate an infant, compared to no PCV the base-case cost per QALY saved were estimated at A$64,900 (current practice, PCV-7; 3+0), A$50,200 (PHiD-CV; 3+1) and A$55,300 (PCV-13; 3+0), respectively. However, assumptions regarding herd protection, serotype protection, otitis media efficacy, and vaccination cost changed the relative cost-effectiveness of alternative PCV programs. The high proportion of current invasive disease caused by serotype 19A (as included in PCV-13) may be a decisive factor in determining vaccine policy in Australia. Copyright © 2011 Elsevier Ltd. All rights reserved.

The role of pneumolysin in pneumococcal pneumonia and meningitis.

PubMed

Hirst, R A; Kadioglu, A; O'callaghan, C; Andrew, P W

2004-11-01

Diseases caused by Streptococcus pneumoniae include pneumonia, septicaemia and meningitis. All these are associated with high morbidity and mortality. The pneumococcus can colonize the nasopharynx, and this can be a prelude to bronchopneumonia and invasion of the vasculature space. Proliferation in the blood can result in a breach of the blood-brain barrier and entry into the cerebrospinal fluid (CSF) where the bacteria cause inflammation of the meningeal membranes resulting in meningitis. The infected host may develop septicaemia and/or meningitis secondary to bronchopneumonia. Also septicaemia is a common precursor of meningitis. The mechanisms surrounding the sequence of infection are unknown, but will be dependent on the properties of both the host and bacterium. Treatment of these diseases with antibiotics leads to clearance of the bacteria from the infected tissues, but the bacteriolytic nature of antibiotics leads to an acute release of bacterial toxins and thus after antibiotic therapy the patients can be left with organ-specific deficits. One of the main toxins released from pneumococci is the membrane pore forming toxin pneumolysin. Here we review the extensive studies on the role of pneumolysin in the pathogenesis of pneumococcal diseases.

Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion.

PubMed

Gilley, Ryan P; González-Juarbe, Norberto; Shenoy, Anukul T; Reyes, Luis F; Dube, Peter H; Restrepo, Marcos I; Orihuela, Carlos J

2016-05-01

Streptococcus pneumoniae (the pneumococcus) is capable of invading the heart. Herein we observed that pneumococcal invasion of the myocardium occurred soon after development of bacteremia and was continuous thereafter. Using immunofluorescence microscopy (IFM), we observed that S. pneumoniae replication within the heart preceded visual signs of tissue damage in cardiac tissue sections stained with hematoxylin and eosin. Different S. pneumoniae strains caused distinct cardiac pathologies: strain TIGR4, a serotype 4 isolate, caused discrete pneumococcus-filled microscopic lesions (microlesions), whereas strain D39, a serotype 2 isolate, was, in most instances, detectable only using IFM and was associated with foci of cardiomyocyte hydropic degeneration and immune cell infiltration. Both strains efficiently invaded the myocardium, but cardiac damage was entirely dependent on the pore-forming toxin pneumolysin only for D39. Early microlesions caused by TIGR4 and microlesions formed by a TIGR4 pneumolysin-deficient mutant were infiltrated with CD11b(+) and Ly6G-positive neutrophils and CD11b(+) and F4/80-positive (F4/80(+)) macrophages. We subsequently demonstrated that macrophages in TIGR4-infected hearts died as a result of pneumolysin-induced necroptosis. The effector of necroptosis, phosphorylated mixed-lineage kinase domain-like protein (MLKL), was detected in CD11b(+) and F4/80(+) cells associated with microlesions. Likewise, treatment of infected mice and THP-1 macrophages in vitro with the receptor-interacting protein 1 kinase (RIP1) inhibitor necrostatin-5 promoted the formation of purulent microlesions and blocked cell death, respectively. We conclude that pneumococci that have invaded the myocardium are an important cause of cardiac damage, pneumolysin contributes to cardiac damage in a bacterial strain-specific manner, and pneumolysin kills infiltrated macrophages via necroptosis, which alters the immune response. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Infiltrated Macrophages Die of Pneumolysin-Mediated Necroptosis following Pneumococcal Myocardial Invasion

PubMed Central

Gilley, Ryan P.; González-Juarbe, Norberto; Shenoy, Anukul T.; Reyes, Luis F.; Dube, Peter H.; Restrepo, Marcos I.

2016-01-01

Streptococcus pneumoniae (the pneumococcus) is capable of invading the heart. Herein we observed that pneumococcal invasion of the myocardium occurred soon after development of bacteremia and was continuous thereafter. Using immunofluorescence microscopy (IFM), we observed that S. pneumoniae replication within the heart preceded visual signs of tissue damage in cardiac tissue sections stained with hematoxylin and eosin. Different S. pneumoniae strains caused distinct cardiac pathologies: strain TIGR4, a serotype 4 isolate, caused discrete pneumococcus-filled microscopic lesions (microlesions), whereas strain D39, a serotype 2 isolate, was, in most instances, detectable only using IFM and was associated with foci of cardiomyocyte hydropic degeneration and immune cell infiltration. Both strains efficiently invaded the myocardium, but cardiac damage was entirely dependent on the pore-forming toxin pneumolysin only for D39. Early microlesions caused by TIGR4 and microlesions formed by a TIGR4 pneumolysin-deficient mutant were infiltrated with CD11b+ and Ly6G-positive neutrophils and CD11b+ and F4/80-positive (F4/80+) macrophages. We subsequently demonstrated that macrophages in TIGR4-infected hearts died as a result of pneumolysin-induced necroptosis. The effector of necroptosis, phosphorylated mixed-lineage kinase domain-like protein (MLKL), was detected in CD11b+ and F4/80+ cells associated with microlesions. Likewise, treatment of infected mice and THP-1 macrophages in vitro with the receptor-interacting protein 1 kinase (RIP1) inhibitor necrostatin-5 promoted the formation of purulent microlesions and blocked cell death, respectively. We conclude that pneumococci that have invaded the myocardium are an important cause of cardiac damage, pneumolysin contributes to cardiac damage in a bacterial strain-specific manner, and pneumolysin kills infiltrated macrophages via necroptosis, which alters the immune response. PMID:26930705

Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

PubMed

Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Ganaie, Feroze; Bhaskar, Arun; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Ravikumar, Kadahalli Lingegowda; Das, Ranjan Saurav; Mandal, Sutapa

2018-05-01

Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.

Pneumococcal vaccine (image)

MedlinePlus

Pneumococcal vaccine is an immunization against Streptococcus pneumoniae , a bacterium that frequently causes meningitis and pneumonia in the elderly, and people with chronic illnesses. Pneumococcal pneumonia accounts for 10 ...

Structure of Pneumococcal Peptidoglycan Hydrolase LytB Reveals Insights into the Bacterial Cell Wall Remodeling and Pathogenesis*

PubMed Central

Bai, Xiao-Hui; Chen, Hui-Jie; Jiang, Yong-Liang; Wen, Zhensong; Huang, Yubin; Cheng, Wang; Li, Qiong; Qi, Lei; Zhang, Jing-Ren; Chen, Yuxing; Zhou, Cong-Zhao

2014-01-01

Streptococcus pneumoniae causes a series of devastating infections in humans. Previous studies have shown that the endo-β-N-acetylglucosaminidase LytB is critical for pneumococcal cell division and nasal colonization, but the biochemical mechanism of LytB action remains unknown. Here we report the 1.65 Å crystal structure of the catalytic domain (residues Lys-375–Asp-658) of LytB (termed LytBCAT), excluding the choline binding domain. LytBCAT consists of three structurally independent modules: SH3b, WW, and GH73. These modules form a “T-shaped” pocket that accommodates a putative tetrasaccharide-pentapeptide substrate of peptidoglycan. Structural comparison and simulation revealed that the GH73 module of LytB harbors the active site, including the catalytic residue Glu-564. In vitro assays of hydrolytic activity indicated that LytB prefers the peptidoglycan from the lytB-deficient pneumococci, suggesting the existence of a specific substrate of LytB in the immature peptidoglycan. Combined with in vitro cell-dispersing and in vivo cell separation assays, we demonstrated that all three modules are necessary for the optimal activity of LytB. Further functional analysis showed that the full catalytic activity of LytB is required for pneumococcal adhesion to and invasion into human lung epithelial cells. Structure-based alignment indicated that the unique modular organization of LytB is highly conserved in its orthologs from Streptococcus mitis group and Gemella species. These findings provided structural insights into the pneumococcal cell wall remodeling and novel hints for the rational design of therapeutic agents against pneumococcal growth and thereby the related diseases. PMID:25002590

A Modified Surface Killing Assay (MSKA) as a Functional in vitro Assay for Identifying Protective Antibodies Against Pneumococcal Surface Protein A (PspA)

PubMed Central

Genschmer, Kristopher R.; Accavitti-Loper, Mary Ann; Briles, David E.

2013-01-01

Streptococcus pneumoniae causes otitis media, meningitis and pneumonia in patients worldwide; predominantly affecting young children, the elderly, and the immune compromised. Current vaccines against invasive pneumococcal disease are based on the polysaccharide capsules of the most clinically relevant serotypes. Due to serotype replacement, non-vaccine serotypes of S. pneumoniae have become more clinically relevant and as a result pneumococcal vaccines are becoming increasingly complex. These events emphasize the need to evaluate the potential for pneumococcal cross-reactive proteins to contribute to future vaccines. Antibody elicited by the immunization of humans with pneumococcal surface protein A (PspA) can passively protect mice from infection. However, robust in vitro functional assays for antibody to PspA are not available to predict the protective capacity of immune serum. For polysaccharide based vaccines, a standardized opsonophagocytosis killing assay (OPKA) is used. Antibody to PspA, however, does not work well in the standard OPKA. The present studies take advantage of past observations that phagocytosis is more efficient on tissue surfaces than in solution. In a modified surface killing assay (MSKA), monoclonal antibody to PspA, in the presence of complement, opsonized pneumococci for killing by phagocytes on an agar surface. Five monoclonal antibodies to PspA were tested; three demonstrated increased amounts of killing compared to the diluent control and protected mice by passive protection against type 3 pneumococci. The two antibodies that were not functional in the MSKA also failed to protect mice. Thus, an MSKA might be useful as a functional assay for immunity to PspA. PMID:24211169

Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases.

PubMed

Rivera-Olivero, Ismar A; Del Nogal, Berenice; Fuentes, Mariana; Cortez, Rossana; Bogaert, Debby; Hermans, Peter W M; Waard, Jacobus H de

2014-06-30

We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD). 82 children (age 2-59 months) with sickle cell anemia (n=22), chronic heart disease (n=19), HIV infection (n=12), immune-suppressive therapy (n=11) and other IPD-predisposing conditions (n=18) were vaccinated with PCV7 according to CDC-recommended age-related immunization schedules. Blood samples were taken to determine the concentration of IgG antibody, and nasopharyngeal swabs were obtained to isolate Streptococcus pneumoniae, before the first vaccine dose and 1 month after completion of the vaccination schedule. Pneumococcal carriage prior to the first immunization was 27% (n=22), with the most frequently carried serotypes being vaccine serotypes 6B (22%) and 14 (13%). One month after completion of the vaccination scheme pneumococcal carriage was 22% (n=17), dominated by non-vaccine serotypes 19A (24%) and 7F (12%). Before immunization, 65% of the subjects had IgG antibody titers >0.35 μg/mL for five serotypes tested. Post-vaccination, 100% of the subjects showed titers >1.0 μg/mL for all PCV7 serotypes with geometric mean concentrations (GMC) ranging from 1.75 μg/mL (serotype 23F) to 17.16 μg/mL (serotype 14). Children previously colonized with serotype 6B had a significantly lower GMC to this serotype following immunization than children not carrying 6B prior to the first PCV dose (p<0.05). PCV7 is highly immunogenic in Venezuelan children at high-risk for IPD. Vaccination was associated with an immediate shift in nasopharyngeal carriage toward non-PCV7 serotypes. Finally, we observed serotype-specific hyporesponsiveness to immunization after natural carriage with the same serotype in high-risk children. Copyright © 2014 Elsevier Ltd. All rights reserved.

PCR deduction of invasive and colonizing pneumococcal serotypes from Venezuela: a critical appraisal.

PubMed

Bello Gonzalez, Teresita; Rivera-Olivero, Ismar Alejandra; Sisco, María Carolina; Spadola, Enza; Hermans, Peter W; de Waard, Jacobus H

2014-04-15

Serotype surveillance of Streptococcus pneumoniae is indispensable for evaluating the potential impact of pneumococcal conjugate vaccines. Serotyping by the standard Quellung reaction is technically demanding, time consuming, and expensive. A simple and economical strategy is multiplex PCR-based serotyping. We evaluated the cost effectiveness of a modified serial multiplex PCR (mPCR), resolving 24 serotypes in four PCR reactions and optimally targeting the most prevalent invasive and colonizing pneumococcal serotypes found in Venezuela. A total of 223 pneumococcal isolates, 140 invasive and 83 carriage isolates, previously serotyped by the Quellung reaction and representing the 18 most common serotypes/groups identified in Venezuela, were serotyped with the adapted mPCR. The mPCR serotyped 76% of all the strains in the first two PCR reactions and 91% after four reactions, correctly identifying 17 serotypes/groups. An isolate could be serotyped with mPCR in less than 2 minutes versus 15 minutes for the Quellung reaction, considerably lowering labor costs. A restrictive weakness of mPCR was found for the detection of 19F strains. Most Venezuelan 19F strains were not typeable using the mPCR, and two 19F cps serotype variants were identified. The mPCR assay is an accurate, rapid, and economical method for the identification of the vast majority of the serotypes from Venezuela and can be used in place of the standard Quellung reaction. An exception is the identification of serotype 19F. In this setting, most 19F strains were not detectable with mPCR, demonstrating a need of serology-based quality control for PCR-based serotyping.

Meningitis - pneumococcal

MedlinePlus

Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type of bacteria is the most common cause of bacterial meningitis in adults. ...

Elucidating the impact of the pneumococcal conjugate vaccine programme on pneumonia, sepsis and otitis media hospital admissions in England using a composite control.

PubMed

Thorrington, Dominic; Andrews, Nick; Stowe, Julia; Miller, Elizabeth; van Hoek, Albert Jan

2018-02-08

The seven-valent pneumococcal conjugate vaccine (PCV) was introduced in England in September 2006, changing to the 13-valent vaccine in April 2010. PCV impact on invasive pneumococcal disease (IPD) has been extensively reported, but less described is its impact on the burden of pneumonia, sepsis and otitis media in the hospital. Using details on all admissions to hospitals in England, we compared the incidence of pneumococcal-specific and syndromic disease endpoints in a 24-month pre-PCV period beginning April 2004 to the 24-month period ending March 2015 to derive incidence rate ratios (IRRs). To adjust for possible secular trends in admission practice, IRRs were compared to the IRRs for five control conditions over the same period and the relative change assessed using the geometric mean of the five control IRRs as a composite, and individually for each control condition to give the min-max range. Relative changes were also compared with IRRs for IPD from the national laboratory database. The effect of stratifying cases into those with and without clinical risk factors for pneumococcal infection was explored. Relative reductions in pneumococcal pneumonia were seen in all age groups and in those with and without risk factors; in children under 15 years old reductions were similar in magnitude to reductions in IPD. For pneumonia of unspecified cause, relative reductions were seen in those under 15 years old (maximum reduction in children under 2 years of 34%, min-max: 11-49%) with a relative increase in 65+ year olds most marked in those with underlying risk conditions (41%, min-max: 0-82%). Reductions in pneumococcal sepsis were seen in all age groups, with the largest reduction in children younger than 2 years (67%, min-max 56-75%). Reductions in empyema and lung abscess were also seen in under 15 year olds. Results for other disease endpoints were varied. For disease endpoints showing an increase in raw IRR, the increase was generally reduced when expressed as a relative change. Use of a composite control and stratification by risk group status can help elucidate the impact of PCV on non-IPD disease endpoints and in vulnerable population groups. We estimate a substantial reduction in the hospitalised burden of pneumococcal pneumonia in all age groups and pneumonia of unspecified cause, empyema and lung abscess in children under 15 years of age since PCV introduction. The increase in unspecified pneumonia in high-risk 65+ year olds may in part reflect their greater susceptibility to develop pneumonia from less pathogenic serotypes that are replacing vaccine types in the nasopharynx.

Pneumococcal Disease

MedlinePlus

... infection that causes pneumonia, meningitis, and bloodstream infection (sepsis). About one million US adults get pneumococcal pneumonia ... from it. Fewer will get pneumococcal meningitis or sepsis, but the mortality rate in this group is ...

Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin

PubMed Central

Lebensburger, Jeffrey D.; Howard, Thad; Hu, Yunming; Pestina, Tamara I.; Gao, Geli; Johnson, Melissa; Zakharenko, Stanislav S.; Ware, Russell E.; Tuomanen, Elaine I.; Persons, Derek A.

2012-01-01

Sickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of hydroxyurea was found to significantly improve survival. Hydroxyurea treatment decreased neutrophil extravasation into the infected lung coincident with significantly reduced levels of E-selectin in serum and on pulmonary epithelia. The protective effect of hydroxyurea was abrogated in mice deficient in E-selectin. The decrease in E-selectin levels was also evident in human sickle cell patients receiving hydroxyurea therapy. These data indicate that in addition to induction of fetal hemoglobin, hydroxyurea attenuates leukocyte–endothelial interactions in sickle cell anemia, resulting in protection against lethal pneumococcal sepsis. PMID:22130804

Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and deficits in current interventions

PubMed Central

Muller, Martha; Obert, Caroline; Burnham, Corinna; Mann, Beth; Li, Yimei; Hayden, Randall T; Pestina, Tamara; Persons, Derek; Camilli, Andrew

2014-01-01

Summary Sickle cell disease (SCD) patients are at high risk of contracting pneumococcal infection. To address this risk, they receive pneumococcal vaccines, and antibiotic prophylaxis and treatment. To assess the impact of SCD and these interventions on pneumococcal genetic architecture, we examined the genomes of over 300 pneumococcal isolates from SCD patients over 20 years. Modern SCD strains retained invasive capacity but shifted away from the serotypes used in vaccines. These strains had specific genetic changes related to antibiotic resistance, capsule biosynthesis, metabolism and metal transport. A murine SCD model coupled with Tn-seq mutagenesis identified 60 non-capsular pneumococcal genes under differential selective pressure in SCD, which correlated with aspects of SCD pathophysiology. Further, virulence determinants in the SCD context were distinct from the general population and protective capacity of potential antigens was lost over time in SCD. This highlights the importance of understanding bacterial pathogenesis in the context of high-risk individuals. PMID:24832453

Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs.

PubMed

Shigayeva, Altynay; Rudnick, Wallis; Green, Karen; Chen, Danny K; Demczuk, Walter; Gold, Wayne L; Johnstone, Jennie; Kitai, Ian; Krajden, Sigmund; Lovinsky, Reena; Muller, Matthew; Powis, Jeff; Rau, Neil; Walmsley, Sharon; Tyrrell, Gregory; Bitnun, Ari; McGeer, Allison

2016-01-15

In 2012/2013, a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for immunocompromised adults in the United States and Canada. To assess the potential benefits of this recommendation, we assessed the serotype-specific burden of invasive pneumococcal disease (IPD) among immunocompromised individuals. From 1995 to 2012, population-based surveillance for IPD was conducted in Metropolitan Toronto and Peel Region, Canada. Disease incidence and case fatality were measured in immunocompromised populations over time, and the contribution of different serotypes determined. Overall, 2115/7604 (28%) episodes of IPD occurred in immunocompromised persons. IPD incidence was 12-fold higher (95% confidence interval [CI], 8.7-15) in immunocompromised compared to immunocompetent persons; the case fatality rate was elevated in both younger (odds ratio [OR] 1.8) and older (OR 1.3) adults. Use of immunosuppressive medications was associated with a 2.1-2.7 fold increase in the risk of IPD. Five years after PPV23 program implementation, IPD incidence had declined significantly in immunocompromised adults (IRR 0.57, 95% CI, .40-.82). Ten years after pediatric PCV7 authorization, IPD due to PCV7 serotypes had decreased by 90% (95% CI, 77%-96%) in immunocompromised persons of all ages. In 2011/2012, 37% of isolates causing IPD in immunocompromised persons were PCV13 serotypes and 27% were PPV23/not PCV13 serotypes. Immunocompromised individuals comprised 28% of IPD. Both PPV23 and herd immunity from pediatric PCV7 were associated with reductions in IPD in immunocompromised populations. PCV13 vaccination of immunocompromised adults may substantially reduce the residual burden until herd immunity from pediatric PCV13 is fully established. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Invasive pneumococcal disease in Northern Alberta, not a Red Queen but a dark horse.

PubMed

Marrie, Thomas J; Tyrrell, Gregory J; Majumdar, Sumit R; Eurich, Dean T

2018-05-17

The consequences of the introduction of various pneumococcal protein conjugate vaccines (PCV) for children and adults is poorly understood. We undertook a population-based cohort study of invasive pneumococcal disease (IPD) in Northern Alberta (Canada) from 2000 to 2014, years spanning pre-and early PCV (2000-2004) vs PCV-7 (2005-2009) vs PCV-13 (2010-2014) time periods. We collected clinical, laboratory, and Streptococcus pneumoniae serotype information on all patients from 2000 to 2014. We determined changes in presentation, outcomes, serotypes, and incidence in children and adults across time periods. There were 509 cases of IPD in children, an 80% decrease over time. Rates of empyema (4.0-15.7%, p < 0.001), ICU admission (13.1-20%), and mortality (1.8-8.4%, p < 0.001) increased over time. There were 2417 cases of IPD in adults. Unlike children, incidence of IPD did not change nor did rates of empyema. ICU admissions increased (p = 0.004) and mortality decreased (18.7-16.5%, p = 0.002). The total number of serotypes causing IPD remained stable in children (22 vs 26 vs 20) while they decreased in adults (49 vs 47 vs 42). For children, PCV vaccination strategies resulted in decreased overall rates of IPD and we observed increased rates of empyema and mortality; for adults, there was no change in IPD rates although disease severity increased while mortality decreased. On a population-wide basis, our results suggest that current PCV vaccination strategies are associated with an overall decrease in IPD but disease severity seems to be increasing in both children and adults. Copyright © 2018 Elsevier Ltd. All rights reserved.

Three Decades of Follow-up of Adults After Recovery From Invasive Pneumococcal Pneumonia.

PubMed

Ajayi, Oluwadamilare O; Norton, Nancy B; Gress, Todd W; Stanek, Ronald J; Mufson, Maurice A

2017-05-01

Streptococcus pneumoniae infection is the most common cause of community-acquired pneumonia in adults. Invasive pneumococcal disease (IPD) carries a high case fatality rate. We investigated the lifespan of adults who recovered from IPD during a 32-year follow-up. We determined whether adults discharged after an episode of IPD from hospitals affiliated with the Marshall University Joan C. Edwards School of Medicine in Huntington, West Virginia from 1983-2003 were alive on June 30, 2014. Lifespan was assessed by Kaplan-Meier methodology, Cox proportional hazards multivariate analysis, life expectancy using life tables for West Virginia, years of potential life lost and serotype occurrence. The study group comprised 155 adults who survived IPD. They had a mean age at discharge of 64.6 years, mean lifespan after IPD of 7.1 years, mean expected lifespan after IPD of 17.0 years, mean age at death of 71.6 years and a mean life expectancy of 81.6 years. Only 14 (9.0%) patients lived longer than their life expectancy. Of the 13 comorbid diseases analyzed, cancer and neurologic diseases and the number of comorbid diseases suffered by each patient were the significant variables associated with survival. The mean years of potential life lost was 9.936 years. Only serotype 12 of 31 serotypes recovered occurred more often in patients who survived for 11 or more years after discharge (relative risk = 3.44, 95% CI: 1.19-9.95). The fact that most adult patients who recovered from IPD died before their documented life expectancy argues for the pernicious severity of IPD and the importance of immunization of adults with pneumococcal vaccines. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Recurrent bacterial meningitis by three different pathogens in an isolated asplenic child.

PubMed

Uchida, Yoshiko; Matsubara, Kousaku; Wada, Tamaki; Oishi, Kazunori; Morio, Tomohiro; Takada, Hidetoshi; Iwata, Aya; Yura, Kazuo; Kamimura, Katsunori; Nigami, Hiroyuki; Fukaya, Takashi

2012-08-01

Isolated congenital asplenia (ICA) is a rare condition at risk for overwhelming infection. When complicated by invasive infection, the mortality remains high, at greater than 60%. We describe a girl with ICA who developed recurrent meningitis by three different pathogens. The first, meningitis by Escherichia coli, occurred 4 days after premature birth. The other two pathogens were serotype 6B Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), at 18 and 25 months of age, respectively. The patient was successfully treated with prompt antimicrobial therapy in all episodes. Serum anti-polyribosylribitol phosphate (PRP) and anti-6B-type pneumococcal antibodies were below the levels for protective activity after natural infections. Although anti-PRP antibody was significantly increased after Hib vaccination, two (6B and 19F) of seven serotype-specific pneumococcal antibodies were not elevated to protective levels after the second 7-valent pneumococcal conjugate vaccine (PCV7). We, therefore, added a third PCV7. To our knowledge, this is the first neonatal ICA patient with invasive infection and the first case of bacterial meningitis occurring three times. Our findings indicate that monitoring of immune responses after natural infections and vaccinations, and reevaluations of vaccine schedule, are important for ICA patients to prevent subsequent invasive infections.

Invasive pneumococcal disease and socioeconomic deprivation: a population study from the North East of England.

PubMed

Chapman, K E; Wilson, D; Gorton, R

2013-12-01

Some communicable diseases disproportionately affect poor and vulnerable groups. Invasive pneumococcal disease (IPD) is an important cause of morbidity and mortality; however, the relationship between IPD and deprivation has not been well described. Population based study assessing the relationship between incidence of IPD and deprivation in the North East of England using data from an enhanced IPD surveillance system and the 2010 Indices of Multiple Deprivation and the Rural and Urban Area Classification. The incidence of IPD increased linearly with increasing deprivation from 7.0 per 100 000 population to 13.6 per 100 000 population. This association was demonstrated for the 16-64 and ≥65 year age groups, but not the <16 year age group. IPD incidence was strongly associated with all individual domains of deprivation except for the 'barriers to housing and services' domain. IPD incidence was higher in urban than rural areas. The risk of IPD is strongly associated with deprivation in adults, but not children. The mechanisms producing the associations observed remain unclear and require further investigation. Findings from this study reinforce the need to address social inequalities to reduce the burden of disease. Targeting vaccination at adults living in deprived areas could reduce the burden of IPD.

Dosing regimen of the 23-valent pneumococcal vaccination: a systematic review.

PubMed

Caya, Chelsea A; Boikos, Constantina; Desai, Shalini; Quach, Caroline

2015-03-10

Currently, one lifetime booster of a 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for those at highest risk of invasive pneumococcal disease (IPD) 3-5 years after initial vaccination. Due to a lack of evidence on multiple revaccinations, recommendations on repeat revaccination do not exist. We aimed to determine the optimal dose and timing of PPV23 booster in high-risk groups. We searched Google Scholar, Cochrane, EMBASE, Classic EMBASE, and PubMed for articles published in English and French using the MeSH terms pneumococcal infection, invasive pneumococcal disease, pneumonia, pneumo23, pneumovax 23, PPV23, and 23-valent. Articles were included if they examined dosing regimens of PPV23 (i.e., PPV23 priming and boosting) in adult populations, pediatric populations or both. Two authors independently assessed all titles and abstracts. All potentially relevant articles were chosen by consensus and retrieved for full text review. Two authors independently conducted the inclusion assessment. Database searches resulted in a total of 1233 articles. The review by title and abstracts resulted in the exclusion of 1170 articles, 53 articles were fully reviewed, 2 articles were identified using Google Scholar and 12 articles were finally included. The majority of evidence consistently indicated an increase in antibody response following PPV23 revaccination in both adult and pediatric populations. Evidence on multiple revaccinations was limited and mixed. Revaccination with PPV23 was well tolerated. The majority of evidence reviewed supports PPV23 revaccination in both adult and pediatric populations. However, data on multiple booster PPV23 vaccinations in these populations is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Density and Duration of Pneumococcal Carriage Is Maintained by Transforming Growth Factor β1 and T Regulatory Cells

PubMed Central

Coward, William R.; Gritzfeld, Jenna F.; Richards, Luke; Garcia-Garcia, Francesc J.; Dotor, Javier; Gordon, Stephen B.

2014-01-01

Rationale: Nasopharyngeal carriage of Streptococcus pneumoniae is a prerequisite for invasive disease, but the majority of carriage episodes are asymptomatic and self-resolving. Interactions determining the development of carriage versus invasive disease are poorly understood but will influence the effectiveness of vaccines or therapeutics that disrupt nasal colonization. Objectives: We sought to elucidate immunological mechanisms underlying noninvasive pneumococcal nasopharyngeal carriage. Methods: Pneumococcal interactions with human nasopharyngeal and bronchial fibroblasts and epithelial cells were investigated in vitro. A murine model of nasopharyngeal carriage and an experimental human pneumococcal challenge model were used to characterize immune responses in the airways during carriage. Measurements and Main Results: We describe the previously unknown immunological basis of noninvasive carriage and highlight mechanisms whose perturbation may lead to invasive disease. We identify the induction of active transforming growth factor (TGF)-β1 by S. pneumoniae in human host cells and highlight the key role for TGF-β1 and T regulatory cells in the establishment and maintenance of nasopharyngeal carriage in mice and humans. We identify the ability of pneumococci to drive TGF-β1 production from nasopharyngeal cells in vivo and show that an immune tolerance profile, characterized by elevated TGF-β1 and high nasopharyngeal T regulatory cell numbers, is crucial for prolonged carriage of pneumococci. Blockade of TGF-β1 signaling prevents prolonged carriage and leads to clearance of pneumococci from the nasopharynx. Conclusions: These data explain the mechanisms by which S. pneumoniae colonize the human nasopharynx without inducing damaging host inflammation and provide insight into the role of bacterial and host constituents that allow and maintain carriage. PMID:24749506

Streptococcus pneumoniae bacteraemia due to parotitis in a patient with systemic sclerosis and secondary Sjögren's syndrome.

PubMed

Yii, Irene Yuen Lin; Tan, Jamie Bee Xian; Fong, Warren Weng Seng

2016-10-01

Invasive pneumococcal disease is an uncommon and notifiable disease in Singapore. It is often associated with significant morbidity and mortality. We report a rare case of invasive pneumococcal bacteraemia due to parotitis in a patient with systemic sclerosis and secondary Sjögren's syndrome. We also present a retrospective review of Streptococcus pneumoniae bacteraemia cases in Singapore General Hospital from January 2011 to April 2016. A 59-year-old Malay lady with a history of systemic sclerosis with secondary Sjögren's syndrome presented with fever and left parotid gland swelling. Clinical examination revealed poor salivary pooling and left parotid swelling without fluctuance. Ultrasound of the left parotid gland confirmed acute parotitis without evidence of abscess or sialolithiasis. Blood cultures were positive for S. pneumoniae . She was diagnosed to have invasive pneumococcal bacteraemia secondary to acute parotitis, and treated with intravenous benzylpenicillin with clearance of bacteraemia after 3 days. Upon discharge, her antibiotics were changed to intravenous ceftriaxone to facilitate outpatient parenteral antibiotic therapy for another 2 weeks. She responded favourably to antibiotics at follow-up, with no complications from the bacteraemia. A review of the microbiological records of the Singapore General Hospital revealed 116 cases of pneumococcal bacteraemia, most (80.3 %) of which were due to pneumonia. None were due to parotitis. S. pneumoniae parotitis and subsequent bacteraemia is rare. Prompt recognition of the disease and appropriate use of antibiotics are important. This case highlights that close communication between healthcare workers (microbiologist, rheumatologist and infectious disease specialist) is essential in ensuring good clinical outcomes in patients with a potentially fatal disease.

The role of television advertising in increasing pneumococcal vaccination coverage among the elderly, North Coast, New South Wales, 2006.

PubMed

Wallace, Cate; Corben, Paul; Turahui, John; Gilmour, Robin

2008-10-01

North Coast Area Health Service (NCAHS) conducted a seven week television advertising campaign to raise community awareness of the availability of free adult pneumococcal vaccination and to increase coverage among North Coast residents in high risk groups. Effectiveness of the campaign was evaluated by examining vaccine ordering patterns of North Coast vaccination providers from 2005/2006 as a proxy for vaccination coverage. In the months during and immediately following (June-September 2006) the advertising campaign, a significantly higher proportion of vaccines were despatched to North Coast immunisation service providers. The advertising campaign was an effective strategy to promote vaccination among NCAHS residents not immunised in the first year of the National Pneumococcal Program for Older Australians. This higher immunisation coverage is expected to contribute to the statewide trend of significant reductions in invasive pneumococcal disease (IPD) notifications.

CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae.

PubMed

Wu, Kaifeng; Xu, Hongmei; Zheng, Yuqiang; Wang, Libin; Zhang, Xuemei; Yin, Yibing

2016-07-08

Transcriptional regulation of capsule expression is critical for pneumococcal transition from carriage to infection, yet the underlying mechanism remains incompletely understood. Here, we describe the regulation of capsular polysaccharide, one of the most important pneumococcal virulence factor by a GntR family regulator, CpsR. Electrophoretic mobility-shift assays have shown the direct interaction between CpsR and the cps promoter (cpsp), and their interaction could be competitively interfered by glucose. DNase I footprinting assays localized the binding site to a region -146 to -114 base pairs relative to the transcriptional start site of the cps locus in S. pneumoniae D39. We found that CpsR negatively controlled the transcription of the cps locus and hence CPS production, which was confirmed by fine-tuning expression of CpsR in a ΔcpsR complemented strain. Increased expression of CpsR in complemented strain led to a decreased resistance to the whole-blood-mediated killing, suggesting a protective role for CpsR-cpsp interaction in the establishment of invasive infection. Finally, animal experiments showed that CpsR-cpsp interaction was necessary for both pneumococcal colonization and invasive infection. Taken together, our results provide a thorough insight into the regulation of capsule production mediated by CpsR and its important roles in pneumococcal pathogenesis.

Health and economic impact of PHiD-CV in Canada and the UK: a Markov modelling exercise.

PubMed

Knerer, Gerhart; Ismaila, Afisi; Pearce, David

2012-01-01

The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13). The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature. The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively. The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper. This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV's potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.

Hospital admission rates for meningitis and septicaemia caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in children in England over five decades: a population-based observational study.

PubMed

Martin, Natalie G; Sadarangani, Manish; Pollard, Andrew J; Goldacre, Michael J

2014-05-01

Infection with Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae causes substantial mortality and long-term morbidity in children. We know of no study to assess the long-term trends in hospital admission rates for meningitis and septicaemia caused by these pathogens in children in England. We aimed to do such a study using routinely reported data in England. In this population-based observational study, we used datasets that include routinely collected administrative statistics for hospital care: the Hospital In-Patient Enquiry (data for England from 1968 to 1985), the Hospital Episode Statistics dataset (data for England from 1989 onwards), and the Oxford record linkage study (data for Oxfordshire and surrounding areas from 1963 to 2011). We analysed annual age-specific and age-standardised admission rates in children younger than 15 years with H influenzae, meningococcal and pneumococcal meningitis, and septicaemia. We saw a reduction in hospital admission rates for childhood invasive bacterial disease after the introduction of conjugate vaccines against H influenzae, N meningitidis, and S pneumoniae in England. Annual incidence of H influenzae meningitis per 100,000 children decreased from 6·72 admissions (95% CI 6·18-7·26) in 1992 to 0·39 admissions (0·26-0·52) in 1994, after the introduction of routine H influenzae type b vaccination. We saw a small rise in admissions in the early 2000s, peaking at 1·24 admissions per 100,000 children (0·99-1·48) in 2003, which decreased to 0·28 per 100,000 children (0·17-0·39) by 2008 after the introduction of catch-up (2003) and routine (2006) booster programmes for young children. Meningococcal disease increased during the 1990s, reaching a peak in 1999, with 34·54 admissions (33·30-35·78) per 100,000 children. Hospital admissions decreased after the meningococcal serogroup C vaccine was introduced in 1999 and was 12·40 admissions (11·68-13·12) per 100,000 in 2011. Admissions for invasive pneumococcal disease increased from the 1990s reaching a peak in 2006 at 4·45 admissions for meningitis (95% CI 4·0-4·9) per 100,000 children and 2·81 admissions for septicaemia (2·45-3·17) per 100,000 children. A reduction in admissions occurred after the introduction of the pneumococcal conjugate vaccine in 2006: hospital admission rates in 2011 were 2·03 per 100,000 children for meningitis and 1·12 per 100,000 children for septicaemia. Vaccine-preventable invasive bacterial disease in children has decreased substantially in England in the past five decades, most notably with the advent of effective conjugate vaccines since the 1990s. Ongoing disease surveillance and continued development and implementation of vaccines against additional pneumococcal serotypes and serogroup B meningococcal disease are important. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

A public health and budget impact analysis of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK.

PubMed

Jiang, Yiling; Gauthier, Aline; Keeping, Sam; Carroll, Stuart

2014-12-01

Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits.

Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children.

PubMed

Ruiz-Contreras, Jesus; Picazo, Juan; Casado-Flores, Juan; Baquero-Artigao, Fernando; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina; Del Amo, María; Balseiro, César

2017-08-16

To evaluate the impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children. Children younger than 15years of age attending 27 hospitals in the Region of Madrid with confirmed pneumococcal meningitis were identified in a prospective surveillance study, from 2007 to 2015. Clinical data, neurological sequelae, pneumococcal vaccination status, serotyping and antibiotic susceptibility were recorded. One hundred and four cases of pneumococcal meningitis were identified, 63 during the period of routine 7-valent pneumococcal conjugate vaccine immunisation (May 2007-April 2010) and 41 during the period of 13-valent pneumococcal conjugate vaccine immunisation (May 2010-April 2015). When both periods were compared, a 62% (95% CI: 45-75%) decrease in the incidence of pneumococcal meningitis was observed, from 2.19 cases per 100,000 inhabitants in the PCV7 period to 0.81 per 100,000 inhabitants in the PCV13 period (p=0.0001), mainly due to an 83% (95% CI: 30-96%) reduction in cases caused by serotype 19A. Isolates not susceptible to cefotaxime (MIC>0.5μg/L) decreased from 27% to 8%, (p=0.02). Mean patient ages rose from 28.7months to 38.5months (p<0.05). Case fatality rate across both periods was 5%. An unfavourable outcome (death or neurological sequelae) occurred in 27% of patients, while the rate was similar in both periods. There was no increase in meningitis caused by pneumococcal serotypes not included in 13-valent pneumococcal conjugate vaccine throughout the years of the study. Immunisation with 13-valent pneumococcal conjugate vaccine has reduced the rate of pneumococcal meningitis in children less than 15years, with a near-elimination of cefotaxime-resistant isolates, but morbidity has remained unchanged. A shift of pneumococcal meningitis towards slightly higher age groups was also observed. Copyright © 2017. Published by Elsevier Ltd.

Acute suppurative parotitis caused by Streptococcus pneumoniae in an HIV-infected man.

PubMed

Guzman Vinasco, Luis; Bares, Sara; Sandkovsky, Uriel

2015-03-02

We report a case of a 32-year-old man who presented with progressive unilateral parotid gland enlargement and subsequently tested positive for HIV. A CT scan of the neck performed with contrast showed a phlegmon in the region of the right parotid tail measuring approximately 2.5×2.4 cm. Cultures of the aspirated fluid grew Streptococcus pneumoniae and the S. pneumoniae urinary antigen test was also positive. The patient underwent surgical debridement and received antimicrobial therapy with complete resolution of the parotitis. Parotitis caused by S. pneumoniae is rare, and HIV infection should be suspected in any case of invasive pneumococcal disease. 2015 BMJ Publishing Group Ltd.

Acute suppurative parotitis caused by Streptococcus pneumoniae in an HIV-infected man

PubMed Central

Guzman Vinasco, Luis; Bares, Sara; Sandkovsky, Uriel

2015-01-01

We report a case of a 32-year-old man who presented with progressive unilateral parotid gland enlargement and subsequently tested positive for HIV. A CT scan of the neck performed with contrast showed a phlegmon in the region of the right parotid tail measuring approximately 2.5×2.4 cm. Cultures of the aspirated fluid grew Streptococcus pneumoniae and the S. pneumoniae urinary antigen test was also positive. The patient underwent surgical debridement and received antimicrobial therapy with complete resolution of the parotitis. Parotitis caused by S. pneumoniae is rare, and HIV infection should be suspected in any case of invasive pneumococcal disease. PMID:25733094

Serotype distribution of invasive Streptococcus pneumoniae in Canada during the introduction of the 13-valent pneumococcal conjugate vaccine, 2010.

PubMed

Demczuk, Walter H B; Martin, Irene; Griffith, Averil; Lefebvre, Brigitte; McGeer, Allison; Shane, Amanda; Zhanel, George G; Tyrrell, Gregory J; Gilmour, Matthew W

2012-08-01

A baseline serotype distribution was established by age and region for 2058 invasive Streptococcus pneumoniae isolates collected during the implementation period of the 13-valent pneumococcal conjugate vaccine (PCV13) program in many parts of Canada in 2010. Serotypes 19A, 7F, and 3 were the most prevalent in all age groups, accounting for 57% in <2 year olds, 62% in 2-4 year olds, 45% in 5-14 year olds, 44% in 15-49 year olds, 41% in 50-64 year olds, and 36% in ≥65 year olds. Serotype 19A was most predominant in Western and Central Canada representing 15% and 22%, respectively, of the isolates from those regions, whereas 7F was most common in Eastern Canada with 20% of the isolates. Other prevalent serotypes include 15A, 23B, 12F, 22F, and 6C. PCV13 serotypes represented 65% of the pneumococci isolated from <2 year olds, 71% of 2-4 year olds, 61% of 5-14 year olds, 60% of 15-49 year olds, 53% of 50-64 year olds, and 49% of the ≥65 year olds. Continued monitoring of invasive pneumococcal serotypes in Canada is important to identify epidemiological trends and assess the impact of the newly introduced PCV13 vaccine on public health.

Title: Incidence of invasive pneumococcal disease in immunocompromised patients: A systematic review and meta-analysis.

PubMed

van Aalst, Mariëlle; Lötsch, Felix; Spijker, René; van der Meer, Jan T M; Langendam, Miranda W; Goorhuis, Abraham; Grobusch, Martin P; de Bree, Godelieve J

2018-05-31

Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines recommend pneumococcal vaccination for these patients. However, guidelines are scarcely underpinned with references to incidence studies of IPD in this population. This, potentially results in unawareness of the importance of vaccination and low vaccination rates. The objective of this systematic review and meta-analysis was to assess the incidence of IPD in ICPs. We systematically searched PubMed and Embase to identify studies in English published before December 6th, 2017 that included terms related to 'incidence', 'rate', 'pneumococcal', 'pneumoniae', 'meningitis', 'septicemia', or 'bacteremia'. We focused on patients with HIV, transplantation and chronic inflammatory diseases. We included 45 studies in the systematic review reporting an incidence or rate of IPD, defined as isolation of Streptococcus pneumoniae from a normally sterile site. Random effects meta-analysis of 38 studies showed a pooled IPD incidence of 331/100,000 person years in patients with HIV in the late-antiretroviral treatment era in non-African countries, and 318/100,000 in African countries; 696 and 812/100,000 in patients who underwent an autologous or allogeneic stem cell transplantation, respectively; 465/100,000 in patients with a solid organ transplantation; and 65/100,000 in patients with chronic inflammatory diseases. In healthy control cohorts, the pooled incidence was 10/100,000. ICPs are at increased risk of contracting IPD, especially those with HIV, and those who underwent transplantation. Based on our findings, we recommend pneumococcal vaccination in immunocompromised patients. ID: CRD42016048438. Copyright © 2018. Published by Elsevier Ltd.

A reflection on invasive pneumococcal disease and pneumococcal conjugate vaccination coverage in children in Southern Europe (2009-2016).

PubMed

Moreira, Marta; Castro, Olga; Palmieri, Melissa; Efklidou, Sofia; Castagna, Stefano; Hoet, Bernard

2017-06-03

Higher-valent pneumococcal conjugate vaccines (PCVs) were licensed from 2009 in Europe; similar worldwide clinical effectiveness was observed for PCVs in routine use. Despite a proven medical need, PCV vaccination in Southern Europe remained suboptimal until 2015/16. We searched PubMed for manuscripts published between 2009 and mid-2016. Included manuscripts had to contain data about invasive pneumococcal disease (IPD) incidence, or vaccination coverage with higher-valent PCVs. This review represents the first analysis of vaccination coverage and impact of higher-valent PCVs on overall IPD in Southern European countries (Portugal, Spain, Italy, Greece, Cyprus). Vaccination coverage in the Portuguese private market peaked around 2008 at 75% (children ≤ 2 years) but declined to 63% in 2012. In Madrid, coverage was 95% (2007-2012) but dropped to 67% (2013/14; children ≤ 2 years) after funding termination in May 2012. PCVs were recently introduced in the national immunisation program (NIP) of Portugal (2015) and Spain (2015/16). In Italy, coverage for the complete PCV schedule (children ≤ 2 years) was 88% in 2013, although highly variable between regions (45-99%). In Greece, in 2013, 82.3% had received 3 PCV doses by 12 months, while 62.3% received the fourth dose by 24 months. Overall IPD (net benefit: effect on vaccine types, vaccine-related types, and non-vaccine types) has decreased; in Greece, pneumococcal meningitis incidence remained stable. Continued IPD surveillance or national registers using ICD-10 codes of clinically suspected IPD are necessary, with timely publicly available reports and adequate national vaccination registers to assess trends in vaccination coverage, allowing evaluation of PCVs in NIPs.

Estimating health service utilization for treatment of pneumococcal disease: the case of Brazil.

PubMed

Sartori, A M C; Novaes, C G; de Soárez, P C; Toscano, C M; Novaes, H M D

2013-07-02

Health service utilization (HSU) is an essential component of economic evaluations of health initiatives. Defining HSU for cases of pneumococcal disease (PD) is particularly complex considering the varying clinical manifestations and diverse severity. We describe the process of developing estimates of HSU for PD as part of an economic evaluation of the introduction of pneumococcal conjugate vaccine in Brazil. Nationwide inpatient and outpatient HSU by children under-5 years with meningitis (PM), sepsis (PS), non-meningitis non-sepsis invasive PD (NMNS), pneumonia, and acute otitis media (AOM) was estimated. We assumed that all cases of invasive PD (PM, PS, and NMNS) required hospitalization. The study perspective was the health system, including both the public and private sectors. Data sources were obtained from national health information systems, including the Hospital Information System (SIH/SUS) and the Notifiable Diseases Information System (SINAN); surveys; and community-based and health care facility-based studies. We estimated hospitalization rates of 7.69 per 100,000 children under-5 years for PM (21.4 for children <1 years of age and 4.3 for children aged 1-4 years), 5.89 for PS (20.94 and 2.17), and 4.01 for NMNS (5.5 and 3.64) in 2004, with an overall hospitalization rate of 17.59 for all invasive PD (47.27 and 10.11). The estimated incidence rate of all-cause pneumonia was 93.4 per 1000 children under-5 (142.8 for children <1 years of age and 81.2 for children aged 1-4 years), considering both hospital and outpatient care. Secondary data derived from health information systems and the available literature enabled the development of national HSU estimates for PD in Brazil. Estimating HSU for noninvasive disease was challenging, particularly in the case of outpatient care, for which secondary data are scarce. Information for the private sector is lacking in Brazil, but estimates were possible with data from the public sector and national population surveys. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Pneumococcal vaccine: protection of adults and reduction of antibiotic resistence by vaccination of children with a conjugated vaccine].

PubMed

Pletz, Mathias W

2011-06-01

Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers, immunocompromised and the elderly. Main reservoir of pneumococci is the nasopharyngeal zone of healthy carriers, especially of toddlers. Currently, two types of pneumococcal vaccines are in clinical use, which induce production of antibodies against capsular polysaccharides. The older vaccine consists of pure capsular polysaccharides. It induces a limited immunity, because polysaccharides are poor antigens that stimulate mainly B-cells. In children under two years of age this vaccine is not used, because it does not induce a sufficient immunologic response, presumably because of the immaturity of their immune system. In 2000, a vaccination program with a novel pneumococcal vaccine was launched in the USA. This vaccine contains capsular polysaccharides, that are conjugated with a highly immunogenic protein. It induces both a T cell and B cell response that results in specific humoral and mucosal immunity. U.S. data demonstrate, that serotypes covered by the conjugated vaccine can be reduced in the whole population by vaccination of children being the main reservoir of pneumococci. This so called ,,herd protection" results in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates by reducing resistant pneumococcal cones.

Transmission of Streptococcus pneumoniae in an Urban Slum Community

PubMed Central

Palma, Tania; Ribeiro, Guilherme S.; Pinheiro, Ricardo M; Ribeiro, Cassio Tâmara; Cordeiro, Soraia Machado; da Silva Filho, H. P.; Moschioni, Monica; Thompson, Terry A.; Spratt, Brian; Riley, Lee W.; Barocchi, Michele A.; Reis, Mitermayer G.; Ko, Albert I.

2008-01-01

Background Inhabitants of slum settlements represent a significant proportion of the population at risk for pneumococcal disease in developing countries. Methods We conducted a household survey of pneumococcal carriage among residents of a slum community in the city of Salvador, Brazil. Results Among 262 subjects, 95 (36%) were colonized with S. pneumoniae. Children <5 years of age (OR, 8.0; 95%CI, 3.5-18.6) and those who attended schools (OR 2.7, 95%CI, 1.2-6.0) had significantly higher risk of being colonized. Of 94 isolates obtained from colonized individuals, 51% had serotypes included in the seven-valent pneumococcal conjugate vaccine. Overall, 10% (9 of 94 isolates) were nonsusceptible to penicillin and 28% (27 of 94 isolates) were resistant to cotrimoxazole. BOX-PCR, PFGE and MLST analysis found that 44% of the carriage isolates belonged to 14 distinct clonal groups. Strains of the same clonal group were isolated from multiple members of 9 out of the 39 study households. Nineteen carriage isolates had genotypes that were the same as those identified among 362 strains obtained from active surveillance for meningitis. Conclusions The study's findings indicate that there is significant intra and inter-household spread of S. pneumoniae in the slum community setting. However, a limited number of clones encountered during carriage among slum residents were found to cause invasive disease. PMID:18672297

Vaccinating welders against pneumonia

PubMed Central

Palmer, Keith T; Cosgrove, Martin P

2013-01-01

Background In 2011 the Department of Health in England recommended that welders should each receive a single dose of the 23-valent pneumococcal vaccine (PPV23). This review assesses the evidence behind the advice and its practical implications. Method The review was informed by a systematic search in Medline, which related pneumonia to welding and/or exposure to metal fume, and was supplemented using the personal libraries of the authors. Findings There is consistent evidence that welders die more often of pneumonia, especially lobar pneumonia, are hospitalised more often with lobar and pneumococcal pneumonia, and more often develop invasive pneumococcal disease (IPD). It is estimated that one case of IPD may be prevented over a 10-year period by vaccinating 588 welders against pneumococcal infection. Conclusions A good case exists that employers should offer PPV23 vaccination to welders and other employees exposed to metal fume. Additionally, reasonable measures must be taken to minimise exposure to welding fume and welders should be encouraged not to smoke. PMID:22764269

66 FR 13540 - Proposed Vaccine Information Materials for Pneumococcal Conjugate, Diphtheria, Tetanus, Acellular...

Federal Register 2010, 2011, 2012, 2013, 2014

2001-03-06

.... (Meningitis is a serious infection of the covering of the brain). Each year pneumococcal disease causes in... pneumococcal disease, such as meningitis and blood infections. It also prevents some ear infections. But ear... Vaccine Injury Compensation Program: hepatitis B, haemophilus influenzae type b (Hib), and varicella...

Cost-effectiveness analysis of pneumococcal vaccination of adults and elderly persons in Belgium.

PubMed

De Graeve, D; Lombaert, G; Goossens, H

2000-06-01

To analyse the direct medical costs and effectiveness of vaccinating adults aged between 18 and 64 years and elderly persons > or = 65 years of age with the 23-valent pneumococcal polysaccharide vaccine. This was a decision-analytic modelling study from the societal perspective in Belgium. The analysis compared 'vaccination' with 'no vaccination and treatment'. Calculations were based on the assumption that vaccination is as effective against all pneumococcal infections as it is against invasive pneumococcal disease. Data on the incidence of pneumococcal pneumonia and meningitis, frequency of hospitalisation, mortality rates and vaccine effectiveness were derived from the international literature. Costs were derived from analysis of historical data for cases of pneumococcal infection in Belgium. Vaccinating 1000 adults between the ages of 18 and 64 years gains approximately 2 life-years in comparison with the no vaccination option. However, to realise these additional health benefits requires additional costs of 11,800 European Currency Units (ECU; 1995 values) per life-year saved. Vaccinating 1000 elderly people (> or = 65 years) leads to > 9 life-years gained as well as a small monetary benefit of ECU1250. An extensive sensitivity analysis did not greatly affect the results for the elderly population: vaccination in this age group always remained favourable, and thus it is clearly indicated from an economic point of view. A crucial assumption for both age groups is that the effectiveness of the vaccine holds for all pneumococcal pneumonia. It is clear that the results will become less favourable if this assumption is dropped. Preventing pneumococcal infections by vaccination clearly benefits people's health. Reimbursement can be recommended for the elderly group; however, more accurate epidemiological data are still needed to make decisions concerning routine pneumococcal vaccination in adults < 65 years of age. Unfortunately, the issue of whether the effectiveness of the vaccine holds for all pneumococcal pneumonia is as yet unresolved in the medical literature.

Age-Specific Cluster of Cases of Serotype 1 Streptococcus pneumoniae Carriage in Remote Indigenous Communities in Australia ▿

PubMed Central

Smith-Vaughan, H.; Marsh, R.; Mackenzie, G.; Fisher, J.; Morris, P. S.; Hare, K.; McCallum, G.; Binks, M.; Murphy, D.; Lum, G.; Cook, H.; Krause, V.; Jacups, S.; Leach, A. J.

2009-01-01

Seven-valent pneumococcal conjugate vaccination commenced in 2001 for Australian indigenous infants. Pneumococcal carriage surveillance detected substantial replacement with nonvaccine serotypes and a cluster of serotype 1 carriage. Our aim was to review Streptococcus pneumoniae serotype 1 carriage and invasive pneumococcal disease (IPD) data for this population and to analyze serotype 1 isolates. Carriage data were collected between 1992 and 2004 in the Darwin region, one of the five regions in the Northern Territory. Carriage data were also collected in 2003 and 2005 from four regions in the Northern Territory. Twenty-six cases of serotype 1 IPD were reported from 1994 to 2007 in the Northern Territory. Forty-four isolates were analyzed by BOX typing and 11 by multilocus sequence typing. In the Darwin region, 26 children were reported carrying serotype 1 (ST227) in 2002 but not during later surveillance. Scattered cases of serotype 1 carriage were noted in two other regions. Cocolonization of serotype 1 with other pneumococcal serotypes was common (34% serotype 1-positive swabs). In conclusion, pneumococcal carriage studies detected intermittent serotype 1 carriage and an ST227 cluster in children in indigenous communities in the Northern Territory of Australia. There was no apparent increase in serotype 1 IPD during this time. The rate of serotype 1 cocolonization with other pneumococcal serotypes suggests that carriage of this serotype may be underestimated. PMID:19091995

Antibiotic non-susceptibility among Streptococcus pneumoniae and Haemophilus influenzae isolates identified in African cohorts: a meta-analysis of three decades of published studies.

PubMed

Ginsburg, Amy Sarah; Tinkham, Laura; Riley, Katherine; Kay, Noa A; Klugman, Keith P; Gill, Christopher J

2013-12-01

Management of community-acquired pneumonia caused by Streptococcus pneumoniae and Haemophilus influenzae type B (Hib) can be complicated by emerging antimicrobial non-susceptibility. We conducted a meta-analysis to examine the antibiotic susceptibility of community-acquired invasive infections with S. pneumoniae and Hib in Africa from 1978 to 2011. With the notable exceptions of widespread trimethoprim/sulfamethoxazole (SXT) and tetracycline non-susceptibility, the majority of pneumococci remain susceptible to ampicillin/amoxicillin. However, 23.8% of pneumococcal meningitis isolates are non-susceptible to penicillin. Similarly, Hib isolates show non-susceptibility to SXT, tetracycline, erythromycin and chloramphenicol. β-Lactamase production among Hib isolates is increasing, a new observation for Africa, but is mitigated somewhat by Hib vaccination scale-up. In summary, pneumococcal susceptibility to amoxicillin remains high throughout Africa, and amoxicillin can be effectively and safely used as first-line treatment for childhood pneumonia. Data support first-line treatment of bacterial meningitis with ceftriaxone or cefotaxime. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae strains in the south of Tunisia: A five-year study (2012-2016) of pediatric and adult populations.

PubMed

Ktari, Sonia; Jmal, Ikram; Mroua, Manel; Maalej, Sonda; Ben Ayed, Nour ElHouda; Mnif, Basma; Rhimi, Faouzia; Hammami, Adnene

2017-12-01

To analyze the serotype distribution of Streptococcus pneumoniae clinical isolates collected in the south of Tunisia over a 5-year period in different age groups and to assess their antimicrobial susceptibility patterns. A total of 305 non-duplicate S. pneumoniae isolates were collected between January 2012 and December 2016 at the university hospital in Sfax, Tunisia. All isolates were serotyped by multiplex PCR. The antibiotic susceptibility of all isolates was determined using the disk diffusion test or Etest assay. Among the 305 pneumococcal isolates, 76 (24.9%) were invasive and 229 (75.1%) were non-invasive. The most common serotypes were 19F (20%), 14 (16.7%), 3 (9.2%), 23F (7.5%), 19A (5.9%), and 6B (5.9%). Potential immunization coverage rates for pneumococcal conjugate vaccines PCV7, PCV10, and PCV13 were 58%, 59.3%, and 78.7%, respectively. Three-quarters (75.3%) of pneumococcal isolates were non-susceptible to penicillin. The resistance rate to erythromycin was 71.4%. Only two isolates were resistant to levofloxacin. 19F and 14 were the most prevalent serotypes in the south of Tunisia. The inclusion of a PCV in the immunization program could be useful for reducing the burden of pneumococcal diseases. The high resistance rate to penicillin and macrolides is alarming. Prudent use of antibiotics is crucial to prevent the selection of multidrug-resistant pneumococci. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effectiveness of pneumococcal polysaccharide vaccine 23 (PPV23) in the general population of 50 years of age and older: A systematic review and meta-analysis.

PubMed

Kraicer-Melamed, Hannah; O'Donnell, Shauna; Quach, Caroline

2016-03-18

Two pneumococcal vaccines currently exist and have been recommended for the prevention of pneumococcal infection in adults 65 years of age and older: the 23-valent polysaccharide (PPV23) and the conjugate 13-valent (PCV13) vaccine. To evaluate and summarize the results from all studies reporting on the vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) in individuals over the age of 50. Systematic database searches were completed in PubMed, Medline, Embase, CINAHL, Web of Science, and Cochrane. Google Scholar and hand searches of seminal articles and past systematic reviews were employed. Studies were included if they independently evaluated the effect of PPV23 on IPD and/or CAP in adults (50+). Data extraction and quality assessment were both completed independently by two researchers. Quality was assessed using the National Advisory Committee on Immunization methodology for quality assessment. All conflicts were resolved by consensus. The vaccine effectiveness for PPV23 in preventing IPD was 50% (95% CI: 21%-69%) for cohort studies and 54% (95% CI: 32%-69%) for case-control studies. The VE estimates for CAP were 4% (95% CI: -26%-26%) for trials, 17% (95% CI: -26%-45%) for cohort studies, and 7% (95% CI: -10%-21%) for case-control studies. The vaccine effectiveness of PPV23 in preventing IPD and all-cause CAP was consistent with past systematic reviews and similar to the estimates that were reported in the CAPiTA trial evaluating the vaccine effectiveness of PCV13. Consistent benefits were also reported across ecological studies and reports of surveillance data for the general population 50 years and older. The results suggests that the current practice of vaccinating the adults 65 years of age and older with PPV23 would have similar benefits to PCV13 in preventing potential cases of all-serotype IPD and all-cause CAP. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recommendations for pneumococcal immunization outside routine childhood immunization programs in Western Europe.

PubMed

Castiglia, Paolo

2014-10-01

The global burden of pneumococcal diseases is high, with young children and adults≥50 years of age at highest risk of infection. Two types of vaccine are available for the prevention of pneumococcal diseases caused by specific Streptococcus pneumoniae serotypes: the pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccine (PCV7, PCV10, and PCV13). Despite pneumococcal immunization programs in adults and children, the burden in adults has remained high. Most European countries have national or local/regional vaccination recommendations. The objective of this review was to provide an overview of the government recommendations for pneumococcal vaccination outside routine childhood vaccination programs for 16 Western European countries as of August 2014. We found that recommendations for pneumococcal immunization across Europe are complex and vary greatly among countries in terms of age groups and risk groups recommended for vaccination, as well as which vaccine should be administered. Clarifying or simplifying these recommendations and improving their dissemination could help to increase pneumococcal vaccine uptake and decrease the high burden of pneumococcal diseases in adults, both through a direct effect of the vaccine and via a herd effect in unvaccinated individuals.

Serotype distribution of Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease in Brazil before and after ten-pneumococcal conjugate vaccine implementation.

PubMed

dos Santos, Silvia R; Passadore, Lilian F; Takagi, Elizabeth H; Fujii, Cristiane M; Yoshioka, Cristina R M; Gilio, Alfredo E; Martinez, Marina B

2013-12-09

The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cost-effectiveness of 13-valent pneumococcal conjugate vaccine in Switzerland.

PubMed

Blank, Patricia R; Szucs, Thomas D

2012-06-13

The 7-valent pneumococcal conjugate vaccine (PCV7) has been shown to be highly cost-effective. The 13-valent pneumococcal conjugate vaccine (PCV13) offers seroprotection against six additional serotypes. A decision-analytic model was constructed to estimate direct medical costs and clinical effectiveness of PCV13 vaccination on invasive pneumococcal disease (IPD), pneumonia, and otitis media relative to PCV7 vaccination. The option with an one-dose catch-up vaccination in children of 15-59 months was also considered. Assuming 83% vaccination coverage and considering indirect effects, 1808 IPD, 5558 pneumonia and 74,136 otitis media cases could be eliminated from the entire population during a 10-year modelling period. The PCV13 vaccination programme would lead to additional costs (+€26.2 Mio), but saved medical costs of -€77.1 Mio due to cases averted and deaths avoided, overcompensate these costs (total cost savings -€50.9 Mio). The national immunisation programmes with PCV13 can be assumed cost saving when compared with the current vaccine PCV7 in Switzerland. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lack of Effectiveness of the 23-Valent Polysaccharide Pneumococcal Vaccine in Reducing All-Cause Pneumonias Among Healthy Young Military Recruits: A Randomized, Double-Blind, Placebo-Controlled Trial

DTIC Science & Technology

2015-01-08

pneumococcal capsu- lar polysaccharide vaccine with emphasis on the cross-reactive types within groups. J Infect Dis 1983;148:1136–59. [2] Update...pneumococcal polysaccharide vaccine usage–United States. Morb Mortal Wkly Rep 1984;33:273–327, 81. [3] Skull SA, Andrews RM, Byrnes GB, Kelly HA...Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study. Clin Infect Dis 2006;43:860–8

Near-elimination of otitis media caused by 13-valent pneumococcal conjugate vaccine (PCV) serotypes in southern Israel shortly after sequential introduction of 7-valent/13-valent PCV.

PubMed

Ben-Shimol, Shalom; Givon-Lavi, Noga; Leibovitz, Eugene; Raiz, Simon; Greenberg, David; Dagan, Ron

2014-12-15

Otitis media (OM) is common in early childhood. Streptococcus pneumoniae caused approximately 30%-60% of episodes before the pneumococcal conjugate vaccine (PCV) era. The 7-valent PCV (PCV7) was introduced to the Israeli National Immunization Plan in July 2009, and was gradually replaced by the 13-valent PCV (PCV13) starting in November 2010. We aimed at assessing the impact of PCV7/PCV13 sequential introduction on pneumococcal and overall OM necessitating middle ear fluid culture in children aged <2 years in southern Israel. This was a prospective, population-based, active surveillance. Our medical center is the only one in the region, enabling incidence calculation. All pneumococcal episodes submitted for culture between July 2004 and June 2013 were included. Three subperiods were defined: pre-PCV, PCV7, and PCV13. Overall, 6122 OM episodes were recorded, and 1893 were pneumococcal. Compared with the pre-PCV period, OM caused by PCV7 plus serotype 6A and the 5 additional PCV13 serotypes (5VT : 1, 3, 5, 7F, 19A) decreased by 96% and 85%, respectively (incidence rate ratios [IRRs], 0.04 [95% confidence interval {CI}, .02-.08] and 0.15 [95% CI, .07-.30], respectively) in a 2-step pattern: In the PCV7 period, only OM caused by PCV7 + 6A serotypes was decreased; in the PCV13 period, 5VT OM rates decreased, along with an additional PCV7 + 6A OM reduction. A nonsignificant increase in non-PCV13 serotype OM was observed (IRR, 1.07 [95% CI, .72-1.58]). In total, 77% and 60% reductions of all-pneumococcal and all-cause OM incidences, respectively, were observed. A substantial 2-step reduction of pneumococcal OM rates, with near-elimination of PCV13 disease, was observed shortly after PCV7/PCV13 introduction. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Changing disparities in invasive pneumococcal disease by socioeconomic status and race/ ethnicity in Connecticut, 1998-2008.

PubMed

Soto, Kristen; Petit, Susan; Hadler, James L

2011-01-01

We compared invasive pneumococcal disease (IPD) incidence by race/ethnicity and neighborhood poverty level and assessed their relative utility to describe disparities in IPD in 1998-1999 and again in 2007-2008, after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). We conducted laboratory surveillance for pneumococcal isolates from sterile body sites and serotyped the isolates. Home address was geocoded to the census-tract level. Census-tract data on the percentage of people below poverty were grouped into three categories. The difference in the magnitude of incidence by race/ethnicity and by census-tract socioeconomic status (SES) (high poverty minus low poverty) was compared for 1998-1999 and 2007-2008 for PCV7 and non-PCV7 serotypes. In 1998-1999, incidence difference (all per 100,000 population) for PCV7 serotypes for black people compared with white people was 14.3 and by poverty level was 13.9. The highest rate was among white people in high-poverty tracts (77.3). By 2007-2008, there were only slight differences between rates for black and white people (0.7) and SES (1.4). In 1998-1999, the incidence difference for non-PCV7 serotypes was 4.7 between black and white people and 6.0 by SES. By 2007-2008, the differences were 11.6 and 11.7, respectively. Among those living in the highest-poverty tracts, white people had the highest rate (42.9). In the absence of vaccine, IPD incidence is higher among people living in higher-poverty census tracts and among black people. Emerging serotypes also follow this trend. Differences in neighborhood poverty levels reveal disparities in rates of IPD as large as those seen by race/ethnicity and could be used to routinely describe disparities and target prevention.

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study.

PubMed

Gattarello, Simone; Lagunes, Leonel; Vidaur, Loreto; Solé-Violán, Jordi; Zaragoza, Rafael; Vallés, Jordi; Torres, Antoni; Sierra, Rafael; Sebastian, Rosa; Rello, Jordi

2015-09-10

We aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000-2002 and 2008-2014, and the impact of the improvement in antibiotic strategies on outcomes. This was a matched case-control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000-2002 database (CAPUCI I group) were paired with 72 from the 2008-2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. The most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1%) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7%); prevalence of shock was 59.7%, while 73.6% of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7% versus 16.7%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5% in CAPUCI I and 92.7% in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3% and 37.5 versus 63.9%; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95% CI 0.07-0.74) and early antibiotic treatment (OR 0.07, 95% CI 0.02-0.22) were independently associated with decreased intensive care unit mortality. In non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period.

Pneumococcal Vaccination Among Medicare Beneficiaries Occurring After the Advisory Committee on Immunization Practices Recommendation for Routine Use Of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine for Adults Aged ≥65 Years.

PubMed

Black, Carla L; Williams, Walter W; Warnock, Rob; Pilishvili, Tamara; Kim, David; Kelman, Jeffrey A

2017-07-14

On September 19, 2014, CDC published the Advisory Committee on Immunization Practices (ACIP) recommendation for the routine use of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged ≥65 years, to be used in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) (1). This replaced the previous recommendation that adults aged ≥65 years should be vaccinated with a single dose of PPSV23. As a proxy for estimating PCV13 and PPSV23 vaccination coverage among adults aged ≥65 years before and after implementation of these revised recommendations, CDC analyzed claims for vaccination submitted for reimbursement to the Centers for Medicare & Medicaid Services (CMS). Claims from any time during a beneficiary's enrollment in Medicare Parts A (hospital insurance) and B (medical insurance) since reaching age 65 years were assessed among beneficiaries continuously enrolled in Medicare Parts A and B during annual periods from September 19, 2009, through September 18, 2016. By September 18, 2016, 43.2% of Medicare beneficiaries aged ≥65 years had claims for at least 1 dose of PPSV23 (regardless of PCV13 status), 31.5% had claims for at least 1 dose of PCV13 (regardless of PPSV23 status), and 18.3% had claims for at least 1 dose each of PCV13 and PPSV23. Claims for either type of pneumococcal vaccine were highest among beneficiaries who were older, white, or with chronic and immunocompromising medical conditions than among healthy adults. Implementation of the National Vaccine Advisory Committee's standards for adult immunization practice to assess vaccination status at every patient encounter, recommend needed vaccines, and administer vaccination or refer to a vaccinating provider might help increase pneumococcal vaccination coverage and reduce the risk for pneumonia and invasive pneumococcal disease among older adults (2).

Cost-effectiveness and cost utility analysis of three pneumococcal conjugate vaccines in children of Peru

PubMed Central

2013-01-01

Background The clinical and economic burden associated with invasive and non-invasive pneumococcal and non-typeable Haemophilus influenzae (NTHi) diseases is substantial in the Latin America and Caribbean region, where pneumococcal vaccines have only been introduced to a few countries. This study analyzed the cost-effectiveness and cost utility of three different pneumococcal conjugate vaccines (PCVs) for Peru. Methods A Markov model that simulated the disease processes in a birth cohort over a lifetime, within 1,128 month cycles was used to evaluate the cost-effectiveness of 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and 7- and 13-valent PCVs (PCV-7 and PCV-13). Expected quality-adjusted life years (QALYs), cost-savings and incremental cost-effectiveness ratios (ICERs) were calculated. Results Without vaccination, pneumonia was associated with the greatest health economic burden (90% of QALYs lost and 63% of lifetime direct medical costs); while acute otitis media (AOM) was responsible for 1% of QALYs lost and 25% of direct medical costs. All vaccines were predicted to be cost-effective for Peru, with PHiD-CV being most cost-effective. PHiD-CV was predicted to generate 50 more QALYs gained and required a reduced investment (−US$ 3.4 million) versus PCV-13 (discounted data), and was therefore dominant and cost saving. The probabilistic sensitivity analysis showed that PHiD-CV generated more QALYs gained at a reduced cost than PCV-13 in 84% of the simulations and less QALYs gains at a reduced cost in 16%. Additional scenarios using different assumptions on vaccine efficacies based on previous evidence were explored, but no significant change in the overall cost-effective results were observed. Conclusions The results of this modeling study predict that PCVs are likely to be a cost-effective strategy to help relieve the epidemiological and economic burden associated with pediatric pneumococcal and NTHi diseases for Peru. PHiD-CV is likely to be a dominant (better health gains at a reduced net cost) intervention compared to PCV-13 or PCV-7. The most significant drivers for these results are the better health and economic profile of PHiD-CV against AOM and its reduced cost per dose available through the PAHO Revolving Fund in the LAC region. PMID:24171921

Cost-effectiveness and cost utility analysis of three pneumococcal conjugate vaccines in children of Peru.

PubMed

Gomez, Jorge Alberto; Tirado, Juan Carlos; Navarro Rojas, Aldo Amador; Castrejon Alba, Maria Mercedes; Topachevskyi, Oleksandr

2013-10-30

The clinical and economic burden associated with invasive and non-invasive pneumococcal and non-typeable Haemophilus influenzae (NTHi) diseases is substantial in the Latin America and Caribbean region, where pneumococcal vaccines have only been introduced to a few countries. This study analyzed the cost-effectiveness and cost utility of three different pneumococcal conjugate vaccines (PCVs) for Peru. A Markov model that simulated the disease processes in a birth cohort over a lifetime, within 1,128 month cycles was used to evaluate the cost-effectiveness of 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and 7- and 13-valent PCVs (PCV-7 and PCV-13). Expected quality-adjusted life years (QALYs), cost-savings and incremental cost-effectiveness ratios (ICERs) were calculated. Without vaccination, pneumonia was associated with the greatest health economic burden (90% of QALYs lost and 63% of lifetime direct medical costs); while acute otitis media (AOM) was responsible for 1% of QALYs lost and 25% of direct medical costs. All vaccines were predicted to be cost-effective for Peru, with PHiD-CV being most cost-effective. PHiD-CV was predicted to generate 50 more QALYs gained and required a reduced investment (-US$ 3.4 million) versus PCV-13 (discounted data), and was therefore dominant and cost saving. The probabilistic sensitivity analysis showed that PHiD-CV generated more QALYs gained at a reduced cost than PCV-13 in 84% of the simulations and less QALYs gains at a reduced cost in 16%. Additional scenarios using different assumptions on vaccine efficacies based on previous evidence were explored, but no significant change in the overall cost-effective results were observed. The results of this modeling study predict that PCVs are likely to be a cost-effective strategy to help relieve the epidemiological and economic burden associated with pediatric pneumococcal and NTHi diseases for Peru. PHiD-CV is likely to be a dominant (better health gains at a reduced net cost) intervention compared to PCV-13 or PCV-7. The most significant drivers for these results are the better health and economic profile of PHiD-CV against AOM and its reduced cost per dose available through the PAHO Revolving Fund in the LAC region.

Epidemiological profile of invasive bacterial diseases in children in Casablanca, Morocco: antimicrobial susceptibilities and serotype distribution.

PubMed

El Mdaghri, N; Jilali, N; Belabbes, H; Jouhadi, Z; Lahssoune, M; Zaid, S

2012-11-01

The aim of this prospective study in Morocco was to investigate the causes of invasive bacterial diseases in children in order to inform antibiotic therapy and vaccine choices. Of 238 children aged < or = 5 years admitted to the Children's Hospital of Casablanca for invasive diseases over a 12-month period, 185 were diagnosed with bacterial infection: 76 had chest-X-ray-confirmed pneumonia, 59 had meningitis and 50 had sepsis. Streptococcus pneumoniae was the most common pathogen identified (n = 24), followed by Neisseria meningitidis (n = 18, all group B) and Haemophilus influenzae (n = 11). The rate of penicillin non-susceptibility was 62.5% among Str. pneumoniae isolates and 11.1% among N. meningitidis and all isolates were ceftriaxone-susceptible. Of the 11 H. influenzae isolates, only 1 produced a beta-lactamase. The 5 predominant Str. pneumoniae serotypes were 19F, 14, 23F, 6B and 19A and the theoretical coverage of the 7, 10 and 13-valent pneumococcal conjugate vaccines was 60%, 78% and 91% respectively.

Cost-effectiveness of polysaccharide pneumococcal vaccination in people aged 65 and above in Poland

PubMed Central

Grzesiowski, Pawel; Aguiar-Ibáñez, Raquel; Kobryń, Aleksandra; Durand, Laure; Puig, Pierre-Emmanuel

2012-01-01

Introduction: Invasive pneumococcal disease is associated with substantial morbidity, mortality and cost implications, which could be reduced by vaccination. Aim: To assess the cost-effectiveness of a 23-valent pneumococcal vaccine in the elderly (65 and older) in Poland. Methods: A Markov model with a 1-year cycle length was developed, allowing up to 10 cohorts to enter the model over the lifetime horizon (35 years). In the base case, costs and benefits were assessed using the public health care payer (NFZ) perspective. The analysis included routine vaccination of all elderly and high-risk (HR) elderly versus no vaccination. The analysis assumed that the government would reimburse 50% of the vaccine price. Costs and benefits were discounted 5%, with costs expressed in 2009 Polish Zloty (PLN). Extensive sensitivity analyses were carried out. Results: PPV23 vaccination targeting all elderly and HR elderly in Poland would avoid 8,935 pneumococcal infections, 2,542 hospitalisations, 671 deaths and 5,886 infections, 1,673 hospitalisations and 441 deaths respectively. The incremental cost per QALY gained would be PLN 3,382 in all elderly and PLN2,148 in HR elderly. Conclusion: Vaccinating adults 65 and older regardless of risk status with a 23-valent pneumococcal vaccine, is cost-effective, resulting in clinical and economic benefits including a non-negligible reduction of ambulatory doctor visits, hospitalizations and, deaths in Poland. PMID:23095867

Risk Factors for Pneumococcal Colonization of the Nasopharynx in Alaska Native Adults and Children.

PubMed

Reisman, Jonathan; Rudolph, Karen; Bruden, Dana; Hurlburt, Debby; Bruce, Michael G; Hennessy, Thomas

2014-06-01

Alaska Native children have high invasive pneumococcal disease (IPD) rates, and lack of in-home running water has been shown to have a significant association with infection. Pneumococcal conjugate vaccines reduced IPD; however, this population saw substantial replacement disease and colonization with nonvaccine serotypes. We evaluated risk factors for nasopharyngeal pneumococcal colonization in Alaska Native adults and children. We conducted annual surveys from 2008 through 2011 of residents of all ages in 8 rural Alaskan villages. Interviews were conducted, medical charts were reviewed, and nasopharyngeal swabs were cultured for Streptococcus pneumoniae. Multivariate logistic regression models were developed for 3 age groups (under 10 years, 10-17 years, and 18 years and older) to determine risk factors for colonization. We obtained 12 535 nasopharyngeal swabs from 4980 participants. Our population lived in severely crowded conditions, and 48% of households lacked in-home running water. In children <10 years, colonization was associated with lack of in-home running water, household crowding, and more children in the home. Pneumococcal vaccination status was not associated with colonization. In older children and adults, increased number of persons in the household was associated with pneumococcal colonization. Higher colonization prevalence may partially explain increased IPD rates seen in those lacking in-home water services. Improving availability of sanitation services and reducing household crowding may reduce the burden of IPD in this population. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comparing health outcomes and costs of general vaccination with pneumococcal conjugate vaccines in Sweden: a Markov model.

PubMed

By, Asa; Sobocki, Patrik; Forsgren, Arne; Silfverdal, Sven-Arne

2012-01-01

Two new pneumococcal conjugate vaccines were licensed to immunize infants and young children against pneumococcal disease. The objective of this study was to estimate the expected health benefits, costs, and incremental cost-effectiveness of routine vaccination with the 10-valent pneumococcal nontypeable hemophilus influenza protein-D conjugate vaccine (PHiD-CV) compared with the 13-valent pneumococcal conjugate vaccine (PCV13) in Sweden. A Markov cohort model was used to estimate the effect of vaccination at vaccine steady state, taking a societal perspective and using a 2+1 vaccination schedule. Price parity was assumed between the vaccines. Outcomes were measured by reduction in disease burden, costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio. The results predicted that PCV13 would prevent 3 additional cases of invasive pneumococcal disease and 34 additional cases of pneumonia, whereas PHiD-CV would avoid 3 additional cases of mastoiditis, 1010 tube insertions, and 10,420 cases of ambulatory acute otitis media compared with PCV13. By combining morbidity and mortality benefits of all clinical outcomes, PHiD-CV would generate 45.3 additional QALYs compared with PCV13 and generate savings of an estimated 62 million Swedish kronors. The present study predicted lower costs and better health outcome (QALYs) gained by introducing PHiD-CV compared with PCV13 in routine vaccination. Our results indicated that PHiD-CV is cost-effective compared with PCV13 in Sweden. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Incidence of Hospitalized Pneumococcal Pneumonia among Adults in Guatemala, 2008-2012

PubMed Central

Contreras, Carmen Lucía; Verani, Jennifer R.; Lopez, María Renee; Paredes, Antonio; Bernart, Chris; Moscoso, Fabiola; Roldan, Aleida; Arvelo, Wences; Lindblade, Kim A.; McCracken, John P.

2015-01-01

Background Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described. Methods Data from 2008–2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI). Results Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18–24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%. Conclusions An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala. PMID:26488871

Incidence of Hospitalized Pneumococcal Pneumonia among Adults in Guatemala, 2008-2012.

PubMed

Contreras, Carmen Lucía; Verani, Jennifer R; Lopez, María Renee; Paredes, Antonio; Bernart, Chris; Moscoso, Fabiola; Roldan, Aleida; Arvelo, Wences; Lindblade, Kim A; McCracken, John P

2015-01-01

Streptococcus pneumoniae is a leading cause of pneumonia worldwide. However, the burden of pneumococcal pneumonia among adults in low- and middle-income countries is not well described. Data from 2008-2012 was analyzed from two surveillance sites in Guatemala to describe the incidence of pneumococcal pneumonia in adults. A case of hospitalized pneumococcal pneumonia was defined as a positive pneumococcal urinary antigen test or blood culture in persons aged ≥ 18 years hospitalized with an acute respiratory infection (ARI). Among 1595 adults admitted with ARI, 1363 (82%) had either urine testing (n = 1286) or blood culture (n = 338) performed. Of these, 188 (14%) had pneumococcal pneumonia, including 173 detected by urine only, 8 by blood culture only, and 7 by both methods. Incidence rates increased with age, with the lowest rate among 18-24 year-olds (2.75/100,000) and the highest among ≥65 year-olds (31.3/100,000). The adjusted incidence of hospitalized pneumococcal pneumonia was 18.6/100,000 overall, with in-hospital mortality of 5%. An important burden of hospitalized pneumococcal pneumonia in adults was described, particularly for the elderly. However, even adjusted rates likely underestimate the true burden of pneumococcal pneumonia in the community. These data provide a baseline against which to measure the indirect effects of the 2013 introduction of the pneumococcal conjugate vaccine in children in Guatemala.

Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

PubMed

Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

2014-09-15

A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pneumococcal conjugate vaccine provides early protective antibody responses in children after related and unrelated allogeneic hematopoietic stem cell transplantation.

PubMed

Meisel, Roland; Kuypers, Lisa; Dirksen, Uta; Schubert, Ralf; Gruhn, Bernd; Strauss, Gabriele; Beutel, Karin; Groll, Andreas H; Duffner, Ulrich; Blütters-Sawatzki, Renate; Holter, Wolfgang; Feuchtinger, Tobias; Grüttner, Hans-Peter; Schroten, Horst; Zielen, Stefan; Ohmann, Christian; Laws, Hans-Jürgen; Dilloo, Dagmar

2007-03-15

Following allogeneic hematopoietic stem cell transplantation (alloHSCT), children are at risk of life-threatening pneumococcal infections. Whereas vaccination with polysaccharide vaccines fails to elicit protective immunity in most alloHSC transplant recipients, pneumococcal conjugate vaccines may effectively prevent invasive disease by eliciting T-cell-dependent antibody responses. Here, we report safety and immunogenicity in 53 children immunized with a regimen of 3 consecutive doses of a heptavalent pneumococcal conjugate vaccine (7vPCV) in monthly intervals starting 6 to 9 months after alloHSCT. Immunization was well tolerated with no vaccine-related serious adverse events. Serologic response rates evaluable in 43 patients ranged from 41.9% to 86.0% and 58.1% to 93.0% after 2 and 3 vaccinations, respectively, with 55.8% and 74.4% of patients achieving protective antibody levels to all 7 vaccine serotypes. Our study provides the first evidence that vaccination with 7vPCV is safe and elicits protective antipneumococcal antibody responses in pediatric recipients of related or unrelated donor alloHSC transplants within the first year following transplantation. This trial was registered at www.clinicaltrials.gov as NCT00169728.

A current and historical perspective on disparities in US childhood pneumococcal conjugate vaccine adherence and in rates of invasive pneumococcal disease: Considerations for the routinely-recommended, pediatric PCV dosing schedule in the United States

PubMed Central

McLaughlin, John M; Utt, Eric A; Hill, Nina M; Welch, Verna L; Power, Edward; Sylvester, Gregg C

2016-01-01

Previous research has suggested that reducing the US 4-dose PCV13 schedule to a 3-dose schedule may provide cost savings, despite more childhood pneumococcal disease. The study also stressed that dose reduction should be coupled with improved PCV adherence, however, US PCV uptake has leveled-off since 2008. An estimated 24–36% of US children aged 5–19 months are already receiving a reduced PCV schedule (i.e., missing ≥1 dose). This raises a practical concern that, under a reduced, 3-dose schedule, a similar proportion of children may receive ≤2 doses. It is also unknown if a reduced, 3-dose PCV schedule in the United States will afford the same disease protection as 3-dose schedules used elsewhere, given lower US PCV adherence. Finally, more assurance is needed that, under a reduced schedule, racial, socioeconomic, and geographic disparities in PCV adherence will not correspond with disproportionately higher rates of pneumococcal disease among poor or minority children. PMID:26376039

Pneumococcal vaccination and chronic respiratory diseases.

PubMed

Froes, Filipe; Roche, Nicolas; Blasi, Francesco

2017-01-01

Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases.

Increased Protection against Pneumococcal Disease by Mucosal Administration of Conjugate Vaccine plus Interleukin-12

PubMed Central

Lynch, Joyce M.; Briles, David E.; Metzger, Dennis W.

2003-01-01

Streptococcus pneumoniae is a common cause of respiratory tract infections, its main entry route being the nasal mucosa. The recent development of pneumococcal polysaccharide conjugate vaccines has led to a dramatic improvement in protection against invasive disease in infants and children, but these vaccines have been found to be only 50 to 60% protective against bacterial carriage. In this study, we investigated the efficacy of intranasal (i.n.) conjugate vaccine delivery using interleukin-12 (IL-12) as a mucosal adjuvant. Immunized mice treated with IL-12 demonstrated increased expression of lung and splenic gamma interferon and IL-10 mRNAs; high levels of antibody, particularly serum immunoglobulin G2a (IgG2a) and respiratory IgA; and significantly increased opsonic activity. After intraperitoneal challenge with type 3 pneumococci, there was 75% survival of i.n. vaccinated mice compared to 0% survival of unvaccinated mice. In addition, after i.n. challenge with type 14 pneumococci, vaccinated mice possessed fewer bacterial colonies in the upper respiratory tract than unvaccinated mice. However, no significant difference in type 14 carriage was observed between vaccinated and unvaccinated groups following intramuscular vaccination, the typical route of vaccination in humans. Using mice with a genetic disruption in IgA expression, it was found that pneumococcus-specific IgA played a significant role in the clearance of bacteria from the upper respiratory tract. We conclude that i.n vaccination in the presence of IL-12 is able to enhance systemic and mucosal immune responses to pneumococci and efficiently protect against both invasive infection and bacterial carriage. PMID:12874361

Community-Acquired Pneumonia in Adults: Diagnosis and Management.

PubMed

Kaysin, Alexander; Viera, Anthony J

2016-11-01

Community-acquired pneumonia is a leading cause of death. Risk factors include older age and medical comorbidities. Diagnosis is suggested by a history of cough, dyspnea, pleuritic pain, or acute functional or cognitive decline, with abnormal vital signs (e.g., fever, tachycardia) and lung examination findings. Diagnosis should be confirmed by chest radiography or ultrasonography. Validated prediction scores for pneumonia severity can guide the decision between outpatient and inpatient therapy. Using procalcitonin as a biomarker for severe infection may further assist with risk stratification. Most outpatients with community-acquired pneumonia do not require microbiologic testing of sputum or blood and can be treated empirically with a macrolide, doxycycline, or a respiratory fluoroquinolone. Patients requiring hospitalization should be treated with a fluoroquinolone or a combination of beta-lactam plus macrolide antibiotics. Patients with severe infection requiring admission to the intensive care unit require dual antibiotic therapy including a third-generation cephalosporin plus a macrolide alone or in combination with a fluoroquinolone. Treatment options for patients with risk factors for Pseudomonas species include administration of an antipseudomonal antibiotic and an aminoglycoside, plus azithromycin or a fluoroquinolone. Patients with risk factors for methicillin-resistant Staphylococcus aureus should be given vancomycin or linezolid, or ceftaroline in resistant cases. Administration of corticosteroids within 36 hours of hospital admission for patients with severe community-acquired pneumonia decreases the risk of adult respiratory distress syndrome and length of treatment. The 23-valent pneumococcal polysaccharide and 13-valent pneumococcal conjugate vaccinations are both recommended for adults 65 years and older to decrease the risk of invasive pneumococcal disease, including pneumonia.

Cost-benefit and cost-effectiveness of the incorporation of the pneumococcal 7-valent conjugated vaccine in the routine vaccination schedule of Catalonia (Spain).

PubMed

Navas, E; Salleras, L; Gisbert, R; Domínguez, A; Timoner, E; Ibáñez, D; Prat, A

2005-03-18

The health and economic costs and benefits of vaccinating a cohort of 60,000 children born in Catalonia in the year 2000 with the pneumococcal 7-valent conjugated vaccine were compared with the alternative of not implementing the vaccination programme. The time horizon fixed for the programme was 10 years for invasive disease, 2 years for all episodes of pneumonia and otitis media and 3.5 years for the placement of tympanostomy tubes. In the base case (incidence rate of invasive disease of 160 per 100,000 and price of the vaccine 50 euros) the net present value was negative, both from the societal perspective (-5.1million euros) and from the provider's perspective (-9.2million euros). The benefit-cost ratio was 0.59 euros from the societal perspective. The cost per disability adjusted life year (DALY) gained was 44,307 euros from the societal perspective and 80,291 euros from the provider's perspective.

A nationwide surveillance of invasive pneumococcal disease in adults in Israel before an expected effect of PCV7.

PubMed

Regev-Yochay, Gili; Rahav, Galia; Strahilevitz, Jacob; Bishara, Jihad; Katzir, Michal; Chowers, Michal; Finkelstein, Renato; Chazan, Bibiana; Zimhony, Oren; Dagan, Ron

2013-05-01

Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons ≥18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among ≥85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for ≥75y or those with ≥3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age ≥75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in ≥75y; p<0.01). The predominant serotypes among patients ≥75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Changing Epidemiology of Invasive Pneumococcal Disease Among the Indigenous and Non-indigenous Population of Northwestern Ontario, Canada, from 2006 Through 2015 and Emergence of Non-vaccine Serotypes

PubMed Central

Dalcin, Daniel; Sieswerda, Lee; Ulanova, Marina

2017-01-01

Abstract Background Rates of invasive pneumococcal disease (IPD) among indigenous populations remain substantially higher than their non-indigenous counterparts. The goal of this study was to analyze the epidemiology and demographic features of IPD in northwestern Ontario (NWO) among the indigenous and non-indigenous population in the context of recent changes in the provincial pneumococcal vaccination programs. Methods Two databases were used to identify cases of IPD in NWO: Thunder Bay Regional Health Sciences Centre and the Thunder Bay District Health Unit. Adult patients with a diagnosis of IPD at the TBRHSC from January 1, 2006 to December 31, 2015 had their medical charts retrospectively reviewed; TBDHU data contained only serotype, age, and gender data. Results Table 1. Number of IPD cases and case fatality rate by indigenous status at the TBRHSC, 2006–2015 # of cases # of deaths year indigenous non-indigenous total indigenous non-indigenous total 2006 3 7 10 0 0 0 2007 0 8 8 0 1 1 2008 5 11 16 0 1 1 2009 8 20 28 2 0 2 2010 5 17 22 0 2 2 2011 6 22 28 1 1 2 2012 3 8 11 0 1 1 2013 10 12 22 1 3 4 2014 10 11 21 0 0 0 2015 3 13 16 0 2 2 total 53 129 182 4 11 15 53 of 182 (29.0%) of patients were indigenous. 35 of 53 (66.0%) of indigenous patients were immunocompromised, whereas 38 of 129 (29.5%) of non-indigenous patients were immunocompromised and the difference was statistically significant (P < 0.001, by chi square test). 35 of 73 (48.0%) of immunocompromised patients were indigenous. Table 2. Serotype distribution of Streptococcus pneumoniae causing IPD in northwestern Ontario, Canada, 2006–2015 (includes both TBRHSC + TBDHU data). year PCV7 PCV13 PCV23 non-vaccine serotypes unknown serotypes total 2006 0 0 0 0 26 26 2007 1 0 2 1 12 16 2008 2 2 5 4 14 27 2009 3 12 9 3 16 43 2010 0 7 8 4 12 31 2011 2 10 12 4 9 37 2012 0 2 11 8 4 25 2013 0 3 21 2 8 34 2014 1 2 9 3 8 23 2015 1 0 7 6 9 23 total 10 38 84 35 118 285 The proportion of non-vaccine serotypes has increased, on average, by 16% per year (P = 0.024, 95% CI: 1.02, 1.32). Conclusion High rates of IPD were found to occur among immunocompromised indigenous adults in NWO. Our findings identify a vulnerable cohort of the population that would benefit from pneumococcal vaccination coverage. The proportion of non-vaccine serotypes causing IPD has increased during the 10-year observation period. Disclosures M. Ulanova, Pfizer: Grant Investigator, Grant recipient

Streptococcus pneumoniae non-susceptibility and outpatient antimicrobial prescribing rates at the Alaska Native Medical Center

PubMed Central

Stevens, Ryan W.; Wenger, Jay; Bulkow, Lisa; Bruce, Michael G.

2013-01-01

Background American Indian/Alaska Native (AI/AN) people suffer substantially higher rates of invasive pneumococcal disease (IPD) than the general US population. We evaluated antimicrobial prescribing data and their association with non-susceptibility in Streptococcus pneumoniae causing IPD in AI/AN people between 1992 and 2009. Methods Antimicrobial use data were gathered from the electronic patient management system and included all prescriptions dispensed to Alaska Native patients aged 5 years and older from outpatient pharmacies at the Alaska Native Medical Center (ANMC). Antimicrobial susceptibility data were gathered from pneumococcal isolates causing IPD among Anchorage Service Unit AI/AN residents aged 5 years and older. Data were restricted to serotypes not contained in the pneumococcal vaccine (PCV7). Results Over the study period, overall antimicrobial prescribing increased 59% (285/1,000 persons/year in 1992 to 454/1,000 persons per year in 2009, p<0.001). Trimethoprim/sulfamethoxazole prescribing increased (43/1,000 persons/year in 1992 to 108/1,000 persons/year in 2009, p<0.001) and non-susceptibility to trimethoprim/sulfamethoxazole in AI/AN patients ≥5 years of age increased in non-PCV7 serotypes (0–12%, p<0.05). Similarly, prescribing rates increased for macrolide antibiotics (46/1,000 persons/year in 1992 to 84/1,000 persons/year in 2009, p<0.05). We observed no statistically significant change over time in erythromycin non-susceptibility among non-PCV7 serotypes in AI/AN patients aged 5 years or greater (0–7%, p=0.087). Conclusion Antimicrobial prescribing patterns of some antibiotics in the AI/AN population corresponded to increased antimicrobial resistance in clinical isolates. This study highlights the on-going threat of antimicrobial resistance, the critical importance of judicious prescribing of antibiotics and the potential utility of prescribing data for addressing this issue. PMID:24358456

The Human Polymeric Immunoglobulin Receptor Facilitates Invasion of Epithelial Cells by Streptococcus pneumoniae in a Strain-Specific and Cell Type-Specific Manner

PubMed Central

Brock, Sean C.; McGraw, Patricia A.; Wright, Peter F.; Crowe Jr., James E.

2002-01-01

Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes invasive life-threatening disease worldwide. This organism also commonly colonizes the upper respiratory epithelium in an asymptomatic fashion. To invade, this pathogen must traverse the respiratory epithelial barrier, allowing it to cause disease locally or disseminate hematogenously throughout the body. Previous work has demonstrated that S. pneumoniae choline-binding protein A, a pneumococcal surface protein, interacts specifically with the human polymeric immunoglobulin receptor, which is expressed by cells in the respiratory epithelium. Choline-binding protein A is required for efficient colonization of the nasopharynx in vivo. Additionally, a recent study showed that the R6x laboratory strain of S. pneumoniae invades a human pharyngeal cell line in a human polymeric immunoglobulin receptor-dependent manner. These findings raised the possibility that the interaction between choline-binding protein A and human polymeric immunoglobulin receptor may be a key determinant of S. pneumoniae pathogenesis. However, the strain used in prior invasion studies, R6x, is an unencapsulated, nonpathogenic strain. In the present study we determined the relative ability of strain R6x or pathogenic strains to invade a variety of human polymeric immunoglobulin receptor-expressing epithelial cell lines. The results of this work suggest that human polymeric immunoglobulin receptor-dependent enhanced invasion of epithelial cells by S. pneumoniae is a limited phenomenon that occurs in a strain-specific and cell type-specific manner. PMID:12183558

Additive impact of pneumococcal conjugate vaccines on pneumonia and empyema hospital admissions in England.

PubMed

Saxena, Sonia; Atchison, Christina; Cecil, Elizabeth; Sharland, Mike; Koshy, Elizabeth; Bottle, Alex

2015-10-01

A wider spectrum 13-valent pneumococcal vaccine (PCV13) replaced PCV7 in the child immunization schedule in England from 2010. We assessed the additional impact of PCV13 over PCV7 on all-cause pneumonia and empyema admissions. We extracted Hospital Episode Statistics data from 2001 to 2014 on all-cause pneumonia (ICD-10 codes J12-18) and empyema admissions (J86.0, J86.9) for children <16 years in England. Trend analysis and rate ratios (RR) were calculated comparing the Pre-vaccine era to September 2006, the PCV7 era and the PCV13 era from April 2010. Annual hospital admissions for pneumonia and empyema were increasing in the Pre-vaccine era peaking in 2005 at 15,733 pneumonia and 382 empyema cases (158.6 and 3.9 per 100,000 children, respectively). These rates fell following PCV7 introduction in 2006 but began to climb soon afterwards until PCV13 was introduced. By 2013, admission rates for pneumonia and empyema were 102.2 and 1.9 per 100,000 children, respectively. We found no added benefit of PCV13 over PCV7 on pneumonia admissions following PCV13 introduction but there was a significant decrease in empyema admissions in children aged <2 years (RR 0.58; 95% CI 0.34-0.99). Additional serotypes covered by PCV13 may be more important in the aetiology of empyema and invasive disease than as a cause of uncomplicated pneumonia. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The 23-valent pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis: a double-blinded, randomized, placebo-controlled trial.

PubMed

Izumi, Yasumori; Akazawa, Manabu; Akeda, Yukihiro; Tohma, Shigeto; Hirano, Fuminori; Ideguchi, Haruko; Matsumura, Ryutaro; Miyamura, Tomoya; Mori, Shunsuke; Fukui, Takahiro; Iwanaga, Nozomi; Jiuchi, Yuka; Kozuru, Hideko; Tsutani, Hiroshi; Saisyo, Kouichirou; Sugiyama, Takao; Suenaga, Yasuo; Okada, Yasumasa; Katayama, Masao; Ichikawa, Kenji; Furukawa, Hiroshi; Kawakami, Kenji; Oishi, Kazunori; Migita, Kiyoshi

2017-01-25

Pneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients. A prospective, multicenter, double-blinded, randomized, placebo-controlled (1:1) trial was conducted across departments of rheumatology in Japanese National Hospital Organization hospitals. RA patients (n = 900) who had been treated with biological or immunosuppressive agents were randomly assigned PPSV23 or placebo (sodium chloride). The primary endpoints were the incidences of all-cause pneumonia and pneumococcal pneumonia. The secondary endpoint was death from pneumococcal pneumonia, all-cause pneumonia, or other causes. Cox regression models were used to estimate the risk of pneumonia overall for the placebo group compared with the vaccine group. Seventeen (3.7%) of 464 patients in the vaccine group and 15 (3.4%) of 436 patients in the placebo group developed pneumonia. There was no difference in the rates of pneumonia between the two study groups. The overall rate of pneumonia was 21.8 per 1000 person-years for patients with RA. The presence of interstitial pneumonia (hazard ratio: 3.601, 95% confidence interval: 1.547-8.380) was associated with an increased risk of pneumonia in RA patients. PPSV23 does not prevent against pneumonia overall in RA patients at relative risk for infections. Our results also confirm that the presence of interstitial lung disease is associated with pneumonia in Japanese patients with RA. UMIN-CTR UMIN000009566 . Registered 17 December 2012.

Comparison of dual influenza and pneumococcal polysaccharide vaccination with influenza vaccination alone for preventing pneumonia and reducing mortality among the elderly: A meta-analysis

PubMed Central

Zhang, Yan-Yang; Tang, Xue-Feng; Du, Chang-Hui; Wang, Bin-Bing; Bi, Zhen-Wang; Dong, Bi-Rong

2016-01-01

ABSTRACT The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination for the prevention of pneumonia and mortality in adults ≥ 65 years of age. Medline, Cochrane, CENTRAL, EMBASE, and Google Scholar databases were searched. Inclusion criteria were: 1) Randomized controlled trials (RCTs), 2-arm prospective studies, or retrospective cohort studies; 2) Patients were ≥ 65 years of age with or without chronic respiratory disease; 3) Patients received the influenza vaccine alone or dual pneumococcal and influenza vaccination; 4) Results included incidence of recurrent respiratory tract infections, length of hospital stay, and overall mortality rate. The outcomes were pneumonia and all-cause mortality rates. Of 142 studies identified in the database searches, 6 were ultimately included in the systematic review, and 5 were included in meta-analysis. The number of patients that received the influenza vaccination alone ranged from 211 to 29,346 (total = 53,107), and the number that received influenza+pneumococcal vaccination ranged from 246 to 72,107 (total = 102,068). Influenza+pneumococcal vaccination was associated with a significantly lower pneumonia rate than influenza vaccination alone (relative risk [RR] = 0.835, 95% confidence interval [CI]: 0.718–0.971, P = 0.019), and with a significantly lower all-cause mortality rate than influenza vaccination alone (relative risk [RR] = 0.771, 95% confidence interval [CI]: 0.707–0.842, P = 0.001). In conclusion, the results of this study support concomitant pneumococcal and influenza vaccination of the elderly as a dual vaccination strategy is associated with lower pneumonia and all-cause mortality rates. PMID:27629584

Impairment of pneumococcal antigen specific isotype-switched Igg memory B-cell immunity in HIV infected Malawian adults.

PubMed

Iwajomo, Oluwadamilola H; Finn, Adam; Ogunniyi, Abiodun D; Williams, Neil A; Heyderman, Robert S

2013-01-01

Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+) CD27(+) IgM(+) IgD(+)) depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.

Characteristics and prognosis of pneumococcal endocarditis: a case-control study.

PubMed

Daudin, M; Tattevin, P; Lelong, B; Flecher, E; Lavoué, S; Piau, C; Ingels, A; Chapron, A; Daubert, J-C; Revest, M

2016-06-01

Case series have suggested that pneumococcal endocarditis is a rare disease, mostly reported in patients with co-morbidities but no underlying valve disease, with a rapid progression to heart failure, and high mortality. We performed a case-control study of 28 patients with pneumococcal endocarditis (cases), and 56 patients with non-pneumococcal endocarditis (controls), not matched for sex and age, during the years 1991-2013, in one referral centre. Alcoholism (39.3% versus 10.7%; p <0.01), smoking (60.7% versus 21.4%; p <0.01), the absence of previously known valve disease (82.1% versus 60.7%; p 0.047), heart failure (64.3% versus 23.2%; p <0.01) and shock (53.6% versus 23.2%; p <0.01) were more common in pneumococcal than in non-pneumococcal endocarditis. Cardiac surgery was required in 64.3% of patients with pneumococcal endocarditis, much earlier than in patients with non-pneumococcal endocarditis (mean time from symptom onset, 14.1 ± 18.2 versus 69.0 ± 61.1 days). In-hospital mortality rates were similar (7.1% versus 12.5%). Streptococcus pneumoniae causes rapidly progressive endocarditis requiring life-saving early cardiac surgery in most cases. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[Pneumococcal vaccines. New conjugate vaccines for adults].

PubMed

Campins Martí, Magda

2015-11-01

Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

PubMed

Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

2016-01-01

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

Immunogenicity of 23-Valent Pneumococcal Vaccine in Children with Systemic Lupus Erythematosus.

PubMed

Alyasin, Soheila; Adab, Marzieh; Hosseinpour, Asieh; Amin, Reza; Babaei, Maryam

2016-09-01

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease which is characterized by B-cell abnormality and auto-antibody generation. Since bacterial infections are the most important causes of mortality in these patients, pneumococcal vaccination is recommended for children with SLE. To investigate humoral immunity and specific-antibody formation in response to a 23-valent polysaccharide pneumococcal vaccination in SLE children and asthmatic control group. The case and control groups consisted of 30 children with the mean age of 13 years who were matched by sex and age. Anti-pneumococcal antibody titers were determined using Enzyme-Linked Immunosorbent Assay (ELISA) before the vaccination with the 23-valent pneumococcal vaccine and 3 weeks later in both groups. Also the correlation between anti-pneumococcal antibody titer and different factors including age, sex, lupus activity, disease duration, medications, history of recurrent infections, and laboratory data were investigated. Both groups showed significant increases in anti-pneumococcal antibody level after vaccination (p≤0.001). The increase in antibody level were almost the same in both groups (p≥0.05) such that 77.7% of SLE children and 86.2% of control children showed at least 2-fold increase in anti-pneumococcal antibody titer following immunization. Significant correlations were seen between the level of post-immunization anti-pneumococcal antibody with the age of children with SLE (p=0.02) and their age of disease onset (p=0.02). It is concluded that pneumococcal vaccination is generally immunogenic in children with SLE. However, a small group of patients show impaired response to the vaccine.

Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis.

PubMed

Falkenhorst, Gerhard; Remschmidt, Cornelius; Harder, Thomas; Hummers-Pradier, Eva; Wichmann, Ole; Bogdan, Christian

2017-01-01

Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries. We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias. We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35-80%) in two clinical trials and 48% (95%CI: 25-63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity. Our meta-analysis revealed significant VE of PPV23 against both IPD and pneumococcal pneumonia by any serotype in the elderly, comparable to the efficacy of PCV13 against vaccine-serotype disease in a recent clinical trial in elderly people. Due to its broader serotype coverage and the decrease of PCV13 serotypes among adults resulting from routine infant immunization with PCV13, PPV23 continues to play an important role for protecting adults against IPD and pneumococcal pneumonia.

Persistent Sex Disparities in Invasive Pneumococcal Diseases in the Conjugate Vaccine Era.

PubMed

de St Maurice, Annabelle; Schaffner, William; Griffin, Marie R; Halasa, Natasha; Grijalva, Carlos G

2016-09-01

Few studies have characterized the role of sex on the incidence of invasive pneumococcal disease (IPD). We examined sex differences in rates of IPD, and trends after the introduction of pneumococcal conjugate vaccines (PCVs). We used active population and laboratory-based IPD surveillance data from the Centers for Disease Control and Prevention Active Bacterial Core surveillance program (1998-2013) in Tennessee. Population-based rates of IPD by sex, race, age group, and PCV era were calculated. Rates were compared using incidence rate ratios. Throughout the study years, rates of IPD were higher in male than in female subjects, particularly in children <2 years and adults 40-64 years of age, with male subjects having IPD rates 1.5-2 times higher than female subjects. The proportions of comorbid conditions were similar in male and female subjects . Sex rate differences persisted after stratification by race. Although the introductions of 7-valent PCV (PCV7) and 13-valent PCV (PCV13) were associated with declines in IPD rates in both sexes, rates of IPD after PCV13 were still significantly higher in male than in female subjects among children and adults 40-64 and >74 years of age. Rates of IPD were generally higher in male than in female subjects. These sex differences were observed in different race groups and persisted after introduction of both PCVs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Pneumococcal septic arthritis in adults: clinical analysis and review.

PubMed

Belkhir, L; Rodriguez-Villalobos, H; Vandercam, B; Marot, J C; Cornu, O; Lambert, M; Yombi, J C

2014-01-01

Septic arthritis (SA) is a rheumatological emergency that can lead to rapid joint destruction and irreversible loss of function. The most common pathogen causing SA is Staphylococcus aureus which is responsible for 37-65% of cases. Streptococcus pneumoniae is traditionally described as an uncommon cause of SA of a native joint. The objective of our study was to analyse clinical characteristics, treatment, and outcome of all cases of pneumococcal septic arthritis treated in our institution, and to compare them with other series published in the literature. We conducted a retrospective study of pneumococcal SA identified among all cases of SA diagnosed in a teaching hospital of one thousand beds between 2004 and 2009. Diagnosis was based on culture of joint liquid or by the presence of pneumococcal bacteraemia and purulent (more than 50 000/mm(3) white blood cells with more than 90% neutrophils) joint fluid aspiration. Among 266 cases of SA, nine patients (3·3%) were diagnosed as having pneumococcal SA. The median age was 75 years. The main affected joint was the knee (7/9). No patient had more than one joint involved. Four patients suffered from concomitant pneumonia. Joint culture and blood cultures were positive in 7/9 and 5/9, respectively. Median (range) length of stay was 18 days (3-47 days). One patient with associated pneumococcal bacteraemia died 19 days after admission. Seven patients recovered completely. Streptococcus pneumoniae is now being increasingly recognized as a common agent of SA. This organism is frequently associated with pneumococcal pneumonia or bacteraemia, particularly in patients with advanced age and comorbidities. Direct inoculation of joint fluid into blood culture medium BACTEC system increases the probability of microbiological diagnosis. The prognosis is usually favourable if the disease is promptly recognized and treated (antibiotic therapy combined with joint drainage).

Case report: Guillain-Barre syndrome with pneumococcus - A new association in pediatrics.

PubMed

Khatib, Hassan El; Naous, Amal; Ghanem, Soha; Dbaibo, Ghassan; Rajab, Mariam

2018-01-01

Guillain-Barre Syndrome, an acute flaccid paralysis known to be caused by recent Gastro-intestinal infections mainly campylobacter, and Respiratory infections mainly mycoplasma pneumoniae and influenza. One reported case of severe invasive pneumococcal disease in a 68 year old female, that presented with Austrian's triad of meningitis, pneumonia and endocarditis, and progressed to develop Guillain Barre syndrome, an association never been documented before. We present a case of 13 year old male, presented with hypoactivity and inability to bare his own weight, developed septic shock due to pneumococcus with Acute Respiratory Distress Syndrome, and was found to have neurological findings of Guillain-Barre Syndrome. A new association in pediatric age group, never been reported before.

Role of an Iron-Dependent Transcriptional Regulator in the Pathogenesis and Host Response to Infection with Streptococcus pneumoniae

PubMed Central

Gupta, Radha; Bhatty, Minny; Swiatlo, Edwin; Nanduri, Bindu

2013-01-01

Iron is a critical cofactor for many enzymes and is known to regulate gene expression in many bacterial pathogens. Streptococcus pneumoniae normally inhabits the upper respiratory mucosa but can also invade and replicate in lungs and blood. These anatomic sites vary considerably in both the quantity and form of available iron. The genome of serotype 4 pneumococcal strain TIGR4 encodes a putative iron-dependent transcriptional regulator (IDTR). A mutant deleted at idtr (Δidtr) exhibited growth kinetics similar to parent strain TIGR4 in vitro and in mouse blood for up to 48 hours following infection. However, Δidtr was significantly attenuated in a murine model of sepsis. IDTR down-regulates the expression of ten characterized and putative virulence genes in nasopharyngeal colonization and pneumonia. The host cytokine response was significantly suppressed in sepsis with Δidtr. Since an exaggerated inflammatory response is associated with a poor prognosis in sepsis, the decreased inflammatory response could explain the increased survival with Δidtr. Our results suggest that IDTR, which is dispensable for pneumococcal growth in vitro, is associated with regulation of pneumococcal virulence in specific host environments. Additionally, IDTR ultimately modulates the host cytokine response and systemic inflammation that contributes to morbidity and mortality of invasive pneumococcal disease. PMID:23437050

Prevotella intermedia Induces Severe Bacteremic Pneumococcal Pneumonia in Mice with Upregulated Platelet-Activating Factor Receptor Expression

PubMed Central

Nagaoka, Kentaro; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

2014-01-01

Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells. PMID:24478074

Prevotella intermedia induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression.

PubMed

Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

2014-02-01

Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in HIV-Infected and -Uninfected Children in South Africa: A Matched Case-Control Study

PubMed Central

Cohen, Cheryl; von Mollendorf, Claire; de Gouveia, Linda; Naidoo, Nireshni; Meiring, Susan; Quan, Vanessa; Nokeri, Vusi; Fortuin-de Smit, Melony; Malope-Kgokong, Babatyi; Moore, David; Reubenson, Gary; Moshe, Mamokgethi; Madhi, Shabir A.; Eley, Brian; Hallbauer, Ute; Kularatne, Ranmini; Conklin, Laura; O'Brien, Katherine L.; Zell, Elizabeth R.; Klugman, Keith; Whitney, Cynthia G.; von Gottberg, Anne; Moore, David; Verwey, Charl; Varughese, Sheeba; Archary, Moherndran; Naby, Fathima; Dawood, Khathija; Naidoo, Ramola; Elliott, Gene; Hallbauer, Ute; Eley, Brian; Nuttall, James; Cooke, Louise; Finlayson, Heather; Rabie, Helena; Whitelaw, Andrew; Perez, Dania; Jooste, Pieter; Naidoo, Dhamiran; Kularatne, Ranmini; Reubenson, Gary; Cohen, Cheryl; de Gouveia, Linda; du Plessis, Mignon; Govender, Nevashan; Meiring, Susan; Quan, Vanessa; von Mollendorf, Claire; Fortuin-de Smidt, Melony; Naidoo, Nireshni; Malope-Kgokong, Babatyi; Nokeri, Vusi; Ncha, Relebohile; Lindani, Sonwabo; von Gottberg, Anne; Spies, Barry; Sono, Lino; Maredi, Phasweni; Hamese, Ken; Moshe, Mamokgethi; Nchabeleng, Maphosane; Ngcobo, Ntombenhle; van den Heever, Johann; Madhi, Shabir; Conklin, Laura; Verani, Jennifer; Whitney, Cynthia; Zell, Elizabeth; Loo, Jennifer; Nelson, George; Klugman, Keith; O'Brien, Katherine

2014-01-01

Background. South Africa introduced 7-valent pneumococcal conjugate vaccine (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We estimated the effectiveness of ≥2 PCV7 doses against invasive pneumococcal disease (IPD) in human immunodeficiency virus (HIV)–infected and -uninfected children. Methods. IPD (pneumococcus identified from a normally sterile site) cases were identified through national laboratory-based surveillance. Specimens were serotyped by Quellung or polymerase chain reaction. Four controls, matched for age, HIV status, and hospital were sought for each case. Using conditional logistic regression, we calculated vaccine effectiveness (VE) as 1 minus the adjusted odds ratio for vaccination. Results. From March 2010 through November 2012, we enrolled 187 HIV-uninfected (48 [26%] vaccine serotype) and 109 HIV-infected (43 [39%] vaccine serotype) cases and 752 HIV-uninfected and 347 HIV-infected controls aged ≥16 weeks. Effectiveness of ≥2 PCV7 doses against vaccine-serotype IPD was 74% (95% confidence interval [CI], 25%–91%) among HIV-uninfected and −12% (95% CI, −449% to 77%) among HIV-infected children. Effectiveness of ≥3 doses against vaccine-serotype IPD was 90% (95% CI, 14%–99%) among HIV-uninfected and 57% (95% CI, −371% to 96%) among HIV-infected children. Among HIV-exposed but -uninfected children, effectiveness of ≥2 doses was 92% (95% CI, 47%–99%) against vaccine-serotype IPD. Effectiveness of ≥2 doses against all-serotype multidrug-resistant IPD was 96% (95% CI, 62%–100%) among HIV-uninfected children. Conclusions. A 2 + 1 PCV7 schedule was effective in preventing vaccine-serotype IPD in HIV-uninfected and HIV-exposed, uninfected children. This finding supports the World Health Organization recommendation for this schedule as an alternative to a 3-dose primary series among HIV-uninfected individuals. PMID:24917657

Are risk factors associated with invasive pneumococcal disease according to different serotypes?

PubMed Central

Ciruela, Pilar; Soldevila, Núria; Selva, Laura; Hernández, Sergi; Garcia-Garcia, Juan Jose; Moraga, Fernando; de Sevilla, Mariona F.; Codina, Gemma; Planes, Ana Maria; Esteva, Cristina; Coll, Francis; Cardeñosa, Neus; Jordan, Iolanda; Batalla, Joan; Salleras, Luis; Muñoz-Almagro, Carmen; Domínguez, Angela

2013-01-01

The aim of this study was to investigate risk factors for the most common serotypes of invasive pneumococcal disease (IPD). A total of 293 IPD cases were analyzed in children aged 3–59 mo in a community with intermediate vaccination coverage with the 7-valent pneumococcal vaccine (PCV7). IPD cases were reviewed during 2007–2009 in two pediatric hospitals in Catalonia (Spain). A multivariate analysis using unconditional logistic regression was performed to estimate the adjusted odds ratio. PCV7 coverage was 45.4%. Pneumonia with empyema (64.5%) was the most frequent clinical manifestation. The most common serotypes were: serotype 1 (21.2%), 19A (16.0%), 3 (12.6%) and 7F/A (6.8%). 70.0% of serotypes found were included in the 13-valent conjugate vaccine (PCV13), 39.2% in the 10-valent conjugate vaccine and 8.1% in the PCV7. PCV7 was protective in IPD cases due to PCV7-serotypes (aOR: 0.15, 95% CI:0.04–0.55). Serotype 1 was positively associated with attending day care or school (aOR: 3.55, 95% CI: 1.21–10.38) and age 24–59 mo (aOR: 7.70, 95% CI:2.70–21.98). Serotype 19A was positively associated with respiratory infection in the previous month (aOR: 2.26, 95% CI: 1.03–4.94), non-penicillin susceptible IPD (aOR: 1.89, 95% CI:1.13–3.16) and negatively associated with age 24–59 mo (aOR: 0.19, 95% CI:0.09–0.41). Serotype 3 was positively associated with vaccination (aOR: 4.87, 95% CI:2.05–11.59). No factors were associated with serotype 7F/A. Vaccination with pneumococcal vaccines including more serotypes may reduce the risk of disease in our setting. PMID:23295982

Are risk factors associated with invasive pneumococcal disease according to different serotypes?

PubMed

Ciruela, Pilar; Soldevila, Núria; Selva, Laura; Hernández, Sergi; Garcia-Garcia, Juan Jose; Moraga, Fernando; de Sevilla, Mariona F; Codina, Gemma; Planes, Ana Maria; Esteva, Cristina; Coll, Francis; Cardeñosa, Neus; Jordan, Iolanda; Batalla, Joan; Salleras, Luis; Muñoz-Almagro, Carmen; Domínguez, Angela

2013-03-01

The aim of this study was to investigate risk factors for the most common serotypes of invasive pneumococcal disease (IPD). A total of 293 IPD cases were analyzed in children aged 3-59 mo in a community with intermediate vaccination coverage with the 7-valent pneumococcal vaccine (PCV7). IPD cases were reviewed during 2007-2009 in two pediatric hospitals in Catalonia (Spain). A multivariate analysis using unconditional logistic regression was performed to estimate the adjusted odds ratio. PCV7 coverage was 45.4%. Pneumonia with empyema (64.5%) was the most frequent clinical manifestation. The most common serotypes were: serotype 1 (21.2%), 19A (16.0%), 3 (12.6%) and 7F/A (6.8%). 70.0% of serotypes found were included in the 13-valent conjugate vaccine (PCV13), 39.2% in the 10-valent conjugate vaccine and 8.1% in the PCV7. PCV7 was protective in IPD cases due to PCV7-serotypes (aOR: 0.15, 95% CI:0.04-0.55). Serotype 1 was positively associated with attending day care or school (aOR: 3.55, 95% CI: 1.21-10.38) and age 24-59 mo (aOR: 7.70, 95% CI:2.70-21.98). Serotype 19A was positively associated with respiratory infection in the previous month (aOR: 2.26, 95% CI: 1.03-4.94), non-penicillin susceptible IPD (aOR: 1.89, 95% CI:1.13-3.16) and negatively associated with age 24-59 mo (aOR: 0.19, 95% CI:0.09-0.41). Serotype 3 was positively associated with vaccination (aOR: 4.87, 95% CI:2.05-11.59). No factors were associated with serotype 7F/A. Vaccination with pneumococcal vaccines including more serotypes may reduce the risk of disease in our setting.

Generalisability of vaccine effectiveness estimates: an analysis of cases included in a postlicensure evaluation of 13-valent pneumococcal conjugate vaccine in the USA

PubMed Central

Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Rosen, Jennifer B; Motala, Tasneem; Mascola, Laurene; Eason, Jeffery; Scherzinger, Karen; Holtzman, Corinne; Reingold, Arthur L; Barnes, Meghan; Petit, Susan; Farley, Monica M; Harrison, Lee H; Zansky, Shelley; Thomas, Ann; Schaffner, William; McGee, Lesley; Whitney, Cynthia G; Moore, Matthew R

2017-01-01

Objectives External validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case–control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA. Design Matched case–control study. Setting Thirteen active surveillance sites for invasive pneumococcal disease in the USA. Participants Cases were identified from active surveillance and controls were age and zip code matched. Outcome measures Socioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment. Results We enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p<0.01). Enrolled cases also tended to come from more affluent census tracts. Despite these differences, our best predictive model for enrolment yielded a concordance statistic of only 0.703, indicating mediocre predictive value. Variables retained in the final model were assessed for effect measure modification, and none were found to be significant modifiers of vaccine effectiveness. Conclusions We conclude that although enrolled cases are somewhat more affluent than unenrolled cases, our estimates are externally valid with respect to socioeconomic status. Our analysis provides evidence that this study design can yield valid estimates and the assessing generalisability of observational data is feasible, even when unenrolled individuals cannot be contacted. PMID:28851801

The full benefits of adult pneumococcal vaccination: A systematic review.

PubMed

Cafiero-Fonseca, Elizabeth T; Stawasz, Andrew; Johnson, Sydney T; Sato, Reiko; Bloom, David E

2017-01-01

Pneumococcal disease causes substantial morbidity and mortality, including among adults. Adult pneumococcal vaccines help to prevent these burdens, but they are underused. Accounting for the full benefits of adult pneumococcal vaccination may promote more rational resource allocation decisions with respect to adult pneumococcal vaccines. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review to assess the extent to which the literature has empirically captured (e.g., through measurement or modeling) the full benefits of adult pneumococcal vaccination. We systematically searched PubMed and Embase to identify studies published between January 1, 2010 and April 10, 2016 that examine adult pneumococcal vaccination. We included articles if they captured any health or economic benefit of an adult pneumococcal vaccine administered to adults age ≥ 50 or ≥ 18 in risk groups. Finally, we summarized the literature by categorizing the types of benefits captured, the perspective taken, and the strength of the evidence presented. Our protocol is number 42016038335 in the PROSPERO International prospective register of systematic reviews. We identified 5,857 papers and included 150 studies for analysis. While most capture health gains and healthcare cost savings, far fewer studies consider additional benefit categories, such as productivity gains. However, the studies with a broader approach still exhibit significant limitations; for example, many present only abstracts, while others offer no new measurements. Studies that examine the 13-valent pneumococcal conjugate vaccine focus more on broad economic benefits, but still have limitations. This review highlights the need for more robust empirical accounting of the full benefits of adult pneumococcal vaccination. Literature outside this realm indicates that these broad benefits may be substantial. Failing to investigate the full benefits may lead society to undervalue vaccines' contributions and therefore underinvest in their development and adoption.

A cohort study of the impact and acquisition of naspharyngeal carriage of Streptococcus pneumoniae during the Hajj.

PubMed

Memish, Ziad A; Al-Tawfiq, Jaffar A; Almasri, Malak; Akkad, Nadia; Yezli, Saber; Turkestani, Abdulhafeez; van der Linden, Mark; Assiri, Abdullah

2016-01-01

The annual Muslim pilgrimage attracts over two million pilgrims who gather in a limited time and space. The pilgrimage carries the potential risk of increase risk of the acquisition of Streptococcus pneumonia. In this cohort study, we evaluate the effect of the Hajj on the prevalence of pneumococcal serotype nasopharyngeal carriage in the Hajj pilgrim population. The secondary objective is to evaluate the effects of the mass gathering on carriage of invasive pneumococcal serotypes. This is a prospective cohort study with two data collection periods: at the beginning and at the end of the Hajj. Nasopharyngeal samples were taken via a standardized swabbing method. A total of 1175 pilgrims were enrolled at the beginning of the study and 1155 (98.3%) were included at the second part of the study. The pre-Hajj samples were obtained at a mean of 0 days and the post-Hajj sampling occurred at a mean of 15 days after arrival to Saudi Arabia. The overall carriage rate of Streptococcus pneumoniae in the pre- and post-Hajj was 1.8% and 7.1% (P = 0.0016). The potential coverage of the 7-valent pneumococcal conjugate vaccine (PCV7), PCV10 and PCV13 were 15.5%, 19.1%; and 35.5%, respectively. The coverage for the 23-valent pneumococcal polysaccharide vaccine (PPV23) was 40%. Although there was an increase in the acquisition of S. pneumoniae, its magnitude is low which does not support public health recommendations for general pneumococcal vaccination of pilgrims except those at risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

Promoting pneumococcal immunizations among rural Medicare beneficiaries using multiple strategies.

PubMed

Johnson, Elizabeth A; Harwell, Todd S; Donahue, Peg M; Weisner, M'liss A; McInerney, Michael J; Holzman, Greg S; Helgerson, Steven D

2003-01-01

Vaccine-preventable diseases among adults are major contributing causes of morbidity and mortality in the United States. However, adult immunizations continue to be underutilized in both urban and rural areas. To evaluate the effectiveness of a community-wide education campaign and mailed reminders promoting pneumococcal immunizations to rural Medicare beneficiaries. We implemented a community-wide education campaign, and mailed reminders were sent to Medicare beneficiaries in 1 media market in Montana to increase pneumococcal immunizations. In a second distinct media market, mailed reminders only were sent to beneficiaries. The proportion of respondents aged 65 years and older aware of pneumococcal immunizations increased significantly from baseline to follow-up among respondents both in the education-plus-reminder (63% to 78%, P = 0.04) and the reminder-only (64% to 74%, P = 0.05) markets. Overall from 1998 to 1999, there was a 3.7-percentage-point increase in pneumococcal immunization claims for Medicare beneficiaries in the education-plus-reminder market and a 1.5-percentage-point increase in the reminder-only market. Medicare beneficiaries sent reminders in the education-plus-reminder market compared to those in the reminder-only market were more likely to have a claim for pneumococcal immunization in 1999 (odds ratio 1.18, 95% confidence interval 1.08 to 1.28). The results suggest that these quality improvement strategies (community education plus reminders and reminders alone) modestly increased pneumococcal immunization awareness and pneumococcal immunization among rural adults. Mailed reminder exposure was associated with an increased prevalence of pneumococcal immunizations between 1998 and 1999 and was augmented somewhat by the education campaign.

[Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age].

PubMed

Albrecht, Piotr; Antczak, Adam; Hryniewicz, Waleria; Skoczyńska, Anna; Radzikowski, Andrzej; Kedziora-Kornatowska, Kornelia; Bernatowska, Ewa; Stompór, Tomasz; Grodzicki, Tomasz; Gyrczuk, Ewa; Imiela, Jacek; Jedrzejczak, Wiesław; Windak, Adam

2014-02-01

Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD risk groups in the age > 19 years. At these work research findings were described above PPV23 and PCV13 at adults and world recommendations of applying both vaccines in risk groups from 19 years up to the advanced years. Also Polish recommendations of optimum applying of these vaccines were presented. They are recommending applying PCV13 at first in them, while PPV23, if to her readings exist should be given to > or = 8 of weeks from PCV13. In persons > or = 19 years which earlier received 1 or should receive more PPV23 doses first PCV13 dose should be given after the year or later than the last PPV23 dose, and then again PPV23 > or = 8 of weeks from PCV13 and the second PPV23 dose not earlier than 5 years from last PPV23. If the PPV23 application seems to be justified, it is irrespective of the more previous state vaccination against pneumococci, PCV13 should be given to as first.

Estimating the proportion of pneumonia attributable to pneumococcus in Kenyan adults: latent class analysis.

PubMed

Jokinen, Jukka; Scott, J Anthony G

2010-09-01

Community-acquired pneumonia is a common cause of hospitalization among African adults, and Streptococcus pneumoniae is assumed to be a frequent cause. Pneumococcal conjugate vaccine is currently being introduced into childhood immunization programs in Africa. The case for adult vaccination is dependent on the contribution of the pneumococcus to the hospital pneumonia burden. Pneumococcal diagnosis is complex because there is no gold standard, and culture methods are invalidated by antibiotic use. We used latent class analysis to estimate the proportion of pneumonia episodes caused by pneumococcus. Furthermore, we extended this methodology to evaluate the effect of antimicrobial treatment on test accuracies and the prevalence of the disease. The study combined data from 5 validation studies of pneumococcal diagnostic tests performed on 281 Kenyan adults with pneumonia. The proportion of pneumonia episodes attributable to pneumococcus was 0.46 (95% confidence interval = 0.36-0.57). Failure to account for the effect of antimicrobial exposure underestimates this proportion as 0.32. A history of antibiotic exposure was a poor predictor of antimicrobial activity in patients' urine. Blood culture sensitivity for pneumococcus was estimated at 0.24 among patients with antibiotic exposure, and 0.75 among those without. The large contribution of pneumococcus to adult pneumonia provides a strong case for the investigation of pneumococcal vaccines in African adults.

Cost-effectiveness of 13-valent pneumococcal conjugate vaccination in Mongolia.

PubMed

Sundaram, Neisha; Chen, Cynthia; Yoong, Joanne; Luvsan, Munkh-Erdene; Fox, Kimberley; Sarankhuu, Amarzaya; La Vincente, Sophie; Jit, Mark

2017-02-15

The Ministry of Health (MOH), Mongolia, is considering introducing 13-valent pneumococcal conjugate vaccine (PCV13) in its national immunization programme to prevent the burden of disease caused by Streptococcus pneumoniae. This study evaluates the cost-effectiveness and budget impact of introducing PCV13 compared to no PCV vaccination in Mongolia. The incremental cost-effectiveness ratio (ICER) of introducing PCV13 compared to no PCV vaccination was assessed using an age-stratified static multiple cohort model. The risk of various clinical presentations of pneumococcal disease (meningitis, pneumonia, non-meningitis non-pneumonia invasive pneumococcal disease and acute otitis media) at all ages for thirty birth cohorts was assessed. The analysis considered both health system and societal perspectives. A 3+0 vaccine schedule and price of US$3.30 per dose was assumed for the baseline scenario based on Gavi, the Vaccine Alliance's advance market commitment tail price. The ICER of PCV13 introduction is estimated at US$52 per disability-adjusted life year (DALY) averted (health system perspective), and cost-saving (societal perspective). Although indirect effects of PCV have been well-documented, a conservative scenario that does not consider indirect effects estimated PCV13 introduction to cost US$79 per DALY averted (health system perspective), and US$19 per DALY averted (societal perspective). Vaccination with PCV13 is expected to cost around US$920,000 in 2016, and thereafter US$820,000 every year. The programme is likely to reduce direct disease-related costs to MOH by US$440,000 in the first year, increasing to US$510,000 by 2025. Introducing PCV13 as part of Mongolia's national programme appears to be highly cost-effective when compared to no vaccination and cost-saving from a societal perspective at vaccine purchase prices offered through Gavi. Notwithstanding uncertainties around some parameters, cost-effectiveness of PCV introduction for Mongolia remains robust over a range of conservative scenarios. Availability of high-quality national data would improve future economic analyses for vaccine introduction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

New vaccines against otitis media: projected benefits and cost-effectiveness.

PubMed

O'Brien, Megan A; Prosser, Lisa A; Paradise, Jack L; Ray, G Thomas; Kulldorff, Martin; Kurs-Lasky, Marcia; Hinrichsen, Virginia L; Mehta, Jyotsna; Colborn, D Kathleen; Lieu, Tracy A

2009-06-01

New vaccines that offer protection against otitis media caused by nontypeable Haemophilus influenzae and by Moraxella catarrhalis are under development. However, the potential health benefits and economic effects of such candidate vaccines have not been systematically assessed. We created a computerized model to compare the projected benefits and costs of (1) the currently available 7-valent pneumococcal conjugate vaccine, (2) a candidate pneumococcal-nontypeable H influenzae vaccine that has been tested in Europe, (3) a hypothetical pneumococcal-nontypeable H influenzae-Moraxella vaccine, and (4) no vaccination. The clinical probabilities of acute otitis media and of otitis media with effusion were generated from multivariate analyses of data from 2 large health maintenance organizations and from the Pittsburgh Child Development/Otitis Media Study cohort. Other probabilities, costs, and quality-of-life values were derived from published and unpublished sources. The base-case analysis assumed vaccine dose costs of $65 for the 7-valent pneumococcal conjugate vaccine, $100 for the pneumococcal-nontypeable H influenzae vaccine, and $125 for the pneumococcal-nontypeable H influenzae-Moraxella vaccine. With no vaccination, we projected that 13.7 million episodes of acute otitis media would occur annually in US children aged 0 to 4 years, at an annual cost of $3.8 billion. The 7-valent pneumococcal conjugate vaccine was projected to prevent 878,000 acute otitis media episodes, or 6.4% of those that would occur with no vaccination; the corresponding value for the pneumococcal-nontypeable H influenzae vaccine was 3.7 million (27%) and for the pneumococcal-nontypeable H influenzae-Moraxella vaccine was 4.2 million (31%). Using the base-case vaccine costs, pneumococcal-nontypeable H influenzae vaccine use would result in net savings compared with nontypeable 7-valent pneumococcal conjugate use. Conversely, pneumococcal-nontypeable H influenzae-Moraxella vaccine use would not result in savings compared with pneumococcal-nontypeable H influenzae vaccine use, but would cost $48 000 more per quality-adjusted life-year saved. The results were sensitive to variations in assumptions on vaccine effectiveness and vaccine dose costs but not to variations in other assumptions. New candidate vaccines against otitis media have the potential to prevent millions of disease episodes in the United States annually. If priced comparably with other recently introduced vaccines, these new otitis vaccines could achieve cost-effectiveness comparable with or more favorable than that of the 7-valent pneumococcal conjugate vaccine.

Development and preliminary data on the use of a mobile app specifically designed to increase community awareness of invasive pneumococcal disease and its prevention.

PubMed

Panatto, Donatella; Domnich, Alexander; Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Bragazzi, Nicola Luigi; Signori, Alessio; Landa, Paolo; Bechini, Angela; Boccalini, Sara

2016-04-02

Given the growing use and great potential of mobile apps, this project aimed to develop and implement a user-friendly app to increase laypeople's knowledge and awareness of invasive pneumococcal disease (IPD). Despite the heavy burden of IPD, the documented low awareness of IPD among both laypeople and healthcare professionals and far from optimal pneumococcal vaccination coverage, no app specifically targeting IPD has been developed so far. The app was designed to be maximally functional and conceived in accordance with user-centered design. Its content, layout and usability were discussed and formally tested during several workshops that involved the principal stakeholders, including experts in IPD and information technology and potential end-users. Following several workshops, it was decided that, in order to make the app more interactive, its core should be a personal "checker" of the risk of contracting IPD and a user-friendly risk-communication strategy. The checker was populated with risk factors identified through both Italian and international official guidelines. Formal evaluation of the app revealed its good readability and usability properties. A sister web site with the same content was created to achieve higher population exposure. Seven months after being launched in a price- and registration-free modality, the app, named "Pneumo Rischio," averaged 20.9 new users/day and 1.3 sessions/user. The first in-field results suggest that "Pneumo Rischio" is a promising tool for increasing the population's awareness of IPD and its prevention through a user-friendly risk checker.

Influence of the pneumococcal conjugate vaccines on the temporal variation of pneumococcal carriage and the nasal microbiota in healthy infants: a longitudinal analysis of a case-control study.

PubMed

Mika, Moana; Maurer, Josua; Korten, Insa; Allemann, Aurélie; Aebi, Suzanne; Brugger, Silvio D; Qi, Weihong; Frey, Urs; Latzin, Philipp; Hilty, Markus

2017-07-24

Bacterial colonization of the upper airways is a prerequisite for subsequent invasive disease. With the introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13), changes in pneumococcal upper airway colonization have been described. It is, however, less evident whether the vaccines lead to compositional changes of the upper airway microbiota. Here, we performed a case-control study using samples from a longitudinal infant cohort from Switzerland. We compared pneumococcal carriage and the nasal microbiota within the first year of life of healthy infants vaccinated with either PCV7 (n = 20, born in 2010) or PCV13 (n = 21, born between 2011 and 2013). Nasal swabs were collected every second week (n = 763 in total). Pneumococcal carriage was analyzed by quantitative PCR of the pneumococcal-specific lytA gene. Analysis of the bacterial core microbiota was performed based on 16S rRNA sequencing and subsequent oligotyping. We exclusively performed oligotyping of the core microbiota members, which were defined as the five most abundant bacterial families (Moraxellaceae, Streptococcaceae, Staphylococcaceae, Corynebacteriaceae, and Pasteurellaceae). Linear mixed effect (LME) and negative binomial regression models were used for statistical analyses. We found a higher number of samples positive for pneumococcal carriage in PCV7- compared to PCV13-vaccinated infants (LME model; P = 0.01). In contrast, infants vaccinated in the PCV13 era had an increased alpha diversity as measured by the richness and the Shannon Diversity Index (LME model; P = 0.003 and P = 0.01, respectively). Accordingly, the PCV13 era was associated with clusters of a higher diversity than PCV7-associated clusters. Furthermore, infants vaccinated with PCV13 had a higher binary-based within-subject microbiota similarity, as well as a decreased Jensen-Shannon distance over time as compared to PCV7-vaccinated infants, indicating a higher microbiota stability in the PCV13 era (LME model and t test; P = 0.06 and P = 0.03, respectively). We hypothesize that the higher diversity and stability of the upper airway microbiota in the PCV13 era is the result of the lower pneumococcal carriage rate. This seems to indicate that the nasal bacterial microbiota of infants has changed in recent years as compared to the beginning of this study.

Impact of Pneumococcal Conjugate Vaccination on Otitis Media: A Systematic Review

PubMed Central

Taylor, Sylvia; Marchisio, Paola; Vergison, Anne; Harriague, Julie; Hausdorff, William P.; Haggard, Mark

2012-01-01

Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%–9% in randomized trials and 17%–23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3–5 years before 7vCRM introduction (mean change, −15%; range, +14% to −24%) and continued to decline afterward (mean, −19%; range, +7% to −48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM. PMID:22423134

67 FR 61110 - Vaccine Information Materials for Pneumococcal Conjugate, Diphtheria, Tetanus, acellular...

Federal Register 2010, 2011, 2012, 2013, 2014

2002-09-27

... cause of bacterial meningitis in the United States. (Meningitis is an infection of the covering of the... meningitis [sbull] 13,000 blood infections, and [sbull] About 5 million ear infections It can also lead to... pneumococcal disease, such as meningitis and blood infections. It can also prevent some ear infections. But ear...

Genetic factors regulating lung vasculature and immune cell functions associate with resistance to pneumococcal infection.

PubMed

Jonczyk, Magda S; Simon, Michelle; Kumar, Saumya; Fernandes, Vitor E; Sylvius, Nicolas; Mallon, Ann-Marie; Denny, Paul; Andrew, Peter W

2014-01-01

Streptococcus pneumoniae is an important human pathogen responsible for high mortality and morbidity worldwide. The susceptibility to pneumococcal infections is controlled by as yet unknown genetic factors. To elucidate these factors could help to develop new medical treatments and tools to identify those most at risk. In recent years genome wide association studies (GWAS) in mice and humans have proved successful in identification of causal genes involved in many complex diseases for example diabetes, systemic lupus or cholesterol metabolism. In this study a GWAS approach was used to map genetic loci associated with susceptibility to pneumococcal infection in 26 inbred mouse strains. As a result four candidate QTLs were identified on chromosomes 7, 13, 18 and 19. Interestingly, the QTL on chromosome 7 was located within S. pneumoniae resistance QTL (Spir1) identified previously in a linkage study of BALB/cOlaHsd and CBA/CaOlaHsd F2 intercrosses. We showed that only a limited number of genes encoded within the QTLs carried phenotype-associated polymorphisms (22 genes out of several hundred located within the QTLs). These candidate genes are known to regulate TGFβ signalling, smooth muscle and immune cells functions. Interestingly, our pulmonary histopathology and gene expression data demonstrated, lung vasculature plays an important role in resistance to pneumococcal infection. Therefore we concluded that the cumulative effect of these candidate genes on vasculature and immune cells functions as contributory factors in the observed differences in susceptibility to pneumococcal infection. We also propose that TGFβ-mediated regulation of fibroblast differentiation plays an important role in development of invasive pneumococcal disease. Gene expression data submitted to the NCBI Gene Expression Omnibus Accession No: GSE49533 SNP data submitted to NCBI dbSNP Short Genetic Variation http://www.ncbi.nlm.nih.gov/projects/SNP/snp_viewTable.cgi?handle=MUSPNEUMONIA.

Pneumococcal conjugate vaccine use in adults - Addressing an unmet medical need for non-bacteremic pneumococcal pneumonia.

PubMed

Sings, Heather L

2017-09-25

Streptococcus pneumoniae is a frequent cause of community acquired pneumonia (CAP), with the largest burden of disease attributed to non-bacteremic pneumonia. Due to the high persistent burden of disease, pneumococcal pneumonia, particularly non-bacteremic pneumococcal pneumonia, continues to be a major public health concern. There are currently two pneumococcal vaccines approved for use in adults in the United States (US) and other countries worldwide: a 23-valent pneumococcal simple polysaccharide vaccine (PPV23), and a 13-valent pneumococcal conjugate vaccine (PCV13). The capsular polysaccharides included in PPV23 induce antibodies primarily by a T-cell independent mechanism, thus the immune response is short lived and lacks the ability to elicit an anamnestic response. PCV13, on the other hand, has the bacterial polysaccharides covalently conjugated to an immunogenic carrier protein resulting in the formation of memory B lymphocytes, thus proving long-acting immunologic memory and an anamnestic response. Despite 30years of use, the question of PPV23 vaccine efficacy, particularly with respect to efficacy for non-bacteremic pneumonia, has been extensively debated and investigated; whereas PCV13 efficacy against vaccine-type pneumococcal CAP, both bacteremic and non-bacteremic, was confirmed in a large randomized controlled trial in older adults. PCV13 was approved under the US Food and Drug Administration's accelerated pathway, which allows for earlier approval of products that provide meaningful benefit over existing treatments - in this case, protection of adults from non-bacteremic pneumococcal pneumonia. Its use is now increasingly recommended globally. This article summarizes the history and use of PPV23 and PCV13 in adults and how vaccination of adults with PCV13 addresses an unmet medical need. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rise of multidrug-resistant non-vaccine serotype 15A Streptococcus pneumoniae in the United Kingdom, 2001 to 2014

PubMed Central

Sheppard, Carmen; Fry, Norman K.; Mushtaq, Shazad; Woodford, Neil; Reynolds, Rosy; Janes, Regina; Pike, Rachel; Hill, Robert; Kimuli, Maimuna; Staves, Peter; Doumith, Michel; Harrison, Timothy; Livermore, David M

2016-01-01

Conjugate vaccines have reduced pneumococcal disease in vaccinated children and unvaccinated adults, but non-vaccine serotypes are of concern, particularly if antibiotic resistant. We reviewed Streptococcus pneumoniae collected via: (i) the British Society for Antimicrobial Chemotherapy (BSAC) surveillances from 2001–2014; (ii) Public Health England’s (PHE) invasive isolate surveillance from 2005–2014 and (iii) referral to PHE for resistance investigation from 2005–2014. Serotype 15A increased in all series, with many representatives showing triple resistance to macrolides, tetracyclines and penicillin. 15A was consistently among the 10 most prevalent serotypes from 2011 in PHE and BSAC invasive isolate/bacteraemia surveillance but never previously; 26–33% of these invasive 15A isolates had triple resistance. BSAC respiratory isolates were only serotyped in 2013/14 and 2014/15 (October to September); 15A was most prevalent serotype in both periods, comprising 9–11% of isolates, 38–48% of them with triple resistance. Serotype 15A represented 0–4% of S. pneumoniae referred to PHE for reference investigation annually until 2008 but rose to 29% (2013) and 32% (2014). Almost all multidrug-resistant 15A isolates were sequence type (ST) 63 variants, whereas susceptible 15A isolates were clonally diverse. The rise of serotype 15A suggests that pneumococcal conjugate vaccines will need ongoing adaptation. PMID:28006650

Factors associated with pneumococcal polysaccharide vaccination of the elderly in Spain: A cross-sectional study

PubMed Central

Domínguez, Angela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Torner, Núria; Force, Luis; Castilla, Jesús; Mayoral, José María; Tamames, Sonia; Martín, Vicente; Egurrola, Mikel; Sanz, Francisco; Astray, Jenaro; Project PI12/02079 Working Group

2016-01-01

ABSTRACT Vaccination of the elderly is an important factor in limiting the impact of pneumonia in the community. The aim of this study was to investigate the factors associated with pneumococcal polysaccharide vaccination in patients aged ≥ 65 years hospitalized for causes unrelated to pneumonia, acute respiratory disease, or influenza-like illness in Spain. We made a cross-sectional study during 2013-2014. A bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking into account sociodemographic variables and risk medical conditions. A multivariate analysis was performed using multilevel regression models. 921 patients were included; 403 (43.8%) had received the pneumococcal vaccine (394 received the polysaccharide vaccine). Visiting the general practitioner ≥ 3 times during the last year (OR = 1.79; 95% CI 1.25-2.57); having received the influenza vaccination in the 2013-14 season (OR = 2.57; 95% CI 1.72-3.84) or in any of the 3 previous seasons (OR = 11.70; 95% CI 7.42-18.45) were associated with receiving the pneumococcal polysaccharide vaccine. Pneumococcal vaccination coverage of hospitalized elderly people is low. The elderly need to be targeted about pneumococcal vaccination and activities that encourage healthcare workers to proactively propose vaccination might be useful. Educational campaigns aimed at the elderly could also help to increase vaccination coverages and reduce the burden of pneumococcal disease in the community. PMID:27064311

Development of a rapid recombinase polymerase amplification assay for the detection of Streptococcus pneumoniae in whole blood.

PubMed

Clancy, Eoin; Higgins, Owen; Forrest, Matthew S; Boo, Teck Wee; Cormican, Martin; Barry, Thomas; Piepenburg, Olaf; Smith, Terry J

2015-10-29

Streptococcus pneumoniae is an important cause of microbial disease in humans. The introduction of multivalent vaccines has coincided with a dramatic decrease in the number of pneumococcal-related deaths. In spite of this, at a global level, pneumococcal infection remains an important cause of death among children under 5 years of age and in adults 65 years of age or older. In order to properly manage patients and control the spread of infection, a rapid and highly sensitive diagnostic method is needed for routine implementation, especially in resource-limited regions where pneumococcal disease is most prevalent. Using the gene encoding leader peptidase A as a molecular diagnostics target, a real-time RPA assay was designed and optimised for the detection of S. pneumoniae in whole blood. The performance of the assay was compared to real-time PCR in terms of its analytical limit of detection and specificity. The inhibitory effect of human genomic DNA on amplification was investigated. The potential clinical utility of the assay was investigated using a small number of clinical samples. The RPA assay has a limit of detection equivalent to PCR (4.0 and 5.1 genome equivalents per reaction, respectively) and was capable of detecting the equivalent of <1 colony forming unit of S. pneumoniae when spiked into human whole blood. The RPA assay was 100 % inclusive (38/38 laboratory reference strains and 19/19 invasive clinical isolates) and 100 % exclusive; differentiating strains of S. pneumoniae species from other viridans group streptococci, including S. pseudopneumoniae. When applied to the analysis of a small number (n = 11) of clinical samples (blood culture positive for S. pneumoniae), the RPA assay was demonstrated to be both rapid and sensitive. The RPA assay developed in this work is shown to be as sensitive and as specific as PCR. In terms of reaction kinetics, the RPA assay is shown to exceed those of the PCR, with the RPA running to completion in 20 minutes and capable generating a positive signal in as little as 6 minutes. This work represents a potentially suitable assay for application in point-of-care settings.

Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea.

PubMed

Choe, Young June; Lee, Hoan Jong; Lee, Hyunju; Oh, Chi Eun; Cho, Eun Young; Choi, Jae Hong; Kang, Hyun Mi; Yoon, In Ae; Jung, Hyun Joo; Choi, Eun Hwa

2016-09-14

This study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs). From April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility. A total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, P<0.001), while completion of PCV vaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P=0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one. High rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea. Copyright © 2016 Elsevier Ltd. All rights reserved.

Streptococcus pneumoniae pharyngeal colonization in school-age children and adolescents with cancer.

PubMed

Principi, Nicola; Preti, Valentina; Gaspari, Stefania; Colombini, Antonella; Zecca, Marco; Terranova, Leonardo; Cefalo, Maria Giuseppina; Ierardi, Valentina; Pelucchi, Claudio; Esposito, Susanna

2016-01-01

Patients with cancer, particularly those with hematologic malignancies, are at an increased risk of invasive pneumococcal disease (IPD) and they are included in the list of subjects for whom pneumococcal vaccination is recommended. The main aim of this study was to evaluate Streptococcus pneumoniae colonization in school-aged children and adolescents with cancer to determine the potential protective efficacy of 13-valent pneumococcal conjugate vaccine (PCV13). An oropharyngeal swab was obtained from 277 patients (age range 6-17 years) with cancer during routine clinical visits and analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in 52 patients (18.8%), including 47/235 (20.0%) with hematologic malignancies and 5/42 (11.9%) with solid tumors. Colonization declined significantly with an increase in age (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.16-0.71, and OR 0.30, 95% CI 0.11-0.82 in children aged 10-14 and ≥15 years, respectively, as compared to those <10 years). Carriage was more common among patients with leukemia or lymphoma than in children with solid tumors. Co-trimoxazole prophylaxis was significantly associated with reduced pneumococcal carriage (OR 0.41, 95% CI 0.19-0.89). A total of 15/58 (25.9%) and 26/216 (12.0%) children were colonized by PCV13 serotypes among cancer patients previously vaccinated and not vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7), respectively. In conclusion, this study indicates that children and adolescents with cancer are frequently colonized by S. pneumoniae. Because most of the carried serotypes are included in PCV13, this vaccine is presently the best solution to reduce the risk of IPD in these patients.

Complement Regulator Factor H Mediates a Two-step Uptake of Streptococcus pneumoniae by Human Cells*

PubMed Central

Agarwal, Vaibhav; Asmat, Tauseef M.; Luo, Shanshan; Jensch, Inga; Zipfel, Peter F.; Hammerschmidt, Sven

2010-01-01

Streptococcus pneumoniae, a human pathogen, recruits complement regulator factor H to its bacterial cell surface. The bacterial PspC protein binds Factor H via short consensus repeats (SCR) 8–11 and SCR19–20. In this study, we define how bacterially bound Factor H promotes pneumococcal adherence to and uptake by epithelial cells or human polymorphonuclear leukocytes (PMNs) via a two-step process. First, pneumococcal adherence to epithelial cells was significantly reduced by heparin and dermatan sulfate. However, none of the glycosaminoglycans affected binding of Factor H to pneumococci. Adherence of pneumococci to human epithelial cells was inhibited by monoclonal antibodies recognizing SCR19–20 of Factor H suggesting that the C-terminal glycosaminoglycan-binding region of Factor H mediates the contact between pneumococci and human cells. Blocking of the integrin CR3 receptor, i.e. CD11b and CD18, of PMNs or CR3-expressing epithelial cells reduced significantly the interaction of pneumococci with both cell types. Similarly, an additional CR3 ligand, Pra1, derived from Candida albicans, blocked the interaction of pneumococci with PMNs. Strikingly, Pra1 inhibited also pneumococcal uptake by lung epithelial cells but not adherence. In addition, invasion of Factor H-coated pneumococci required the dynamics of host-cell actin microfilaments and was affected by inhibitors of protein-tyrosine kinases and phosphatidylinositol 3-kinase. In conclusion, pneumococcal entry into host cells via Factor H is based on a two-step mechanism. The first and initial contact of Factor H-coated pneumococci is mediated by glycosaminoglycans expressed on the surface of human cells, and the second step, pneumococcal uptake, is integrin-mediated and depends on host signaling molecules such as phosphatidylinositol 3-kinase. PMID:20504767

The effect of various types of patients' reminders on the uptake of pneumococcal vaccine in adults: A randomized controlled trial.

PubMed

Ghadieh, Alexandra S; Hamadeh, Ghassan N; Mahmassani, Dina M; Lakkis, Najla A

2015-10-26

Invasive pneumococcal disease is one of the most important vaccine-preventable diseases threatening the adult community due to missed opportunities for vaccination. This study compares the effect of three different types of patient reminder system on adulthood Streptococcus pneumoniae immunization in a primary care setting. The study targeted patients aged 40 and older eligible for pneumococcal vaccine, but did not receive it yet (89.5% of 3072 patients) based on their electronic medical records in a family medicine center in Beirut. The sample population was randomized using an automated computer randomization system into six equal groups, receiving short phone calls, short text messaging system (sms-text) or e-mails each with or without patient education. Each group received three identical reminders spaced by a period of four weeks. Documentation of vaccine administration was then added to the longitudinal electronic patient record. The primary outcome was the vaccine administration rate in the clinics. Of the eligible patients due for the pneumococcal 23-polyvalent vaccine, 1380 who had mobile phone numbers and e-mails were randomized into six equal intervention groups. The various reminders increased vaccination rate to 14.9%: 16.5% of the short phone calls group, 7.2% of the sms-text group and 5.7% of the e-mail group took the vaccine. The vaccination rate was independent of the age, associated education message and the predisposing condition. Use of electronic text reminders via e-mails and mobile phones seems to be a feasible and sustainable model to increase pneumococcal vaccination rates in a primary care center. Copyright © 2015 Elsevier Ltd. All rights reserved.

The descriptive epidemiology of Streptococcus pneumoniae and Haemophilus influenzae nasopharyngeal carriage in children and adults in Kilifi District, Kenya

PubMed Central

Abdullahi, Osman; Nyiro, Joyce; Lewa, Pole; Slack, Mary; Scott, J. Anthony G.

2008-01-01

Background Transmission and nasopharyngeal colonization are necessary steps en route to invasive pneumococcal or Haemophilus influenzae disease but their patterns vary geographically. In East Africa we do not know how these pathogens are transmitted between population sub-groups nor which serotypes circulate commonly. Methods We did two cross-sectional nasopharyngeal swab surveys selecting subjects randomly from a population register to estimate prevalence and risk-factors for carriage in 2004. H. influenzae type b vaccine was introduced in 2001. Results Of 450 individuals sampled in the dry season, 414 were resampled during the rainy season. Among subjects 0-4, 5-9 and 10-85 years old pneumococcal carriage prevalence was 57%, 41% and 6.4%, respectively. H. influenzae prevalence was 26%, 24% and 3.0%, respectively. Prevalence of H. influenzae type b in children <5 years was 1.7%. Significant risk factors for pneumococcal carriage were rainy season (OR 1.65), coryza (OR 2.29) and co-culture of non-capsulate H. influenzae (OR 7.46). Coryza was also a risk factor for H. influenzae carriage (OR 1.90). Of 128 H. influenzae isolates 113 were non-capsulate. Among 279 isolates of Streptococcus pneumoniae 40 serotypes were represented and the distribution of serotypes varied significantly with age; 7-valent vaccine-types, vaccine-related types and non-vaccine types comprised 47%, 19% and 34% of strains from children aged <5 years. Among older persons they comprised 25%, 28% and 47%, respectively (p=0.005). Conclusions The study shows that pneumococcal carriage is common up to 9 years of age and that the majority of serotypes carried at all ages, are not covered specifically by the 7-valent pneumococcal conjugate vaccine. PMID:18162940

Bacterial invasion of the inner ear in association with pneumococcal meningitis.

PubMed

Møller, Martin Nue; Brandt, Christian; Østergaard, Christian; Caye-Thomasen, Per

2014-06-01

To examine the pathways of bacterial invasion and subsequent spreading in the inner ear during pneumococcal meningitis. A well-established adult rat model of Streptococcus pneumoniae meningitis was used. Thirty rats were inoculated intrathecally with S. pneumoniae serotype 1, 3 or 9 V and received no additional treatment. The rats were sacrificed when reaching terminal illness or on Day 7 and then prepared for serial sectioning and PAS-Alcian blue staining for light microscopy. During the first few days after inoculation, bacteria invade the inner ear through the cochlear aqueduct, into the scala tympani of the cochlea (perilymphatic space). From here, bacteria spreads apically toward the helicotrema and subsequently basally through the scala vestibuli, toward the vestibule and the vestibular system. When the bacteria after 5 to 6 days had reached scala vestibuli of the basal turn of the cochlea, hematogenous spreading occurred to the spiral ligament and into the cochlear endolymph, subsequently to the vestibular endolymph. We found no evidence of alternative routes for bacterial invasion in the inner ear. Several internal barriers to bacterial spreading were found within the inner ear. Bacterial elimination was evidenced by engulfment by macrophages within the inner ear. From the meninges, pneumococci invade the inner ear through the cochlear aqueduct during the first days of infection, whereas hematogenous invasion via the spiral ligament capillary bed occur at later stages. Although internal barriers exist within the inner ear, the spreading of bacteria occurs via the natural pathways of the fluid compartments. Bacterial elimination occurs by local macrophage engulfment.

The full benefits of adult pneumococcal vaccination: A systematic review

PubMed Central

Stawasz, Andrew; Johnson, Sydney T.; Sato, Reiko; Bloom, David E.

2017-01-01

Background Pneumococcal disease causes substantial morbidity and mortality, including among adults. Adult pneumococcal vaccines help to prevent these burdens, but they are underused. Accounting for the full benefits of adult pneumococcal vaccination may promote more rational resource allocation decisions with respect to adult pneumococcal vaccines. Objectives Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review to assess the extent to which the literature has empirically captured (e.g., through measurement or modeling) the full benefits of adult pneumococcal vaccination. Methods We systematically searched PubMed and Embase to identify studies published between January 1, 2010 and April 10, 2016 that examine adult pneumococcal vaccination. We included articles if they captured any health or economic benefit of an adult pneumococcal vaccine administered to adults age ≥ 50 or ≥ 18 in risk groups. Finally, we summarized the literature by categorizing the types of benefits captured, the perspective taken, and the strength of the evidence presented. Our protocol is number 42016038335 in the PROSPERO International prospective register of systematic reviews. Results We identified 5,857 papers and included 150 studies for analysis. While most capture health gains and healthcare cost savings, far fewer studies consider additional benefit categories, such as productivity gains. However, the studies with a broader approach still exhibit significant limitations; for example, many present only abstracts, while others offer no new measurements. Studies that examine the 13-valent pneumococcal conjugate vaccine focus more on broad economic benefits, but still have limitations. Conclusions This review highlights the need for more robust empirical accounting of the full benefits of adult pneumococcal vaccination. Literature outside this realm indicates that these broad benefits may be substantial. Failing to investigate the full benefits may lead society to undervalue vaccines' contributions and therefore underinvest in their development and adoption. PMID:29088258

Effectiveness of pneumococcal vaccination in older adults with chronic respiratory diseases: results of the EVAN-65 study.

PubMed

Ochoa-Gondar, Olga; Vila-Corcoles, Angel; Ansa, Xavier; Rodriguez-Blanco, T; Salsench, Elisabeth; de Diego, Cinta; Raga, Xavier; Gomez, Frederic; Valdivieso, Empar; Fuentes, Cruzma; Palacios, Laura

2008-04-07

A prospective cohort study evaluating the clinical effectiveness of the 23-valent pneumococcal polysaccharide vaccine was conducted among 1298 Spanish older adults with chronic respiratory diseases (bronchitis, emphysema or asthma) who were followed between 2002 and 2005. Main outcomes were all-cause community-acquired pneumonia (CAP) and 30 days mortality from CAP. The association between vaccination and the risk of each outcome was evaluated by multivariable Cox proportional-hazard models adjusted for age and comorbidity pneumococcal vaccination did not alter significantly the risk of overall CAP (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.56-1.07) and 30 days mortality from CAP (HR: 0.87; 95% CI: 0.33-2.28). However, a borderline significant reduction of 30% in the risk of all-cause hospitalisation for CAP was observed among vaccinated subjects (HR: 0.70; 95% CI: 0.48-1.00; p=0.052). The effectiveness of the vaccine on the combined endpoint of pneumococcal and unknown organism infections reached 34% (HR: 0.66; 95% CI: 0.43-1.01; p=0.059). Although our findings suggest moderate benefits from the vaccination, the evidence of clinical effectiveness appears limited.

A variable region within the genome of Streptococcus pneumoniae contributes to strain-strain variation in virulence.

PubMed

Harvey, Richard M; Stroeher, Uwe H; Ogunniyi, Abiodun D; Smith-Vaughan, Heidi C; Leach, Amanda J; Paton, James C

2011-05-05

The bacterial factors responsible for the variation in invasive potential between different clones and serotypes of Streptococcus pneumoniae are largely unknown. Therefore, the isolation of rare serotype 1 carriage strains in Indigenous Australian communities provided a unique opportunity to compare the genomes of non-invasive and invasive isolates of the same serotype in order to identify such factors. The human virulence status of non-invasive, intermediately virulent and highly virulent serotype 1 isolates was reflected in mice and showed that whilst both human non-invasive and highly virulent isolates were able to colonize the murine nasopharynx equally, only the human highly virulent isolates were able to invade and survive in the murine lungs and blood. Genomic sequencing comparisons between these isolates identified 8 regions >1 kb in size that were specific to only the highly virulent isolates, and included a version of the pneumococcal pathogenicity island 1 variable region (PPI-1v), phage-associated adherence factors, transporters and metabolic enzymes. In particular, a phage-associated endolysin, a putative iron/lead permease and an operon within PPI-1v exhibited niche-specific changes in expression that suggest important roles for these genes in the lungs and blood. Moreover, in vivo competition between pneumococci carrying PPI-1v derivatives representing the two identified versions of the region showed that the version of PPI-1v in the highly virulent isolates was more competitive than the version from the less virulent isolates in the nasopharyngeal tissue, blood and lungs. This study is the first to perform genomic comparisons between serotype 1 isolates with distinct virulence profiles that correlate between mice and humans, and has highlighted the important role that hypervariable genomic loci, such as PPI-1v, play in pneumococcal disease. The findings of this study have important implications for understanding the processes that drive progression from colonization to invasive disease and will help direct the development of novel therapeutic strategies.

Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis

PubMed Central

de Cellès, Matthieu Domenech; Pons-Salort, Margarita; Varon, Emmanuelle; Vibet, Marie-Anne; Ligier, Caroline; Letort, Véronique; Opatowski, Lulla; Guillemot, Didier

2015-01-01

Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections. PMID:26063589

Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis.

PubMed

de Cellès, Matthieu Domenech; Pons-Salort, Margarita; Varon, Emmanuelle; Vibet, Marie-Anne; Ligier, Caroline; Letort, Véronique; Opatowski, Lulla; Guillemot, Didier

2015-06-11

Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.

Penicillin treatment accelerates middle ear inflammation in experimental pneumococcal otitis media.

PubMed Central

Kawana, M; Kawana, C; Giebink, G S

1992-01-01

Most Streptococcus pneumoniae strains are killed by very low concentrations of penicillin and other beta-lactam antibiotics, yet middle ear inflammation and effusion persist for days to weeks after treatment in most cases of pneumococcal otitis media. To study the effect of beta-lactam antibiotic treatment on pneumococci and the middle ear inflammatory response during pneumococcal otitis media, we measured concentrations of pneumococci, inflammatory cells, and lysozyme in middle ear fluid (MEF) by using the chinchilla model. Procaine penicillin G given intramuscularly 12 and 36 h after inoculation of pneumococci into the middle ear caused a significant acceleration in the MEF inflammatory cell concentration compared with that in untreated controls, with a significant peak in the inflammatory cell concentration 24 h after pneumococcal inoculation. The lysozyme concentration in MEF also increased more rapidly in treated than in control animals. Viable pneumococci were not detected in MEF after the second dose of penicillin, but the total pneumococcal cell concentration remained unchanged for at least 45 days. Therefore, penicillin treatment accelerated middle ear inflammation while killing pneumococci, but treatment did not accelerate clearance of the nonviable pneumococcal cells from MEF. Further studies will need to define the contribution of these responses to acute and chronic tissue injury. PMID:1563782

Innovative Strategies Designed to Improve Adult Pneumococcal Immunizations in Safety Net Patient-Centered Medical Homes.

PubMed

Park, Nina J; Sklaroff, Laura Myerchin; Gross-Schulman, Sandra; Hoang, Khathy; Tran, Helen; Campa, David; Scheib, Geoffrey; Guterman, Jeffrey J

2016-08-01

Streptococcus pneumoniae is a principal cause of serious illness, including bacteremia, meningitis, and pneumonia, worldwide. Pneumococcal immunization is proven to reduce morbidity and mortality in high-risk adult and elderly populations. Current pneumococcal vaccination practices are suboptimal in part because of recommendation complexity, the high cost of provider-driven immunization interventions, and outreach methods that are not patient-centric. These barriers are amplified within the safety net. This paper identifies efforts by the Los Angeles County Department of Health Services to increase pneumococcal immunization rates for adult indigent patient populations. A 4-part approach will be used to increase vaccination rates: (1) protocol driven care, (2) staff education, (3) electronic identification of eligible patients, and (4) automated patient outreach and scheduling. The proposed analytics plan and potential for scalability are described. (Population Health Management 2016;19:240-247).

Streptococcus pneumoniae: distribution of serotypes and antimicrobial susceptibility in patients with cancer.

PubMed

Soto-Noguerón, Araceli; Carnalla-Barajas, María Noemí; Cornejo-Juárez, Patricia; Volkow-Fernández, Patricia; Velázquez-Meza, María Elena; Echániz-Aviles, Gabriela

2018-01-01

To describe the distribution of pneumococcal serotypes causing infectious diseases in patients with hematological malignancies and solid tumors and their antimicrobial susceptibility before and after introduction of pneumococcal conjugate vaccine (PCV7) in Mexico. Consecutive pneumococcal isolates from hospitalized patients from the SIREVA-network were serotyped using the Quellung reaction and antimicrobial susceptibility was performed using the broth microdilution method. A total of 175 pneumococcal isolates were recovered, 105 from patients with hematological malignancies and 70 with solid tumors. Serotypes 19A (22.7%), 19F (20.4%), and 35B (17.7%) were the most frequent isolates in the first group and serotypes 3 (27.2%) and 19A (28.6%) in the second group. No decreased susceptibility to beta-lactams or TMP/SMX was observed after introduction of PCV7. An increase in non-vaccine types is observed without significate changes in antimicrobial susceptibility after introduction of PCV7.

Invasive pneumococcal diseases in children in Hokkaido, Japan from April 2000, to March 2015.

PubMed

Sakata, Hiroshi

2016-01-01

In Japan, the 7-valent pneumococcal conjugate vaccine (PCV-7) became commercially available as a voluntary vaccine in March 2010. It was included in the routine immunization schedule in April 2013 and was replaced by PCV-13 in November 2013. We evaluated 146 cases of invasive pneumococcal disease (IPD) in 142 children (2 developed the disease twice, and 1 developed it three times) treated in the northern district of Hokkaido, Japan from April 2000 to March 2015, before and after the introduction of PCV-7. The incidence rate per 100,000 people aged <5 years showed an increasing trend between April 2000 and March 2010, and reached 87.5 per 100,000 people per year between April 2009 and March 2010, which was immediately before the introduction of PCV-7. Subsequently, the incidence rate started to show a decreasing trend and reached as low as 9.5 per 100,000 people per year between April 2013 and March 2014. However, the incidence rate showed an increasing trend again between April 2014 and March 2015, reaching 33.4 per 100,000 people per year. Serotyping was performed for the 77 strains collected between April 2000 and March 2010. The most frequently isolated serotype was 6B (31.2%), followed by 23F (14.3%) and 19F (13.0%). Among them, 55 strains were covered by PCV-7 (71.4%), and 64 strains were covered by PCV-13 (83.1%). Of the 33 strains collected between April 2010 and March 2015, 14 were covered by PCV-7 (42.4%) and 16 were covered by PCV-13 (48.4%), showing a significant decrease (p < 0.01). Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Clinical presentation of invasive pneumococcal disease in Spain in the era of heptavalent conjugate vaccine.

PubMed

de Sevilla, Maria F; García-García, Juan-José; Esteva, Cristina; Moraga, Fernando; Hernández, Sergi; Selva, Laura; Coll, Francisco; Ciruela, Pilar; Planes, Ana Maria; Codina, Gemma; Salleras, Luis; Jordan, Iolanda; Domínguez, Angela; Muñoz-Almagro, Carmen

2012-02-01

The aim of this study was to analyze the rate of incidence, clinical presentation, serotype, and clonal distribution of invasive pneumococcal disease (IPD) in the era of heptavalent pneumococcal conjugate vaccine (PCV7) in Barcelona, Spain. This was a prospective study comprising all children <5 years with IPD who were managed in 2 tertiary-care, pediatric hospitals between January 2007 and December 2009. IPD was defined as the presence of clinical findings of infection together with isolation or detection of DNA of Streptococcus pneumoniae in a sterile fluid sample. In this study, 319 patients (53.3% male), mean age 29.6 months, were included. Comparing rates in 2007 and 2009 (76.2 and 109.9 episodes/100,000 population, respectively), an increase of 44% (95% confidence interval, 10%-89%) was observed. The main clinical presentation was pneumonia (254 episodes, 79.6%), followed by meningitis (29, 9.1%), and bacteremia (25, 7.8%).The diagnosis was made by positive culture in 123 (38.6%) patients and in 196 (61.4%) by real-time polymerase chain reaction. Serotype study was performed in 300 episodes, and 273 (91%) were non-PCV7 serotypes. The most frequent serotypes were 1 (20.7%), 19A (15.7%), and 3 (12.3%). A minimal inhibitory concentration ≥0.12 μg/mL to penicillin was detected in 34.4% of isolates. Sequence type 306 expressing serotype 1 was the most frequent clonal type detected (20.3% of studied strains). IPD continues to increase in Barcelona, and the rate is higher than previously reported as a result of low sensitivity of bacterial culture. Non-PCV7 serotypes were responsible for 91% of episodes and pneumonia was the main clinical presentation.

Dynamics of Severe and Non-Severe Invasive Pneumococcal Disease in Young Children in Israel Following PCV7/PCV13 Introduction.

PubMed

Glikman, Daniel; Dagan, Ron; Barkai, Galia; Averbuch, Diana; Guri, Alex; Givon-Lavi, Noga; Ben-Shimol, Shalom

2018-05-10

The introduction of the pneumococcal conjugated vaccines (PCVs) resulted in a substantial reduction of invasive pneumococcal disease (IPD) rates. However, impact on non-severe IPD (mostly occult bacteremia) has not yet been fully elucidated.We assessed severe and non-severe IPD (SIPD and NSIPD, respectively) rate dynamics in children <5 years in Israel before and after PCV7/PCV13 implementation. A prospective, population-based, nationwide surveillance. All IPD episodes recorded from 1999 through 2015, were included. NSIPD was defined as IPD episodes without meningitis, pneumonia or mastoiditis in a child with a favorable outcome (not-hospitalized or hospitalized in a non-intensive care unit <5 days, without mortality). Three sub-periods were defined: pre-PCV (1999-2008), PCV7 (2010-2011) and PCV13 (2013-2015). Incidence rate ratios (IRRs) were calculated. Overall, 4,457 IPD episodes were identified; 3,398 (76.2%) SIPD, 1,022 (22.9%) NSIPD and 37 (0.8%) unknown. In 90% of NSIPD episodes, no focus was identified.In the PCV7 period, NSIPD rates significantly declined by 52%, while SIPD rates declined less prominently by 24%. Following PCV13 introduction, compared with the PCV7 period, NSIPD rates declined non-significantly by 17% while SIPD rates declined significantly further by an additional 53%. These trends resulted in overall reductions (comparing PCV13 and pre-PCV periods) of NSIPD and SIPD of 60% (IRR=0.4; 0.32-0.51) and 64% (IRR=0.36; 0.32-0.42), respectively. Following PCV7/PCV13 introduction, SIPD and NSIPD rates substantially declined, with differences in rate-dynamics, alluding to differences in serotype distribution between the two groups. Future surveillance is warranted when considering modification in treatment protocols for suspected occult bacteremia/NSIPD cases.

Clonal Expansion of the Macrolide Resistant ST386 within Pneumococcal Serotype 6C in France

PubMed Central

Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle

2014-01-01

In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002–2003) to the PCV13 era (2010–2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter. PMID:24603763

Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors.

PubMed

Backhaus, Erik; Berg, Stefan; Andersson, Rune; Ockborn, Gunilla; Malmström, Petter; Dahl, Mats; Nasic, Salmir; Trollfors, Birger

2016-08-03

Incidence, manifestations and case-fatality rate (CFR) of invasive pneumococcal disease (IPD) vary with age and comorbidities. New vaccines, changing age distribution, prolonged survival among immunocompromised patients and improved sepsis management have created a need for an update of basic facts to inform vaccine recommendations. Age, gender and comorbidities were related to manifestations and death for 2977 consecutive patients with IPD in a Swedish region with 1.5 million inhabitants during 13 years before introduction of pneumococcal conjugate vaccines (PCV) in the infant vaccination program. These data were related to population statistics and prevalence of several comorbidities, and compared with two previous studies giving a total follow-up of 45 years in the same area. The annual incidence was 15/100,000 for any IPD and 1.1/100,000 for meningitis; highest among elderly followed by children < 2 years. It was 2238/100,000 among myeloma patients, followed by chronic lymphatic leukemia, hemodialysis and lung cancer, but not elevated among asthma patients. CFR was 10 % among all patients, varying from 3 % below 18 years to 22 % ≥ 80 years. During 45 years, the IPD incidence increased threefold and CFR dropped from 20 to 10 %. Meningitis incidence remained stable (1.1/100,000/year) but CFR dropped from 33 to 13 %. IPD-specific mortality decreased among children <2 years from 3.1 to 0.46/100,000/year but tripled among those ≥65 years. IPD incidence and CFR vary widely between age and risk groups and over time even without general infant vaccination. Knowledge about specific epidemiological characteristics is important for informing and evaluating vaccination policies.

Streptococcus pneumoniae and Haemophilus influenzae type b carriage in Chinese children aged 12-18 months in Shanghai, China: a cross-sectional study.

PubMed

Hu, Jiayu; Sun, Xiaodong; Huang, Zhuoying; Wagner, Abram L; Carlson, Bradley; Yang, Jianping; Tang, Suwen; Li, Yunyi; Boulton, Matthew L; Yuan, Zhengan

2016-04-14

The bacteria Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) are leading causes of childhood pneumonia and meningitis and are major contributors to worldwide mortality in children younger than 5 years of age. Asymptomatic nasopharyngeal carriage of pneumococcus and Hib was determined for healthy children in Shanghai in 2009. Children from 5 immunization clinics were enrolled in this study. Specimens from the nasopharynx were collected and cultured in Columbia and chocolate agar to identify pneumococcal and Hib carriage. Pneumococcal specimens were serotyped with the Neufeld test, and antibiotic resistance for pneumococcal and Hib specimens used the E-test method. Significance of risk factors for carriage was assessed through chi-square tests. Among 614 children, 16.6% had pneumococcal carriage and 8.0% Hib carriage. The predominant serotype of pneumococcus that was isolated was 19 F (52.9%); serotype coverage was 68.6% for both 7-valent pneumococcal conjugate vaccine (PCV) and PCV-10, and 82.3% for PCV-13. Household residency and father's education were both significantly related to pneumococcal and Hib carriage. The majority of S. pneumoniae isolates were sensitive to most antimicrobials but there were high levels of resistance to azithromycin (51.0 %) and erythromycin (51.0%). Haemophilus influenzae isolates were sensitive to almost all antimicrobials tested although 12.2% of isolates were resistant to ampicillin. The pneumococcal and Hib vaccines require payment, and the children with the highest burden of disease may not be receiving these vaccines. Moreover, the presence of high antibiotic susceptibility towards pneumococcus, and to a lesser extent towards Hib, underscores the need for preventive protection against these diseases. Public funding of pneumococcal and Hib vaccines would be one mechanism to increase uptake of these vaccines.

Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia

PubMed Central

Albrich, Werner C; Madhi, Shabir A; Adrian, Peter V; van Niekerk, Nadia; Telles, Jean-Noel; Ebrahim, N; Messaoudi, Melina; Paranhos-Baccalà, Glaucia; Giersdorf, Sven; Vernet, Guy; Mueller, Beat; Klugman, Keith P

2014-01-01

Objective A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. Methods Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. Results There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). Conclusions In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults. PMID:25113557

Impact of pneumococcal conjugate vaccines on pneumococcal meningitis cases in France between 2001 and 2014: a time series analysis.

PubMed

Alari, Anna; Chaussade, Hélène; Domenech De Cellès, Matthieu; Le Fouler, Lénaig; Varon, Emmanuelle; Opatowski, Lulla; Guillemot, Didier; Watier, Laurence

2016-12-21

Pneumococcal meningitis (PM) is a major invasive pneumococcal disease. Two pneumococcal conjugate vaccines (PCVs) have been introduced in France: PCV7 was recommended in 2003 and replaced in 2010 by PCV13, which has six additional serotypes. The impact of introducing those vaccines on the evolution of PM case numbers and serotype distributions in France from 2001 to 2014 is assessed herein. Data on 5166 Streptococcus pneumoniae strains isolated from cerebrospinal fluid between 2001 and 2014 in the 22 regions of France were obtained from the National Reference Center for Pneumococci. The effects of the different vaccination campaigns were estimated using time series analyses through autoregressive moving-average models with exogenous variables ("flu-like" syndromes incidence) and intervention functions. Intervention functions used 11 dummy variables representing each post vaccine epidemiological period. The evolution of serotype distributions was assessed for the entire population and the two most exposed age groups (<5 and > 64 years old). For the first time since PCV7 introduction in 2003, total PM cases decreased significantly after starting PCV13 use: -7.1 (95% CI, -10.85 to -3.35) cases per month during 2013-2014, and was confirmed in children < 5 years old (-3.5; 95% CI, -4.81 to -2.13) and adults > 64 years old (-2.0; 95% CI, -3.36 to -0.57). During 2012-2014, different non-vaccine serotypes emerged: 12F, 24F in the entire population and children, 6C in the elderly; serotypes 3 and 19F persisted in the entire population. Unlike other European countries, the total PM cases in France declined only after introduction of PCV13. This suggests that vaccine pressure alone does not explain pneumococcal epidemiological changes and that other factors could play a role. Serotype distribution had changed substantially compared to the pre-vaccine era, as in other European countries, but very differently from the US. A highly reactive surveillance system is thus necessary not only to monitor evolutions due to vaccine pressure and to verify the local serotypic appropriateness of new higher-valent pneumococcal vaccines, but also to recognise and prevent unexpected changes due to other internal or external factors.

Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States.

PubMed

Marshall, Gary S; Marchant, Colin D; Blatter, Mark; Friedland, Leonard R; Aris, Emmanuel; Miller, Jacqueline M

2011-02-01

An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ≥0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.

Reduced susceptibility to penicillin among pneumococci causing invasive infection in children - Canada, 1991 to 1998

PubMed Central

Scheifele, David; Halperin, Scott; Pelletier, Louise; Talbot, James; Lovgren, Marguerite; Vaudry, Wendy; Jadavji, Taj; Law, Barbara; MacDonald, Noni; Gold, Ron; Wang, Elaine; Mills, Elaine; Lebel, Marc; Déry, Pierre; Morris, Rob

2001-01-01

OBJECTIVE: To determine, over time, the rate and serotypes of pneumococci with reduced penicillin susceptibility obtained from children with invasive infection. DESIGN: Active, hospital-based, multicentre surveillance spanning from 1991 to 1998. SETTING: Eleven Canadian tertiary care paediatric facilities located from coast to coast. POPULATION STUDIED: 1847 children with invasive pneumococcal infection whose isolates (from a normally sterile site) were available for serotyping and standardized testing for penicillin susceptibility at the National Centre for Streptococcus. MAIN RESULTS: The prevalence of reduced penicillin susceptibility increased from 2.5% of 197 cases in 1991 to 13.0% of 276 cases in 1998. In the latter year, 8.7% of isolates had intermediate level resistance, and 4.3% had high level resistance. Since they were first detected in 1992, strains with high level resistance have been encountered only sporadically at most centres, but by 1998, all centres but two had encountered examples. Of 40 isolates with high level resistance and 101 isolates with intermediate level resistance, serotypes matched those included in new seven-valent conjugate vaccines for children in 97.5% and 79.2% of cases, respectively. CONCLUSIONS: Pneumococci with reduced susceptibility to penicillin are increasing in frequency across Canada among children with invasive infection. The Immunization Monitoring Program, Active data indicate that new conjugate vaccines could help to curb infections due to pneumococci with reduced susceptibility to penicillin but are unlikely to control completely the problem of antibiotic resistance. PMID:18159346

Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation.

PubMed

Mina, Michael J

2017-06-01

Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive disease in the population, especially among the elderly and others most susceptible to pneumococcal disease. However, these effects may also be beneficial, for example the large reductions in all-cause mortality noted following measles vaccines. Here we discuss evidence for these novel vaccine effects and suggest that vaccine monitoring and evaluation programs should consider generalized herd effects to appreciate the full impacts of vaccines, beneficial or detrimental, across species and scales that are inevitably hiding in plain sight, affecting human health and disease. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Predicting pneumococcal community-acquired pneumonia in the emergency department: evaluation of clinical parameters.

PubMed

Huijts, S M; Boersma, W G; Grobbee, D E; Gruber, W C; Jansen, K U; Kluytmans, J A J W; Kuipers, B A F; Palmen, F; Pride, M W; Webber, C; Bonten, M J M

2014-12-01

The aim of this study was to quantify the value of clinical predictors available in the emergency department (ED) in predicting Streptococcus pneumoniae as the cause of community-acquired pneumonia (CAP). A prospective, observational, cohort study of patients with CAP presenting in the ED was performed. Pneumococcal aetiology of CAP was based on either bacteraemia, or S. pneumoniae being cultured from sputum, or urinary immunochromatographic assay positivity, or positivity of a novel serotype-specific urinary antigen detection test. Multivariate logistic regression was used to identify independent predictors and various cut-off values of probability scores were used to evaluate the usefulness of the model. Three hundred and twenty-eight (31.0%) of 1057 patients with CAP had pneumococcal CAP. Nine independent predictors for pneumococcal pneumonia were identified, but the clinical utility of this prediction model was disappointing, because of low positive predictive values or a small yield. Clinical criteria have insufficient diagnostic capacity to predict pneumococcal CAP. Rapid antigen detection tests are needed to diagnose S. pneumoniae at the time of hospital admission. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease.

PubMed

Weimer, Kristin E D; Armbruster, Chelsie E; Juneau, Richard A; Hong, Wenzhou; Pang, Bing; Swords, W Edward

2010-10-01

Otitis media is an extremely common pediatric infection and is mostly caused by bacteria that are carried within the nasopharyngeal microbiota. It is clear that most otitis media cases involve simultaneous infection with multiple agents. Chinchillas were infected with nontypeable Haemophilus influenzae, Streptococcus pneumoniae, or a combination of both organisms, and the course of disease was compared. In vitro experiments were also performed to address how coinfection impacts biofilm formation. The incidence of systemic disease was reduced in coinfected animals, compared with those infected with pneumococcus alone. Pneumococci were present within surface-attached biofilms in coinfected animals, and a greater proportion of translucent colony type was observed in the coinfected animals. Because this colony type has been associated with pneumococcal biofilms, the impact of coinfection on pneumococcal biofilm formation was investigated. The results clearly show enhanced biofilm formation in vitro by pneumococci in the presence of H. influenzae. Based on these data, we conclude that coinfection with H. influenzae facilitates pneumococcal biofilm formation and persistence on the middle ear mucosal surface. This enhanced biofilm persistence correlates with delayed emergence of opaque colony variants within the bacterial population and a resulting decrease in systemic infection.

Bacterial Cytolysin during Meningitis Disrupts the Regulation of Glutamate in the Brain, Leading to Synaptic Damage

PubMed Central

Wippel, Carolin; Maurer, Jana; Förtsch, Christina; Hupp, Sabrina; Bohl, Alexandra; Ma, Jiangtao; Mitchell, Timothy J.; Bunkowski, Stephanie; Brück, Wolfgang; Nau, Roland; Iliev, Asparouh I.

2013-01-01

Streptococcus pneumoniae (pneumococcal) meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage. PMID:23785278

Pediatric Complicated Pneumonia Caused by Streptococcus pneumoniae Serotype 3 in 13-Valent Pneumococcal Conjugate Vaccinees, Portugal, 2010-2015.

PubMed

Silva-Costa, Catarina; Brito, Maria João; Pinho, Marcos D; Friães, Ana; Aguiar, Sandra I; Ramirez, M; Melo-Cristino, Jose

2018-07-01

Despite use of 7-valent pneumococcal conjugate vaccine, incidence of pleural effusion and empyema (pediatric complicated pneumococcal pneumonia [PCPP]) is reportedly increasing globally. We cultured and performed PCR on 152 pleural fluid samples recovered from pediatric patients in Portugal during 2010-2015 to identify and serotype Streptococcus pneumoniae. We identified only 17 cases by culture, but molecular methods identified S. pneumoniae in 68% (92/135) of culture-negative samples. The most frequent serotypes were 3, 1, and 19A, together accounting for 62% (68/109) of cases. Nineteen cases attributable to 13-valent pneumococcal conjugate vaccine (PCV13) serotypes (mostly serotype 3) were detected among 22 children age-appropriately vaccinated with PCV13. The dominance of the additional serotypes included in PCV13 among PCPP cases in Portugal continues, even with PCV13 available on the private market (without reimbursement) since 2010 and with average annual coverage of 61% among age-eligible children. Our data suggest reduced effectiveness of PCV13 against serotype 3 PCPP.

Immunizations, neonatal jaundice, and animal-induced injuries.

PubMed

Morris, Shaine A; Bernstein, Henry H

2004-08-01

Published studies during the past year about three topics important to the pediatric clinician-- immunizations, neonatal jaundice, and animal-induced injuries-are concisely reviewed. Recent updates regarding vaccines including the questionable link with autism, implementation of universal influenza vaccination for young children, the efficacy of pneumococcal vaccine against invasive disease, and new information on pertussis, varicella, hepatitis A, hepatitis B, measles, and rotavirus vaccination are discussed. No association between measles/mumps/rubella vaccine or thimerosal-containing pertussis vaccine and autism is evident. Universal influenza vaccination for children 6 to 23 months of age will be recommended for the 2004-2005 flu season, and this implementation should reduce significant school absenteeism as well as complications seen last year including encephalopathy, seizures, respiratory failure, and pneumonia. Pneumococcal vaccine significantly reduces rates of invasive pneumococcal vaccine in healthy and HIV-infected children, although it does not appear to greatly affect otitis media rates. A reduction in post-vaccine febrile seizures appears to be present since the introduction of acellular pertussis vaccine. Multiple outbreaks in varicella have been reported since the introduction of the varicella vaccine, and a booster vaccination may be necessary in the future. Methods for detecting and preventing severe neonatal hyperbilirubinemia are reviewed, as well as anticipated recommendations from the American Academy of Pediatrics for the detection and management of hyperbilirubinemia. High bilirubin levels in preterm infants may result in hearing dysfunction and developmental impairment. The American Academy of Pediatrics has recommended a higher level of monitoring for newborn jaundice and treatment of hyperbilirubinemia in an effort to prevent kernicterus and sequelae from elevated bilirubin levels, including post-discharge follow-up appointment by day 3 to 5 of age. Dog bites in children with resultant post-traumatic stress disorder, rabies, and salmonellosis from pet reptiles in the home are also addressed. Clinicians need to be aware of the risk for rabies bites, need to recognize that dog bites in children appear to cause post-traumatic stress disorder in more than half of cases, and need to know how to educate patients on how to prevent salmonellosis from pet reptiles and amphibians. Progress has been made in immunizations, especially immunization for influenza, pneumonia, and pertussis. It is recommended that monitoring for neonatal hyperbilirubinemia be more thorough to prevent the consequences of this condition. Rabies, post-traumatic stress disorder from dog bites, and salmonellosis associated with pet reptiles constitute an important area for patient education.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury.

PubMed

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-10-05

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B 4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection.

Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury

PubMed Central

Shigematsu, Misako; Koga, Tomoaki; Ishimori, Ayako; Saeki, Kazuko; Ishii, Yumiko; Taketomi, Yoshitaka; Ohba, Mai; Jo-Watanabe, Airi; Okuno, Toshiaki; Harada, Norihiro; Harayama, Takeshi; Shindou, Hideo; Li, Jian-Dong; Murakami, Makoto; Hoka, Sumio; Yokomizo, Takehiko

2016-01-01

Although pneumococcal infection is a serious problem worldwide and has a high mortality rate, the molecular mechanisms underlying the lethality caused by pneumococcus remain elusive. Here, we show that BLT2, a G protein-coupled receptor for leukotriene B4 and 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury caused by a pneumococcal toxin, pneumolysin (PLY). Intratracheal injection of PLY caused lethal acute lung injury (ALI) in BLT2-deficient mice, with evident vascular leakage and bronchoconstriction. Large amounts of cysteinyl leukotrienes (cysLTs), classically known as a slow reactive substance of anaphylaxis, were detected in PLY-treated lungs. PLY-dependent vascular leakage, bronchoconstriction, and death were markedly ameliorated by treatment with a CysLT1 receptor antagonist. Upon stimulation by PLY, mast cells produced cysLTs that activated CysLT1 expressed in vascular endothelial cells and bronchial smooth muscle cells, leading to lethal vascular leakage and bronchoconstriction. Treatment of mice with aspirin or loxoprofen inhibited the production of 12-HHT and increased the sensitivity toward PLY, which was also ameliorated by the CysLT1 antagonist. Thus, the present study identifies the molecular mechanism underlying PLY-dependent ALI and suggests the possible use of CysLT1 antagonists as a therapeutic tool to protect against ALI caused by pneumococcal infection. PMID:27703200

Pneumococcal vaccination in patients with systemic lupus erythematosus: A multicenter placebo-controlled randomized double-blind study.

PubMed

Grabar, Sophie; Groh, Matthieu; Bahuaud, Mathilde; Le Guern, Véronique; Costedoat-Chalumeau, Nathalie; Mathian, Alexis; Hanslik, Thomas; Guillevin, Loïc; Batteux, Frédéric; Launay, Odile

2017-09-05

Invasive pneumococcal disease and respiratory tract infections are both frequent and severe in patients with systemic lupus erythematosus (SLE). This study aimed to compare the immunological efficacy and safety of pneumococcal vaccination with the 23-valent polysaccharide (PPS) vaccine alone to a sequential immunization with the 7-valent pneumococcal conjugate (PnCj) vaccine followed by PPS in patients with SLE and stable diseaase. Multicenter randomized placebo-controlled double-blind trial: PPS vaccine alone (placebo-PPS group) or PnCj vaccine followed by PPS vaccine (PnCj-PPS group) 24weeks later. The primary endpoint was the rate of responders at week 28 to at least 5 of the 7 serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) shared by both PPS and PnCj. Pneumococcal IgG antibodies' opsonophagocytic activity (OPA) were also assessed. Twenty-five patients in the placebo-PPS group and 17 in the PnCj-PPS group were included in a modified intention-to-treat analysis. The primary endpoint was reached in 72% (18/25) in the placebo-PPS and 76% (13/17) in the PnCj-PPS group (p=0.75). There was no difference in the rates of responders with OPA. At week 52, 13/18 (72%) patients in the placebo-PPS group and 10/13 (77%) patients in the PnCj-PPS group (p=0.77) that met the primary endpoint at week 28 were still responders to ≥5/7 serotypes shared by both PPS and PnCj vaccines. Nine SLE flares were reported in 6 patients (4 in the placebo-PPS and 2 in the PnCj-PPS groups respectively, p=0.70). Sequential administration of PnCj vaccine followed by PPS vaccine is safe and shows short-term immunological efficacy in patients with SLE but was not superior to the PPS vaccine alone. www.clinicaltrials.gov, NCT NCT00611663. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systematic Review of the Indirect Effect of Pneumococcal Conjugate Vaccine Dosing Schedules on Pneumococcal Disease and Colonization

PubMed Central

2014-01-01

Background: To aid decision making for pneumococcal conjugate vaccine (PCV) use in infant national immunization programs, we summarized the indirect effects of PCV on clinical outcomes among nontargeted age groups. Methods: We systematically reviewed the English literature on infant PCV dosing schedules published from 1994 to 2010 (with ad hoc addition of 2011 articles) for outcomes on children >5 years of age and adults including vaccine-type nasopharyngeal carriage (VT-NP), vaccine-type invasive pneumococcal disease (VT-IPD) and syndromic pneumonia. Results: Of 12,980 citations reviewed, we identified 21 VT-IPD, 6 VT-NP and 9 pneumonia studies. Of these 36, 21 (58%) included 3 primary doses plus PCV or pneumococcal polysaccharide vaccine (PPV23) booster schedule (3+1 or 3+PPV23), 5 (14%) 3+0, 9 (25%) 2+1 and 1 (3%) 2+0. Most (95%) were PCV7 studies. Among observational VT-IPD studies, all schedules (2+1, 3+0 and 3+1) demonstrated reductions in incidence among young adult groups. Among syndromic pneumonia observational studies (2+1, 3+0 and 3+1), only 3+1 schedules showed significant indirect impact. Of 2 VT-NP controlled trials (3+0 and 3+1) and 3 VT-NP observational studies (2+1, 3+1 and 3+PPV23), 3+1 and 3+PPV23 schedules showed significant indirect effect. The 1 study to directly compare between schedules was a VT-NP study (2+0 vs. 2+1), which found no indirect effect on older siblings and parents of vaccinated children with either schedule. Conclusions: Indirect benefit of a 3+1 infant PCV dosing schedule has been demonstrated for VT-IPD, VT-NP and syndromic pneumonia; 2+1 and 3+0 schedules have demonstrated indirect effect only for VT-IPD. The choice of optimal infant PCV schedule is limited by data paucity on indirect effects, especially a lack of head-to-head studies and studies of PCV10 and PCV13. PMID:24336058

Antibody Kinetics and Response to Routine Vaccinations in Infants Born to Women Who Received an Investigational Trivalent Group B Streptococcus Polysaccharide CRM197-Conjugate Vaccine During Pregnancy

PubMed Central

Madhi, Shabir A; Koen, Anthonet; Cutland, Clare L; Jose, Lisa; Govender, Niresha; Wittke, Frederick; Olugbosi, Morounfolu; Sobanjo-ter Meulen, Ajoke; Baker, Sherryl; Dull, Peter M; Narasimhan, Vas; Slobod, Karen

2017-01-01

Abstract Background Maternal vaccination against group B Streptococcus (GBS) might provide protection against invasive GBS disease in infants. We investigated the kinetics of transplacentally transferred GBS serotype-specific capsular antibodies in the infants and their immune response to diphtheria toxoid and pneumococcal vaccination. Methods This phase 1b/2, observer-blind, single-center study (NCT01193920) enrolled infants born to women previously randomized (1:1:1:1) to receive either GBS vaccine at dosages of 0.5, 2.5, or 5.0 μg of each of 3 CRM197-glycoconjugates (serotypes Ia, Ib, and III), or placebo. Infants received routine immunization: combination diphtheria vaccine (diphtheria-tetanus-acellular pertussis–inactivated poliovirus/Haemophilus influenzae type b vaccine; age 6/10/ 14 weeks) and 13-valent pneumococcal CRM197-conjugate vaccine (PCV13; age 6/14 weeks and 9 months). Antibody levels were assessed at birth, day (D) 43, and D91 for GBS serotypes; 1 month postdose 3 (D127) for diphtheria; and 1 month postprimary (D127) and postbooster (D301) doses for pneumococcal serotypes. Results Of 317 infants enrolled, 295 completed the study. In infants of GBS vaccine recipients, GBS serotype-specific antibody geometric mean concentrations were significantly higher than in the placebo group at all timepoints and predictably decreased to 41%–61% and 26%–76% of birth levels by D43 and D91, respectively. Across all groups, ≥95% of infants were seroprotected against diphtheria at D127 and ≥91% of infants had seroprotective antibody levels against each PCV13 pneumococcal serotype at D301. Conclusions Maternal vaccination with an investigational CRM197-glycoconjugate GBS vaccine elicited higher GBS serotype-specific antibody levels in infants until 90 days of age, compared with a placebo group, and did not affect infant immune responses to diphtheria toxoid and pneumococcal vaccination. Clinical Trials Registration NCT01193920. PMID:29029127

[Conjugated vaccines].

PubMed

Fritzell, Bernard

2005-01-01

Encapsulated bacterial pathogens (e.g. Haemophilus influenzae type b [Hib], Neisseria meningitidis, or Streptococcus pneumoniae) target infants and young children who have lost any protective anti-capsular antibodies supplied maternally and whose immune systems are ineffective against T-independent antigens such as the polysaccharides of the capsule. The polysaccharide-protein conjugate vaccines overcome this limitation by converting the polysaccharide to a T-dependent antigen, which allows a vaccinated infant to mount a protective immune response. Where conjugated vaccines have been introduced into paediatric vaccination schedules, the incidence of invasive diseases caused by Hib, the group C meningococcus, or the pneumococcus has plummeted by at least 80%, a major public health success. Furthermore, surveillance has demonstrated that the conjugate vaccines provide 'herd protection' through their beneficial impact on nasopharyngeal colonisation among vaccinated children. Promising future approaches include enhancement of the number of capsular serogroups targeted by the meningococcal or pneumococcal conjugate vaccines.

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule

PubMed Central

Andam, Cheryl P.; Harris, Simon R.; Cornick, Jennifer E.; Yang, Marie; Bricio-Moreno, Laura; Kamng’ona, Arox W.; French, Neil; Heyderman, Robert S.; Kadioglu, Aras; Everett, Dean B.; Bentley, Stephen D.

2016-01-01

ABSTRACT Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. PMID:27677790

Effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine in preventing hospitalization with laboratory confirmed influenza during the 2009-2010 and 2010-2011 seasons

PubMed Central

Domínguez, Angela; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Saez, Marc; Soldevila, Núria; Astray, Jenaro; Mayoral, José María; Martín, Vicente; Quintana, José María; González-Candelas, Fernando; Galán, Juan Carlos; Tamames, Sonia; Castro, Ady; Baricot, Maretva; Garín, Olatz; Pumarola, Tomas; Working Group (Spain), CIBERESP Cases and Controls in Pandemic Influenza

2013-01-01

Background: Since influenza predisposes to bacterial pneumonia caused by Streptococcus pneumoniae, studies have suggested that pneumococcal vaccination might reduce its occurrence during pandemics. We assessed the effectiveness of pneumococcal polysaccharide vaccination alone and in combination with influenza vaccination in preventing influenza hospitalization during the 2009–2010 pandemic wave and 2010–2011 influenza epidemic. Methods: We conducted a multicenter case-control study in 36 Spanish hospitals. We selected patients aged ≥ 18 y hospitalized with confirmed influenza and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the pneumococcal or seasonal influenza vaccine > 14 d (or > 7 d for pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms in matched cases (controls). Results: 1187 cases and 2328 controls were included. The adjusted estimate of effectiveness of pneumococcal vaccination in preventing influenza hospitalization was 41% (95% CI 8–62) in all patients and 43% (95% CI 2–78) in patients aged ≥ 65 y. The adjusted effectiveness of dual PPV23 and influenza vaccination was 81% (95% CI 65–90) in all patients and 76% (95% CI 46–90) in patients aged ≥ 65 y. The adjusted effectiveness of influenza vaccination alone was 58% (95% CI 38–72). Conclusions: In elderly people and adults with chronic illness, pneumococcal vaccination may reduce hospitalizations during the influenza season. In people vaccinated with both the influenza and pneumococcal vaccines, the benefit in hospitalizations avoided was greater than in those vaccinated only against influenza. PMID:23563516

Combination of Pneumococcal Surface Protein A (PspA) with Whole Cell Pertussis Vaccine Increases Protection Against Pneumococcal Challenge in Mice

PubMed Central

Ferreira, Daniela M.; Moreno, Adriana T.; Ferreira, Patricia C. D.; Lima, Fernanda A.; Santos, Fernanda L.; Sakauchi, Maria Aparecida; Takata, Célia S.; Higashi, Hisako G.; Raw, Isaías; Kubrusly, Flavia S.; Ho, Paulo L.

2010-01-01

Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA) is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines. Efficient immune responses directed to PspA in animal models have already been described. Nevertheless, few low cost adjuvants for a subunit pneumococcal vaccine have been proposed to date. Here, we have tested the adjuvant properties of the whole cell Bordetella pertussis vaccine (wP) that is currently part of the DTP (diphtheria-tetanus-pertussis) vaccine administrated to children in several countries, as an adjuvant to PspA. Nasal immunization of BALB/c mice with a combination of PspA5 and wP or wPlow – a new generation vaccine that contains low levels of B. pertussis LPS – conferred protection against a respiratory lethal challenge with S. pneumoniae. Both PspA5-wP and PspA5-wPlow vaccines induced high levels of systemic and mucosal antibodies against PspA5, with similar profile, indicating no essential requirement for B. pertussis LPS in the adjuvant properties of wP. Accordingly, nasal immunization of C3H/HeJ mice with PspA5-wP conferred protection against the pneumococcal challenge, thus ruling out a role for TLR4 responses in the adjuvant activity and the protection mechanisms triggered by the vaccines. The high levels of anti-PspA5 antibodies correlated with increased cross-reactivity against PspAs from different clades and also reflected in cross-protection. In addition, passive immunization experiments indicated that antibodies played an important role in protection in this model. Finally, subcutaneous immunization with a combination of PspA5 with DTPlow protected mice against challenge with two different pneumococcal strains, opening the possibility for the development of a combined infant vaccine composed of DTP and PspA. PMID:20523738

Serotype Distribution and Antibiotic Susceptibility of Streptococcus pneumoniae Strains Carried by Children Infected with Human Immunodeficiency Virus

PubMed Central

Safari, Dodi; Kurniati, Nia; Waslia, Lia; Khoeri, Miftahuddin Majid; Putri, Tiara; Bogaert, Debby; Trzciński, Krzysztof

2014-01-01

Abstract Background We studied the serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates carried by children infected with HIV in Jakarta, Indonesia. Methods Nasopharyngeal swabs were collected from 90 HIV infected children aged 4 to 144 months. S. pneumoniae was identified by conventional and molecular methods. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. Results We identified S. pneumoniae carriage in 41 children (46%). Serotype 19F was most common among 42 cultured strains (19%) followed by 19A and 6A/B (10% each), and 23F (7%). Most isolates were susceptible to chloramphenicol (86%), followed by clindamycin (79%), erythromycin (76%), tetracycline (43%), and sulphamethoxazole/trimethoprim (41%). Resistance to penicillin was most common with only 33% of strains being susceptible. Strains of serotypes targeted by the 13-valent pneumococcal conjugate polysaccharide vaccine (PCV13) were more likely to be multidrug resistant (13 of 25 or 52%) compared to non-PCV13 serotype isolates (3 of 17 or 18%; Fisher exact test p = 0.05). Conclusion Our study provides insight into the epidemiology of pneumococcal carriage in young HIV patients in Indonesia. These findings may facilitate potential preventive strategies that target invasive pneumococcal disease in Indonesia. PMID:25343448

Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study.

PubMed

Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Holtzman, Corinne; Scherzinger, Karen; Reingold, Arthur; Schaffner, William; Harrison, Lee H; Rosen, Jennifer B; Petit, Susan; Farley, Monica; Thomas, Ann; Eason, Jeffrey; Wigen, Christine; Barnes, Meghan; Thomas, Ola; Zansky, Shelley; Beall, Bernard; Whitney, Cynthia G; Moore, Matthew R

2016-12-01

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

Exploring the acceptability of the available pneumococcal conjugate vaccines in Canadian health care professionals and immunization experts.

PubMed

Berman, Melissa; Dubé, Eve; Quach, Caroline

2017-06-05

In children, the 13 and 10-valent pneumoccocal conjugate vaccines (PCV13/10) are currently approved for the prevention of invasive pneumococcal disease (IPD). Acceptability is a key consideration in the implementation of a vaccine program and it is recognized that health professional's attitudes and opinions towards vaccines are independent predictors of the success of an immunization program. We aimed to survey the beliefs and attitudes for the two available PCVs in health care professionals and immunization experts. We interviewed 21 members of Canadian immunization committees and/or participants working in frontline healthcare delivery. Overall, participants predominantly preferred PCV-13 over PCV10. For most, AOM should not be taken into considerations in decisions for pneumococcal vaccination programs implementation. AOM was considered an important endpoint of the program but an ineffective measure of program success due to the lack of surveillance for the condition. Recent evidence pertaining to PCV10 cross-protection against 19A did not affect preference but had an impact on perceptions regarding pricing. To consider implementing any changes to the current program, most participants would require more evidence regarding PCV10 cross-protection and effectiveness against OM. Decreasing vaccine price was cited as a positive outcome of funding both vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

c-di-GMP is an Effective Immunomodulator and Vaccine Adjuvant Against Pneumococcal Infection

PubMed Central

Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.

2009-01-01

Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167

Pneumococcal LytA Autolysin, a Potent Therapeutic Agent in Experimental Peritonitis-Sepsis Caused by Highly β-Lactam-Resistant Streptococcus pneumoniae▿

PubMed Central

Rodríguez-Cerrato, Violeta; García, Pedro; Huelves, Lorena; García, Ernesto; del Prado, Gema; Gracia, Matilde; Ponte, Carmen; López, Rubens; Soriano, Francisco

2007-01-01

The in vitro and in vivo antipneumococcal activities of the main pneumococcal autolysin (LytA) and Cpl-1, a lysozyme encoded by phage Cp-1, were studied. Intraperitoneal therapy with LytA or high-dose Cpl-1 remarkably reduced peritoneal bacterial counts (>5 log10 CFU/ml) compared with those for the controls. After intravenous injection, LytA was the most effective treatment. PMID:17576844

New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media.

PubMed

Auranen, Kari; Syrjänen, Ritva; Leino, Tuija; Kilpi, Terhi

2016-01-01

For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media.

Cost-effectiveness of vaccination against invasive pneumococcal disease among people 50 through 64 years of age: role of comorbid conditions and race.

PubMed

Sisk, Jane E; Whang, William; Butler, Jay C; Sneller, Vishnu-Priya; Whitney, Cynthia G

2003-06-17

Guidelines are increasingly recommending preventive services starting at 50 years of age, and policymakers are considering such a recommendation for pneumococcal polysaccharide vaccination. The finding that pneumococcal vaccination is cost-saving for people 65 years of age or older raises the question of the vaccination's implications for other older adults, especially black people, whose disease incidence exceeds that of nonblack people, and those with high-risk conditions. To assess the implications of vaccinating black and nonblack people 50 through 64 years of age against invasive pneumococcal disease. Cost-effectiveness analysis. Published literature for vaccination effectiveness and cost estimates; data on disease incidence and case-fatality rates from the Centers for Disease Control and Prevention. Hypothetical cohort 50 through 64 years of age with the 1995 U.S. age distribution. Lifetime. Societal. Pneumococcal polysaccharide vaccination compared with no vaccination. Incremental medical costs and health effects, in quality-adjusted life-years per vaccinee. Vaccination saved medical costs and improved health among high-risk black people (27.55 dollars savings per vaccinee) and nonblack people (5.92 dollars savings per vaccinee), excluding survivors' future costs. For low-risk black and nonblack people and the overall general population, vaccination cost 2477 dollars, 8195 dollars, and 3434 dollars, respectively, to gain 1 year of healthy life. Excluding survivors' future costs, in the general immunocompetent population, cost per quality-adjusted life-year in global worst-case results ranged from 21 513 dollars for black people to 68 871 dollars for nonblack people; in the high-risk population, cost ranged from 11 548 dollars for black people to 39 000 dollars for nonblack people. In the global best case, vaccination was cost-saving for black and nonblack people in the general immunocompetent and high-risk populations, excluding survivors' future costs. The cost-effectiveness range was narrower in probabilistic sensitivity analyses, with 95% probabilistic intervals ranging from cost-saving to 1594 dollars for black people and from cost-saving to 12 273 dollars for nonblack people in the general immunocompetent population. Costs per quality-adjusted life-year for low-risk people with case-fatality rates from 1998 were 2477 dollars for black people and 8195 dollars for nonblack people, excluding survivors' medical costs. These results support the current recommendation to vaccinate high-risk people and provide useful information for considering extending the recommendation to the general population 50 through 64 years of age. Lack of evidence about the effectiveness of revaccination for people 65 years of age or older, when disease risks are higher, argues for further research to guide vaccination policy.

Potential cost-effectiveness and benefit-cost ratios of adult pneumococcal vaccination in Germany

PubMed Central

2012-01-01

Background Invasive (IPD, defined as detection of pneumococci in sterile body fluids like meningitis or bacteremic pneumonia) and non-invasive Streptococcus pneumoniae infections (i.e. non-bacteremic pneumonia, otitis media) in adults are associated with substantial morbidity, mortality and costs. In Germany, Pneumococcal polysaccharide vaccination (PPV23) is recommended for all persons >60 years and for defined risk groups (age 5–59). The aim of this model was to estimate the potential cost-effectiveness and benefit-cost ratios of the adult vaccination program (18 years and older), considering the launch of the pneumococcal conjugate vaccine for adults (PCV13). Methods A cross-sectional steady state Markov model was developed to estimate the outcomes of PCV13, PPV23 vaccination schemes and ‘no vaccination’. Conservative assumptions were made if no data were available for PCV13 and PPV23 respectively. The effectiveness of individual pneumococcal vaccination in adults was adjusted for expected indirect effects due to the vaccination in infants. Data on incidences, effectiveness and costs were derived from scientific literature and publicly available databases. All resources used are indicated. Benefit-cost ratios and cost-effectiveness were evaluated from the perspective of the German Statutory Health Insurance as well as from social perspective. Results Under the assumption that PCV13 has a comparable effectiveness to PCV7, a vaccination program with PCV13 revealed the potential to avoid a greater number of yearly cases and deaths in IPD and pneumonia in Germany compared to PPV23. For PCV13, the costs were shown to be overcompensated by monetary savings resulting from reduction in the use of health care services. These results would render the switch from PPV23 to PCV13 as a dominant strategy compared to PPV23 and ‘no vaccination’. Given the correctness of the underlying assumptions every Euro spent on the PCV13 vaccination scheme yields savings of 2.09 € (social perspective: 2.16 €) compared to PPV23 and 1.27 € (social perspective: 1.32 €) compared to ‘no vaccination’, respectively. Conclusions Results of the model indicate that the health economic benefit of immunizing adults with PCV13 can be expected to outperform the sole use of PPV23, if the effectiveness of PCV13 is comparable to the effectiveness of PCV7. PMID:22828176

The changing epidemiology of invasive pneumococcal disease in aboriginal and non-aboriginal western Australians from 1997 through 2007 and emergence of nonvaccine serotypes.

PubMed

Lehmann, Deborah; Willis, Judith; Moore, Hannah C; Giele, Carolien; Murphy, Denise; Keil, Anthony D; Harrison, Catherine; Bayley, Kathy; Watson, Michael; Richmond, Peter

2010-06-01

BACKGROUND. In 2001, Australia introduced a unique 7-valent pneumococcal conjugate vaccine (7vPCV) 2-, 4-, and 6-month schedule with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster for Aboriginal children, and in 2005, 7vPCV alone in a 2-, 4-, and 6-month schedule for non-Aboriginal children. Aboriginal adults are offered 23vPPV but coverage is poor. We investigated trends in invasive pneumococcal disease (IPD) in Western Australia (WA). METHODS. Enhanced IPD surveillance has been ongoing since 1996. We calculated IPD incidence rates for Aboriginal and non-Aboriginal Australians before and after introduction of 7vPCV. RESULTS. A total of 1792 cases occurred during the period 1997-2007; the IPD incidence rate was 47 cases per 100,000 population per year among Aboriginal people and 7 cases per 100,000 population per year in non-Aboriginal people. After introduction of 7vPCV, IPD rates among Aboriginal children decreased by 46% for those <2 years of age and by 40% for those 2-4 years of age; rates decreased by 64% and 51% in equivalent age groups for non-Aboriginal children. IPD rates decreased by >30% in non-Aboriginal people 50 years of age but increased among Aboriginal adults (eg, from 59.1 to 109.6 cases per 100,000 population per year among those 30-49 years of age). Although IPD due to 7vPCV serotypes decreased in all age groups, IPD incidence due to non-7vPCV serotypes increased, and it almost doubled among Aboriginal adults 30-49 years of age (from 48.3 to 97.0 cases per 100,000 population per year). Among non-Aboriginal children, 37% of IPD is now due to serotype 19A. CONCLUSIONS. IPD incidence rates have decreased markedly among children and non-Aboriginal adults with a 3-dose infant 7vPCV schedule. However, IPD due to non-7vPCV serotypes has increased and is of particular concern among young Aboriginal adults, for whom an intensive 23vPPV campaign is needed. An immunization register covering all age groups should be established.

Long-term Impact of a "3 + 0" Schedule for 7- and 13-Valent Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease in Australia, 2002-2014.

PubMed

Jayasinghe, Sanjay; Menzies, Rob; Chiu, Clayton; Toms, Cindy; Blyth, Christopher C; Krause, Vicki; McIntyre, Peter

2017-01-15

Australia introduced universal 7-valent pneumococcal conjugate vaccine (PCV7) from 2005, replaced by 13-valent PCV (PCV13) in 2011, uniquely among high-income countries giving doses at 2, 4, and 6 months (3 + 0 schedule). Data on impact of a timely 3 + 0 PCV schedule with high coverage are sparse, with none for PCV13. We used national surveillance of invasive pneumococcal disease (IPD) from 2002 for baseline and appropriate later comparison periods to calculate incidence rate ratios (IRRs) by serotype and age using a Poisson model. PCV coverage was assessed from the Australian Childhood Immunisation Register. After 9 years of timely 3-dose PCV coverage of >92%, all-age IPD in Australia almost halved (IRR, 0.53; 95% confidence interval [CI], .50-.57), but differed by PCV era. Reductions in IPD due to vaccine serotypes from PCV7 (IRR, 0.20; CI, .17-.22) were about 2-fold greater than for IPD due to extra serotypes in PCV13 (13v-non7v) in a similar period (IRR, 0.58; CI, .51-.66). Post-PCV13 declines in serotype 19A IPD in persons aged <2 years (IRR, 0.23; CI, .13-.35) and ≥2 years (IRR, 0.35; CI, .28-.44) differed from other 13v-non7v IPD (IRR, 0.73; CI, .35-1.48 for those aged <2 years and IRR, 0.96; CI, .81-1.15 for those ≥2 years). Meningitis due to vaccine serotypes nearly disappeared in children eligible for 3 PCV13 doses. IPD due to non-PCV13 serotypes increased by 30% compared with 76% for non-PCV7 serotypes in equivalent period of vaccine use. Reductions in vaccine-type IPD post-PCV13 were inferior to Australian experience with PCV7 and reports from high-income countries giving a PCV booster dose. Applicability of findings to other settings would depend on age of IPD onset, serotype profile, and timeliness of vaccination. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice

PubMed Central

Shen, Pamela; Whelan, Fiona J.; Schenck, L. Patrick; McGrath, Joshua J. C.; Vanderstocken, Gilles; Bowdish, Dawn M. E.; Surette, Michael G.

2017-01-01

ABSTRACT Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium, Gemella, and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization. PMID:28760931

Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease

PubMed Central

Weimer, Kristin E.D.; Armbruster, Chelsie E.; Juneau, Richard A.; Hong, Wenzhou; Pang, Bing; Swords, W. Edward

2010-01-01

Background Otitis media is an extremely common pediatric infection, and is mostly caused by bacteria that are carried within the nasopharyngeal microbiota. It is clear that most otitis media cases involve simultaneous infection with multiple agents. Methods Chinchillas were infected with nontypeable Haemophilus influenzae, Streptococcus pneumoniae, or a combination of both organisms, and the course of disease was compared. In vitro experiments were also performed to address how coinfection impacts biofilm formation. Results The incidence of systemic disease was reduced in coinfected animals as compared to those infected with pneumococcus alone. Pneumococci were present within surface-attached biofilms in coinfected animals, and a greater proportion of translucent colony type was observed in the coinfected animals. As this colony type has been associated with pneumococcal biofilms, the impact of coinfection on pneumococcal biofilm formation was investigated. The results clearly show enhanced biofilm formation in vitro by pneumococci in the presence of H. influenzae. Conclusions Based on these data, we conclude that coinfection with H. influenzae facilitates pneumococcal biofilm formation and persistence on the middle-ear mucosal surface. This enhanced biofilm persistence correlates with delayed emergence of opaque colony variants within the bacterial population, and a resulting decrease in systemic infection. PMID:20715928

Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice.

PubMed

Shen, Pamela; Whelan, Fiona J; Schenck, L Patrick; McGrath, Joshua J C; Vanderstocken, Gilles; Bowdish, Dawn M E; Surette, Michael G; Stämpfli, Martin R

2017-10-01

Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium , Gemella , and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization. Copyright © 2017 American Society for Microbiology.

The burden of nonencapsulated Haemophilus influenzae in children and potential for prevention.

PubMed

Gkentzi, Despoina; Slack, Mary P E; Ladhani, Shamez N

2012-06-01

In countries with established Haemophilus influenzae serotype b (Hib) immunization programmes, nonencapsulated H. influenzae (ncHi) is responsible for most invasive H. influenzae infections across all age groups and is associated with higher case fatality. A pneumococcal conjugate vaccine has recently been licensed, which may potentially also protect against invasive H. influenzae infections. Invasive ncHi disease is uncommon in childhood but has a much higher incidence in the first month of life. Most neonates with invasive ncHi infections are born prematurely and develop septicaemia in the first 48 h of life which can be fatal. After this period, invasive ncHi incidence falls rapidly and remains low throughout childhood. Most infants and children who develop invasive ncHi disease have significant underlying comorbidities, particularly neurological disease, malignancy and other conditions requiring immunosuppressive therapy. Although characteristically associated with respiratory tract infections, at least a quarter of invasive ncHi infections present with meningitis. A vaccine against ncHi could have an important preventive role in children with comorbidities. Future studies should focus on assessing specific risk factors for neonatal and childhood ncHi disease and long-term outcomes of children with invasive ncHi meningitis.

Pneumococcal conjugate vaccine introduction in Latin America and the Caribbean: progress and lessons learned.

PubMed

de Oliveira, Lucia Helena; Trumbo, Silas Pierson; Ruiz Matus, Cuauhtémoc; Sanwogou, N Jennifer; Toscano, Cristiana M

2016-10-01

In Latin America and the Caribbean, pneumococcus has been estimated to cause 12,000-28,000 deaths, 182,000 hospitalizations, and 1.4 million clinic visits annually. Countries in the Americas have been among the first developing nations to introduce pneumococcal conjugate vaccines into their Expanded Programs on Immunization, with 34 countries and territories having introduced these vaccines as of September 2015. Lessons learned for successful vaccine introduction include the importance of coordination between political and technical decision makers, adjustments to the cold chain prior to vaccine introduction, and the need for detailed plans addressing the financial and technical sustainability of introduction. Though many questions on the Pneumococcal Conjugate Vaccine remain unanswered, the experience of the Americas suggests that the vaccines can be introduced quickly and effectively.

Trends of invasive pneumococcal disease and its serotypes in the Autonomous Community of Madrid.

PubMed

Latasa Zamalloa, Pello; Sanz Moreno, Juan Carlos; Ordobás Gavín, María; Barranco Ordoñez, María Dolores; Insúa Marisquerena, Esther; Gil de Miguel, Ángel; Fernández Chávez, Abelardo Claudio; García-Comas, Luis

2017-12-05

Streptococcus pneumoniae is an important cause of morbidity. Vaccination is the most effective measure to prevent it. The aim of this study is to analyse the evolution of invasive pneumococcal disease (IPD). Observational study of IPD cases notified to the Epidemiological Surveillance Network of the Autonomous Community of Madrid between 2008 and 2015. The IPD case was defined as the disease caused by Streptococcus pneumoniae, with isolation and DNA or antigen detection, in samples from normally sterile sites. The isolated strains were sent to the Regional Public Health Laboratory for identification of the serotype. Serotypes were classified according to their inclusion in the 7-valent conjugate vaccine (PCV7), in the 13-valent vaccine, but not in the 7-valent vaccine (PCV13-additional) and not included in the 13-valent vaccine (non-PCV). The Incidence Rate Ratios (IRRs) were calculated comparing the 2011-2012 and 2013-2015 periods with the 2008-2010 period. 4,307 cases were reported. 86.6% were serotyped. The IRR of IPD was 0.67 and 0.67 for all serotypes; 0.43 and 0.45 for PCV7 serotypes; 0.46 and 0.25 for PCV13-additional serotypes, and 1.01 and 1.32 for non-PCV13 serotypes in the 2011-2012 and 2013-2015 periods. The incidence of serotypes 8, 9N, 10A, 23B, 24F and serogroup 33 increased significantly in the 2013-2015 period. Serotypes 15B and 24F accounted for 24% of non-PCV13 cases in children under 5years, serotypes 8 and 9N for 51% in the population aged 5 to 59years and serotypes 8 and 22F for 25% in the population aged over 59years. The incidence of serotypes not included in conjugate vaccines has increased, especially in children under 5years, but the total incidence of IPD has decreased. It is important to continue with the epidemiological and microbiological surveillance programmes to assess the effect of vaccination on the incidence of IPD. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

[Warning about risk of invasive infections in splenectomized patients. Experiences from University Hospital Brno, Czech Republic, in 2011].

PubMed

Polák, P; Freibergerová, M; Husa, P; Slesinger, P; Svoboda, R; Sťásek, J; Frola, L; Macháček, C

2012-09-01

Syndrome of fulminant sepsis in splenectomized (overwhelming postsplenectomy infection - OPSI) is feared and often fatal infectious complication in patients after splenectomy. The risk of syndrome of fulminant sepsis in splenectomized in these persons persists lifelong and doesn't diminish during the time. Etiologically, encapsulated bacterias like Streptococcus pneumoniae, Haemophilus influenzae group b and Neisseria meningitidis are involved. As the mortality of syndrome of fulminant sepsis in splenectomized is very high, it is indispensable to educate and vaccinate persons in risk. The authors present case reports of three splenectomized patients who were hospitalized for invasive pneumococcal infection in the University Hospital Brno, Czech Republic, in 2011.

Increased risk for and mortality from invasive pneumococcal disease in HIV-exposed but uninfected infants aged <1 year in South Africa, 2009-2013.

PubMed

von Mollendorf, Claire; von Gottberg, Anne; Tempia, Stefano; Meiring, Susan; de Gouveia, Linda; Quan, Vanessa; Lengana, Sarona; Avenant, Theunis; du Plessis, Nicolette; Eley, Brian; Finlayson, Heather; Reubenson, Gary; Moshe, Mamokgethi; O'Brien, Katherine L; Klugman, Keith P; Whitney, Cynthia G; Cohen, Cheryl

2015-05-01

High antenatal human immunodeficiency virus (HIV) seroprevalence rates (∼ 30%) with low perinatal HIV transmission rates (2.5%), due to HIV prevention of mother-to-child transmission program improvements in South Africa, has resulted in increasing numbers of HIV-exposed but uninfected (HEU) children. We aimed to describe the epidemiology of invasive pneumococcal disease (IPD) in HEU infants. We conducted a cross-sectional study of infants aged <1 year with IPD enrolled in a national, laboratory-based surveillance program for incidence estimations. Incidence was reported for 2 time points, 2009 and 2013. At enhanced sites we collected additional data including HIV status and in-hospital outcome. We identified 2099 IPD cases in infants from 2009 to 2013 from all sites. In infants from enhanced sites (n = 1015), 92% had known HIV exposure status and 86% had known outcomes. IPD incidence was highest in HIV-infected infants, ranging from 272 to 654 per 100,000 population between time points (2013 and 2009), followed by HEU (33-88 per 100,000) and HIV-unexposed and uninfected (HUU) infants (18-28 per 100,000). The case-fatality rate in HEU infants (29% [74/253]) was intermediate between HUU (25% [94/377]) and HIV-infected infants (34% [81/242]). When restricted to infants <6 months of age, HEU infants (37% [59/175]) were at significantly higher risk of dying than HUU infants (32% [51/228]; adjusted relative risk ratio, 1.76 [95% confidence interval, 1.09-2.85]). HEU infants are at increased risk of IPD and mortality from IPD compared with HUU children, especially as young infants. HEU infants, whose numbers will likely continue to increase, should be prioritized for interventions such as pneumococcal vaccination along with HIV-infected infants and children. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Detection of macrolide resistance genes in culture-negative specimens from Bangladeshi children with invasive pneumococcal diseases.

PubMed

Hasanuzzaman, Md; Malaker, Roly; Islam, Maksuda; Baqui, Abdullah H; Darmstadt, Gary L; Whitney, Cynthia G; Saha, Samir K

2017-03-01

In recent years, an increasing prevalence of macrolide resistance among pneumococci in Bangladesh has been observed. However, the scenario remains incomplete, as few isolates (<1%) are available from pneumonia cases and most pneumococcal meningitis cases (>80%) are culture-negative. This study optimised a triplex PCR method to detect macrolide resistance genes (MRGs) (mefA and ermB) and cpsA from culture-negative pneumococcal cases to predict the prevalence and level of macrolide resistance. The presence of MRGs among pneumococcal strains (n=153) with a wide range of erythromycin MICs (<0.5 to ≥256mg/L) was determined by PCR. Triplex PCR was validated by simultaneous detection of MRG(s) and cpsA in culture-negative clinical specimens and corresponding isolates. The known impact of the presence of specific MRG(s) on MICs of strains was used to predict the MICs of non-culturable strains based on the presence/absence of MRG(s) in the specimens. None of the erythromycin-susceptible isolates possessed any of the MRGs, and all non-susceptible strains had ≥1 MRG. MICs were 2-16mg/L and ≥256mg/L for 93% of strains with mefA and ermB, respectively, whereas 100% of isolates with both genes had MICs≥256mg/L. PCR for body fluids showed 100% concordance with corresponding isolates when tested for MRG(s) in parallel. Erythromycin MICs can be predicted for non-culturable strains with 93-100% precision based on detection of ermB and/or mefA. This method will be useful for establishing comprehensive surveillance for macrolide resistance among pneumococci, specifically in the population with prior antibiotic use. Copyright © 2017. Published by Elsevier Ltd.

Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting β-Lactam Resistance Levels in Streptococcus pneumoniae

PubMed Central

Metcalf, Benjamin J.; Chochua, Sopio; Li, Zhongya; Gertz, Robert E.; Walker, Hollis; Hawkins, Paulina A.; Tran, Theresa; Whitney, Cynthia G.; McGee, Lesley; Beall, Bernard W.

2016-01-01

ABSTRACT β-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of β-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking β-lactam resistance could benefit disease surveillance. Here we developed a classification system in which a pneumococcal isolate is assigned to a “PBP type” based on sequence signatures in the transpeptidase domains (TPDs) of the three critical penicillin-binding proteins (PBPs), PBP1a, PBP2b, and PBP2x. We identified 307 unique PBP types from 2,528 invasive pneumococcal isolates, which had known MICs to six β-lactams based on broth microdilution. We found that increased β-lactam MICs strongly correlated with PBP types containing divergent TPD sequences. The PBP type explained 94 to 99% of variation in MICs both before and after accounting for genomic backgrounds defined by multilocus sequence typing, indicating that genomic backgrounds made little independent contribution to β-lactam MICs at the population level. We further developed and evaluated predictive models of MICs based on PBP type. Compared to microdilution MICs, MICs predicted by PBP type showed essential agreement (MICs agree within 1 dilution) of >98%, category agreement (interpretive results agree) of >94%, a major discrepancy (sensitive isolate predicted as resistant) rate of <3%, and a very major discrepancy (resistant isolate predicted as sensitive) rate of <2% for all six β-lactams. Thus, the PBP transpeptidase signatures are robust indicators of MICs to different β-lactam antibiotics in clinical pneumococcal isolates and serve as an accurate alternative to phenotypic susceptibility testing. PMID:27302760

Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil.

PubMed

de Soárez, Patrícia Coelho; Sartori, Ana Marli Christovam; Freitas, Angela Carvalho; Nishikawa, Álvaro Mitsunori; Novaes, Hillegonda Maria Dutilh

2015-01-01

To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the National Immunization Program (NIP) in Brazil. Economic evaluation using a Markov model to compare two strategies: (1) universal vaccination of adults aged 60 years with one dose of PPV23 and 2) current practice (vaccination of institutionalized elderly and elderly with underlying diseases). The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD) including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS). Univariate and multivariate sensitivity analysis were performed. The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective. The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil.

Comparison of the clinical presentations of Naegleria fowleri primary amoebic meningoencephalitis with pneumococcal meningitis: a case-control study.

PubMed

Zahid, Mohammad Faizan; Saad Shaukat, Muhammad Hamza; Ahmed, Bilal; Beg, Mohammad Asim; Kadir, Muhammad Masood; Mahmood, Syed Faisal

2016-08-01

Primary amoebic meningoencephalitis (PAM) is a rare but fatal infection caused by Naegleria fowleri. The infection is acquired by deep nasal irrigation with infected water. Patients present with signs and symptoms similar to pneumococcal meningitis, leading to delayed diagnosis and treatment and hence high mortality. We conducted a case-control study comparing culture proven cases of PAM with pneumococcal meningitis presenting to our center between April 2008 and September 2014. Only patients with blood and/or cerebrospinal fluid cultures positive for Streptococcus pneumoniae during the same time period were included for comparison. There were 19 cases of PAM and pneumococcal meningitis, each. When comparing PAM with pneumococcal meningitis, patients with PAM were more likely to be male (89.5 vs. 36.8 %), younger (mean age: 30 vs. 59 years), present with seizures (42.1 vs. 5.3 %). Both groups of patients presented with similar vital signs and there were no remarkable differences on physical examinations, Glasgow Coma Scale scores, laboratory and radiological investigations and cerebrospinal fluid parameters. PAM was also more likely to present if the city's average maximum temperature was higher in the previous week (mean: 34.6 vs. 30 °C). There was history of fresh water contact in only one patient. On multivariate analysis, PAM was more likely if patients presented when the city's average maximum temperature was high, being young males. PAM and pneumococcal meningitis remain virtually indistinguishable; however, these predictive features should be validated in a prospective study and may lead to a viable algorithm for early management of these patients.

Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection

PubMed Central

Wren, John T.; Blevins, Lance K.; Pang, Bing; Basu Roy, Ankita; Oliver, Melissa B.; Reimche, Jennifer L.; Wozniak, Jessie E.; Alexander-Miller, Martha A.

2017-01-01

ABSTRACT Even in the vaccine era, Streptococcus pneumoniae (the pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large part because of the high prevalence of nasal colonization with the pneumococcus in children. The primary pneumococcal neuraminidase, NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease by S. pneumoniae, in part via the synergistic contributions of the viral neuraminidase. The specific role of its pneumococcal counterpart, NanA, in this interaction, however, is less well understood. We demonstrate in a mouse model that NanA-deficient pneumococci are impaired in their ability to cause both nasal colonization and middle ear infection. Coinfection with neuraminidase-expressing influenza virus and S. pneumoniae potentiates both colonization and infection but not to wild-type levels, suggesting an intrinsic role of NanA. Using in vitro models, we show that while NanA contributes to both epithelial adherence and biofilm viability, its effect on the latter is actually independent of its sialidase activity. These data indicate that NanA contributes both enzymatically and nonenzymatically to pneumococcal pathogenesis and, as such, suggest that it is not a redundant bystander during coinfection with influenza A virus. Rather, its expression is required for the full synergism between these two pathogens. PMID:28096183

Effect of early measles vaccine on pneumococcal colonization: A randomized trial from Guinea-Bissau

PubMed Central

Byberg, Stine; Hervig Jacobsen, Lars; Bjerregaard-Andersen, Morten; Jensen, Aksel Karl Georg; Martins, Cesario; Aaby, Peter; Skov Jensen, Jørgen; Stabell Benn, Christine; Whittle, Hilton

2017-01-01

Background Measles vaccine (MV) may have non-specific beneficial effects for child health and particularly seems to prevent respiratory infections. Streptococcus pneumoniae is the leading cause of bacterial pneumonia among children worldwide, and nasopharyngeal colonization precedes infection. Objective We investigated whether providing early MV at 18 weeks of age reduced pneumococcal colonization and/or density up to 9 months of age. Method The study was conducted in 2013–2014 in Guinea-Bissau. Pneumococcal vaccine was not part of the vaccination program. Infants aged 18 weeks were block-randomized 2:1 to early or no early MV; at age 9 months, all children were offered MV as per current policy. Nasopharyngeal swabs were taken at baseline, age 6.5 months, and age 9 months. Pneumococcal density was determined by q-PCR. Prevalence ratios of pneumococcal colonization and recent antibiotic treatment (yes/no) by age 6.5 months (PR6.5) and age 9 months (PR9) were estimated using Poisson regression with robust variance estimates while the pneumococcal geometric mean ratio (GMR6.5 and GMR9) was obtained using OLS regression. Results Analyses included 512 children; 346 early MV-children and 166 controls. At enrolment, the pneumococcal colonization prevalence was 80% (411/512). Comparing early MV-children with controls, the PR6.5 was 1.02 (95%CI = 0.94–1.10), and the PR9 was 1.04 (0.96–1.12). The GMR6.5 was 1.02 (0.55–1.89), and the GMR9 was 0.69 (0.39–1.21). Early MV-children tended to be less frequently treated with antibiotics prior to follow up (PR6.5 0.60 (0.34–1.05) and PR9 0.87 (0.50–1.53)). Antibiotic treatment was associated with considerably lower colonization rates, PR6.5 0.85 (0.71–1.01) and PR9 0.66 (0.52–0.84), as well as lower pneumococcal density, GMR6.5 0.32 (0.12–0.86) and GMR9 0.52 (0.18–1.52). Conclusion Early MV at age 18 weeks had no measurable effect on pneumococcal colonization prevalence or density. Higher consumption of antibiotics among controls may have blurred an effect of early MV. Trial registration clinicaltrials.gov NCT01486355 PMID:28545041

Cost-effectiveness analysis of 10- and 13-valent pneumococcal conjugate vaccines in Peru.

PubMed

Mezones-Holguin, Edward; Canelo-Aybar, Carlos; Clark, Andrew David; Janusz, Cara Bess; Jaúregui, Bárbara; Escobedo-Palza, Seimer; Hernandez, Adrian V; Vega-Porras, Denhiking; González, Marco; Fiestas, Fabián; Toledo, Washington; Michel, Fabiana; Suárez, Víctor J

2015-05-07

To evaluate the cost-effectiveness of introducing the 10-valent pneumococcal conjugate vaccine (PCV10) versus the 13-valent PCV (PCV13) to the National Immunization Schedule in Peru for prevention of pneumococcal disease (PD) in children <5 years of age. The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (version 2.0) was applied from the perspective of the Government of Peru. Twenty successive cohorts of children from birth to 5 years were evaluated. Clinical outcomes were pneumococcal pneumonia (PP), pneumococcal meningitis (PM), pneumococcal sepsis (PS) and acute otitis media from any causes (AOM). Measures included prevention of cases, neurological sequelae (NS), auditory sequelae (AS), deaths and disability adjusted life years (DALYs). A sensitivity analyses was also performed. For the 20 cohorts, net costs with PCV10 and PCV13 were US$ 363.26 million and US$ 408.26 million, respectively. PCV10 prevented 570,273 AOM; 79,937 PP; 2217 PM; 3049 PS; 282 NS; 173 AS; and 7512 deaths. PCV13 prevented 419,815 AOM; 112,331 PN; 3116 PM; 4285 PS; 404 NS; 248 AS; and 10,386 deaths. Avoided DALYs were 226,370 with PCV10 and 313,119 with PCV13. Saved treatment costs were US$ 37.39 million with PCV10 and US$ 47.22 million with PCV13. Costs per DALY averted were US$ 1605 for PCV10, and US$ 1304 for PCV13. Sensitivity analyses showed similar results. PCV13 has an extended dominance over PCV10. Both pneumococcal vaccines are cost effective in the Peruvian context. Although the net cost of vaccination with PCV10 is lower, PCV13 prevented more deaths, pneumococcal complications and sequelae. Costs per each prevented DALY were lower with PCV13. Thus, PCV13 would be the preferred policy; PCV10 would also be reasonable (and cost-saving relative to the status quo) if for some reason 13-valent were not feasible. Copyright © 2015. Published by Elsevier Ltd.

Antibody blocks acquisition of bacterial colonization through agglutination

PubMed Central

Roche, A. M.; Richard, A. L.; Rahkola, J. T.; Janoff, E. N.; Weiser, J. N.

2014-01-01

Invasive infection often begins with asymptomatic colonization of mucosal surfaces. A murine model of bacterial colonization with Streptococcus pneumoniae was used to study the mechanism for mucosal protection by immunoglobulin. In previously colonized immune mice, bacteria were rapidly sequestered within large aggregates in the nasal lumen. To further examine the role of bacterial agglutination in protection by specific antibodies, mice were passively immunized with IgG purified from anti-pneumococcal sera or pneumococcal type-specific monoclonal human IgA (hIgA1 or hIgA2). Systemically-delivered IgG accessed the mucosal surface and blocked acquisition of colonization and transmission between littermates. Optimal protection by IgG was independent of Fc fragment and complement and, therefore, did not involve an opsonophagocytic mechanism. Enzymatic digestion or reduction of IgG prior to administration showed that protection required divalent binding that maintained its agglutinating effect. Divalent hIgA1 is cleaved by the pneumococcal member of a family of bacterial proteases that generate monovalent Fabα fragments. Thus, passive immunization with hIgA1 blocked colonization by an IgA1-protease deficient mutant (agglutinated), but not the protease-producing wild-type parent (not agglutinated), whereas protease-resistant hIgA2 agglutinated and blocked colonization by both. Our findings highlight the importance of agglutinating antibodies in mucosal defense and reveal how successful pathogens evade this effect. PMID:24962092

Impact of routine PCV7 (Prevenar) vaccination of infants on the clinical and economic burden of pneumococcal disease in Malaysia

PubMed Central

2011-01-01

Background Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7. Methods A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population. Results At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million). Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million) to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261) per life year gained. Conclusions PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261). This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922). PMID:21936928

Impact of routine PCV7 (Prevenar) vaccination of infants on the clinical and economic burden of pneumococcal disease in Malaysia.

PubMed

Aljunid, Syed; Abuduxike, Gulifeiya; Ahmed, Zafar; Sulong, Saperi; Nur, Amrizal Muhd; Goh, Adrian

2011-09-21

Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7. A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population. At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million). Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million) to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261) per life year gained. PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261). This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922).

Recurrent invasive pneumococcal disease in children--host factors and vaccination response.

PubMed

Ingels, Helene Andrea Sinclair

2015-07-01

Streptococcus pneumoniae is still a leading cause of septicaemia, pneumonia and meningitis in young children world-wide with over half a million children dying annually from pneumococcal disease.  Some children are prone to repeated episodes of invasive pneumococcal disease (IPD) because of an underlying predisposing disease. Recurrent IPD (rIPD) is a rarity and published reports on rIPD are limited by having few children included, selected groups of patients or short follow-up periods. Deficiencies in the innate or adaptive immune system have been described in children with rIPD, but the frequency of immunodeficiency among such patients is unknown. The aim of this PhD thesis was to examine paediatric cases of laboratory-confirmed rIPD, over a 33-year period in Denmark, to determine risk factors and study aspects of the immunological background for this problem in children. In October 2007, a seven-valent pneumococcal conjugate vaccine (PCV7) was implemented in the Danish infant immunization programme. An additional aim of the thesis was to examine the impact of vaccination on a population level, following the first three years of general PCV7 vaccination in Denmark. The thesis consists of three papers, which are all directly or indirectly based on data retrieved from the National Streptococcus Pneumoniae Registry. This registry is nationwide and dates back to 1938. The registry contains data from all laboratory-confirmed cases of IPD in Denmark and is continually updated for national surveillance. In Paper 1, we conducted a 33-year retrospective nationwide study of paediatric rIPD. By using data from the National Streptococcus Pneumoniae Registry combined with clinical data from hospital records, we could describe one of the largest known cohorts of children (n:59) with rIPD . We covered epidemiological, microbiological, and clinical features of this clinical entity. Of all children experiencing rIPD, 47% had a known predisposing underlying disease at the time of the rIPD. Most common was immune deficiency due to transplantation. In 19% the episode of rIPD was the clinical manifestation that subsequently led to a diagnosis of an underlying disease. Finally, in 31% of the children no underlying disease was detected. Paper 2 covers data from a follow-up of the cohort of children described in Paper 1. Of this unselected cohort of rIPD, all children without an obvious underlying disease predisposing to pneumococcal disease (such as malignancy, HIV or cerebrospinal-fluid leakage) were invited to participate in the study by undergoing a thorough immunological evaluation. Basic immunological parameters including activity of complement-pathways and T-, B-, NK-cell count were examined in the children and their families. Furthermore, B-cell function including antibody response to polysaccharide-based pneumococcal vaccination and somatic hypermutation was evaluated. Toll like receptor (TLR) signalling function was evaluated in a functional assay. When children with classical risk factors for IPD were excluded, 15 individuals were eligible. Of whom, sex (40%) children with complement C2 deficiency were identified. Moreover, impaired vaccination response was found in six children: three with concurrent C2 deficiency and three with no other immune abnormality. One patient with a severe TLR signalling dysfunction was diagnosed. In Paper 3, we aimed to assess the impact of PCV7 in Denmark following the first three years of infant immunization. By comparing age-specific disease incidences of IPD in the pre-PCV7 (years 2000-2007) and the PCV7 periods (years 2008-2010) we sought to assess direct and indirect effects on incidence of IPD. In addition, changes in pneumococcal serotype distribution and IPD-related mortality were assessed. We documented a marked decline in the incidence of IPD in both vaccinated and non-vaccinated age groups. The overall incidence of IPD among children aged 0-5 years declined from 26.7 to 16.3 cases per 100,000 (IRR 0.58; 95% confidence interval (CI) [0.48-0.69]). A minor but statistically significant increase in the incidence of IPD due to non-vaccine type IPD was observed in both vaccinated and non-vaccinated groups, but with predominance of serotypes covered by the higher valence pneumococcal conjugate vaccines. This thesis confirms the existing knowledge on underlying diseases predisposing children to IPD, such as cerebrospinal fluid leakage, congenital heart disease and malignant diseases. Our findings support the notion that rIPD in a child should prompt a thorough search for an underlying disease. Moreover, our results underline that rIPD in a child without a known predisposing disease is a major pointer towards primary immune deficiency, such as complement deficiency and B cell dysfunction. This is in line with the guidelines put forward by various specialist committees. Finally, we reported data from the first three years of PCV7 vaccination in the Danish immunization programme, suggesting that the vaccine is effective against all serotypes included in the vaccine when administered in a 2+1 schedule.

Meningitis complicated by subdural empyema and deafness caused by pneumoccoccal serotype 7F in a 17-month-old child: a case report.

PubMed

Bosis, S; Semino, M; Picciolli, I; Pinzani, R; Genitori, L; Principi, N; Esposito, S

2012-06-01

Despite the availability of effective antibacterial agents and vaccines, pneumococcal meningitis and sepsis are still associated with high mortality rates and a high risk of neurological sequelae. We describe the case of a 17-month-old boy vaccinated with heptavalent pneumococcal conjugate vaccine (PCV7) who developed bacterial meningitis complicated by subdural empyema and deafness caused by Streptococcus pneumoniae serotype 7F. The 7F strain is not contained in PCV7 (the only vaccine on the market at the time of the onset of meningitis) but is included in the new pediatric 13-valent PCV, which may therefore prevent cases such as this in the future.

Post-hoc analysis of a randomized controlled trial: Diabetes mellitus modifies the efficacy of the 13-valent pneumococcal conjugate vaccine in elderly.

PubMed

Huijts, Susanne M; van Werkhoven, Cornelis H; Bolkenbaas, Marieke; Grobbee, Diederick E; Bonten, Marc J M

2017-08-03

The 13-valent pneumococcal conjugate-vaccine (PCV13) was effective in preventing vaccine-type Community-Acquired Pneumonia (VT-CAP) and Invasive Pneumococcal Disease (VT-IPD) in elderly subjects, but vaccine efficacy (VE) in patients with comorbidities at time of vaccination is unknown. This is a post hoc analysis of the CAPiTA study, a double blind, randomized controlled trial with 84,496 immunocompetent participants aged ⩾65years, receiving PCV13 or placebo vaccination. Presence of diabetes mellitus (DM), heart disease, respiratory disease, liver disease, asplenia, and smoking at the time of immunization was verified on medical records in 139 subjects developing the primary endpoint of VT-CAP. Presence of DM and respiratory disease based on International Classification of Primary Care (ICPC) coding was also determined in 40,427 subjects. In the 139 subjects developing VT-CAP, DM caused significant effect modification (p-value 0.002), yielding VE of 89.5% (95%CI, 65.5-96.8) and 24.7% (95%CI, -10.4 to 48.7) for those with and without DM, respectively. Comparable effect modification (p-value 0.020) was found in the 40,427 subjects with and without ICPC-based classification of DM with VE of 85.6% (95%CI, 36.7-96.7) and of 7.0% (95%CI, -58.5 to 45.5) respectively. Effect modification through respiratory disease was not statistically significant, although the point estimate of VE was lower for those with respiratory disease in both analyses. There was no evidence of effect modification in subjects stratified by heart disease, smoking, and presence of any comorbidity. Among immunocompetent elderly, VE of PCV13 was modified by DM with higher VE among subjects with DM. Significant effect modification was not observed for subjects with heart disease, respiratory disease, smoking, or presence of any comorbidity. CAPiTA trial registration number: www.ClinicalTrials.gov; trial number NCT00744263. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Nasopharyngeal Carriage of Streptococcus pneumoniae among Children in an Urban Setting in Brazil prior to PCV10 Introduction

PubMed Central

Menezes, Ana Paula de O.; Azevedo, Jailton; Leite, Mariela C.; Campos, Leila C.; Cunha, Marcelo; Carvalho, Maria da Gloria S.; Reis, Mitermayer G.; Ko, Albert I.; Weinberger, Daniel M.; Ribeiro, Guilherme; Reis, Joice N.

2015-01-01

Information on pneumococcal carriage in the pre-vaccine period is essential to predict and assess the impact of PCV in settings where disease surveillance is particularly difficult. Therefore, we present data on pneumococcal carriage before the introduction of the 10-valent-pneumococcal conjugate vaccine (PCV10) in Brazil. We conducted a prospective study on a cohort of 203 children aged < 5 years-old, randomly selected in an urban community located in the periphery of the city of Salvador, Brazil and followed them from January/2008 to January/2009. Nasopharyngeal swabs were collected from each child at four times. In total, 721 swabs were collected, yielding a pneumococcal carriage prevalence of 55% (n=398). In multivariate analyses, the variables associated with carriage were having contact with three or more children <2 years old (OR, 2.00; 95% CI 1.33–2.89) and living in a house with an average of 3 residents per room (OR, 1.77; 95% CI 1.05–3.10). Also, white participants were more likely to be protected from colonization (OR, 0.52; 95% CI 0.29–0.93), and prevalence of carriage varied over time, with lower prevalence occurring from February to June (OR, 0.53; 95% CI 0.37–0.78) compared to July to January. Contact with children under two years of age and living in crowded housing also were associated with colonization by highly invasive serotypes, although this relationship was not significant. The most prevalent vaccine serotypes were 6A/B (25.4%), 19F (10.1%) and 14 (9.0%), while the most prevalent non-vaccine serotypes were 16F (4.8%), 15B/C (4.5%) and 6C/D (3.5%). Overall, 38.4% (153/398) of the isolates were non-susceptible to penicillin, and of those, 73.8% (113/153) were non-susceptible to trimethoprim/sulfamethoxazole. Colonization rate by PCV10 serotypes was 52.2%. Routine PCV10 vaccination can lead to significant changes in pneumococcal serotypes found in NP colonization, indicating a need for continued monitoring, especially in crowded settings, as occurs in Brazil’s slums. PMID:26742946

A public health evaluation of 13-valent pneumococcal conjugate vaccine impact on adult disease outcomes from a randomized clinical trial in the Netherlands.

PubMed

Gessner, Bradford D; Jiang, Qin; Van Werkhoven, Cornelis H; Sings, Heather L; Webber, Chris; Scott, Daniel; Neuzil, Kathleen M; O'Brien, Katherine L; Wunderink, Richard G; Grobbee, Diederick E; Bonten, Marc J M; Jodar, Luis

2018-05-31

We conducted a post-hoc analysis of a double blind, randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged 65 years or older to assess public health impact. For all outcomes, we included all randomized subjects, using a modified intention-to-treat (mITT) approach to determine vaccine efficacy (VE), vaccine preventable disease incidence (VPDI) defined as control minus vaccinated group incidence, and numbers needed to vaccinate (NNV) (based on a five-year duration of protection). Results are reported for, in order, clinical, adjudicated (clinical plus radiologic infiltrate determined by committee), pneumococcal, and vaccine-type pneumococcal (VT-Sp) community-acquired pneumonia; invasive pneumococcal disease (IPD) and VT-IPD. VEs (95% CI) for all hospital episodes were 8.1% (-0.6%, 16.1%), 6.7% (-4.1%, 16.3%), 22.2% (2.0%, 38.3%), 37.5% (14.3%, 54.5%), 49.3% (23.2%, 66.5%), and 75.8% (47.6%, 88.8%). VPDIs per 100,000 person-years of observation (PYOs) were 72, 37, 25, 25, 20, and 15 with NNVs of 277, 535, 816, 798, 1016, and 1342. For clinical CAP, PCV13 was associated with a reduction of 909 (-115, 2013) hospital days per 100,000 PYOs translating to a reduction over 5 years of one hospital day for every 22 people vaccinated. When comparing at-risk persons (defined by self-report of diabetes, chronic lung disease, or other underlying conditions) to not at-risk persons, VEs were similar or lower, but because baseline incidences were higher the VPDIs were approximately 2-10 times higher and NNVs 50-90% lower. A public health analysis of pneumonia and IPD outcomes in a randomized controlled trial found substantial burden reduction following adult PCV13 immunization implemented in a setting with an ongoing infant PCV7-PCV10 program. VPDIs were higher among at-risk adults. The original study and the current analysis were funded by Pfizer. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Self-assembling choline mimicks with enhanced binding affinities to C-LytA protein

PubMed Central

Shi, Yang; Zhou, Hao; Zhang, Xiaoli; Wang, Jingyu; Long, Jiafu; Yang, Zhimou; Ding, Dan

2014-01-01

Streptococcus pneumoniae (pneumococcus) causes multiple illnesses in humans. Exploration of effective inhibitors with multivalent attachment sites for choline-binding modules is of great importance to reduce the pneumococcal virulence. In this work, we successfully developed two self-assembling choline mimicks, Ada-GFFYKKK' and Nap-GFFYKKK', which have the abilities to self-assemble into nanoparticles and nanofibers, respectively, yielding multivalent architectures. Additionally, the best characterized choline-binding module, C-terminal moiety of the pneumococcal cell-wall amidase LytA (C-LytA) was also produced with high purity. The self-assembling Ada-GFFYKKK' and Nap-GFFYKKK' show strong interactions with C-LytA, which possess much higher association constant values to the choline-binding modules as compared to the individual peptide Fmoc-K'. This study thus provides a self-assembly approach to yield inhibitors that are very promising for reducing the pneumococcal virulence. PMID:25315737

A novel flow cytometry-based assay for the quantification of antibody-dependent pneumococcal agglutination

PubMed Central

van der Gaast—de Jongh, Christa E.; Diavatopoulos, Dimitri A.; de Jonge, Marien I.

2017-01-01

The respiratory pathogen Streptococcus pneumoniae is a major cause of diseases such as otitis media, pneumonia, sepsis and meningitis. The first step towards infection is colonization of the nasopharynx. Recently, it was shown that agglutinating antibodies play an important role in the prevention of mucosal colonization with S. pneumoniae. Here, we present a novel method to quantify antibody-dependent pneumococcal agglutination in a high-throughput manner using flow cytometry. We found that the concentration of agglutinating antibodies against pneumococcal capsule are directly correlated with changes in the size and complexity of bacterial aggregates, as measured by flow cytometry and confirmed by light microscopy. Using the increase in size, we determined the agglutination index. The cutoff value was set by measuring a series of non-agglutinating antibodies. With this method, we show that not only anti-polysaccharide capsule antibodies are able to induce agglutination but that also anti-PspA protein antibodies have agglutinating capabilities. In conclusion, we have described and validated a novel method to quantify pneumococcal agglutination, which can be used to screen sera from murine or human vaccination studies, in a high-throughput manner. PMID:28288168

Immune cell activation and cytokine release after stimulation of whole blood with pneumococcal C-polysaccharide and capsular polysaccharides.

PubMed

Sundberg-Kövamees, Marianne; Grunewald, Johan; Wahlström, Jan

2016-11-01

Streptococcus pneumonia is a major cause of morbidity and mortality in children and adults worldwide. Lack of fully effective pneumococcal vaccines is a problem. Streptococcus pneumoniae exposes on its surface C-polysaccharide (cell wall polysaccharide, CWPS) and serospecific capsular polysaccharides, used in pneumococcal vaccines. We investigated the effect of CWPS and individual capsular polysaccharides, with regard to activation of subsets of immune cells of healthy controls. Three different capsular polysaccharides, CWPS and LPS were used for in vitro stimulation of whole blood. Cell activation (CD69 expression) was assessed in CD4+ and CD4- T cells, NK-like T cells, NK cells and monocytes by flow cytometry. Cytokine levels in supernatants were quantified by Cytometric Bead Array (CBA). CWPS and the capsules activated immune cell subsets, but to different degrees. NK cells and NK-like T cells showed the strongest activation, followed by monocytes. Among the three capsules, capsule type 23 induced the strongest activation and cytokine release, followed by type 9 and type 3. This study increases the understanding of how the human immune system reacts to pneumococcal vaccine components. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates.

PubMed

Mahdi, Layla K; Higgins, Melanie A; Day, Christopher J; Tiralongo, Joe; Hartley-Tassell, Lauren E; Jennings, Michael P; Gordon, David L; Paton, Adrienne W; Paton, James C; Ogunniyi, Abiodun D

2017-04-01

Streptococcus pneumoniae (the pneumococcus) is a major human pathogen, causing a broad spectrum of diseases including otitis media, pneumonia, bacteraemia and meningitis. Here we examined the role of a potential pneumococcal meningitis vaccine antigen, alpha-glycerophosphate oxidase (SpGlpO), in nasopharyngeal colonization. We found that serotype 4 and serotype 6A strains deficient in SpGlpO have significantly reduced capacity to colonize the nasopharynx of mice, and were significantly defective in adherence to human nasopharyngeal carcinoma cells in vitro. We also demonstrate that intranasal immunization with recombinant SpGlpO significantly protects mice against subsequent nasal colonization by wild type serotype 4 and serotype 6A strains. Furthermore, we show that SpGlpO binds strongly to lacto/neolacto/ganglio host glycan structures containing the GlcNAcβ1-3Galβ disaccharide, suggesting that SpGlpO enhances colonization of the nasopharynx through its binding to host glycoconjugates. We propose that SpGlpO is a promising vaccine candidate against pneumococcal carriage, and warrants inclusion in a multi-component protein vaccine formulation that can provide robust, serotype-independent protection against all forms of pneumococcal disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Infection of zebrafish embryos with live fluorescent Streptococcus pneumoniae as a real-time pneumococcal meningitis model.

PubMed

Jim, Kin Ki; Engelen-Lee, JooYeon; van der Sar, Astrid M; Bitter, Wilbert; Brouwer, Matthijs C; van der Ende, Arie; Veening, Jan-Willem; van de Beek, Diederik; Vandenbroucke-Grauls, Christina M J E

2016-08-19

Streptococcus pneumoniae is one of the most important causes of bacterial meningitis, an infection where unfavourable outcome is driven by bacterial and host-derived toxins. In this study, we developed and characterized a pneumococcal meningitis model in zebrafish embryos that allows for real-time investigation of early host-microbe interaction. Zebrafish embryos were infected in the caudal vein or hindbrain ventricle with green fluorescent wild-type S. pneumoniae D39 or a pneumolysin-deficient mutant. The kdrl:mCherry transgenic zebrafish line was used to visualize the blood vessels, whereas phagocytic cells were visualized by staining with far red anti-L-plastin or in mpx:GFP/mpeg1:mCherry zebrafish, that have green fluorescent neutrophils and red fluorescent macrophages. Imaging was performed by fluorescence confocal and time-lapse microscopy. After infection by caudal vein, we saw focal clogging of the pneumococci in the blood vessels and migration of bacteria through the blood-brain barrier into the subarachnoid space and brain tissue. Infection with pneumolysin-deficient S. pneumoniae in the hindbrain ventricle showed attenuated growth and migration through the brain as compared to the wild-type strain. Time-lapse and confocal imaging revealed that the initial innate immune response to S. pneumoniae in the subarachnoid space mainly consisted of neutrophils and that pneumolysin-mediated cytolytic activity caused a marked reduction of phagocytes. This new meningitis model permits detailed analysis and visualization of host-microbe interaction in pneumococcal meningitis in real time and is a very promising tool to further our insights in the pathogenesis of pneumococcal meningitis.

Pneumococcal Neuraminidase A (NanA) Promotes Biofilm Formation and Synergizes with Influenza A Virus in Nasal Colonization and Middle Ear Infection.

PubMed

Wren, John T; Blevins, Lance K; Pang, Bing; Basu Roy, Ankita; Oliver, Melissa B; Reimche, Jennifer L; Wozniak, Jessie E; Alexander-Miller, Martha A; Swords, W Edward

2017-04-01

Even in the vaccine era, Streptococcus pneumoniae (the pneumococcus) remains a leading cause of otitis media, a significant public health burden, in large part because of the high prevalence of nasal colonization with the pneumococcus in children. The primary pneumococcal neuraminidase, NanA, which is a sialidase that catalyzes the cleavage of terminal sialic acids from host glycoconjugates, is involved in both of these processes. Coinfection with influenza A virus, which also expresses a neuraminidase, exacerbates nasal colonization and disease by S. pneumoniae , in part via the synergistic contributions of the viral neuraminidase. The specific role of its pneumococcal counterpart, NanA, in this interaction, however, is less well understood. We demonstrate in a mouse model that NanA-deficient pneumococci are impaired in their ability to cause both nasal colonization and middle ear infection. Coinfection with neuraminidase-expressing influenza virus and S. pneumoniae potentiates both colonization and infection but not to wild-type levels, suggesting an intrinsic role of NanA. Using in vitro models, we show that while NanA contributes to both epithelial adherence and biofilm viability, its effect on the latter is actually independent of its sialidase activity. These data indicate that NanA contributes both enzymatically and nonenzymatically to pneumococcal pathogenesis and, as such, suggest that it is not a redundant bystander during coinfection with influenza A virus. Rather, its expression is required for the full synergism between these two pathogens. Copyright © 2017 American Society for Microbiology.

Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine

PubMed Central

Elemraid, Mohamed A.; Sails, Andrew D.; Eltringham, Gary J.A.; Perry, John D.; Rushton, Stephen P.; Spencer, David A.; Thomas, Matthew F.; Eastham, Katherine M.; Hampton, Fiona; Gennery, Andrew R.; Clark, Julia E.

2013-01-01

We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006. Prospective studies were conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) of children aged 0–16 years with radiologically confirmed pneumonia seen in hospital. Investigations included culture, serology, immunofluorescence antibody and urine antigen testing, with an increased use of PCR assays and expanded panels of pathogens in the post-vaccine study. 241 and 160 children were enrolled in the pre- and post-vaccine studies, respectively (73% aged <5 years). Identification of a causative pathogen was higher post-vaccination (61%) than pre-vaccination (48.5%) (p=0.019). Rates of bacterial infections were not different between post- and pre-vaccine studies (17.5% versus 24%, p=0.258). Viral (31%) and mixed (12.5%) infections were found more often post-vaccination (19.5%, p=0.021) than pre-vaccination (5%, p=0.015). Rates of identified pneumococcal infections were comparable between pre- and post-vaccine studies (14.7% versus 17.4%, p=0.557). Diagnosis of pneumococcal infection post-vaccination improved when PCR was used compared to culture (21.6% versus 6%, p=0.0004). Serotypes included in PCV13 but not PCV7 were identified in 75% (18 out of 24) post-vaccination. Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK. PMID:23598951

The adult nasopharyngeal microbiome as a determinant of pneumococcal acquisition.

PubMed

Cremers, Amelieke Jh; Zomer, Aldert L; Gritzfeld, Jenna F; Ferwerda, Gerben; van Hijum, Sacha Aft; Ferreira, Daniela M; Shak, Joshua R; Klugman, Keith P; Boekhorst, Jos; Timmerman, Harro M; de Jonge, Marien I; Gordon, Stephen B; Hermans, Peter Wm

2014-01-01

Several cohort studies have indicated associations between S. pneumoniae and other microbes in the nasopharynx. To study causal relationships between the nasopharyngeal microbiome and pneumococcal carriage, we employed an experimental human pneumococcal carriage model. Healthy adult volunteers were assessed for pneumococcal carriage by culture of nasal wash samples (NWS). Those without natural pneumococcal carriage received an intranasal pneumococcal inoculation with serotype 6B or 23F. The composition of the nasopharyngeal microbiome was longitudinally studied by 16S rDNA pyrosequencing on NWS collected before and after challenge. Among 40 selected volunteers, 10 were natural carriers and 30 were experimentally challenged. At baseline, five distinct nasopharyngeal microbiome profiles were identified. The phylogenetic distance between microbiomes of natural pneumococcal carriers was particularly large compared to non-carriers. A more diverse microbiome prior to inoculation was associated with the establishment of pneumococcal carriage. Perturbation of microbiome diversity upon pneumococcal challenge was strain specific. Shifts in microbiome profile occurred after pneumococcal exposure, and those volunteers who acquired carriage more often diverted from their original profile. S. pneumoniae was little prominent in the microbiome of pneumococcal carriers. Pneumococcal acquisition in healthy adults is more likely to occur in a diverse microbiome and appears to promote microbial heterogeneity.

Concurrent Infection with Hepatitis C Virus and Streptococcus pneumoniae.

PubMed

Marrie, Thomas J; Tyrrell, Gregory J; Majumdar, Sumit R; Eurich, Dean T

2017-07-01

Little is known about concurrent infection with hepatitis C virus (HCV) and Streptococcus pneumoniae, which causes invasive pneumococcal disease (IPD). We hypothesized that co-infection with HCV and S. pneumoniae would increase risk for death and complications. We captured sociodemographic and serologic data for adults with IPD in a population-based cohort study in northern Alberta, Canada, during 2000-2014. IPD patients infected with HCV were compared with IPD patients not infected with HCV for risk of in-hospital deaths and complications by using multivariable logistic regression. A total of 355 of 3,251 patients with IPD were co-infected with HCV. The in-hospital mortality rate was higher for IPD patients infected with HCV. Prevalence of most IPD-related complications (e.g., cellulitis, acute kidney injury, mechanical ventilation) was also higher in HCV-infected patients. Infection with HCV is common in patients with IPD, and HCV is independently associated with an increased risk for serious illness and death.

Effect of Serotype on Pneumococcal Competition in a Mouse Colonization Model.

PubMed

Trzciński, Krzysztof; Li, Yuan; Weinberger, Daniel M; Thompson, Claudette M; Cordy, Derrick; Bessolo, Andrew; Malley, Richard; Lipsitch, Marc

2015-09-15

Competitive interactions between Streptococcus pneumoniae strains during host colonization could influence the serotype distribution in nasopharyngeal carriage and pneumococcal disease. We evaluated the competitive fitness of strains of serotypes 6B, 14, 19A, 19F, 23F, and 35B in a mouse model of multiserotype carriage. Isogenic variants were constructed using clinical strains as the capsule gene donors. Animals were intranasally inoculated with a mixture of up to six pneumococcal strains of different serotypes, with separate experiments involving either clinical isolates or isogenic capsule-switch variants of clinical strain TIGR4. Upper-respiratory-tract samples were repeatedly collected from animals in order to monitor changes in the serotype ratios using quantitative PCR. A reproducible hierarchy of capsular types developed in the airways of mice inoculated with multiple strains. Serotype ranks in this hierarchy were similar among pneumococcal strains of different genetic backgrounds in different strains of mice and were not altered when tested under a range of host conditions. This rank correlated with the measure of the metabolic cost of capsule synthesis and in vitro measure of pneumococcal cell surface charge, both parameters considered to be predictors of serotype-specific fitness in carriage. This study demonstrates the presence of a robust competitive hierarchy of pneumococcal serotypes in vivo that is driven mainly, but not exclusively, by the capsule itself. Streptococcus pneumoniae (pneumococcus) is the leading cause of death due to respiratory bacterial infections but also a commensal frequently carried in upper airways. Available vaccines induce immune responses against polysaccharides coating pneumococcal cells, but with over 90 different capsular types (serotypes) identified, they can only target strains of the selected few serotypes most prevalent in disease. Vaccines not only protect vaccinated individuals against disease but also protect by reducing carriage of vaccine-targeted strains to induce herd effects across whole populations. Unfortunately, reduction in the circulation of vaccine-type strains is offset by increase in carriage and disease from nonvaccine strains, indicating the importance of competitive interactions between pneumococci in shaping the population structure of this pathogen. Here, we showed that the competitive ability of pneumococcal strains to colonize the host strongly depends on the type of capsular polysaccharide expressed by pneumococci and only to a lesser degree on strain or host genetic backgrounds or on variation in host immune responses. Copyright © 2015 Trzciński et al.

Regulation of neuraminidase expression in Streptococcus pneumoniae

PubMed Central

2012-01-01

Background Sialic acid (N-acetylneuraminic acid; NeuNAc) is one of the most important carbohydrates for Streptococcus pneumoniae due of its role as a carbon and energy source, receptor for adhesion and invasion and molecular signal for promotion of biofilm formation, nasopharyngeal carriage and invasion of the lung. Results In this work, NeuNAc and its metabolic derivative N-acetyl mannosamine (ManNAc) were used to analyze regulatory mechanisms of the neuraminidase locus expression. Genomic and metabolic comparison to Streptococcus mitis, Streptococcus oralis, Streptococcus gordonii and Streptococcus sanguinis elucidates the metabolic association of the two amino sugars to different parts of the locus coding for the two main pneumococcal neuraminidases and confirms the substrate specificity of the respective ABC transporters. Quantitative gene expression analysis shows repression of the locus by glucose and induction of all predicted transcriptional units by ManNAc and NeuNAc, each inducing with higher efficiency the operon encoding for the transporter with higher specificity for the respective amino sugar. Cytofluorimetric analysis demonstrated enhanced surface exposure of NanA on pneumococci grown in NeuNAc and ManNAc and an activity assay allowed to quantify approximately twelve times as much neuraminidase activity on induced cells as opposed to glucose grown cells. Conclusions The present data increase the understanding of metabolic regulation of the nanAB locus and indicate that experiments aimed at the elucidation of the relevance of neuraminidases in pneumococcal virulence should possibly not be carried out on bacteria grown in glucose containing media. PMID:22963456

Pneumococcal Vaccination Guidance for Post-Acute and Long-Term Care Settings: Recommendations From AMDA's Infection Advisory Committee.

PubMed

Nace, David A; Archbald-Pannone, Laurie R; Ashraf, Muhammad S; Drinka, Paul J; Frentzel, Elizabeth; Gaur, Swati; Mahajan, Dheeraj; Mehr, David R; Mercer, William C; Sloane, Philip D; Jump, Robin L P

2017-02-01

Efforts at preventing pneumococcal disease are a national health priority, particularly in older adults and especially in post-acute and long-term care settings The Advisory Committee on Immunization Practices recommends that all adults ≥65 years of age, as well as adults 18-64 years of age with specific risk factors, receive both the recently introduced polysaccharide-protein conjugate vaccine against 13 pneumococcal serotypes as well as the polysaccharide vaccine against 23 pneumococcal serotypes. Nursing facility licensure regulations require facilities to assess the pneumococcal vaccination status of each resident, provide education regarding pneumococcal vaccination, and administer the appropriate pneumococcal vaccine when indicated. Sorting out the indications and timing for 13 pneumococcal serotypes and 23 pneumococcal serotypes administration is complex and presents a significant challenge to healthcare providers. Here, we discuss the importance of pneumococcal vaccination for older adults, detail AMDA-The Society for Post-Acute and Long-Term Care Medicine (The Society)'s recommendations for pneumococcal vaccination practice and procedures, and offer guidance to postacute and long-term care providers supporting the development and effective implementation of pneumococcal vaccine policies. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.

Pneumococcal vaccination reduces the risk of community-acquired pneumonia in children.

PubMed

Hasegawa, Junko; Mori, Mitsuru; Ohnishi, Hirofumi; Tsugawa, Takeshi; Hori, Tsukasa; Yoto, Yuko; Tsutsumi, Hiroyuki

2017-03-01

The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to Japan in 2009, after which there was a rapid decline in invasive pneumococcal disease. There are few data, however, on the effectiveness of PCV7 against community-acquired pneumonia (CAP). We conducted an ambispective cohort study among children aged 0-6 years old who attended day-care centers. A total of 624 children at 10 day-care centers in Sapporo, Japan participated in the study. The parents reported whether their child had received PCV7 one or more times, as well as the exact dates of vaccination from records in maternal and child health handbooks marked by pediatricians. Each CAP event was reported by parents according to doctor diagnosis. A Cox proportional hazards regression model was used to calculate the hazard ratio (HR) and 95%CI of CAP incidence reduced by PCV7 inoculation. During the observational period, 94 subjects contracted CAP. After adjusting for potentially confounding variables, inoculation with PCV7 was significantly associated with a reduced risk of CAP (HR, 0.22; 95%CI: 0.13-0.34). On stratified analysis by age, PCV7 was significantly associated with a reduced risk of CAP in both children aged <3 years (HR, 0.31; 95%CI: 0.14-0.71), and those ≥3 years (HR, 0.20; 95%CI: 0.09-0.43). PCV7 is highly effective in reducing the risk of CAP in children attending day-care centers. © 2016 Japan Pediatric Society.

Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates

PubMed Central

Farooqui, Habib; Jit, Mark; Heymann, David L.; Zodpey, Sanjay

2015-01-01

The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results highlight the need to improve access to care and increase coverage and equity of pneumonia preventing vaccines in states with high pneumonia burden. PMID:26086700

Non-invasive pneumococcal serotypes and antimicrobial susceptibilities in a paediatric hospital in the era of conjugate vaccines.

PubMed

McElligott, Martha; Vickers, Imelda; Cafferkey, Mary; Cunney, Robert; Humphreys, Hilary

2014-06-12

To evaluate the effects of 7-valent pneumococcal conjugate vaccine (PCV7) introduction to the routine childhood immunisation schedule in 2008 and its replacement by PCV13 in 2010 in Ireland, we surveyed the serotypes and antimicrobial susceptibilities of 339 pneumococci associated with carriage and non-invasive infection (NII) in a Dublin paediatric hospital from 2009 to 2012. Furthermore, we compared the distribution of pneumococcal serotypes collected from 2009 to 2012 to 105 NII pneumococci isolated in 2007, the year before conjugate vaccine introduction. PCV7 serotypes declined from 2007 to 2012 as follows: carriage, 67-23% (p=0.0004); conjunctivitis, 58-0% (p<0.0001); non-bacteraemic lower respiratory tract infection, 50-19% (p=0.0363) and otitis media 54-27%. Notably, antimicrobial resistant (AMR) PCV7 serotypes showed a significant decrease by the end of the study period (i.e. 2012) (p<0.0001). Compared with 2007 the overall occurrence of serotype 19A increased from 1.9 to 10% in 2010 (p=0.0132) and to 15% in 2011 (p=0.0005). Importantly, serotype 19A declined significantly from 2011 levels to an overall prevalence of 4.8% in 2012 (p=0.0243). Most striking was the significant reduction of AMR 19A (p=0.0195). Conversely, increases were observed in non-vaccine type (NVT) pneumococci in 2009-2012, of which serotypes 11A (n=30), 15B/C (n=17), 22F (n=14), 35Bn=13), non-typeable pneumococci (n=13) and 23A (n=12) were the most prevalent. Moreover, an increase in NVT non-susceptible to at least one antimicrobial in 2009-2012 was noted, attributable to serotypes 35B (n=10) and 15A (n=7). In summary, this study has shown that PCV7 and PCV13 introduction has had a positive impact on their target serotypes and antimicrobial resistance amongst pneumococci within a paediatric hospital within a short time period. However, the increase in NVT prevalence highlights the need for continued surveillance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Streptococcus pneumoniae oropharyngeal colonization in school-age children and adolescents with type 1 diabetes mellitus: Impact of the heptavalent pneumococcal conjugate vaccine.

PubMed

Principi, Nicola; Iughetti, Lorenzo; Cappa, Marco; Maffeis, Claudio; Chiarelli, Franco; Bona, Gianni; Gambino, Monia; Ruggiero, Luca; Patianna, Viviana; Matteoli, Maria Cristina; Marigliano, Marco; Cipriano, Paola; Parlamento, Silvia; Esposito, Susanna

2016-01-01

This study evaluated Streptococcus pneumoniae colonization in children and adolescents with type 1 diabetes mellitus (DM1) to investigate the theoretical risk of invasive pneumococcal disease (IPD) in these patients and the potential protective efficacy of pneumococcal conjugate vaccines (PCVs). An oropharyngeal swab was obtained from 299 patients aged 6-17 y with DM1 who were enrolled during routine clinical visits. DNA from swabs was analyzed for S. pneumoniae using real-time polymerase chain reaction. S. pneumoniae was identified in the swabs of 148 subjects (49.8%). Colonization was strictly age-related and declined significantly in the group aged ≥15 years (odds ratio [OR] 0.28; 95% confidence interval [CI], 0.14-0.57). Carriage was also significantly influenced by sex (lower in females: OR 0.56; 95% CI, 0.35-0.91), ethnicity (less common among non-Caucasians: OR 0.34; 95% CI, 0.13-0.89), parental smoking habit (more frequent among children with at least one smoker between parents: OR 1.76; 95% CI, 0.90-2.07), and the administration of antibiotic therapy in the previous 3 months (less frequent among patients who received antibiotics: OR 0.21; 95% CI, 0.07-0.62). Multivariate analyses of the entire study population showed no association between carriage and PCV7 vaccination status. Serotypes 19F, 9V, and 4 were the most frequently identified serotypes. In conclusion, school-age children and adolescents with DM1 are frequently colonized by S. pneumoniae, and protection against pneumococcal carriage following infant and toddler vaccination was not effective after several years. Together with the need to increase vaccine uptake in all the children aged <2 years, these results suggest that PCV booster doses are needed in DM1 patients to maintain the protection offered by these vaccinations.

Pneumococcal vaccine targeting strategy for older adults: customized risk profiling.

PubMed

Balicer, Ran D; Cohen, Chandra J; Leibowitz, Morton; Feldman, Becca S; Brufman, Ilan; Roberts, Craig; Hoshen, Moshe

2014-02-12

Current pneumococcal vaccine campaigns take a broad, primarily age-based approach to immunization targeting, overlooking many clinical and administrative considerations necessary in disease prevention and resource planning for specific patient populations. We aim to demonstrate the utility of a population-specific predictive model for hospital-treated pneumonia to direct effective vaccine targeting. Data was extracted for 1,053,435 members of an Israeli HMO, age 50 and older, during the study period 2008-2010. We developed and validated a logistic regression model to predict hospital-treated pneumonia using training and test samples, including a set of standard and population-specific risk factors. The model's predictive value was tested for prospectively identifying cases of pneumonia and invasive pneumococcal disease (IPD), and was compared to the existing international paradigm for patient immunization targeting. In a multivariate regression, age, co-morbidity burden and previous pneumonia events were most strongly positively associated with hospital-treated pneumonia. The model predicting hospital-treated pneumonia yielded a c-statistic of 0.80. Utilizing the predictive model, the top 17% highest-risk within the study validation population were targeted to detect 54% of those members who were subsequently treated for hospitalized pneumonia in the follow up period. The high-risk population identified through this model included 46% of the follow-up year's IPD cases, and 27% of community-treated pneumonia cases. These outcomes were compared with international guidelines for risk for pneumococcal diseases that accurately identified only 35% of hospitalized pneumonia, 41% of IPD cases and 21% of community-treated pneumonia. We demonstrate that a customized model for vaccine targeting performs better than international guidelines, and therefore, risk modeling may allow for more precise vaccine targeting and resource allocation than current national and international guidelines. Health care managers and policy-makers may consider the strategic potential of utilizing clinical and administrative databases for creating population-specific risk prediction models to inform vaccination campaigns. Copyright © 2013 Elsevier Ltd. All rights reserved.

Influenza A Virus Alters Pneumococcal Nasal Colonization and Middle Ear Infection Independently of Phase Variation

PubMed Central

Wren, John T.; Blevins, Lance K.; Pang, Bing; King, Lauren B.; Perez, Antonia C.; Murrah, Kyle A.; Reimche, Jennifer L.; Alexander-Miller, Martha A.

2014-01-01

Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media. PMID:25156728

Roles of autolysin and pneumolysin in middle ear inflammation caused by a type 3 Streptococcus pneumoniae strain in the chinchilla otitis media model.

PubMed Central

Sato, K; Quartey, M K; Liebeler, C L; Le, C T; Giebink, G S

1996-01-01

Streptococcus pneumoniae cell wall and pneumolysin are important contributors to pneumococcal pathogenicity in some animal models. To further explore these factors in middle ear inflammation caused by pneumococci, penicillin-induced inflammatory acceleration was studied by using three closely related pneumococcal strains: a wild-type 3 strain (WT3), its pneumolysin-negative derivative (P-1), and into autolysin-negative derivative (A-1). Both middle ears of chinchillas were inoculated with one of the three pneumococcal strains. During the first 12 h, all three strains grew in vivo at the same rate, and all three strains induced similar inflammatory cell responses in middle ear fluid (MEF). Procaine penicillin G was given as 12 h to one-half of the animals in each group, and all treated chinchillas had sterile MEF at 24 h. Penicillin significantly accelerated MEF inflammatory cell influx into WT3-and P-1-infected ears at 18 and 24 h in comparison with the rate for penicillin-treated A-1-infected ears. Inflammatory cell influx was slightly, but not significantly, greater after treatment of WT3 infection than after treatment of P-1 infection. Interleukin (IL)-1beta and IL-6, but not IL-8, concentrations in MEF at 24 h reflected the penicillin effect on MEF inflammatory cells; however, differences between treatment groups were not significant. Results suggest that pneumococcal otitis media pathogenesis is triggered principally by the inflammatory effects of intact and lytic cell wall products in the middle ear, with at most a modes additional pneumolysin effect. Investigation strategies that limit the release of these products or neutralize them warrant further investigation. PMID:8606070

Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes

PubMed Central

Self, Wesley H.; Wunderink, Richard G.; Williams, Derek J.; Zhu, Yuwei; Anderson, Evan J.; Balk, Robert A.; Fakhran, Sherene S.; Chappell, James D.; Casimir, Geoffrey; Courtney, D. Mark; Trabue, Christopher; Waterer, Grant W.; Bramley, Anna; Magill, Shelley; Jain, Seema; Edwards, Kathryn M.; Grijalva, Carlos G.

2016-01-01

Background. Prevalence of Staphylococcus aureus community-acquired pneumonia (CAP) and its clinical features remain incompletely understood, complicating empirical selection of antibiotics. Methods. Using a multicenter, prospective surveillance study of adults hospitalized with CAP, we calculated the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) among all CAP episodes. We compared the epidemiologic, radiographic, and clinical characteristics of S. aureus CAP (per respiratory or blood culture) with those of pneumococcal (per respiratory or blood culture or urine antigen) and all-cause non-S. aureus CAP using descriptive statistics. Results. Among 2259 adults hospitalized for CAP, 37 (1.6%) had S. aureus identified, including 15 (0.7%) with MRSA and 22 (1.0%) with MSSA; 115 (5.1%) had Streptococcus pneumoniae. Vancomycin or linezolid was administered to 674 (29.8%) patients within the first 3 days of hospitalization. Chronic hemodialysis use was more common among patients with MRSA (20.0%) than pneumococcal (2.6%) and all-cause non-S. aureus (3.7%) CAP. Otherwise, clinical features at admission were similar, including concurrent influenza infection, hemoptysis, multilobar infiltrates, and prehospital antibiotics. Patients with MRSA CAP had more severe clinical outcomes than those with pneumococcal CAP, including intensive care unit admission (86.7% vs 34.8%) and in-patient mortality (13.3% vs 4.4%). Conclusions. Despite very low prevalence of S. aureus and, specifically, MRSA, nearly one-third of adults hospitalized with CAP received anti-MRSA antibiotics. The clinical presentation of MRSA CAP overlapped substantially with pneumococcal CAP, highlighting the challenge of accurately targeting empirical anti-MRSA antibiotics with currently available clinical tools and the need for new diagnostic strategies. PMID:27161775

A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice.

PubMed

Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

2016-01-01

Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

Neisseria meningitidis and Streptococcus pneumoniae as leading causes of pediatric bacterial meningitis in nine Mexican hospitals following 3 years of active surveillance.

PubMed

Chacon-Cruz, Enrique; Martinez-Longoria, Cesar Adrian; Llausas-Magana, Eduardo; Luevanos-Velazquez, Antonio; Vazquez-Narvaez, Jorge Alejandro; Beltran, Sandra; Limon-Rojas, Ana Elena; Urtiz-Jeronimo, Fernando; Castaneda-Narvaez, Jose Luis; Otero-Mendoza, Francisco; Aguilar-Del Real, Fernando; Rodriguez-Chagoyan, Jesus; Rivas-Landeros, Rosa Maria; Volker-Soberanes, Maria Luisa; Hinojosa-Robles, Rosa Maria; Arzate-Barbosa, Patricia; Aviles-Benitez, Laura Karina; Elenes-Zamora, Fernando Ivan; Becka, Chandra M; Ruttimann, Ricardo

2016-01-01

Meningococcal meningitis is reported as a rare condition in Mexico. There are no internationally published studies on bacterial causes of meningitis in the country based on active surveillance. This study focuses on finding the etiology of bacterial meningitis in children from nine Mexican Hospitals. From January 2010 to February 2013, we conducted a three years of active surveillance for meningitis in nine hospitals throughout Mexico. Active surveillance started at the emergency department for every suspected case, and microbiological studies confirmed/ruled out all potentially bacterial pathogens. We diagnosed based on routine cultures from blood and cerebrospinal fluid (not polymerase chain reaction or other molecular diagnostic tests), and both pneumococcal serotyping and meningococcal serogrouping by using standard methods. Neisseria meningitidis was the leading cause, although 75% of cases occurred in the northwest of the country in Tijuana on the US border. Serogroup C was predominant. Streptococcus pneumoniae followed Neisseria meningitides, but was uniformly distributed throughout the country. Serotype 19A was the most incident but before universal implementation of the 13-valent pneumococcal conjugate vaccine. Other bacteria were much less common, including Enterobacteriaceae and Streptococcus agalactiae (these two affecting mostly young infants). Meningococcal meningitis is endemic in Tijuana, Mexico, and vaccination should be seriously considered in that region. Continuous universal vaccination with the 13-valent pneumococcal conjugate vaccine should be nationally performed, and polymerase chain reaction should be included for bacterial detection in all cultures - negative but presumably bacterial meningitis cases.

Streptococcus pneumoniae-associated pneumonia complicated by purulent pericarditis: case series *

PubMed Central

Cillóniz, Catia; Rangel, Ernesto; Barlascini, Cornelius; Piroddi, Ines Maria Grazia; Torres, Antoni; Nicolini, Antonello

2015-01-01

Abstract Objective: In the antibiotic era, purulent pericarditis is a rare entity. However, there are still reports of cases of the disease, which is associated with high mortality, and most such cases are attributed to delayed diagnosis. Approximately 40-50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, Streptococcus pneumoniae in particular. Methods: We report four cases of pneumococcal pneumonia complicated by pericarditis, with different clinical features and levels of severity. Results: In three of the four cases, the main complication was cardiac tamponade. Microbiological screening (urinary antigen testing and pleural fluid culture) confirmed the diagnosis of severe pneumococcal pneumonia complicated by purulent pericarditis. Conclusions: In cases of pneumococcal pneumonia complicated by pericarditis, early diagnosis is of paramount importance to avoid severe hemodynamic compromise. The complications of acute pericarditis appear early in the clinical course of the infection. The most serious complications are cardiac tamponade and its consequences. Antibiotic therapy combined with pericardiocentesis drastically reduces the mortality associated with purulent pericarditis. PMID:26398760

[Pneumococcal vaccines in children: an update].

PubMed

Potin, Marcela

2014-08-01

Conjugated pneumococal vaccines had a notable impact on prevention of invasive pneumococcal disease (IPD) in vacccinated and non vaccinated (herd immunity) populations. In Chile a 10 valent conjugated vaccine (PCV10) was introduced in the Nacional Immunization Program (NIP) in 2011, initially in a 3+1 schedule at 2, 4, 6 and 12 months of age, and since 2012 in a 2+1 schedule (2, 4 and 12 months). In prematures schedule 3+1 was maintained. No catch up or high risk groups vaccination strategies were used. The inclusion of PCV10 has reduced the rates of IPD; 66% in infants less than 12 months old and a 60% in 12-24 months old. After 3 years of the introduction of PCV10, no herd immunity has been seen. Serotype replacement shows an increase of ST 3 but not ST19A. Surveillance shows that another vaccine with 13 serotypes (PCV13) would cover an additional 5 to 10% of cases. The nule herd immunity and more extense coverage of PCV13, suggests that NIP should switch from PCV10 to PCV13.

Attenuated cerebrospinal fluid leukocyte count and sepsis in adults with pneumococcal meningitis: a prospective cohort study

PubMed Central

Weisfelt, Martijn; van de Beek, Diederik; Spanjaard, Lodewijk; Reitsma, Johannes B; de Gans, Jan

2006-01-01

Background A low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood. Methods We examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years. Results CSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3 (interquartile range 531–6983 per mm3) and 104 patients (33%) had a CSF WBC <1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1–4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02–1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17–5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments 0.67, 95% CI 0.47–0.97) were associated with a CSF WBC <1000/mm3. Conclusion A low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis. PMID:17038166

Cost-effectiveness analysis of a universal mass vaccination program with a PHiD-CV 2+1 schedule in Malaysia.

PubMed

Wang, Xiao Jun; Saha, Ashwini; Zhang, Xu-Hao

2017-01-01

Currently, two pediatric pneumococcal conjugate vaccines are available in the private market of Malaysia-13-valent pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). This study aimed to evaluate the cost-effectiveness of a universal mass vaccination program with a PHiD-CV 2+1 schedule versus no vaccination or with a PCV13 2+1 schedule in Malaysia. A published Markov cohort model was adapted to evaluate the epidemiological and economic consequences of programs with no vaccination, a PHiD-CV 2+1 schedule or a PCV13 2+1 schedule over a 10-year time horizon. Disease cases, deaths, direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated. Locally published epidemiology and cost data were used whenever possible. Vaccine effectiveness and disutility data were based on the best available published data. All data inputs and assumptions were validated by local clinical and health economics experts. Analyses were conducted from the perspective of the Malaysian government for a birth cohort of 508,774. Costs and QALYs were discounted at 3% per annum. One-way and probabilistic sensitivity analyses were performed. Compared with no vaccination, a PHiD-CV 2+1 program was projected to prevent 1109 invasive pneumococcal disease (IPD), 24,679 pneumonia and 72,940 acute otitis media (AOM) cases and 103 IPD/pneumonia deaths over 10 years, with additional costs and QALYs of United States dollars (USD) 30.9 million and 1084 QALYs, respectively, at an ICER of USD 28,497/QALY. Compared with a PCV13 2+1 program, PHiD-CV 2+1 was projected to result in similar reductions in IPD cases (40 cases more) but significantly fewer AOM cases (30,001 cases less), with cost savings and additional QALYs gained of USD 5.2 million and 116 QALYs, respectively, demonstrating dominance over PCV13. Results were robust to variations in one-way and probabilistic sensitivity analyses. A PHiD-CV 2+1 universal mass vaccination program could substantially reduce pneumococcal disease burden versus no vaccination, and was expected to be cost-effective in Malaysia. A PHiD-CV 2+1 program was also expected to be a dominant choice over a PCV13 2+1 program in Malaysia.

Chickenpox complicated by pneumococcal meningitis: a rare coinfection.

PubMed

Rebahi, H; Mouaffak, Y; Soraa, N; Younous, S

2014-11-01

Bacterial complications, particularly skin superinfections, are common during chickenpox. However, reports of acute bacterial meningitis associated with chickenpox are unusual and amount to only a very few observations. For the most part, they are caused by Neisseria meningitidis or Streptococcus pyogenes. We report an infrequent occurrence of pneumococcal meningitis 2 days after the onset of a chickenpox rash in a 7-year-old previously healthy boy. Based on data from the literature, we attempt to understand the possible mechanisms resulting in bacterial complications, particularly meningitis, during chickenpox and to determine the means to prevent it. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Fatal infection caused by a multiply resistant type 3 pneumococcus.

PubMed Central

Lawrenson, J B; Klugman, K P; Eidelman, J I; Wasas, A; Miller, S D; Lipman, J

1988-01-01

The most virulent pneumococcal serotype (type 3) has not to date been associated with multiple antimicrobial resistance. We report an unusual gastrointestinal presentation of fatal septicemia caused by a multiply resistant type 3 pneumococcus in a setting of increasing prevalence of multiple resistance, including resistance to erythromycin, clindamycin, and tetracycline. PMID:3170717

In vitro expression of Streptococcus pneumoniae ply gene in human monocytes and pneumocytes.

PubMed

Hu, Da-Kang; Liu, Yang; Li, Xiang-Yang; Qu, Ying

2015-05-07

Streptococcus pneumoniae is one major cause of pneumonia in human and contains various virulence factors that contribute to pathogenesis of pneumococcal disease. This study investigated the role of pneumolysin, Ply, in facilitating S. pneumoniae invasion into the host blood stream. S. pneumoniae strains were isolated from clinical blood and sputum samples and confirmed by PCR. Expression of ply gene was assessed by infecting human monocytes and pneumocytes. A total of 23 strains of S. pneumoniae isolated from blood (n = 11) and sputum (n = 12) along with S. pneumoniae ATCC49619 were used to infect human monocyte (THP-1) and Type II pneumocyte (A549) cell lines. All clinical strains of S. pneumoniae showed higher expression of ply mRNA than the American Type Culture Collection (ATCC) strain. Among the clinical strains, blood isolates showed higher expression of ply genes than sputum isolates, i.e., 2(1.5)- to 2(1.6)-folds in THP-1 and 2(0.4)- to 2(4.9)-folds in A549 cell lines. The data from the current study demonstrated that ply gene of blood- and sputum-derived S. pneumoniae is differentially expressed in two different cell lines. Under survival pressure, ply is highly expressed in these two cell lines for blood-derived S. pneumoniae, indicating that ply gene may facilitate S. pneumoniae invasion into the host blood system.

Cost effectiveness of adding 7-valent pneumococcal conjugate (PCV-7) vaccine to the Norwegian childhood vaccination program.

PubMed

Wisløff, Torbjørn; Abrahamsen, Tore G; Bergsaker, Marianne A Riise; Løvoll, Øistein; Møller, Per; Pedersen, Maren Kristine; Kristiansen, Ivar Sønbø

2006-07-17

Streptococcus pneumoniae is a frequent bacterial cause of serious infections that may cause permanent sequelae and death. A 7-valent conjugate vaccine may reduce the incidence of pneumococcal disease, but some previous studies have questioned the cost-effectiveness of the vaccine. The aim of this study was to estimate costs and health consequences of adding this pneumococcal vaccine to the Norwegian childhood vaccination programme, taking the possibility of herd immunity into account. We developed a simulation model (Markov-model) using data on the risk of pneumococcal disease in Norway, the efficacy of the vaccine as observed in clinical trials from other countries and adjusted for serotype differences, the cost of the vaccine and quality of life for patients with sequelae from pneumococcal disease. The results were expressed as incremental (additional) costs (in euros; euro1.00 approximately NOK8.37), incremental life years and incremental quality adjusted life years. Four different sets of main results are presented: costs and (quality adjusted) life years, with and without indirect costs (the value of lost production due to work absenteeism) and with and without potential herd immunity (i.e. childhood vaccination protects adults against pneumococcal disease). When indirect costs were disregarded, and four vaccine doses used, the incremental cost per life year gained was euro153,000 when herd immunity was included, and euro311,000 when it was not. When accounting for indirect costs as well, the cost per life year gained was euro58,000 and euro124,000, respectively. Assuming that three vaccine doses provide the same protection as four, the cost per life year gained with this regimen was euro90,000 with herd immunity and euro184,000 without (when indirect costs are disregarded). If indirect costs are also included, vaccination both saves costs and gains life years. In Norway, governmental guidelines indicate that only interventions with cost per life year of less than euro54,000 should be implemented. This implies that four dose vaccination is not cost-effective even if decision makers includes both herd immunity and indirect costs in their decisions. If three doses offer the same protection as four doses, however, vaccination would be cost-saving when indirect costs are included, but not with only herd immunity. In the autumn of 2005, the Norwegian Government decided to include PCV-7 in the vaccination program. This analysis was used by the Ministry of Health and Ministry of Finance during the decision process.

Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites

PubMed Central

Feikin, Daniel R.; Kagucia, Eunice W.; Loo, Jennifer D.; Link-Gelles, Ruth; Puhan, Milo A.; Cherian, Thomas; Levine, Orin S.; Whitney, Cynthia G.; O’Brien, Katherine L.; Moore, Matthew R.

2013-01-01

Background Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. Methods and Findings Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥2 years before and ≥1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0·55, 95% CI 0·46–0·65) and remained relatively stable through year 7 (RR 0·49, 95% CI 0·35–0·68). Point estimates for VT IPD decreased annually through year 7 (RR 0·03, 95% CI 0·01–0·10), while NVT IPD increased (year 7 RR 2·81, 95% CI 2·12–3·71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18–49 year-olds [RR 0·52, 95% CI 0·29–0·91], 50–64 year-olds [RR 0·84, 95% CI 0·77–0·93], and ≥65 year-olds [RR 0·74, 95% CI 0·58–0·95]). Conclusions Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used. Please see later in the article for the Editors' Summary PMID:24086113

Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States.

PubMed

Metcalf, B J; Chochua, S; Gertz, R E; Li, Z; Walker, H; Tran, T; Hawkins, P A; Glennen, A; Lynfield, R; Li, Y; McGee, L; Beall, B

2016-12-01

Our whole genome sequence (WGS) pipeline was assessed for accurate prediction of antimicrobial phenotypes. For 2316 invasive pneumococcal isolates recovered during 2015 we compared WGS pipeline data to broth dilution testing (BDT) for 18 antimicrobials. For 11 antimicrobials categorical discrepancies were assigned when WGS-predicted MICs and BDT MICs predicted different categorizations for susceptibility, intermediate resistance or resistance, ranging from 0.9% (tetracycline) to 2.9% (amoxicillin). For β-lactam antibiotics, the occurrence of at least four-fold differences in MIC ranged from 0.2% (meropenem) to 1.0% (penicillin), although phenotypic retesting resolved 25%-78% of these discrepancies. Non-susceptibility to penicillin, predicted by penicillin-binding protein types, was 2.7% (non-meningitis criteria) and 23.8% (meningitis criteria). Other common resistance determinants included mef (475 isolates), ermB (191 isolates), ermB + mef (48 isolates), tetM (261 isolates) and cat (51 isolates). Additional accessory resistance genes (tetS, tet32, aphA-3, sat4) were rarely detected (one to three isolates). Rare core genome mutations conferring erythromycin-resistance included a two-codon rplD insertion (rplD69-KG-70) and the 23S rRNA A2061G substitution (six isolates). Intermediate cotrimoxazole-resistance was associated with one or two codon insertions within folP (238 isolates) or the folA I100L substitution (38 isolates), whereas full cotrimoxazole-resistance was attributed to alterations in both genes (172 isolates). The two levofloxacin-resistant isolates contained parC and/or gyrA mutations. Of 11 remaining isolates with moderately elevated MICs to both ciprofloxacin and levofloxacin, seven contained parC or gyrA mutations. The two rifampin-resistant isolates contained rpoB mutations. WGS-based antimicrobial phenotype prediction was an informative alternative to BDT for invasive pneumococci. Published by Elsevier Ltd.

Bright fluorescent Streptococcus pneumoniae for live-cell imaging of host-pathogen interactions.

PubMed

Kjos, Morten; Aprianto, Rieza; Fernandes, Vitor E; Andrew, Peter W; van Strijp, Jos A G; Nijland, Reindert; Veening, Jan-Willem

2015-03-01

Streptococcus pneumoniae is a common nasopharyngeal resident in healthy people but, at the same time, one of the major causes of infectious diseases such as pneumonia, meningitis, and sepsis. The shift from commensal to pathogen and its interaction with host cells are poorly understood. One of the major limitations for research on pneumococcal-host interactions is the lack of suitable tools for live-cell imaging. To address this issue, we developed a generally applicable strategy to create genetically stable, highly fluorescent bacteria. Our strategy relies on fusing superfolder green fluorescent protein (GFP) or a far-red fluorescent protein (RFP) to the abundant histone-like protein HlpA. Due to efficient translation and limited cellular diffusion of these fusions, the cells are 25-fold brighter than those of the currently best available imaging S. pneumoniae strain. These novel bright pneumococcal strains are fully virulent, and the GFP reporter can be used for in situ imaging in mouse tissue. We used our reporter strains to study the effect of the polysaccharide capsule, a major pneumococcal virulence factor, on different stages of infection. By dual-color live-cell imaging experiments, we show that unencapsulated pneumococci adhere significantly better to human lung epithelial cells than encapsulated strains, in line with previous data obtained by classical approaches. We also confirm with live-cell imaging that the capsule protects pneumococci from neutrophil phagocytosis, demonstrating the versatility and usability of our reporters. The described imaging tools will pave the way for live-cell imaging of pneumococcal infection and help further understanding of the mechanisms of pneumococcal pathogenesis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Cost-effectiveness of the 13-valent Pneumococcal Conjugate Vaccine in Children in Portugal.

PubMed

Gouveia, Miguel; Fiorentino, Francesca; Jesus, Gonçalo; Costa, João; Borges, Margarida

2017-08-01

Pneumococcal infections are the leading cause of vaccine-preventable death in children. In June 2015, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the Portuguese Immunization Program. We evaluated the cost-effectiveness of children vaccinated with PCV13 versus no vaccination for preventing pneumococcal diseases. A cohort simulation model for 2014 Portuguese newborns was used, considering a lifetime horizon and existence of herd effect on adults. Model outcomes measured life years gained, direct and indirect healthcare costs and net benefits considering &OV0556;20,000 per life years gained. PCV13 clinical effectiveness rate by serotype covered was assumed similar to PCV7. Patients' resource use was based on 2014 diagnostic-related group database and experts' opinion, while national legislation and official drug cost database were the main sources for unitary costs. Univariate sensitivity analyses were conducted to assess results' effectiveness. In base case scenario, PCV13 was a dominant strategy, being associated with better health outcomes and lower costs. In a lifetime, a total of 6238 infections (excluding acute otitis media) and 130 deaths were averted, with a total saving of &OV0556;397,217 ($432,966). Net benefits were estimated above &OV0556;28 million ($30 million). Results were robust in all sensitivity analyses, with positive net benefits, except when herd effect was excluded. Vaccination of children with PCV13 starting in their first year of life is a cost-effective intervention with the potential to save costs to the Portuguese health system and to provide health gains by reducing the burden of pneumococcal disease in the vaccines and through the herd effect of this vaccine.

Nationwide Trends in Bacterial Meningitis before the Introduction of 13-Valent Pneumococcal Conjugate Vaccine-Burkina Faso, 2011-2013.

PubMed

Kambiré, Dinanibè; Soeters, Heidi M; Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Sangare, Lassana; Yaméogo, Issaka; Sawadogo, Guetawendé; Ouédraogo, Abdoul-Salam; Hema-Ouangraoua, Soumeya; McGee, Lesley; Srinivasan, Velusamy; Aké, Flavien; Congo-Ouédraogo, Malika; Sanou, Soufian; Ba, Absatou Ky; Novak, Ryan T; Van Beneden, Chris

2016-01-01

Following introduction of Haemophilus influenzae type b vaccine in 2006 and serogroup A meningococcal conjugate vaccine in 2010, Streptococcus pneumoniae (Sp) became the leading cause of bacterial meningitis in Burkina Faso. We describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the pediatric routine immunization program in October 2013. Nationwide population-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Sp infections are confirmed by culture, real-time polymerase chain reaction (rt-PCR), or latex agglutination, and CSF serotyped using real-time and conventional PCR. We calculated incidence rates in cases per 100,000 persons, adjusting for age and proportion of cases with CSF tested at national reference laboratories, and case fatality ratios (CFR). During 2011-2013, 1,528 pneumococcal meningitis cases were reported. Average annual adjusted incidence rates were 26.9 (<1 year), 5.4 (1-4 years), 7.2 (5-14 years), and 3.0 (≥15 years). Overall CFR was 23% and highest among children aged <1 year (32%) and adults ≥30 years (30%). Of 1,528 cases, 1,036 (68%) were serotyped: 71% were PCV13-associated serotypes, 14% were non-PCV13-associated serotypes, and 15% were non-typeable by PCR. Serotypes 1 (45%) and 12F/12A/12B/44/46 (8%) were most common. Among children aged <1 year, serotypes 5 (15%), 6A/6B (13%) and 1 (12%) predominated. In Burkina Faso, the highest morbidity and mortality due to pneumococcal meningitis occurred among children aged <1 year. The majority of cases were due to PCV13-associated serotypes; introduction of PCV13 should substantially decrease this burden.

Mechanisms of genome evolution of Streptococcus.

PubMed

Andam, Cheryl P; Hanage, William P

2015-07-01

The genus Streptococcus contains 104 recognized species, many of which are associated with human or animal hosts. A globally prevalent human pathogen in this group is Streptococcus pneumoniae (the pneumococcus). While being a common resident of the upper respiratory tract, it is also a major cause of otitis media, pneumonia, bacteremia and meningitis, accounting for a high burden of morbidity and mortality worldwide. Recent findings demonstrate the importance of recombination and selection in driving the population dynamics and evolution of different pneumococcal lineages, allowing them to successfully evade the impacts of selective pressures such as vaccination and antibiotic treatment. We highlight the ability of pneumococci to respond to these pressures through processes including serotype replacement, capsular switching and horizontal gene transfer (HGT) of antibiotic resistance genes. The challenge in controlling this pathogen also lies in the exceptional genetic and phenotypic variation among different pneumococcal lineages, particularly in terms of their pathogenicity and resistance to current therapeutic strategies. The widespread use of pneumococcal conjugate vaccines, which target only a small subset of the more than 90 pneumococcal serotypes, provides us with a unique opportunity to elucidate how the processes of selection and recombination interact to generate a remarkable level of plasticity and heterogeneity in the pneumococcal genome. These processes also play an important role in the emergence and spread of multi-resistant strains, which continues to pose a challenge in disease control and/or eradication. The application of population of genomic approaches at different spatial and temporal scales will help improve strategies to control this global pathogen, and potentially other pathogenic streptococci. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines

PubMed Central

2012-01-01

Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832 PMID:22676626

Incidence of invasive pneumococcal disease in 5-15 year old children with and without comorbidities in Germany after the introduction of PCV13: Implications for vaccinating children with comorbidities.

PubMed

Weinberger, Raphael; Falkenhorst, Gerhard; Bogdan, Christian; van der Linden, Mark; Imöhl, Matthias; von Kries, Rüdiger

2015-11-27

To describe the burden of suffering from IPD in children aged 5-15 years with and without comorbidities up to 5 years after the introduction of PCV13 in Germany and to identify the potential benefit for PCV13 and PPV23 vaccination. The surveillance of IPD for children <16 years was based on two independently reporting sources: active surveillance in pediatric hospitals and a laboratory-based sentinel surveillance system. IPD with cultural detection of pneumococci at a physiologically sterile site in children from 2010 to 2014 in Germany. Incidence was estimated by capture-recapture analysis with stratification by absence/presence of comorbidities. Coverage of the observed serotypes by different vaccines was assessed. 142 (Capture recapture-corrected: 437) cases were reported: 72.5% were healthy children and 27.5% had a comorbidity. The incidence of IPD related to children with comorbidities was 0.2 per 100,000. One third of these cases had serotypes not included in either vaccine. The remaining cases might benefit from pneumococcal vaccination but one third of all cases was not vaccinated. The additional potential benefit of PPV23 compared to PCV13 with respect to coverage was 10%. The incidence of IPD in children with comorbidities in Germany is low. Pneumococcal vaccination uptake in children with comorbidities should be increased, although only about two-thirds of the cases might be preventable by presently available vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pneumococcal pneumonia - Are the new severity scores more accurate in predicting adverse outcomes?

PubMed

Ribeiro, C; Ladeira, I; Gaio, A R; Brito, M C

2013-01-01

The site-of-care decision is one of the most important factors in the management of patients with community-acquired pneumonia. The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision. The aim of this paper was to compare the discriminatory power of four scores - the classic PSI and CURB65 ant the most recent SCAP and SMART-COP - in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support in patients admitted with pneumococcal pneumonia. A five year retrospective study of patients admitted for pneumococcal pneumonia. Patients were stratified based on admission data and assigned to low-, intermediate-, and high-risk classes for each score. Results were obtained comparing low versus non-low risk classes. We studied 142 episodes of hospitalization with 2 deaths and 10 patients needing mechanical ventilation and vasopressor support. The majority of patients were classified as low risk by all scores - we found high negative predictive values for all adverse events studied, the most negative value corresponding to the SCAP score. The more recent scores showed better accuracy for predicting ICU admission and need for ventilation or vasopressor support (mostly for the SCAP score with higher AUC values for all adverse events). The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores appear to have a higher discriminatory power in all adverse events in our study, particularly, the SCAP score. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines.

PubMed

Sanvictores, Diozele Hazel M; Lucero, Marilla G; Nohynek, Hanna; Tallo, Veronica L; Tanskanen, Antti; Nillos, Leilani T; Williams, Gail

2012-06-07

A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Current Controlled Trials ISRCTN62323832.

Pneumococcal Capsular Polysaccharide Immunity in the Elderly

PubMed Central

Ferreira, Daniela M.; Gordon, Stephen B.; Rylance, Jamie

2017-01-01

ABSTRACT Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally acquired immunity to pneumococcal capsular polysaccharides develops during childhood and is robust in young adults but deteriorates with advanced age. In particular, antibody levels and function are reduced in older people. Pneumococcal vaccines are recommended for people >65 years old. However, the benefits of polysaccharide and protein-conjugated vaccines in this population are small, because of both serotype replacement and incomplete protection against vaccine serotype pneumococcal disease. In this review, we overview the immune mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular polysaccharide immunity declines with age, including altered colonization dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired mucosal immunity. PMID:28424198

Intracochlear perfusion of pneumolysin, a pneumococcal protein, rapidly abolishes auditory potentials in the Guinea pig cochlea.

PubMed

Skinner, Liam J; Beurg, Maryline; Mitchell, Timothy J; Darrouzet, Vincent; Aran, Jean-Marie; Dulon, Didier

2004-11-01

Bacterial meningitis and chronic suppurative otitis media caused by Streptococcus pneumoniae are associated with considerable otological morbidity. Specifically, sensorineural hearing loss is a permanent sequela in a third of those who contract pneumococcal meningitis. Pneumolysin, a pneumococcal protein, has been implicated as one of the main virulence/cytotoxic factors. Its pathogenicity is intimately dependent on an ability to form transmembrane pores on binding with cholesterol in target tissues. We perfused wild-type pneumolysin, at a number of different concentrations, into the guinea pig cochlea and used electrocochleography to characterize the effects of this cytolytic exotoxin in the organ of Corti. Intracochlear perfusion of pneumolysin (10 microg/50 microl) reduced the compound action potential of the auditory nerve within seconds. The cochlear microphonics (f1=8 kHz, f2=9.68 kHz) and their distortion product (2f1-f2) were also reduced, albeit in a slightly less dramatic fashion. At lower concentrations (1 microg/50 microl), a selective and earlier effect on inner hair cells was observed. These results clearly show that significant ototoxicity ensues when sensory cells of the organ of Corti are exposed to pneumolysin (and complete cochlear death when the concentration is high enough). Toxicity is dose-dependent and appears to be site-sensitive. This may have implications for any possible future protective strategies against pneumococcal disease in the ear.

Additive benefits of pneumococcal and influenza vaccines among elderly persons aged 75 years or older in Taiwan--a representative population-based comparative study.

PubMed

Chang, Yu-Chia; Chou, Yiing-Jenq; Liu, Jen-Yin; Yeh, Te-Feng; Huang, Nicole

2012-09-01

It remains unclear whether pneumococcal vaccine provides additional protection to the elderly who have already vaccinated with influenza vaccine. This retrospective cohort study aimed to assess the additive effect of pneumococcal and influenza vaccines on the risk of mortality, hospitalization, and inpatient expenditure in the elderly aged 75 years or older in Taiwan. Data were extracted from the National Health Insurance claims data of a nationally representative elderly sample. To reduce potential selection bias, we employed a propensity score matching method to classify the vaccination status into 3 groups. Multivariable logistic and linear regression models were used to compare the outcomes among different groups. Each group contained 8142 subjects. The results indicated that an additive effect of receiving both vaccines was associated with a significantly lower all-cause mortality (relative risk [RR]: 0.74; 95% confidence interval [CI]: 0.57-0.96), hospitalization of all diseases including pneumonia, influenza, chronic obstructive pulmonary disease, respiratory diseases, and congestive heart disease (RR: 0.77; 95% CI: 0.67-0.90), and a 13% reduction (95% CI: 0.81-0.94) in inpatient expenditures of all diseases when compared with receiving influenza vaccine alone. This study confirmed that vaccination of elderly individuals with pneumococcal vaccine and influenza vaccine concomitantly has substantial beneficial effects. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Influenza A virus alters pneumococcal nasal colonization and middle ear infection independently of phase variation.

PubMed

Wren, John T; Blevins, Lance K; Pang, Bing; King, Lauren B; Perez, Antonia C; Murrah, Kyle A; Reimche, Jennifer L; Alexander-Miller, Martha A; Swords, W Edward

2014-11-01

Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Discovery of prenylated flavonoids with dual activity against influenza virus and Streptococcus pneumoniae.

PubMed

Grienke, Ulrike; Richter, Martina; Walther, Elisabeth; Hoffmann, Anja; Kirchmair, Johannes; Makarov, Vadim; Nietzsche, Sandor; Schmidtke, Michaela; Rollinger, Judith M

2016-06-03

Influenza virus neuraminidase (NA) is the primary target for influenza therapeutics. Severe complications are often related to secondary pneumonia caused by Streptococcus pneumoniae (pneumococci), which also express NAs. Recently, a NA-mediated lethal synergism between influenza A viruses and pneumococci was described. Therefore, dual inhibitors of both viral and bacterial NAs are expected to be advantageous for the treatment of influenza. We investigated the traditional Chinese herbal drug sāng bái pí (mulberry root bark) as source for anti-infectives. Two prenylated flavonoid derivatives, sanggenon G (4) and sanggenol A (5) inhibited influenza A viral and pneumococcal NAs and, in contrast to the approved NA inhibitor oseltamivir, also planktonic growth and biofilm formation of pneumococci. Evaluation of 27 congeners of 5 revealed a correlation between the degree of prenylation and bioactivity. Abyssinone-V 4'-methyl ether (27) inhibited pneumococcal NA with IC50 = 2.18 μM, pneumococcal growth with MIC = 5.63 μM, and biofilm formation with MBIC = 4.21 μM, without harming lung epithelial cells. Compounds 5 and 27 also disrupt the synergism between influenza A virus and pneumococcal NA in vitro, hence functioning as dual-acting anti-infectives. The results warrant further studies on whether the observed disruption of this synergism is transferable to in vivo systems.

Discovery of prenylated flavonoids with dual activity against influenza virus and Streptococcus pneumoniae

PubMed Central

Grienke, Ulrike; Richter, Martina; Walther, Elisabeth; Hoffmann, Anja; Kirchmair, Johannes; Makarov, Vadim; Nietzsche, Sandor; Schmidtke, Michaela; Rollinger, Judith M.

2016-01-01

Influenza virus neuraminidase (NA) is the primary target for influenza therapeutics. Severe complications are often related to secondary pneumonia caused by Streptococcus pneumoniae (pneumococci), which also express NAs. Recently, a NA-mediated lethal synergism between influenza A viruses and pneumococci was described. Therefore, dual inhibitors of both viral and bacterial NAs are expected to be advantageous for the treatment of influenza. We investigated the traditional Chinese herbal drug sāng bái pí (mulberry root bark) as source for anti-infectives. Two prenylated flavonoid derivatives, sanggenon G (4) and sanggenol A (5) inhibited influenza A viral and pneumococcal NAs and, in contrast to the approved NA inhibitor oseltamivir, also planktonic growth and biofilm formation of pneumococci. Evaluation of 27 congeners of 5 revealed a correlation between the degree of prenylation and bioactivity. Abyssinone-V 4′-methyl ether (27) inhibited pneumococcal NA with IC50 = 2.18 μM, pneumococcal growth with MIC = 5.63 μM, and biofilm formation with MBIC = 4.21 μM, without harming lung epithelial cells. Compounds 5 and 27 also disrupt the synergism between influenza A virus and pneumococcal NA in vitro, hence functioning as dual-acting anti-infectives. The results warrant further studies on whether the observed disruption of this synergism is transferable to in vivo systems. PMID:27257160

Helminth infections predispose mice to pneumococcal pneumonia but not to other pneumonic pathogens.

PubMed

Apiwattanakul, Nopporn; Thomas, Paul G; Kuhn, Raymond E; Herbert, De'Broski R; McCullers, Jonathan A

2014-10-01

Pneumonia is the leading killer of children worldwide. Here, we report that helminth-infected mice develop fatal pneumonia when challenged with Streptococcus pneumoniae. Mice were chronically infected with either the flatworm Taenia crassiceps or the roundworm Heligmosomoides polygyrus. Upon challenge with a pneumonic type 3 strain of S. pneumoniae (A66.1), the worm-infected mice developed pneumonia at a rate and to a degree higher than age-matched control mice as measured by bioluminescent imaging and lung titers. This predisposition to pneumonia appears to be specific to S. pneumoniae, as worm-infected mice did not show evidence of increased morbidity when challenged with a lethal dose of influenza virus or sublethal doses of Staphylococcus aureus or Listeria monocytogenes. The defect was also present when worm-infected mice were challenged with a type 2 sepsis-causing strain (D39); an increased rate of pneumonia, decreased survival, and increased lung and blood titers were found. Pneumococcal colonization and immunity against acute otitis media were unaffected. Anti-helminthic treatment in the H. polygyrus model reversed this susceptibility. We conclude that helminth coinfection predisposes mice to fatal pneumococcal pneumonia by promoting increased outgrowth of bacteria in the lungs and blood. These data have broad implications for the prevention and treatment for pneumonia in the developing world, where helminth infections are endemic and pneumococcal pneumonia is common.

Neisseria meningitidis and Streptococcus pneumoniae as leading causes of pediatric bacterial meningitis in nine Mexican hospitals following 3 years of active surveillance

PubMed Central

Chacon-Cruz, Enrique; Martinez-Longoria, Cesar Adrian; Llausas-Magana, Eduardo; Luevanos-Velazquez, Antonio; Vazquez-Narvaez, Jorge Alejandro; Beltran, Sandra; Limon-Rojas, Ana Elena; Urtiz-Jeronimo, Fernando; Castaneda-Narvaez, Jose Luis; Otero-Mendoza, Francisco; Aguilar-Del Real, Fernando; Rodriguez-Chagoyan, Jesus; Rivas-Landeros, Rosa Maria; Volker-Soberanes, Maria Luisa; Hinojosa-Robles, Rosa Maria; Arzate-Barbosa, Patricia; Aviles-Benitez, Laura Karina; Elenes-Zamora, Fernando Ivan; Becka, Chandra M.; Ruttimann, Ricardo

2016-01-01

Objectives: Meningococcal meningitis is reported as a rare condition in Mexico. There are no internationally published studies on bacterial causes of meningitis in the country based on active surveillance. This study focuses on finding the etiology of bacterial meningitis in children from nine Mexican Hospitals. Methods: From January 2010 to February 2013, we conducted a three years of active surveillance for meningitis in nine hospitals throughout Mexico. Active surveillance started at the emergency department for every suspected case, and microbiological studies confirmed/ruled out all potentially bacterial pathogens. We diagnosed based on routine cultures from blood and cerebrospinal fluid (not polymerase chain reaction or other molecular diagnostic tests), and both pneumococcal serotyping and meningococcal serogrouping by using standard methods. Results: Neisseria meningitidis was the leading cause, although 75% of cases occurred in the northwest of the country in Tijuana on the US border. Serogroup C was predominant. Streptococcus pneumoniae followed Neisseria meningitides, but was uniformly distributed throughout the country. Serotype 19A was the most incident but before universal implementation of the 13-valent pneumococcal conjugate vaccine. Other bacteria were much less common, including Enterobacteriaceae and Streptococcus agalactiae (these two affecting mostly young infants). Conclusions: Meningococcal meningitis is endemic in Tijuana, Mexico, and vaccination should be seriously considered in that region. Continuous universal vaccination with the 13-valent pneumococcal conjugate vaccine should be nationally performed, and polymerase chain reaction should be included for bacterial detection in all cultures – negative but presumably bacterial meningitis cases. PMID:27551428

Preserved antibody levels and loss of memory B cells against pneumococcus and tetanus after splenectomy: tailoring better vaccination strategies.

PubMed

Rosado, M Manuela; Gesualdo, Francesco; Marcellini, Valentina; Di Sabatino, Antonio; Corazza, Gino Roberto; Smacchia, Maria Paola; Nobili, Bruno; Baronci, Carlo; Russo, Lidia; Rossi, Francesca; Vito, Rita De; Nicolosi, Luciana; Inserra, Alessandro; Locatelli, Franco; Tozzi, Alberto E; Carsetti, Rita

2013-10-01

Splenectomized patients are exposed to an increased risk of septicemia caused by encapsulated bacteria. Defense against infection is ensured by preformed serum antibodies produced by long-lived plasma cells and by memory B cells that secrete immunoglobulin in response to specific antigenic stimuli. Studying a group of asplenic individuals (57 adults and 21 children) without additional immunologic defects, we found that spleen removal does not alter serum anti-pneumococcal polysaccharide (PnPS) IgG concentration, but reduces the number of PnPS-specific memory B cells, of both IgM and IgG isotypes. The number of specific memory B cells was low in splenectomized adults and children that had received the PnPS vaccine either before or after splenectomy. Seven children were given the 13-valent pneumococcal conjugated vaccine after splenectomy. In this group, the number of PnPS-specific IgG memory B cells was similar to that of eusplenic children, suggesting that pneumococcal conjugated vaccine administered after splenectomy is able to restore the pool of anti-PnPS IgG memory B cells. Our data further elucidate the crucial role of the spleen in the immunological response to infections caused by encapsulated bacteria and suggest that glycoconjugated vaccines may be the most suitable choice to generate IgG-mediated protection in these patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Infection and sickle cell anemia].

PubMed

Bégué, P

1999-01-01

Sickle cell disease is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumococcal bacteremia and meningitis are so severe as to warrant prophylactic penicillin therapy, which has provided a dramatic decrease in early mortality. Bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia. Osteomyelitis is generally due to a salmonella, most often S. enteritidis; multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Parvovirus B 19 infection causes acute bone marrow failure. Malaria does not result in cerebral malaria but can lead to severe anemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (septicemia, meningitis, osteomyelitis), and mycoplasmas (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at four months of age and on closely-spaced immunizations, most notably against pneumococci, the hepatitis B virus, S. typhi, and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. Conjugated pneumococcal vaccines are effective in protecting infants and should therefore be used in sickle cell patients.

The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012

PubMed Central

Britz, Erika; Perovic, Olga; von Mollendorf, Claire; von Gottberg, Anne; Iyaloo, Samantha; Quan, Vanessa; Chetty, Verushka; Sriruttan, Charlotte; Ismail, Nazir A.; Nanoo, Ananta; Musekiwa, Alfred; Reddy, Carl; Viljoen, Karien; Cohen, Cheryl; Govender, Nelesh P.

2016-01-01

Introduction Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. Methods We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV-infected populations and used Poisson regression to determine if trends were significant. Results We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV-infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV-infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. Conclusions In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national antiretroviral treatment programme, enhanced tuberculosis control programme and routine childhood immunisation with pneumococcal conjugate vaccines. PMID:27669564

The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012.

PubMed

Britz, Erika; Perovic, Olga; von Mollendorf, Claire; von Gottberg, Anne; Iyaloo, Samantha; Quan, Vanessa; Chetty, Verushka; Sriruttan, Charlotte; Ismail, Nazir A; Nanoo, Ananta; Musekiwa, Alfred; Reddy, Carl; Viljoen, Karien; Cohen, Cheryl; Govender, Nelesh P

Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV-infected populations and used Poisson regression to determine if trends were significant. We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV-infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV-infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national antiretroviral treatment programme, enhanced tuberculosis control programme and routine childhood immunisation with pneumococcal conjugate vaccines.

Pneumococcal infections at Hajj: current knowledge gaps.

PubMed

Ridda, Iman; King, Catherine; Rashid, Harunor

2014-01-01

Hajj attendance increases the risk of respiratory infections including pneumonia. Streptococcus pneumoniae is a frequently identified pathogen, found in about 10% of respiratory tract samples of symptomatic Hajj pilgrims; and at least 20% of these isolates are penicillin resistant. However, the burden of pneumococcal disease at Hajj is not precisely defined at serotypic level, and it is postulated that due to intense mixing of pilgrims the distribution of pneumococcal serotypes at Hajj could be different from pilgrims' country of origin or of Saudi Arabia. In Saudi Arabia, the most prevalent pneumococcal serotypes are 23F, 6B, 19F, 18C, 4, 14, and 19A, and 90% of the serotypes are covered by 13-valent pneumococcal conjugate vaccine (PCV-13) as well as 23-valent pneumococcal polysaccharide vaccine (PPV-23). However, due to lack of Hajj-specific data, the Saudi Arabian Ministry of Health has not yet recommended pneumococcal vaccine for pilgrims, and the immunisation recommendation and uptake vary greatly across countries. As at least one third of Hajj pilgrims are 'at risk' of pneumococcal disease either by virtue of age or pre-existing medical conditions, consideration should be given to vaccinating high risk pilgrims against pneumococcal disease. Other preventive measures such as smoking cessation, pollution reduction and vaccinations against influenza and pertussis should also be considered. Precisely defining the epidemiology of pneumococcal disease to identify an optimum vaccination schedule for Hajj pilgrims is a current research priority.

Mortality reductions for older adults differ by race/ethnicity and gender since the introduction of adult and pediatric pneumococcal vaccines.

PubMed

Soneji, Samir; Metlay, Joshua

2011-01-01

We determined the effectiveness of a 23-valent-polysaccharide pneumococcal vaccine (PPV-23) and pneumococcal conjugate vaccine (PCV-7) in reducing adult pneumococcal mortality by comparing historically predicted declines in pneumococcal disease mortality with observed patterns since the introduction of PPV-23 and PCV-7, including analyses of age, gender, and racial/ethnic subgroups. We analyzed all deaths registered on U.S. death certificates reporting any site of pneumococcal infection (e.g., meningitis, sepsis, pneumonia, bacteremia, and peritonitis) from 1968 to 2006. We used time-series dynamic linear regression on annual pneumococcal mortality rates to determine the percentage reduction in post-1983 mortality rates for a given increase in PPV-23 vaccination rates and post-2000 mortality rates for a given increase in PCV-7 vaccination rates. Pneumococcal mortality decreased well before the introduction of PPV-23 in 1983 and again before the introduction of PCV-7 in 2000. The level of PPV-23 vaccination was associated with a direct and significant reduction in adult mortality, especially white female adults > or = 65 years of age. In contrast, the level of PCV-7 vaccination in the population was not associated with an indirect and significant reduction in pneumococcal mortality beyond the historical pace of decline. PPV-23 introduction was associated with a reduction in pneumococcal mortality among older adults > or = 65 years of age beyond levels predicted by secular trends, whereas PCV-7 introduction was not. Mortality reduction was not uniformly experienced across the population, revealing the need for additional strategies to reduce pneumococcal mortality in older adults.

Pneumonia hospitalisations in Scotland following the introduction of pneumococcal conjugate vaccination in young children.

PubMed

Nair, Harish; Watts, Arun Thor; Williams, Linda J; Omer, Saad B; Simpson, Colin R; Willocks, Lorna J; Cameron, J Claire; Campbell, Harry

2016-08-09

Scotland introduced PCV7 and PCV13 immunisation in young children in 2006 and 2010 respectively. One recent study from the United States reported a decrease in hospitalisation rates for all-cause pneumonia most notably in adults older than 75 years of age following PCV7 introduction in the US child population. We aimed to examine the effect of PCV7 and PCV13 on hospitalisation rates for all-cause pneumonia across all age groups in Scotland. We linked hospital records and death certification datasets for the entire Scottish population for the period 2000 to 2012. We included all cases where the primary / secondary diagnosis was pneumonia. Differences in hospital admission rates for pneumonia by age group were calculated using the difference in average annual rates for each period. We estimated that all-cause pneumonia hospitalisation rates in children <2 years decreased by about 30 % in the post-PCV-13 period compared with the pre-PCV period. However, in adults aged 75-84 years and ≥85 years, all-cause pneumonia hospitalisation rates increased by 63 and 46 % respectively in the post-PCV 13 period compared to the pre-PCV period. This resulted in an additional 7000 hospitalisations across all age groups in Scotland in 2012 about half of which were in adults >75 years. At the same time, the median length of hospital stay decreased by a third in children <2 years and by about 20 % in adults >75 years in the post-PCV13 period compared to the pre-PCV period. Additionally, there was an 11 % reduction in deaths due to all-cause pneumonia, and 30 % reduction in pneumococcal hospitalisations across all age groups in the post-PCV13 period compared with pre-PCV period. The modest and sustained decline in the rates of hospitalisation for all-cause pneumonia in children and the reduction in proportion of pneumonia hospitalisations in children coded as pneumococcal disease in the post-PCV period should alleviate concerns that pneumococcal serotype replacement may have resulted in an increased pneumonia burden in this age group. The indirect impact of child PCV immunisation in those not vaccinated (in terms of reduction in all-cause pneumonia hospitalisations in the elderly) has not been seen in Scotland. Our results are likely to be confounded by changes in clinical coding and healthcare practices over the same period. Our results illustrate that health care planners cannot, with confidence, predict indirect PCV vaccine impacts on hospitalisations. IPD surveillance across all age groups is needed to assess the indirect effects of PCV in the community.

Overview of vaccination policies for the elderly in Western European countries.

PubMed

Samson, Sandrine I; Mégard, Yves

2009-06-01

Age-related changes in the immune system are associated with increased susceptibility to infections, greater disease severity and poorer outcomes in the elderly compared with young adults. Both influenza and pneumonia are important causes of morbidity and mortality in the elderly, and herpes zoster also represents an important disease burden in this population. Vaccinations against influenza and Streptococcus pneumoniae (pneumococcus) have been shown to reduce the incidence of influenza and invasive pneumococcal disease, respectively, in the elderly. In addition, as is the case with diphtheria/tetanus and herpes zoster vaccines, they can help to reduce the associated burden of disease in vaccinated individuals. Despite the evidence of these benefits, there are considerable variations among the countries of Western Europe in their policies for vaccination in the elderly. Western European countries face the prospect of a population in which the proportion of elderly people is increasing, with a consequent increase in demand on the healthcare system. Acknowledgement of the benefits of vaccination in the elderly, together with comprehensive vaccination policies for this age group, could help to reduce some of these demands.

Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis.

PubMed

Klein, Matthias; Brouwer, Matthijs C; Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter; van de Beek, Diederik; Koedel, Uwe

2014-01-01

We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment.

Leukocyte Attraction by CCL20 and Its Receptor CCR6 in Humans and Mice with Pneumococcal Meningitis

PubMed Central

Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter

2014-01-01

We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment. PMID:24699535

42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a doctor...

42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a doctor...

42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a doctor...

42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a doctor...

42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a doctor...

Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

PubMed

Jaeger, Veronika K; Hoffman, Hal M; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A

2017-09-01

Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS patients followed in the β-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The β-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Pneumococcal infection of respiratory cells exposed to welding fumes; Role of oxidative stress and HIF-1 alpha.

PubMed

Grigg, Jonathan; Miyashita, Lisa; Suri, Reetika

2017-01-01

Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR-dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor. We also sought to evaluate the suitability of nasal epithelial PAFR expression in welders as a biomarker of susceptibility to infection. Finally, we investigated the generalisability of the effect of welding fumes on pneumococcal infection and growth using a variety of different welding fume samples. Nasal epithelial PAFR expression in welders and controls was analysed by flow cytometry. WF were collected using standard methodology. The effect of WF on respiratory cell reactive oxygen species production, HIF-1α expression, and pneumococcal infection was determined using flow cytometry, HIF-1α knockdown and overexpression, and pneumococcal infection assays. We found that nasal PAFR expression is significantly increased in welders compared with controls and that WF significantly increased reactive oxygen species production, HIF-1α and PAFR expression, and pneumococcal infection of respiratory cells. In unstimulated cells, HIF-1α knockdown decreased PAFR expression and HIF-1α overexpression increased PAFR expression. However, in knockdown cells pneumococcal infection was paradoxically increased and in overexpressing cells infection was unaffected. Nasal epithelial PAFR expression may be used as a biomarker of susceptibility to pneumococcal infection in order to target individuals, particularly those at high risk such as welders, for the pneumococcal vaccine. Expression of HIF-1α in unexposed respiratory cells inhibits basal pneumococcal infection via PAFR-independent mechanisms.

Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates from adult patients in Jakarta, Indonesia.

PubMed

Said, Wahyu F; Sukoto, Edy; Khoeri, Miftahuddin M; Kumalawati, July; Safari, Dodi

Currently, the data on pneumococcal invasive disease in the Indonesian population are limited. In this study, we investigated the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae. These samples were isolated from the sputum of adult patients with non-specific clinical symptoms aged 18-87 years in Jakarta, Indonesia, from August to October 2014. Of the 349 sputum specimens, thirteen isolates were identified as S. pneumoniae strains (4%), with two strains each for serotype 19F, 3, and 15A, and one strain each for serotype/serogroup 13, 23A, 6, 34, 17F, 16F, and untypeable. Resistance to tetracycline was most common with only 5 of 13 strains being susceptible. In conclusion, these data provide an initial in the surveillance of invasive pneumococcus in the Indonesia population. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cost-effectiveness analysis of the 10- and 13-valent pneumococcal conjugate vaccines in Argentina.

PubMed

Urueña, Analía; Pippo, Tomás; Betelu, María Sol; Virgilio, Federico; Giglio, Norberto; Gentile, Angela; Jimenez, Salvador García; Jáuregui, Bárbara; Clark, Andrew D; Diosque, Máximo; Vizzotti, Carla

2011-07-12

Since the 10-valent pneumococcal conjugate vaccine (PCV-10) and 13-valent pneumococcal conjugate vaccine (PCV-13) were recently licensed for use in Argentina, both vaccines were evaluated to estimate the costs, health benefits and cost-effectiveness of adding a PCV to the routine child immunization schedule. The integrated TRIVAC vaccine cost-effectiveness model from Pan American Health Organization's ProVac Initiative (Version 1.0.65) was used to assess the health outcomes of 20 successive cohorts from birth to 5 years of age. PCV-10 and PCV-13 were each compared to a scenario assuming no PCV vaccination. A 3+1 (three doses+booster) schedule and a vaccination price of US$ 20.75 per dose was assumed in the base case for both vaccines. Introduction of PCV-13 rather than PCV-10 would increase the number of life years gained (LYG) by at least 10%. The number of LYG (and LYG after adjustment for DALY morbidity weights) was 56,882 (64,252) for PCV-10 compared to 65,038 (71,628) for PCV-13. From the health system perspective, the cost per DALY averted was US$ 8973 and US$ 10,948 for PCV-10 and PCV-13 respectively, and US$ 8546 and US$ 10,510 respectively, after incorporating costs saved by households. When PCV13 was compared to PCV10 directly, the additional benefits of PCV-13 was conferred at a cost of US$ 28,147 per DALY averted. Cost-effectiveness was influenced mainly by vaccine price, serotype replacement, pneumonia mortality and discount rate. Routine vaccination against S. pneumoniae in Argentina would be cost-effective with either PCV-10 or PCV-13. PCV-13, with higher coverage of local serotypes, would prevent more cases of pneumonia, invasive pneumococcal disease, sequelae and deaths with a higher number of LYG and DALYs averted, but PCV-10, due its higher impact in the prevention of AOM, would save more costs to the healthcare system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Celiac Disease and Increased Risk of Pneumococcal Infection: A Systematic Review and Meta-Analysis.

PubMed

Simons, Malorie; Scott-Sheldon, Lori A J; Risech-Neyman, Yesenia; Moss, Steven F; Ludvigsson, Jonas F; Green, Peter H R

2018-01-01

Celiac disease has been associated with hyposplenism, and multiple case reports link celiac disease and pneumococcal infections; however, increased risk of pneumococcal infection in celiac disease has not been confirmed. The purpose of this study was to conduct a systematic review to determine the risk of pneumococcal infections in celiac disease. Relevant studies were identified using electronic bibliographic searches of PubMed, OVID, Medline, and EMBASE (1980 to February 2017) and reviewing abstracts from major conferences in gastroenterology. Using number of events in celiac patients and referent patients, we calculated a summary relative risk of pneumococcal infections. All analyses were conducted in Comprehensive Meta-Analysis software using random-effects assumptions. Of a total of 156 articles, 3, representing 3 large databases (the Swedish National Inpatient Register; the Oxford Record Linkage Study; and the English National Hospital Episode Statistics) were included. Each compared patients with celiac disease and confirmed pneumococcal infection to a specific reference group: inpatients and/or the general population. Overall, the odds of pneumococcal infection were higher among hospitalized celiac patients compared with controls (odds ratio 1.66; 95% confidence interval 1.43-1.92). There was no evidence of heterogeneity (Q[1] = 1.17, P = .56, I 2  = 0%). Celiac disease is associated with an increased risk of pneumococcal infection. Preventive pneumococcal vaccination should be considered for those with celiac disease, with special attention to those aged 15-64 years who have not received the scheduled pneumococcal vaccination series as a child. Copyright © 2018 Elsevier Inc. All rights reserved.

Penicillin dosing for pneumococcal pneumonia.

PubMed

Bryan, C S; Talwani, R; Stinson, M S

1997-12-01

Most textbook authors still endorse penicillin G as the specific antibiotic of choice for pneumococcal pneumonia. However, problems with early precise etiologic diagnosis of pneumonia and the emergence of drug-resistant pneumococci cause penicillin to be seldom used for this purpose today. A third explanation for the infrequent use of penicillin is lack of clear consensus dosing guidelines. Emergence of pneumococci resistant to the newer cephalosporins and concerns about overuse of vancomycin, however, have prompted renewed interest in the development of precise, rapid methods for diagnosis of pneumococcal pneumonia with the implication that penicillin might be used more frequently. We review several issues concerning penicillin dosing: intermittent vs continuous therapy, high dose vs low dose, relationship of dose to resistance, and cost-effective pharmacology. An optimum "high-dose" regimen for life-threatening pneumococcal pneumonia in a 70-kg adult consists of a 3 million unit (mu) loading dose followed by continuous infusion of 10 to 12 mu of freshly prepared drug every 12 h. The maintenance dose should be reduced in elderly patients and in patients with renal failure according to the following formula: dose (mu/24 h = 4+[creatinine clearance divided by 7]). This regimen provides a penicillin serum level of 16 to 20 microg/mL, which should suffice for all but the most highly resistant strains (minimum inhibitory concentration > or = 4 microg/mL). Newer cephalosporins and vancomycin can be reserved for patients with suspected meningitis or endocarditis or for localities in which highly resistant pneumococci are known to be prevalent.

RAPID DIAGNOSIS OF PNEUMOCOCCAL PNEUMONIA AMONG HIV-INFECTED ADULTS WITH URINE ANTIGEN DETECTION

PubMed Central

Boulware, David R; Daley, Charles L.; Merrifield, Cynthia; Hopewell, Philip C.; Janoff, Edward N.

2007-01-01

Objectives Streptococcus pneumoniae is the leading cause of bacterial pneumonia and associated bacteremia during HIV infection. Rapid diagnostic assays may limit inappropriate therapy. Methods Clinical signs and symptoms and sera and urine were collected prospectively from 70 adults with pneumococcal pneumonia, including 47 with HIV co-infection. Pneumococcal C-polysaccharide antigen was detected in urine using the Binax® immunochromatographic test (ICT). A systematic review of 24 published studies was conducted. Results Clinical symptoms, signs, and laboratory parameters except leukocytosis, were similar in HIV-infected and HIV-seronegative pneumonia. The performance of the urine antigen ICT was independent of HIV-status (sensitivity 81%, specificity 98%, positive (PPV) and negative predictive values (NPV) 98%, and 82%, respectively). The sensitivity of sputum Gram’s stain was 58% [34/59] with sputum unable to be provided by 16%. The CRP response was identical in HIV-infected (mean ± SD) 133 ± 88 vs. seronegative 135 ± 104 mg/L (p=0.9). In the systematic review, the ICT performance revealed 74% sensitivity (95% CI: 72% to 77%) and 94% specificity (95% CI: 93% to 95%). Urine antigen testing increases etiologic diagnosis by 23% (Range: 10% –59%) when testing adults with community acquired pneumonia of unknown etiology. Conclusions Urinary antigen detection provides a credible rapid diagnostic test for pneumococcal pneumonia regardless of HIV-status. CRP response to acute infection is similar in HIV co-infection and increases diagnostic certainty. PMID:17692384

A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease

PubMed Central

Jump, Robin L.; Banks, Richard; Wilson, Brigid; Montpetite, Michelle M.; Carter, Rebecca; Phillips, Susan; Perez, Federico

2015-01-01

We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients. PMID:26668815

Epidemiology of bacterial meningitis in the North American Arctic, 2000-2010.

PubMed

Gounder, Prabhu P; Zulz, Tammy; Desai, Shalini; Stenz, Flemming; Rudolph, Karen; Tsang, Raymond; Tyrrell, Gregory J; Bruce, Michael G

2015-08-01

To determine the incidence of meningitis caused by Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae in the North American Arctic during 2000-2010. Surveillance data were obtained from the International Circumpolar Surveillance network. We defined a case of bacterial meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae as a culture-positive isolate obtained from a normally sterile site in a resident with a meningitis diagnosis. The annual incidence/100,000 persons for meningitis caused by H. influenzae, N. meningitidis, and S. pneumoniae among all North American Arctic residents was: 0.6, 0.5, and 1.5, respectively; the meningitis incidence among indigenous persons in Alaska and Canada (indigenous status not recorded in Greenland) for those three bacteria was: 2.1, 0.8, and 2.4, respectively. The percentage of pneumococcal isolates belonging to a 7-valent pneumococcal conjugate vaccine serotype declined from 2000-2004 to 2005-2010 (31%-2%, p-value <0.01). During 2005-2010, serotype a caused 55% of H. influenzae meningitis and serogroup B caused 86% of meningococcal meningitis. Compared with all North American Arctic residents, indigenous people suffer disproportionately from bacterial meningitis. Arctic residents could benefit from the development of an H. influenzae serotype a vaccine and implementation of a meningococcal serogroup B vaccine. Published by Elsevier Ltd.

Pneumococcal Polysaccharide Abrogates Conjugate-Induced Germinal Center Reaction and Depletes Antibody Secreting Cell Pool, Causing Hyporesponsiveness

PubMed Central

Bjarnarson, Stefania P.; Benonisson, Hreinn; Del Giudice, Giuseppe; Jonsdottir, Ingileif

2013-01-01

Background Plain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM). Methods Neonatal mice were primed subcutanously (s.c.) or intranasally (i.n.) with pneumococcal conjugate (Pnc1-TT) and the adjuvant LT-K63, and boosted with PPS+LT-K63 or saline 1, 2 or 3 times with 16 day intervals. Seven days after each booster, spleens were removed, germinal centers (GC), IgM+, IgG+ follicles and PPS-specific antibody secreting cells (AbSC) in spleen and BM enumerated. Results PPS booster s.c., but not i.n., compromised the Pnc1-TT-induced PPS-specific Abs by abrogating the Pnc1-TT-induced GC reaction and depleting PPS-specific AbSCs in spleen and limiting their homing to the BM. There was no difference in the frequency of PPS-specific AbSCs in spleen and BM between mice that received 1, 2 or 3 PPS boosters s.c.. Repeated PPS+LT-K63 booster i.n. reduced the frequency of PPS-specific IgG+ AbSCs in BM. Conclusions PPS booster-induced hyporesponsiveness is caused by abrogation of conjugate-induced GC reaction and depletion of PPS-specific IgG+ AbSCs resulting in no homing of new PPS-specific long-lived plasma cells to the BM or survival. These results should be taken into account in design of vaccination schedules where polysaccharides are being considered. PMID:24069152

Dosing Schedules for Pneumococcal Conjugate Vaccine

PubMed Central

2014-01-01

Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses—the schedule—that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses. PMID:24336059

Decline in Early Childhood Respiratory Tract Infections in the Norwegian Mother and Child Cohort Study after Introduction of Pneumococcal Conjugate Vaccination

PubMed Central

Magnus, Maria C.; Vestrheim, Didrik F.; Nystad, Wenche; Håberg, Siri Eldevik; Stigum, Hein; London, Stephanie J.; Bergsaker, Marianne A. R.; Caugant, Dominique A.; Aaberge, Ingeborg S.; Nafstad, Per

2012-01-01

BACKGROUND The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunization Program in 2006. A substantial effectiveness of PCV7 immunization against invasive pneumococcal disease has been demonstrated, while evidence of the impact on respiratory tract infections are less consistent. METHODS This study included children participating in the Norwegian Mother and Child Cohort Study, which recruited pregnant women between 1999 and 2008. Maternal report of acute otitis media (AOM), lower respiratory tract infections (LRTIs) and asthma in the child was compared with PCV7 immunization status, as obtained from the Norwegian Immunization Registry. Generalized linear models with the log link function were used to report adjusted relative risks (RR) and 95% confidence intervals (CI). RESULTS For children who had received three or more PCV7 immunizations by 12 months of age, the adjusted relative risks of AOM and LRTIs between 12 and 18 months were 0.86 [95% CI: 0.81, 0.91] and 0.78 [95% CI: 0.70, 0.87] respectively, when compared with non-immunized children. A reduced risk of AOM, RR 0.92 [95% CI: 0.90, 0.94], and LRTIs, RR 0.75 [95%CI: 0.71, 0.80], between 18 and 36 months of age was also identified among children who had received 3 or more immunizations by 18 months. No association was seen between PCV7 immunization and asthma at 36 months of age. CONCLUSION Reduced incidence proportions of AOM and LRTIs before 36 months of age were observed among children immunized with PCV7 through the childhood immunization program. PMID:22627867

Economic evaluation of universal infant vaccination with 7vPCV in Hong Kong.

PubMed

Lee, Kenneth K C; Rinaldi, Fiona; Chan, Mia K U; Chan, Shirley T H; So, Thomas M T; Hon, Ellis K L; Lee, Vivian W Y

2009-01-01

The purpose of this study was to evaluate the clinical and economic benefits of routine infant vaccination with seven-valent pneumococcal conjugate vaccine (7vPCV) in Hong Kong. A decision-analytic model was populated with local age-specific incidence data to simulate the expected health outcomes resulting from 7vPCV vaccination of a birth cohort of 57,100 children compared with an unvaccinated cohort over a 10-year horizon. Primary analyses were conducted from a payer perspective, using local inpatient and outpatient costs associated with the treatment of pneumococcal disease. Vaccine efficacy rates were consistent with results from pivotal clinical trials. The reduction in adult invasive pneumococcal disease (IPD) and associated cost avoidance due to the indirect effect of vaccination were estimated in line with published overseas rates. Universal 7vPCV vaccination was estimated to prevent 524 cases of IPD and more than 2580 cases of otitis media in the birth cohort over a 10-year period, leading to a reduction of HK$28.7 million (US$3.7 million) in direct medical costs. Additional cost savings from the indirect prevention of 919 adult cases of IPD during this time period also resulted. Overall, 7vPCV vaccination was estimated to have an incremental cost per life-year gained of HK$50,456 (US$6460) from a payer perspective or HK$46,308 (US$5929) when both direct and indirect costs were included. With reference to the World Health Organization's threshold for cost-effectiveness, results from this study indicate that routine infant vaccination with 7vPCV is a cost-effective intervention because of the added cost savings resulting from the indirect effect of vaccination on adult disease.

Cost-effectiveness of programs to eliminate disparities in elderly vaccination rates in the United States

PubMed Central

2014-01-01

Background There are disparities in influenza and pneumococcal vaccination rates among elderly minority groups and little guidance as to which intervention or combination of interventions to eliminate these disparities is likely to be most cost-effective. Here, we evaluate the cost-effectiveness of four hypothetical vaccination programs designed to eliminate disparities in elderly vaccination rates and differing in the number of interventions. Methods We developed a Markov model in which we assumed a healthcare system perspective, 10-year vaccination program and lifetime time horizon. The cohort was the combined African-American and Hispanic 65 year-old birth cohort in the United States in 2009. We evaluated five different vaccination strategies: no vaccination program and four vaccination programs that varied from “low intensity” to “very high intensity” based on the number of interventions deployed in each program, their cumulative cost and their cumulative impact on elderly minority influenza and pneumococcal vaccination rates. Results The very high intensity vaccination program ($24,479/quality-adjusted life year; QALY) was preferred at willingness-to-pay-thresholds of $50,000 and $100,000/QALY and prevented 37,178 influenza cases, 342 influenza deaths, 1,158 invasive pneumococcal disease (IPD) cases and 174 IPD deaths over the birth cohort’s lifetime. In one-way sensitivity analyses, the very high intensity program only became cost-prohibitive (>$100,000/QALY) at less likely values for the influenza vaccination rates achieved in year 10 of the high intensity (>73.5%) or very high intensity (<76.8%) vaccination programs. Conclusions A practice-based vaccination program designed to eliminate disparities in elderly minority vaccination rates and including four interventions would be cost-effective. PMID:25023889

Cost-effectiveness of programs to eliminate disparities in elderly vaccination rates in the United States.

PubMed

Michaelidis, Constantinos I; Zimmerman, Richard K; Nowalk, Mary Patricia; Smith, Kenneth J

2014-07-15

There are disparities in influenza and pneumococcal vaccination rates among elderly minority groups and little guidance as to which intervention or combination of interventions to eliminate these disparities is likely to be most cost-effective. Here, we evaluate the cost-effectiveness of four hypothetical vaccination programs designed to eliminate disparities in elderly vaccination rates and differing in the number of interventions. We developed a Markov model in which we assumed a healthcare system perspective, 10-year vaccination program and lifetime time horizon. The cohort was the combined African-American and Hispanic 65 year-old birth cohort in the United States in 2009. We evaluated five different vaccination strategies: no vaccination program and four vaccination programs that varied from "low intensity" to "very high intensity" based on the number of interventions deployed in each program, their cumulative cost and their cumulative impact on elderly minority influenza and pneumococcal vaccination rates. The very high intensity vaccination program ($24,479/quality-adjusted life year; QALY) was preferred at willingness-to-pay-thresholds of $50,000 and $100,000/QALY and prevented 37,178 influenza cases, 342 influenza deaths, 1,158 invasive pneumococcal disease (IPD) cases and 174 IPD deaths over the birth cohort's lifetime. In one-way sensitivity analyses, the very high intensity program only became cost-prohibitive (>$100,000/QALY) at less likely values for the influenza vaccination rates achieved in year 10 of the high intensity (>73.5%) or very high intensity (<76.8%) vaccination programs. A practice-based vaccination program designed to eliminate disparities in elderly minority vaccination rates and including four interventions would be cost-effective.

Microbial exposure early in life regulates airway inflammation in mice after infection with Streptococcus pneumoniae with enhancement of local resistance.

PubMed

Yasuda, Yasuki; Matsumura, Yoko; Kasahara, Kazuki; Ouji, Noriko; Sugiura, Shigeki; Mikasa, Keiichi; Kita, Eiji

2010-01-01

The immunological explanation for the "hygiene hypothesis" has been proposed to be induction of T helper 1 (Th1) responses by microbial products. However, the protective results of hygiene hypothesis-linked microbial exposures are currently shown to be unlikely to result from a Th1-skewed response. Until now, effect of microbial exposure early in life on airway innate resistance remained unclear. We examined the role of early life exposure to microbes in airway innate resistance to a respiratory pathogen. Specific pathogen-free weanling mice were nasally exposed to the mixture of microbial extracts or PBS (control) every other day for 28 days and intratracheally infected with Streptococcus pneumoniae 10 days after the last exposure. Exposure to microbial extracts facilitated colonization of aerobic gram-positive bacteria, anaerobic microorganisms, and Lactobacillus in the airway, compared with control exposure. In pneumococcal pneumonia, the exposure prolonged mouse survival days by suppressing bacterial growth and by retarding pneumococcal blood invasion, despite significantly low levels of leukocyte recruitment in the lung. Enhancement of airway resistance was associated with a significant decrease in production of leukocyte chemokine (KC) and TNFalpha, and suppression of matrix metalloproteinase (MMP-9) expression/activation with enhancement of tissue inhibitor of MMP (TIMP-3) activation. The exposure increased production of IFN-gamma, IL-4, and monocyte chemoattractant-1 following infection. Furthermore, expression of Toll-like receptor 2, 4, and 9 was promoted by the exposure but no longer upregulated upon pneumococcal infection. Thus, we suggest that hygiene hypothesis is more important in regulating the PMN-dominant inflammatory response than in inducing a Th1-dominant response.

Cost-effectiveness of pneumococcal conjugate vaccine: evidence from the first 5 years of use in the United States incorporating herd effects.

PubMed

Ray, G Thomas; Whitney, Cynthia G; Fireman, Bruce H; Ciuryla, Vincent; Black, Steven B

2006-06-01

Pneumococcal conjugate vaccine (PCV) has been in routine use in the United States for 5 years. Prior U.S. cost-effectiveness analyses have not taken into account the effect of the vaccine on nonvaccinated persons. We revised a previously published model to simulate the effects of PCV on children vaccinated between 2000 and 2004, and to incorporate the effect of the vaccine in reducing invasive pneumococcal disease (IPD) in nonvaccinated persons during those years. Data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention (2000-2004) were used to estimate changes in the burden of IPD in nonvaccinated adults since the introduction of PCV (compared with the baseline years 1997-1999). Results combined the simulated effects of the vaccine on the vaccinated and nonvaccinated populations. Before incorporating herd effects in the model, the PCV was estimated to have averted 38,000 cases of IPD during its first 5 years of use at a cost of dollar 112,000 per life-year saved. After incorporating the reductions in IPD for nonvaccinated individuals, the vaccine averted 109,000 cases of IPD at a cost of dollar 7500 per life-year saved. When the herd effect was assumed to be half that of the base case, the cost per life-year saved was dollar 18,000. IPD herd effects in the nonvaccinated population substantially reduce the cost, and substantially improve the cost-effectiveness, of PCV. The cost-effectiveness of PCV in actual use has been more favorable than predicted by estimates created before the vaccine was licensed.

Pneumococcal conjugate vaccine: economic issues of the introduction of a new childhood vaccine.

PubMed

Ray, G Thomas

2002-06-01

In February 2000, a pneumococcal conjugate vaccine was licensed for use in the USA. This vaccine has been shown to be effective in reducing pneumococcal disease, and has been recommended for universal use in infants. However, pneumococcal conjugate vaccine is by far the most expensive child vaccine series routinely administered in the USA, alone accounting for over 40% of the total purchase price of vaccines for the recommended childhood schedule. This article reviews the existing efficacy and economic studies of pneumococcal conjugate vaccine and discusses the process by which routine use of pneumococcal conjugate vaccine was introduced and the role economic analysis played in that process. Some of the scientific and funding issues relating to its use in both the industrialized and developing world are also discussed.

The Relevance of a Novel Quantitative Assay to Detect up to 40 Major Streptococcus pneumoniae Serotypes Directly in Clinical Nasopharyngeal and Blood Specimens

PubMed Central

Albrich, Werner C.; van der Linden, Mark P. G.; Bénet, Thomas; Chou, Monidarin; Sylla, Mariam; Barreto Costa, Patricia; Richard, Nathalie; Klugman, Keith P.; Endtz, Hubert P.; Paranhos-Baccalà, Gláucia; Telles, Jean-Noël

2016-01-01

For epidemiological and surveillance purposes, it is relevant to monitor the distribution and dynamics of Streptococcus pneumoniae serotypes. Conventional serotyping methods do not provide rapid or quantitative information on serotype loads. Quantitative serotyping may enable prediction of the invasiveness of a specific serotype compared to other serotypes carried. Here, we describe a novel, rapid multiplex real-time PCR assay for identification and quantification of the 40 most prevalent pneumococcal serotypes and the assay impacts in pneumonia specimens from emerging and developing countries. Eleven multiplex PCR to detect 40 serotypes or serogroups were optimized. Quantification was enabled by reference to standard dilutions of known bacterial load. Performance of the assay was evaluated to specifically type and quantify S. pneumoniae in nasopharyngeal and blood samples from adult and pediatric patients hospitalized with pneumonia (n = 664) from five different countries. Serogroup 6 was widely represented in nasopharyngeal specimens from all five cohorts. The most frequent serotypes in the French, South African, and Brazilian cohorts were 1 and 7A/F, 3 and 19F, and 14, respectively. When both samples were available, the serotype in blood was always present as carriage with other serotypes in the nasopharynx. Moreover, the ability of a serotype to invade the bloodstream may be linked to its nasopharyngeal load. The mean nasopharyngeal concentration of the serotypes that moved to the blood was 3 log-fold higher than the ones only found in the nasopharynx. This novel, rapid, quantitative assay may potentially predict some of the S. pneumoniae serotypes invasiveness and assessment of pneumococcal serotype distribution. PMID:26986831

Paediatric invasive pneumococcal disease on the island of Gran Canaria: 16-year prospective study (2001-2016).

PubMed

Santana Hernández, Milagrosa; Aguiar-Santana, Ione Ahedey; Artiles Campelo, Fernando; Colino Gil, Elena

2017-11-24

To calculate the incidence of invasive pneumococcal disease (IPD) in the paediatric population of Gran Canaria (Spain), its clinical and epidemiological characteristics, serotype distribution, antibiotic resistance, and variations in these variables before and after the introduction of the PCV13 vaccine. Prospective hospital-based study including all patients (190) aged 0-14 years admitted with confirmed IPD between January 2001-May 2010 (152 cases) and June 2010-December 2016 (38 cases). Patients were divided into 3 age groups (<2 years; 2-5 years; and >5 years). Clinical symptoms were mutually-exclusively classified as meningitis, bacteraemic pneumonia, pleural effusion (PE), empyema or bacteraemia without a focus. Most cases occurred in boys (59.47%), during autumn-winter (65.79%), in children aged <2 years (55.79%) and with mean age increasing from the pre-PCV13 to the post-PCV13 period (2.5 vs 3.1 years). Incidence between periods reduced by 66.4% (p<0.001): from 13.1/100,000 to 4.4/100,000. PEs (3.9% vs 18.4%, p<0.005) and empyemas (1.5% vs 16.7%, p=NS) increased in the post-PCV13 period whereas all other symptoms decreased, although this was not statistically significant. Vaccine serotypes (77% vs 40.6%, p=0.000), particularly serotypes 19A (23.9% vs 12.5%) and 14 (14.2% vs 9.4%), as well as erythromycin resistance (57.2% vs 7.9%, p=0.000) decreased in the post-PCV13 period. IPD incidence, vaccine serotypes and erythromycin resistance decreased in the post-PCV13 period whereas PEs increased. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Ethanol-induced alcohol dehydrogenase E (AdhE) potentiates pneumolysin in Streptococcus pneumoniae.

PubMed

Luong, Truc Thanh; Kim, Eun-Hye; Bak, Jong Phil; Nguyen, Cuong Thach; Choi, Sangdun; Briles, David E; Pyo, Suhkneung; Rhee, Dong-Kwon

2015-01-01

Alcohol impairs the host immune system, rendering the host more vulnerable to infection. Therefore, alcoholics are at increased risk of acquiring serious bacterial infections caused by Streptococcus pneumoniae, including pneumonia. Nevertheless, how alcohol affects pneumococcal virulence remains unclear. Here, we showed that the S. pneumoniae type 2 D39 strain is ethanol tolerant and that alcohol upregulates alcohol dehydrogenase E (AdhE) and potentiates pneumolysin (Ply). Hemolytic activity, colonization, and virulence of S. pneumoniae, as well as host cell myeloperoxidase activity, proinflammatory cytokine secretion, and inflammation, were significantly attenuated in adhE mutant bacteria (ΔadhE strain) compared to D39 wild-type bacteria. Therefore, AdhE might act as a pneumococcal virulence factor. Moreover, in the presence of ethanol, S. pneumoniae AdhE produced acetaldehyde and NADH, which subsequently led Rex (redox-sensing transcriptional repressor) to dissociate from the adhE promoter. An increase in AdhE level under the ethanol condition conferred an increase in Ply and H2O2 levels. Consistently, S. pneumoniae D39 caused higher cytotoxicity to RAW 264.7 cells than the ΔadhE strain under the ethanol stress condition, and ethanol-fed mice (alcoholic mice) were more susceptible to infection with the D39 wild-type bacteria than with the ΔadhE strain. Taken together, these data indicate that AdhE increases Ply under the ethanol stress condition, thus potentiating pneumococcal virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Epidemiology of vaccine-preventable invasive diseases in Catalonia in the era of conjugate vaccines

PubMed Central

Ciruela, Pilar; Martínez, Ana; Izquierdo, Conchita; Hernández, Sergi; Broner, Sonia; Muñoz-Almagro, Carmen; Domínguez, Àngela; of Catalonia Study Group, the Microbiological Reporting System

2013-01-01

We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p < 0.05 was considered statistically significant. Of the 6,661 cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 105 inhabitants was 16.62 (95% CI 16.20–17.04) for IPD, 1.21 (95% CI 1.09–1.32) for IMD and 0.59 (95% CI 0.51–0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43–1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ≤ 2 y and 2–4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ≤ 2 y and ≥ 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ≥ 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting. PMID:23303166

Pneumococcal carriage among indigenous Warao children in Venezuela: serotypes, susceptibility patterns, and molecular epidemiology.

PubMed

Rivera-Olivero, Ismar A; Bogaert, Debby; Bello, Teresita; del Nogal, Berenice; Sluijter, Marcel; Hermans, Peter W M; de Waard, Jacobus H

2007-12-01

Little attention has been paid to pneumococcal carriage and disease in Amerindians from Latin America. The Warao people, an indigenous population from Venezuela, live in the delta of the Orinoco River in geographically isolated communities with difficult access to medical care. To obtain insight into pneumococcal carriage and the theoretical coverage of pneumococcal vaccines in this population, we investigated pneumococcal colonization, serotype, and genotype distribution among Warao children in 9 distinct, geographically isolated communities in the Delta Amacuro area in the northeast of Venezuela. From April 2004 through January 2005, a total of 161 Streptococcus pneumoniae isolates were recovered from single nasopharyngeal swab samples obtained from 356 children aged 0-72 months. The overall pneumococcal carriage rate was 49%, ranging from 13% to 76%, depending on the community investigated and the age of the children (50% among children aged <2 years and 25% among children aged >2 years). The most frequent serotypes were 23F (19.5% of isolates), 6A (19.5%), 15B (10.4%), 6B (9.1%), and 19F (7.2%). The theoretical coverage of the 7-valent pneumococcal conjugate vaccine, including the cross-reactive nonvaccine serotype 6A, was 65%. A total of 26% of the isolates were resistant to first-line antibiotics, with 70% of these strains being covered by the 7-valent pneumococcal conjugate vaccine. Restriction fragment end labelling analysis revealed 65 different genotypes, with 125 (80%) of the isolates belonging to 27 different genetic clusters, suggesting a high degree of horizontal spread of pneumococcal strains in and between the villages. The high colonization rates and high (registered) acute respiratory tract infection morbidity and mortality in this part of Venezuela suggest that Warao children are at increased risk for pneumococcal disease and, therefore, benefit from vaccination.

Pneumococcal Infections: MedlinePlus Health Topic

MedlinePlus

... Transmission (Centers for Disease Control and Prevention) Pneumococcal Polysaccharide Vaccine: What You Need to Know (Centers for ... Centers for Disease Control and Prevention) - PDF Pneumococcal Polysaccharide Vaccine: What You Need to Know (Centers for ...

Serotype-specific pneumococcal antibody concentrations in children treated for acute leukaemia.

PubMed

Patel, Soonie R; Bate, Jessica; Borrow, Ray; Heath, Paul T

2012-01-01

Children treated for acute leukaemia are at increased risk of infection with Streptococcus pneumoniae. The basis for this may include low levels of pneumococcal antibody but this has not been well studied. The authors measured serotype-specific pneumococcal IgG antibody concentrations in children treated for acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) ≥6 months after completion of standard-dose chemotherapy. Pneumococcal serotype-specific IgG antibody concentrations were low. None of the subjects had protective concentrations against all the heptavalent-pneumococcal conjugate vaccine serotypes. There was no significant difference in antibody concentrations between subjects with ALL and AML (p≥0.05). Children treated for ALL and AML generally have non-protective antibody concentrations against S pneumoniae. There is significant morbidity associated with pneumococcal disease in this patient group and strategies for vaccination are required.

Impact on CDC Guideline Compliance After Incorporating Pharmacy in a Pneumococcal Vaccination Screening Process.

PubMed

Pickren, Elizabeth; Crane, Brad

2016-12-01

Background: Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccinations were updated in 2014. Given the complexity of the guidelines and the fact that hospitals are no longer required to keep records for pneumococcal vaccinations, many hospitals are determining whether to continue this service. Objective: The primary objective of this study was to determine the impact on compliance with the revised pneumococcal vaccination guidelines from the CDC after involving pharmacy in the screening and selection processes. Secondary objectives were to determine the impact of the new process on inappropriate vaccination duplications, the time spent by pharmacy on assessments, and financial outcomes. Methods: This institutional review board (IRB)-approved, retrospective, cohort study examined all patients who received a pneumococcal vaccination from January to February 2016 after implementing a new process whereby pharmacy performed pneumococcal vaccination screening and selection (intervention group). These patients were compared to patients who received a pneumococcal vaccination from January to February 2015 (control group). Results: Of 274 patients who received a pneumococcal vaccine, 273 were included in the study. Compliance to CDC guidelines increased from 42% to 97%. Noncompliant duplications decreased from 16% to 2%. In the intervention group, labor cost for assessments and expenditure for vaccines increased. For Medicare patients, the increased reimbursement balanced the increased expenditure in the intervention group. Conclusions: Involving pharmacy in the pneumococcal vaccine screening and selection process improves compliance to CDC guidelines, but further clinical and financial analysis is needed to determine financial sustainability of the new process.

Pneumococcal pneumonia: clinical features, diagnosis and management in HIV-infected and HIV noninfected patients.

PubMed

Madeddu, Giordano; Fois, Alessandro Giuseppe; Pirina, Pietro; Mura, Maria Stella

2009-05-01

In this review, we focus on the clinical features, diagnosis and management of pneumococcal pneumonia in HIV-infected and noninfected patients, with particular attention to the most recent advances in this area. Classical clinical features are found in young adults, whereas atypical forms occur in immunocompromised patients including HIV-infected individuals. Bacteremic pneumococcal pneumonia is more frequently observed in HIV-infected and also in low-risk patients, according to the Pneumonia Severity Index (PSI). Pneumococcal pneumonia diagnostic process includes physical examination, radiologic findings and microbiologic diagnosis. However, etiologic diagnosis using traditional culture methods is difficult to obtain. In this setting, urinary antigen test, which recognizes Streptococcus pneumoniae cell wall C-polysaccharide, increases the probability of etiologic diagnosis. A correct management approach is crucial in reducing pneumococcal pneumonia mortality. The use of the PSI helps clinicians in deciding between inpatient and outpatient management in immunocompetent individuals, according to Infectious Diseases Society of America (IDSA)-American Thoracic Society (ATS) guidelines. Recent findings support PSI utility also in HIV-infected patients. Recently, efficacy of pneumococcal vaccine in reducing pneumococcal disease incidence has been evidenced in both HIV-infected and noninfected individuals. Rapid diagnosis and correct management together with implementation of preventive measures are crucial in order to reduce pneumococcal pneumonia related incidence and mortality in HIV-infected and noninfected patients.

Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine.

PubMed

Poehling, Katherine A; Szilagyi, Peter G; Grijalva, Carlos G; Martin, Stacey W; LaFleur, Bonnie; Mitchel, Ed; Barth, Richard D; Nuorti, J Pekka; Griffin, Marie R

2007-04-01

Streptococcus pneumoniae is an important cause of otitis media in children. In this study we estimated the effect of routine childhood immunization with heptavalent pneumococcal conjugate vaccine on frequent otitis media (3 episodes in 6 months or 4 episodes in 1 year) and pressure-equalizing tube insertions. The study population included all children who were enrolled at birth in TennCare or selected upstate New York commercial insurance plans as of July 1998 and continuously followed until 5 years old, loss of health plan enrollment, study outcome, or end of the study. We compared the risk of developing frequent otitis media or having pressure-equalizing tube insertion for 4 birth cohorts (1998-1999, 1999-2000, 2000-2001, and 2001-2002) by using Cox regression analysis. We used data from the National Immunization Survey to estimate the heptavalent pneumococcal conjugate vaccine uptake for children in these 4 birth cohorts in Tennessee and New York. The proportion of children in Tennessee and New York who received at least 3 doses of heptavalent pneumococcal conjugate vaccine by 2 years of age increased from < or = 1% for the 1998-1999 birth cohort to approximately 75% for the 2000-2001 birth cohort. By age 2 years, 29% of Tennessee and New York children born in 2000-2001 had developed frequent otitis media, and 6% of each of these birth cohorts had pressure-equalizing tubes inserted. Comparing the 2000-2001 birth cohort to the 1998-1999 birth cohort, frequent otitis media declined by 17% and 28%, and pressure-equalizing tube insertions declined by 16% and 23% for Tennessee and New York children, respectively. For the 2000-2001 to the 2001-2002 birth cohort, frequent otitis media and pressure-equalizing tubes remained stable in New York but increased in Tennessee. After heptavalent pneumococcal conjugate vaccine introduction, children were less likely to develop frequent otitis media or have pressure-equalizing tube insertions.

Adjunctive Dexamethasone Affects the Expression of Genes Related to Inflammation, Neurogenesis and Apoptosis in Infant Rat Pneumococcal Meningitis

PubMed Central

Blaser, Cornelia; Wittwer, Matthias; Grandgirard, Denis; Leib, Stephen L.

2011-01-01

Streptococcus pneumoniae is the most common pathogen causing non-epidemic bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of pneumococcal meningitis, dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after infection when dexamethasone was given to infant rats with pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis or were sham-infected with pyrogen-free saline. Besides antibiotics, animals were either treated with dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR. Protein levels of brain-derived neurotrophic factor, cytokines and chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories “inflammation”, “growth”, “apoptosis” and others. Dexamethasone affected the expression of genes and protein levels of chemokines reflecting diminished activation of microglia. Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as transforming growth factor pathway was reduced by dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of dexamethasone were observed on gene and protein level in experimental pneumococcal meningitis. Further dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by dexamethasone in experimental pneumococcal meningitis. PMID:21412436

Pneumococcal antimicrobial resistance: therapeutic strategy and management in community-acquired pneumonia.

PubMed

Aspa, Javier; Rajas, Olga; de Castro, Felipe Rodríguez

2008-02-01

Streptococcus pneumoniae has been consistently shown to represent the most frequent causative agent of community-acquired pneumonia (CAP) and pneumococcal antibiotic resistance towards different families of antibiotics continues to be a much-debated issue. Microbial resistance causes a great deal of confusion in choosing an empirical treatment for pneumonia and this makes it necessary to know which factors actually determine the real impact of antimicrobial resistance on the outcome of pneumococcal infections. Several different aspects have to be taken into account when analyzing this matter, such as the study design, the condition of the patient at the time of diagnosis, the choice of the initial antimicrobial regimen (combination or monotherapy) and the pharmacokinetic/pharmacodynamic variables of the chosen antibiotic. It is generally accepted that in the treatment of beta-lactam-resistant pneumococcal infections, the use of standard antipneumococcal beta-lactam agents is unlikely to impact negatively on the outcome of CAP when appropriate agents are given in sufficient doses. As a general rule, for infections with penicillin-sensitive strains, penicillin or an aminopenicillin in a standard dosage will be effective; in the cases of strains with intermediate resistance, beta-lactam agents are still considered appropriate treatment although higher dosages are recommended; finally, infections with isolates of high-level penicillin resistance should be treated with alternative agents such as the third-generation cephalosporins or the new antipneumococcal fluoroquinolones. In areas of high prevalence of high-level macrolide resistance, empirical monotherapy with a macrolide is not optimal for the treatment of hospitalised patients with moderate or moderately-severe CAP. Fluoroquinolones are considered to be excellent antibiotics in the treatment of pneumococcal CAP in adults, but their general recommendation has been withheld due to fears of a widespread development of resistance. Most international guidelines recommend combination therapy (beta-lactam plus a macrolide) for the treatment of hospitalised patients with CAP.

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine administered to older infants and children naïve to pneumococcal vaccination.

PubMed

Wysocki, Jacek; Brzostek, Jerzy; Szymański, Henryk; Tetiurka, Bogusław; Toporowska-Kowalska, Ewa; Wasowska-Królikowska, Krystyna; Sarkozy, Denise A; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A

2015-03-30

Streptococcus pneumoniae infections are a major cause of morbidity and mortality in children <5 years old worldwide. To increase serotype coverage globally, a 13-valent pneumococcal conjugate vaccine (PCV13) has been developed and approved in many countries worldwide. Assess the safety and immunogenicity of PCV13 in healthy older infants and children naïve to previous pneumococcal vaccination. This was a phase 3, open-label, multicenter study conducted in Polish children (N=354) who were vaccinated according to 3 age-appropriate catch-up schedules: Group 1 (aged 7 to <12 months) received two PCV13 doses with a booster at 12-16 months of age; Group 2 (aged 12 to <24 months) received two vaccine doses only; and Group 3 (aged 24 to <72 months) received a single dose of PCV13. Statistical analyses were descriptive. The proportion of immunological "responders" achieving serotype-specific antipneumococcal polysaccharide concentrations ≥0.35μg/mL, 1-month after the last dose of vaccine, was determined for each vaccine serotype. In addition, antipolysaccharide immunoglobulin (Ig) G geometric mean concentrations (GMCs) were calculated. Safety assessments included systemic and local reactions, and adverse events. The proportion of immunological responders was ≥88% across groups for all serotypes. Antipolysaccharide IgG GMCs were generally similar across groups. Each schedule elicited immune response levels against all 13 serotypes comparable to or greater than levels previously reported in infants after a 3-dose series. The 3 catch-up schedules had similar tolerability and safety profiles; a trend was present towards greater local tenderness with increasing age and subsequent dose administration. Immunological responses and safety results support the use of PCV13 for catch-up schedules in older infants and children naïve to pneumococcal vaccination. Copyright © 2015. Published by Elsevier Ltd.

Nationwide Trends in Bacterial Meningitis before the Introduction of 13-Valent Pneumococcal Conjugate Vaccine—Burkina Faso, 2011–2013

PubMed Central

Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Sangare, Lassana; Yaméogo, Issaka; Sawadogo, Guetawendé; Ouédraogo, Abdoul-Salam; Hema-Ouangraoua, Soumeya; McGee, Lesley; Srinivasan, Velusamy; Aké, Flavien; Congo-Ouédraogo, Malika; Sanou, Soufian; Ba, Absatou Ky; Novak, Ryan T.; Van Beneden, Chris

2016-01-01

Background Following introduction of Haemophilus influenzae type b vaccine in 2006 and serogroup A meningococcal conjugate vaccine in 2010, Streptococcus pneumoniae (Sp) became the leading cause of bacterial meningitis in Burkina Faso. We describe bacterial meningitis epidemiology, focusing on pneumococcal meningitis, before 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the pediatric routine immunization program in October 2013. Methods Nationwide population-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Sp infections are confirmed by culture, real-time polymerase chain reaction (rt-PCR), or latex agglutination, and CSF serotyped using real-time and conventional PCR. We calculated incidence rates in cases per 100,000 persons, adjusting for age and proportion of cases with CSF tested at national reference laboratories, and case fatality ratios (CFR). Results During 2011–2013, 1,528 pneumococcal meningitis cases were reported. Average annual adjusted incidence rates were 26.9 (<1 year), 5.4 (1–4 years), 7.2 (5–14 years), and 3.0 (≥15 years). Overall CFR was 23% and highest among children aged <1 year (32%) and adults ≥30 years (30%). Of 1,528 cases, 1,036 (68%) were serotyped: 71% were PCV13-associated serotypes, 14% were non-PCV13-associated serotypes, and 15% were non-typeable by PCR. Serotypes 1 (45%) and 12F/12A/12B/44/46 (8%) were most common. Among children aged <1 year, serotypes 5 (15%), 6A/6B (13%) and 1 (12%) predominated. Conclusions In Burkina Faso, the highest morbidity and mortality due to pneumococcal meningitis occurred among children aged <1 year. The majority of cases were due to PCV13-associated serotypes; introduction of PCV13 should substantially decrease this burden. PMID:27832151

Pneumococcal Infections - Multiple Languages

MedlinePlus

... Control and Prevention Vaccine Information Statement (VIS) -- Pneumococcal Polysaccharide Vaccine (PPSV): What You Need to Know - English PDF Vaccine Information Statement (VIS) -- Pneumococcal Polysaccharide Vaccine (PPSV): What You Need to Know - العربية ( ...

Pneumococcal polysaccharide vaccine - what you need to know

MedlinePlus

... taken in its entirety from the CDC Pneumococcal Polysaccharide Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... statements/ppv.html CDC review information for Pneumococcal Polysaccharide VIS: Page last reviewed: April 24, 2015 Page ...

Influenza-Induced Inflammation Drives Pneumococcal Otitis Media

PubMed Central

Reading, Patrick C.; Brown, Lorena E.; Pedersen, John; Gilbertson, Brad; Job, Emma R.; Edenborough, Kathryn M.; Habets, Marrit N.; Zomer, Aldert; Hermans, Peter W. M.; Diavatopoulos, Dimitri A.; Wijburg, Odilia L.

2013-01-01

Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM. PMID:23319557

Fred Neufeld and pneumococcal serotypes: foundations for the discovery of the transforming principle.

PubMed

Eichmann, Klaus; Krause, Richard M

2013-07-01

During the first decade of the twentieth century, the German bacteriologist Fred Neufeld, later Director of the Robert Koch-Institute in Berlin, first described the differentiation of pneumococci into serotypes on the basis of type-specific antisera. This finding was essential for subsequent research at the Rockefeller Institute of Medical Research (RIMR) in New York, and elsewhere, aiming for the conquest of human pneumococcal pneumonia, including antiserum therapy, the discovery that the type-specific antigens were carbohydrates, and the development of effective multivalent pneumococcal polysaccharide vaccines. Moreover, on the basis of pneumococcal serotypes Fred Griffith, in 1928 in London, discovered pneumococcal transformation, and Oswald T. Avery and coworkers, in 1944 at RIMR, identified DNA as the transforming substance. This sequence of events, leading to today's knowledge that genes consist of DNA, was initiated by a farsighted move of Simon Flexner, first Director of the RIMR, who asked Neufeld to send his pneumococcal typing strains, thus setting the stage for pneumococcal research at RIMR. Here, we describe Fred Neufeld's contributions in this development, which have remained largely unknown.

[Osteoarticular pneumococcal infections observed in a tertiary hospital over a period of 11 years].

PubMed

Fernández-García, Magdalena; Casado-Díez, Amaia; Salas-Venero, Carlos Antonio; Hernández-Hernández, José Luis

2015-04-01

Osteoarticular pneumococcal infection is an infrequent complication of pneumococcal bacteremia, due to the advances in antibiotic therapy and in the pattern of immunization. A retrospective study was conducted on patients diagnosed with osteoarticular pneumococcal infection between January 2003 and December 2013 in the University Hospital Marqués de Valdecilla in Santander. Five out of 321 patients diagnosed with pneumococcal bacteremia had osteoarticular infection. All of them had at least one chronic underlying disease and had been immunized according to the standard vaccination schedule. Hip and vertebra were the most common joints involved. Outcome was favorable in all cases. The clinical findings of pneumococcal osteoarticular infection should be borne in mind. Its optimal prevention in high-risk patients should include the 13V conjugate vaccine. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

CXCL16 contributes to neutrophil recruitment to cerebrospinal fluid in pneumococcal meningitis.

PubMed

Woehrl, Bianca; Klein, Matthias; Rupprecht, Tobias A; Schmetzer, Helga; Angele, Barbara; Häcker, Hans; Häcker, Georg; Pfister, Hans-Walter; Koedel, Uwe

2010-11-01

In this study, we analyzed the expression and function of CXCL16 in pneumococcal meningitis. CXCL16 was found to be up‐regulated in RAW264.7 macrophages (but not in neutrophils and endothelial cells) upon pneumococcal stimulation, in the cerebrospinal fluid of patients, and in the brains as well as the cerebrospinal fluid of mice with pneumococcal meningitis. CXCL16 up‐regulation in vivo was dependent on Toll‐like receptor (TLR) 2/TLR4 and MyD88 signaling. Neutralization of CXCL16 in animals before intracisternal pneumococcal infection (using anti‐CXCL16 antibodies) resulted in reduced cerebrospinal fluid pleocytosis. In vitro, murine neutrophils expressed the CXCL16 receptor CXCR6 and showed dose‐dependant migration toward a CXCL16 gradient. Thus, this study implicates CXCL16 as an additional neutrophil chemoattractant in cerebrospinal fluid in early pneumococcal meningitis.

Pneumococcal resistance to antibiotics.

PubMed Central

Klugman, K P

1990-01-01

The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

In vivo screen of genetically conserved Streptococcus pneumoniae proteins for protective immunogenicity.

PubMed

Anderson, Richard J; Guru, Siradanahalli; Weeratna, Risini; Makinen, Shawn; Falconer, Derek J; Sheppard, Neil C; Lang, Susanne; Chang, Bingsheng; Goenaga, Anne-Laure; Green, Bruce A; Merson, James R; Gracheck, Stephen J; Eyles, Jim E

2016-12-07

We evaluated 52 different E. coli expressed pneumococcal proteins as immunogens in a BALB/c mouse model of S. pneumoniae lung infection. Proteins were selected based on genetic conservation across disease-causing serotypes and bioinformatic prediction of antibody binding to the target antigen. Seven proteins induced protective responses, in terms of reduced lung burdens of the serotype 3 pneumococci. Three of the protective proteins were histidine triad protein family members (PhtB, PhtD and PhtE). Four other proteins, all bearing LPXTG linkage domains, also had activity in this model (PrtA, NanA, PavB and Eng). PrtA, NanA and Eng were also protective in a CBA/N mouse model of lethal pneumococcal infection. Despite data inferring widespread genomic conservation, flow-cytometer based antisera binding studies confirmed variable levels of antigen expression across a panel of pneumococcal serotypes. Finally, BALB/c mice were immunized and intranasally challenged with a viulent serotype 8 strain, to help understand the breadth of protection. Those mouse studies reaffirmed the effectiveness of the histidine triad protein grouping and a single LPXTG protein, PrtA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neurological sequelae of bacterial meningitis.

PubMed

Lucas, Marjolein J; Brouwer, Matthijs C; van de Beek, Diederik

2016-07-01

We reported on occurrence and impact of neurological sequelae after bacterial meningitis. We reviewed occurrence of neurological sequelae in children and adults after pneumococcal and meningococcal meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Adults with pneumococcal meningitis have the highest risk of developing focal neurological deficits, which are most commonly caused by cerebral infarction, but can also be due to cerebritis, subdural empyema, cerebral abscess or intracerebral bleeding. Focal deficits may improve during clinical course and even after discharge, but a proportion of patients will have persisting focal neurological deficits that often interfere in patient's daily life. Hearing loss occurs in a high proportion of patients with pneumococcal meningitis and has been associated with co-existing otitis. Children and adults recovering from bacterial meningitis without apparent neurological deficits are at risk for long-term cognitive deficits. Early identification of neurological sequelae is important for children to prevent additional developmental delay, and for adults to achieve successful return in society after the disease. Neurological sequelae occur in a substantial amount of patients following bacterial meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Granulocyte phagocytosis and killing virulent and avirulent serotypes of Streptococcus pneumoniae.

PubMed

Braconier, J H; Odeberg, H

1982-08-01

Five commonly isolated Streptococcus pneumoniae serotypes (3, 6, 14, 19, and 23) and five rarely found serotypes (31, 35, 36, 42, and 43) were compared to elucidate whether increased resistance against granulocyte phagocytosis and killing could explain the restricted number of pneumococcal serotypes found in infections. There was a great variation in sensitivity among the serotypes to granulocyte killing. No consistent pattern was found when pathogenicity and resistance to granulocytes were compared. The results do not indicate that the increased tendency of pathogenic pneumococcal serotypes to cause infections is due to increased resistance to granulocytes. Monocyte killing of some pneumococal serotypes (6, 19, 23, 35, and 43) was also studied and found very similar to granulocyte killing. Defective granulocyte kiling of encapsulated pneumococci was due to impaired phagocytosis. Moreover, no correlation was found between the sensitivity of the serotypes to isolated intragranulocytic microbial systems (i.e., MPO, hydrogen peroxide, or CCP) and the sensitivity to killing by intact granulocytes or pathogenicity. The significance of both the classical and alternative complement pathways for pneumococcal opsonization was indicated by reduced, the residual phagocytosis in C2-deficient and MgEGTA-chelated serum.

Detection of Significant Pneumococcal Meningitis Biomarkers by Ego Network.

PubMed

Wang, Qian; Lou, Zhifeng; Zhai, Liansuo; Zhao, Haibin

2017-06-01

To identify significant biomarkers for detection of pneumococcal meningitis based on ego network. Based on the gene expression data of pneumococcal meningitis and global protein-protein interactions (PPIs) data recruited from open access databases, the authors constructed a differential co-expression network (DCN) to identify pneumococcal meningitis biomarkers in a network view. Here EgoNet algorithm was employed to screen the significant ego networks that could accurately distinguish pneumococcal meningitis from healthy controls, by sequentially seeking ego genes, searching candidate ego networks, refinement of candidate ego networks and significance analysis to identify ego networks. Finally, the functional inference of the ego networks was performed to identify significant pathways for pneumococcal meningitis. By differential co-expression analysis, the authors constructed the DCN that covered 1809 genes and 3689 interactions. From the DCN, a total of 90 ego genes were identified. Starting from these ego genes, three significant ego networks (Module 19, Module 70 and Module 71) that could predict clinical outcomes for pneumococcal meningitis were identified by EgoNet algorithm, and the corresponding ego genes were GMNN, MAD2L1 and TPX2, respectively. Pathway analysis showed that these three ego networks were related to CDT1 association with the CDC6:ORC:origin complex, inactivation of APC/C via direct inhibition of the APC/C complex pathway, and DNA strand elongation, respectively. The authors successfully screened three significant ego modules which could accurately predict the clinical outcomes for pneumococcal meningitis and might play important roles in host response to pathogen infection in pneumococcal meningitis.

Association between Respiratory Syncytial Virus Activity and Pneumococcal Disease in Infants: A Time Series Analysis of US Hospitalization Data

PubMed Central

Weinberger, Daniel M.; Klugman, Keith P.; Steiner, Claudia A.; Simonsen, Lone; Viboud, Cécile

2015-01-01

Background The importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV. Methods and Findings We used data from the State Inpatient Databases (Agency for Healthcare Research and Quality), including >700,000 RSV hospitalizations and >16,000 pneumococcal pneumonia hospitalizations in 36 states (1992/1993–2008/2009). Harmonic regression was used to estimate the timing of the average seasonal peak of RSV, pneumococcal pneumonia, and pneumococcal septicemia. We then estimated the association between the incidence of pneumococcal disease in children and the activity of RSV and influenza (where there is a well-established association) using Poisson regression models that controlled for shared seasonal variations. Finally, we estimated changes in the rate of hospitalizations coded as RSV following the introduction of PCV7. RSV and pneumococcal pneumonia shared a distinctive spatiotemporal pattern (correlation of peak timing: ρ = 0.70, 95% CI: 0.45, 0.84). RSV was associated with a significant increase in the incidence of pneumococcal pneumonia in children aged <1 y (attributable percent [AP]: 20.3%, 95% CI: 17.4%, 25.1%) and among children aged 1–2 y (AP: 10.1%, 95% CI: 7.6%, 13.9%). Influenza was also associated with an increase in pneumococcal pneumonia among children aged 1–2 y (AP: 3.2%, 95% CI: 1.7%, 4.7%). Finally, we observed a significant decline in RSV-coded hospitalizations in children aged <1 y following PCV7 introduction (−18.0%, 95% CI: −22.6%, −13.1%, for 2004/2005–2008/2009 versus 1997/1998–1999/2000). This study used aggregated hospitalization data, and studies with individual-level, laboratory-confirmed data could help to confirm these findings. Conclusions These analyses provide evidence for an interaction between RSV and pneumococcal pneumonia. Future work should evaluate whether treatment for secondary bacterial infections could be considered for pneumonia cases even if a child tests positive for RSV. Please see later in the article for the Editors' Summary PMID:25562317

Influence of bacterial interactions on pneumococcal colonization of the nasopharynx

PubMed Central

Shak, Joshua R.; Vidal, Jorge E.; Klugman, Keith P.

2013-01-01

Streptococcus pneumoniae (the pneumococcus) is a common commensal inhabitant of the nasopharynx and a frequent etiologic agent in serious diseases such as pneumonia, otitis media, bacteremia, and meningitis. Multiple pneumococcal strains can colonize the nasopharynx, which is also home to many other bacterial species. Intraspecies and interspecies interactions influence pneumococcal carriage in important ways. Co-colonization by two or more pneumococcal strains has implications for vaccine serotype replacement, carriage detection, and pneumonia diagnostics. Interactions between the pneumococcus and other bacterial species alter carriage prevalence, modulate virulence, and affect biofilm formation. By examining these interactions, this review highlights how the bacterial ecosystem of the nasopharynx changes the nature and course of pneumococcal carriage. PMID:23273566

Hypoparathyroidism-retardation-Dysmorphism (HRD) syndrome--a review.

PubMed

Hershkovitz, Eli; Parvari, Ruti; Diaz, George A; Gorodischer, Rafael

2004-12-01

Hypoparathyroidism, retardation, and dysmorphism (HRD) is a newly recognized genetic syndrome, described in patients of Arab origin. The syndrome consists of permanent congenital hypoparathyroidism, severe prenatal and postnatal growth retardation, and profound global developmental delay. The patients are susceptible to severe infections including life-threatening pneumococcal infections especially during infancy. The main dysmorphic features are microcephaly, deep-set eyes or microphthalmia, ear abnormalities, depressed nasal bridge, thin upper lip, hooked small nose, micrognathia, and small hands and feet. A single 12-bp deletion (del52-55) in the second coding exon of the tubulin cofactor E (TCFE) gene, located on the long arm of chromosome 1, is the cause of HRD among Arab patients. Early recognition and therapy of hypocalcemia is important as is daily antibiotic prophylaxis against pneumococcal infections.

Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.

PubMed

Deloria Knoll, Maria; Morpeth, Susan C; Scott, J Anthony G; Watson, Nora L; Park, Daniel E; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; O'Brien, Katherine L; Thea, Donald M; Ahmed, Dilruba; Antonio, Martin; Awori, Juliet O; Baillie, Vicky L; Chipeta, James; Deluca, Andrea N; Dione, Michel; Driscoll, Amanda J; Higdon, Melissa M; Jatapai, Anchalee; Karron, Ruth A; Mazumder, Razib; Moore, David P; Mwansa, James; Nyongesa, Sammy; Prosperi, Christine; Seidenberg, Phil; Siludjai, Duangkamon; Sow, Samba O; Tamboura, Boubou; Zeger, Scott L; Murdoch, David R; Madhi, Shabir A

2017-06-15

Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls. Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16-989.9 × 103 copies/mL and 0.01-551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Role of pneumococcal vaccination in prevention of pneumococcal disease among adults in Singapore.

PubMed

Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita

2014-01-01

The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults.

Role of pneumococcal vaccination in prevention of pneumococcal disease among adults in Singapore

PubMed Central

Eng, Philip; Lim, Lean Huat; Loo, Chian Min; Low, James Alvin; Tan, Carol; Tan, Eng Kiat; Wong, Sin Yew; Setia, Sajita

2014-01-01

The burden of disease associated with Streptococcus pneumoniae infection in adults can be considerable but is largely preventable through routine vaccination. Although substantial progress has been made with the recent licensure of the new vaccines for prevention of pneumonia in adults, vaccine uptake rates need to be improved significantly to tackle adult pneumococcal disease effectively. Increased education regarding pneumococcal disease and improved vaccine availability may contribute to a reduction in pneumococcal disease through increased vaccination rates. The increase in the elderly population in Singapore as well as globally makes intervention in reducing pneumococcal disease an important priority. Globally, all adult vaccines remain underused and family physicians give little priority to pneumococcal vaccination for adults in daily practice. Family physicians are specialists in preventive care and can be leaders in ensuring that adult patients get the full benefit of protection against vaccine-preventable diseases. They can play a key role in the immunization delivery of new and routine vaccines by educating the public on the risks and benefits associated with vaccines. Local recommendations by advisory groups on vaccination in adults will also help to tackle vaccine preventable diseases in adults. PMID:24729726

Use of Vaccines to Prevent Meningitis in Persons with Cochlear Implants

MedlinePlus

... candidates for cochlear implants. CDC also recommends pneumococcal polysaccharide vaccine (PPSV23) for people 2 years and older ... pneumococcal conjugate (PCV13) (Prevnar 13®) 23-valent pneumococcal polysaccharide (PPSV23) (Pneumovax®) Haemophilus influenzae type b conjugate (Hib) ( ...

The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

PubMed

Azarian, Taj; Grant, Lindsay R; Arnold, Brian J; Hammitt, Laura L; Reid, Raymond; Santosham, Mathuram; Weatherholtz, Robert; Goklish, Novalene; Thompson, Claudette M; Bentley, Stephen D; O'Brien, Katherine L; Hanage, William P; Lipsitch, Marc

2018-04-01

In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998-2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998-2000) than the preceding period (2006-2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal vaccines.

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries.

PubMed

Morpeth, Susan C; Deloria Knoll, Maria; Scott, J Anthony G; Park, Daniel E; Watson, Nora L; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; O'Brien, Katherine L; Thea, Donald M; Adrian, Peter V; Ahmed, Dilruba; Antonio, Martin; Bunthi, Charatdao; DeLuca, Andrea N; Driscoll, Amanda J; Githua, Louis Peter; Higdon, Melissa M; Kahn, Geoff; Karani, Angela; Karron, Ruth A; Kwenda, Geoffrey; Makprasert, Sirirat; Mazumder, Razib; Moore, David P; Mwansa, James; Nyongesa, Sammy; Prosperi, Christine; Sow, Samba O; Tamboura, Boubou; Whistler, Toni; Zeger, Scott L; Murdoch, David R

2017-06-15

We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries. We tested blood by PCR for the pneumococcal autolysin gene in children aged 1-59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization-defined severe or very severe pneumonia or were age-frequency-matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls. In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%-11.5% among cases and 5.3%-10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus. The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae.

PubMed

Suri, Reetika; Periselneris, Jimstan; Lanone, Sophie; Zeidler-Erdely, Patti C; Melton, Geoffrey; Palmer, Keith T; Andujar, Pascal; Antonini, James M; Cohignac, Vanessa; Erdely, Aaron; Jose, Ricardo J; Mudway, Ian; Brown, Jeremy; Grigg, Jonathan

2016-02-01

Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR). We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model. The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N-acetylcysteine. MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF-stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS-WF-exposed mice CV-3988 reduced BALF CFU values. Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Exposure to welding fumes and lower airway infection with Streptococcus pneumoniae

PubMed Central

Suri, Reetika; Periselneris, Jimstan; Lanone, Sophie; Zeidler-Erdely, Patti C.; Melton, Geoffrey; Palmer, Keith T.; Andujar, Pascal; Antonini, James M.; Cohignac, Vanessa; Erdely, Aaron; Jose, Ricardo J.; Mudway, Ian; Brown, Jeremy; Grigg, Jonathan

2015-01-01

Background Welders are at increased risk of pneumococcal pneumonia. The mechanism for this association is not known. The capacity of pneumococci to adhere to and infect lower airway cells is mediated by host-expressed platelet-activating factor receptor (PAFR). Objective We sought to assess the effect of mild steel welding fumes (MS-WF) on PAFR-dependent pneumococcal adhesion and infection to human airway cells in vitro and on pneumococcal airway infection in a mouse model. Methods The oxidative potential of MS-WF was assessed by their capacity to reduce antioxidants in vitro. Pneumococcal adhesion and infection of A549, BEAS-2B, and primary human bronchial airway cells were assessed by means of quantitative bacterial culture and expressed as colony-forming units (CFU). After intranasal instillation of MS-WF, mice were infected with Streptococcus pneumoniae, and bronchoalveolar lavage fluid (BALF) and lung CFU values were determined. PAFR protein levels were assessed by using immunofluorescence and immunohistochemistry, and PAFR mRNA expression was assessed by using quantitative PCR. PAFR was blocked by CV-3988, and oxidative stress was attenuated by N-acetylcysteine. Results: MS-WF exhibited high oxidative potential. In A549 and BEAS-2B cells MS-WF increased pneumococcal adhesion and infection and PAFR protein expression. Both CV-3988 and N-acetylcysteine reduced MS-WF–stimulated pneumococcal adhesion and infection of airway cells. MS-WF increased mouse lung PAFR mRNA expression and increased BALF and lung pneumococcal CFU values. In MS-WF–exposed mice CV-3988 reduced BALF CFU values. Conclusions Hypersusceptibility of welders to pneumococcal pneumonia is in part mediated by the capacity of welding fumes to increase PAFR-dependent pneumococcal adhesion and infection of lower airway cells. PMID:26277596

Usefulness of Sofia Pneumococcal FIA® test in comparison with BinaxNOW® Pneumococcal test in urine samples for the diagnosis of pneumococcal pneumonia.

PubMed

Burgos, Joaquin; Garcia-Pérez, Jorge N; di Lauro, Sabina González; Falcó, Vicenç; Pumarola, Tomás; Almirante, Benito; Teresa Martín Gomez, M

2018-04-13

The Sofia Pneumococcal FIA® test is a recently introduced immunofluorescent assay automatically read aimed to detect Streptococcus pneumoniae antigen in urine. The aim of this study was to evaluate the usefulness of SofiaFIA® urinary antigen test (UAT) in comparison with classical immunochromatographic BinaxNOW® test for the diagnosis of pneumococcal pneumonia (PP). Observational study was conducted in the Hospital Universitari Vall d'Hebron from December 2015 to August 2016. Consecutive adult patients diagnosed of pneumonia and admitted to the emergency department in whom UAT was requested were prospectively enrolled. Paired pneumococcal UAT was performed (BinaxNOW® and SofiaFIA®) in urine samples. To assess the performance of both tests, patients were categorized into proven PP (isolation of S. pneumoniae in sterile fluid) or probable PP (isolation of S. pneumoniae in respiratory secretion). Sensitivity, specificity, and concordance were calculated. A total of 219 patients with pneumonia were enrolled, of whom 14% had a proven or probable PP, 22% a non-pneumococcal etiology, and 64% an unidentified pathogen. Concordance between tests was good (κ = 0.81). Sensitivity of SofiaFIA® and BinaxNOW® UAT was 78.6 and 50% for proven PP (p = 0.124), and 74.2 and 58% for proven/probable PP (p = 0.063). Specificity for both tests was 83.3 and 85.5% for proven and proven/probable PP. In patients without an identified pathogen, SofiaFIA® test was positive in 33 (23.6%) cases and BinaxNOW® in 25 (17.8%), so Sofia Pneumococcal FIA® detected 32.6% more cases than BinaxNOW® (p = 0.001). Sofia Pneumococcal FIA® test showed an improved sensitivity over visual reading of BinaxNOW® test without a noticeable loss of specificity.

The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome

PubMed Central

Hammitt, Laura L.; Santosham, Mathuram; Goklish, Novalene; Thompson, Claudette M.; Bentley, Stephen D.; O’Brien, Katherine L.

2018-01-01

In the United States, the introduction of the heptavalent pneumococcal conjugate vaccine (PCV) largely eliminated vaccine serotypes (VT); non-vaccine serotypes (NVT) subsequently increased in carriage and disease. Vaccination also disrupts the composition of the pneumococcal pangenome, which includes mobile genetic elements and polymorphic non-capsular antigens important for virulence, transmission, and pneumococcal ecology. Antigenic proteins are of interest for future vaccines; yet, little is known about how the they are affected by PCV use. To investigate the evolutionary impact of vaccination, we assessed recombination, evolution, and pathogen demographic history of 937 pneumococci collected from 1998–2012 among Navajo and White Mountain Apache Native American communities. We analyzed changes in the pneumococcal pangenome, focusing on metabolic loci and 19 polymorphic protein antigens. We found the impact of PCV on the pneumococcal population could be observed in reduced diversity, a smaller pangenome, and changing frequencies of accessory clusters of orthologous groups (COGs). Post-PCV7, diversity rebounded through clonal expansion of NVT lineages and inferred in-migration of two previously unobserved lineages. Accessory COGs frequencies trended toward pre-PCV7 values with increasing time since vaccine introduction. Contemporary frequencies of protein antigen variants are better predicted by pre-PCV7 values (1998–2000) than the preceding period (2006–2008), suggesting balancing selection may have acted in maintaining variant frequencies in this population. Overall, we present the largest genomic analysis of pneumococcal carriage in the United States to date, which includes a snapshot of a true vaccine-naïve community prior to the introduction of PCV7. These data improve our understanding of pneumococcal evolution and emphasize the need to consider pangenome composition when inferring the impact of vaccination and developing future protein-based pneumococcal vaccines. PMID:29617440

An economic analysis of a pneumococcal vaccine programme in people aged over 64 years in a developed country setting.

PubMed

Mangtani, Punam; Roberts, Jennifer A; Hall, Andrew J; Cutts, Felicity T

2005-06-01

Polysaccharide pneumococcal vaccination for older adults is being introduced in developed country settings. Evidence of protection by this vaccine against pneumococcal pneumonia, or confirmation that illness and death from bacteraemia are prevented, is currently limited. Decisions are often made based on partial information. We examined the policy implications by exploring the potential economic benefit to society and the health sector of pneumococcal vaccination in older adults. A model to estimate the potential cost savings and cost-effectiveness of a polysaccharide pneumococcal vaccine programme was based on costs collected from patients, the literature, and routine health-services data. The effect of a pneumococcal vaccine (compared with no vaccination) was examined in a hypothetical cohort aged over 64 years. The duration of protection was assumed to be 10 years, with or without a booster at 5 years. If it were effective against morbidity from pneumococcal pneumonia, the main burden from pneumococcal disease, the vaccine could be cost-neutral to society or the health sector at low efficacy (28 and 37.5%, respectively, without boosting and with 70% coverage). If it were effective against morbidity from bacteraemia only, the vaccine's efficacy would need to be 75 and 89%, respectively. If protection against both morbidity and mortality from pneumococcal bacteraemia was 50%, the net cost to society would be 2500 pounds per year of life saved ( 3365 pounds from the health-sector perspective). Results were sensitive to incidence, case-fatality rates, and costs of illness. A vaccine with moderate efficacy against bacteraemic illness and death would be cost-effective. If it also protected against pneumonia, it would be cost-effective even if its efficacy were low.

Influence of bacterial interactions on pneumococcal colonization of the nasopharynx.

PubMed

Shak, Joshua R; Vidal, Jorge E; Klugman, Keith P

2013-03-01

Streptococcus pneumoniae (the pneumococcus) is a common commensal inhabitant of the nasopharynx and a frequent etiologic agent in serious diseases such as pneumonia, otitis media, bacteremia, and meningitis. Multiple pneumococcal strains can colonize the nasopharynx, which is also home to many other bacterial species. Intraspecies and interspecies interactions influence pneumococcal carriage in important ways. Co-colonization by two or more pneumococcal strains has implications for vaccine serotype replacement, carriage detection, and pneumonia diagnostics. Interactions between the pneumococcus and other bacterial species alter carriage prevalence, modulate virulence, and affect biofilm formation. By examining these interactions, this review highlights how the bacterial ecosystem of the nasopharynx changes the nature and course of pneumococcal carriage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mannose-binding lectin-associated serine protease 2 (MASP-2) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

PubMed

Kasanmoentalib, E Soemirien; Valls Seron, Mercedes; Ferwerda, Bart; Tanck, Michael W; Zwinderman, Aeilko H; Baas, Frank; van der Ende, Arie; Brouwer, Matthijs C; van de Beek, Diederik

2017-01-03

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the pro-inflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. We investigated mannose-binding lectin-associated serine protease (MASP-2) levels in cerebrospinal fluid (CSF) samples derived from the diagnostic lumbar puncture, which was available for 307 of 792 pneumococcal meningitis episodes included in our prospective nationwide cohort study (39%), and the association between these levels and clinical outcome. Subsequently, we studied the role of MASP-2 in our experimental pneumococcal meningitis mouse model using Masp2 -/- mice and evaluated the potential of adjuvant treatment with MASP-2-specific monoclonal antibodies in wild-type (WT) mice. MASP-2 levels in cerebrospinal fluid of patients with bacterial meningitis were correlated with poor functional outcome. Consistent with these human data, Masp2-deficient mice with pneumococcal meningitis had lower cytokine levels and increased survival compared to WT mice. Adjuvant treatment with MASP-2-specific monoclonal antibodies led to reduced complement activation and decreased disease severity. MASP-2 contributes to poor disease outcome in human and mice with pneumococcal meningitis. MASP-2-specific monoclonal antibodies can be used to attenuate the inflammatory response in pneumococcal meningitis.

Therapy for pneumococcal infection at the millennium: doubts and certainties.

PubMed

Ball, P

1999-07-26

Rapidly burgeoning worldwide multiple drug-resistant pneumococcal serotypes pose an urgent demand for new management approaches. Perhaps modern intensive care methods may have alternatives to offer. Indeed, standard assessments such as the admission APACHE II score may overestimate individual risk of death in severe CAP, and mortality can be reduced. However, among those at highest risk for mortality in the early phase of invasive disease, the conclusions reached 2-3 decades ago, that it is questionable whether a more effective drug than penicillin can be developed, and that a reduction in the number of deaths consequent to this infection can be accomplished only by widespread immunoprophylactic measures, remain inescapable. Clearly, as discussed elsewhere in this supplement, the continuing validity of these 20-year-old conclusions and the global prevalence of DRSP demand the development and marketing of new conjugate vaccines, although more widespread use of the existing 23-valent polysaccharide vaccine among high-risk populations is essential in the interim. With respect to resistance selection pressures, antibiotic prescription control may provide the answer. However, patient expectations of antibiotic therapy for trivial respiratory infection is high and, in the United Kingdom, 75% of previously healthy adults will receive it; those who do not will usually consult another physician in an effort to secure such therapy. Thus, without the intervention of government or managed care organizations, self-regulation in prescribing is unlikely. The evidence for beta-lactam treatment failure in meningitis has led to alternative approaches, with vancomycin as the primary agent. Penicillins may remain effective for otitis media, but oral cephalosporins are suspect. Data on pediatric pneumococcal pneumonia continue to suggest use of beta-lactams, at least for disease caused by strains with intermediate penicillin sensitivity. Pallares et al concluded that penicillins and cephalosporins remain the drugs of choice for severe pneumococcal pneumonia in adults. Others who share this conclusion often cite that study as evidence. However, in the case of penicillins, the mortality rate was 6% higher in a subgroup selected for monomicrobial infection and reduced risk factors for mortality when penicillin-resistant infection was present, and the overall mortality was 14% higher with penicillin-resistant strains (taking into account "all comers"). Those who depend on the findings of evidence-based medicine may accept the premise that penicillins and cephalosporins remain the drugs of choice, and agree with Goldstein and Garau that it would indeed be a mistake to adopt alternative therapies. Others may consider the deaths of 6 of 100 patients who were not in the highest-risk group too high a price to pay for statistical significance and may be skeptical of the continued use of beta-lactam therapy on higher-risk patients. In addition, the persistent selection pressure applied by continued use of beta-lactams offers a powerful population-based argument for alternatives. As DRSP continues to spread and resistant strains with penicillin MIC >2 mg/L become more prevalent, new agents such as the azabicyclo-methoxyquinolone, moxifloxacin, and perhaps grepafloxacin, but not the more toxic sparfloxacin and trovafloxacin, will undoubtedly flourish as treatments for CAP. By that time, the results of clinical studies on ketolides and oxazolidinones could offer further choices.

Strain Level Streptococcus Colonization Patterns during the First Year of Life

PubMed Central

Wright, Meredith S.; McCorrison, Jamison; Gomez, Andres M.; Beck, Erin; Harkins, Derek; Shankar, Jyoti; Mounaud, Stephanie; Segubre-Mercado, Edelwisa; Mojica, Aileen May R.; Bacay, Brian; Nzenze, Susan A.; Kimaro, Sheila Z. M.; Adrian, Peter; Klugman, Keith P.; Lucero, Marilla G.; Nelson, Karen E.; Madhi, Shabir; Sutton, Granger G.; Nierman, William C.; Losada, Liliana

2017-01-01

Pneumococcal pneumonia has decreased significantly since the implementation of the pneumococcal conjugate vaccine (PCV), nevertheless, in many developing countries pneumonia mortality in infants remains high. We have undertaken a study of the nasopharyngeal (NP) microbiome during the first year of life in infants from The Philippines and South Africa. The study entailed the determination of the Streptococcus sp. carriage using a lytA qPCR assay, whole metagenomic sequencing, and in silico serotyping of Streptococcus pneumoniae, as well as 16S rRNA amplicon based community profiling. The lytA carriage in both populations increased with infant age and lytA+ samples ranged from 24 to 85% of the samples at each sampling time point. We next developed informatic tools for determining Streptococcus community composition and pneumococcal serotype from metagenomic sequences derived from a subset of longitudinal lytA-positive Streptococcus enrichment cultures from The Philippines (n = 26 infants, 50% vaccinated) and South African (n = 7 infants, 100% vaccinated). NP samples from infants were passaged in enrichment media, and metagenomic DNA was purified and sequenced. In silico capsular serotyping of these 51 metagenomic assemblies assigned known serotypes in 28 samples, and the co-occurrence of serotypes in 5 samples. Eighteen samples were not typeable using known serotypes but did encode for capsule biosynthetic cluster genes similar to non-encapsulated reference sequences. In addition, we performed metagenomic assembly and 16S rRNA amplicon profiling to understand co-colonization dynamics of Streptococcus sp. and other NP genera, revealing the presence of multiple Streptococcus species as well as potential respiratory pathogens in healthy infants. A range of virulence and drug resistant elements were identified as circulating in the NP microbiomes of these infants. This study revealed the frequent co-occurrence of multiple S. pneumoniae strains along with Streptococcus sp. and other potential pathogens such as S. aureus in the NP microbiome of these infants. In addition, the in silico serotype analysis proved powerful in determining the serotypes in S. pneumoniae carriage, and may lead to developing better targeted vaccines to prevent invasive pneumococcal disease (IPD) in these countries. These findings suggest that NP colonization by S. pneumoniae during the first years of life is a dynamic process involving multiple serotypes and species. PMID:28932211

Cost-effectiveness analysis of routine pneumococcal vaccination in the UK: a comparison of the PHiD-CV vaccine and the PCV-13 vaccine using a Markov model.

PubMed

Delgleize, Emmanuelle; Leeuwenkamp, Oscar; Theodorou, Eleni; Van de Velde, Nicolas

2016-11-30

In 2010, the 13-valent pneumococcal conjugate vaccine (PCV-13) replaced the 7-valent vaccine (introduced in 2006) for vaccination against invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) in the UK. Using recent evidence on the impact of PCVs and epidemiological changes in the UK, we performed a cost-effectiveness analysis (CEA) to compare the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with PCV-13 in the ongoing national vaccination programme. CEA was based on a published Markov model. The base-case scenario accounted only for direct medical costs. Work days lost were considered in alternative scenarios. Calculations were based on serotype and disease-specific vaccine efficacies, serotype distributions and UK incidence rates and medical costs. Health benefits and costs related to IPD, pneumonia and AOM were accumulated over the lifetime of a UK birth cohort. Vaccination of infants at 2, 4 and 12 months with PHiD-CV or PCV-13, assuming complete coverage and adherence. The incremental cost-effectiveness ratio (ICER) was computed by dividing the difference in costs between the programmes by the difference in quality-adjusted life-years (QALY). Under our model assumptions, both vaccines had a similar impact on IPD and pneumonia, but PHiD-CV generated a greater reduction in AOM cases (161 918), AOM-related general practitioner consultations (31 070) and tympanostomy tube placements (2399). At price parity, PHiD-CV vaccination was dominant over PCV-13, saving 734 QALYs as well as £3.68 million to the National Health Service (NHS). At the lower list price of PHiD-CV, the cost-savings would increase to £45.77 million. This model projected that PHiD-CV would provide both incremental health benefits and cost-savings compared with PCV-13 at price parity. Using PHiD-CV could result in substantial budget savings to the NHS. These savings could be used to implement other life-saving interventions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk of pneumococcal diseases in adults with underlying medical conditions: a retrospective, cohort study using two Japanese healthcare databases.

PubMed

Imai, Kentaro; Petigara, Tanaz; Kohn, Melvin A; Nakashima, Kei; Aoshima, Masahiro; Shito, Akihito; Kanazu, Shinichi

2018-03-02

To quantify the risk of pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) in adults aged ≥19 years with underlying medical conditions compared with healthy adults of the same age in Japan. An observational, retrospective, cohort study using two healthcare claims databases in Japan: Japan Medical Data Center (JMDC) and Medical Data Vision (MDV) databases. A total of 10.4 million individuals, representing 9.3 million person-years of follow-up, were included in the analysis. Eleven medical conditions as well as PP and IPD were identified by the International Statistical Classification of Diseases and Related Health Problems version 10 diagnostic codes and/or local disease codes used in Japan. Adjusted rate ratios (RRs) for PP and IPD in adults with a medical condition versus adults without any medical condition were calculated using multivariate Poisson regression models with age and/or sex as covariates. In the JMDC and MDV databases, respectively, adults ≥19 years with a medical condition (RRs for PP: 3.3 to 13.4, 1.7 to 5.2; RRs for IPD: 12.6 to 43.3, 4.4 to 7.1), adults with two or more medical conditions (PP: 11.6, 2.8; IPD: 18.7, 5.8) and high-risk adults (PP: 12.9, 1.8; IPD: 29.7, 4.0) were at greater risk of PP and IPD compared with their healthy counterparts. Adults aged 50-64 years with an underlying medical condition (PP rate: 38.6 to 212.1 per 100 000 person-years) had a higher rate of PP than those aged ≥65 years without any condition (PP rate: 13.2 to 93.0 per 100 000 person-years). Adults of all ages with an underlying medical condition are at greater risk of PP and IPD compared with adults without any medical condition. This risk increases with the number of underlying medical conditions. Our results support extending pneumococcal vaccination to younger adults with an underlying medical condition, especially those aged 50-64 years. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Aggregated Antibiograms and Monitoring of Drug-Resistant Streptococcus pneumoniae

PubMed Central

Lexau, Catherine; Baughman, Wendy; Barnes, Brenda; Bennett, Nancy; Cassidy, P. Maureen; Pass, Margaret; Gelling, Lisa; Barrett, Nancy L.; Zell, Elizabeth R.; Whitney, Cynthia G.

2003-01-01

Community-specific antimicrobial susceptibility data may help monitor trends among drug-resistant Streptococcus pneumoniae and guide empiric therapy. Because active, population-based surveillance for invasive pneumococcal disease is accurate but resource intensive, we compared the proportion of penicillin-nonsusceptible isolates obtained from existing antibiograms, a less expensive system, to that obtained from 1 year of active surveillance for Georgia, Tennessee, California, Minnesota, Oregon, Maryland, Connecticut, and New York. For all sites, proportions of penicillin-nonsusceptible isolates from antibiograms were within 10 percentage points (median 3.65) of those from invasive-only isolates obtained through active surveillance. Only 23% of antibiograms distinguished between isolates intermediate and resistant to penicillin; 63% and 57% included susceptibility results for erythromycin and extended-spectrum cephalosporins, respectively. Aggregating existing hospital antibiograms is a simple and relatively accurate way to estimate local prevalence of penicillin-nonsusceptible pneumococcus; however, antibiograms offer limited data on isolates with intermediate and high-level penicillin resistance and isolates resistant to other agents. PMID:14519245

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

PubMed Central

Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

2011-01-01

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination

PubMed Central

Richmond, Peter C.; Fuery, Angela; Anderson, Denise; Opa, Christine; Saleu, Gerard; Lai, Mildred; Francis, Jacinta P.; Alpers, Michael P.; Pomat, William S.; Lehmann, Deborah

2017-01-01

Trial design In an earlier trial, Papua New Guinean (PNG) children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3–5 years of age (n = 132), and in 121 community controls of a similar age with no prior pneumococcal vaccination. Methods Circulating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3–5 years of age for a subgroup of study children. Results Serotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in all groups had serotype-specific titers ≥ 0.35μg/ml and ≥ 1.0 μg/ml, respectively. Post-challenge antibody titers were higher or similar to pre-challenge titers for most children independent of pneumococcal vaccination history. The rise in antibody titers was significantly lower when pre-challenge titers were higher. Overall the relative number of serotype-specific memory B-cells remained the same or increased between 10 months and 3–5 years of age, and there were no differences in serotype-specific memory B-cell numbers at 3–5 years of age between the three groups. Conclusions Immunity induced by PCV7 and/or PPV23 immunization in infancy does not exceed that of naturally acquired immunity in 3-5-year-old children living in a highly endemic area. Also, there was no evidence that PPV23 immunization in the first year of life following PCV7 priming induces longer-term hypo-responsiveness. Trial registration Clinicaltrials.gov NCT01414504 and NCT00219401. PMID:29028802

Is there any connection between a second pneumonia shot and hospitalization among Medicare beneficiaries?

PubMed

Snow, R; Babish, J D; McBean, A M

1995-01-01

To learn whether the risk of revaccination in adults should limit its use, the authors investigated whether adverse events requiring hospitalization occurred in a group of Medicare enrollees revaccinated with pneumococcal polysaccharide vaccine. A prospective cohort analysis and case study of revaccinated people involved five percent of all elderly Medicare enrollees from 1985 through 1988, consisting of 66,256 people receiving one dose of vaccine and 1,099 receiving two doses. Comparison was made of the hospitalization rate within 30 days after revaccination and rates of singly vaccinated persons using discharge diagnosis for all those hospitalized during the 30 days after revaccination. No significant difference was found between the hospitalization rate of the revaccinated cohort and comparison group. No adverse reactions attributable to pneumococcal polysaccharide vaccine causing hospitalization were identified among 39 revaccinated persons who were hospitalized within 30 days of revaccination. Revaccination of elderly Medicare beneficiaries does not cause events serious enough to require hospitalization. Vaccination of persons according to the Public Health Service Immunization Practice Advisory Committee guidelines is recommended when the prior immunization status is unknown.

Nasopharyngeal carriage of pneumococci in Gambian children and in their families.

PubMed

Lloyd-Evans, N; O'Dempsey, T J; Baldeh, I; Secka, O; Demba, E; Todd, J E; Mcardle, T F; Banya, W S; Greenwood, B M

1996-10-01

Nasopharyngeal carriage of pneumococci is prevalent among children in developing countries but little is known about the relationship of nasopharyngeal carriage to invasive disease or about the way in which pneumococci spread within households. To determine the prevalence of nasopharyngeal carriage in healthy and sick Gambian children and to investigate transmission within households. Nasopharyngeal swabs were obtained by the per nasal route and cultured for pneumococci on selective media. Pneumococci were serotyped with the use of latex particles coated with type-specific antisera. Pneumococci were isolated from the nasopharynx of 73 (90.1%) of 81 children with invasive pneumococcal disease, 86 (76.1%) of 113 healthy, age-matched control children and 911 (85.1%) of 1071 sick children. Pneumococci belonging to serotypes 1, 14 and 12 were isolated significantly more frequently from cases than from matched controls. In 43 (76.8%) of 56 children with invasive disease, pneumococci isolated from the nasopharynx and from the blood or other sterile site belonged to the same serotype. Pneumococci of the same serotype as the bacterium responsible for invasive disease in a child were obtained from 72 (8.5%) of 843 family members, most frequently from young siblings of the case patients. Nasopharyngeal carriage of pneumococci is more prevalent among young Gambian children than among adults and invasive infections are probably acquired more frequently from siblings than from parents. However, further studies are needed to confirm this hypothesis with more discriminating markers than polysaccharide serotyping.

Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects.

PubMed

Ciprero, Karen; Zykov, Kirill A; Briko, Nikolay I; Shekar, Tulin; Sterling, Tina M; Bitieva, Elizaveta; Stek, Jon E; Musey, Luwy

2016-08-02

Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD. Approximately 100 subjects from the Russian Federation who were either 2 to 49 y of age with increased risk for PD or ≥50 years of age were enrolled into the study (NCT01734239) to receive a single dose of PPV23 administered intramuscularly. Each subject was followed for local and systemic adverse events (AEs) for 5 and 14 days, respectively. Serious AEs were collected for 28 d postvaccination. Blood samples were collected immediately prior to vaccination and 28 d postvaccination for the measurement of IgG to serotypes 1, 6B, 14, 19F, and 23F. High proportion of subjects had ≥2 -fold increase in IgG following receipt of PPV23. Rates were 92.0%, 83.0%, 89.0%, 81%, 84% for serotypes 1, 6B, 14, 19F, and 23F, respectively. Similar rates of responders and increases in the magnitude of immune responses were observed in both age groups (2-49, ≥50 ). PPV23 was generally safe and well tolerated. Injection site and systemic AEs were reported by 14.7% and 18.6% of study subjects, respectively. PPV23 is generally safe, well tolerated, and highly immunogenic when given as a single dose to Russian individuals 50 y of age and older, as well as Russian individuals 2 to 49 y of age who are at high risk for PD.

Salivary Functional Antibody Secretion Is Reduced in Older Adults: A Potential Mechanism of Increased Susceptibility to Bacterial Infection in the Elderly.

PubMed

Heaney, Jennifer L J; Phillips, Anna C; Carroll, Douglas; Drayson, Mark T

2015-12-01

Bacterial infections in the elderly are common and associated with high morbidity and mortality, with pneumonia the second commonest cause of death. Reductions in antibodies against specific bacterial antigens in saliva and serum could contribute to infection risk in older adults, although they have yet to be examined in relation to age. IgG, IgA and IgM antibody levels in paired saliva and serum samples were measured against 12 pneumococcal, 4 meningococcal and haemophilus polysaccharide antigens and diphtheria and tetanus toxoids in healthy younger (n = 28, 21-34 years) and older (n = 44, 60-80 years) adults. Older adults had lower antibody concentrations in saliva than young adults, with the most striking differences observed for salivary antibody secretion rates. In serum, older adults registered lower concentrations for only a minority of antibodies. Young adults who had previously received a polysaccharide pneumococcal vaccination (PPV23) had higher levels of anti-pneumococcal antibodies in serum and in saliva. Only minor differences were observed in antibody levels between older adults who had/had not received PPV23, and there was no evidence of memory in saliva. Age differences were much greater in salivary antibodies than in serum; older adults had reduced salivary secretion rates of antibodies across bacterial antigens. This decline in local immunity may contribute to increased infection risk in the elderly. The poor memory from pneumococcal vaccination in serum and saliva suggests that PPV23 may be ineffective in older adults for both systemic and local protection. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Role of Influenza and Parainfluenza Infections in Nasopharyngeal Pneumococcal Acquisition Among Young Children

PubMed Central

Grijalva, Carlos G.; Griffin, Marie R.; Edwards, Kathryn M.; Williams, John V.; Gil, Ana I.; Verastegui, Hector; Hartinger, Stella M.; Vidal, Jorge E.; Klugman, Keith P.; Lanata, Claudio F.

2014-01-01

Background. Animal models suggest that influenza infection favors nasopharyngeal acquisition of pneumococci. We assessed this relationship with influenza and other respiratory viruses in young children. Methods. A case-control study was nested within a prospective cohort study of acute respiratory illness (ARI) in Andean children <3 years of age (RESPIRA-PERU study). Weekly household visits were made to identify ARI and obtain nasal swabs for viral detection using real-time reverse-transcription polymerase chain reaction. Monthly nasopharyngeal (NP) samples were obtained to assess pneumococcal colonization. We determined whether specific respiratory viral ARI episodes occurring within the interval between NP samples increased the risk of NP acquisition of new pneumococcal serotypes. Results. A total of 729 children contributed 2128 episodes of observation, including 681 pneumococcal acquisition episodes (new serotype, not detected in prior sample), 1029 nonacquisition episodes (no colonization or persistent colonization with the same serotype as the prior sample), and 418 indeterminate episodes. The risk of pneumococcal acquisition increased following influenza-ARI (adjusted odds ratio [AOR], 2.19; 95% confidence interval [CI], 1.02–4.69) and parainfluenza-ARI (AOR, 1.86; 95% CI, 1.15–3.01), when compared with episodes without ARI. Other viral infections (respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus) were not associated with acquisition. Conclusions. Influenza and parainfluenza ARIs appeared to facilitate pneumococcal acquisition among young children. As acquisition increases the risk of pneumococcal diseases, these observations are pivotal in our attempts to prevent pneumococcal disease. PMID:24621951

Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia.

PubMed

Smith, N Ms; Wasserman, G A; Coleman, F T; Hilliard, K L; Yamamoto, K; Lipsitz, E; Malley, R; Dooms, H; Jones, M R; Quinton, L J; Mizgerd, J P

2018-01-01

As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity. This protection was diminished by depletion of CD4 + cells prior to the final infection. The resolution of previous pneumococcal infections seeded the lungs with CD4 + resident memory T (T RM ) cells, which responded to heterotypic pneumococcus stimulation by producing multiple effector cytokines, particularly interleukin (IL)-17A. Following lobar pneumonias, IL-17-producing CD4 + T RM cells were confined to the previously infected lobe, rather than dispersed throughout the lower respiratory tract. Importantly, pneumonia protection also was confined to that immunologically experienced lobe. Thus regionally localized memory cells provide superior local tissue protection to that mediated by systemic or central memory immune defenses. We conclude that respiratory bacterial infections elicit CD4 + T RM cells that fill a local niche to optimize heterotypic protection of the affected tissue, preventing pneumonia.

Panax ginseng aqueous extract prevents pneumococcal sepsis in vivo by potentiating cell survival and diminishing inflammation.

PubMed

Nguyen, Cuong Thach; Luong, Truc Thanh; Lee, Seung Yeop; Kim, Gyu Lee; Kwon, Hyogyoung; Lee, Hong-Gyun; Park, Chae-Kyu; Rhee, Dong-Kwon

2015-10-15

More than 50% of sepsis cases are caused by Streptococcus pneumoniae, and hospital mortality related to sepsis comprises 52% of all hospital deaths. Therefore, sepsis is a medical emergency, and any treatment against the agent that produces it, is welcome. The role of Panax ginseng C.A. Meyer (Araliaceae) aqueous extract in bacterial infection in vivo is not well understood. Here, the protective effect of Korean red ginseng (KRG) extract against pneumococcal infection and sepsis was elucidated. In this study, mice were administrated KRG (25, 50, 100 mg/kg) for 15 days, and then infected with a lethal S. pneumoniae strain. Survival rate, body weight, and colonization were determined. The RAW 264.7 macrophage cells were infected with S. pneumoniae and cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Inflammation was examined using an enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin (HE) staining while gene expression was determined using western blotting. KRG-pre-treated mice (100 mg/kg of KRG) had significantly higher survival rates and body weights than those of the non-treated controls; KRG-pre-treated mice had lower bacterial number and morbidity than those of the non-treated controls. 100 mg/kg of KRG administration decreased cytokine levels including tumor necrosis factor (TNF)-α (897 and 623 pg/ml, control and KRG groups, respectively, P < 0.05) and interleukin (IL)-1β (175 and 127 pg/ml, control and KRG groups, respectively, P = 0.051), nitric oxide level (149 and 81 nM, control and KRG groups, respectively, P < 0.05), and neutrophil infiltration 48 h post-infection, in vivo. In pneumococcal infection, KRG pre-treatment downregulated toll-like receptor (TLR) 4 and TNF-ɑ expressions in RAW 264.7 macrophage cells and increased cell survival by activating phosphoinositide 3-kinase (PI3K)/AKT signaling. Taken together, 100 mg/kg of KRG appeared to protect host cells from lethal pneumococcal sepsis by inhibiting inflammation as well as by enhancing bacterial clearance thereby reinforcing cell survival against pneumococcal infection. Copyright © 2015 Elsevier GmbH. All rights reserved.

Sampling methods for the study of pneumococcal carriage: a systematic review.

PubMed

Gladstone, R A; Jefferies, J M; Faust, S N; Clarke, S C

2012-11-06

Streptococcus pneumoniae is an important pathogen worldwide. Accurate sampling of S. pneumoniae carriage is central to surveillance studies before and following conjugate vaccination programmes to combat pneumococcal disease. Any bias introduced during sampling will affect downstream recovery and typing. Many variables exist for the method of collection and initial processing, which can make inter-laboratory or international comparisons of data complex. In February 2003, a World Health Organisation working group published a standard method for the detection of pneumococcal carriage for vaccine trials to reduce or eliminate variability. We sought to describe the variables associated with the sampling of S. pneumoniae from collection to storage in the context of the methods recommended by the WHO and those used in pneumococcal carriage studies since its publication. A search of published literature in the online PubMed database was performed on the 1st June 2012, to identify published studies that collected pneumococcal carriage isolates, conducted after the publication of the WHO standard method. After undertaking a systematic analysis of the literature, we show that a number of differences in pneumococcal sampling protocol continue to exist between studies since the WHO publication. The majority of studies sample from the nasopharynx, but the choice of swab and swab transport media is more variable between studies. At present there is insufficient experimental data that supports the optimal sensitivity of any standard method. This may have contributed to incomplete adoption of the primary stages of the WHO detection protocol, alongside pragmatic or logistical issues associated with study design. Consequently studies may not provide a true estimate of pneumococcal carriage. Optimal sampling of carriage could lead to improvements in downstream analysis and the evaluation of pneumococcal vaccine impact and extrapolation to pneumococcal disease control therefore further in depth comparisons would be of value. Copyright © 2012 Elsevier Ltd. All rights reserved.

Systematic review of incremental non-vaccine cost estimates used in cost-effectiveness analysis on the introduction of rotavirus and pneumococcal vaccines.

PubMed

De la Hoz-Restrepo, Fernando; Castañeda-Orjuela, Carlos; Paternina, Angel; Alvis-Guzman, Nelson

2013-07-02

To review the approaches used in the cost-effectiveness analysis (CEAs) literature to estimate the cost of expanded program on immunization (EPI) activities, other than vaccine purchase, for rotavirus and pneumococcal vaccines. A systematic review in PubMed and NHS EED databases of rotavirus and pneumococcal vaccines CEAs was done. Selected articles were read and information on how EPI costs were calculated was extracted. EPI costing approaches were classified according to the method or assumption used for estimation. Seventy-nine studies that evaluated cost effectiveness of rotavirus (n=43) or pneumococcal (n=36) vaccines were identified. In general, there are few details on how EPI costs other than vaccine procurement were estimated. While 30 studies used some measurement of that cost, only one study on pneumococcal vaccine used a primary cost evaluation (bottom-up costing analysis) and one study used a costing tool. Twenty-seven studies (17 on rotavirus and 10 on pneumococcal vaccine) assumed the non-vaccine costs. Five studies made no reference to additional costs. Fourteen studies (9 rotavirus and 5 pneumococcal) did not consider any additional EPI cost beyond vaccine procurement. For rotavirus studies, the median for non-vaccine cost per dose was US$0.74 in developing countries and US$6.39 in developed countries. For pneumococcal vaccines, the median for non-vaccine cost per dose was US$1.27 in developing countries and US$8.71 in developed countries. Many pneumococcal (52.8%) and rotavirus (60.4%) cost-effectiveness analyses did not consider additional EPI costs or used poorly supported assumptions. Ignoring EPI costs in addition to those for vaccine procurement in CEA analysis of new vaccines may lead to significant errors in the estimations of ICERs since several factors like personnel, cold chain, or social mobilization can be substantially affected by the introduction of new vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pneumococcal meningitis: development of a new animal model

PubMed Central

Wei, Benjamin P.C.; Shepherd, Robert K.; Robins-Browne, Roy M.; Clark, Graeme M.; O’Leary, Stephen J.

2007-01-01

Hypothesis The rat is a suitable animal to establish a model for the study of pneumococcal meningitis post cochlear implantation Background There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis post implantation and are based on relatively small animal numbers, making it difficult to assess the cause and effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant. Methods Eighteen non-implanted rats were infected with 1× 106 and 1 × 108 colony forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear and intraperitoneal) to examine for evidence of meningitis over 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 × 1010 CFU intraperitoneal, 3 × 108CFU middle ear, 1 × 106 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. Histological pattern of cochlear infections for each of the three different inoculating routes were examined. Results Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system either via the cochlear aqueduct or canaliculi perforantes of osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 non-implanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours post-inoculation. Conclusion Meningitis in implanted rats following inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 non-implanted rats suggests longer post-inoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work we have developed a new animal model that will allow quantitative risk assessment of meningitis post cochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies. PMID:16936571

Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa Rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the National Immunization Program: acute otitis media microbiology in Costa Rican children.

PubMed

Abdelnour, Arturo; Arguedas, Adriano; Dagan, Ron; Soley, Carolina; Porat, Nurith; Castrejon, Maria Mercedes; Ortega-Barria, Eduardo; Colindres, Romulo; Pirçon, Jean-Yves; DeAntonio, Rodrigo; Van Dyke, Melissa K

2015-01-01

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥ 2 PCV7 doses or ≥ 1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.

Aetiology of paediatric pneumonia with effusion in the Dominican Republic and the potential impact of pneumococcal conjugate vaccines.

PubMed

Feris-Iglesias, Jesús; Fernández, Josefina; Sánchez, Jacqueline; Pimenta, Fabiana; Peña, Chabela; Coradin, Hilma; Perez-Then, Eddy; Peinado, Maria; Floren, Angélica; Del Moral, Teresa; Erdman, Dean; da Gloria Carvalho, Maria; Verani, Jennifer R

2014-01-01

Pleural effusion is a serious complication of pneumonia, and Streptococcus pneumoniae is a leading cause. We describe the aetiology of pneumonia with effusion among children in the Dominican Republic before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV) in 2013 and the performance characteristics of a rapid immunochromatographic test (ICT) for detecting S. pneumoniae in pleural fluid. From July 2009 to June 2011, we enrolled children <15 years old admitted with pneumonia and pleural effusion to Robert Reid Cabral Children's Hospital, Dominican Republic. Pleural fluid was tested by culture, polymerase chain reaction (PCR) for bacterial ( S. pyogenes, S. pneumoniae ) and viral (respiratory syncytial virus and human rhinovirus) pathogens, and by ICT for S. pneumoniae . We calculated the performance of ICT and culture compared with PCR. Among 121 cases, the median age was 31 months (range 1 week to 14 years). Pleural fluid culture ( n = 121) and PCR testing ( n = 112) identified an aetiology in 85 (70.2%) cases, including 62 S. pneumoniae (51.2%) and 19 Staphylococcus aureus (15.7%). The viruses tested were not detected. The most prevalent pneumococcal serotypes were 14 ( n = 20), 1 ( n = 13), and 3 ( n = 12). Serotype coverage of the 10- and 13-valent PCVs would be 70.5% and 95.1%, respectively. The sensitivity of point-of-care ICT was 100% (95% confidence interval [CI] 94.1%-100%), while specificity was 86.3% (95% CI 73.7%-94.3%). S. pneumoniae caused more than half of paediatric pneumonia with effusion cases; introduction of PCV in the Dominican Republic could reduce the burden by 36-49%. ICT is a practical, valid diagnostic tool for clinical care and surveillance in settings with limited laboratory capacity.

Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

PubMed Central

Dransfield, Mark T.; Harnden, Sarah; Burton, Robert L.; Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Han, MeiLan K.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; McEvoy, Charlene; Nahm, Moon H.; Niewoehner, Dennis E.; Porszasz, Janos; Reilly, John; Scanlon, Paul D.; Scharf, Steven M.; Sciurba, Frank C.; Washko, George R.; Woodruff, Prescott G.; Lazarus, Stephen C.

2012-01-01

Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977. PMID:22652582

Effectiveness of different vaccine schedules for heptavalent and 13-valent conjugate vaccines against pneumococcal disease in the Community of Madrid.

PubMed

Latasa, P; Ordobás, M; Garrido-Estepa, M; Gil de Miguel, A; Sanz, J C; Barranco, M D; Insúa, E; García-Comas, L

2017-09-25

The heptavalent pneumococcal conjugate vaccine (PCV-7) was added to the childhood routine vaccination program in the Community of Madrid in November of 2006 with 3+1 recommended doses and a catch-up for those under 2years old. In June 2010, PCV-7 was replaced by 13-valent vaccine (PCV-13) with 2+1 recommended doses. In July of 2012, the PCV-13 was removed from the funded program and reintroduced again (2+1 recommended doses) in December 2014. In between, children were vaccinated privately with 3+1 recommended doses of PCV-13. The aim of this study was to evaluate the effectiveness of each vaccination schedule used in the Community of Madrid. We included all cases of invasive pneumococcal disease (IPD) reported between 2007 and 2015 to the Notifiable Diseases Surveillance System. Vaccination information was obtained from the Immunization Registry. Vaccine effectiveness (VE) was estimated using the indirect cohort design for cases with serotype information. A total 779 cases were included in the study. Among them 47.6% of the cases were primo-vaccinated with booster, 20% primo-vaccinated, 15.9% incompletely primo-vaccinated and 16.5% not vaccinated. The VE for ≥1 doses of any PCV was 82% (CI 95%: 67.8-89.9%): 91.9% (CI 95%: 76.5-97.2%) for PCV-7 and 77.2% (48.6-89.9%) for PCV-13. VE in those receiving the full 2+1 or 3+1 schedules was 100% for both vaccines. A high number of vaccine failures were reported in children before they had the opportunity to receive the booster dose, especially due to PCV-13-non-PCV-7 serotypes. VE was higher for PCV-7 compared to PCV-13, except for those that received the complete schedule with booster that achieved 100% of VE, which shows the relevance of the vaccines and complying with all doses scheduled. Copyright © 2017 Elsevier Ltd. All rights reserved.

Health benefit for the child and promotion of the common good were the two most important reasons for participation in the FinIP vaccine trial.

PubMed

Nieminen, Heta; Syrjänen, Ritva K; Puumalainen, Taneli; Sirén, Päivi; Palmu, Arto A

2015-07-17

The Finnish Invasive Pneumococcal disease (FinIP) vaccine trial was a nationwide cluster-randomised double-blind trial designed to demonstrate the effectiveness of pneumococcal conjugate vaccine in vaccinated children and indirect effects in unvaccinated populations. Together with the parallel carriage/AOM trial, over 47,000 children were enrolled, 52% of the initial target. We conducted a questionnaire study to find out which factors affected parents' decision on their child's study participation. A questionnaire designed to evaluate parents' attitudes to vaccine trial participation in general and the FinIP trial in particular was mailed after the trial enrolment period had ended to parents of randomly selected children: 1484 who participated in the trial and 1485 who did not participate. Altogether 1438 parents (48%) responded to the questionnaire. The response rate was higher among FinIP participants (65%, 965/1484) than among FinIP non-participants (32%, 473/1485). The two most important reasons for giving consent to the FinIP trial were the potential benefit of immunisation against pneumococcal diseases (75% of consenters) and the promotion of the common good and public health (11%). The reasons reported as most important for declining consent were suspicions of vaccine safety (36%) and the double-blind trial design (12%). Up to 65% of the non-consenters declared that drug and vaccine trials should not be conducted in children at all. The expected health benefit for the child was by far the most important reason for consenting to the vaccine trial. Safety concern was the main reason for decline. Importance and necessity of clinical drug and vaccine trials among children and the rationale of the blinded studies should be thoroughly explained to the public. This may increase participation in future vaccine trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Estimates of Target Population for Pneumococcal Vaccination in People over 50 years in Catalonia and Spain].

PubMed

Vila-Córcoles, Angel; Ochoa-Gondar, Olga; Satué, Eva; de Diego, Cinta; Vila-Rovira, Marc; Jariod, Manel

2017-03-15

Published data about prevalence of distinct risk condictions for pneumococcal disease is scarce. This study investigated the prevalence of distinct risk conditions for pneumococal disease in Catalonian adults and stimated the potential size of target population for pneumococcal vaccination in Catalonia and Spain. Cross-sectional population-based study that included 2,033,465 individuals older than 49 years-old assigned to the Catalonian Health Institute (Catalonia, Spain) at 01/01/2015. The Catalonian Health Institute Information System for the Development of Research in Primary Care (SIDIAP) was used to identify comorbidities and/or underlying conditions in each subject and establish potential target population for pneumococcal vaccination on the basis of their risk for suffering pneumococcal infections: 1) immunocompromised subjects; 2) immunocompetents subjects with any risk condition; 3) immunocompetents subjects without risk conditions. Of the 2,033,465 study subjects, 1,053,155 (51.8%) had no risk conditions, 649,014 (31.9%) had one risk condition and 331,296 (16.3%) had multiple risk conditions (11.4% in 50-64 years vs 21.2% in people older than 65 years, p smaller than 0.001; 21.8% in men vs 11.6% in women, p smaller than 0.001). Overall, 176,600 (8.7%) and 803,710 (39.5%) were classified in risk stratum 1 and 2, respectively. According to distinct risk strata considered, the target population for pneumococcal vaccination varied between 0.2-1.9 million in Catalonia and 1.5-2.3 million in Spain. In our setting, almost fifty percent of people ≥50 years have at least one risk condition to suffert pneumococcal disease. Adult population susceptible for pneumococal vaccination largely varies depending on the risk stratum considered as targeted people for pneumococcal vaccination.

Do influenza and pneumococcal vaccines prevent community-acquired respiratory infections among older people with diabetes and does this vary by chronic kidney disease? A cohort study using electronic health records

PubMed Central

McDonald, Helen I; Thomas, Sara L; Millett, Elizabeth R C; Quint, Jennifer; Nitsch, Dorothea

2017-01-01

Objective We aimed to estimate the effectiveness of influenza and 23-valent pneumococcal polysaccharide vaccination on reducing the burden of community-acquired lower respiratory tract infection (LRTI) among older people with diabetes, and whether this varied by chronic kidney disease (CKD) status. Research design and methods We used linked UK electronic health records for a retrospective cohort study of 190 492 patients ≥65 years with diabetes mellitus and no history of renal replacement therapy, 1997–2011. We included community-acquired LRTIs managed in primary or secondary care. Infection incidence rate ratios were estimated using the Poisson regression. Pneumococcal vaccine effectiveness (VE) was calculated as (1−effect measure). To estimate influenza VE, a ratio-of-ratios analysis (winter effectiveness/summer effectiveness) was used to address confounding by indication. Final VE estimates were stratified according to estimated glomerular filtration rate and proteinuria status. Results Neither influenza nor pneumococcal vaccine uptake varied according to CKD status. Pneumococcal VE was 22% (95% CI 11% to 31%) against community-acquired pneumonia for the first year after vaccination, but was negligible after 5 years. In the ratio-of-ratios analysis, current influenza vaccination had 7% effectiveness for preventing community-acquired LRTI (95% CI 3 to 12). Pneumococcal VE was lower among patients with a history of proteinuria than among patients without proteinuria (p=0.04), but otherwise this study did not identify variation in pneumococcal or influenza VE by markers of CKD. Conclusions The public health benefits of influenza vaccine may be modest among older people with diabetes. Pneumococcal vaccination protection against community-acquired pneumonia declines swiftly: alternative vaccination schedules should be investigated. PMID:28461899

Pneumococcal Colonization Rates in Patients Admitted to a United Kingdom Hospital with Lower Respiratory Tract Infection: a Prospective Case-Control Study

PubMed Central

Johnstone, Catherine M. K.; Gritzfeld, Jenna F.; Banyard, Antonia; Hancock, Carole A.; Wright, Angela D.; Macfarlane, Laura; Ferreira, Daniela M.

2016-01-01

Current diagnostic tests are ineffective for identifying the etiological pathogen in hospitalized adults with lower respiratory tract infections (LRTIs). The association of pneumococcal colonization with disease has been suggested as a means to increase the diagnostic precision. We compared the pneumococcal colonization rates and the densities of nasal pneumococcal colonization by (i) classical culture and (ii) quantitative real-time PCR (qPCR) targeting lytA in patients with LRTIs admitted to a hospital in the United Kingdom and control patients. A total of 826 patients were screened for inclusion in this prospective case-control study. Of these, 38 patients were recruited, 19 with confirmed LRTIs and 19 controls with other diagnoses. Nasal wash (NW) samples were collected at the time of recruitment. Pneumococcal colonization was detected in 1 patient with LRTI and 3 controls (P = 0.6) by classical culture. By qPCR, pneumococcal colonization was detected in 10 LRTI patients and 8 controls (P = 0.5). Antibiotic usage prior to sampling was significantly higher in the LRTI group than in the control group (19 versus 3; P < 0.001). With a clinically relevant cutoff of >8,000 copies/ml on qPCR, pneumococcal colonization was found in 3 LRTI patients and 4 controls (P > 0.05). We conclude that neither the prevalence nor the density of nasal pneumococcal colonization (by culture and qPCR) can be used as a method of microbiological diagnosis in hospitalized adults with LRTI in the United Kingdom. A community-based study recruiting patients prior to antibiotic therapy may be a useful future step. PMID:26791364

Pediatric Acute Otitis Media in the Era of Pneumococcal Vaccination.

PubMed

Tawfik, Kareem O; Ishman, Stacey L; Altaye, Mekibib; Meinzen-Derr, Jareen; Choo, Daniel I

2017-05-01

Objectives (1) Describe longitudinal trends in annual prevalence of hospital admission for pediatric acute otitis media (AOM) and complications of AOM (CAOM) since introduction of pneumococcal vaccination in 2000 and (2) describe the longitudinal trend of prevalence of hospital admission for pneumococcal meningitis in children with AOM-related diagnoses in the postvaccination era. Study Design Retrospective analysis of Kids' Inpatient Database from 2000 to 2012. Setting Community, nonrehabilitation hospitals. Subjects and Methods To determine annual prevalence of admission for AOM/CAOM, nationally weighted frequencies of children aged <21 years with acute suppurative otitis media, acute mastoiditis, suppurative labyrinthitis, and/or acute petrositis were collected. The frequency of coexisting pneumococcal meningitis diagnoses among these patients was also collected. Trend analysis of prevalences of admission for AOM/CAOM and for pneumococcal meningitis occurring in the setting of AOM/CAOM from 2000 to 2012 was performed. Results Between 2000 and 2012, annual prevalence of admission for AOM/CAOM decreased from 3.956 to 2.618 per 100,000 persons ( P < .0001) (relative risk reduction 34%). Declines in admission prevalence were most pronounced in children <1 year of age (from 22.647 to 8.715 per 100,000 persons between 2000 and 2012, P < .0001) and 1 to 2 years of age (from 13.652 to 5.554 per 100,000 persons between 2000 and 2012, P < .0001). For all ages, the admission prevalence for pneumococcal meningitis and concomitant AOM/CAOM decreased (from 1.760 to 0.717 per 1,000,000 persons, P < .0001) over the study period. Conclusions The prevalence of hospital admission for pediatric AOM/CAOM has declined since the advent of pneumococcal vaccination. Admission rates for pneumococcal meningitis with AOM/CAOM have similarly declined.

Cord blood Streptococcus pneumoniae‐specific cellular immune responses predict early pneumococcal carriage in high‐risk infants in Papua New Guinea

PubMed Central

Francis, J. P.; Richmond, P. C.; Strickland, D.; Prescott, S. L.; Pomat, W. S.; Michael, A.; Nadal‐Sims, M. A.; Edwards‐Devitt, C. J.; Holt, P. G.; Lehmann, D.

2016-01-01

Summary In areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high‐risk areas have pre‐existing pneumococcal‐specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA‐induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA‐specific interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐5, IL‐6, IL‐10 and IL‐13 responses, and lower dPly‐IL‐6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA‐IL‐5 and PspA‐IL‐13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly‐IL‐6 responses with a higher frequency of cord antigen‐presenting cells. In the PNG cohort, higher PspA‐specific IL‐5 and IL‐6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA‐IL‐10 CBMC responses. Pneumococcus‐specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease. PMID:27859014

Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis

PubMed Central

2013-01-01

Background Inflammasomes are multi-protein intracellular signaling complexes that have recently been hypothesized to play a role in the regulation of the inflammation response. We studied associations between inflammasome-associated cytokines IL-1β and IL-18 in cerebrospinal fluid (CSF) of patients with bacterial meningitis and clinical outcome, and pneumococcal serotype. In a murine model of pneumococcal meningitis we examined the pathophysiological roles of two inflammasome proteins, NLRP3 (Nod-like receptor protein-3) and adaptor protein ASC (apoptosis-associated speck-like protein). Methods In a nationwide prospective cohort study, CSF cytokine levels were measured and related to clinical outcome and pneumococcal serotype. In a murine model of pneumococcal meningitis using Streptococcus pneumoniae serotype 3, we examined bacterial titers, cytokine profiles and brain histology at 6 and 30 hours after inoculation in wild-type (WT), Asc and Nlrp3 deficient mice. Results In patients with bacterial meningitis, CSF levels of inflammasome associated cytokines IL-1β and IL-18 were related to complications, and unfavorable disease outcome. CSF levels of IL-1β were associated with pneumococcal serotype (p<0.001). In our animal model, Asc and Nlrp3 deficient mice had decreased systemic inflammatory responses and bacterial outgrowth as compared to WT mice. Differences between Asc−/− and WT mice appeared sooner after bacterial inoculation and were more widespread (lower pro-inflammatory cytokine levels in both blood and brain homogenate) than in Nlrp3-/-mice. Nlrp3 deficiency was associated with an increase of cerebral neutrophil infiltration and cerebral hemorrhages when compared to WT controls. Conclusions Our results implicate an important role for inflammasome proteins NLRP3 and ASC in the regulation of the systemic inflammatory response and the development of cerebral damage during pneumococcal meningitis, which may dependent on the pneumococcal serotype. PMID:23902681

Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

NASA Astrophysics Data System (ADS)

May, J. C.; Rey, L.; Lee, Chi-Jen; Arciniega, Juan

2004-09-01

Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

Capture-Recapture Estimators in Epidemiology with Applications to Pertussis and Pneumococcal Invasive Disease Surveillance

PubMed Central

Braeye, Toon; Verheagen, Jan; Mignon, Annick; Flipse, Wim; Pierard, Denis; Huygen, Kris; Schirvel, Carole; Hens, Niel

2016-01-01

Introduction Surveillance networks are often not exhaustive nor completely complementary. In such situations, capture-recapture methods can be used for incidence estimation. The choice of estimator and their robustness with respect to the homogeneity and independence assumptions are however not well documented. Methods We investigated the performance of five different capture-recapture estimators in a simulation study. Eight different scenarios were used to detect and combine case-information. The scenarios increasingly violated assumptions of independence of samples and homogeneity of detection probabilities. Belgian datasets on invasive pneumococcal disease (IPD) and pertussis provided motivating examples. Results No estimator was unbiased in all scenarios. Performance of the parametric estimators depended on how much of the dependency and heterogeneity were correctly modelled. Model building was limited by parameter estimability, availability of additional information (e.g. covariates) and the possibilities inherent to the method. In the most complex scenario, methods that allowed for detection probabilities conditional on previous detections estimated the total population size within a 20–30% error-range. Parametric estimators remained stable if individual data sources lost up to 50% of their data. The investigated non-parametric methods were more susceptible to data loss and their performance was linked to the dependence between samples; overestimating in scenarios with little dependence, underestimating in others. Issues with parameter estimability made it impossible to model all suggested relations between samples for the IPD and pertussis datasets. For IPD, the estimates for the Belgian incidence for cases aged 50 years and older ranged from 44 to58/100,000 in 2010. The estimates for pertussis (all ages, Belgium, 2014) ranged from 24.2 to30.8/100,000. Conclusion We encourage the use of capture-recapture methods, but epidemiologists should preferably include datasets for which the underlying dependency structure is not too complex, a priori investigate this structure, compensate for it within the model and interpret the results with the remaining unmodelled heterogeneity in mind. PMID:27529167

Pneumococcal Capsules and Their Types: Past, Present, and Future

PubMed Central

Geno, K. Aaron; Gilbert, Gwendolyn L.; Song, Joon Young; Skovsted, Ian C.; Klugman, Keith P.; Jones, Christopher; Konradsen, Helle B.

2015-01-01

SUMMARY Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules. PMID:26085553

Pneumococcal Capsules and Their Types: Past, Present, and Future.

PubMed

Geno, K Aaron; Gilbert, Gwendolyn L; Song, Joon Young; Skovsted, Ian C; Klugman, Keith P; Jones, Christopher; Konradsen, Helle B; Nahm, Moon H

2015-07-01

Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Climate induces seasonality in pneumococcal transmission

PubMed Central

Numminen, Elina; Chewapreecha, Claire; Turner, Claudia; Goldblatt, David; Nosten, Francois; Bentley, Stephen D.; Turner, Paul; Corander, Jukka

2015-01-01

Streptococcus pneumoniae is a significant human pathogen and a leading cause of infant mortality in developing countries. Considerable global variation in the pneumococcal carriage prevalence has been observed and the ecological factors contributing to it are not yet fully understood. We use data from a cohort of infants in Asia to study the effects of climatic conditions on both acquisition and clearance rates of the bacterium, finding significantly higher transmissibility during the cooler and drier months. Conversely, the length of a colonization period is unaffected by the season. Independent carriage data from studies conducted on the African and North American continents suggest similar effects of the climate on the prevalence of this bacterium, which further validates the obtained results. Further studies could be important to replicate the findings and explain the mechanistic role of cooler and dry air in the physiological response to nasopharyngeal acquisition of the pneumococcus. PMID:26067932

Climate induces seasonality in pneumococcal transmission.

PubMed

Numminen, Elina; Chewapreecha, Claire; Turner, Claudia; Goldblatt, David; Nosten, Francois; Bentley, Stephen D; Turner, Paul; Corander, Jukka

2015-06-12

Streptococcus pneumoniae is a significant human pathogen and a leading cause of infant mortality in developing countries. Considerable global variation in the pneumococcal carriage prevalence has been observed and the ecological factors contributing to it are not yet fully understood. We use data from a cohort of infants in Asia to study the effects of climatic conditions on both acquisition and clearance rates of the bacterium, finding significantly higher transmissibility during the cooler and drier months. Conversely, the length of a colonization period is unaffected by the season. Independent carriage data from studies conducted on the African and North American continents suggest similar effects of the climate on the prevalence of this bacterium, which further validates the obtained results. Further studies could be important to replicate the findings and explain the mechanistic role of cooler and dry air in the physiological response to nasopharyngeal acquisition of the pneumococcus.

Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older.

PubMed

Jackson, Lisa A; Gurtman, Alejandra; van Cleeff, Martin; Frenck, Robert W; Treanor, John; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

2013-08-02

Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Molecular Characterization of Streptococcus pneumoniae Serotype 12F Isolates Associated with Rural Community Outbreaks in Alaska

PubMed Central

Wenger, Jay D.; Rudolph, Karen; Robinson, D. Ashley; Rakov, Alexey V.; Bruden, Dana; Singleton, Rosalyn J.; Bruce, Michael G.; Hennessy, Thomas W.

2013-01-01

Outbreaks of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 12F were observed in two neighboring regions of rural Alaska in 2003 to 2006 and 2006 to 2008. IPD surveillance data from 1986 to 2009 and carriage survey data from 1998 to 2004 and 2008 to 2009 were reviewed to identify patterns of serotype 12F transmission. Pulsed-field gel electrophoresis was performed on all available isolates, and selected isolates were characterized by additional genetic subtyping methods. Serotype 12F IPD occurred in two waves in Alaska between 1986 and 2008. While cases of disease occurred nearly every year in Anchorage, in rural regions, 12F IPD occurred with rates 10- to 20-fold higher than those in Anchorage, often with many years between disease peaks and generally caused by a single predominant genetic clone. Carriage occurred predominantly in adults, except early in the rural outbreaks, when most carriage was in persons <18 years old. In rural regions, carriage of 12F disappeared completely after outbreaks. Different 12F clones appear to have been introduced episodically into rural populations, spread widely in young, immunologically naïve populations (leading to outbreaks of IPD lasting 1 to 3 years), and then disappeared rapidly from the population. Larger population centers might have been the reservoir for these clones. This epidemiologic pattern is consistent with a highly virulent, but immunogenic, form of pneumococcus. PMID:23408692

Babies and shots

MedlinePlus

... MMR - shots; Pneumococcal - shots; Polio - shots; IPV - shots; Rotavirus - shots; Tdap - shots ... conjugate vaccine Pneumococcal polysaccharide vaccine Polio immunization (vaccine) Rotavirus vaccine Tdap vaccine

New South Wales annual vaccine-preventable disease report, 2012

PubMed Central

Spokes, Paula; Gilmour, Robin

2014-01-01

We aim to describe the epidemiology of selected vaccine-preventable diseases in New South Wales (NSW) for 2012. Data from the NSW Notifiable Conditions Information Management System were analysed by: local health district of residence, age, Aboriginality, vaccination status and organism, where available. Risk factor and vaccination status data were collected by public health units for cases following notification under the NSW Public Health Act 2010. The largest outbreak of measles since 1998 was reported in 2012. Pacific Islander and Aboriginal people were at higher risk as were infants less than 12 months of age. Notifications of invasive pneumococcal disease (IPD) in children less than five years declined; however, the overall number of notifications for IPD increased. Mumps case notifications were also elevated. There were no Haemophilus influenzae type b case notifications in children less than five years of age for the first time since the vaccine was introduced. Invasive meningococcal disease case notifications were at their lowest rates since case notification began in 1991. Case notification rates for other selected vaccine-preventable diseases remained stable. Vaccine-preventable disease control is continually strengthening in NSW with notable successes in invasive bacterial infections. However, strengthening measles immunization in Pacific Islander and Aboriginal communities remains essential to maintain measles elimination. PMID:25077033

New South Wales annual vaccine-preventable disease report, 2012.

PubMed

Rosewell, Alexander; Spokes, Paula; Gilmour, Robin

2014-01-01

We aim to describe the epidemiology of selected vaccine-preventable diseases in New South Wales (NSW) for 2012. Data from the NSW Notifiable Conditions Information Management System were analysed by: local health district of residence, age, Aboriginality, vaccination status and organism, where available. Risk factor and vaccination status data were collected by public health units for cases following notification under the NSW Public Health Act 2010. The largest outbreak of measles since 1998 was reported in 2012. Pacific Islander and Aboriginal people were at higher risk as were infants less than 12 months of age. Notifications of invasive pneumococcal disease (IPD) in children less than five years declined; however, the overall number of notifications for IPD increased. Mumps case notifications were also elevated. There were no Haemophilus influenzae type b case notifications in children less than five years of age for the first time since the vaccine was introduced. Invasive meningococcal disease case notifications were at their lowest rates since case notification began in 1991. Case notification rates for other selected vaccine-preventable diseases remained stable. Vaccine-preventable disease control is continually strengthening in NSW with notable successes in invasive bacterial infections. However, strengthening measles immunization in Pacific Islander and Aboriginal communities remains essential to maintain measles elimination.

Evaluation of pneumococcal vaccination rates after vaccine protocol changes and nurse education in a tertiary care teaching hospital.

PubMed

Smith, Jennifer G; Metzger, Nicole L

2011-11-01

Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post-intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4-month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the criteria included aged 65 years or older, admitting diagnosis of pneumonia, at least 1 of several chronic diseases, immunocompromising condition, cochlear implant, cerebrospinal fluid leak, current tobacco smoking, pregnancy or having a child in the home less than aged 6 months, or awaiting solid organ transplantation. Patients who had vaccine contraindications/precautions or had been vaccinated in the previous 5 years were ineligible. Data on demographics, presence of vaccine screening, indication, administration, rescheduling, and refusal were collected. The primary endpoint was the rate of pneumococcal vaccine administration in eligible medicine patients. Secondary endpoints included changes in screening rates, vaccine refusal, and order rescheduling. Descriptive statistics and Student's t-test were used to evaluate patient demographic data. Pearson chi-square was used to compare the pre- and post-implementation periods. The rate of pneumococcal vaccine administration in eligible patients significantly improved post-implementation compared with pre-implementation (74.2% vs. 19.1%, respectively, P < 0.001). Rates of vaccine screening were similar pre-implementation (96.0%) and post-implementation (99.3%, P = 0.056). The rates of vaccine refusal in the pre- and post-implementation periods did not significantly differ (10.6% vs. 22.6%, respectively, P = 0.203). Implementation of vaccine protocol changes was associated with improved pneumococcal vaccination rates in eligible medicine patients. Protocol changes were relatively easy to implement in a large institution, and a similar approach may be implemented at other institutions as an effective way to improve pneumococcal vaccination rates.

Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes virulence determinants that are dependent or independent of competence induction.

PubMed

Zhu, Luchang; Lin, Jingjun; Kuang, Zhizhou; Vidal, Jorge E; Lau, Gee W

2015-07-01

The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 'late' competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes. © 2015 John Wiley & Sons Ltd.

Identification of PblB mediating galactose-specific adhesion in a successful Streptococcus pneumoniae clone

PubMed Central

Hsieh, Yu-Chia; Lin, Tzu-Lung; Lin, Che-Ming; Wang, Jin-Town

2015-01-01

The pneumococcal genome is variable and there are minimal data on the influence of the accessory genome on phenotype. Pneumococcal serotype 14 sequence type (ST) 46 had been the most prevalent clone causing pneumonia in children in Taiwan. A microarray was constructed using the genomic DNA of a clinical strain (NTUH-P15) of serotype 14 ST46. Using DNA hybridization, genomic variations in NTUH-P15 were compared to those of 3 control strains. Microarray analysis identified 7 genomic regions that had significant increases in hybridization signals in the NTUH-P15 strain compared to control strains. One of these regions encoded PblB, a phage-encoded virulence factor implicated (in Streptococcus mitis) in infective endocarditis. The isogenic pblB mutant decreased adherence to A549 human lung epithelial cell compared to wild-type NTUH-P15 strain (P = 0.01). Complementation with pblB restored the adherence. PblB is predicted to contain a galactose-binding domain-like region. Preincubation of NTUH-P15 with D-galactose resulted in decreases of adherence to A549 cell in a dose-dependent manner. Challenge of mice with NTUH-P15, isogenic pblB mutant and pblB complementation strains determined that PblB was required for bacterial persistence in the nasopharynx and lung. PblB, as an adhesin mediating the galactose-specific adhesion activity of pneumococci, promote pneumococcal clonal success. PMID:26193794

Functional anti-polysaccharide IgG titres induced by unadjuvanted pneumococcal-conjugate vaccine when delivered by microprojection-based skin patch.

PubMed

Pearson, Frances E; Muller, David A; Roalfe, Lucy; Zancolli, Marta; Goldblatt, David; Kendall, Mark A F

2015-11-27

Adequate access to effective and affordable vaccines is essential for the prevention of mortality due to infectious disease. Pneumonia--a consequence of Streptococcus pneumoniae infection--is the world's leading cause of death in children aged under 5 years. The development of a needle-free, thermostable pneumococcal-conjugate vaccine (PCV) could revolutionise the field by reducing cold-chain and delivery constraints. Skin patches have been used to deliver a range of vaccines, with some inducing significantly higher vaccine-specific immunogenicity than needle-injected controls in pre-clinical models, though they have yet to be used to deliver a PCV. We dry-coated a licensed PCV onto a microprojection-based patch (the Nanopatch) and delivered it to mouse skin. We analysed resulting anti-polysaccharide IgG responses. With and without adjuvant, anti-polysaccharide IgG titres induced by Nanopatch immunisation were significantly higher than dose-matched intramuscular controls. These improved responses were primarily obtained against pneumococcal serotypes 4 and 14. Importantly, capsule-specific IgG correlated with functionality in an opsonophagocytic killing assay. We demonstrate enhanced anti-PCV immunogenicity when delivered by Nanopatch over intramuscular injection. As the first study of a PCV delivered by a skin vaccination technology, this report indicates the potential for reduced costs and greater global distribution of such a vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Postintroduction Study of Cost Effectiveness of Pneumococcal Vaccine PCV10 from Public Sector Payer's Perspective in the State of Santa Catarina, Brazil.

PubMed

Kupek, Emil; Viertel, Ilse

2018-05-14

To evaluate cost effectiveness of 10-valent pneumococcal conjugate vaccine in the routine immunization program for children younger than 5 years in Brazil by a postintroduction study. Ecological study of prevaccine (2006-2009) versus postvaccine (2011-2014) period related the changes in mortality rate and hospitalization rate to direct cost of pneumonia treatment from the payer's perspective to estimate the cost effectiveness regarding lives saved, life-years gained, and disability-adjusted life-year for children younger than 5 years in the southern Brazilian state of Santa Catarina. All-cause pneumonia (ICD-10 J12-J18) deaths, hospital admissions, and associated costs were retrieved from the Brazilian Ministry of Health official Web site. Life expectancy at birth, population, ambulatory costs, cost savings, and plausible range of these parameters were used from published sources. Computer simulations with sensitivity analysis were performed to obtain the cost-effectiveness estimates. About 27 lives were saved and 2573 hospitalizations averted by the 10-valent pneumococcal conjugate vaccine vaccination in the 2011 to 2014 period at the cost of US $24,348 per life-year gained and US $27,748 per disability-adjusted life-year. The latter cost is 81% of Brazilian gross domestic product per capita over the same period. The vaccine was very cost-effective according to the World Health Organization criterion. Copyright © 2018. Published by Elsevier Inc.

Lung abscess caused by Streptococcus pneumoniae serotype 6B.

PubMed

Ito, Yuhei; Toyoshima, Hirokazu; Suzuki, Takehiro; Iwamoto, Keisuke; Sasano, Hajime; Itani, Hidetoshi; Kondo, Shigeto; Tanigawa, Motoaki

2018-01-01

Lung abscess has been considered to be a rare complication of pneumococcal infection, and most cases are reported to be Streptococcus pneumoniae serotype 3. A 67-year-old man presented with fever and was diagnosed to have lung abscess caused by S. pneumoniae serotype 6B. The minimal inhibitory concentration (MIC) of penicillin for the isolate was 1 μg/mL. He was treated with high-dose intravenous sulbactam/ampicillin as definitive therapy based on susceptibility testing for S. pneumoniae and recovered successfully without surgical intervention. S. pneumoniae serotype 6B can cause lung abscess.

Operation of pneumococcal polysaccharide radioimmunoassay reference laboratory: coordination of the serological aspects of otitis media field trials. Annual report 28 Jun 77--27 Jun 78

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiffman, G.

1978-04-03

The contract supports a serologic reference laboratory for the performance of radioimmunoassay of antibodies to pneumococcal polysaccharides. Antibody assays have been performed for a number of investigators studying the response of humans to pneumococcal vaccines. In addition, a large quantity of labeled polysaccharides for use in the assay have been prepared and stored.

Safety of the 11-valent pneumococcal vaccine conjugated to non-typeable Haemophilus influenzae-derived protein D in the first 2 years of life and immunogenicity of the co-administered hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio virus, Haemophilus influenzae type b and control hepatitis A vaccines.

PubMed

Prymula, Roman; Chlibek, Roman; Splino, Miroslav; Kaliskova, Eva; Kohl, Igor; Lommel, Patricia; Schuerman, Lode

2008-08-18

This randomized (1:1), double-blind, multicenter study, included 4,968 healthy infants to receive either the 11-valent pneumococcal protein D (PD)-conjugate study vaccine or the hepatitis A vaccine (HAV) (control) at 3, 4, 5, and 12-15 months of age. The three-dose primary course of both vaccines was co-administered with combined hexavalent DTPa-HBV-IPV/Hib vaccine. The pneumococcal PD-conjugate study vaccine did not impact the immune response of co-administered hexavalent vaccine and the control HAV vaccine induced seropositivity (antibodies >or=15 mIU/mL) in all infants. The incidence of solicited symptoms was higher with the 11-valent pneumococcal PD-conjugate study vaccine, yet similar to that induced by concomitant DTPa-HBV-IPV/Hib vaccine. Overall, the reactogenicity and safety profile of the 11-valent pneumococcal PD-conjugate vaccine when co-administered with the hexavalent DTPa-HBV-IPV/Hib vaccine, as well as the immunogenicity of the co-administered hexavalent vaccine, were consistent with previous reports for the licensed DTPa-HBV-IPV/Hib and pneumococcal conjugate vaccines.

Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection

PubMed Central

Zafar, M. Ammar; Kono, Masamitsu; Wang, Yang; Zangari, Tonia

2016-01-01

One of the least understood aspects of the bacterium Streptococcus pneumoniae (pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized “index” pups to uncolonized “contact” pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection. PMID:27400721

Testing Pneumonia Vaccines in the Elderly: Determining a Case Definition for Pneumococcal Pneumonia in the Absence of a Gold Standard.

PubMed

Jokinen, Jukka; Snellman, Marja; Palmu, Arto A; Saukkoriipi, Annika; Verlant, Vincent; Pascal, Thierry; Devaster, Jeanne-Marie; Hausdorff, William P; Kilpi, Terhi M

2018-06-01

Clinical assessments of vaccines to prevent pneumococcal community-acquired pneumonia (CAP) require sensitive and specific case definitions, but there is no gold standard diagnostic test. To develop a new case definition suitable for vaccine efficacy studies, we applied latent class analysis (LCA) to the results from 7 diagnostic tests for pneumococcal etiology on clinical specimens from 323 elderly persons with radiologically confirmed pneumonia enrolled in the Finnish Community-Acquired Pneumonia Epidemiology study during 2005-2007. Compared with the conventional use of LCA, which is mainly to determine sensitivities and specificities of different tests, we instead used LCA as an appropriate instrument to predict the probability of pneumococcal etiology for each CAP case based on individual test profiles, and we used the predictions to minimize the sample size that would be needed for a vaccine efficacy trial. When compared with the conventional laboratory criteria of encapsulated pneumococci in culture, in blood culture or high-quality sputum culture, or urine antigen positivity, our optimized case definition for pneumococcal CAP resulted in a trial sample size that was almost 20,000 subjects smaller. We believe that the novel application of LCA detailed here to determine a case definition for pneumococcal CAP could also be similarly applied to other diseases without a gold standard.

Otitis-Prone Children Produce Functional Antibodies to Pneumolysin and Pneumococcal Polysaccharides

PubMed Central

Wiertsema, Selma P.; Corscadden, Karli J.; Mateus, Tulia; Mullaney, Gemma L.; Zhang, Guicheng; Richmond, Peter C.; Thornton, Ruth B.

2016-01-01

ABSTRACT The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group (P < 0.05). The production of functional antipneumococcal antibodies in otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children. PMID:28031178

Cost-effectiveness analysis of pneumococcal polysaccharide vaccination from age 60 in São Paulo State, Brazil.

PubMed

Neto, Joao Tonolio; de Araujo, Gabriela Tannus Branco; Gagliardi, Anna; Pinho, Amanda; Durand, Laure; Fonseca, Marcelo

2011-10-01

Vaccination of adults aged 60 years and older against Streptococcus pneumonia is not recommended in Brazil. The 23-valent polysaccharide pneumococcal vaccine (PPV23) is only available for institutionalized persons or with underlying diseases despite the substantial medical and economic burden related to pneumococcal infections in adults over than 59 years. The study aimed at evaluating the cost effectiveness of implementing a large PPV program in this population. This analysis was performed using a static decision tree model. Demographic and epidemiological data were obtained from Brazilian official sources and international literature. Economic data were obtained from a study performed in 2007 in a public and a private hospital located in Sao Paulo. Vaccination was assumed to protect for 5 years with 60% effectiveness against bacteremic pneumococcal pneumonia (BPP) and 21% effectiveness against non bacteremic pneumococcal pneumonia (NBPP). Deterministic and sensitivity analyses were performed. The pneumococcal polysaccharide vaccination saved 5,218 life year gained (LYG). The vaccination program was found to be cost effective in the social security and public health care perspectives with a mean incremental cost-effectiveness ratio of R$10,887 and R$8,281 per LYG respectively. Results were sensitive to the vaccine effectiveness against NBPP, the incidence and case-fatality rate of NBPP. From a societal perspective, PPV23 program for adults 60 and older was found to be cost-saving. Pneumococcal polysaccharide vaccination is clinically and economically favored over the present vaccination strategy, in which persons aged over 59 years in Sao Paulo, have not been vaccinated.

Determinants of adult vaccination at inner-city health centers: a descriptive study.

PubMed

Nowalk, Mary Patricia; Zimmerman, Richard K; Tabbarah, Melissa; Raymund, Mahlon; Jewell, Ilene K

2006-01-10

Pneumococcal polysaccharide vaccination rates among adults 65 years and older or less than 65 years with high risk medical conditions are still below Healthy People 2010 recommended levels of 90%. This study was designed to: 1) assess self-reported pneumococcal vaccination rates following health center level interventions to increase adult vaccination rates; and 2) determine factors associated with vaccination. Tailored interventions to increase immunizations were implemented at two inner-city health centers. We surveyed 375 patients 50 years of age and older. Multivariate logistic regression examines the predictors of 1) self-reported pneumococcal vaccination and 2) combined self-reported influenza and pneumococcal vaccination. Both of these models were stratified by age group (50-64 years and 65 years and older). Pneumococcal vaccination rates were 45% by self-report, 55% by medical record review, 69% for patients 65 years old and older, 32% for patients 50-64 years; they did not differ by race. Receipt of the previous season's influenza vaccine was significantly related to pneumococcal vaccination among both younger and older patients. Receiving both the pneumococcal vaccine and the most recent influenza vaccine compared with receiving neither, among younger patients was related to unemployment, more frequent physician visits, and belief that those who do not receive the flu shot are more susceptible to the flu. For older patients, receipt of both vaccines was related to nonsmoking status, believing that friends/family think the patient should be vaccinated, seeing posters advertising flu shot clinics, and belief that those who do not receive the flu shot are more susceptible to the flu. Our findings suggest that improving overall pneumococcal vaccination rates among eligible adults, has the potential to eliminate racial disparities. Interventions delivering vaccination messages specific to older and younger adult groups may be the best strategy for improving adult vaccination rates.

The effect of physicians' awareness on influenza and pneumococcal vaccination rates and correlates of vaccination in patients with diabetes in Turkey: an epidemiological Study "diaVAX".

PubMed

Satman, Ilhan; Akalin, Sema; Cakir, Bekir; Altinel, Serdar

2013-12-01

We aimed to examine the effect of increased physician awareness on the rate and determinants of influenza and pneumococcal vaccinations in diabetic patients. Diabetic patients (n = 5682, mean [SD] age: 57.3 [11.6] years, 57% female) were enrolled by 44 physicians between Sept 2010 and Jan 2011. The physicians were initially questioned regarding vaccination practices, and then, they attended a training program. During the last five years, the physicians recommended influenza and pneumococcal vaccinations to 87.9% and 83.4% of the patients, respectively; however; only 27% of the patients received the influenza and 9.8% received the pneumococcal vaccines. One year after the training, the vaccination rates increased to 63.3% and 40.7%, respectively. The logistic regression models revealed that variables which increased the likelihood of having been vaccinated against influenza were: longer duration of diabetes, presence of hyperlipidemia and more use of concomitant medications whereas more use of anti-hyperglycemic medications was associated with increased odds of vaccination. On the other hand, older age, longer duration of diabetes and presence of a cardiovascular disease were variables which decreased the likelihood of having been vaccinated against pneumococcal disease during the past five years. However, during the study period, variables which decreased the odds of having been vaccinated included: older age and anti-hyperglycemic medications for influenza, and presence of hyperlipidemia and a family history of hypertension for pneumococcal disease. While variables which increased the likelihood of vaccination in the same period were: increased number of co-morbidities for influenza, and family history of diabetes for pneumococcal disease. We conclude that increased awareness of physicians may help improve vaccination rates against influenza and pneumococcal disease. However, diabetic patients with more severe health conditions are less likely to having been vaccinated. More structural/systematic vaccination programs are needed to increase the vaccination rates in patients with diabetes.

Association of Streptococcus pneumoniae common protein antigen (CPA) antibodies and pneumococcal nasopharyngeal colonization in HIV-infected and HIV-uninfected African children.

PubMed

Ditse, Z; Adrian, P V; Kuwanda, L; Madhi, S A

2013-09-13

Due to the high cost and limited serotype coverage of pneumococcal conjugate vaccines (PCV), pneumococcal common protein antigens (CPAs) are being investigated as potential vaccine candidates. CPAs are likely to be immunogenic in infants and could confer serotype-independent protection. There are limited data on natural antibody kinetics against CPAs in African populations. We aimed to determine the prevalence of naturally acquired antibody titres to 15 CPAs and explore their association to concurrent pneumococcal nasopharyngeal colonization in children aged 4-7 years with and without underlying HIV-infection and/or previous PCV-vaccination. A 15-plex Luminex assay was established to measure serum IgG titres against "cell-wall associated or surface-exposed" proteins (PspA, PspC, LytB, IgA1-proteinase, SP0082, PdB and PcsB), "membrane-associated" proteins (PsaA, SP0609, SP0749, PpmA, SlrA, StkP and SP2194) as well as the hypothetical protein, SP2027. Archived serum samples from HIV-uninfected (n=212) and HIV-infected (n=74) children were analyzed. Concurrent pneumococcal nasopharyngeal colonization was determined with standard microbiological methods. HIV-uninfected children had significantly higher antibody titres against PspA, PspC, PdB, SP0082, LytB, IgA1 proteinase and PcsB compared to HIV-infected children. In contrast, antibody titres against membrane associated proteins (PsaA, SP2027, PpmA and SlrA) were significantly lower in HIV-uninfected compared to HIV-infected children. Higher antibody titres against PdB, and PcsB were associated with the absence of pneumococcal colonization. There was no association between anti-CPA titres and PCV vaccination. In conclusion PdB and PcsB antigens are potential vaccine-candidates which may protect against pneumococcal colonization and consequently pneumococcal disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unraveling the Pore-Forming Steps of Pneumolysin from Streptococcus pneumoniae.

PubMed

van Pee, Katharina; Mulvihill, Estefania; Müller, Daniel J; Yildiz, Özkan

2016-12-14

Pneumolysin (PLY) is the main virulence factor of Streptococcus pneumoniae that causes pneumonia, meningitis, and invasive pneumococcal infection. PLY is produced as monomers, which bind to cholesterol-containing membranes, where they oligomerize into large pores. To investigate the pore-forming mechanism, we determined the crystal structure of PLY at 2.4 Å and used it to design mutants on the surface of monomers. Electron microscopy of liposomes incubated with PLY mutants revealed that several mutations interfered with ring formation. Mutants that formed incomplete rings or linear arrays had strongly reduced hemolytic activity. By high-resolution time-lapse atomic force microscopy of wild-type PLY, we observed two different ring-shaped complexes. Most of the complexes protruded ∼8 nm above the membrane surface, while a smaller number protruded ∼11 nm or more. The lower complexes were identified as pores or prepores by the presence or absence of a lipid bilayer in their center. The taller complexes were side-by-side assemblies of monomers of soluble PLY that represent an early form of the prepore. Our observations suggest a four-step mechanism of membrane attachment and pore formation by PLY, which is discussed in the context of recent structural models. The functional separation of these steps is necessary for the understanding how cholesterol-dependent cytolysins form pores and lyse cells.

Estimating meningitis hospitalization rates for sentinel hospitals conducting invasive bacterial vaccine-preventable diseases surveillance.

PubMed

2013-10-04

The World Health Organization (WHO)-coordinated Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) sentinel hospital surveillance network provides data for decision making regarding use of pneumococcal conjugate vaccine and Haemophilus influenzae type b (Hib) vaccine, both recommended for inclusion in routine childhood immunization programs worldwide. WHO recommends that countries conduct sentinel hospital surveillance for meningitis among children aged <5 years, including collection of cerebrospinal fluid (CSF) for laboratory detection of bacterial etiologies. Surveillance for pneumonia and sepsis are recommended at selected hospitals with well-functioning laboratories where meningitis surveillance consistently meets process indicators (e.g., surveillance performance indicators). To use sentinel hospital surveillance for meningitis to estimate meningitis hospitalization rates, WHO developed a rapid method to estimate the number of children at-risk for meningitis in a sentinel hospital catchment area. Monitoring changes in denominators over time using consistent methods is essential for interpreting changes in sentinel surveillance incidence data and for assessing the effect of vaccine introduction on disease epidemiology. This report describes the method and its use in The Gambia and Senegal.

The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck

PubMed Central

Furi, Leonardo; Braccini, Tiziana; Manso, Ana Sousa; Pammolli, Andrea; Wang, Bo; Vivi, Antonio; Tassini, Maria; van Rooijen, Nico; Pozzi, Gianni; Ricci, Susanna; Andrew, Peter W.; Koedel, Uwe; Moxon, E. Richard; Oggioni, Marco R.

2014-01-01

The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease. PMID:24651834

Issues and Challenges in the Development of Pneumococcal Protein Vaccines: A Two Day International Symposium

PubMed Central

Ginsburg, Amy S.; Nahm, Moon H.; Khambaty, Farukh M.; Alderson, Mark R.

2013-01-01

In view of the increasing licensure and use of pneumococcal conjugate vaccines (PCVs), their relatively high cost, and growing issues with serotype emergence, there is a need to re-evaluate the role of pneumococcal protein vaccines (PPVs) and pathways to their licensure. This paper summarizes the discussion and viewpoints from an expert meeting regarding the development of PPVs. A wide spectrum of pneumococcal vaccine researchers, developers, and regulators met to review the state of PPVs, identify research and development needs, and provide consensus opinions to support the introduction of new PPVs where possible. They also discussed clinical and regulatory aspects pertinent to these vaccines and generated a series of recommendations for moving the field forward. PMID:22380821

Pneumococcal Conjugate Vaccine and Pneumonia Prevention in Children with Congenital Heart Disease.

PubMed

Solórzano-Santos, Fortino; Espinoza-García, Lilia; Aguilar-Martínez, Glorinella; Beirana-Palencia, Luisa; Echániz-Avilés, Gabriela; Miranda-Novales, Guadalupe

2017-01-01

A successful strategy to prevent Streptococcus pneumoniae infections is the administration of pneumococcal conjugate vaccines (PCVs). To analyze the effectiveness of the 7- and 13-valent PCV for the prevention of all-cause pneumonia. A retrospective cohort of children younger than 5 years of age, with congenital heart disease (CHD) and different vaccination schedules, was analyzed. History of vaccination was confirmed with verifiable records. The outcome measure was all-cause pneumonia or bronchopneumonia. Protocol was approved by the Institutional Review Board. For comparisons, we used inferential statistics with Chi-square and Fisher's exact test; a p ≤ 0.5 was considered statistically significant. Relative and absolute risks reduction and number needed to treat were also calculated. A total of 348 patients were included: 196 with two or more doses of PCV (considered the vaccinated group), and 152 in the unvaccinated group. There was a statistically significant difference for pneumonia events (p < 0.001) between the vaccinated (26/196) and unvaccinated (51/152) groups. The relative risk reduction was 60.5%, and the absolute risk reduction, 20.3%. There were no differences between patients who received two, three or four doses. The number needed to vaccinate to prevent one event of pneumonia was 5 children. At least two doses of PCV in children with CHD reduced the risk of all-cause pneumonia.

Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

PubMed

Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Ceretta, Renan A; Dominguini, Diogo; Ferrari, Pâmela; Gubert, Carolina; Jornada, Luciano K; Budni, Josiane; Kapczinski, Flávio; Quevedo, João

2014-10-01

Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis. © 2014 by the Society for Experimental Biology and Medicine.

Using Standardized Interpretation of Chest Radiographs to Identify Adults with Bacterial Pneumonia--Guatemala, 2007-2012.

PubMed

Wortham, Jonathan M; Gray, Jennifer; Verani, Jennifer; Contreras, Carmen Lucia; Bernart, Chris; Moscoso, Fabiola; Moir, Juan Carlos; Reyes Marroquin, Emma Lissette; Castellan, Rigoberto; Arvelo, Wences; Lindblade, Kim; McCracken, John P

2015-01-01

Bacterial pneumonia is a leading cause of illness and death worldwide, but quantifying its burden is difficult due to insensitive diagnostics. Although World Health Organization (WHO) protocol standardizes pediatric chest radiograph (CXR) interpretation for epidemiologic studies of bacterial pneumonia, its validity in adults is unknown. Patients (age ≥ 15 years) admitted with respiratory infections to two Guatemalan hospitals between November 2007 and March 2012 had urine and nasopharyngeal/oropharyngeal (NP/OP) swabs collected; blood cultures and CXR were also performed at physician clinical discretion. 'Any bacterial infection' was defined as a positive urine pneumococcal antigen test, isolation of a bacterial pneumonia pathogen from blood culture, or detection of an atypical bacterial pathogen by polymerase chain reaction (PCR) of nasopharyngeal/oropharyngeal (NP/OP) specimens. 'Viral infection' was defined as detection of viral pathogens by PCR of NP/OP specimens. CXRs were interpreted according to the WHO protocol as having 'endpoint consolidation', 'other infiltrate', or 'normal' findings. We examined associations between bacterial and viral infections and endpoint consolidation. Urine antigen and/or blood culture results were available for 721 patients with CXR interpretations; of these, 385 (53%) had endpoint consolidation and 253 (35%) had other infiltrate. Any bacterial infection was detected in 119 (17%) patients, including 106 (89%) pneumococcal infections. Any bacterial infection (Diagnostic Odds Ratio [DOR] = 2.9; 95% confidence Interval (CI): 1.3-7.9) and pneumococcal infection (DOR = 3.4; 95% CI: 1.5-10.0) were associated with 'endpoint consolidation', but not 'other infiltrate' (DOR = 1.7; 95% CI: 0.7-4.9, and 1.7; 95% CI: 0.7-4.9 respectively). Viral infection was not significantly associated with 'endpoint consolidation', 'other infiltrate,' or 'normal' findings. 'Endpoint consolidation' was associated with 'any bacterial infection,' specifically pneumococcal infection. Therefore, endpoint consolidation may be a useful surrogate for studies measuring the impact of interventions, such as conjugate vaccines, against bacterial pneumonia.

Restoration of Akt activity by the bisperoxovanadium compound bpV(pic) attenuates hippocampal apoptosis in experimental neonatal pneumococcal meningitis

PubMed Central

Sury, Matthias D; Vorlet-Fawer, Lorianne; Agarinis, Claudia; Yousefi, Shida; Grandgirard, Denis; Leib, Stephen L; Christen, Stephan

2010-01-01

Pneumococcal meningitis causes apoptosis of developing neurons in the dentate gyrus of the hippocampus. The death of these cells is accompanied with long-term learning and memory deficits in meningitis survivors. Here, we studied the role of the PI3K/Akt (protein kinase B) survival pathway in hippocampal apoptosis in a well-characterized infant rat model of pneumococcal meningitis. Meningitis was accompanied by a significant decrease of the PI3K product phosphatidylinositol 3,4,5-triphosphate (PIP3) and of phosphorylated (i.e., activated) Akt in the hippocampus. At the cellular level, phosphorylated Akt was decreased in both the granular layer and the subgranular zone of the dentate gyrus, the region where the developing neurons undergo apoptosis. Protein levels and activity of PTEN, the major antagonist of PI3K, were unaltered by infection, suggesting that the observed decrease in PIP3 and Akt phosphorylation is a result of decreased PI3K signaling. Treatment with the PTEN inhibitor bpV(pic) restored Akt activity and significantly attenuated hippocampal apoptosis. Co-treatment with the specific PI3K inhibitor LY294002 reversed restoration of Akt activity and attenuation of hippocampal apoptosis, while it had no significant effect on these parameters on its own. These results indicate that the inhibitory effect of bpV(pic) on apoptosis was mediated by PI3K-dependent activation of Akt, strongly suggesting that bpV(pic) acted on PTEN. Treatment with bpV(pic) also partially inhibited the concentration of bacteria and cytokines in the CSF, but this effect was not reversed by LY294002, indicating that the effect of bpV(pic) on apoptosis was independent of its effect on CSF bacterial burden and cytokine levels. These results indicate that the PI3K/Akt pathway plays an important role in the death and survival of developing hippocampal neurons during the acute phase of pneumococcal meningitis. PMID:20875857

[Incidence of admissions due to pneumonia in children under 24 months old before and after the introduction of the 10-valent pneumococcal conjugate vaccine into the National Immunization Program of Chile].

PubMed

Fernández V, José Pablo; Goecke H, Carola; von Borries, Cecilia; Tapia R, Natalia; Santolaya de P, María Elena

2015-01-01

Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children, especially in the hospitalized population. The 10-valent pneumococcal vaccine was included in the National Immunization Program of Chile in 2011. This study aims to evaluate the incidence of pneumonia in hospitalized children<24 months of age in the Luis Calvo Mackenna Hospital before and after the introduction of the pneumococcal vaccine into the National Immunization Program. Passive surveillance study. Patients<24 months with discharge diagnosis of bacterial pneumonia from Luis Calvo Mackenna Hospital were studied between 2009 and 2013. Data were obtained from the Luis Calvo Mackenna Hospital's Statistical Service. The incidence of pneumonia was evaluated in the pre-vaccination period (2009-2010) and in the post-vaccination period (2012-2013). During the study period, an average of 4,321 discharges/year was observed in children<24 months (range: 3,587-4,702), with a significant decrease from pre- to post-vaccination vaccine period (4,644 vs 4,013, P<.001). The average incidence of pneumonia ranged from 3.4/100,000 to 1.5/100,000 in the pre- and post-vaccine period, respectively (P=.009), with an annual mean of 157 cases of pneumonia in the pre- vaccine period, and 62 cases in the postvaccine period (P<.001) and a decrease in incidence between the two periods of 56%. This study confirms information previously obtained in other countries, which show a decrease in the incidence of pneumonia associated with the implementation of a pneumococcal vaccine at the population level. Ongoing surveillance is required to evaluate if this effect is maintained over time and expands to older populations. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

PubMed Central

Rodrigues, Tasson C.; Oliveira, Maria Leonor S.; Soares-Schanoski, Alessandra; Chavez-Rico, Stefanni L.; Figueiredo, Douglas B.; Gonçalves, Viviane M.; Ferreira, Daniela M.; Kunda, Nitesh K.; Saleem, Imran Y.

2018-01-01

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles—NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2. PMID:29360883

The health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) during an annual influenza epidemic and influenza pandemic in China.

PubMed

Caldwell, Ronald; Roberts, Craig S; An, Zhijie; Chen, Chieh-I; Wang, Bruce

2015-07-24

China has experienced several severe outbreaks of influenza over the past century: 1918, 1957, 1968, and 2009. Influenza itself can be deadly; however, the increase in mortality during an influenza outbreak is also attributable to secondary bacterial infections, specifically pneumococcal disease. Given the history of pandemic outbreaks and the associated morbidity and mortality, we investigated the cost-effectiveness of a PCV7 vaccination program in China from the context of typical and pandemic influenza seasons. A decision-analytic model was employed to evaluate the impact of a 7-valent pneumococcal vaccine (PCV7) infant vaccination program on the incidence, mortality, and cost associated with pneumococcal disease during a typical influenza season (15% flu incidence) and influenza pandemic (30% flu incidence) in China. The model incorporated Chinese data where available and included both direct and indirect (herd) effects on the unvaccinated population, assuming a point in time following the initial introduction of the vaccine where the impact of the indirect effects has reached a steady state, approximately seven years following the implementation of the vaccine program. Pneumococcal disease incidence, mortality, and costs were evaluated over a one year time horizon. Healthcare costs were calculated using a payer perspective and included vaccination program costs and direct medical expenditures from pneumococcal disease. The model predicted that routine PCV7 vaccination of infants in China would prevent 5,053,453 cases of pneumococcal disease and 76,714 deaths in a single year during a normal influenza season.The estimated incremental-cost-effectiveness ratios were ¥12,281 (US$1,900) per life-year saved and ¥13,737 (US$2,125) per quality-adjusted-life-year gained. During an influenza pandemic, the model estimated that routine vaccination with PCV7 would prevent 8,469,506 cases of pneumococcal disease and 707,526 deaths, and would be cost-saving. Routine vaccination with PCV7 in China would be a cost-effective strategy at limiting the negative impact of influenza during a typical influenza season. During an influenza pandemic, the benefit of PCV7 in preventing excess pneumococcal morbidity and mortality renders a PCV7 vaccination program cost-saving.

The LuxS/AI-2 Quorum-Sensing System of Streptococcus pneumoniae Is Required to Cause Disease, and to Regulate Virulence- and Metabolism-Related Genes in a Rat Model of Middle Ear Infection.

PubMed

Yadav, Mukesh K; Vidal, Jorge E; Go, Yoon Y; Kim, Shin H; Chae, Sung-Won; Song, Jae-Jun

2018-01-01

Objective: Streptococcus pneumoniae colonizes the nasopharynx of children, and from nasopharynx it could migrate to the middle ear and causes acute otitis media (AOM). During colonization and AOM, the pneumococcus forms biofilms. In vitro biofilm formation requires a functional LuxS/AI-2 quorum-sensing system. We investigated the role of LuxS/AI-2 signaling in pneumococcal middle ear infection, and identified the genes that are regulated by LuxS/AI-2 during pneumococcal biofilm formation. Methods: Streptococcus pneumoniae D39 wild-type and an isogenic D39Δ luxS strain were utilized to evaluate in vitro biofilm formation, and in vivo colonization and epithelial damage using a microtiter plate assay and a rat model of pneumococcal middle ear infection, respectively. Biofilm structures and colonization and epithelial damage were evaluated at the ultrastructural level by scanning electron microscopy and confocal microscopy. Microarrays were used to investigate the global genes that were regulated by LuxS/AI-2 during biofilm formation. Results: The biofilm biomass and density of D39Δ luxS were significantly ( p < 0.05) lower than those of D39 wild-type. SEM and confocal microscopy revealed that D39Δ luxS formed thin biofilms in vitro compared with D39 wild-type. The in vivo model of middle ear infection showed that D39Δ luxS resulted in ~60% less ( p < 0.05) bacterial colonization than the wild-type. SEM analysis of the rat middle ears revealed dense biofilm-like cell debris deposited on the cilia in wild-type D39-infected rats. However, little cell debris was deposited in the middle ears of the D39Δ luxS -inoculated rats, and the cilia were visible. cDNA-microarray analysis revealed 117 differentially expressed genes in D39Δ luxS compared with D39 wild-type. Among the 66 genes encoding putative proteins and previously characterized proteins, 60 were significantly downregulated, whereas 6 were upregulated. Functional annotation revealed that genes involved in DNA replication and repair, ATP synthesis, capsule biosynthesis, cell division, the cell cycle, signal transduction, transcription regulation, competence, virulence, and carbohydrate metabolism were downregulated in the absence of LuxS/AI-2. Conclusion: The S. pneumoniae LuxS/AI-2 quorum-sensing system is necessary for biofilm formation and the colonization of the ear epithelium, and caused middle ear infection in the rat model. LuxS/AI-2 regulates the expression of the genes involved in virulence and bacterial fitness during pneumococcal biofilm formation.

Clinical and microbiological characterization of serotype 6D pneumococcal infections in South Korea.

PubMed

Cheong, Hee Jin; Song, Joon Young; Choi, Min Joo; Jeon, Ji Ho; Kang, Seong Hee; Jeong, Eun Joo; Noh, Ji Yun; Kim, Woo Joo

2016-08-01

The prevalence of Serotype 6D Streptococcus pneumoniae was reported relatively high in South Korea. Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), serotype replacement was observed. This study was designed to better clarify genetic diversity of pneumococcal serotype 6D and its clinical characteristics after introduction of PCV7 in 2000. We performed serotyping analysis with 1298 pneumococcal isolates from clinical specimens in South Korea from 2004 to 2011. Multilocus sequence typing was performed, and minimal inhibitory concentration was determined for the available serotype 6D and nontypeable (NT) pneumococcal isolates during the 2006-2007 period. The proportion of serotype 6D pneumococci increased from 0.8% (2004-2007) to 2.9% (2008-2011) of all clinical pneumococcal isolates, accounting for 14.9% of serogroup 6 pneumococci in South Korea. NT pneumococci markedly increased to 13.3% during 2006-2007 in advance of the increase in serotype 6D. Among the 26 available serotype 6D pneumococcal isolates, ST282 was predominant (23 isolates, 88.5%). The STs of NT pneumococci (26 isolates) were diverse, but clonal complex 271 was the dominant clone. The oral penicillin non-susceptibility rate was 92.3% (24 among 26 isolates) for both serotype 6D and NT pneumococci. The ceftriaxone non-susceptibility rates of serotype 6D and NT pneumococci were 7.7% and 3.8%, respectively. ST228(6D) strain expanded, particularly among old adults with comorbidities in South Korea. Both antibiotic and PCV7 pressure might have contributed to the selective increase of NT and serotype 6D pneumococci. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Successful introduction of an underutilized elderly pneumococcal vaccine in a national immunization program by integrating the pre-existing public health infrastructure.

PubMed

Yang, Tae Un; Kim, Eunsung; Park, Young-Joon; Kim, Dongwook; Kwon, Yoon Hyung; Shin, Jae Kyong; Park, Ok

2016-03-18

Although pneumococcal vaccines had been recommended for the elderly population in South Korea for a considerable period of time, the coverage has been well below the optimal level. To increase the vaccination rate with integrating the pre-existing public health infrastructure and governmental funding, the Korean government introduced an elderly pneumococcal vaccination into the national immunization program with a 23-valent pneumococcal polysaccharide vaccine in May 2013. The aim of this study was to assess the performance of the program in increasing the vaccine coverage rate and maintaining stable vaccine supply and safe vaccination during the 20 months of the program. We qualitatively and quantitatively analyzed the process of introducing and the outcomes of the program in terms of the systematic organization, efficiency, and stability at the national level. A staggered introduction during the first year utilizing the public sector, with a target coverage of 60%, was implemented based on the public demand for an elderly pneumococcal vaccination, vaccine supply capacity, vaccine delivery capacity, safety, and sustainability. During the 20-month program period, the pneumococcal vaccine coverage rate among the population aged ≥65 years increased from 5.0% to 57.3% without a noticeable vaccine shortage or safety issues. A web-based integrated immunization information system, which includes the immunization registry, vaccine supply chain management, and surveillance of adverse events following immunization, reduced programmatic errors and harmonized the overall performance of the program. Introduction of an elderly pneumococcal vaccination in the national immunization program based on strong government commitment, meticulous preparation, financial support, and the pre-existing public health infrastructure resulted in an efficient, stable, and sustainable increase in vaccination coverage. Copyright © 2016. Published by Elsevier Ltd.

Factors predictive of increased influenza and pneumococcal vaccination coverage in long-term care facilities: the CMS-CDC standing orders program Project.

PubMed

Bardenheier, Barbara H; Shefer, Abigail; McKibben, Linda; Roberts, Henry; Rhew, David; Bratzler, Dale

2005-01-01

Between 1999 and 2002, a multistate demonstration project was conducted in long-term care facilities (LTCFs) to encourage implementation of standing orders programs (SOP) as evidence-based vaccine delivery strategies to increase influenza and pneumococcal vaccination coverage in LTCFs. Examine predictors of increase in influenza and pneumococcal vaccination coverage in LTCFs. Intervention study. Self-administered surveys of LTCFs merged with data from OSCAR (On-line Survey Certification and Reporting System) and immunization coverage was abstracted from residents' medical charts in LTCFs. Twenty LTCFs were sampled from 9 intervention and 5 control states in the 2000 to 2001 influenza season for baseline and during the 2001 to 2002 influenza season for postintervention. Each state's quality improvement organization (QIO) promoted the use of standing orders for immunizations as well as other strategies to increase immunization coverage among LTCF residents. Multivariate analysis included Poisson regression to determine independent predictors of at least a 10 percentage-point increase in facility influenza and pneumococcal vaccination coverage. Forty-two (20%) and 59 (28%) of the facilities had at least a 10 percentage-point increase in influenza and pneumococcal immunizations, respectively. In the multivariate analysis, predictors associated with increase in influenza vaccination coverage included adoption of requirement in written immunization protocol to document refusals, less-demanding consent requirements, lower baseline influenza coverage, and small facility size. Factors associated with increase in pneumococcal vaccination coverage included adoption of recording pneumococcal immunizations in a consistent place, affiliation with a multifacility chain, and provision of resource materials. To improve the health of LTCF residents, strategies should be considered that increase immunization coverage, including written protocol for immunizations and documentation of refusals, documenting vaccination status in a consistent place in medical records, and minimal consent requirements for vaccinations.

220D-F2 from Rubus ulmifolius kills Streptococcus pneumoniae planktonic cells and pneumococcal biofilms.

PubMed

Talekar, Sharmila J; Chochua, Sopio; Nelson, Katie; Klugman, Keith P; Quave, Cassandra L; Vidal, Jorge E

2014-01-01

Streptococcus pneumoniae (pneumococcus) forms organized biofilms to persist in the human nasopharynx. This persistence allows the pneumococcus to produce severe diseases such as pneumonia, otitis media, bacteremia and meningitis that kill nearly a million children every year. While bacteremia and meningitis are mediated by planktonic pneumococci, biofilm structures are present during pneumonia and otitis media. The global emergence of S. pneumoniae strains resistant to most commonly prescribed antibiotics warrants further discovery of alternative therapeutics. The present study assessed the antimicrobial potential of a plant extract, 220D-F2, rich in ellagic acid, and ellagic acid derivatives, against S. pneumoniae planktonic cells and biofilm structures. Our studies first demonstrate that, when inoculated together with planktonic cultures, 220D-F2 inhibited the formation of pneumococcal biofilms in a dose-dependent manner. As measured by bacterial counts and a LIVE/DEAD bacterial viability assay, 100 and 200 µg/ml of 220D-F2 had significant bactericidal activity against pneumococcal planktonic cultures as early as 3 h post-inoculation. Quantitative MIC's, whether quantified by qPCR or dilution and plating, showed that 80 µg/ml of 220D-F2 completely eradicated overnight cultures of planktonic pneumococci, including antibiotic resistant strains. When preformed pneumococcal biofilms were challenged with 220D-F2, it significantly reduced the population of biofilms 3 h post-inoculation. Minimum biofilm inhibitory concentration (MBIC)50 was obtained incubating biofilms with 100 µg/ml of 220D-F2 for 3 h and 6 h of incubation. 220D-F2 also significantly reduced the population of pneumococcal biofilms formed on human pharyngeal cells. Our results demonstrate potential therapeutic applications of 220D-F2 to both kill planktonic pneumococcal cells and disrupt pneumococcal biofilms.

Streptococcus pneumoniae and Haemophilus influenzae in paediatric meningitis patients at Goroka General Hospital, Papua New Guinea: serotype distribution and antimicrobial susceptibility in the pre-vaccine era.

PubMed

Greenhill, Andrew R; Phuanukoonnon, Suparat; Michael, Audrey; Yoannes, Mition; Orami, Tilda; Smith, Helen; Murphy, Denise; Blyth, Christopher; Reeder, John; Siba, Peter; Pomat, William; Lehmann, Deborah

2015-10-27

Bacterial meningitis remains an important infection globally, with the greatest burden in children in low-income settings, including Papua New Guinea (PNG). We present serotype, antimicrobial susceptibility and outcome data from paediatric meningitis patients prior to introduction of Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCVs) in PNG, providing a baseline for evaluation of immunisation programs. Cerebrospinal fluid (CSF) was collected from children admitted to Goroka General Hospital with suspected meningitis between 1996 and 2005. Culture and sensitivity was conducted, and pneumococci and H. influenzae were serotyped. Laboratory findings were linked to clinical outcomes. We enrolled 1884 children. A recognised pathogen was identified in 375 children (19.9%). Streptococcus pneumoniae (n = 180) and Hib (n = 153) accounted for 88.8% of pathogens isolated. 24 different pneumococcal serogroups were identified; non-PCV types 2, 24 and 46 accounted for 31.6% of pneumococcal meningitis. 10- and 13-valent PCVs would cover 44.1% and 45.4% of pneumococcal meningitis respectively. Pneumococcal isolates were commonly resistant to penicillin (21.5%) and 23% of Hib isolates were simultaneously resistant to ampicillin, co-trimoxazole and chloramphenicol. The case fatality rate in patients with a recognised bacterial pathogen was 13.4% compared to 8.5% in culture-negative patients. If implemented in routine expanded programme of immunisation (EPI) with high coverage, current PCVs could prevent almost half of pneumococcal meningitis cases. Given the diversity of circulating serotypes in PNG serotype replacement is of concern. Ongoing surveillance is imperative to monitor the impact of vaccines. In the longer term vaccines providing broader protection against pneumococcal meningitis will be needed.

Otitis-Prone Children Produce Functional Antibodies to Pneumolysin and Pneumococcal Polysaccharides.

PubMed

Kirkham, Lea-Ann S; Wiertsema, Selma P; Corscadden, Karli J; Mateus, Tulia; Mullaney, Gemma L; Zhang, Guicheng; Richmond, Peter C; Thornton, Ruth B

2017-03-01

The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group ( P < 0.05). The production of functional antipneumococcal antibodies in otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children. Copyright © 2017 Kirkham et al.

A novel chimeric phage lysin with high in vitro and in vivo bactericidal activity against Streptococcus pneumoniae.

PubMed

Díez-Martínez, Roberto; De Paz, Héctor D; García-Fernández, Esther; Bustamante, Noemí; Euler, Chad W; Fischetti, Vincent A; Menendez, Margarita; García, Pedro

2015-01-01

Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide and new antimicrobials are urgently needed. Our aim was new chimeric phage endolysins, or lysins, with improved bactericidal activity by swapping the structural components of two pneumococcal phage lysozymes: Cpl-1 (the best lysin tested to date) and Cpl-7S. The bactericidal effects of four new chimeric lysins were checked against several bacteria. The purified enzymes were added at different concentrations to resuspended bacteria and viable cells were measured after 1 h. Killing capacity of the most active lysin, Cpl-711, was tested in a mouse bacteraemia model, following mouse survival after injecting different amounts (25-500 μg) of enzyme. The capacity of Cpl-711 to reduce pneumococcal biofilm formation was also studied. The chimera Cpl-711 substantially improved the killing activity of the parental phage lysozymes, Cpl-1 and Cpl-7S, against pneumococcal bacteria, including multiresistant strains. Specifically, 5 μg/mL Cpl-711 killed ≥7.5 log of pneumococcal R6 strain. Cpl-711 also reduced pneumococcal biofilm formation and killed 4 log of the bacterial population at 1 μg/mL. Mice challenged intraperitoneally with D39_IU pneumococcal strain were protected by treatment with a single intraperitoneal injection of Cpl-711 1 h later, resulting in about 50% greater protection than with Cpl-1. Domain swapping among phage lysins allows the construction of new chimeric enzymes with high bactericidal activity and a different substrate range. Cpl-711, the most powerful endolysin against pneumococci, offers a promising therapeutic perspective for the treatment of multiresistant pneumococcal infections. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Immunogenicity of a combined schedule of 7-valent pneumococcal conjugate vaccine followed by a 23-valent polysaccharide vaccine in adult recipients of heart or lung transplants.

PubMed

Gattringer, R; Winkler, H; Roedler, S; Jaksch, P; Herkner, H; Burgmann, H

2011-10-01

A combined schedule of 7-valent pneumococcal conjugate vaccine (PCV7) followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) was evaluated retrospectively in 26 adult recipients of heart or lung transplants. PCV7 was immunogenic in these patients but there appeared to be no benefit from the additional PPV23 dose. © 2011 John Wiley & Sons A/S.

Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

PubMed

Shak, Joshua R; Cremers, Amelieke J H; Gritzfeld, Jenna F; de Jonge, Marien I; Hermans, Peter W M; Vidal, Jorge E; Klugman, Keith P; Gordon, Stephen B

2014-01-01

Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

Pneumococcal pneumonia in adults 60 years or older: Incidence, mortality and prevention.

PubMed

Vila-Corcoles, Angel; Ansa, Xabier; Ochoa-Gondar, Olga; Satue, Eva; de Diego, Cinta; Rodriguez-Blanco, Teresa

2016-03-04

This study investigated the burden (incidence, mortality and serotype distribution) of pneumococcal pneumonia among older adults in the region of Tarragona (Spain). Population-based cohort study involving 27,204 individuals ≥60 years in Tarragonès county (Southern Catalonia), who were prospectively followed between 01/12/2008 and 30/11/2011. Bacteremic and nonbacteremic (positive sputum culture and/or urinary antigen test) pneumococcal pneumonias were recruited. A total of 125 pneumococcal pneumonias (16 bacteremic and 109 nonbacteremic) was observed. Incidence rates (per 1000 person-years) were 0.21 (95% confidence interval [CI]: 0.13-0.35) for bacteremic cases and 1.45 (95% CI: 1.20-1.75) for nonbacteremic cases. Case-fatality rate was 10.4% (12.5% in bacteremic and 10.1% in nonbacteremic cases). Five serotypes (types 3, 6C, 19A, 22F and 35B) were the most common serotypes, accounting for 64.3% of overall isolated serotypes. 73.1% of cases were due to the strains included in the 23-valent vaccine whereas 53.6% were due to the strains included in the 13-valent vaccine. The burden of pneumococcal pneumonia remains considerable (especially among oldest people and nursing-home residents) despite a publicly funded anti-pneumococcal vaccination program operative for several years. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Prevention of pneumococcal infections during mass gathering.

PubMed

Al-Tawfiq, Jaffar A; Memish, Ziad A

2016-01-01

The interest in mass gathering and its implications has been increasing due to globalization and international travel. The potential occurrence of infectious disease outbreaks during mass gathering is most feared. In this context, respiratory tract infections are of great concern due to crowding in a limited space which facilitates and magnifies the potential of disease spread among attendees. Pneumococcal disease is best described among pilgrims to Makkah and vaccination is one of the methods for the prevention of this disease. Pneumonia was described in a mass gathering with a prevalence of 4.8/100,000 pilgrims and contributes to 15-39% of hospitalizations. Various studies showed that 7-37% of pilgrims are 65 y of age or older. The uptake of pneumococcal vaccine among pilgrims is low at 5%. There is no available data to make strong recommendations for S. pneumoniae vaccination of all pilgrims, it is important that a high risk population receive the indicated vaccination. We reviewed the available literature on the burden of pneumococcal infections during mass gathering and evaluate the available literature on pneumococcal vaccinations for attendees of mass gathering.

Preclinical evaluation of a chemically detoxified pneumolysin as pneumococcal vaccine antigen.

PubMed

Hermand, Philippe; Vandercammen, Annick; Mertens, Emmanuel; Di Paolo, Emmanuel; Verlant, Vincent; Denoël, Philippe; Godfroid, Fabrice

2017-01-02

The use of protein antigens able to protect against the majority of Streptococcus pneumoniae serotypes is envisaged as stand-alone and/or complement to the current capsular polysaccharide-based pneumococcal vaccines. Pneumolysin (Ply) is a key virulence factor that is highly conserved in amino acid sequence across pneumococcal serotypes, and therefore may be considered as a vaccine target. However, native Ply cannot be used in vaccines due to its intrinsic cytolytic activity. In the present work a completely, irreversibly detoxified pneumolysin (dPly) has been generated using an optimized formaldehyde treatment. Detoxi-fication was confirmed by dPly challenge in mice and histological analysis of the injection site in rats. Immunization with dPly elicited Ply-specific functional antibodies that were able to inhibit Ply activity in a hemolysis assay. In addition, immunization with dPly protected mice against lethal intranasal challenge with Ply, and intranasal immunization inhibited nasopharyngeal colonization after intranasal challenge with homologous or heterologous pneumococcal strain. Our findings supported dPly as a valid candidate antigen for further pneumococcal vaccine development.

Preclinical evaluation of a chemically detoxified pneumolysin as pneumococcal vaccine antigen

PubMed Central

Hermand, Philippe; Vandercammen, Annick; Mertens, Emmanuel; Di Paolo, Emmanuel; Verlant, Vincent; Denoël, Philippe; Godfroid, Fabrice

2017-01-01

ABSTRACT The use of protein antigens able to protect against the majority of Streptococcus pneumoniae serotypes is envisaged as stand-alone and/or complement to the current capsular polysaccharide-based pneumococcal vaccines. Pneumolysin (Ply) is a key virulence factor that is highly conserved in amino acid sesec-typsecquence across pneumococcal serotypes, and therefore may be considered as a vaccine target. However, native Ply cannot be used in vaccines due to its intrinsic cytolytic activity. In the present work a completely, irreversibly detoxified pneumolysin (dPly) has been generated using an optimized formaldehyde treatment. Detoxi-fication was confirmed by dPly challenge in mice and histological analysis of the injection site in rats. Immunization with dPly elicited Ply-specific functional antibodies that were able to inhibit Ply activity in a hemolysis assay. In addition, immunization with dPly protected mice against lethal intranasal challenge with Ply, and intranasal immunization inhibited nasopharyngeal colonization after intranasal challenge with homologous or heterologous pneumococcal strain. Our findings supported dPly as a valid candidate antigen for further pneumococcal vaccine development. PMID:27768518

Effectiveness of 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine for pneumonia among the elderly - Selection of controls in a case-control study.

PubMed

Kondo, Kyoko; Suzuki, Kanzo; Washio, Masakazu; Ohfuji, Satoko; Fukushima, Wakaba; Maeda, Akiko; Hirota, Yoshio

2017-08-24

We conducted a case-control study to elucidate associations between pneumonia in elderly individuals and 23-valent pneumococcal polysaccharide vaccine (PPSV23) and seasonal influenza vaccine (influenza vaccine). Here, we examined selection of controls in our study using an analytic epidemiology approach. The study period was from October 1, 2009 through September 30, 2014. Cases comprised ≥65-year-old patients newly diagnosed with pneumonia. For every case with pneumonia, two patients with other diseases (one respiratory medicine, one non-respiratory medicine) who were sex-, age-, visit date- and visit hospital-matched were selected as controls. Odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for pneumonia were calculated using conditional logistic regression model. Similar analyses were also conducted based on the clinical department of controls. Analysis was conducted in 234 cases and 438 controls. Effectiveness of pneumococcal vaccination or influenza vaccination against pneumonia was not detected. Proportions of either vaccination in controls were greater among respiratory medicine (pneumococcal vaccine, 38%; influenza vaccine, 55%) than among non-respiratory medicine (23%; 48%). Analysis using controls restricted to respiratory medicine showed marginally significant effectiveness of pneumococcal vaccination (OR, 0.59; 95%CI, 0.34-1.03; P=0.064) and influenza vaccination (0.64; 0.40-1.04; 0.072). However, this effectiveness might have been overestimated by selection bias of controls, as pneumonia cases are not necessarily respiratory medicine patients. In the analysis using controls restricted to non-respiratory medicine, OR of pneumococcal vaccination for pneumonia was close to 1, presumably because the proportion of pneumococcal vaccination was higher in cases than in controls. Because pneumococcal vaccine was not routinely administered during the study period, differences in recommendations of vaccination by physician in different clinical departments might have greatly affected vaccination proportions. When we select controls, we should consider the background factors (underlying diseases, clinical department, etc.) which affect physicians' recommendation of vaccination. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Vaccination against community acquired pneumonia in adult patients. A position paper by Neumoexpertos en Prevención].

PubMed

Redondo, E; Rivero, I; Vargas, D A; Mascarós, E; Díaz-Maroto, J L; Linares, M; Valdepérez, J; Gil, A; Molina, J; Jimeno, I; Ocaña, D; Martinón-Torres, F

2016-10-01

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in adults. The annual incidence of CAP in adults in Spain ranges from 3 to 14 cases per 1,000 inhabitants. Current clinical guidelines primarily focus on the therapeutic approach to CAP rather than its prevention. The aim of this study is to develop and propose a practical guide for CAP prevention through vaccination in Spain according to available vaccines and evidence. A literature review and expert opinion. Pneumococcal and influenza vaccines are the main preventive tools available against CAP. Age, chronic diseases, and immunosuppression are risk factors for pneumonia, so these populations should be a priority for vaccination. In addition, influenza and pneumococcal vaccination is considered advisable in healthy adults under 60 years of age, and anyone with risk condition for CAP, irrespective of age. The influenza vaccine will be administered seasonally, while pneumococcal vaccination can be administered at any time of the year. Vaccination against pneumococcus and influenza in adults can help to reduce the burden of CAP and its associated complications. The available evidence supports the priority indications set out in this guide, and it would be advisable to try to achieve a wide circulation and practical implementation of these recommendations. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Sequencing of the variable region of rpsB to discriminate between Streptococcus pneumoniae and other streptococcal species.

PubMed

Wyllie, Anne L; Pannekoek, Yvonne; Bovenkerk, Sandra; van Engelsdorp Gastelaars, Jody; Ferwerda, Bart; van de Beek, Diederik; Sanders, Elisabeth A M; Trzciński, Krzysztof; van der Ende, Arie

2017-09-01

The vast majority of streptococci colonizing the human upper respiratory tract are commensals, only sporadically implicated in disease. Of these, the most pathogenic is Mitis group member, Streptococcus pneumoniae Phenotypic and genetic similarities between streptococci can cause difficulties in species identification. Using ribosomal S2-gene sequences extracted from whole-genome sequences published from 501 streptococci, we developed a method to identify streptococcal species. We validated this method on non-pneumococcal isolates cultured from cases of severe streptococcal disease ( n = 101) and from carriage ( n = 103), and on non-typeable pneumococci from asymptomatic individuals ( n = 17) and on whole-genome sequences of 1157 pneumococcal isolates from meningitis in the Netherlands. Following this, we tested 221 streptococcal isolates in molecular assays originally assumed specific for S. pneumoniae , targeting cpsA , lytA , piaB , ply , Spn9802, zmpC and capsule-type-specific genes. Cluster analysis of S2-sequences showed grouping according to species in line with published phylogenies of streptococcal core genomes. S2-typing convincingly distinguished pneumococci from non-pneumococcal species (99.2% sensitivity, 100% specificity). Molecular assays targeting regions of lytA and piaB were 100% specific for S. pneumoniae , whereas assays targeting cpsA , ply , Spn9802, zmpC and selected serotype-specific assays (but not capsular sequence typing) showed a lack of specificity. False positive results were over-represented in species associated with carriage, although no particular confounding signal was unique for carriage isolates. © 2017 The Authors.

Sequencing of the variable region of rpsB to discriminate between Streptococcus pneumoniae and other streptococcal species

PubMed Central

Pannekoek, Yvonne; Bovenkerk, Sandra; van Engelsdorp Gastelaars, Jody; Ferwerda, Bart; van de Beek, Diederik; Sanders, Elisabeth A. M.; Trzciński, Krzysztof; van der Ende, Arie

2017-01-01

The vast majority of streptococci colonizing the human upper respiratory tract are commensals, only sporadically implicated in disease. Of these, the most pathogenic is Mitis group member, Streptococcus pneumoniae. Phenotypic and genetic similarities between streptococci can cause difficulties in species identification. Using ribosomal S2-gene sequences extracted from whole-genome sequences published from 501 streptococci, we developed a method to identify streptococcal species. We validated this method on non-pneumococcal isolates cultured from cases of severe streptococcal disease (n = 101) and from carriage (n = 103), and on non-typeable pneumococci from asymptomatic individuals (n = 17) and on whole-genome sequences of 1157 pneumococcal isolates from meningitis in the Netherlands. Following this, we tested 221 streptococcal isolates in molecular assays originally assumed specific for S. pneumoniae, targeting cpsA, lytA, piaB, ply, Spn9802, zmpC and capsule-type-specific genes. Cluster analysis of S2-sequences showed grouping according to species in line with published phylogenies of streptococcal core genomes. S2-typing convincingly distinguished pneumococci from non-pneumococcal species (99.2% sensitivity, 100% specificity). Molecular assays targeting regions of lytA and piaB were 100% specific for S. pneumoniae, whereas assays targeting cpsA, ply, Spn9802, zmpC and selected serotype-specific assays (but not capsular sequence typing) showed a lack of specificity. False positive results were over-represented in species associated with carriage, although no particular confounding signal was unique for carriage isolates. PMID:28931649