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.

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.

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.

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.

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

Diversity of pneumococcal surface protein A (PspA) and relation to sequence typing in Streptococcus pneumoniae causing invasive disease in Chinese children.

PubMed

Qian, J; Yao, K; Xue, L; Xie, G; Zheng, Y; Wang, C; Shang, Y; Wang, H; Wan, L; Liu, L; Li, C; Ji, W; Wang, Y; Xu, P; Yu, S; Tang, Y-W; Yang, Y

2012-03-01

The objective of this paper was to investigate the sequence types (STs) and diversity of surface antigen pneumococcal surface protein A (PspA) in 171 invasive Streptococcus pneumoniae isolates from Chinese children. A total of 171 pneumococci isolates were isolated from Chinese children with invasive pneumococcal diseases (IPD) in 11 hospitals between 2006 and 2008. The pneumococci samples were characterized by serotyping, PspA classification, and multilocus sequence typing (MLST). The PspA of these strains could be assigned to two families. The PspA family 2 was the most common (120/171, 70.1%). No PspA family 3 isolates were detected. Family 1 could be subdivided into two clades, with 42 strains in clade 1 and 9 strains in clade 2, and family 2 could be subdivided into clades 3, 4, and 5, which respectively contained 5, 21, and 14 strains. In total, 65 STs were identified, of which ST320 (30/171, 17.5%), ST271 (23/171, 13.5%), and ST876 (18/171, 10.5%) were the most common types. PspA family 2 and family 1 were dominant among pneumococcal clones isolated from Chinese children with invasive disease. The strains with the same ST always presented in the same PspA family.

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

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

PubMed

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

2017-06-01

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. 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. 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. 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.

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.

[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.

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.

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.

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.

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

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.

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

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.

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.

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.

[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,-.

The effect of pneumococcal conjugate vaccines on the incidence of invasive pneumococcal disease caused by ten non-vaccine serotypes in Denmark.

PubMed

Slotved, Hans-Christian; Dalby, Tine; Hoffmann, Steen

2016-02-03

Surveillance data on invasive pneumococcal disease (IPD) in Denmark (1999-2014) was analysed regarding the incidence and age-distribution due to ten selected non-PCV serotypes (10-Non-PCV). The effect of PCV-7 and PCV-13 vaccines on the 10-Non-PCV IPD incidence was examined. IPD cases caused by serotypes included in PCV-7, the additional six serotypes included in PCV-13 and 10-Non-PCV serotypes were identified (8, 9N, 11A, 12F, 15A, 22F, 24F, 20, 23B, 33F). The IPD incidence was stratified by three age groups: 0-4 years, 5-64 years and 65+ years. The predominant IPD cases were caused by serotypes that are not included in PCV-13 (71%), followed by the six additional PCV-13 serotypes. The IPD incidence of serotypes included in the PCV-7 decreased markedly after PCV-7 introduction but are still diagnosed at a low level. The IPD incidence for the 10-Non-PCV serotypes was low for age groups 0-4 years and 5-64 years but high for 65+ years. Future vaccinations of the young age group alone with a vaccine targeting some of the 10-Non-PCV serotypes may not elicit the desired effect on herd protection since these serotypes are primarily causing IPD among the elderly. Future pneumococcal vaccination strategies in Denmark may therefore need carriage studies in order to identify among whom the pneumococcal serotypes causing IPD are carried. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Use of Pneumococcal Disease Epidemiology to Set Policy and Prevent Disease during 20 Years of the Emerging Infections Program.

PubMed

Moore, Matthew R; Whitney, Cynthia G

2015-09-01

Two decades ago, the Emerging Infections Program of the US Centers for Disease Control and Prevention implemented what seemed like a simple yet novel idea: a population- and laboratory-based surveillance system designed to identify and characterize invasive bacterial infections, including those caused by Streptococcus pneumoniae. This system, known as Active Bacterial Core surveillance, has since served as a flexible platform for following trends in invasive pneumococcal disease and studying vaccination as the most effective method for prevention. We report the contributions of Active Bacterial Core surveillance to every pneumococcal vaccine policy decision in the United States during the past 20 years.

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.

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.

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

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

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

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.

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.

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.

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.

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

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.

The epidemiology of pneumococcal carriage and infections in Malaysia.

PubMed

Le, Cheng-Foh; Jefferies, Johanna M; Yusof, Mohd Yasim Mohd; Sekaran, Shamala Devi; Clarke, Stuart C

2012-06-01

In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.

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.

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

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.

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.

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.

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 ...

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.

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

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.

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

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

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.

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.

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

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.

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

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.

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.

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

[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

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.

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

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

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.

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.

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.

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

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.

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.

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.

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.

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

Changing trends in serotypes of S. pneumoniae isolates causing invasive and non-invasive diseases in unvaccinated population in Mexico (2000-2014).

PubMed

Carnalla-Barajas, María Noemí; Soto-Noguerón, Araceli; Sánchez-Alemán, Miguel Angel; Solórzano-Santos, Fortino; Velazquez-Meza, María Elena; Echániz-Aviles, Gabriela

2017-05-01

Introduction of pneumococcal conjugate vaccines (PCV) targeted against a limited number of serotypes substantially decreased invasive (IPD) and non-invasive pneumococcal diseases (NIPD) but it was accompanied by non-vaccine type replacement disease. After 9 years of introduction of PCV in Mexico, we analyze the evidence of the indirect effects on IPD and NIPD serotype distribution among groups not targeted to receive the vaccine. From January 2000 to December 2014, pneumococcal strains isolated from IPD and NIPD cases from patients ≥5 years of age from participant hospitals of the SIREVA II (Sistema Regional de Vacunas) network were serotyped. A regression analysis was performed considering year and proportion of serotypes included in the different vaccine formulations (PCV7, PCV10 and PCV13). The slope was obtained for each regression line and their correspondent p-value. The proportion of each serotype in the pre-PCV7 and post-PCV7 periods was evaluated by χ2 test. From a total of 1147 pneumococcal strains recovered, 570 corresponded to the pre-PCV7 and 577 to the post-PCV7 periods. The proportion of vaccine serotypes included in the three PCV formulations decreased by 2.4, 2.6 and 1.3%, respectively per year during the study period. A significant increase of serotype 19A was observed in the post-vaccine period in all age groups. A percentage of annual decline of serotypes causing IPD and NIPD included in PCV was detected among groups not targeted to receive the vaccine, probably due to herd effect. Considering pneumococcal serotype distribution is a dynamic process, we highlight the importance of surveillance programs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The post-vaccine microevolution of invasive Streptococcus pneumoniae

PubMed Central

Cremers, Amelieke J. H.; Mobegi, Fredrick M.; de Jonge, Marien I.; van Hijum, Sacha A. F. T.; Meis, Jacques F.; Hermans, Peter W. M.; Ferwerda, Gerben; Bentley, Stephen D.; Zomer, Aldert L.

2015-01-01

The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S. pneumoniae isolated from IPD patients in Nijmegen between 2001 and 2011. Introduction of PCV7 in the Dutch National Immunization Program in 2006 preluded substantial alterations in the IPD population structure caused by serotype replacement. No evidence could be found for vaccine induced capsular switches. We observed that after a temporary bottleneck in gene diversity after the introduction of PCV7, the accessory gene pool re-expanded mainly by genes already circulating pre-PCV7. In the post-vaccine genomic population a number of genes changed frequency, certain genes became overrepresented in vaccine serotypes, while others shifted towards non-vaccine serotypes. Whether these dynamics in the invasive pneumococcal population have truly contributed to invasiveness and manifestations of disease remains to be further elucidated. We suggest the use of whole genome sequencing for surveillance of pneumococcal population dynamics that could give a prospect on the course of disease, facilitating effective prevention and management of IPD. PMID:26492862

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.

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

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

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.

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.

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

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

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.

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.

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

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.

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.

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.

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.

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

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.

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 Cl

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

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

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.

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.

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.

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.

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.

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

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.

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.

[Seasonal changes of invasive pneumococcal disease in children and association with day care attendance].

PubMed

Matsubara, Kousaku; Nigami, Hiroyuki; Iwata, Aya; Uchida, Yoshiko; Yamamoto, Go; Chang, Bin; Wada, Akihito

2012-01-01

To determine seasonal changes in the incidence of invasive pneumococcal disease (IPD) in children, we retrospectively analyzed 69 children with 72 episodes of IPD, admitted to a regional center in Kobe, Japan, between July 1994 and June 2011. IPD episodes involved occult bacteremia (n = 48), pneumonia (n = 10), meningitis (n = 10), periorbital cellulitis (n = 3), and mastoiditis (n = 1), including 3 cases of two IPD recurrences. We analyzed 5 IPD-associated factors previously documented in Europe and North Amrica with inconsistent results--1) age at onset, 2) sibling number, 3) preschool sibling number, 4) subjects' day care attendance, and 5) siblings' day care attendance. We collected information on these factors by reviewing medical charts or contacting subjects' parents or guardians by telephone. IPD peaked bimodally in April and May (n = 21) and in November and December (n = 20), decreasing prominently between July and September (n = 8). Subjects with IPD attending day care formed a significantly higher propotion during April and May than did those developing IPD during other months: 12/21 [57.1%] vs. 12/51 [23.5%], odds ratio 4.3, 95% confidence interval, 1.5-12.8; p = 0.006. Combined day care attendance among subjects with IPD and/or their siblings also differed significantly between these two groups: 17/21 [80.9%] vs. 27/51 [52.9%], odds ratio 3.8, 95% confidence interval, 1.1-12.8; p = 0.027. Not significant differences were seen in age at onset, sibling number, or preschool sibling number. In contrast, however children with IPD onset during November and December showed no significant difference in association with any of the 5 factors, compared to children with IPD onset in other months. Our findings showed a bimodal peak in IPD in children, the first and highest of which occurred in April and May and was significantly associated with day care attendance by those with IPD and/or their siblings. This first peak may, however, be related to circumstances in

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

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.

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.

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 ...

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

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.

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

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.

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

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.

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.

Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination

PubMed Central

Nurhonen, Markku; Cheng, Allen C.; Auranen, Kari

2013-01-01

Background The degree and time frame of indirect effects of vaccination (serotype replacement and herd immunity) are key determinants in assessing the net effectiveness of vaccination with pneumococcal conjugate vaccines (PCV) in control of pneumococcal disease. Using modelling, we aimed to quantify these effects and their dependence on coverage of vaccination and the vaccine's efficacy against susceptibility to pneumococcal carriage. Methods and Findings We constructed an individual-based simulation model that explores the effects of large-scale PCV programmes and applied it in a developed country setting (Finland). A population structure with transmission of carriage taking place within relevant mixing groups (families, day care groups, schools and neighbourhoods) was considered in order to properly assess the dependency of herd immunity on coverage of vaccination and vaccine efficacy against carriage. Issues regarding potential serotype replacement were addressed by employing a novel competition structure between multiple pneumococcal serotypes. Model parameters were calibrated from pre-vaccination data about the age-specific carriage prevalence and serotype distribution. The model predicts that elimination of vaccine-type carriage and disease among those vaccinated and, due to a substantial herd effect, also among the general population takes place within 5–10 years since the onset of a PCV programme with high (90%) coverage of vaccination and moderate (50%) vaccine efficacy against acquisition of carriage. A near-complete replacement of vaccine-type carriage by non-vaccine-type carriage occurs within the same time frame. Conclusions The changed patterns in pneumococcal carriage after PCV vaccination predicted by the model are unequivocal. The overall effect on disease incidence depends crucially on the magnitude of age- and serotype-specific case-to-carrier ratios of the remaining serotypes relative to those of the vaccine types. Thus the availability of

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

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.

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.

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.

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.

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

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

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

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

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

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).

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

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

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).

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

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.

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.

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

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.

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.

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.

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

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

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.

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

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.

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...

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

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.

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.

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

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.

[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.

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

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

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.

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.

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

An eHealth Project on Invasive Pneumococcal Disease: Comprehensive Evaluation of a Promotional Campaign

PubMed Central

Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Carozzo, Stefano; Signori, Alessio; Bechini, Angela; Boccalini, Sara

2016-01-01

Background The recently launched Pneumo Rischio eHealth project, which consists of an app, a website, and social networking activity, is aimed at increasing public awareness of invasive pneumococcal disease (IPD). The launch of this project was prompted by the inadequate awareness of IPD among both laypeople and health care workers, the heavy socioeconomic burden of IPD, and the far from optimal vaccination coverage in Italy, despite the availability of safe and effective vaccines. Objective The objectives of our study were to analyze trends in Pneumo Rischio usage before and after a promotional campaign, to characterize its end users, and to assess its user-rated quality. Methods At 7 months after launching Pneumo Rischio, we established a 4-month marketing campaign to promote the project. This intervention used various approaches and channels, including both traditional and digital marketing strategies. To highlight usage trends, we used different techniques of time series analysis and modeling, including a modified Mann-Kendall test, change-point detection, and segmented negative binomial regression of interrupted time series. Users were characterized in terms of demographics and IPD risk categories. Customer-rated quality was evaluated by means of a standardized tool in a sample of app users. Results Over 1 year, the app was accessed by 9295 users and the website was accessed by 143,993 users, while the project’s Facebook page had 1216 fans. The promotional intervention was highly effective in increasing the daily number of users. In particular, the Mann-Kendall trend test revealed a significant (P ≤.01) increasing trend in both app and website users, while change-point detection analysis showed that the first significant change corresponded to the start of the promotional campaign. Regression analysis showed a significant immediate effect of the intervention, with a mean increase in daily numbers of users of 1562% (95% CI 456%-4870%) for the app and 620

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.

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

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

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.

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

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.

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.

An eHealth Project on Invasive Pneumococcal Disease: Comprehensive Evaluation of a Promotional Campaign.

PubMed

Panatto, Donatella; Domnich, Alexander; Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Carozzo, Stefano; Signori, Alessio; Bechini, Angela; Boccalini, Sara

2016-12-02

The recently launched Pneumo Rischio eHealth project, which consists of an app, a website, and social networking activity, is aimed at increasing public awareness of invasive pneumococcal disease (IPD). The launch of this project was prompted by the inadequate awareness of IPD among both laypeople and health care workers, the heavy socioeconomic burden of IPD, and the far from optimal vaccination coverage in Italy, despite the availability of safe and effective vaccines. The objectives of our study were to analyze trends in Pneumo Rischio usage before and after a promotional campaign, to characterize its end users, and to assess its user-rated quality. At 7 months after launching Pneumo Rischio, we established a 4-month marketing campaign to promote the project. This intervention used various approaches and channels, including both traditional and digital marketing strategies. To highlight usage trends, we used different techniques of time series analysis and modeling, including a modified Mann-Kendall test, change-point detection, and segmented negative binomial regression of interrupted time series. Users were characterized in terms of demographics and IPD risk categories. Customer-rated quality was evaluated by means of a standardized tool in a sample of app users. Over 1 year, the app was accessed by 9295 users and the website was accessed by 143,993 users, while the project's Facebook page had 1216 fans. The promotional intervention was highly effective in increasing the daily number of users. In particular, the Mann-Kendall trend test revealed a significant (P ≤.01) increasing trend in both app and website users, while change-point detection analysis showed that the first significant change corresponded to the start of the promotional campaign. Regression analysis showed a significant immediate effect of the intervention, with a mean increase in daily numbers of users of 1562% (95% CI 456%-4870%) for the app and 620% (95% CI 176%-1777%) for the website

[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.

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 NCT

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.

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

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 PCV

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

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

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

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...

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

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

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 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.

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.

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 ...

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.

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

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.

Using Dynamic Transmission Modeling to Determine Vaccination Coverage Rate Based on 5-Year Economic Burden of Infectious Disease: An Example of Pneumococcal Vaccine.

PubMed

Wen, Yu-Wen; Wu, Hsin; Chang, Chee-Jen

2015-05-01

Vaccination can reduce the incidence and mortality of an infectious disease and thus increase the years of life and productivity for the entire society. But when determining the vaccination coverage rate, its economic burden is usually not taken into account. This article aimed to use a dynamic transmission modeling (DTM), which is based on a susceptible-infectious-recovered model and is a system of differential equations, to find the optimal vaccination coverage rate based on the economic burden of an infectious disease. Vaccination for pneumococcal diseases was used as an example to demonstrate the main purpose. 23-Valent pneumococcal polysaccharide vaccines (PPV23) and 13-valent pneumococcal conjugate vaccines (PCV13) have shown their cost-effectiveness in elderly and children, respectively. Scenarios analysis of PPV23 to elderly aged 65+ years and of PCV13 to children aged 0 to 4 years was applied to assess the optimal vaccination coverage rate based on the 5-year economic burden. Model parameters were derived from Taiwan's National Health Insurance Research Database, government data, and published literature. Various vaccination coverage rates, the vaccine efficacy, and all epidemiologic parameters were substituted into DTM, and all differential equations were solved in R Statistical Software. If the coverage rate of PPV23 for the elderly and of PCV13 for the children both reach 50%, the economic burden due to pneumococcal disease will be acceptable. This article provided an alternative perspective from the economic burden of diseases to obtain a vaccination coverage rate using the DTM. This will provide valuable information for vaccination policy decision makers. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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.

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

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 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.

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.

An audit of influenza and pneumococcal vaccination in rheumatology outpatients.

PubMed

Sowden, Evin; Mitchell, William S

2007-07-04

Influenza and pneumococcal vaccination are recommended for a number of clinical risk groups including patients treated with major immunosuppressant disease modifying anti-rheumatic drugs. Such immunisation is not only safe but immunogenic in patients with rheumatic diseases. We sought to establish dual vaccination rates and significant influencing factors amongst our hospital rheumatology outpatients. We audited a sample of 101 patients attending hospital rheumatology outpatient clinics on any form of disease modifying treatment by clinical questionnaire and medical record perusal. Further data were collected from the local immunisation coordinating agency and analysed by logistic regression modelling. Although there was a high rate of awareness with regard to immunisation, fewer patients on major immunosuppressants were vaccinated than patients with additional clinical risk factors against influenza (53% vs 93%, p < 0.001) or streptococcus pneumoniae (28% vs 64%, p = 0.001). The presence of additional risk factors was confirmed as significant in determining vaccination status by logistic regression for both influenza (OR 10.89, p < 0.001) and streptococcus pneumoniae (OR 4.55, p = 0.002). The diagnosis of rheumatoid arthritis was also found to be a significant factor for pneumococcal vaccination (OR 5.1, p = 0.002). There was a negative trend suggesting that patients on major immunosuppressants are less likely to be immunised against pneumococcal antigen (OR 0.35, p = 0.067). Influenza and pneumococcal immunisation is suboptimal amongst patients on current immunosuppressant treatments attending rheumatology outpatient clinics. Raising awareness amongst patients may not be sufficient to improve vaccination rates and alternative strategies such as obligatory pneumococcal vaccination prior to treatment initiation and primary care provider education need to be explored.

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.

[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.

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.

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.

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

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

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

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.

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.

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 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.

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.

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

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

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

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.

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.

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

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 ( ...

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

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.

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

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

Exome Array Analysis of Susceptibility to Pneumococcal Meningitis

PubMed Central

Kloek, Anne T.; van Setten, Jessica; van der Ende, Arie; Bots, Michiel L.; Asselbergs, Folkert W.; Serón, Mercedes Valls; Brouwer, Matthijs C.; van de Beek, Diederik; Ferwerda, Bart

2016-01-01

Host genetic variability may contribute to susceptibility of bacterial meningitis, but which genes contribute to the susceptibility to this complex disease remains undefined. We performed a genetic association study in 469 community-acquired pneumococcal meningitis cases and 2072 population-based controls from the Utrecht Health Project in order to find genetic variants associated with pneumococcal meningitis susceptibility. A HumanExome BeadChip was used to genotype 102,097 SNPs in the collected DNA samples. Associations were tested with the Fisher exact test. None of the genetic variants tested reached Bonferroni corrected significance (p-value <5 × 10−7). Our strongest signals associated with susceptibility to pneumococcal meningitis were rs139064549 on chromosome 1 in the COL11A1 gene (p = 1.51 × 10−6; G allele OR 3.21 [95% CI 2.05–5.02]) and rs9309464 in the EXOC6B gene on chromosome 2 (p = 6.01 × 10−5; G allele OR 0.66 [95% CI 0.54–0.81]). The sequence kernel association test (SKAT) tests for associations between multiple variants in a gene region and pneumococcal meningitis susceptibility yielded one significant associated gene namely COL11A1 (p = 1.03 × 10−7). Replication studies are needed to validate these results. If replicated, the functionality of these genetic variations should be further studied to identify by which means they influence the pathophysiology of pneumococcal meningitis. PMID:27389768

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.

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

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

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

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.

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.

[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.

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).

[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.

Single-Plex Quantitative Assays for the Detection and Quantification of Most Pneumococcal Serotypes

PubMed Central

Chochua, Sopio; Satzke, Catherine; Dunne, Eileen M.; Mulholland, Kim; Klugman, Keith P.

2015-01-01

Streptococcus pneumoniae globally kills more children than any other infectious disease every year. A prerequisite for pneumococcal disease and transmission is colonization of the nasopharynx. While the introduction of pneumococcal conjugate vaccines has reduced the burden of pneumococcal disease, understanding the impact of vaccination on nasopharyngeal colonization has been hampered by the lack of sensitive quantitative methods for the detection of >90 known S. pneumoniae serotypes. In this work, we developed 27 new quantitative (q)PCR reactions and optimized 26 for a total of 53 qPCR reactions targeting pneumococcal serotypes or serogroups, including all vaccine types. Reactions proved to be target-specific with a limit of detection of 2 genome equivalents per reaction. Given the number of probes required for these assays and their unknown shelf-life, the stability of cryopreserved reagents was evaluated. Our studies demonstrate that two-year cryopreserved probes had similar limit of detection as freshly-diluted probes. Moreover, efficiency and limit of detection of 1-month cryopreserved, ready-to-use, qPCR reaction mixtures were similar to those of freshly prepared mixtures. Using these reactions, our proof-of-concept studies utilizing nasopharyngeal samples (N=30) collected from young children detected samples containing ≥2 serotypes/serogroups. Samples colonized by multiple serotypes/serogroups always had a serotype that contributes at least 50% of the pneumococcal load. In addition, a molecular approach called S6-q(PCR)2 was developed and proven to individually detect and quantify epidemiologically-important serogroup 6 strains including 6A, 6B, 6C and 6D. This technology will be useful for epidemiological studies, diagnostic platforms and to study the pneumobiome. PMID:25798884

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.

[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

Cost-effectiveness analysis of pneumococcal vaccination for infants in China.

PubMed

Maurer, Kristin A; Chen, Huey-Fen; Wagner, Abram L; Hegde, Sonia T; Patel, Tejasi; Boulton, Matthew L; Hutton, David W

2016-12-07

Although China has a high burden of pneumococcal disease among young children, the government does not administer publicly-funded pneumococcal conjugate vaccines (PCV) through its Expanded Program on Immunization (EPI). We evaluated the cost-effectiveness of publicly-funded PCV-7, PCV-10, and PCV-13 vaccination programs for infants in China. Using a Markov model, we simulated a cohort of 16 million Chinese infants to estimate the impact of PCV-7, PCV-10, and PCV-13 vaccination programs from a societal perspective. We extrapolated health states to estimate the effects of the programs over the course of a lifetime of 75years. Parameters in the model were derived from a review of the literature. We found that PCV-7, PCV-10, and PCV-13 vaccination programs would be cost-effective compared to no vaccination. However, PCV-13 had the lowest incremental cost-effectiveness ratio ($11,464/QALY vs $16,664/QALY for PCV-10 and $18,224/QALY for PCV-7) due to a reduction in overall costs. Our sensitivity analysis revealed that the incremental cost-effectiveness ratios were most sensitive to the utility of acute otitis media, the cost of PCV-13, and the incidence of pneumonia and acute otitis media. The Chinese government should take steps to reduce the burden of pneumococcal diseases among young children through the inclusion of a pneumococcal conjugate vaccine in its EPI. Although all vaccinations would be cost-effective, PCV-13 would save more costs to the healthcare system and would be the preferred strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vaccines against invasive Salmonella disease

PubMed Central

MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

2014-01-01

Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

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.

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

Pharmacists as providers: targeting pneumococcal vaccinations to high risk populations.

PubMed

Taitel, Michael; Cohen, Ed; Duncan, Ian; Pegus, Cheryl

2011-10-19

Older adults and persons with chronic conditions are at increased risk for pneumococcal disease. Severe pneumococcal disease represents a substantial humanistic and economic burden to society. Although pneumococcal vaccination (PPSV) can decrease risk for serious consequences, vaccination rates are suboptimal. As more people seek annual influenza vaccinations at community pharmacies, pharmacists have the ability to identify at-risk patients and provide PPSV. The objective of this study was to evaluate the impact of pharmacists educating at-risk patients on the importance of receiving a pneumococcal vaccination. Using de-identified claims from a large, national pharmacy chain, all patients who had received an influenza vaccination between August 1, 2010 and November 14, 2010 and who were eligible for PPSV were identified for the analysis. Based on the Advisory Committee on Immunization Practices recommendations, at-risk patients were identified as over 65 years of age or as aged 2-64 with a comorbid conditions. A benchmark medical and pharmacy claims database of commercial and Medicare health plan members was used to derive a PPSV vaccination rate typical of traditional care delivery to compare to pharmacy-based vaccination. Period incidence of PPSV was calculated and compared. Among the 1.3 million at-risk patients who were vaccinated by a pharmacist during the study period, 65,598 (4.88%) also received a pneumococcal vaccine. This vaccination rate was significantly higher than the benchmark rate of 2.90% (34,917/1,204,104; p<.001) representing traditional care. Patients aged 60-70 years had the highest vaccination rate (6.60%; 26,430/400,454) of any age group. Pharmacists were successful at identifying at-risk patients and providing additional immunization services. Concurrent immunization of PPSV with influenza vaccination by pharmacists has potential to improve PPSV coverage. These results support the expanding role of community pharmacists in the provision of

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.

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.

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. ...

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.

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.

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

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.

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

Pneumococcal Vaccine to Counter Emerging Infectious Disease Threat in the Military

DTIC Science & Technology

2001-12-01

Medical Center. San pathogen is an even greater threat to some subpopulations in Diego, CA; Wyeth Lederle Vaccines: LT David Cute, MC USN, Erica...Butler JC. Tenover FC, Elliott JA, Facklam RR. Emergence of 43. Musher DM, Luchi MJ, Watson DA, Hamilton R, Baughn RE: Pneumococcal drug-resistant

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.

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.

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

Pneumococcal and influenza vaccine uptake in adults with inflammatory bowel disease in France: Results from a web-based study.

PubMed

Loubet, Paul; Verger, Pierre; Abitbol, Vered; Peyrin-Biroulet, Laurent; Launay, Odile

2018-06-01

Despite specific immunization guidelines for immunocompromised patients, there is a dearth of studies on inflammatory bowel disease (IBD) population in France. To estimate the prevalence and predictors of influenza and pneumococcal vaccination rates in a sample of French IBD adults. An anonymous online survey was submitted to members of several French immunocompromised patients' associations during the winter 2016. Overall, there were 199/1625 (12%) participants with an IBD. Among these, 32% were <30 years old, 85% were male, and 62% were treated with immunosuppressive therapy. Self-reported influenza vaccine uptake was 34% (95% CI [28-41]) and 38% (95% CI [31-44]) for pneumococcal vaccines. Healthcare provider's (HCP) recommendation for vaccination (adjusted OR 12.7 95% CI [5.6-28.8]), immunosuppressive therapy (aOR 2.3 [1.1-5.3]), better knowledge of vaccination (aOR 3.2 [1.1-9.2]) and favorable attitudes towards vaccination (aOR 3.4 [1.2-9.5]) were positively associated with influenza vaccine uptake. Vaccine recommendation by HCPs was the only independently associated factor with pneumococcal vaccines uptake (OR 187.7 [24.8-1422.5]). Immunization rates in our sample do not reach recommended levels. Factors associated with vaccination included high knowledge, favorable attitudes towards vaccination and recommendation for vaccination. This underlines the role of health care providers in contact with IBD patients. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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.

Comparative cost effectiveness of varicella, hepatitis A, and pneumococcal conjugate vaccines.

PubMed

Jacobs, R J; Meyerhoff, A S

2001-12-01

Several state and local U.S. governments are considering making varicella, hepatitis A, and/or pneumococcal conjugate vaccination conditions of day care or school entry. These requirements will likely be issued sequentially, because simultaneous mandates exacerbate budget constraints and complicate communication with parents and providers. Cost-effectiveness assessments should aid the establishment of vaccination priorities, but comparing results of published studies is confounded by their dissimilar methods. We reviewed U.S. cost-effectiveness studies of childhood varicella, hepatitis A, and pneumococcal conjugate vaccines and identified four providing data required to standardize methods. Vaccination, disease treatment, and work-loss costs were estimated from original study results and current prices. Estimated life-years saved were derived from original study results, epidemiological evidence, and alternative procedures for discounting to present values. Hepatitis A vaccine would have the lowest health system costs per life-year saved. Varicella vaccine would provide the greatest reduction in societal costs, mainly through reduced parent work loss. Pneumococcal conjugate vaccine would cost twice the amount of varicella and hepatitis A vaccines combined and be less cost effective than the other vaccines. Hepatitis A and varicella vaccines, but not pneumococcal conjugate vaccine, meet or exceed conventional standards of cost effectiveness. Copyright 2001 American Health Foundation and Elsevier Science.

Changes in the pneumococcal disease-related hospitalisations in Spain after the replacement of 7-valent by 13-valent conjugate vaccine.

PubMed

Georgalis, L; Mozalevskis, A; Martínez de Aragón, M V; Garrido-Estepa, M

2017-03-01

In Spain, anti-pneumococcal vaccination is recommended for all children under 2 years old, high-risk groups and adults ≥65 years old. However, it is not funded in most autonomous communities. This study aims to compare pneumococcal disease hospitalisation rates between Period 1 (2007-2009), when 7-valent (PCV7) vaccine was available, and Period 2 (2011-2013), after the change to 13-valent (PCV13) vaccine in Spain. Data on hospitalisations were obtained from the National Registry of Hospitalisations. We calculated hospitalisation rates (HRs) and hospitalisation rate ratios (HRRs) among periods by age group and autonomous community, for all and by clinical presentation. From 138,361 patients hospitalised, 83,528 (60.4 %) were males. The median age was 73.8 years. The most common clinical presentation was pneumonia (133,204 hospitalisations; 96.3 %), followed by septicaemia (7053 hospitalisations; 5.1 %) and meningitis (3182 hospitalisations; 2.3 %). In Period 2, hospitalisations among children <5 years old decreased for pneumonia [HRR: 0.37; 95 % confidence interval (95 % CI): 0.35 to 0.39] and meningitis (HRR: 0.53; 95 % CI: 0.44 to 0.65). For adults ≥65 years old, pneumonia (HRR: 0.49; 95 % CI: 0.49 to 0.50) and peritonitis (HRR: 0.34; 95 % CI: 0.19 to 0.63) hospitalisations decreased and septicaemia hospitalisations (HRR: 1.27; 95 % CI: 1.18 to 1.36) increased. Significant changes in HRs for pneumococcal disease were observed even without an integrated and continuous vaccination programme after the introduction of PCV13, especially in children <5 years old and for pneumonia. The impact of the PCV13 adult vaccination new recommendations on the septicaemia increase reported should be evaluated in the future.

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

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

Pre-vaccination nasopharyngeal pneumococcal carriage in a Nigerian population: epidemiology and population biology.

PubMed

Adetifa, Ifedayo M O; Antonio, Martin; Okoromah, Christy A N; Ebruke, Chinelo; Inem, Victor; Nsekpong, David; Bojang, Abdoulie; Adegbola, Richard A

2012-01-01

Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria. This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST). The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage. Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for

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.

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

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

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.

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.

Parental knowledge, attitudes and perception of pneumococcal disease and pneumococcal conjugate vaccines in Singapore: a questionnaire-based assessment.

PubMed

How, Choon How; Phua See Chun, Priscilla; Shafi, Fakrudeen; Jakes, Rupert W

2016-09-02

Under the National Childhood Immunisation Schedule (NCIS) in Singapore most vaccines are provided free while some, including pneumococcal conjugate vaccines (PCV), added to the NCIS in October 2009, are not free. In contrast to ≥95 % coverage achieved for recommended childhood vaccines that are free, 2013 coverage of the PCV booster dose was 58.9 % (for unclear reasons). To date, no population impact on pneumococcal disease (PD) has been observed. We conducted a questionnaire-based study of parents of young children to assess the value of PCV to parents, and to quantify the extent to which vaccine cost is a barrier to PCV uptake in Singapore. A single, trained interviewer administered a questionnaire to 200 parents ≥21 years of age with young children attending the Singapore Sengkang Polyclinic. The questionnaire asked closed-ended questions on parents' knowledge about PD and PCV. A 5-point Likert scale measured perceived benefits and barriers to PCV vaccination. There were 162 parents whose children were either PCV-vaccinated or who intended to vaccinate their child with PCV (Vaccinated group), and 38 whose children were non-PCV vaccinated or who did not intend to vaccinate (Unvaccinated group). The odds ratio for PCV vaccination among parents who perceived cost as a barrier was 0.16 (95%CI 0.02-1.23). Compared to the Vaccinated group, parents in the Unvaccinated group were less willing to pay for PCV (50.0 %/94.4 %). Compared to the Vaccinated group, fewer parents in the Unvaccinated group had heard about PD (34.2 %/82.1 %) or PCV (36.8 %/69.1 %), or perceived that PD was a threat to their child. Fewer parents in the Unvaccinated group knew that vaccination could prevent PD (28.9 %/77.8 %), or reported that PCV vaccination was recommended to them by any source (63.2 % had no PCV recommendation, versus 20.4 %). When informed that PCV is included in the NCIS only 65.8 % of parents in the Unvaccinated group, versus 98.8 % in the Vaccinated group

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

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.

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.

Impact of Experimental Human Pneumococcal Carriage on Nasopharyngeal Bacterial Densities in Healthy Adults

PubMed Central

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. PMID:24915552

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.

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

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.

Improving pneumococcal and herpes zoster vaccination uptake: expanding pharmacist privileges.

PubMed

Taitel, Michael S; Fensterheim, Leonard E; Cannon, Adam E; Cohen, Edward S

2013-09-01

To investigate how state-authorized pharmacist immunization privileges influence pharmacist intervention effectiveness in delivering pneumococcal and herpes zoster vaccinations and assess the implications these privileges have on vaccination rates. Cross-sectional study of Walgreens vaccination records from August 2011 to March 2012. A random sample of patients having a claim for influenza vaccination in the study period was selected. Vaccination uptake rates for pneumococcal disease and herpes zoster were calculated for previously unvaccinated patients at high risk for these conditions. Rates were examined by state-level pharmacist privileges. For states authorizing immunization by protocol or prescriptive authority, the 1-year pneumococcal vaccination uptake rate for previously unvaccinated, high-risk persons was 6.6%, compared with 2.5% for states requiring a prescription (P <.0001), and 2.8% for states with no authorization (P <.0001). For herpes zoster, the 1-year vaccination uptake rate was 3.3% for states authorizing per protocol/prescriptive authority, compared with 2.8% (not significant, P <.05) for states authorizing by prescription, and 1.0% for states with no authorization (P <.0001). A 148% increase of pneumococcal vaccination and a 77% increase of herpes zoster vaccination would result if all states granted pharmacists full immunization privileges. This analysis demonstrates that states that offer pharmacists full immunization privileges have higher vaccination uptake rates than states with restricted or no authorization. Considering the suboptimal vaccination rates of pneumonia and shingles and the public health goals of 2020, states with limited or no immunization authorization for pharmacists should consider expanding pharmacist privileges for these vaccinations.

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.

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 ...

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.

Pre-Vaccination Nasopharyngeal Pneumococcal Carriage in a Nigerian Population: Epidemiology and Population Biology

PubMed Central

Adetifa, Ifedayo M. O.; Antonio, Martin; Okoromah, Christy A. N.; Ebruke, Chinelo; Inem, Victor; Nsekpong, David; Bojang, Abdoulie; Adegbola, Richard A.

2012-01-01

Background Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria. Methods This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST). Results The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage. Conclusions Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our

Invasive streptococcal disease: a review for clinicians.

PubMed

Parks, Tom; Barrett, Lucinda; Jones, Nicola

2015-09-01

Streptococci are a genus of Gram-positive bacteria which cause diverse human diseases. Many of these species have the potential to cause invasive infection resulting from the presence of bacteria in a normally sterile site. Original articles, reviews and guidelines. Invasive infection by a streptococcus species usually causes life-threatening illness. When measured in terms of deaths, disability and cost, these infections remain an important threat to health in the UK. Overall they are becoming more frequent among the elderly and those with underlying chronic illness. New observational evidence has become available to support the use of clindamycin and intravenous immunoglobulin in invasive Group A streptococcal disease. Few interventions for the treatment and prevention of these infections have undergone rigorous evaluation in clinical trials. For example, the role of preventative strategies such as screening of pregnant women to prevent neonatal invasive Group B streptococcal disease needs to be clarified. Studies of invasive streptococcal disease are challenging to undertake, not least because individual hospitals treat relatively few confirmed cases. Instead clinicians and scientists must work together to build national and international networks with the aim of developing a more complete evidence base for the treatment and prevention of these devastating infections. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

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.

Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision analytical model.

PubMed

Bakır, Mustafa; Türel, Ozden; Topachevskyi, Oleksandr

2012-11-09

Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7). We compare the cost effectiveness of a 13-valent PCV (PCV-13) and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with that of PCV-7 in Turkey. A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population <10 years old that would experience 10 mutually exclusive outcomes over the course of 1 year from a perspective of a healthcare system. Model outcomes were adjusted according to the population demographics and region-specific serotype distribution in Turkey. Health outcomes and direct healthcare costs were simulated for PCV-7, PCV-13 and PHiD-CV. PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs) and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children.

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

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

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

Invasive Paget Disease of the Vulva.

PubMed

Borghi, Chiara; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Perotto, Stefania; Leone Roberti Maggiore, Umberto; Recalcati, Dario; Lorusso, Domenica; Raspagliesi, Francesco

2018-01-01

Extramammary Paget disease of the vulva (EPDV) is a rare occurrence with an indolent and relapsing course. Progression to invasion occurs in 4% to 19% of cases. The aim of this study is to report clinical-pathological features and outcomes of patients treated for invasive EPDV. Data of consecutive patients treated between 2000 and 2017 for invasive EPDV were reviewed. Among 79 patients with EPDV, 10 (12.7%) presented a microinvasive or invasive form at first diagnosis or during follow-up. All of them underwent upfront radical surgery; 7 (70%) received subsequent radiotherapy, chemotherapy, or both. The mortality rate was 40%. The recurrence rate after treatment for invasive forms was 60%, with a mean time to first recurrence of 20 (range, 5-36) months. Our study confirms that invasive EPDV remains a rare gynecological neoplasm with a poor prognosis. Multicentre trials or well-organized prospective data collection could improve the knowledge about the management of invasive EPDV.

Impact of bacterial coinfection on clinical outcomes in pneumococcal pneumonia.

PubMed

Kumagai, S; Ishida, T; Tachibana, H; Ito, Y; Ito, A; Hashimoto, T

2015-09-01

The aim of this study was to investigate the influence of bacterial coinfection on patients with pneumococcal pneumonia. We retrospectively analyzed the incidence, clinical features, microbial distributions, and outcomes of patients with bacterial coinfection in a cohort of 433 hospitalized patients with pneumococcal pneumonia. Eighty-five patients (19.6 %) were diagnosed with bacterial coinfection; the most frequent pathogens were Haemophilus influenzae (25 patients, 33.3 %), methicillin-susceptible Staphylococcus aureus (MSSA) (15 patients, 20.0 %), and Moraxella catarrhalis (13 patients, 17.3 %). The CURB-65 score and pneumonia severity index (PSI) were significantly higher in patients with bacterial coinfection (both P < 0.001). In addition, the proportion of patients with bacterial coinfection who met the Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria was significantly higher (P < 0.001). Multivariate logistic regression analysis identified three risk factors for bacterial coinfection in patients with pneumococcal pneumonia: alcoholism (odds ratio [OR], 5.12; 95 % confidence interval (95 % CI), 1.60-16.4; P = 0.006), hospitalization for 2 days or more within 90 days preceding admission (OR, 2.02; 95 % CI, 1.03-3.98; P = 0.041), and residence in a nursing home or extended care facility (OR, 3.22; 95 % CI, 1.48-6.97; P = 0.003). Multivariate analysis for 30-day mortality showed that bacterial coinfection was a significant adverse prognostic factor (OR, 2.50; 95 % CI, 1.13-5.53; P = 0.023), independent of IDSA/ATS severe pneumonia, PSI, or healthcare-associated pneumonia. In conclusion, bacterial coinfection may have an adverse impact on severity and outcomes of pneumococcal pneumonia.

Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia.

PubMed

Naucler, Pontus; Darenberg, Jessica; Morfeldt, Eva; Ortqvist, Ake; Henriques Normark, Birgitta

2013-06-01

Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia. To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia. A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden. Data on host factors and initial antibiotic treatment were collected from patient records. Antibiotic resistance and serotype were determined for bacterial isolates. Logistic regression analyses were performed to assess risk factors for 30-day mortality. Smoking, alcohol abuse, solid tumour, liver disease and renal disease attributed to 14.9%, 13.1%, 13.1%, 8.0% and 7.4% of the mortality, respectively. Age was the strongest predictor, and mortality increased exponentially from 1.3% in patients <45 years of age to 26.1% in patients aged ≥85 years. There was considerable confounding by host factors on the association between serotype and mortality. Increasing age, liver disease and serotype were associated with mortality in patients admitted to the ICU. Combined treatment with β-lactam antibiotics and macrolide/quinolone was associated with reduced mortality in patients in the ICU, although confounding could not be ruled out. Host factors appear to be more important than the specific serotype as determinants of mortality in patients with bacteraemic pneumococcal pneumonia. Several host factors were identified that contribute to mortality, which is important for prognosis and to guide targeted prevention strategies.

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.

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.

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.

Inhibition of pneumococcal choline-binding proteins and cell growth by esters of bicyclic amines.

PubMed

Maestro, Beatriz; González, Ana; García, Pedro; Sanz, Jesús M

2007-01-01

Streptococcus pneumoniae is one of the major pathogens worldwide. The use of currently available antibiotics to treat pneumococcal diseases is hampered by increasing resistance levels; also, capsular polysaccharide-based vaccination is of limited efficacy. Therefore, it is desirable to find targets for the development of new antimicrobial drugs specifically designed to fight pneumococcal infections. Choline-binding proteins are a family of polypeptides, found in all S. pneumoniae strains, that take part in important physiologic processes of this bacterium. Among them are several murein hydrolases whose enzymatic activity is usually inhibited by an excess of choline. Using a simple chromatographic procedure, we have identified several choline analogs able to strongly interact with the choline-binding module (C-LytA) of the major autolysin of S. pneumoniae. Two of these compounds (atropine and ipratropium) display a higher binding affinity to C-LytA than choline, and also increase the stability of the protein. CD and fluorescence spectroscopy analyses revealed that the conformational changes of C-LytA upon binding of these alkaloids are different to those induced by choline, suggesting a different mode of binding. In vitro inhibition assays of three pneumococcal, choline-dependent cell wall lytic enzymes also demonstrated a greater inhibitory efficiency of those molecules. Moreover, atropine and ipratropium strongly inhibited in vitro pneumococcal growth, altering cell morphology and reducing cell viability, a very different response than that observed upon addition of an excess of choline. These results may open up the possibility of the development of bicyclic amines as new antimicrobials for use against pneumococcal pathologies.

Estimated public health impact of nationwide vaccination of infants with 7-valent pneumococcal conjugate vaccine (PCV7) in China.

PubMed

Hu, ShanLian; Shi, Qiang; Chen, Chieh-I; Caldwell, Ronald; Wang, Bruce; Du, LiXia; He, JiangJiang; Roberts, Craig S

2014-09-01

The goal of this study was to provide a comprehensive analysis of the potential health impact of universal vaccination of infants with the 7-valent pneumococcal conjugate vaccine (PCV7) in China. A decision-analytic model designed for pneumococcal disease and outcomes of pneumococcal infection was populated with local age-specific incidence and mortality data to estimate the expected health benefits of vaccinating birth cohorts of approximately 16 million infants per year over a 10-year time horizon in China. The model incorporates both the direct impact on vaccinated children and the indirect effect of herd protection on unvaccinated children and adults. The model predicts that more than 16.2 million cases of pneumococcal disease and 709 411 deaths could be prevented in China over the initial 10-year period following the introduction of the PCV7 vaccine. The majority of these health benefits are due to the indirect effectiveness of the vaccine on the unvaccinated population, resulting in approximately 10.8 million cases prevented and 636 371 lives saved over 10 years. The results suggest that a policy of universal PCV7 vaccination among infants in China would have a substantial positive public health impact on the population of China. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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.

Description of the Pathogenic Features of Streptococcus pyogenes Isolates from Invasive and Non-Invasive Diseases in Aichi, Japan.

PubMed

Matsumoto, Masakado; Yamada, Kazuhiro; Suzuki, Masahiro; Adachi, Hirokazu; Kobayashi, Shinichi; Yamashita, Teruo; Minagawa, Hiroko; Tatsuno, Ichiro; Hasegawa, Tadao

2016-07-22

We identified hypervirulent Streptococcus pyogenes in 27 and 420 isolates from patients with invasive and non-invasive diseases, respectively, in Aichi Prefecture, Japan, between 2003 and 2012, in an attempt to understand why the prevalence of streptococcal toxic shock syndrome (STSS) suddenly increased in this location during 2011. Hypervirulent strains belong to the emm1 genotype, with a mutation in the covR/S genes that regulate many other genes, encoding virulence determinants and resulting in the absence of the proteinase streptococcal exotoxin B and the production of virulence factors such as the superantigen streptococcal exotoxin A, the nuclease streptococcal DNase, the cytotoxin NAD-glycohydrolase, and the hemolysin streptolysin O. We found 1 strain from invasive disease and 1 from non-invasive disease with traits similar to those of hypervirulent strains, except that the sda1 gene was absent. We also found 1 non-emm1 strain with phenotypic and genetic traits identical to those of the emm1 hypervirulent strains except that it did not belong to emm1 genotype, from non-invasive diseases cases in 2011. These findings suggested that hypervirulent and hypervirulent-like strains from invasive and non-invasive disease cases could have at least partially contributed to the sudden increase in the number of patients with STSS in Aichi during 2011.

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.

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...

Cost-effectiveness of pneumococcal conjugate vaccination in Croatia.

PubMed

Vučina, V Višekruna; Filipović, S Kurečić; Kožnjak, N; Stamenić, V; Clark, A D; Mounaud, B; Blau, J; Hoestlandt, C; Kaić, B

2015-05-07

Pneumococcus is a known cause of meningitis, pneumonia, sepsis, and acute otitis media in children and adults globally. Two new vaccines for children have the potential to prevent illness, disability, and death, but these vaccines are expensive. The Croatian Ministry of Health has considered introducing the vaccine in the past, but requires economic evidence to ensure that the limited funds available for health care will be used in the most effective way. Croatia appointed a multidisciplinary team of experts to evaluate the cost-effectiveness of introducing pneumococcal conjugate vaccination (PCV) into the national routine child immunization program. Both 10-valent and 13-valent PCV (PCV10 and PCV13) were compared to a scenario assuming no vaccination. The TRIVAC decision-support model was used to estimate cost-effectiveness over the period 2014-2033. We used national evidence on demographics, pneumococcal disease incidence and mortality, the age distribution of disease in children, health service utilization, vaccine coverage, vaccine timeliness, and serotype coverage. Vaccine effectiveness was based on evidence from the scientific literature. Detailed health care costs were not available from the Croatian Institute for Health Insurance at the time of the analysis so assumptions and World Health Organization (WHO) estimates for Croatia were used. We assumed a three-dose primary vaccination schedule, and an initial price of US$ 30 per dose for PCV10 and US$ 35 per dose for PCV13. We ran univariate sensitivity analyses and multivariate scenario analyses. Either vaccine is estimated to prevent approximately 100 hospital admissions and one death each year in children younger than five in Croatia. Compared to no vaccine, the discounted cost-effectiveness of either vaccine is estimated to be around US$ 69,000-77,000 per disability-adjusted life-years (DALYs) averted over the period 2014-2033 (from the government or societal perspective). Only two alternative scenarios

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.

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

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

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.

Advance market commitment for pneumococcal vaccines: putting theory into practice

PubMed Central

Cernuschi, Tania; Schwalbe, Nina; Jones, Andrew; Berndt, Ernst R; McAdams, Susan

2011-01-01

Abstract Markets for life-saving vaccines do not often generate the most desired outcomes from a public health perspective in terms of product quantity, quality, affordability, programmatic suitability and/or sustainability for use in the lowest income countries. The perceived risks and uncertainties about sustainably funded demand from developing countries often leads to underinvestment in development and manufacturing of appropriate products. The pilot initiative Advance Market Commitment (AMC) for pneumococcal vaccines, launched in 2009, aims to remove some of these market risks by providing a legally binding forward commitment to purchase vaccines according to predetermined terms. To date, 14 countries have already introduced pneumococcal vaccines through the AMC with a further 39 countries expected to introduce before the end of 2013. This paper describes early lessons learnt on the selection of a target disease and the core design choices for the pilot AMC. It highlights the challenges faced with tailoring the AMC design to the specific supply situation of pneumococcal vaccines. It points to the difficulty – and the AMC’s apparent early success – in establishing a long-term, credible commitment in a constantly changing unpredictable environment. It highlights one of the inherent challenges of the AMC: its dependence on continuous donor funding to ensure long-term purchases of products. The paper examines alternative design choices and aims to provide a starting point to inform discussions and encourage debate about the potential application of the AMC concept to other fields. PMID:22271949

Advance market commitment for pneumococcal vaccines: putting theory into practice.

PubMed

Cernuschi, Tania; Furrer, Eliane; Schwalbe, Nina; Jones, Andrew; Berndt, Ernst R; McAdams, Susan

2011-12-01

Markets for life-saving vaccines do not often generate the most desired outcomes from a public health perspective in terms of product quantity, quality, affordability, programmatic suitability and/or sustainability for use in the lowest income countries. The perceived risks and uncertainties about sustainably funded demand from developing countries often leads to underinvestment in development and manufacturing of appropriate products. The pilot initiative Advance Market Commitment (AMC) for pneumococcal vaccines, launched in 2009, aims to remove some of these market risks by providing a legally binding forward commitment to purchase vaccines according to predetermined terms. To date, 14 countries have already introduced pneumococcal vaccines through the AMC with a further 39 countries expected to introduce before the end of 2013.This paper describes early lessons learnt on the selection of a target disease and the core design choices for the pilot AMC. It highlights the challenges faced with tailoring the AMC design to the specific supply situation of pneumococcal vaccines. It points to the difficulty - and the AMC's apparent early success - in establishing a long-term, credible commitment in a constantly changing unpredictable environment. It highlights one of the inherent challenges of the AMC: its dependence on continuous donor funding to ensure long-term purchases of products. The paper examines alternative design choices and aims to provide a starting point to inform discussions and encourage debate about the potential application of the AMC concept to other fields.

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.

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

Apoptosis is essential for neutrophil functional shutdown and determines tissue damage in experimental pneumococcal meningitis.

PubMed

Koedel, Uwe; Frankenberg, Tobias; Kirschnek, Susanne; Obermaier, Bianca; Häcker, Hans; Paul, Robert; Häcker, Georg

2009-05-01

During acute bacterial infections such as meningitis, neutrophils enter the tissue where they combat the infection before they undergo apoptosis and are taken up by macrophages. Neutrophils show pro-inflammatory activity and may contribute to tissue damage. In pneumococcal meningitis, neuronal damage despite adequate chemotherapy is a frequent clinical finding. This damage may be due to excessive neutrophil activity. We here show that transgenic expression of Bcl-2 in haematopoietic cells blocks the resolution of inflammation following antibiotic therapy in a mouse model of pneumococcal meningitis. The persistence of neutrophil brain infiltrates was accompanied by high levels of IL-1beta and G-CSF as well as reduced levels of anti-inflammatory TGF-beta. Significantly, Bcl-2-transgenic mice developed more severe disease that was dependent on neutrophils, characterized by pronounced vasogenic edema, vasculitis, brain haemorrhages and higher clinical scores. In vitro analysis of neutrophils demonstrated that apoptosis inhibition completely preserves neutrophil effector function and prevents internalization by macrophages. The inhibitor of cyclin-dependent kinases, roscovitine induced apoptosis in neutrophils in vitro and in vivo. In wild type mice treated with antibiotics, roscovitine significantly improved the resolution of the inflammation after pneumococcal infection and accelerated recovery. These results indicate that apoptosis is essential to turn off activated neutrophils and show that inflammatory activity and disease severity in a pyogenic infection can be modulated by targeting the apoptotic pathway in neutrophils.

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.

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

V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

PubMed

Valls Serón, Mercedes; Ferwerda, Bart; Engelen-Lee, JooYeon; Geldhoff, Madelijn; Jaspers, Valery; Zwinderman, Aeilko H; Tanck, Michael W; Baas, Frank; van der Ende, Arie; Brouwer, Matthijs C; van de Beek, Diederik

2016-05-18

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. Here, we have performed a prospective nationwide genetic association study using the Human Exome BeadChip and identified gene variants in encoding dynactin 4 (DCTN4), retinoic acid early transcript 1E (RAET1E), and V-akt murine thymoma viral oncogene homolog 3 (AKT3) to be associated with unfavourable outcome in patients with pneumococcal meningitis. No clinical replication cohort is available, so we validated the role of one of these targets, AKT3, in a pneumococcal meningitis mouse model. Akt3 deficient mice had worse survival and increased histopathology scores for parenchymal damage (infiltration) and vascular infiltration (large meningeal artery inflammation) but similar bacterial loads, cytokine responses, compared to wild-type mice. We found no differences in cerebrospinal fluid cytokine levels between patients with risk or non-risk alleles. Patients with the risk genotype (rs10157763, AA) presented with low scores on the Glasgow Coma Scale and high rate of epileptic seizures. Thus, our results show that AKT3 influences outcome of pneumococcal meningitis.

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.

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.

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

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.

[Health economic evaluation of a 23 value pneumococcal polysaccharide vaccination pilot programme among elderly chronic obstructive pulmonary disease patients in China].

PubMed

Qiu, Y P; Zhao, K; Li, X; Shi, L W; Guo, W D; Qi, X R; Sui, B Y; Zhou, R M

2016-12-06

Objective: From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods: In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results: By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient

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

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

A Pneumococcal Protein Array as a Platform to Discover Serodiagnostic Antigens Against Infection*

PubMed Central

Olaya-Abril, Alfonso; Jiménez-Munguía, Irene; Gómez-Gascón, Lidia; Obando, Ignacio; Rodríguez-Ortega, Manuel J.

2015-01-01

Pneumonia is one of the most common and severe diseases associated with Streptococcus pneumoniae infections in children and adults. Etiological diagnosis of pneumococcal pneumonia in children is generally challenging because of limitations of diagnostic tests and interference with nasopharyngeal colonizing strains. Serological assays have recently gained interest to overcome some problems found with current diagnostic tests in pediatric pneumococcal pneumonia. To provide insight into this field, we have developed a protein array to screen the antibody response to many antigens simultaneously. Proteins were selected by experimental identification from a collection of 24 highly prevalent pediatric clinical isolates in Spain, using a proteomics approach consisting of “shaving” the cell surface with proteases and further LC/MS/MS analysis. Ninety-five proteins were recombinantly produced and printed on an array. We probed it with a collection of sera from children with pneumococcal pneumonia. From the set of the most seroprevalent antigens, we obtained a clear discriminant response for a group of three proteins (PblB, PulA, and PrtA) in children under 4 years old. We validated the results by ELISA and an immunostrip assay showed the translation to easy-to-use, affordable tests. Thus, the protein array here developed presents a tool for broad use in serodiagnostics. PMID:26183717

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.

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

Identification, variation and transcription of pneumococcal repeat sequences

PubMed Central

2011-01-01

Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

Invasive pests—insects and diseases

Treesearch

Donald A. Duerr; Paul A. Mistretta

2013-01-01

Key FindingsNonnative pest species have increasing impacts in the South regardless of climate change, patterns of land ownership, or changes in the composition of vegetation.“New” nonnative invasive insects and diseases will have serious impacts on southern forests over the next 50 years. Some species such as emerald ash borer...

Apoptosis Is Essential for Neutrophil Functional Shutdown and Determines Tissue Damage in Experimental Pneumococcal Meningitis

PubMed Central

Kirschnek, Susanne; Obermaier, Bianca; Häcker, Hans; Paul, Robert; Häcker, Georg

2009-01-01

During acute bacterial infections such as meningitis, neutrophils enter the tissue where they combat the infection before they undergo apoptosis and are taken up by macrophages. Neutrophils show pro-inflammatory activity and may contribute to tissue damage. In pneumococcal meningitis, neuronal damage despite adequate chemotherapy is a frequent clinical finding. This damage may be due to excessive neutrophil activity. We here show that transgenic expression of Bcl-2 in haematopoietic cells blocks the resolution of inflammation following antibiotic therapy in a mouse model of pneumococcal meningitis. The persistence of neutrophil brain infiltrates was accompanied by high levels of IL-1β and G-CSF as well as reduced levels of anti-inflammatory TGF-β. Significantly, Bcl-2-transgenic mice developed more severe disease that was dependent on neutrophils, characterized by pronounced vasogenic edema, vasculitis, brain haemorrhages and higher clinical scores. In vitro analysis of neutrophils demonstrated that apoptosis inhibition completely preserves neutrophil effector function and prevents internalization by macrophages. The inhibitor of cyclin-dependent kinases, roscovitine induced apoptosis in neutrophils in vitro and in vivo. In wild type mice treated with antibiotics, roscovitine significantly improved the resolution of the inflammation after pneumococcal infection and accelerated recovery. These results indicate that apoptosis is essential to turn off activated neutrophils and show that inflammatory activity and disease severity in a pyogenic infection can be modulated by targeting the apoptotic pathway in neutrophils. PMID:19478887

Arachidonic Acid Stress Impacts Pneumococcal Fatty Acid Homeostasis

PubMed Central

Eijkelkamp, Bart A.; Begg, Stephanie L.; Pederick, Victoria G.; Trapetti, Claudia; Gregory, Melissa K.; Whittall, Jonathan J.; Paton, James C.; McDevitt, Christopher A.

2018-01-01

Free fatty acids hold dual roles during infection, serving to modulate the host immune response while also functioning directly as antimicrobials. Of particular importance are the long chain polyunsaturated fatty acids, which are not commonly found in bacterial organisms, that have been proposed to have antibacterial roles. Arachidonic acid (AA) is a highly abundant long chain polyunsaturated fatty acid and we examined its effect upon Streptococcus pneumoniae. Here, we observed that in a murine model of S. pneumoniae infection the concentration of AA significantly increases in the blood. The impact of AA stress upon the pathogen was then assessed by a combination of biochemical, biophysical and microbiological assays. In vitro bacterial growth and intra-macrophage survival assays revealed that AA has detrimental effects on pneumococcal fitness. Subsequent analyses demonstrated that AA exerts antimicrobial activity via insertion into the pneumococcal membrane, although this did not increase the susceptibility of the bacterium to antibiotic, oxidative or metal ion stress. Transcriptomic profiling showed that AA treatment also resulted in a dramatic down-regulation of the genes involved in fatty acid biosynthesis, in addition to impacts on other metabolic processes, such as carbon-source utilization. Hence, these data reveal that AA has two distinct mechanisms of perturbing the pneumococcal membrane composition. Collectively, this work provides a molecular basis for the antimicrobial contribution of AA to combat pneumococcal infections. PMID:29867785

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

In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

PubMed Central

Li, Yi; Beitelshees, Marie; Fang, Lei; Hill, Andrew; Ahmadi, Mahmoud Kamal; Chen, Mingfu; Davidson, Bruce A.; Knight, Paul; Smith, Randall J.; Andreadis, Stelios T.; Hakansson, Anders P.; Jones, Charles H.; Pfeifer, Blaine A.

2016-01-01

The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector. PMID:27419235

Identification of the psaA Gene, Coding for Pneumococcal Surface Adhesin A, in Viridans Group Streptococci other than Streptococcus pneumoniae

PubMed Central

Jado, Isabel; Fenoll, Asunción; Casal, Julio; Pérez, Amalia

2001-01-01

The gene encoding the pneumococcal surface adhesin A (PsaA) protein has been identified in three different viridans group streptococcal species. Comparative studies of the psaA gene identified in different pneumococcal isolates by sequencing PCR products showed a high degree of conservation among these strains. PsaA is encoded by an open reading frame of 930 bp. The analysis of this fragment in Streptococcus mitis, Streptococcus oralis, and Streptococcus anginosus strains revealed a sequence identity of 95, 94, and 90%, respectively, to the corresponding open reading frame of the previously reported Streptococcus pneumoniae serotype 6B strain. Our results confirm that psaA is present and detectable in heterologous bacterial species. The possible implications of these results for the suitability and potential use of PsaA in the identification and diagnosis of pneumococcal diseases are discussed. PMID:11527799

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.

A Perspective on Invasive Salmonella Disease in Africa.

PubMed

Crump, John A; Heyderman, Robert S

2015-11-01

Salmonella enterica is a leading cause of community-acquired bloodstream infection in Africa. The contribution of typhoidal and nontyphoidal Salmonella serovars to invasive disease varies considerably in place and time, even within the same country. Nonetheless, many African countries are now thought to experience typhoid fever incidence >100 per 100,000 per year with approximately 1% of patients dying. Invasive nontyphoidal Salmonella (iNTS) disease was estimated to cause 3.4 million illnesses and 681 316 deaths in 2010, with the most disease in Africa. Antimicrobial drug resistance is a growing problem in S. enterica that threatens to further compromise patient outcomes. Reservoirs for nontyphoidal Salmonella and the predominant routes of transmission for typhoidal and nontyphoidal Salmonella are not well understood in Africa, hampering the design of evidence-based, non-vaccine- and vaccine-based prevention measures. It is difficult to distinguish clinically invasive Salmonella disease from febrile illnesses caused by other pathogens. Blood cultures are the mainstay of laboratory diagnosis, but lack sensitivity due to the low magnitude of bacteremia, do not produce results at point of care, and are not widely available in Africa. Serologic approaches to diagnosis remain inaccurate, and nucleic acid amplification tests are also compromised by low concentrations of bacteria. High-throughput whole-genome sequencing, together with a range of novel analytic pipelines, has provided new insights into the complex pattern of epidemiology, pathogenesis, and host adaptation. Concerted efforts are therefore needed to apply these new tools in the context of high-quality field surveillance to improve diagnosis, patient management, control, and prevention of invasive Salmonella infections in Africa. © 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.

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.

Haemophilus influenzae serotype a invasive disease, Alaska, USA, 1983-2011.

PubMed

Bruce, Michael G; Zulz, Tammy; DeByle, Carolynn; Singleton, Ros; Hurlburt, Debby; Bruden, Dana; Rudolph, Karen; Hennessy, Thomas; Klejka, Joseph; Wenger, Jay D

2013-06-01

Before introduction of Haemophilus influenzae type b (Hib) vaccines, rates of Hib disease in Alaska's indigenous people were among the highest in the world. Vaccination reduced rates dramatically; however, invasive H. influenzae type a (Hia) disease has emerged. Cases of invasive disease were identified through Alaska statewide surveillance during 1983-2011. Of 866 isolates analyzed for serotype, 32 (4%) were Hia. No Hia disease was identified before 2002; 32 cases occurred during 2002-2011 (p<0.001). Median age of case-patients was 0.7 years; 3 infants died. Incidence of Hia infection (2002-2011) among children <5 years was 5.4/100,000; 27 cases occurred in Alaska Native children (18/100,000) versus 2 cases in non-Native children (0.5/100,000) (risk ratio = 36, p<0.001). From 12/2009 to 12/2011, 15 cases of Hia disease occurred in southwestern Alaska (in children <5 years, rate = 204/100,000). Since introduction of the Hib conjugate vaccine, Hia infection has become a major invasive bacterial disease in Alaska Native children.

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

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.

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.

Invasive Disease Caused by Nontypeable Haemophilus influenzae

PubMed Central

de Jonge, Marien I.

2015-01-01

The incidence of severe Haemophilus influenza infections, such as sepsis and meningitis, has declined substantially since the introduction of the H. influenzae serotype b vaccine. However, the H. influenzae type b vaccine fails to protect against nontypeable H. influenzae strains, which have become increasingly frequent causes of invasive disease, especially among children and the elderly. We summarize recent literature supporting the emergence of invasive nontypeable H. influenzae and describe mechanisms that may explain its increasing prevalence over the past 2 decades. PMID:26407156

[Invasive meningococcal disease--management and treatment].

PubMed

Garlicki, Aleksander; Bociqga-Jasik, Monika; Kalinowska-Nowak, Anna

2008-01-01

Invasive meningococcal disease is life threatening disease and in fulminant cases mortality rate may be as high as 70%. Rapid introduction of treatment and monitoring on intensive care unit is crucial for prognosis. The understanding of patomechanism responsible for sepsis development allow to introduce supportive treatment including glicocorticoids and recombinant human activated protein C. Very important is suitable prophylaxis among risk groups with, additional considering vaccination in the case of infection caused by A, C, Y, W-135 serogroups.

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.

Using the impact of pneumococcal vaccines on nasopharyngeal carriage to aid licensing and vaccine implementation; a PneumoCarr meeting report March 27-28, 2012, Geneva.

PubMed

Goldblatt, David; Ramakrishnan, Meena; O'Brien, Katherine

2013-12-17

An international consultation was convened in March 2012 to provide feedback on the Case for Carriage, a summary statement by the Pneumococcal Carriage Consortium (PneumoCarr) proposing nasopharyngeal (NP) colonization as a supplementary or alternative endpoint in vaccine licensure. PneumoCarr members provided information to vaccine manufacturers, regulators and the WHO on the evidence for NP carriage as a precursor to pneumococcal disease, standardization of laboratory methods for the detection of multiple serotype carriage, definition and estimation of pneumococcal vaccine efficacy against carriage (VE-col), and the direct and indirect impact of vaccination on carriage. Manufacturers and regulators had the opportunity to respond to the information compiled by PneumoCarr and share their perspectives. VE-col as a licensure endpoint may be more useful for the next generation pneumococcal vaccine products, particularly those for which the immunological correlate of protection is not established, whereas it may be less needed for pneumococcal conjugate vaccines which have an established licensure pathway. The consultation supported the importance of NP carriage data as a critical element linking vaccine impact on the individual direct risk of disease to the population-level impact: indirect effects such as herd protection and serotype replacement. The indirect effects of vaccination, however, are not currently established as part of the licensure process and to include them would be a paradigm shift for regulatory agencies who currently consider this information in the post-licensure setting. More discussion and consensus-building is needed around the rationale and optimal mechanism to include carriage data in the licensure pathway for new pneumococcal vaccines. The WHO and national advisory groups on immunization policy may have an important role in considering the evidence for the indirect benefit of vaccination as informed by its impact on NP carriage. Copyright �

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

Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah, USA.

PubMed

Rubach, Matthew P; Bender, Jeffrey M; Mottice, Susan; Hanson, Kimberly; Weng, Hsin Y C; Korgenski, Kent; Daly, Judy A; Pavia, Andrew T

2011-09-01

Since the introduction of the Haemophilus influenzae type b vaccine, the incidence of invasive H. influenzae type b disease among children has fallen dramatically, but the effect on invasive H. influenzae disease among adults may be more complex. In this population-based study we examined the epidemiology and outcomes of invasive disease caused by typeable and nontypeable H. influenzae among Utah adults during 1998-2008. The overall incidence increased over the study period from 0.14/100,000 person-years in 1998 to 1.61/100,000 person-years in 2008. The average incidence in persons >65 years old was 2.74/100,000 person-years, accounting for 51% of cases and 67% of deaths. The incidence was highest for nontypeable H. influenzae (0.23/100,000 person-years), followed by H. influenzae type f (0.14/100,000 person-years). The case-fatality rate was 22%. The incidence of invasive H. influenzae in Utah adults appears to be increasing. Invasive H. influenzae infection disproportionately affected the elderly and was associated with a high mortality rate.

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.

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.

Treatment with belimumab in systemic lupus erythematosus does not impair antibody response to 13-valent pneumococcal conjugate vaccine.

PubMed

Nagel, J; Saxne, T; Geborek, P; Bengtsson, A A; Jacobsen, S; Svaerke Joergensen, C; Nilsson, J-Å; Skattum, L; Jönsen, A; Kapetanovic, M C

2017-09-01

Background/purpose The objective of this study was to explore the impact of systemic lupus erythematosus and belimumab given in addition to standard of care therapy on 13-valent conjugated pneumococcal vaccine (PCV13) response. Methods Forty-seven systemic lupus erythematosus patients and 21 healthy controls were immunized with a single dose of 13-valent conjugated pneumococcal vaccine. Forty systemic lupus erythematosus patients were treated with traditional disease-modifying anti rheumatic drugs, 11 of those received belimumab in addition, and 32 patients were treated with concomitant prednisolone. Quantification of serotype specific IgG levels to 12 pneumococcal capsular polysaccharides was performed in serum taken before and four to six weeks after vaccination using multiplex fluorescent microsphere immunoassay. IgG levels against serotypes 23F and 6B were also analyzed using standard enzyme-linked immunosorbent assays. Opsonophagocytic assay was performed on serotype 23F to evaluate the functionality of the antibodies. Pre- and post-vaccination log transformed antibody levels were compared to determine the impact of systemic lupus erythematosus diagnosis and different treatments on antibody response. Results Systemic lupus erythematosus patients as a group showed lower post-vaccination antibody levels and lower fold increase of antibody levels after vaccination compared to controls ( p = 0.02 and p = 0.009, respectively). Systemic lupus erythematosus patients treated with belimumab in addition to standard of care therapy or with only hydroxychloroquine did not differ compared to controls, whereas the other treatment groups had significantly lower fold increase of post-vaccination antibody levels. Higher age was associated with lower post-vaccination antibody levels among systemic lupus erythematosus patients. Conclusion Belimumab given in addition to traditional disease-modifying anti rheumatic drugs or prednisolone did not further impair antibody

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

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

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.

Invasive plants, insects, and diseases in the forests of the Anthropocene

Treesearch

Alexander M. Evans

2014-01-01

Invasive species, non-native plants, insects, and diseases can devastate forests. They outcompete native species, replace them in the ecosystem, and even drive keystone forest species to functional extinction. Invasives have negative effects on forest hydrology, carbon storage, and nutrient cycling. The damage caused by invasive species exacerbates the other forest...

Clinical "pneumococcal pneumonia" due to Moraxella osloensis: case report and a review.

PubMed

Vuori-Holopainen, E; Salo, E; Saxen, H; Vaara, M; Tarkka, E; Peltola, H

2001-01-01

A previously healthy 6-y-old girl presented with a disease very similar to pneumococcal pneumonia. However, Moraxella osloensis was isolated by lung tap. The patient responded well to a course of parenteral penicillin. This is probably the first documented case of community-acquired pneumonia associated with this agent. Clinical isolates of M. osloensis are rare and its pathogenesis has not been delineated; however, a literature review suggests that the organism is more common than is generally recognized.

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

Economic evaluation of pneumococcal conjugate vaccination in The Gambia.

PubMed

Kim, Sun-Young; Lee, Gene; Goldie, Sue J

2010-09-03

Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars) per disability-adjusted life year (DALY) averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Assuming 90% coverage, a program using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Based on the information available now, infant PCV vaccination would be expected to reduce pneumococcal diseases caused by S. pneumoniae in The Gambia

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.

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.

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

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.

Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes

PubMed Central

Walter, Katharine S.; Pepin, Kim M.; Webb, Colleen T.; Gaff, Holly D.; Krause, Peter J.; Pitzer, Virginia E.; Diuk-Wasser, Maria A.

2016-01-01

Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach—occupancy modelling—to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease. PMID:27252022

Cost-effectiveness of vaccination against pneumococcal bacteremia among elderly people.

PubMed

Sisk, J E; Moskowitz, A J; Whang, W; Lin, J D; Fedson, D S; McBean, A M; Plouffe, J F; Cetron, M S; Butler, J C

Clinical, epidemiologic, and policy considerations support updating the cost-effectiveness of pneumococcal vaccination for elderly people and targeting the evaluation only to prevention of pneumococcal bacteremia. To assess the implications for medical costs and health effects of vaccination against pneumococcal bacteremia in elderly people. Cost-effectiveness analysis of pneumococcal vaccination compared with no vaccination, from a societal perspective. The elderly population aged 65 years and older in the United States in 3 geographic areas: metropolitan Atlanta, Ga; Franklin County, Ohio; and Monroe County, New York. Incremental medical costs and health effects, expressed in quality-adjusted life-years per person vaccinated. Vaccination was cost saving, ie, it both reduced medical expenses and improved health, for all age groups and geographic areas analyzed in the base case. For people aged 65 years and older, vaccination saved $8.27 and gained 1.21 quality-adjusted days of life per person vaccinated. Vaccination of the 23 million elderly people unvaccinated in 1993 would have gained about 78000 years of healthy life and saved $194 million. In univariate sensitivity analysis, the results remained cost saving except for doubling vaccination costs, including future medical costs of survivors, and lowering vaccination effectiveness. With assumptions most unfavorable to vaccination, cost per quality-adjusted life-year ranged from $35 822 for ages 65 to 74 years to $598 487 for ages 85 years and older. In probabilistic sensitivity analysis, probability intervals were more narrow, with less than 5% probability that the ratio for ages 85 years and older would exceed $100000. Pneumococcal vaccination saves costs in the prevention of bacteremia alone and is greatly underused among the elderly population, on both health and economic grounds. These results support recent recommendations of the Advisory Committee on Immunization Practices and public and private efforts

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

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

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

Prospective Surveillance of Invasive Group A Streptococcal Disease, Fiji, 2005–2007

PubMed Central

Jenney, Adam; Kado, Joseph; Good, Michael F.; Batzloff, Michael; Waqatakirewa, Lepani; Mullholland, E. Kim; Carapetis, Jonathan R.

2009-01-01

We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005–2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6–12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1–92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention. PMID:19193265

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

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 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 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.

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.

Minimally invasive technology in the management of breast disease.

PubMed

Hung, W K; Ying, M; Chan, C M; Lam, H S; Mak, K L

2009-01-01

Minimally invasive surgery is gaining popularity around the world because it achieves the same or even superior results when compared to standard surgery but with less morbidity. Minimally invasive breast surgery is a broad concept encompassing new developments in the field of breast surgery that work on this minimally invasive principle. In this regard, breast-conserving surgery and sentinel lymph node biopsy are good illustrations of this concept. There are three major areas of progress in the minimally invasive management of breast disease. First, percutaneous excisional devices are now available that can replace the surgical excision of breast mass lesions. Second, various ablative treatments are capable of destroying breast cancers in situ instead of surgical excision. Third, mammary ductoscopy provides a new approach to the investigation of mammary duct pathology. Clinical experience and potential applications of these new technologies are reviewed.

Use of a low-literacy patient education tool to enhance pneumococcal vaccination rates. A randomized controlled trial.

PubMed

Jacobson, T A; Thomas, D M; Morton, F J; Offutt, G; Shevlin, J; Ray, S

1999-08-18

Pneumococcal immunization rates for elderly and high-risk patients are only one third to one half the target rate of 60% established by the US Public Health Service. Limited or marginal literacy, which affects nearly 100 million Americans, especially the elderly, may contribute to these low rates of immunization. To determine whether the use of a simple, low-literacy educational tool enhances patient-physician dialogue about pneumococcal vaccination and increases rates of immunization. A randomized controlled trial conducted between May and June of 1998. Ambulatory care clinic of a 900-bed public teaching hospital serving a predominantly indigent, low-literate, African American, inner-city population. Of 433 patients who presented for routine primary care, had vaccine indications (age > or =65 years or chronic disease), and had not been previously vaccinated, 221 were randomly assigned to the intervention group and 212 to the control group. Of the total patient population (mean age, 63 years), 280 (64.7%) had less than a high school education, 401 (92.6%) were African American, and 300 (69.3%) were female. One-page, low-literacy (below fifth-grade level) educational handout encouraging patients to "ask your doctor about the pneumonia shot" vs a control group (1 -page, low-literacy educational handout conveying information about nutrition). Vaccination rates (documented by chart audit) of patients who received pneumococcal vaccination and rates of patients who self-reported having discussed vaccination with their physicians. Patients in the intervention group were 4 times more likely to have discussed the pneumococcal vaccine with their physicians than patients in the control group (87/221 [39.4%] vs 21/212 [9.9%]; relative risk [RR], 3.97 [95% confidence interval [CI], 2.71-5.83]), and were more than 5 times as likely to have received the pneumococcal vaccine than the control group (44/221 [19.9%] vs 8/212 [3.8%]; RR, 5.28 [95% CI, 2.80-9.93]). In a multivariate

A randomised, clinical trial comparing the effectiveness of hospital and community-based reminder systems for increasing uptake of influenza and pneumococcal vaccine in hospitalised patients aged 65 years and over.

PubMed

MacIntyre, C R; Kainer, M A; Brown, G V

2003-01-01

Hospitalisation represents an opportunity to identify unimmunised people at risk for the complications of influenza and pneumococcal disease. We conducted a randomised controlled trial of two strategies to increase uptake of influenza and pneumococcal vaccines in eligible, hospitalised subjects aged 65 years or more, admitted between May and September 1998 to a Melbourne hospital. Unvaccinated participants were allocated randomly to alert systems for hospital staff or community general practitioners (GPs). Follow-up occurred at 1 and 3 months. The baseline vaccination rates were 70% for influenza (426/606) and 41% (248/606) for pneumococcal disease. For unvaccinated subjects, the hospital alert resulted in 67% uptake compared to 55% following a GP alert for pneumococcal vaccine; and 63% in hospital compared to 53% following a GP alert for influenza vaccine. Although there was a trend toward a higher uptake in hospital, neither of these differences was statistically significant. The majority (75%) of vaccinations following a GP alert occurred within 1 month of discharge. Despite hospital and community-based reminder systems, there are still significant missed opportunities for vaccination. We did not demonstrate significant differences between hospital and GP reminder systems, but there was a trend towards higher uptake with opportunistic vaccination in hospital. Copyright 2003 S. Karger AG, Basel

[Economic evaluation of an infant immunization program in Mexico, based on 13-valent pneumococcal conjugated vaccines].

PubMed

Muciño-Ortega, Emilio; Mould-Quevedo, Joaquín Federico; Farkouh, Raymond; Strutton, David

2011-01-01

Vaccination is an effective intervention for reduce child morbidity and mortality associated to pneumococcus. The availability of new anti-pneumococcal vaccines makes it necessary to evaluate its potential impact on public health and costs related to their implementation. The aim of this study was to estimate the cost-effectiveness and cost-utility of immunization strategies based on pneumococcal conjugated vaccines (PCV's) currently available in Mexico from a third payer perspective. A decision tree model was developed to assess both, economic and health impact, of anti-pneumococcal vaccination in children <2 years (lifetime time horizon, discount rate: 5% annual). Comparators were: no-vaccination (reference) and strategies based on 7, 10 and 13-valent PCV's. Effectiveness measures were: child deaths avoided, life-years gained (LYG) and quality adjusted life years (QALY's) gained. Effectiveness, utility, local epidemiology and cost of treating pneumococcal diseases were extracted from published sources. Univariate sensitivity analysis were performed. Immunization dominates no-vaccination: strategy based on 13-valent vaccine prevented 16.205 deaths, gained 331.230 LY's and 332.006 QALY's and saved US$1.307/child vaccinated. Strategies based on 7 and 10-valent PCV's prevented 13.806 and 5.589 deaths, gained 282.193 and 114.251 LY's, 282.969 and 114.972 QALY's and saved US$1.084 and US$731/child vaccinated, respectively. These results were robust to variations in herd immunity and lower immunogenicity of 10-valent vaccine. In Mexico, immunization strategies based on 7, 10 and 13-valent PCV's would be cost-saving interventions, however, health outcomes and savings of the strategy based on 13-valent vaccine are greater than those estimated for 7 and 10-valent PCV's. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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.

No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine.

PubMed

Licciardi, Paul V; Toh, Zheng Quan; Clutterbuck, Elizabeth A; Balloch, Anne; Marimla, Rachel A; Tikkanen, Leena; Lamb, Karen E; Bright, Kathryn J; Rabuatoka, Uraia; Tikoduadua, Lisi; Boelsen, Laura K; Dunne, Eileen M; Satzke, Catherine; Cheung, Yin Bun; Pollard, Andrew J; Russell, Fiona M; Mulholland, Edward K

2016-06-01

A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013

PubMed Central

Bruce, Michael G.; Bruden, Dana; Zulz, Tammy; Reasonover, Alisa; Hurlburt, Debby; Hennessy, Thomas

2015-01-01

The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n = 8), 5.8% (n = 20), and 1.2% (n = 4) of the isolates, respectively. A total of 51 emm types were identified, of which emm1 (11.1%) was the most prevalent, followed by emm82 (8.8%), emm49 (7.8%), emm12 and emm3 (6.6% each), emm89 (6.2%), emm108 (5.5%), emm28 (4.7%), emm92 (4%), and emm41 (3.8%). The five most common emm types accounted for 41% of isolates. The emm types in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development. PMID:26560536

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia

PubMed Central

Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom

2016-01-01

Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections. PMID:26511795

Viability and virulence of pneumolysin, pneumococcal surface protein A, and pneumolysin/pneumococcal surface protein A mutants in the ear.

PubMed

Schachern, Patricia A; Tsuprun, Vladimir; Goetz, Sarah; Cureoglu, Sebahattin; Juhn, Steven K; Briles, David E; Paparella, Michael M; Ferrieri, Patricia

2013-09-01

Understanding how pneumococcal proteins affect the pathology of the middle ear and inner ear is important for the development of new approaches to prevent otitis media and its complications. To determine the viability and virulence of Streptococcus pneumoniae mutants deficient in pneumolysin (Ply-) and pneumococcal surface protein A (PspA-) in the chinchilla middle ear. Bullae of chinchillas were inoculated bilaterally with wild-type (Wt), Ply-, PspA-, and Ply-/PspA- strains. Bacterial colony-forming units (CFUs) in middle ear effusions were counted at 48 hours. The CFUs of the PspA- group were also counted at 6 to 36 hours after inoculation. Temporal bone histopathological results were compared. Twenty-seven chinchillas in an academic research laboratory. Chinchilla middle ears were inoculated with S pneumoniae to produce sufficient volumes of effusions and noticeable histopathological changes in the ears. The CFU counts in the middle ear effusions and histopathological changes were compared to determine the effect of pneumococcal protein mutations on chinchilla ears. At 48 hours, CFUs in middle ears were increased for the Wt and Ply-/PspA- strains, but Ply- remained near inoculum level. No bacteria were detected in the PspA- group. The CFUs of PspA- decreased over time to a low level at 30 to 36 hours. In vitro, PspA- in Todd-Hewitt broth showed an increase in bacterial growth of 2 logs at 43 hours, indicating PspA- susceptibility to host defenses in vivo. The PspA- and Ply- groups had fewer pathologic findings than the Wt or Ply-/PspA- groups. Histopathological analysis showed significant differences in the number of bacteria in the scala tympani in the Wt group compared with the Ply-, PspA-, and Ply-/PspA- groups. The PspA- strain was the least virulent. The PspA- mutant was much less viable and less virulent in the ear than the Wt, Ply-, and Ply-/PspA- strains. There was no significant attenuation in the viability and virulence of the Ply-/PspA- mutant

Pneumococcal vaccination and risk of myocardial infarction

PubMed Central

Lamontagne, François; Garant, Marie-Pierre; Carvalho, Jean-Christophe; Lanthier, Luc; Smieja, Marek; Pilon, Danielle

2008-01-01

Background Based on promising results from laboratory studies, we hypothesized that pneumococcal vaccination would protect patients from myocardial infarction. Methods We conducted a hospital-based case–control study that included patients considered to be at risk of myocardial infarction. We used health databases to obtain hospital diagnoses and vaccination status. We compared patients who had been admitted for treatment of myocardial infarction with patients admitted to a surgical department in the same hospital for a reason other than myocardial infarction between 1997 and 2003. Results We found a total of 43 209 patients who were at risk; of these, we matched 999 cases and 3996 controls according to age, sex and year of hospital admission. Cases were less likely than controls to have been vaccinated (adjusted odds ratio [OR] 0.53, 95% confidence interval [CI] 0.40–0.70). This putative protective role of the vaccine was not observed for patients who had received the vaccine up to 1 year before myocardial infarction (adjusted OR 0.85, 95% CI 0.54–1.33). In contrast, if vaccination had occurred 2 years or more before the hospital admission, the association was stronger (adjusted OR 0.33, 95% CI 0.20–0.46). Interpretation Pneumococcal vaccination was associated with a decrease of more than 50% in the rate myocardial infarction 2 years after exposure. If confirmed, this association should generate interest in exploring the putative mechanisms and may offer another reason to promote pneumococcal vaccination. PMID:18838452

Safety and tolerability of 13-valent pneumococcal conjugate vaccine in the elderly

PubMed Central

Durando, Paolo; Rosselli, Roberto; Cremonesi, Ilaria; Orsi, Andrea; Albanese, Erika; Barberis, Ilaria; Paganino, Chiara; Trucchi, Cecilia; Martini, Mariano; Marensi, Lorenzo; Turello, Valter; Study Group, the Ligurian Pneumococcal; Bregante, Alessandro; Cacciani, Roberto; Iudici, Rocco; La Marca, Diego; Pedano, Leonardo; Petrucci, Amadio Franco; Santolini, Maria; Sbisà, Valentina; Zacconi, Monica

2014-01-01

Background In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged ≥70 years. Methods An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted

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

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

The spread of invasive species and infectious disease as drivers of ecosystem change.

Treesearch

Todd A. Crowl; Thomas O. Crist; Robert R. Parmenter; Gary Belovsky; Ariel E. Lugo

2008-01-01

Invasive species, disease vectors, and pathogens affect biodiversity, ecosystem function and services, and human health. Climate change, land use, and transport vectors interact in complex ways to determine the spread of native and non-native invasive species, pathogens, and their effects on ecosystem dynamics. Early detection and in-depth understanding of invasive...

Invasive Non-typhoidal Salmonella Disease – epidemiology, pathogenesis and diagnosis

PubMed Central

Gordon, Melita A

2012-01-01

Purpose of review To highlight and discuss important publications over the past 12 months providing new insights on invasive non-typhoidal Salmonella disease (iNTS). Recent findings There have been informative new estimates of the burden of iNTS in Asia and in high-resource low-incidence settings. Important information has emerged in the last year about the relationships between HIV, malaria, iNTS and typhoid fever in adults and children in Africa. HIV causes susceptibility to iNTS disease, but has been shown to be protective against typhoid fever. Clinical guidelines for presumptive diagnosis frequently fail to identify iNTS disease in Africa, and there remains a need for improved diagnostic tools. Experimental studies in humans have helped us to understand the intracellular pathogenesis of iNTS and to direct the search for appropriate protein vaccine targets. Summary The most important remaining gap in our knowledge is probably an understanding of how NTS are transmitted, and the nature of the relationship between diarrhoeal disease, carriage and invasive disease in Africa, so that diagnostic and prevention tools can be appropriately directed. PMID:21844803

Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea.

PubMed

Lehmann, Deborah; Kirarock, Wendy; van den Biggelaar, Anita H J; Passey, Megan; Jacoby, Peter; Saleu, Gerard; Masiria, Geraldine; Nivio, Birunu; Greenhill, Andrew; Orami, Tilda; Francis, Jacinta; Ford, Rebecca; Kirkham, Lea-Ann; Solomon, Vela; Richmond, Peter C; Pomat, William S

2017-01-01

Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5 th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal

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.

[Severe Legionnaire's disease revealing an invasive aspergillosis in an apparently immunocompetent patient].

PubMed

Vergne, S; Lathuile, D; Bénosa, B; Fragnier, F; Destrac, S; Avedan, M; Alzieu, M; Campistron, J

2003-10-18

Invasive aspergillosis, a sever disease, usually occurs in immuno-depressed patients. However, it may also develop in presumably immuno-competent patients. A 54-year-old man, smoker, was hospitalised for hypoxemia of the right lung and septic shock, rapidly requiring mechanical ventilation combined with administration of vasopressors, and followed by dialysis because of the rapid worsening of an acute kidney failure. The diagnosis of pulmonary Legionnaire's disease was made on the second day in view of the positivity of the urinary legionella antigen. The progression of the disease was marked by the discovery of a histologically documented gastric aspergillosis and three abscessed intracerebral lesions within the context of a strongly positive aspergillus antigenemia. The disease worsened and the patient died on D 17, despite the antibiotic and anti-aspergillus treatments, haemodynamic support and dialysis. To our knowledge, the association of invasive aspergillosis and severe Legionnaire's disease has never been described in an presumably immunocompetent patient. This clinical case suggests the existence, other than the usual risk factors of invasive aspergillosis that characterise profound states of immunodepression, of more subtle alterations in the immune system that may enhance this type of infection.

Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in young Latin American children: A double-blind randomized controlled trial.

PubMed

Tregnaghi, Miguel W; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejón, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P; Borys, Dorota; Ruiz Guiñazú, Javier; Ortega-Barría, Eduardo; Yarzábal, Juan P; Schuerman, Lode

2014-06-01

The relationship between pneumococcal conjugate vaccine-induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed. This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15-18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization-defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28-30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: -1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

PubMed

van Lier, Alies; McDonald, Scott A; Bouwknegt, Martijn; Kretzschmar, Mirjam E; Havelaar, Arie H; Mangen, Marie-Josée J; Wallinga, Jacco; de Melker, Hester E

2016-01-01

Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. The average annual disease burden was computed for the period 2007-2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911-9961) and influenza (8670 DALYs/year; 95% UI: 8468-8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be attributed to the

Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011

PubMed Central

Bouwknegt, Martijn; Kretzschmar, Mirjam E.; Mangen, Marie-Josée J.; Wallinga, Jacco; de Melker, Hester E.

2016-01-01

Background Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. Methods and Findings The average annual disease burden was computed for the period 2007–2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911–9961) and influenza (8670 DALYs/year; 95% UI: 8468–8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five

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

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.

Economic aspects of pneumococcal pneumonia: a review of the literature.

PubMed

De Graeve, Diana; Beutels, Philippe

2004-01-01

In this review, the economic aspects of pneumococcal pneumonia are analysed, including the costs, cost effectiveness and cost benefit of treatment and prevention. We identified eight cost-of-illness studies, 15 analyses comparing the costs of different treatment options and 15 economic evaluations of prevention that met our search criteria. The studies were conducted largely in Europe and the US. Most pertained to community-acquired pneumonia (CAP) in general, without specific analysis of pneumococcus-related illness. Many of the studies were considered to be of poor quality for the following reasons: comparison without randomisation or control variables, disregard of health outcomes, small sample size, restriction of costs to drug costs and vague or disputable sources of cost information. In the US, hospitalisation costs resulting from CAP can be estimated to be between US 7,000 dollars and US 8,000 dollars per admission or US 4 million dollars per 100,000 population. Hospitalisation costs are significant (representing about 90% of total costs), but are much lower in Europe than in the US (one-third to one-ninth of the US estimates in the UK and Spain, respectively). In general, economic studies of treatment for pneumococcal pneumonia are in line with clinical evidence. A drug with proven clinical effectiveness would also appear to be supported from an economic stand point. Furthermore, economic data support an early switch from an intravenous to an oral antibacterial, the use of quinolones for inpatients with CAP, and also the use of guidelines built on clinical evidence. Of all the possible preventive strategies for pneumococcal pneumonia, only vaccination has been subjected to economic evaluation. Pneumococcal polysaccharide vaccine seems relatively cost effective (and potentially cost saving) for those between 65 and 75 years of age, for military recruits and for HIV positive patients with a sufficiently high CD4 cell count. Evaluations of the pneumococcal

Can we predict pneumococcal bacteremia in patients with severe community-acquired pneumonia?

PubMed

Pereira, José Manuel; Teixeira-Pinto, Armando; Basílio, Carla; Sousa-Dias, Conceição; Mergulhão, Paulo; Paiva, José Artur

2013-12-01

This study aimed to evaluate the role of biomarkers as markers of pneumococcal bacteremia in severe community-acquired pneumonia (SCAP). A prospective, single-center, observational cohort study of 108 patients with SCAP admitted to the intensive care department of a university hospital in Portugal was conducted. Leucocytes, C-reactive protein (CRP), lactate, procalcitonin (PCT), d-dimer, brain natriuretic peptide (BNP), and cortisol were measured within 12 hours after the first antibiotic dose. Fifteen patients (14%) had bacteremic pneumococcal pneumonia (BPP). They had significantly higher levels of median CRP (301 [interquartile range, or IQR], 230-350] mg/L vs 201 [IQR, 103-299] mg/L; P = .023), PCT (40 [IQR, 25-102] ng/mL vs 8 [IQR, 2-26] ng/mL; P < .001), BNP (568 [IQR, 478-2841] pg/mL vs 407 [IQR, 175-989] pg/mL; P = .027), and lactate (5.5 [IQR, 4.5-9.8] mmol/L vs 3.1 [IQR, 1.9-6.2] mmol/L; P = .009) than did patients without BPP. The discriminatory power evaluated by the area under the receiver operating characteristic curve (aROC) for PCT (aROC, 0.79) was superior to lactate (aROC, 0.71), BNP (aROC, 0.67), and CRP (aROC, 0.70). At a cutoff point of 17 ng/mL, PCT showed a sensitivity of 87%, a specificity of 67%, a positive predictive value of 30% and a negative predictive value of 97%, as a marker of pneumococcal bacteremia. In this cohort, significantly higher PCT, BNP, lactate, and CRP levels were found in BPP, and PCT presented the best ability to identify pneumococcal bacteremia. A PCT serum level lower than 17 ng/mL could identify patients with SCAP unlikely to have pneumococcal bacteremia. Copyright © 2013 Elsevier Inc. All rights reserved.

Pneumococcal conjugate vaccination at birth in a high-risk setting: no evidence for neonatal T-cell tolerance.