von Gottberg, Anne; de Gouveia, Linda; Tempia, Stefano; Quan, Vanessa; Meiring, Susan; von Mollendorf, Claire; Madhi, Shabir A; Zell, Elizabeth R; Verani, Jennifer R; O'Brien, Katherine L; Whitney, Cynthia G; Klugman, Keith P; Cohen, Cheryl
In South Africa, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 with a three-dose schedule for infants at 6, 14, and 36 weeks of age; a 13-valent vaccine (PCV13) replaced PCV7 in 2011. In 2012, it was estimated that 81% of 12-month-old children had received three doses of vaccine. We assessed the effect of vaccination on invasive pneumococcal disease. We conducted national, active, laboratory-based surveillance for invasive pneumococcal disease. We calculated the change in the incidence of the disease from a prevaccine (baseline) period (2005 through 2008) to postvaccine years 2011 and 2012, with a focus on high-risk age groups. Surveillance identified 35,192 cases of invasive pneumococcal disease. The rates among children younger than 2 years of age declined from 54.8 to 17.0 cases per 100,000 person-years from the baseline period to 2012, including a decline from 32.1 to 3.4 cases per 100,000 person-years in disease caused by PCV7 serotypes (-89%; 95% confidence interval [CI], -92 to -86). Among children not infected with the human immunodeficiency virus (HIV), the estimated incidence of invasive pneumococcal disease caused by PCV7 serotypes decreased by 85% (95% CI, -89 to -79), whereas disease caused by nonvaccine serotypes increased by 33% (95% CI, 15 to 48). Among adults 25 to 44 years of age, the rate of PCV7-serotype disease declined by 57% (95% CI, -63 to -50), from 3.7 to 1.6 cases per 100,000 person-years. Rates of invasive pneumococcal disease among children in South Africa fell substantially by 2012. Reductions in the rates of disease caused by PCV7 serotypes among both children and adults most likely reflect the direct and indirect effects of vaccination. (Funded by the National Institute for Communicable Diseases of the National Health Laboratory Service and others.).
Paulke-Korinek, Maria; Kollaritsch, Herwig; Kundi, Michael; Schmidle-Loss, Birgit; Zwazl, Ines; Laaber, Brigitte; Lakovits, Karin; Vecsei, Andreas; Wiedermann, Ursula; Burgmann, Heinz
In a prospective surveillance study covering all pediatric wards in Austria, 308 cases of invasive pneumococcal disease (IPD) were reported in hospitalized children <5 years of age between 2002 and 2012. Incidence was 7.1 per 100,000 per year for IPD with a case fatality rate of 3 %, and 1.9 per 100,000 per year for pneumococcal meningitis with a case fatality rate of 9 %. At hospital discharge, 17 % of the children were not fully recovered and suffered from problems such as hearing or motor deficits. Persistent sequelae 6 months after hospital discharge were present in 13 % of the children, a finding that emphasizes the seriousness of IPD. From 2007 onwards, we observed a shift of pneumococcal serotypes from those covered by the heptavalent vaccine to serotypes consequently added to 10- and 13-valent vaccines, particularly regarding serotype 19A. Among antimicrobial resistances detected, macrolide resistance was predominant; however, between 2002 and 2012, we saw an overall decrease of resistance rates. Considering this change of serotypes and the high rate of permanent sequelae after IPD, our data show the importance of pediatric pneumococcal vaccination and the relevance of continuous monitoring of circulating serotypes. By the end of 2012, which was the first year of universal mass vaccination against pneumococcal disease in Austria, no change in the incidence of invasive pneumococcal disease was observed yet.
Yildirim, Inci; Shea, Kimberly M; Little, Brent A; Silverio, Amy L; Pelton, Stephen I
Children with underlying conditions remain at increased risk for invasive pneumococcal diseases (IPD). This study describes the epidemiology, serotype distribution, clinical presentations, and outcomes of IPD in children with and without comorbidity. Cases of childhood IPD in Massachusetts were identified via enhanced surveillance from 2002 through 2014. Demographic and clinical data were collected via follow-up telephone interviews with parents and/or primary care providers. Underlying conditions were classified according to the 2012 Report of the Committee on Infectious Diseases and 2013 recommendations by the Advisory Committee on Immunization Practices. Among 1052 IPD cases in Massachusetts children <18 years old, 22.1% had at least 1 comorbidity. Immunocompromising conditions (32.7%) and chronic respiratory diseases (22.4%) were most common. Children with comorbidities were older at the time of IPD diagnosis (median 54 vs 23 months, P < .001), had higher hospitalization (odds ratio 2.5; 95% confidence interval 1.7-3.6) and case-fatality rates (odds ratio 3.7; 95% confidence interval 1.5-8.9) compared with children without known underlying conditions after adjusting for age, gender, year of diagnosis, and pneumococcal vaccination status. During the last 2 years of the study, IPD among children with comorbidities was caused by non-pneumococcal conjugate vaccine 13 serotypes in 23-valent polysaccharide pneumococcal vaccine (6/12, 50%) or serotypes that are not included in any of the vaccines (6/12; 50%). In children with comorbidity, IPD results in higher mortality, and a large proportion of disease is due to serotypes not included in current conjugate vaccines. Further research is needed, specifically to develop and evaluate additional strategies for prevention of IPD in the most vulnerable children. Copyright © 2015 by the American Academy of Pediatrics.
John, T J; Pai, R; Lalitha, M K; Jesudason, M V; Brahmadathan, K N; Sridharan, G; Steinhoff, M C
Forty two pneumococcal strains obtained in Vellore, Tamil Nadu, from 42 patients with invasive diseases, namely pneumonia, meningitis, or peritonitis were typed. Over one-third of pneumococci in children and nearly half in adults were serotype followed by serogroups/types 5, 6 and 7 which were most common in children and adults taken together. These 4 serogroups/types accounted for 11 (79%) of 14 strains in children and 20 (71%) of 28 strains in adults. The remaining 11 strains belonged to 8 serogroups/types, namely 3, 4, 10, 11, 12, 13, 19 and 20.
Chun, Colleen S; Weinmann, Sheila; Riedlinger, Karen; Mullooly, John P
To investigate whether passive cigarette smoke exposure increases the risk of invasive pneumococcal disease in children. In a population-based case-control study, 171 children aged 0 to 12 years with culture-confirmed invasive pneumococcal disease during the years 1994 to 2004 were identified. Two controls were matched to each case on age and patterns of Health Plan membership. We reviewed medical records of subjects and family members for information on household cigarette smoke exposure within 2 years of the diagnosis of invasive pneumococcal disease. We collected information on sex, race, pneumococcal vaccination, selected medical conditions, and medications in the 3 months before the diagnosis. Similar proportions of cases (25%) and controls (30%) had definite or probable passive smoke exposure (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.47-1.2). Cases of invasive pneumococcal disease were more likely to be nonwhite than controls (OR = 4.4, 95% CI = 2.3-8.2). Elevated risk of invasive pneumococcal disease was found in subjects with recent pulmonary diagnoses (OR = 2.2, 95% CI = 1.2-4.0) and recent antibiotic use (OR = 1.6, 95% CI = 1.1-2.3). Passive cigarette smoke exposure was not associated with invasive pneumococcal disease in this pediatric population. Invasive pneumococcal disease was associated with recent pulmonary diagnoses and recent antibiotic use.
Background The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended in elderly and high-risk adults. However, its efficacy in preventing pneumococcal infections remains controversial. This study assessed the clinical effectiveness of vaccination against invasive pneumococcal disease (IPD) among people over 60 years. Methods Population-based case-control study that included 88 case patients over 60 years-old with a laboratory-confirmed IPD (bacteraemic pneumonia, meningitis or sepsis) and 176 outpatient control subjects who were matched by primary care centre, age, sex and risk stratum. Adjusted odds ratios (ORs) for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was estimated as (1 - OR) ×100. Results Pneumococcal vaccination rate was significantly lower in cases than in control subjects (38.6% vs 59.1%; p = 0.002). The adjusted vaccine effectiveness was 72% (OR: 0.28; 95% CI: 0.15-0.54) against all IPD and 77% (OR: 0.23; 95% CI: 0.08-0.60) against vaccine-type IPD. Vaccination was significantly effective against all IPD in both age groups: 60-79 years-old (OR 0.32; 95% CI: 0.14-0.74) and people 80 years or older (OR: 0.29; 95% CI: 0.09-0.91). Vaccination appears significantly effective as for high-risk immunocompetent subjects (OR: 0.29; 95% CI: 0.11-0.79) as well as for immunocompromised subjects (OR: 0.12; 95% CI: 0.03-0.53). Conclusion These findings confirm the effectiveness of the 23-valent PPV against IPD, and they also support the benefit of vaccination in preventing invasive infections among high-risk and older people. PMID:20298596
Mohale, Thabo; Wolter, Nicole; Allam, Mushal; Ndlangisa, Kedibone; Crowther-Gibson, Penny; du Plessis, Mignon; von Gottberg, Anne
The capsular polysaccharide is the principal virulence factor of Streptococcus pneumoniae and a target for current pneumococcal vaccines. However, some pathogenic pneumococci are serologically nontypeable [nontypeable pneumococci (NTPn)]. Due to their relative rarity, NTPn are poorly characterized, and, as such, limited data exist which describe these organisms. We aimed to describe disease and genotypically characterize NTPn causing invasive pneumococcal disease in South Africa. Isolates were detected through national, laboratory-based surveillance for invasive pneumococcal disease in South Africa and characterized by whole genome analysis. We predicted ancestral serotypes (serotypes from which NTPn may have originated) for Group I NTPn using multilocus sequence typing and capsular region sequence analyses. Antimicrobial resistance patterns and mutations potentially causing nontypeability were identified. From 2003-2013, 39 (0.1 %, 39/32,824) NTPn were reported. Twenty-two (56 %) had partial capsular genes (Group I) and 17 (44 %) had complete capsular deletion of which 15 had replacement by other genes (Group II). Seventy-nine percent (31/39) of our NTPn isolates were derived from encapsulated S. pneumoniae. Ancestral serotypes 1 (27 %, 6/22) and 8 (14 %, 3/22) were most prevalent, and 59 % (13/22) of ancestral serotypes were serotypes included in the 13-valent pneumococcal conjugate vaccine. We identified a variety of mutations within the capsular region of Group I NTPn, some of which may be responsible for the nontypeable phenotype. Nonsusceptibility to tetracycline and erythromycin was higher in NTPn than encapsulated S. pneumoniae. NTPn are currently a rare cause of invasive pneumococcal disease in South Africa and represent a genetically diverse collection of isolates.
Manoharan, Anand; Manchanda, Vikas; Balasubramanian, Sundaram; Lalwani, Sanjay; Modak, Meera; Bai, Sushama; Vijayan, Ajith; Shet, Anita; Nagaraj, Savitha; Karande, Sunil; Nataraj, Gita; Yewale, Vijay N; Joshi, Shrikrishna A; Iyer, Ranganathan N; Santosham, Mathuram; Kahn, Geoffrey D; Knoll, Maria Deloria
Invasive pneumococcal disease continues to be a major cause of morbidity and mortality among children younger than 5 years of age in India. We aimed to provide nationally representative data for the pattern of disease due to Streptococcus pneumoniae, trends in the serotype of invasive pneumococci, and invasive pneumococci antimicrobial resistance patterns, in India. In this prospective hospital-based and retrospective laboratory-based surveillance study, we prospectively enrolled children aged younger than 5 years with suspected or proven invasive pneumococcal disease from 18 hospitals or institutional centres and retrospectively included laboratory-confirmed pneumococcal isolates from ten sentinel laboratories, together representing 11 states in India. Eligibility criteria were fever higher than 38°C without localising symptoms, clinical presentation of suspected meningitis or pneumonia, and evidence of radiographic pneumonia. We cultured blood and other normally sterile body fluids, reconfirmed and serotyped pneumococcal isolates, and established antimicrobial susceptibility using standard study protocols. Between Jan 1, 2011, and June 30, 2015, we enrolled 4377 patients. Among 361 (8%) patients with culture-proven pneumococcal disease, all clinical data were known for 226 (63%); among these patients, 132 (58%) presented with pneumonia, 78 (35%) presented with meningitis, and 16 (7%) had other clinical conditions. 131 (3%) died overall and 29 (8%) patients with invasive pneumococcal disease died. Serotypes 14 (52 [14%] of 361), 1 (49 [14%]), 5 (37 [10%]), and 19F (33 [9%]) were the most common. Penicillin non-susceptibility occurred in isolates from 29 (8%) patients, co-trimoxazole resistance occurred in 239 (66%), erythromycin resistance occurred in 132 (37%), and chloramphenicol resistance occurred in 33 (9%). We found multidrug resistance in 33 (9%) of 361 patients. The proportion of positive blood cultures, number of isolates, geographical representation
Savulescu, Camelia; Krizova, Pavla; Lepoutre, Agnes; Mereckiene, Jolita; Vestrheim, Didrik F; Ciruela, Pilar; Ordobas, Maria; Guevara, Marcela; McDonald, Eisin; Morfeldt, Eva; Kozakova, Jana; Varon, Emmanuelle; Cotter, Suzanne; Winje, Brita A; Munoz-Almagro, Carmen; Garcia, Luis; Castilla, Jesus; Smith, Andrew; Henriques-Normark, Birgitta; Celentano, Lucia Pastore; Hanquet, Germaine
The Streptococcus pneumoniae Invasive Disease network (SpIDnet) actively monitors populations in nine sites in seven European countries for invasive pneumococcal disease. Five sites use 13-valent pneumococcal conjugate vaccine (PCV13) alone and four use the ten-valent PCV (PCV10) and PCV13. Vaccination uptake is greater than 90% in six sites and 67-78% in three sites. We measured the effects of introducing high-valency PCVs on the incidence of invasive pneumococcal disease in children younger than 5 years. We compared the incidence of invasive pneumococcal disease in each of the 4 years after the introduction of PCV13 alone or PCV10 and PCV13 with the average incidence during the preceding period of heptavalent PCV (PCV7) use, overall and by serotype category. We calculated incidence rate ratios (IRRs) and 95% CIs for each year and pooled the values for all sites in a random effects meta-analysis. 4 years after the introduction of PCV13 alone or PCV10 and PCV13, the pooled IRR was 0·53 (95% CI 0·43-0·65) for invasive pneumococcal disease in children younger than 5 years caused by any serotype, 0·16 (0·07-0·40) for disease caused by PCV7 serotypes, 0·17 (0·07-0·42) for disease caused by 1, 5, and 7F serotypes, and 0·41 (0·25-0·69) for that caused by 3, 6A and 19A serotypes. We saw a similar pattern when we restricted the analysis to sites where only PCV13 was used. The pooled IRR for invasive pneumococcal disease caused by non-PCV13 serotypes was 1·62 (1·09-2·42). The incidence of invasive pneumococcal disease caused by all serotypes decreased due to a decline in the incidence of vaccine serotypes. By contrast, that of invasive pneumococcal disease caused by non-PCV13 serotypes increased, which suggests serotype replacement. Long-term surveillance will be crucial to monitor the further effects of PCV10 and PCV13 vaccination programmes in young children. European Centre for Disease Prevention and Control, Czech National Institute of Public Health
Rolo, Dora; Fenoll, Asunción; Fontanals, Dionísia; Larrosa, Nieves; Giménez, Montserrat; Grau, Immaculada; Pallarés, Román; Liñares, Josefina; Ardanuy, Carmen
In this study, we analyzed the clinical and molecular epidemiology of invasive serotype 5 (Ser5) pneumococcal isolates in four teaching hospitals in the Barcelona, Spain, area (from 1997 to 2011). Among 5,093 invasive pneumococcal isolates collected, 134 (2.6%) Ser5 isolates were detected. Although the overall incidence of Ser5-related invasive pneumococcal disease (IPD) was low (0.25 cases/100,000 inhabitants), three incidence peaks were detected: 0.63/100,000 in 1999, 1.15/100,000 in 2005, and 0.37/100,000 in 2009. The rates of Ser5 IPD were higher among young adults (18 to 64 years old) and older adults (>64 years old) in the first two peaks, whereas they were higher among children in 2009. The majority (88.8%) of the patients presented with pneumonia. Comorbid conditions were present in young adults (47.6%) and older adults (78.7%), the most common comorbid conditions being chronic obstructive pulmonary disease (20.6% and 38.3%, respectively) and cardiovascular diseases (11.1% and 38.3%, respectively). The mortality rates were higher among older adults (8.5%). All Ser5 pneumococci tested were fully susceptible to penicillin, cefotaxime, erythromycin, and ciprofloxacin. The resistance rates were 48.5% for co-trimoxazole, 6.7% for chloramphenicol, and 6% for tetracycline. Two major related sequence types (STs), ST1223 (n = 65) and ST289 (n = 61), were detected. The Colombia(5)-ST289 clone was responsible for all the cases in the Ser5 outbreak in 1999, whereas the ST1223 clone accounted for 73.8% and 61.5% of the isolates in 2005 and 2009, respectively. Ser5 pneumococci are a frequent cause of IPD outbreaks in the community and involve children and adults with or without comorbidities. The implementation of the new pneumococcal conjugated vaccines (PCV10 and PCV13) might prevent such outbreaks.
Rolo, Dora; Fenoll, Asunción; Fontanals, Dionísia; Larrosa, Nieves; Giménez, Montserrat; Grau, Immaculada; Pallarés, Román; Liñares, Josefina
In this study, we analyzed the clinical and molecular epidemiology of invasive serotype 5 (Ser5) pneumococcal isolates in four teaching hospitals in the Barcelona, Spain, area (from 1997 to 2011). Among 5,093 invasive pneumococcal isolates collected, 134 (2.6%) Ser5 isolates were detected. Although the overall incidence of Ser5-related invasive pneumococcal disease (IPD) was low (0.25 cases/100,000 inhabitants), three incidence peaks were detected: 0.63/100,000 in 1999, 1.15/100,000 in 2005, and 0.37/100,000 in 2009. The rates of Ser5 IPD were higher among young adults (18 to 64 years old) and older adults (>64 years old) in the first two peaks, whereas they were higher among children in 2009. The majority (88.8%) of the patients presented with pneumonia. Comorbid conditions were present in young adults (47.6%) and older adults (78.7%), the most common comorbid conditions being chronic obstructive pulmonary disease (20.6% and 38.3%, respectively) and cardiovascular diseases (11.1% and 38.3%, respectively). The mortality rates were higher among older adults (8.5%). All Ser5 pneumococci tested were fully susceptible to penicillin, cefotaxime, erythromycin, and ciprofloxacin. The resistance rates were 48.5% for co-trimoxazole, 6.7% for chloramphenicol, and 6% for tetracycline. Two major related sequence types (STs), ST1223 (n = 65) and ST289 (n = 61), were detected. The Colombia5-ST289 clone was responsible for all the cases in the Ser5 outbreak in 1999, whereas the ST1223 clone accounted for 73.8% and 61.5% of the isolates in 2005 and 2009, respectively. Ser5 pneumococci are a frequent cause of IPD outbreaks in the community and involve children and adults with or without comorbidities. The implementation of the new pneumococcal conjugated vaccines (PCV10 and PCV13) might prevent such outbreaks. PMID:23966486
van der Linden, Mark; Falkenhorst, Gerhard; Perniciaro, Stephanie; Imöhl, Matthias
This study describes the effects of the introduction of universal infant pneumococcal conjugate vaccination in 2006 on invasive pneumococcal disease (IPD) among children and adults in Germany with a focus on the dynamics of serotype distribution in vaccinated and non-vaccinated age groups. Over a period of 22 years (1992-2014), microbiological diagnostic laboratories from all over Germany have been sending isolates of IPD cases to the German National Reference Center for Streptococci on a voluntary basis. Streptococcus pneumoniae isolates were serotyped using Neufeld's Quellung method. Among children <16 years, the proportion of PCV7 serotypes among isolates from IPD cases decreased from 61.8% before vaccination (1997-2006) to 23.5% in the early vaccination period (2007-2010; p = 1.30E-72) and sank further to 5.2% in the late vaccination period (2010-2014; p = 4.59E-25). Similar reductions were seen for the separate age groups <2 years, 2-4 years and 5-15 years. Among adults, the proportion of PCV7 serotypes decreased from 43.4% in the pre-vaccination period (1992-2006) to 24.7% (p = 3.78E-88) in the early vaccination period and 8.2% (p = 5.97E-161) in the late vaccination period. Both among children and among adults, the non-PCV7 serotypes 1, 3, 7F and 19A significantly increased in the early vaccination period. After the switch from PCV7 to PVC10/PCV13 for infant vaccination in 2010, serotypes 1, 6A and 7F significantly decreased. A decrease in serotype 19A was only observed in 2013-2014, as compared to 2010-2011 (children p = 4.16E-04, adults p = 6.98E-06). Among adults, serotype 3, which strongly increased in the early vaccination period (p = 4.44E-15), remained at a constant proportion in the late vaccination period. The proportion of non-PCV13 vaccine serotypes increased over the whole vaccination period, with serotypes 10A, 12F, 23B, 24F and 38 most significantly increasing among children and serotypes 6C, 12F, 15A, 22F and 23B increasing among adults. Eight
Bar-Zeev, Naor; Mtunthama, Neema; Gordon, Stephen B; Mwafulirwa, Gershom; French, Neil
Invasive pneumococcal disease causes substantial morbidity and mortality in Africa. Evaluating population level indirect impact on adult disease of pneumococcal conjugate vaccine (PCV) programmes in infants requires baseline population incidence rates but these are often lacking in areas with limited disease surveillance. We used hospital based blood culture and cerebrospinal fluid surveillance to calculate minimal incidence of invasive pneumococcal disease in the adult (≥15 years old) population of Blantyre, a rapidly growing urban centre in southern Malawi, in the period preceding vaccine introduction. Invasive pneumococcal disease incidence in Blantyre district was high, mean 58.1 (95% confidence interval (CI): 53.7, 62.7) per 100,000 person years and peaking among 35 to 40 year olds at 108.8 (95%CI: 89.0, 131.7) mirroring the population age prevalence of HIV infection. For pneumococcal bacteraemia in urban Blantyre, mean incidence was 60.6 (95% CI: 55.2, 66.5) per 100,000 person years, peaking among 35 to 40 year olds at 114.8 (95%CI: 90.3, 143.9). We suspected that our surveillance may under-ascertain the true burden of disease, so we used location data from bacteraemic subjects and projected population estimates to calculate local sub-district incidence, then examined the impact of community level socio-demographic covariates as possible predictors of local sub-district incidence of pneumococcal and non-pneumococcal pathogenic bacteraemia. Geographic heterogeneity in incidence was marked with localised hotspots but ward level covariates apart from prison were not associated with pneumococcal bacteraemia incidence. Modelling suggests that the current sentinel surveillance system under-ascertains the true burden of disease. We outline a number of challenges to surveillance for pneumococcal disease in our low-resource setting. Subsequent surveillance in the vaccine era will have to account for geographic heterogeneity when evaluating population level indirect
Marrie, Thomas J; Tyrrell, Gregory J; Majumdar, Sumit R; Eurich, Dean T
Most are aware of pneumococcal infection as a complication of splenectomy and the increased risk of severe invasive pneumococcal disease (IPD) in asplenic patients. However little is known of the current status of this entity in a population with an active pneumococcal conjugate vaccine program for children. All IPD cases reported from 2000 to 2014 in Northern Alberta, Canada were collected prospectively. Socio-demographic variables, clinical characteristics, and IPD-related outcomes were compared between patients with and without a spleen using the Student t-test, Chi-square test, or Fisher's exact test, as appropriate. Thirty-seven of 2435 patients with IPD (1.5%) were asplenic. Asplenic patients were significantly more likely to require mechanical ventilation or admission to the intensive care unit and had more complications (e.g., acute kidney injury). However, in-hospital mortality rates were similar in those with and without a spleen (19% vs. 16%, p=0.58). Pneumococcal serotype 22B was 33-fold higher in asplenic patients compared to those with a spleen. In patients with IPD, those who are asplenic have a more severe infection than those with a spleen; however, the mortality rate is not significantly different. The reason for the predominance of serotype 22B requires further investigation and if replicated may warrant attention to current vaccination strategies. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Singh, Jyotsana; Sundaresan, Suba; Manoharan, Anand; Shet, Anita
Streptococcus pneumoniae is a leading cause of childhood diseases that result in significant morbidity and mortality in India. Commercially licensed and available pneumococcal conjugate vaccines (PCVs) include ten (PCV-10) and 13 (PCV-13) pneumococcal serotypes. Vaccines with other serotype combinations are under development. Reviewing and reporting trends and distribution of pneumococcal serotypes causing invasive pneumococcal disease in India will be useful for policy making as PCV is being introduced into India's universal immunization program. We conducted a systematic literature review of hospital based observational studies (both peer reviewed and gray literature published in English) from India available from January 1990 to December 2016. Studies that documented data on the prevalence of serotype distribution and the antimicrobial resistance pattern of S. pneumoniae in children≤5years of age were included. We screened a total number of 116 studies, of which 109 studies were excluded. Final analysis included seven studies. The most frequent pneumococcal serotypes causing invasive disease among children≤5years were 14, 1, 19F, 6B, 5, 6A, 9V and 23F. Serotype 14 and 19A were represented in most of the geographical regions studied in the reviewed articles. Currently available PCV formulations included 67.3-78.4% of all serotypes contributing to IPD among Indian children≤5years. Pneumococcal resistance to trimethoprim/sulfamethoxazole, erythromycin, penicillin, chloramphenicol, levofloxacin and cefotaxime was seen in 81%, 37%, 10%, 8%, 6% and 4% of all pneumococcal isolates respectively, while vancomycin resistance was not reported. The present review demonstrates that up to 78.4% of reported invasive pneumococcal disease in children≤5years in India are currently caused by serotypes that are included in the available licensed PCVs. However, sentinel surveillance must be continued in representative parts of the country to assess the changing trends in
... is a very serious infection that causes pneumonia, meningitis, and bloodstream infection (sepsis). About one million US ... will die from it. Fewer will get pneumococcal meningitis or sepsis, but the mortality rate in this ...
Capeding, Maria Rosario; Bravo, Lulu; Santos, Jaime; Kilgore, Paul E; Kim, Soon Ae; Balter, Ivana; Hubler, Robin; Ye, Jian; Moscariello, Michele
Worldwide, invasive pneumococcal disease (IPD) causes considerable morbidity and mortality among children, but incidence data in Asia are lacking. This 2-year hospital-based, prospective, surveillance study was conducted at 3 study sites in urban areas of the Philippines to estimate IPD and pneumonia incidence in children and describe the serotype distribution of invasive Streptococcus pneumoniae isolates. Children aged 28 days to <60 months residing within the 3 surveillance areas presenting with possible IPD were enrolled. Initial diagnosis, history of pneumococcal vaccine receipt and previous antimicrobial treatment were recorded. Blood specimens were collected for S. pneumoniae identification and serotyping. Final diagnosis was determined for hospitalized subjects, subjects whose culture yielded S. pneumoniae and subjects with clinically suspected meningitis. A total of 5940 subjects were enrolled, 47 IPD cases identified. IPD site rates were 33.49 per 100,000, 25.38 per 100,000 and 25.85 per 100,000. Chest radiograph-confirmed pneumonia incidence ranged from 633.74 to 1683.59 per 100,000. Highest chest radiograph-confirmed pneumonia incidence occurred in those 28 days to <6 months of age at 2 sites (2166.16 and 3891.94 per 100,000) and those 6-12 months of age at the third site (3847.52 per 100,000). Thirty-five S. pneumoniae isolates were serotyped; most commonly identified were serotypes 1, 2, 5, 6B, 14 and 18F. One serotype 14 isolate was erythromycin resistant. Previous antibiotic therapy was documented in 17-53% of subjects; 2 subjects had received pneumococcal vaccine. At 2 sites, one-third of IPD subjects died. IPD is an important cause of morbidity and mortality among urban children in the Philippines. Our data support the expectation that widespread immunization would decrease IPD disease burden.
Sousa, Adrian; Pérez-Rodríguez, Maria Teresa; Nodar, Andrés; Martínez-Lamas, Lucía; Vasallo, Francisco Jose; Álvarez-Fernández, Maximiliano; Crespo, Manuel
Invasive pneumococcal disease (IPD) typically presents as bacterial pneumonia, meningitis or primary bacteraemia. However, Streptococcus pneumoniae can produce infection at any level of the body (endocarditis, arthritis, spontaneous bacterial peritonitis, etc.), which is also known as unusual IPD (uIPD). There are very limited data available about the clinical and microbiological profile of these uncommon manifestations of pneumococcal disease. Our aim was to analyse clinical forms, microbiological profile, epidemiology and prognosis of a cohort of patients with unusual invasive pneumococcal disease (uIPD). We present a retrospective study of 389 patients (all adult and paediatric patients diagnosed during the period) diagnosed with IPD at our hospital (Complejo Hospitalario Universitario de Vigo) between 1992 and 2014. We performed an analysis of clinical, microbiological and demographical characteristics of patients comparing the pre-pneumococcal conjugate vaccine (PCV) period with the post-vaccination phase. IPD and uIPD were defined as follows; IPD: infection confirmed by the isolation of S. pneumoniae from a normally sterile site, which classically presented as bacterial pneumonia, meningitis or primary bacteraemia; uIPD: any case of IPD excluding pneumonia, meningitis, otitis media, rhinosinusitis or primary bacteraemia. A total of 22 patients (6%) met the criteria of uIPD. A Charlson index >2 was more prevalent in uIPD patients than IPD patients (45% vs 24%; p=0.08). The most common clinical presentation of uIPD was osteoarticular infection (8 patients, 36%), followed by gastrointestinal disease (4 patients, 18%). Infection with serotypes included in PCV-13 was significantly higher in IPD patients (65%) than in patients with uIPD, 35% (p=0.018). Conversely, infection with multidrug-resistant strains was higher among patient with uIPD (27% vs 9%; p=0.014). The all-cause mortality rate was 15%, 13% in the IPD group and 32% among patients with uIPD (p=0
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.
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
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
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. 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]). Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the
Gaensbauer, James T; Asturias, Edwin J; Soto, Monica; Holt, Elizabeth; Olson, Daniel; Halsey, Neal A
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.
Tendais-Almeida, Marta; Ferreira-Magalhães, Manuel; Alves, Inês; Tavares, Margarida; Azevedo, Inês
In Portugal, pneumococcal vaccination is free of charge and recommended by the Directorate-General of Health for the pediatric population at high risk of invasive pneumococcal disease. Our main aim was to describe the vaccination uptake in a pediatric population attending a hospital outpatient clinic. Cross-sectional observational survey of a pediatric population attending a referral hospital outpatient clinic, from July to December 2014. Data was collected from clinical records, Individual Health Bulletin or the registry from Plataforma de Dados da Saúde®. Of the 122 participants, 95.9% had, at least, one shot of pneumococcal vaccine, but only 64.8% of these completed the age recommended vaccination scheme. Uptake was higher in children < 5 years old. The proportion of complete vaccination schemes was 100% in hemoglobinopathies and human immunodeficiency virus infection groups, 66.7% in prematures, 62.5% in splenectomized and 54.7% in Down syndrome. Children had better complete vaccination schemes when they attended the Pediatric Infectious Disease (100%) and Pulmonology Clinics (88.2%). Children > 5 years old had a higher uptake of 23-valent polysaccharide vaccine than the 2 to 5-years old ones (74.5% vs 40.5%; p < 0.001). Most of our pediatric population at high risk of IPD was vaccinated; nevertheless, only two-thirds had completed the scheme for their age. The main failure was on the 23-valent polysaccharide vaccine administration. Although these results are better than those reported in other European countries with similar recommendations, it is essential to explore the causes for the observed flaws in order to optimize vaccination rates.
Sugimoto, Naomi; Yamagishi, Yuka; Hirai, Jun; Sakanashi, Daisuke; Suematsu, Hiroyuki; Nishiyama, Naoya; Koizumi, Yusuke; Mikamo, Hiroshige
Among the different serotypes of Streptococcus pneumoniae, serotype 3 has received global attention. We report the fatal case of a 76-year-old Japanese man who had an invasive pneumococcal disease associated with pneumonia caused by serotype 3 S. pneumoniae. The patient had a history of hypertension, laryngeal cancer, chronic obstructive pulmonary disease, and type 2 diabetes mellitus. Following a cerebral arteriovenous malformation hemorrhage, he underwent surgery to remove the hematoma and began rehabilitation. On day 66 of hospitalization, he suddenly developed a fever, and coarse crackles and wheezes were heard in his right lung. A diagnosis of hospital-acquired aspiration pneumonia was made, and initial treatment with piperacillin/tazobactam was started. Teicoplanin was added after S. pneumoniae was isolated from the blood culture, however, the patient died 5 days later. The S. pneumoniae detected in the sputum smear was serotype 3, showed mucoid colonies and susceptibility to penicillins, cephalosporins, carbapenems, and levofloxacin, but resistance to erythromycin. We experienced a fatal case of pneumonia caused by mucoid serotype 3 S. pneumoniae with a thick capsule. Serotype 3-associated pneumonia may develop a wider pulmonary infiltrative shadow, a prolonged therapeutic or hospitalization course, and a poor outcome. Careful observation and intervention are required, and the use of additional antibiotics or intravenous immunoglobulins should be considered in such cases. Pneumococcal immunization is also an important public health measure to minimize the development of severe infections caused by serotype 3 strains.
Meichtry, Jurka; Born, Rita; Küffer, Marianne; Zwahlen, Marcel; Albrich, Werner C; Brugger, Silvio D; Mühlemann, Kathrin; Hilty, Markus
In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected. Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003-2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007-2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively. The proportion of PCV7 serotypes among all IPD cases (n=7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P<0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P=0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P=0.008), 19A (P=0.03) and 19F (P=0.005), compared to serotype 1 and 7F. There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Cohen, Cheryl; von Mollendorf, Claire; de Gouveia, Linda; Lengana, Sarona; Meiring, Susan; Quan, Vanessa; Nguweneza, Arthermon; Moore, David P; Reubenson, Gary; Moshe, Mamokgethi; Madhi, Shabir A; Eley, Brian; Hallbauer, Ute; Finlayson, Heather; Varughese, Sheeba; O'Brien, Katherine L; Zell, Elizabeth R; Klugman, Keith P; Whitney, Cynthia G; von Gottberg, Anne
The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine effectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the effectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. Cases of invasive pneumococcal disease in children aged 5 years or younger were identified through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine effectiveness as a percentage, with the equation 1 - [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine effectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The effectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (-35 to 100) among three case-control sets of children with HIV infection. PCV13 effectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI -12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine
Ingels, Helene Andrea Sinclair
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
Pérez-Rodríguez, Maria Teresa; Sopeña, Bernardo; Méndez-Lage, Susana; Casares, M de los Angeles; Constenla, Lucía; Argibay, Ana; Nodar, Andrés; Villaverde, Iria; Martínez-Vázquez, César; Álvarez-fernández, Maximiliano
Invasive pneumococcal disease (IPD) shows different epidemiological characteristics depending on age and pneumococcus serotype. The aims of the work were to analyze the clinical manifestations and mortality associated with IPD, the serotype isolated and the antibiotic resistance rates in different age groups. Retrospectively, 141 patients with IPD diagnosed between 2002 and 2008 were studied. Patients were classified in 4 age groups: ≤ 2 year-old, 3-14 year-old, 15-64 year-old and ≥ 65 year-old. Pneumonia was the most common manifestation in all age groups (71%). Pneumococcal meningitis was more prevalent in patients ≤ 2 year-old (28 vs. 9%, P=.054) and empyema was more frequent in those between 3-14 year-old (31 vs. 5%, P<.001). Mortality was associated with age ≥ 65 year-old (odds ratio [OR] 7, 95% confidence interval [95% CI] 1.9-28.9), primary bacteremia (OR 7, 95% CI 1.9-28.9) and orotracheal intubation (OR 9, 95% CI 1.9-41.1). The more prevalent serotypes among patients ≤ 2 year-old were 14, 19A and 19F. The serotype 1 was most common in patients between 3-14 year-old and serotype 3 in those ≥ 65 year-old. A higher rate of non-susceptible penicillin strains was observed in pediatric population (42 vs. 19%, P=.007). Age was related to the clinical manifestations, mortality and antibiotic resistance rates. Primary bacteremia was one of the risk factors of mortality. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
Marrie, T J; Tyrrell, G J; Majumdar, Sumit R; Eurich, Dean T
Background. Large studies of invasive pneumococcal disease (IPD) are frequently lacking detailed clinical information. Methods. A population-based 15-year study of IPD in Northern Alberta. Results. 2435 patients with a mean age of 54.2 years formed the study group. Males outnumbered females and Aboriginal and homeless persons were overrepresented. High rates of smoking, excessive alcohol use, and illicit drug use were seen. Almost all (87%) had a major comorbidity and 15% had functional limitations prior to admission. Bacteremia, pneumonia, and meningitis were the most common major manifestations of IPD. Almost half of the patients had alteration of mental status at the time of admission and 22% required mechanical ventilation. Myocardial infarction, pulmonary embolism, and new onset stroke occurred in 1.7, 1.3, and 1.1% of the patients, respectively; of those who had echocardiograms, 35% had impaired ventricular function. The overall in-hospital mortality was 15.6%. Conclusions. IPD remains a serious infection in adults. In addition to immunization, preventative measures need to consider the sociodemographic features more carefully. A standard set of data need to be collected so that comparisons can be made from study to study. Future investigations should target cardiac function and pulmonary embolism prevention in this population.
Ciruela, Pilar; Broner, Sonia; Izquierdo, Conchita; Hernández, Sergi; Muñoz-Almagro, Carmen; Pallarés, Roman; Jané, Mireia; Domínguez, Angela
To study the impact of meteorological data and respiratory viral infections on invasive pneumococcal disease (IPD) rates. We analysed all notifications of IPD and respiratory viral infections to the Microbiological Reporting System of Catalonia (2006-2012). Correlations between rates of IPD and viral infections (influenza virus, respiratory syncytial virus [RSV] and adenovirus), and meteorological variables (temperature, humidity, hours of sunshine, wind speed and number of days with rainfall) were assessed using Spearman's correlation coefficient and negative binomial regression models. We found significant correlations between monthly rates of IPD and monthly rates of all respiratory viruses and meteorological factors. However, after multiple regression analysis, associations remained between IPD rates and influenza rates and reductions in temperature in the total population, and between IPD rates and adenovirus rates in children aged <5 years. When models were repeated for the total population using data from the preceding month, IPD rates increased when RSV was circulating and when the temperature was lower. In children aged <5 years, RSV circulation was associated with increased IPD rates. IPD rates were linked to increased activity of some respiratory viruses and reductions in temperature. Preventive measures, including influenza vaccination, may help reduce IPD.
Rojas, Juan Pablo; Leal, Aura Lucia; Patiño, Jaime; Montañez, Anita; Camacho, Germán; Beltrán, Sandra; Bonilla, Carolina; Barrero, Rocio; Mariño, Cristina; Ramos, Nicolás
Streptococcus pneumoniae (S. pneumoniae), also known as pneumococcus, is one of the main bacteria associated with mortality in children under 2 years of age, with a morbidity and mortality incidence that varies according to demographics and exposure to risk, or protective factors. To describe the child mortality due to invasive pneumococcal disease (IPD) between 2008 -2014 (6 years), in 8 Medical Centres in Bogotá, Colombia. Descriptive observational case series of patients who died of IPD, aged 28 days to 18 years, in 8 tertiary care institutions in Bogota, Colombia. The study period was from 1 January 2008 to 15 January 2014. 239 patients. A total of 239 registered cases of IPD were reviewed, showing a mortality of 8% (n 18). The mean age of patients that died was 43.7 months, with an age range from 2 to 176 months (14 years), with 66% of the cases being male. Serotypes were identified in 8 patients, finding: 6A, 6B, 10A, 14, 18C, 23B, 23F, and 35B. The most common clinical presentation of the cases was meningitis with mortality of 33% (6 cases), followed by bacteraemia without focus in 28% (5 cases), and pneumonia with 27% (5 cases). Combined clinical situations were presented, such as pneumonia and meningitis in 11% (2 cases). Two of the patients had clearly documented risk factors for IPD (asplenia and chronic respiratory disease). IPD mortality is particularly high in children under 2 years in male patients, especially when presented with a meningeal focus (44%). Serotyping was not possible in all patients who died, since no strain isolated was sent to the National Institute of Health. Continuous and systematic vigilance is required to evaluate the impact of vaccination and possible changes in the pattern of presentation of disease. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
Ramdani-Bouguessa, N.; Ziane, H.; Bekhoucha, S.; Guechi, Z.; Azzam, A.; Touati, D.; Naim, M.; Azrou, S.; Hamidi, M.; Mertani, A.; Laraba, A.; Annane, T.; Kermani, S.; Tazir, M.
Pneumococcal infections are a major cause of morbidity and mortality in developing countries. The introduction of pneumococcal conjugate vaccines (PCVs) has dramatically reduced the incidence of pneumococcal diseases. PCVs are not currently being used in Algeria. We conducted a prospective study from 2005 to 2012 in Algeria to determine antimicrobial drug resistance and serotype distribution of Streptococcus pneumoniae from children with pneumococcal disease. Among 270 isolated strains from children, 97 (36%) were invasive disease; of these, 48% were not susceptible to penicillin and 53% not susceptible to erythromycin. A high rate of antimicrobial nonsusceptibility was observed in strains isolated from children with meningitis. The serotype distribution from pneumococci isolated from children with invasive infections was (by order of prevalence): 14, 1, 19F, 19A, 6B, 5, 3, 6A and 23F. Multidrug resistance was observed in serotypes 14, 19F, 19A and 6B. The vaccine coverage of serotypes isolated from children aged <5 years was 55.3% for PCV7, 71.1% for PCV10 and 86.8% for PCV13. Our results highlight the burden of pneumococcal disease in Algeria and the increasing S. pneumoniae antibiotic resistance. The current pneumococcal vaccines cover a high percentage of the circulating strains. Therefore, vaccination would reduce the incidence of pneumococcal disease in Algeria. PMID:26106481
Kuster, Stefan P; Rudnick, Wallis; Shigayeva, Altynay; Green, Karen; Baqi, Mahin; Gold, Wayne L; Lovinsky, Reena; Muller, Matthew P; Powis, Jeff E; Rau, Neil; Simor, Andrew E; Walmsley, Sharon L; Low, Donald E; McGeer, Allison
Estimating the risk of antibiotic resistance is important in selecting empiric antibiotics. We asked how the timing, number of courses, and duration of antibiotic therapy in the previous 3 months affected antibiotic resistance in isolates causing invasive pneumococcal disease (IPD). We conducted prospective surveillance for IPD in Toronto, Canada, from 2002 to 2011. Antimicrobial susceptibility was measured by broth microdilution. Clinical information, including prior antibiotic use, was collected by chart review and interview with patients and prescribers. Clinical information and antimicrobial susceptibility were available for 4062 (90%) episodes; 1193 (29%) of episodes were associated with receipt of 1782 antibiotic courses in the prior 3 months. Selection for antibiotic resistance was class specific. Time elapsed since most recent antibiotic was inversely associated with resistance (cephalosporins: adjusted odds ratio [OR] per day, 0.98; 95% confidence interval [CI], .96-1.00; P = .02; macrolides: OR, 0.98; 95% CI, .96-.99; P = .005; penicillins: OR [log(days)], 0.62; 95% CI, .44-.89; P = .009; fluoroquinolones: profile penalized-likelihood OR [log(days)], 0.62; 95% CI, .39-1.04; P = .07). Risk of resistance after exposure declined most rapidly for fluoroquinolones and penicillins and reached baseline in 2-3 months. The decline in resistance was slowest for macrolides, and in particular for azithromycin. There was no significant association between duration of therapy and resistance for any antibiotic class. Too few patients received multiple courses of the same antibiotic class to assess the significance of repeat courses. Time elapsed since last exposure to a class of antibiotics is the most important factor predicting antimicrobial resistance in pneumococci. The duration of effect is longer for macrolides than other classes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved
Mothibeli, Kedibone M; du Plessis, Mignon; von Gottberg, Anne; de Gouveia, Linda; Adrian, Peter; Madhi, Shabir A; Klugman, Keith P
We reviewed pneumococcal serotype 3 cases reported from 2000 through 2005 to a laboratory-based surveillance system for invasive pneumococcal disease in South Africa. The prevalence of serotype 3 invasive isolates was compared to their prevalence in carriage isolates to determine the odds of invasiveness due to serotype 3 among South African children. Three groups of serotype 3 strains were characterized by pulsed-field gel electrophoresis (PFGE) or Box element PCR (BOX-PCR), randomly selected invasive isolates from one province, isolates from a carriage study involving children in the same province, and antimicrobial-resistant invasive isolates collected nationally. Examples of the PFGE types identified were further characterized by multilocus sequence typing. In total, 15,980 viable isolates causing invasive disease were submitted, of which 661 (4%) were serotype 3, mostly from adults (85% [489/575]). Fewer serotype 3 isolates were nonsusceptible to antimicrobial agents tested (40/661 [6%]) than non-serotype 3 isolates (8,480/15,319 [55%]) (P < 0.001). Compared to non-serotype 3 cases, there was no association with HIV coinfection (2,212/2,569 [86%] versus 72/78 [92%]; P = 0.1) or increased case fatality ratio (1,190/4,211 [28%] versus 54/154 [35%]; P = 0.7). Serotype 3 in children had a low but statistically insignificant invasive disease potential (odds ratio [OR] of 0.15; 95% confidence interval [CI] of 0.01 to 1.06). Strains were grouped into 3 PFGE clusters, with the largest, cluster A, representing 54% (84/155), including 14 isolates confirmed as sequence type 458 (ST458). It was confirmed that 3 isolates from cluster B, which represented only 12% (18/155) of the isolates, were the serotype 3 global strain, ST180. We have therefore identified ST458 as predominating in South Africa, but with an invasive potential similar to that of the predominant global clone ST180.
Medeiros, Marta Inês Cazentini; Negrini, Bento Vidal de Moura; Silva, Jorgete Maria E; Almeida, Samanta Cristine Grassi; Leopoldo, Maria Luiza; Guerra, Silva; Andrade, Denise de
Infections caused by Streptococcus pneumoniae (pneumococcus) still represent a challenge for health systems around the world. The objective of this study was to assess microbiological and clinical aspects in hospitalized patients with invasive pneumococcus disease between 1998 and 2013. This was a retrospective study that analyzed the results of pneumococcus identification, serotyping, and susceptibility testing found in the Adolfo Lutz Institute databank. Personal variables, medical history and clinical outcome of patients admitted with invasive pneumococcal disease were analyzed. These were obtained from records of a public teaching hospital - Hospital das Clínicas Faculdade de Medicina Ribeirão Preto. The sample comprised 332 patients. Patient age ranged from less than one month to 89 years old (mean 20.3 years) and the sample was predominately male. Pneumonia (67.8%) was the most common disease, accounting for 18.2% of deaths. Serotypes 14, 1, 3, 9V, 6B, 6A, 23F, 19A, 18C, 19F, 12F, and 4 were the most common (75.3%). Most patients, or 67.5%, were cured without any complication (success), 6.9% had some type of sequela (failure), and 25.6% died (failure). In the case of deaths due to meningitis, strains of fully penicillin resistant pneumococcus were isolated. Furthermore, 68.2% of patients who died presented some type of comorbidity. The 60 and older age group presented the most significant association (Odds Ratio=4.2), with outcome failure regardless of the presence of comorbidity. Serotype 18C was the most significant risk factor both in raw analysis (Odds Ratio=3.8) and when adjusted for comorbidity (Odds Ratio=5.0) or age (Odds Ratio=5.4). The same occurred with serotype 12F (respectively, Odds Ratio=5.1, Odds Ratio=5.0, and Odds Ratio=4.7) CONCLUSION: The present findings highlight the importance of IPD among young adults and older adults. In the era of conjugate vaccines, monitoring serotypes in different age groups is essential to assess the impact and
Braeye, Toon; Verheagen, Jan; Mignon, Annick; Flipse, Wim; Pierard, Denis; Huygen, Kris; Schirvel, Carole; Hens, Niel
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. 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. 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. We encourage the use of capture-recapture methods, but epidemiologists should preferably include datasets for which the underlying
Braeye, Toon; Verheagen, Jan; Mignon, Annick; Flipse, Wim; Pierard, Denis; Huygen, Kris; Schirvel, Carole; Hens, Niel
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
Slotved, Hans-Christian; Dalby, Tine; Hoffmann, Steen
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.
Ciancotti Oliver, Lucía Rosa; Huertas Zarco, Isabel; Pérez Pérez, Elvira; Carmona Martí, Esther; Carbó Malonda, Rosa; Gil Bru, Ana; González Moran, Francisco
The introduction of conjugated anti-pneumonia vaccines has led to a change in the epidemiology of Invasive Pneumococcal Disease (IPD). The aim of this study is to describe the trends in IPD in the Community of Valencia during the period 2007-2012. A retrospective, descriptive and longitudinal study was conducted on IPD in the Community of Valencia during the period 2007-2012, The information sources used were the Epidemiological Surveillance Analysis (Análisis de la Vigilancia Epidemiológica (AVE)) and the Valencian Microbiology Network (Red Microbiológica Valenciana (RedMIVA)) of the Valencia Health Department. The incidence of IPD decreased between 2007 and 2012 in all age groups, mainly in the under 5 year-olds, dropping from 30.5 cases to 12.3 cases per 10(5) inhabitants (p< .001). Pneumonia was the principal presentation of the disease, with a decrease in its rates from 6.9 to 4.1 cases per 10(5) inhabitants (p< .001). A gradual, non-significant, reduction from 26% to 12% (p=.23) was observed in the proportion of cases due to the serotypes contained in the heptavalent vaccine (PCV7), mainly in the under 5 year-olds. The cases due to additional serotypes in 13-valent conjugated vaccine (1, 3, 5, 6A, 7F and 19A) also showed a decreasing trend, mainly in vaccinated under 5 year-olds (52.6% vs 14.3%; p=.03), while the cases due to non-vaccine serotypes significantly increased from 42.3% to 56.7% in the general population (p=.002), and from 47.4% to 78.6% in vaccinated under 5 year-olds (p=.08). The results of this study show a reduction in the incidence of IPD, with a decrease in the proportion of cases produced by vaccine serotypes, and an increase in the proportion of those not vaccinated. Epidemiological Surveillance is necessary to monitor the trends in the disease. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Fukusumi, Munehisa; Chang, Bin; Tanabe, Yoshinari; Oshima, Kengo; Maruyama, Takaya; Watanabe, Hiroshi; Kuronuma, Koji; Kasahara, Kei; Takeda, Hiroaki; Nishi, Junichiro; Fujita, Jiro; Kubota, Tetsuya; Sunagawa, Tomimasa; Matsui, Tamano; Oishi, Kazunori
In Japan, the clinical characteristics and recent serotype distribution among adult patients of invasive pneumococcal disease (IPD) have not been fully investigated since the introduction of the pneumococcal conjugate vaccine (PCV) in children. From November 2010, PCV7 was encouraged by an official program, funded by government, subsequently included in the routine schedule in April 2013, and replaced with a PCV13 in November 2013. Between April 2013 and March 2015, patients with IPD older than 15 years were evaluated based on the enhanced national surveillance in ten prefectures of Japan. The serotype distribution of the isolates was analyzed in these patients. The analysis included 291 patients: 107 patients (37%) were female and the median age was 70 years. Of 281 patients with available data, 202 (72%) had underlying diseases, including 107 patients (38%) with immunocompromised status. The case fatality proportion for all case was 20%. In subgroup analysis, the case fatality proportion (29%) in immunocompromised patients was much higher than that (0-16%) in each age group of nonimmunocompromised patients (15-39 years, 40-64 years, and ≥ 65 years). While the proportion of bacteremia without any focus (27%) was higher than that (8-10%) in nonimmunocompromised patients, the proportions of vaccine types (PCV13, 32%; PPSV23, 51%) of the causative isolates were lower than those in each age group of nonimmunocompromised patients. Among 291 isolates, the most frequent serotypes were 3 (17%), 19A (13%), and 22F (10%). Twelve percent of the isolates were PCV7 serotypes, 46% were PCV13 serotypes, and 66% were PPSV23 serotypes. The majority of adult patients of IPD had underlying diseases, including immunocompromised conditions. A low proportion (12%) of PCV7-type IPD was observed in this population where PCV7 for children had been included in the routine immunization schedule.
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
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
van Werkhoven, Cornelis H
Quantification of pneumococcal conjugate vaccines (PCVs) herd effects are mainly performed on invasive pneumococcal disease (IPD) but there is conflicting evidence regarding herd effects of PCVs on non-IPD pneumococcal community-acquired pneumonia. This review summarizes the available literature on herd effects of PCVs on non-IPD pneumococcal community-acquired pneumonia.
Cremers, Amelieke J.; van der Gaast-de Jongh, Christa E.; Ferwerda, Gerben; Meis, Jacques F.; Roeleveld, Nel; Bentley, Stephen D.; Pastura, Alexander S.; van Hijum, Sacha A. F. T.; van der Ven, Andre J.; de Mast, Quirijn; Zomer, Aldert
ABSTRACT To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of Streptococcus pneumoniae and disease outcomes for 349 bacteremic patients. A pneumococcal genome-wide association study (GWAS) demonstrated a strong correlation between 30-day mortality and the presence of the phage-derived gene pblB, encoding a platelet-binding protein whose effects on platelet activation were previously unknown. Platelets are increasingly recognized as key players of the innate immune system, and in sepsis, excessive platelet activation contributes to microvascular obstruction, tissue hypoperfusion, and finally multiorgan failure, leading to mortality. Our in vitro studies revealed that pblB expression was induced by fluoroquinolones but not by the beta-lactam antibiotic penicillin G. Subsequently, we determined pblB induction and platelet activation by incubating whole blood with the wild type or a pblB knockout mutant in the presence or absence of antibiotics commonly administered to our patient cohort. pblB-dependent enhancement of platelet activation, as measured by increased expression of the α-granule protein P-selectin, the binding of fibrinogen to the activated αIIbβ3 receptor, and the formation of platelet-monocyte complex occurred irrespective of antibiotic exposure. In conclusion, the presence of pblB on the pneumococcal chromosome potentially leads to increased mortality in patients with an invasive S. pneumoniae infection, which may be explained by enhanced platelet activation. This study highlights the clinical utility of a bacterial GWAS, followed by functional characterization, to identify bacterial factors involved in disease severity. PMID:28096486
Cabaj, Jason L; Nettel-Aguirre, Alberto; MacDonald, Judy; Vanderkooi, Otto G; Kellner, James D
Pneumococcal conjugate vaccine (PCV) was introduced into Alberta, Canada's routine childhood immunization programs in 2002 (7-valent [PCV7]) and 2010 (13-valent [PCV13]). We assessed the effect of these programs on the epidemiology of invasive pneumococcal disease (IPD) to determine if PCV-associated indirect protection was relatively reduced in adults with underlying comorbidities. Demographic and clinical data were collected by a prospective, population-based surveillance system in Calgary, Alberta, Canada, from January 2000 to December 2013. An indirect cohort study design was used to assess for changes in the proportion of IPD cases with underlying comorbidities. There were 1598 overall and 1346 adult IPD cases from 1 January 2000 to 31 December 2013. Overall IPD incidence decreased 33% (age 0-5 months), 86% (6-23 months), 67% (2-4 years), 26% (5-17 years), 22% (18-64 years), 36% (65-84 years), and 42% (≥85 years) from the prevaccine (January 2000-July 2002) to the post-PCV13 (July 2010-December 2013) period. Over the same timeframe, PCV7 serotype disease incidence declined to ≤1 case per 100 000 persons in all age groups. Neither the proportion of adult cases with immunocompetent comorbidities (relative risk ratio [RRR], 0.93; 95% confidence interval [CI], .62-1.40) nor immunocompromising comorbidities (RRR, 0.99; 95% CI, .61-1.61) differed between the pre-PCV period and post-PCV era. Childhood PCV programs have provided considerable benefit, with substantial declines in overall and vaccine-serotype IPD in vaccinated children and in unvaccinated persons. Conjugate vaccine-associated indirect protection for adults with comorbidities was similar to that for healthy adults. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail email@example.com.
Gaviria-Agudelo, Claudia L; Jordan-Villegas, Alejandro; Garcia, Carla; McCracken, George H
Invasive pneumococcal disease (IPD) continues to be a significant burden in children despite the implementation of two generations of conjugate vaccines. Serotype replacement by nonvaccine serotypes is reported in multiple areas around the world. This study is a continuation of previous studies and describes the incidence, serotype distribution, and antibiotic resistance pattern of Streptococcus pneumoniae serotypes causing IPD at Children's Medical Center Dallas after introduction of 13-valent pneumococcal conjugate vaccine (PCV13). Streptococcus pneumoniae isolates from normally sterile sites were collected from January 1, 1999 to June 30, 2014. Demographic and clinical information was extracted for analysis. Incidence of IPD was calculated using inpatient and emergency center admissions to Children's Medical Center of Dallas as the denominator. Isolates were serotyped and penicillin/cefotaxime susceptibilities were determined. Selected nontypeable isolates were further characterized by multilocus sequence typing. A χ2 test and the Cochran-Armitage Trend Test for trend analysis were used to evaluate change in serotype and antibiotic susceptibility patterns over time. Comparison of the different study periods showed a significant reduction in the incidence of IPD in PCV13 era compared with prevaccine era and PCV7 era (P < .05). Children younger than 24 months showed the largest reduction of disease incidence. More than 40% of patients with IPD had a documented comorbidity. Cases of pneumonia continued to decrease in the PCV13 era (P < .002). The most common non-PCV13 serotypes after vaccine introduction were as follows: 23B, 6C, 23A, 9N/L, and 12. Penicillin resistance by meningitis breakpoint decreased significantly in the PCV13 era. After introduction of PCV13 in Dallas, incidence of IPD caused by strains contained in the vaccine and penicillin resistance continued to decrease. Serotype replacement phenomena and persistence of PCV7 serotypes were documented
Diawara, Idrissa; Zerouali, Khalid; Katfy, Khalid; Zaki, Bahija; Belabbes, Houria; Najib, Jillali; Elmdaghri, Naima
The purpose of this study was to compare the incidence rate of invasive pneumococcal disease, the rates of antibiotic resistance and serotype distribution among children ≤5 years old before and after PCVs introduction in Casablanca, Morocco. This study was conducted at the Ibn Rochd University Hospital Centre of Casablanca during two periods encompassing pre-and post-implementation of PCVs, respectively from January 2007 to October 2010 and from January 2011 to December 2014. All the non-duplicate invasive S. pneumoniae isolates recovered during the study periods were included. There were 136 cases of IPD, 91 before and 45 after PCVs introduction. The greatest decrease in incidence rate of IPD occurred in children ≤ 2 years of age declining from 34.6 to 13.5 per 100,000 populations (p<0.0001) before and after vaccination, respectively. The incidence rate of PCV-7, PCV-10 non-PCV-7 and PCV-13 non-PCV-10 serotypes decrease significantly from 18.0 to 4.6, from 5.7 to 1.3 and from 5.7 to 0.8/100,000 population (p<0.001) in the same age, respectively. Shifts in the distribution of IPD serotypes and reductions in the incidence rate of disease suggest an effective reduction of the burden of IPD in children, but continued high quality surveillance is critical to assess the changes in serotype distributions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
van der Linden, Mark; Falkenhorst, Gerhard; Perniciaro, Stephanie; Fitzner, Christina; Imöhl, Matthias
In this study we calculate the effectiveness of pneumococcal conjugate vaccines (PCV) against invasive pneumococcal disease (IPD) among children under the age of two years using the indirect cohort method. We also discuss the timeliness of vaccination and the residual cases of vaccine type IPD. From July 2006 until June 2015, 921 IPD cases were reported and for 618 children (67.1%), the vaccination status at the time of infection could be accurately determined. Of these, 379 (61.3%) were vaccinated and 239 (38.7%) were not vaccinated. The adjusted vaccine effectiveness (VE) of PCV7 for all included serotypes + 6A was 80% (95% CI: 63-89) for at least one dose, 97% (89-100) after three primary doses (post primary) and 95% (57-100) post booster. The adjusted overall VE of PCV13 was 86% (74-93) for at least one dose, 85% (62-94) post primary and 91% (61-99) post booster. For the additional serotypes included in PCV13, the adjusted VE was 82% (66-91), 80% (46-93) and 90% (54-98) respectively. The serotype specific VE for at least one dose was high for serotypes 1 (83%; 15-97), 3 (74%; 2-93), 7F (84%; 18-98) and 19A (77%; 47-90). Only 39.5% of children with IPD obtained their first dose of PCV7 according to schedule (2nd dose: 32.9%, 3rd dose: 22.0%, booster dose: 63.6%). For children vaccinated with PCV13 values were slightly better: 43.8%, 33.5%, 26.3% and 74.3% respectively. Among 90 residual cases with PCV7 serotypes, 73 (81.1%) were in unvaccinated children, and 15 (16.7%) in children who had not obtained the number of doses recommended for their age, and only two (2.2%) in children vaccinated according to age. Of 82 cases with PCV13 serotypes occurring after the switch from PCV7 to PCV13, 56 (68.3%) were not vaccinated, 22 (26.8%) were incompletely vaccinated, and four (4.9%) were vaccinated according to age. Our data show a high effectiveness of pneumococcal conjugate vaccination in Germany. However, the administration of vaccine doses among children with IPD is
Panatto, Donatella; Domnich, Alexander; Gasparini, Roberto; Bonanni, Paolo; Icardi, Giancarlo; Amicizia, Daniela; Arata, Lucia; Carozzo, Stefano; Signori, Alessio; Bechini, Angela; Boccalini, Sara
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
Munier, Anne-Lise; de Lastours, Victoire; Porcher, Raphaël; Donay, Jean-Luc; Pons, Jean-Louis; Molina, Jean-Michel
Invasive pneumococcal diseases remain frequent and severe in HIV-infected subjects. To identify opportunities for prevention, we assessed risk factors of invasive pneumococcal diseases (IPD) in HIV-infected patients over a 10-year period in France. We performed a retrospective case-control study in a reference centre of HIV management in Paris. All HIV-infected patients having suffered from IPD between 2000 and 2011 were included. Control subjects were HIV-infected with no history of IPD or pneumonia, matched by date of diagnosis of HIV with controls. Two controls were randomly selected for each subject. In all, 42 HIV-infected patients presented 44 IPD episodes during the study period and were compared to 84 controls. In the multivariate analysis, patients with IPD were more likely than controls to have a Charlson Comorbidity Index ≥2 (adjusted OR = 7.07, 95% CI 1.99-25.1, p = 0.003), CD4-cell count <200/cells/µL (aOR = 6.93, 95% CI 1.80-26.7, p = 0.005), HIV-RNA viral load >400 copies/mL (aOR = 5.56, 95% CI 1.58-19.5, p = 0.007) and a non-European origin (aOR = 4.26, 95% CI 1.02-17.9, p = 0.047). HIV-infected patients with a higher burden of comorbidities, uncontrolled HIV replication, low CD4-cell counts and/or of non-European origin are at higher risk of developing IPD. Better screening for and management of HIV infection is necessary to reduce the risk of IPD. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Regev-Yochay, Gili; Rahav, Galia; Strahilevitz, Jacob; Bishara, Jihad; Katzir, Michal; Chowers, Michal; Finkelstein, Renato; Chazan, Bibiana; Zimhony, Oren; Dagan, Ron
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
Black, Steven; France, Eric K; Isaacman, Daniel; Bracken, Laura; Lewis, Edwin; Hansen, John; Fireman, Bruce; Austrian, Robert; Graepel, Jay; Gray, Sharon; Klein, Nicola P
To assess the incidence of invasive pneumococcal disease (IPD) in all children younger than 5 years of age in the Northern California Kaiser Permanente (NCKP) health care system during a 5-year surveillance period (2000-2005) after the introduction in April 2000 of routine use of 7-valent pneumococcal conjugate vaccine (PCV7). This was a laboratory-based surveillance study of all children younger than 5 years of age in the NCKP health care system from April 2000 to March 2005. The comparison group was all children younger than 5 years of age in the NCKP health care system from April 1996 to March 2000. Data obtained from clinical databases included microbiologic identification and susceptibility testing; serotyping of isolates; immunization records; and IPD diagnoses for inpatients and outpatients. IPD was defined as a positive culture of Streptococcus pneumoniae from a normally sterile body site. For all serotypes, the mean annual incidence of IPD during the postlicensure surveillance period was 15.3 cases/100,000 person-years (10(5) p-y) compared with 62.5 cases/10(5) p-y in the prelicensure years of 1996-2000. The average incidence of IPD caused by vaccine serotypes was reduced from 50.1 cases/10(5) p-y during the prelicensure years to 4.9 cases/10(5) p-y during the postlicensure period. The average incidences of IPD caused by cross-reactive and by nonvaccine serotypes were 5.8 and 5.3 cases/10(5) p-y, respectively, during the prelicensure years and 2.5 and 6.2 cases/10(5) p-y, respectively, during the postlicensure period. Of the 131 IPD cases observed during the postlicensure surveillance period, bacteremia (50.4%) and pneumonia (31.3%) were the most common diagnoses. During the 5-year postlicensure surveillance period, only 3 subjects who were identified to be fully vaccinated for age with PCV7 (3 doses by 7 months of age or 4 doses by 18 months of age) developed vaccine-serotype IPD. The incidence of IPD has significantly decreased in a large population of
Jaiswal, Nishant; Singh, Meenu; Thumburu, Kiran Kumar; Bharti, Bhavneet; Agarwal, Amit; Kumar, Ajay; Kaur, Harpreet; Chadha, Neelima
Objective The primary objective was to estimate the burden of invasive pneumococcal disease (IPD) in children aged 1 month to 12 years in South Asian countries. Methods We searched three electronic databases (PubMed, Embase and the Cochrane Library) using a comprehensive search strategy, we manually searched published databases (Index Medicus and Current Contents) and we also searched the bibliographies of the included studies and retrieved reviews. The searches were current through June 2013. Eligible studies (community-based and hospital-based) were pooled and a separate analysis for India was also completed. A meta-regression analysis and heterogeneity analysis were performed. The protocol was registered with PROSPERO registration number CRD42013004483. Results A total of 22 studies surveying 36,714 children were included in the systematic review. Hospital-based prospective studies from South Asia showed that 3.57% of children had IPD, and 15% of all bacterial pneumonia cases were due to Streptococcus pneumoniae. Indian studies showed that the incidence of IPD was 10.58% in children admitted to hospitals with suspected invasive bacterial diseases, and 24% of all bacterial pneumonia cases were due to S. pneumonia. Population-based studies from South Asian countries showed that 12.8% of confirmed invasive bacterial diseases were caused by S. pneumonia whereas retrospective hospital-based studies showed that 28% of invasive bacterial diseases were due to S. pneumoniae. Meta-regression showed that there was a significant influence of the antigen testing method for diagnosing IPD on IPD prevalence. Conclusion S. pneumoniae is responsible for a substantial bacterial disease burden in children of South Asian countries including India despite the presence of high heterogeneity in this meta-analysis. Treatment guidelines must be formulated, and preventive measures like vaccines must also be considered. PMID:24798424
González Martínez, F; Saavedra Lozano, J; Navarro Gómez, M L; Santos Sebastián, M M; Rodríguez Fernández, R; González Sánchez, M; Hernández-Sampelayo Matos, T
To describe the epidemiology, clinical syndromes and microbiological characteristics of serotype 19A as the main cause of invasive pneumococcal disease (IPD) in children admitted to a tertiary hospital in Spain. A retrospective (1998-2004) and prospective (2005-2009) study was conducted on children with IPD produced by serotype 19A. The study was divided into three periods (P): P1 (1998-2001) when PCV7 had not been commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. A total of 155 isolates of Streptococcus pneumoniae (SP) producing IPD were analysed, with 21 of them being serotype 19A (14%). An increased prevalence of serotype 19A was found: 2/45 cases (4.4%) in P1, 3/41 cases (7.3%) in P2 and 16/69 cases (23.2%) in P3. It occurred mostly in children younger than 2 years (16/21; 76%). This serotype was the main cause of meningitis (5/20; 25%), pleural empyema (3/22; 14%) and bacteraemic mastoiditis (2/4; 50%). Thirteen isolates (61.5%) had an MIC ≥ 0.12μ/ml for penicillin in extra-meningeal infections, and 3 of the 5 isolates causing meningitis (60%) had an MIC ≥ 1μ/ml for cefotaxime. Serotype 19A was the main causal agent of IPD in the PCV7 era (P3), with high antibiotic resistance rates. This serotype was responsible for all types of IPD, being the main cause of meningitis. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
González Martínez, F; Navarro Gómez, M L; Saavedra Lozano, J; Santos Sebastián, M M; Rodríguez Fernández, R; González Sanchéz, M; Cercenado Mansilla, E; Hernández-Sampelayo Matos, T
There has been an increased incidence in invasive pneumococcal disease (IPD) produced by non-vaccine serotype (NVS) of Streptococcus pneumoniae after the introduction of PCV7. Our objective was to describe the epidemiological, clinical and microbiological characteristics of IPD caused by NVS in a tertiary hospital in Madrid. Retrospective (1998-2004) and prospective (2005-2009) study evaluating IPD caused by NVS in children. The study was divided into three periods: P1 (1998-2001) when PCV7 was not commercialized; P2 (2002-2005) with 40% vaccine coverage among children; and P3 (2006-2009) when the vaccine was added to the Childhood Immunization Schedule in Madrid. We analyzed 155 cases of IPD. One hundred and fifty of these isolates were serotyped (100 were NVS). There was an increase in the prevalence of IPD from P1 (31%) to P2 (54%) and P3 (91%). The most relevant emerging serotypes were 19A, 7F, 1, 5, 3 and 15C. The most significant clinical syndromes produced by some specific serotypes were as follows: lower respiratory tract infection (LRTI) by serotypes 1, 3, 5 and 15C; LRTI, primary bacteremia and meningitis by serotype 19A; and primary bacteremia by serotype 7F (66%). The large majority (83.8%) of NVS were sensitive to penicillin. There has been an increased prevalence of IPD caused by NVS since the introduction of PCV7. These changes should prompt the introduction of new pneumococcal vaccines, which include most of the NVS, in the childhood immunization calendar to prevent IPD in children. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
Tempia, Stefano; Wolter, Nicole; Cohen, Cheryl; Walaza, Sibongile; von Mollendorf, Claire; Cohen, Adam L; Moyes, Jocelyn; de Gouveia, Linda; Nzenze, Susan; Treurnicht, Florette; Venter, Marietjie; Groome, Michelle J; Madhi, Shabir A; von Gottberg, Anne
The use of molecular diagnostic techniques for the evaluation of the impact of pneumococcal conjugate vaccines (PCVs) has not been documented. We aimed to evaluate the impact of PCVs on invasive pneumococcal disease (IPD) using polymerase chain reaction (PCR)-based techniques and compare with results obtained from culture-based methods. We implemented two independent surveillance programs for IPD among individuals hospitalized at one large surveillance site in Soweto, South Africa during 2009-2012: (i) PCR-based (targeting the lytA gene) syndromic pneumonia surveillance; and (ii) culture-based laboratory surveillance. Positive samples were serotyped. The molecular serotyping assay included targets for 42 serotypes including all serotypes/serogroups included in the 7-valent (PCV-7) and 13-valent (PCV-13) PCV. The Quellung reaction was used for serotyping of culture-positive cases. We calculated the change in rates of IPD (lytA- or culture-positive) among HIV-uninfected children aged <2 years from the year of PCV-7 introduction (2009) to the post-vaccine years (2011 or 2012). During the study period there were 607 lytA-positive and 1,197 culture-positive cases that were serotyped. Samples with lytA cycle threshold (Ct)-values ≥35 (30.2 %; 123/407) were significantly less likely to have a serotype/serogroup detected for serotypes included in the molecular serotyping assay than those with Ct-values <35 (78.0 %; 156/200) (p < 0.001). From 2009 to 2012 rates of PCV-7 serotypes/serogroups decreased -63.8 % (95 % CI: -79.3 % to -39.1 %) among lytA-positive cases and -91.7 % (95 % CI: -98.8 % to -73.6 %) among culture-positive cases. Rates of lytA-positive non-vaccine serotypes/serogroups also significantly decreased (-71.7 %; 95 % CI: -81.1 % to -58.5 %) over the same period. Such decline was not observed among the culture-positive non-vaccine serotypes (1.2 %; 95 % CI: -96.7 % to 58.4 %). Significant downward trends in IPD PCV-7 serotype-associated rates were observed
Ceyhan, Mehmet; Dagan, Ron; Sayiner, Abdullah; Chernyshova, Liudmyla; Dinleyici, Ener Çağrı; Hryniewicz, Waleria; Kulcsár, Andrea; Mad'arová, Lucia; Pazdiora, Petr; Sidorenko, Sergey; Streinu-Cercel, Anca; Tambić-Andrašević, Arjana; Yeraliyeva, Lyazzat
Pneumococcal infection is a major cause of morbidity and mortality worldwide. The burden of disease associated with S. pneumoniae is largely preventable through routine vaccination. Pneumococcal conjugate vaccines (e.g. PCV7, PCV13) provide protection from invasive pneumococcal disease as well as non-invasive infection (pneumonia, acute otitis media), and decrease vaccine-type nasopharyngeal colonisation, thus reducing transmission to unvaccinated individuals. PCVs have also been shown to reduce the incidence of antibiotic-resistant pneumococcal disease. Surveillance for pneumococcal disease is important to understand local epidemiology, serotype distribution and antibiotic resistance rates. Surveillance systems also help to inform policy development, including vaccine recommendations, and monitor the impact of pneumococcal vaccination. National pneumococcal surveillance systems exist in a number of countries in Central and Eastern Europe (such as Croatia, Czech Republic, Hungary, Poland, Romania and Slovakia), and some have introduced PCVs (Czech Republic, Hungary, Kazakhstan, Russia, Slovakia and Turkey). Those countries without established programs (such as Kazakhstan, Russia and Ukraine) may be able to learn from the experiences of those with national surveillance systems. The serotype distributions and impact of PCV13 on pediatric pneumococcal diseases are relatively similar in different parts of the world, suggesting that approaches to vaccination used elsewhere are also likely to be effective in Central and Eastern Europe. This article briefly reviews the epidemiology of pneumococcal disease, presents the latest surveillance data from Central and Eastern Europe, and discusses any similarities and differences in these data as well the potential implications for vaccination policies in the region.
Martin, Irene; Hoang, Linda; Van Caeseele, Paul; Lefebvre, Brigitte; Horsman, Greg; Haldane, David; Gubbay, Jonathan; Ratnam, Sam; German, Gregory; Daley Bernier, Jennifer; Strudwick, Lori; McGeer, Allison; Zhanel, George G.; Van Domselaar, Gary; Graham, Morag; Mulvey, Michael R.
Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005–2015. Six phylogenetic lineages (n = 117) were identified among a serotype 22F/ST433 clonal complex (CC), including a recently expanding erythromycin-resistant clone. Erythromycin-resistance was observed in 25 isolates possessing ermB, mef or a 23S rRNA A2061G point mutation; 2 penicillin-resistant isolates had recombinant pbp1a, pbp2a and/or pbp2x; 3 tetracycline-resistant isolates contained tetM; and 1 isolate was multidrug-resistant. Virulence factor analysis indicated a high level of homogeneity among the 22F/ST433 clonal complex strains. A group of 6 phylogenetic outlier strains had differing MLST, antimicrobial resistance and molecular profiles suggestive of capsule switching events. While capsule switch events among S. pneumoniae serotype 22F has been observed, increasing prevalence of S. pneumoniae serotype 22F can be attributed to an evolving homogenous clone expanding nationally through local transmission events. PMID:28531208
Sahni, Vanita; Naus, Monika; Hoang, Linda; Tyrrell, Gregory J; Martin, Irene; Patrick, David M
In 2003, British Columbia (BC) introduced a universal heptavalent pneumococcal conjugate vaccine (PCV-7) program for infants, and in 2007 revised the recommended schedule from four doses to three doses. We describe trends in the incidence of invasive pneumococcal disease (IPD) in association with these program changes. All confirmed cases are reported to the BC Centre for Disease Control (BCCDC) using a standardized data collection process; isolates are forwarded to the BCCDC Public Health and Reference Microbiology Laboratory for serotyping and to the National Reference Laboratory for confirmation. Upon implementation of the reduced dose program in 2007, additional epidemiological data, including immunization history, were collected for children < or = 16 years. Seven years after implementation of the program, a 78% decline in incidence of IPD among children under five has been achieved; this is largely a direct effect of the PCV-7 program. Among those >16 years of age, herd immunity is evident and decreasing trends of PCV-7 serotypes continued even after the dose reduction program was introduced. However, gains in disease reduction were offset by increases in replacement serotypes, particularly among the over-65 age group. This has resulted in no net change in adult IPD rates. The implementation of the PCV-7 program has changed the epidemiology of IPD in BC through direct effects of the vaccine, herd immunity and serotype replacement. The introduction of a three-dose schedule was not associated with an excess of vaccine failures.
Ricketson, Leah J; Conradi, Nicholas G; Vanderkooi, Otto G; Kellner, James D
Since the introduction of childhood pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) incidence has decreased in children and the predominant serotypes causing disease have changed. This study describes changes in the clinical features of IPD in children (<18 years) before and after the conjugate vaccine introduction. The Calgary Area Streptococcus pneumoniae Epidemiology Research study collects information on all IPD cases in Calgary, Alberta, Canada. Descriptive and regression analyses were used to compare IPD in the pre-vaccine (January 2000 to August 2002), post-7-valent protein-polysaccharide conjugate vaccine (September 2002 to June 2010) and post-13-valent protein-polysaccharide conjugate vaccine (PCV13) (July 2010 to December 2015) periods; intensive care unit and inpatient admissions were outcome measures. The incidence of IPD in children (<18 years) decreased from an average of 17 cases/100,000/yr in 2000-2001 to 4 cases/100,000/yr in 2015. The median age of children presenting with IPD shifted from 2.0 years (interquartile range: 2.5) in the pre-vaccine period to 3.9 years (interquartile range: 6.2) in the post-PCV13 period. The proportion of children with a comorbidity that is an indication for pneumococcal vaccination did not change. Invasive disease with focus (meningitis, pneumonia, empyema, peritonitis) compared with invasive disease with bacteremia only increased from 44.6% in pre-vaccine to 64.0% and 61.4% in the post-7-valent protein-polysaccharide conjugate vaccine and post-PCV13 periods, respectively (P = 0.017). Having IPD in the post-PCV13 period compared with the pre-vaccine period was associated with an increased odds of hospitalization [Odds ratio (OR): 2.9; 95% Confidence Interval (CI): 1.4-6.2]. Clinical features of IPD have changed since pneumococcal conjugate vaccines were introduced, with a shift toward more focal infections requiring hospitalization. Although overall IPD cases have declined, disease that does occur
Santana Hernández, Milagrosa; Aguiar-Santana, Ione Ahedey; Artiles Campelo, Fernando; Colino Gil, Elena
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.
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
Picazo, Juan; Ruiz-Contreras, Jesús; Casado-Flores, Juan; Negreira, Sagrario; Baquero, Fernando; Hernández-Sampelayo, Teresa; Otheo, Enrique; Méndez, Cristina
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
Background Streptococcus pneumoniae is a common cause of community acquired pneumonia and bacteremia. Excess wintertime mortality related to pneumonia has been noted for over a century, but the seasonality of invasive pneumococcal disease (IPD) has been described relatively recently and is poorly understood. Improved understanding of environmental influence on disease seasonality has taken on new urgency due to global climate change. Methods We evaluated 602 cases of IPD reported in Philadelphia County, Pennsylvania, from 2002 to 2007. Poisson regression models incorporating seasonal smoothers were used to identify associations between weekly weather patterns and case counts. Associations between acute (day-to-day) environmental fluctuations and IPD occurrence were evaluated using a case-crossover approach. Effect modification across age and sex strata was explored, and meta-regression models were created using stratum-specific estimates for effect. Results IPD incidence was greatest in the wintertime, and spectral decomposition revealed a peak at 51.0 weeks, consistent with annual periodicity. After adjustment for seasonality, yearly increases in reporting, and temperature, weekly incidence was found to be associated with clear-sky UV index (IRR per unit increase in index: 0.70 [95% CI 0.54-0.91]). The effect of UV index was highest among young strata and decreased with age. At shorter time scales, only an association with increases in ambient sulphur oxides was linked to disease risk (OR for highest tertile of exposure 0.75, 95% CI 0.60 to 0.93). Conclusion We confirmed the wintertime predominance of IPD in a major urban center. The major predictor of IPD in Philadelphia is extended periods of low UV radiation, which may explain observed wintertime seasonality. The mechanism of action of diminished light exposure on disease occurrence may be due to direct effects on pathogen survival or host immune function via altered 1,25-(OH)2-vitamin-D metabolism. These
Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A
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.
Azzari, Chiara; Cortimiglia, Martina; Nieddu, Francesco; Moriondo, Maria; Indolfi, Giuseppe; Mattei, Romano; Zuliani, Massimo; Adriani, Beatrice; Degl'Innocenti, Roberto; Consales, Guglielmo; Aquilini, Donatella; Bini, Giancarlo; Di Natale, Massimo Edoardo; Canessa, Clementina; Ricci, Silvia; de Vitis, Elisa; Mangone, Giusi; Bechini, Angela; Bonanni, Paolo; Pasinato, Angela; Resti, Massimo
The 7-valent pneumococcal conjugate vaccine (PCV7) produced a significant herd protection in unvaccinated adult population mostly because of pneumococcus carriage decrease in vaccinated children. It is not known if the 13-valent pneumococcal vaccine can give similar effect on adults. Aims of the work were to evaluate whether the 6 additional serotypes are present in nasopharynx of children and serotype distribution in invasive pneumococcal infections (IPD) in adults. Realtime-PCR was used to evaluate pneumococcal serotypes in adults with confirmed IPD and in nasopharyngeal swabs (NP) from 629 children not vaccinated or vaccinated with PCV7 and resident in the same geographical areas. Two hundred twenty-one patients (116 males, median 67.9 years) with IPD were studied (pneumonia n = 103, meningitis n = 61 sepsis n = 50, other n = 7). Two hundred twelve were serotyped. The most frequent serotypes were 3, (31/212; 14.6%), 19A, (19/212; 9.0%), 12 (17/212; 8.0%), 7F, (14/212; 6.6%). In NP of children, the frequency of those serotypes causing over 50% of IPD in adults was very low, ranging from 0.48% for serotype 7F to 7.9% for serotype 19A. On the other side serotype 5, very frequent in NP (18.7%) caused <1% IPD. In conclusion serotypes causing IPD in adults are very rarely found in children NP. We suggest that herd protection obtainable with the additional 6 serotypes included in PCV13 may be more limited than that demonstrated with PCV7 in the past. In order to reduce the burden of disease in adults, adults should be offered a specific vaccination program with highly immunogenic PCV.
Flasche, Stefan; Le Polain de Waroux, Olivier; O’Brien, Katherine L.; Edmunds, W. John
Pneumococcal conjugate vaccines (PCVs) have substantially reduced morbidity and mortality of pneumococcal disease. The impact of the 7-valent PCV on all-serotype invasive pneumococcal disease (IPD) among children was reported to vary between high-income countries. We investigate the ability to predict this heterogeneity from pre-vaccination data. We propose a parsimonious model that predicts the impact of PCVs from the odds of vaccine serotype (VT) among carriers and IPD cases in the pre-PCV period, assuming that VT are eliminated in a mature PCV programme, that full serotype replacement occurs in carriage and that invasiveness of the NVT group is unchanged. We test model performance against the reported impact of PCV7 on childhood IPD in high-income countries from a recent meta-analysis. The odds of pre-PCV7 VT IPD, PCV schedule, PCV coverage and whether a catch up campaign was used for introduction was gathered from the same analysis. We conducted a literature review and meta-analysis to obtain the odds of pre-PCV7 VT carriage in the respective settings. The model predicted the reported impact on childhood IPD of mature PCV programmes; the ratio of predicted and observed incidence risk ratios was close to 1 in all settings. In the high income settings studied differences in schedule, coverage, and catch up campaigns were not associated with the observed heterogeneity in impact of PCV7 on childhood all-serotype IPD. The pre-PCV7 proportion of VT IPD alone also had limited predictive value. The pre-PCV7 proportion of VT carriage and IPD are the main determinants for the impact of PCV7 on childhood IPD and can be combined in a simple model to provide predictions of the vaccine preventable burden of IPD. PMID:25879748
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
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.
Horácio, Andreia N; Silva-Costa, Catarina; Lopes, Joana P; Ramirez, Mário; Melo-Cristino, José
Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012-2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009-2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 ( p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012-2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates.
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Crowther-Gibson, Penny; Cohen, Cheryl; Klugman, Keith P; de Gouveia, Linda; von Gottberg, Anne
The emergence of multidrug-resistant (MDR) Streptococcus pneumoniae complicates disease management. We aimed to determine risk factors associated with MDR invasive pneumococcal disease (IPD) in South Africa and evaluate the potential for vaccination to reduce disease burden. IPD data collected by laboratory-based surveillance from 2003 through 2008 were analyzed. Multidrug resistance was defined as nonsusceptibility to any three or more different antibiotic classes. Risk factors for multidrug resistance were evaluated using multivariable logistic regression. Of 20,100 cases of IPD identified, 3,708 (18%) had MDR isolates, with the proportion increasing from 16% (461/2,891) to 20% (648/3,326) (P < 0.001) over the study period. Serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) accounted for 94% of MDR strains. Significant risk factors for MDR IPD included PCV13 (1,486/6,407; odds ratio [OR] of 6.3; 95% confidence interval [CI] of 5.0 to 7.9) and pediatric (3,382/9,980; OR of 12.8; 95% CI of 10.6 to 15.4) serotypes, age of <5 (802/3,110; OR of 2.0; 95% CI of 1.8 to 2.3) or ≥65 (39/239; OR of 1.5; 95% CI of 1.0 to 2.2) years versus age of 15 to 64 years, HIV infection (975/4,636; OR of 1.5; 95% CI of 1.2 to 1.8), previous antibiotic use (242/803; OR of 1.7; 95% CI of 1.4 to 2.1), previous hospital admissions (579/2,450; OR of 1.2; 95% CI of 1.03 to 1.4), urban location (883/4,375; OR of 2.0; 95% CI of 1.1 to 3.5), and tuberculosis treatment (246/1,021; OR of 1.2; 95% CI of 1.03 to 1.5). MDR IPD prevalence increased over the study period. The effect of many of the MDR risk factors could be reduced by more judicious use of antibiotics. Because PCV13 serotypes account for most MDR infections, pneumococcal vaccination may reduce the prevalence of multidrug resistance.
Regev-Yochay, Gili; Katzir, Michal; Strahilevitz, Jacob; Rahav, Galia; Finn, Talya; Miron, Dan; Maor, Yasmin; Chazan, Bibiana; Schindler, Yehudith; Dagan, Ron
Introduction of pneumococcal conjugate vaccine (PCV) has nearly eliminated vaccine-type (VT) invasive pneumococcal disease (IPD) in children, yet the reported resulting reduction of adult IPD is variable. We present the indirect impact of sequential PCV7/PCV13 implementation in Israel on adult IPD. An ongoing nationwide active surveillance was initiated on July 2009 when PCV7 was implemented (with Catch-up). PCV7 was gradually replaced by PCV13 since November 2010. Comorbidity and outcome data were collected from medical files. Incidence rates were calculated for overall and vaccine-type IPD. A total of 2579 IPD cases were diagnosed among a population of 5.0-5.5 million adults >18y (2009-2015). Incidence rates were 9.15/100,000 and 10.16/100,000 in the first and second study years, respectively. However, after PCV13 implementation, the rates decreased to 7.19 within four years, and remained stable in the two following years. Within 6years, PCV7-VT-IPD incidence decreased from 2.52 to 0.52 (79%) and PCV13-VT-IPD from 6.15 to 1.81 (71%). Concurrently, non-VT13 incidence increased from 2.99 to 5.25. Approximately 50% of all patients were adults ≥65y, in whom the decrease in PCV13-VT-IPD incidence was smaller and slower (65% vs. >80% decrease in adults <50y). Despite continued reduction in PCV13-VT-IPD, overall IPD was stable during the last two years due to serotype replacement. Yet, the significant decrease in adult IPD, six years post-PCV7/13 implementation emphasizes the importance of indirect protection in achieving overall population impact and should be considered when discussing the potential additional benefits of direct adult PCV vaccination. Copyright © 2017 Elsevier Ltd. All rights reserved.
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
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.
De Wals, Philippe; Lefebvre, Brigitte; Defay, Fannie; Deceuninck, Geneviève; Boulianne, Nicole
The 10-valent protein D pneumococcal conjugate vaccine (PHiD-CV) was licensed on the basis of immunogenicity studies and there are no published data on its effectiveness to prevent invasive pneumococcal disease (IPD). In the province of Quebec, Canada, PHiD-CV was introduced in the summer of 2009, replacing the 7-valent CRM197 vaccine (PCV-7). Transition to the new vaccine was recommended regardless of the number of PCV7 doses already administered. IPD rates in children born in 2007-2010 and observed up to the end of 2010 were computed from laboratory surveillance data. The main vaccine used for the infant primary immunization series (mainly 2 doses at 2-4 months) and the toddler (12 months) booster dose was inferred from the Quebec City Immunization Registry data. IPD rates were significantly lower in the cohorts exposed to PHiD-CV (35/100,000 person-years) as compared with those exposed to PCV-7 (64/100,000 person-years; p=0.03). There was no breakthrough vaccine-type IPD case among children who had received ≥2 PHiD-CV doses for the primary series or a single PHiD-CV dose as a booster. There was also a statistically non-significant lower frequency of 19A and other non-vaccine types IPD cases in children exposed to 2+1 PHiD-CV doses as compared with those exposed to PCV-7. Results are compatible with a high level of protection induced by PHiD-CV against IPD caused by homologous serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.
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
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: firstname.lastname@example.org.
Boccalini, Sara; Varone, Ornella; Chellini, Martina; Pieri, Luca; Sala, Antonino; Berardi, Cesare; Bonanni, Paolo; Bechini, Angela
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.
Deng, Xianding; Memari, Nader; Teatero, Sarah; Athey, Taryn; Isabel, Marc; Mazzulli, Tony; Fittipaldi, Nahuel; Gubbay, Jonathan B.
Background: Molecular typing is essential for inferring genetic relatedness between bacterial pathogens. In this study, we applied whole genome sequencing (WGS) for rapid prediction of sequence type and antibiotic resistance for invasive pneumococcal isolates. Methods: 240 isolates from adults (≥50 years old) in Ontario, Canada during 2009 to 2013 were subjected to WGS. Sequence type, antibiotic susceptibility and resistance were predicted directly from short reads. Emerging non-vaccine serotype 22F was further characterized by WGS. Results: Sequence type was successfully determined for 98.3% of isolates. The overall sensitivity and specificity for antibiotic resistance prediction were 95 and 100% respectively, compared to standard susceptibility testing methods. WGS-based phylogeny divided emerging 22F (ST433) strains into two distinct clades: clade A harboring a 23 kb-prophage and anti-phage PhD/Doc system and clade B with virulence-related proteases. Five isolates in clade A developed macrolide resistance via 5.1 kb mega element recombination (encoding mefE and msrD), while one isolate in clade B displayed quinolone resistance via a gyrA mutation. Conclusions: WGS is valuable for routine surveillance of pneumococcal clinical isolates and facilitates prediction of genotype and antibiotic resistance. The emergence of 22F in Ontario in the post-vaccine era and evidence of evolution and divergence of the 22F population warrants heightened pneumococcal molecular surveillance. PMID:28082965
Boccalini, Sara; Bechini, Angela; Gasparini, Roberto; Panatto, Donatella; Amicizia, Daniela; Bonanni, Paolo
Many evaluations have been performed on the economic impact of pneumococcal vaccination in older adults (>64 y of age) in several countries, including Italy. However, these studies did not include the new data on the effectiveness of 13-valent conjugate pneumococcal vaccine (PCV13) in the elderly reported by the CAPiTA Study. The aim of the present study was to update our previous budget impact analysis of multi-cohort PCV13 vaccination in adults in Italy by including new scientific evidence. We also compared single-cohort vaccination strategies per year, in order to identify the cohort with the most favorable economic profile, in the event of the multi-cohort approach not being economically sustainable for the National Health System (NHS). The new impact analysis highlights that the vaccination of one, two or three adult cohorts per year in Italy would lead to a considerable reduction in pneumococcal disease and its related costs over 5 y. The strategies proved cost-effective (ICERs ranging from €14,605 to €15,412/QALY), i.e. well below the threshold of €50,000/QALY. The ICERs were slightly lower than those calculated in the first published analysis and vaccination continued to be economically favorable. In the case of a mono-cohort strategy, the vaccination of 65-year-old subjects, albeit more expensive, proved to be more favorable than the vaccination of 70- or 75-year-old cohorts. Finally, after the inclusion of the recent clinical evidence, the age-based PCV13 vaccination of the elderly in Italy continued to be economically justified from the NHS perspective in the short period. Vaccination of the elderly should therefore be strongly recommended nationwide in Italy.
Ojal, John; Flasche, Stefan; Hammitt, Laura L; Akech, Donald; Kiti, Moses C; Kamau, Tatu; Adetifa, Ifedayo; Nurhonen, Markku; Scott, J Anthony G; Auranen, Kari
In 2011, Kenya introduced the 10-valent pneumococcal conjugate vaccine together with a catch-up campaign for children aged <5years in Kilifi County. In a post-vaccination surveillance study based in Kilifi, there was a substantial decline in invasive pneumococcal disease (IPD). However, given the continued circulation of the vaccine serotypes it is possible that vaccine-serotype disease may re-emerge once the effects of the catch-up campaign wear off. We developed a compartmental, age-structured dynamic model of pneumococcal carriage and invasive disease for three serotype groups: the 10-valent vaccine serotypes and two groups of non-vaccine serotypes based on their susceptibility to mutual competition. The model was calibrated to age- and serotype-specific data on carriage and IPD in the pre-vaccination era and used to predict carriage prevalence and IPD up to ten years post-vaccination in Kilifi. The model was validated against the observed carriage prevalence after vaccine introduction. The model predicts a sustained reduction in vaccine-type pneumococcal carriage prevalence from 33% to 8% in infants and from 30% to 8% in 1-5year olds over the 10-year period following vaccine introduction. The incidence of IPD is predicted to decline across all age groups resulting in an overall reduction of 56% in the population, corresponding to 10.4 cases per 100,000 per year. The vaccine-type IPD incidence is estimated to decline by 83% while non-vaccine-type IPD incidence is predicted to increase by 52%. The model's predictions of carriage prevalence agrees well with the observed data in the first five years post-vaccination. We predict a sustained and substantial decline in IPD through PCV vaccination and that the current regimen is insufficient to fully eliminate vaccine-serotype circulation in the model. We show that the observed impact is likely to be sustained despite waning effects of the catch-up campaign. Copyright © 2017 The Author(s). Published by Elsevier Ltd
Capsular serotypes and antimicrobial susceptibilities of Streptococcus pneumoniae causing invasive pneumococcal disease from 2009-2012 with an emphasis on serotype 19A in bacteraemic pneumonia and empyema and β-lactam resistance.
Lee, Meng-Rui; Chen, Chung-Ming; Chuang, Tzu-Yi; Huang, Yu-Tsung; Hsueh, Po-Ren
Capsular serotypes and antimicrobial susceptibilities of Streptococcus pneumoniae isolates that cause invasive pneumococcal disease (IPD) were studied and the role of serotype 19A in the development of bacteraemic pneumonia and empyema was investigated. Subjects comprised 98 patients (56 adults and 42 children) who were treated for IPD at a university-affiliated tertiary referral centre in Taiwan during 2009-2012. Serotypes of the isolates were identified using the latex agglutination method. In vitro susceptibilities of the isolates to 13 antimicrobial agents were determined using the broth microdilution method and were interpreted as recommended by the Clinical and Laboratory Standards Institute. During the study period, bacteraemic pneumonia was the most common type of infection (43/98; 43.9%), followed by primary bacteraemia (30/98; 30.6%). Serotype 19A was the most common serotype (23/98; 23.5%) in all patients. Fourteen (70.0%) of 20 children (47.6% of all children) with serotype 19A infection had pneumonia with empyema, whilst eight patients had concomitant bacteraemia. 7-valent pneumococcal conjugated vaccine (PCV-7), PCV-10, PCV-13 and 23-valent pneumococcal polysaccharide vaccine (PPV-23) had coverage rates of 37.8%, 38.8%, 79.6% and 77.6%, respectively. A substantial increase in the proportion of serotype 15A (6.1%) and 6A (8.2%) was found. In addition, there was a significant reduction in rates of susceptibility of serotype 19A isolates to penicillin, cefotaxime and ceftriaxone but not to azithromycin or any quinolone tested compared with those of non-19A isolates. The prevalence of serotypes 19A, 15A and 6A in patients with IPD increased markedly during the period, especially in children with bacteraemic pneumonia and empyema. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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.
Aguiar, S I; Brito, M J; Horacio, A N; Lopes, J P; Ramirez, M; Melo-Cristino, J
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.
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
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.
Pneumococcal Vaccine bers are affected by pneumococcal disease; however, because of Board 35 recommended that the 23 - valent ...clinical trial of the currently In 1945, the first successful trial of a polyvalent polysaccha- available 23 - valent pneumococcal vaccine . The purpose... 23 . Butler JC, Dowell SF, Brelman RF: Epidemiology of emerging pneumococcal drug 42, Hirschmann JV: Use of the pneumococcal polysaccharide vaccine
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Moïsi, Jennifer C.; Makawa, Makawa-Sy; Tall, Haoua; Agbenoko, Kodjo; Njanpop-Lafourcade, Berthe-Marie; Tamekloe, Stanislas; Amidou, Moussa; Mueller, Judith E.; Gessner, Bradford D.
Background S. pneumoniae is a leading cause of meningitis morbidity and mortality in the African meningitis belt, but little is known of its contribution to the burden of pneumonia in the region. We aimed to estimate the incidence of pneumococcal disease in children and adults in northern Togo, before the introduction of pneumococcal conjugate vaccine (PCV). Methods and findings From May 1st 2010 to April 30th 2013, we systematically enrolled all hospitalized patients meeting a case definition of suspected meningitis or clinical pneumonia, residing in Tone or Cinkasse districts, northern Togo and providing informed consent. We collected clinical data and tested biological specimens according to standardized procedures, including bacteriology and PCR testing of cerebro-spinal fluid for meningitis patients and blood cultures and whole blood lytA PCR for pneumonia patients. Chest X-rays (CXR) were interpreted using the WHO methodology. We included 404 patients with meningitis (104 <5 years of age) and 1550 with pneumonia (251 <5 years) over the study period. Of these, 78 (19%) had pneumococcal meningitis (13 <5 years), 574 (37%) had radiologically-confirmed pneumonia (83 <5 years) and 73 (5%) had culture-confirmed pneumococcal pneumonia (2 <5 years). PCV13 serotypes caused 79% (54/68) of laboratory-confirmed pneumococcal meningitis and 83% (29/35) of culture-confirmed pneumococcal pneumonia. Serotype 1 predominated in meningitis (n = 33) but not in pneumonia patients (n = 1). The incidence of pneumococcal disease was 7.5 per 100,000 among children <5 years of age and 14.8 in persons 5 years of age and above in the study area. When considering CXR-confirmed and blood PCR-positive pneumonia cases as likely pneumococcal, incidence estimates increased to 43.7 and 66.0 per 100,000 in each of these age groups, respectively. Incidence was at least 3-fold higher when we restricted the analysis to the urban area immediately around the study hospitals. Conclusions Our findings
Muley, Vrishali Avinash; Ghadage, Dnyaneshwari Purushottam; Yadav, Gauri Eknath; Bhore, Arvind Vamanrao
Invasive pneumococcal infections often prove rapidly fatal, even where good medical treatment is readily available. In developed countries, up to 20% of people who contract pneumococcal meningitis die; however, in developing world, mortality is closer to 50%, even among hospitalized patients. The World Health Organization estimated 600,000-800,000 adult deaths each year from pneumococcal pneumonia, meningitis, and sepsis. This study aims to estimate isolation rate of invasive pneumococcal infection in adults, to determine the antimicrobial susceptibility profile of Streptococcus pneumoniae isolates and to study the associated risk factors. A total of 120 patients with suspected invasive infection such as meningitis, septicemia, and pleural effusion, were included in the study. Various clinical specimens such as pus, cerebrospinal fluid, and other sterile body fluids were processed for isolation and identification of S. pneumoniae. Kirby-Bauer disc diffusion method was performed to determine the antimicrobial susceptibility profile. Minimum inhibitory concentration test was performed to determine the penicillin resistance. Of 120 patients, 40 (33.33%) cases were proven by culture to have an invasive pneumococcal infection. The most common clinical condition observed was meningitis followed by pneumonia with pleural effusion and sepsis. Pneumococcal isolates exhibited 40% resistance to cotrimoxazole and 12.73% to chloramphenicol. Two meningeal isolates exhibited penicillin resistance. Comorbidities observed in 21 (52.5%) cases were mainly Diabetes mellitus, smoking, and alcoholism. Invasive pneumococcal infection has poor prognosis and penicillin-resistant strains have become increasingly common. This study emphasizes the importance of judicious use of antibiotics, especially to refrain their use in mild self-limiting upper respiratory infections.
Castro, Juan D; Siccha, Sofía M; Egoavil, Martha; Chaparro, Eduardo; Hernandez, Roger; Silva, Wilda; Águila, Olguita Del; Saenz, Andrés; Campos, Francisco; Reyes, Isabel; Castillo, María E; Ochoa, Theresa J
To describe the clinical characteristics, antibiotic resistance, and distribution of serotypes of bacterial strains that cause invasive pneumococcal disease (IPD) in adults. Case series. Pneumococcal strains were isolated from 2009 to 2011 from hospitalized adult patients with IPD in five hospitals and two laboratories located in Lima. The analysis of data from 43 patients with IPD indicated that 58.2% were older than 60 years. The most common complications were pneumonia (39.5%), meningitis (30.2%), bacteremia (13.9%), peritonitis (11.6%), and septic arthritis (4.8%). The mortality rate was 28.9%, and 72.7% of cases involved patients older than 60 years. The pneumococcal strains were resistant to the following antibiotics: penicillin, 0% and 30.8% in non-meningitis and meningitis strains, respectively; ceftriaxone, 4.5% and 16.7% in non-meningitis and meningitis strains, respectively; trimethoprim/sulfamethoxazole, 69.0%; and erythromycin, 35.7%. The most common serotypes were 19F, 23F, 6B, 14, and 6C. The percentage of vaccine strains was 44.2% for the 7-valent conjugate pneumococcal vaccine (PCV7) and PCV10, 51.2% for PCV13, and 60.4% for the 23-valent polysaccharide vaccine (PPV23). Pneumococcus is an important pathogen in adults, particularly in older adults, owing to its high mortality rate.
Jefferies, Johanna M.; Mohd Yusof, Mohd Yasim; Devi Sekaran, Shamala; Clarke, Stuart C.
Although Streptococcus pneumoniae is a leading cause of childhood disease in South East Asia, little has previously been reported regarding the epidemiology of invasive pneumococcal disease in Malaysia and very few studies have explored pneumococcal epidemiology using multilocus sequence typing (MLST). Here we describe serotype, multilocus sequence type (ST), and penicillin susceptibility of thirty pneumococcal invasive disease isolates received by the University of Malaya Medical Centre between February 2000 and January 2007 and relate this to the serotypes included in current pneumococcal conjugate vaccines. A high level of diversity was observed; fourteen serotypes and 26 sequence types (ST), (11 of which were not previously described) were detected from 30 isolates. Penicillin non-susceptible pneumococci accounted for 33% of isolates. The extent of molecular heterogeneity within carried and disease-causing Malaysian pneumococci remains unknown. Larger surveillance and epidemiological studies are now required in this region to provide robust evidence on which to base future vaccine policy. PMID:24941079
Falkenhorst, Gerhard; Remschmidt, Cornelius; Harder, Thomas; Hummers-Pradier, Eva; Wichmann, Ole; Bogdan, Christian
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
Neill, Daniel R.; Fernandes, Vitor E.; Wisby, Laura; Haynes, Andrew R.; Ferreira, Daniela M.; Laher, Ameera; Strickland, Natalie; Gordon, Stephen B.; Denny, Paul; Kadioglu, Aras; Andrew, Peter W.
Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3+Helios+ T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design. PMID:22563306
Loo, Jennifer D; Conklin, Laura; Fleming-Dutra, Katherine E; Knoll, Maria Deloria; Park, Daniel E; Kirk, Jennifer; Goldblatt, David; O'Brien, Katherine L; Whitney, Cynthia G
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. 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. 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. 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.
Betriu, Anna Sangil; Arranz, María J; Güerri-Fernández, Roberto; Pérez, Maite; Monzón, Helena; Payeras, Antoni; Andrés, Marta; Torviso, Jorge; Ibañez, Laura; Garau, Javier; Calbo, Esther
The pathogenesis of IPD remains unknown, especially among middle-aged individuals without risk factors (WRF). The aim of the present study was to investigate the role of single nucleotide polymorphisms (SNP) within key genes involved in innate immune response on IPD susceptibility. Forty-three SNPs within 10 immunological genes were investigated in a cohort of 144 Caucasian IPD patients and 280 ethnically matched controls. The allele distribution of the NFKBIA rs1050851 and NFKBIE rs2282151 variants were associated with IPD susceptibility (χ 2 = 4.23, p = 0.04 and χ 2 = 5.13, p = 0.02, respectively). Additionally, the genotype distribution of NFKBIZ rs645781 (χ 2 = 8.25, p = 0.02) and IL1R1 rs3917254 (χ 2 = 6.70, p = 0.04) were also associated with IPD risk. When only IPD-WRF patients were considered; the allele distribution of IL1R1 rs2160227 (χ 2 = 5.62, p = 0.03), rs13020778 (χ 2 = 5.73, p = 0.02), rs3917267 (χ 2 = 3.72, p = 0.05) and IL4 rs2227284 (χ 2 = 3.76, p = 0.05) and the genotype distribution of IL10 rs3024509 (χ 2 = 7.70, p = 0.02), IL1R1 rs3917254 (χ 2 = 13.40, p = 0.001), NFKBIZ rs645781 (χ 2 = 13.86, p = 0.001) and rs677011 (χ 2 = 9.06, p = 0.01) variants were associated with IPD risk. We found several associations between variants in the IL1R1, IL4, IL10, NFKBIE, NFKBIA, and NFKBIZ genes and risk of IPD. If validated, these biomarkers may help to identify people with higher risk of IPD. Copyright © 2018 Elsevier B.V. All rights reserved.
Burgess, Laura; Southern, Kevin W
Invasive pneumococcal disease is associated with significant mortality and many countries have introduced routine pneumococcal vaccination into their childhood immunisation programmes. Whilst pneumococcal disease in cystic fibrosis is uncommon, pneumococcal immunisation may offer some protection against pulmonary exacerbations caused by this pathogen. In the USA and UK pneumococcal vaccination is currently recommended for all children and adults with cystic fibrosis. This is an update of a previously published review. To assess the efficacy of pneumococcal vaccines in reducing morbidity in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, the pharmaceutical manufacturers of the polysaccharide and conjugate pneumococcal vaccines were approached.Date of the most recent search: 27 June 2016. Randomised and quasi-randomised controlled trials comparing pneumococcal vaccination (with either a polysaccharide or conjugate pneumococcal vaccine) with non-vaccination or placebo in children or adults with cystic fibrosis were eligible for inclusion. No relevant trials were identified. There are no trials included in this review. As no trials were identified we cannot draw conclusions on the efficacy of routine pneumococcal immunisation in people with cystic fibrosis in reducing their morbidity or mortality. As many countries now include pneumococcal immunisation in their routine childhood vaccination schedule it is unlikely that future randomised controlled trials will be initiated. Rigorously conducted epidemiological studies may offer the opportunity to evaluate the efficacy of pneumococcal vaccination in reducing morbidity and mortality in people with cystic fibrosis.
González, Roser; Armadans, Lluís; Rodrigo, José Ángel; Campins, Magda
Streptococcus pneumoniae is a significant cause of morbidity and mortality. Children with certain conditions are at risk of developing pneumococcal disease, including invasive pneumococcal disease (IPD). The aim of this study is to estimate admission rates for IPD in children with risk conditions in Catalonia, and to describe their characteristics. Retrospective longitudinal study of admission rates due to IPD between 2005 and 2012 in children younger than 16 years referred by Primary Care Centres of the Catalan Institute of Health, with risk conditions for invasive pneumococcal disease. Information was obtained from electronic medical records in the Primary Care Centres and from the Minimum Basic Data Set (MBDS) of acute hospital admissions. The overall IPD hospital admission rate in children with underlying conditions was 43.1 cases per 100,000 persons-year (95% CI: 32.2-57.7). The rate was higher in children <2 years old (107.8 per 100,000 persons-year; 95% CI: 69-168.3), and in those with neuromuscular disease and/or cerebrospinal fluid leak (141.6 per 100,000 persons-year), and Down's syndrome (133.5 per 100,000 persons-year). The hospital admission rate due to IPD in children with risk conditions in Catalonia is similar to that observed in other series, and higher than that described in the general population. It is necessary to implement immunisation strategies aimed directly at these risk groups. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Hawkins, Paulina; Mercado, Erik; Chochua, Sopio; Castillo, Maria E; Reyes, Isabel; Chaparro, Eduardo; Gladstone, Rebecca; Bentley, Stephen D; Breiman, Robert F; Metcalf, Benjamin J; Beall, Bernard; Ochoa, Theresa J; McGee, Lesley
Before PCV7 introduction, invasive pneumococcal disease (IPD) was responsible for approximately 12,000-18,000 deaths annually among children <5years in Latin America. In Peru, PCV7 was introduced in 2009. We used whole genome sequencing to deduce key features of invasive strains collected in Lima, Peru from 2006 to 2011. We sequenced 212 IPD isolates from 16 hospitals in Lima pre (2006-2009; n=133) and post (2010-2011; n=79) PCV7 introduction; 130 (61.3%) isolates were from children≤5years old. CDC's Streptococcus lab bioinformatics pipeline revealed serotypes, sequence types (STs), pilus genes, PBP types and other resistance determinants. During the pre-PCV7 period, serotype 14 was the most common serotype (24.8%), followed by 6B (20.3%), 19F (10.5%), and 23F (6.8%). Post-PCV7, the proportion of PCV7 serotype 6B decreased significantly (to 6.3%), while 19F (16.3%), 14 (15.0%), 23F (7.5%), and 19A (7.5%) were the most common serotypes; only serotypes 3 and 10A increased significantly. Overall, 82% (n=173) of all isolates carried at least one resistance determinant, including 72 (34%) isolates that carried resistance determinants against 3 or more antimicrobial classes; of these 72 isolates, 56 (78%) belonged to a PCV7 serotype. Eighty-two STs were identified, with 53 of them organized in 14 clonal complexes. ST frequencies were distributed differently pre and post-PCV7 introduction, with only 18 of the 57 STs identified in years 2006-2009 isolates also observed in years 2010-2011 isolates. The apparent expansion of a 19F/ST1421 lineage with predicted β-lactam resistance (PBP type 13:16:20) and carrying resistance determinants against four additional antimicrobial classes was observed. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.
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Bello Gonzalez, Teresita; Rivera-Olivero, Ismar Alejandra; Sisco, María Carolina; Spadola, Enza; Hermans, Peter W; de Waard, Jacobus H
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.
Simons, Malorie; Scott-Sheldon, Lori A J; Risech-Neyman, Yesenia; Moss, Steven F; Ludvigsson, Jonas F; Green, Peter H R
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 = 1.17, 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.
Rumlarová, Š; Kosina, P; Kračmarová, R; Plíšek, S; Rejtar, P
Presented are the authors' own experiences with invasive pneumococcal diseases in a group of pediatric inpatients with pneumococcal meningitis treated in the Department of Infectious Diseases, University Hospital and Charles University Faculty of Medicine in Hradec Králové over the last 10 years. A group of patients aged 0-18 years and hospitalized in the above facility in 2002-2011 was retrospectively assessed. The patients' basic clinical characteristics and treatment outcomes are shown below. Over the study period, 27 children with pneumococcal meningitis were treated; of those, 15 were boys and 12 were girls. The patients' ages ranged from 2 days to 17 years; seventeen children (63 %) were younger than 2 years. On admission, 11 children (40 %) had the infection in the middle ear or paranasal sinuses; intracranial complications were noted in 10 cases. Cerebrospinal fluid culture was positive for Streptococcus pneumoniae in 21 cases. In 6 patients, pneumococcal DNA was determined in the cerebrospinal fluid by PCR. None of the studied patients died. Eight children (29 %) were left with permanent damage; of those, seven had hearing impairment. Even today, pneumococcal meningitis in children remains a serious condition posing a risk of dangerous consequence or even death. To the maximum extent possible, prevention should include vaccination, especially in infants and children with the predisposing factors.
Weil-Olivier, Catherine; Gaillat, Jacques
Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children. As highlighted in this paper, differences exist between children and adults for PD manifestations (incidence, morbidity and mortality) and serotypes isolated in nasopharyngeal carriage and diseases, so benefits from adult vaccination must be considered in this light. PCV13 induces an immune response in adults that is non-inferior for all serotypes common with the 23-valent plain polysaccharide vaccine that is currently recommended for adults and even superior for many serotypes. Although there is no evidence that this immune response translates to clinical efficacy in adults as seen in children, the results from a randomised trial in The Netherlands, expected in 2014, should provide the missing evidence. This evidence and efficient surveillance systems should provide the necessary data, essential for policy makers in their decisions on adult pneumococcal vaccination policies. Copyright © 2014 Elsevier Ltd
Jauneikaite, E; Jefferies, J M; Hibberd, M L; Clarke, S C
Streptococcus pneumoniae is a major cause of bacterial infections resulting in significant morbidity and mortality worldwide. Currently, up to 13 serotypes are included in pneumococcal conjugate vaccines (PCVs). However, the serotype formulation of these vaccines was initially designed to protect children against serotypes most commonly causing invasive disease in North America, and may not reflect the serotype distribution across the world. Data regarding pneumococcal epidemiology from the other parts of the world, in particular South East Asia, has not been reviewed. This systematic literature review analyses published serotype data regarding S. pneumoniae isolates from South East Asian countries (defined as countries belonging to the Association of South East Asian Nations, ASEAN): Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam up to 3rd of March 2012. Analysis of data from six ASEAN countries, from which information on pneumococcal serotypes was available, showed that the most common disease causing serotypes (in rank order) were 19F, 23F, 14, 6B, 1, 19A and 3. Serotype distribution of pneumococcal isolates was similar across the ASEAN region. Serotype level data was more commonly reported for pneumococcal isolates causing invasive pneumococcal disease than for those from non-invasive disease. Studies from Malaysia, Thailand and Singapore contributed the largest proportion of pneumococcal isolates, and serotype data, when compared to other ASEAN countries. This review demonstrates that the majority of IPD causing serotypes in SE Asia are included in currently licensed PCVs. However, PCV's are included in the routine childhood immunisation schedule of only one of the ten countries included in this analysis. Our findings demonstrate the scarcity of information available on serotype prevalence and distribution of pneumococci in SE Asia. Copyright © 2012 Elsevier Ltd. All rights reserved.
De Wals, Philippe; Black, Steven; Borrow, Ray; Pearce, David
A heptavalent pneumococcal conjugate vaccine (PCV-7) is available to immunize infants against pneumococcal disease. However, a recently developed vaccine, pneumococcal nontypable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV), has recently been licensed. PHiD-CV contains 3 additional Streptococcus pneumoniae serotypes and may provide protection against nontypable H influenzae (NTHi) infection. New health economic models are required to model the impact of PHiD-CV and compare its effectiveness with PCV-7. The aim of this article was to design a model capable of projecting the pneumococcal and NTHi disease burden on the entire UK population under different schedules of PCV-7 and PHiD-CV. This model should also be capable of modeling the net indirect effect of vaccination (ie, the sum of serotype replacement and herd protection). A static, deterministic, age-compartmental model was created based on published information and the input of a board of experts in pneumococcal disease. The model presents results from both a payer-based and societal perspective. A 1-way sensitivity analysis was used to demonstrate the robustness of the model. Key parameters included the case fatality ratio for bacteremia, the hospitalization rate for acute otitis media (AOM), and parameters surrounding the extent of the net indirect effect of vaccination. Excluding net indirect effect, 325 cases of invasive pneumococcal disease (IPD), 619 hospitalizations for pneumonia, and 9016 general practitioner visits for AOM would be prevented annually with the current PCV-7 2 + 1 program. These numbers would increase to 374, 755, and 30,920, respectively, using a PHiD-CV 2 + 1 regimen, or to 503, 994, and 47,180 using a PHiD-CV 3 + 1 regimen. When a net indirect effect of 38% is considered, health benefits could be much larger; 2417, 2451, and 3045 IPD cases would be prevented in the 3 scenarios, respectively. It is predicted that any vaccination program in the United Kingdom would have
Møller, Martin Nue; Brandt, Christian; Østergaard, Christian; Caye-Thomasen, Per
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.
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
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
Hirst, Ceri; Owusu-Ofori, Shirley
People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. To assess the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 28 March 2012. All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug. Both authors independently extracted data and assessed trial quality. Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with sickle cell disease (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five. Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions
Dommaschk, Anne; Ding, Nadine; Tort Tarres, Meritxell; Bittersohl, Lara F; Maus, Regina; Stolper, Jennifer; Jonigk, Danny; Braubach, Peter; Lippmann, Torsten; Welte, Tobias; Maus, Ulrich A
Nasopharyngeal colonization with Streptococcus pneumoniae (Spn) is an important precondition for the development of pneumococcal pneumonia. At the same time, nasopharyngeal colonization with Spn has been shown to mount adaptive immune responses against Spn in mice and humans. Cellular responses of the nasopharyngeal compartment, including the nasal-associated lymphoid tissue, to pneumococcal colonization and their importance for developing adaptive immune responses are poorly defined. We show that nasopharyngeal colonization with S. pneumoniae led to substantial expansion of dendritic cells (DCs) both in nasopharyngeal tissue and nasal-associated lymphoid tissue of mice. Depletion of DCs achieved by either diphtheria toxin (DT) treatment of chimeric zDC+/DTR mice, or by use of FMS-like tyrosine kinase 3 ligand (Flt3L) KO mice exhibiting congenitally reduced DC pool sizes, significantly diminished antibody responses after colonization with Spn, along with impaired protective immunity against invasive pneumococcal disease. Collectively, the data show that classical DCs contribute to pneumococcal colonization induced adaptive immune responses against invasive pneumococcal disease in two different mouse models. These data may be useful for future nasopharyngeal vaccination strategies against pneumococcal diseases in humans. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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
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
Kumar, Rakesh; Arora, Narendra; Santosham, Mathuram
Despite the licensure of the pneumococcal conjugate vaccine (PCV) in the US and other Western countries for over 14 years, as of September 2014 only 4 South Asian countries were using PCV in their universal immunization program. To generate momentum toward addressing this issue a “South Asia symposium on pneumococcal disease and the promise of vaccines” was organized just prior to the 9th international symposium on pneumococci and pneumococcal diseases held in India recently. Leading scientists, program managers, and decision makers including ministry officials from the region participated in the meeting. The participants discussed available data on pneumococcal disease burden in South Asia, surveillance methods, efficacy and safety of pneumococcal conjugate vaccines (PCV), the status of PCV introduction, programmatic challenges in introducing PCV and available data on the impact of PCV in South Asia and globally. There was a strong consensus that available data on disease burden and the global experience with PCV justified the introduction PCV in all Asian countries in order to accelerate the gains in child survival in the region. PMID:27026150
Riddington, C; Owusu-Ofori, S
People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the Cooperative Study of Sickle Cell Disease observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimes may be advisable for this population. To assess the effects of prophylactic antibiotic regimes for preventing pneumococcal infection in children with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and hand searching abstract books of conference proceedings. Date of the most recent search: December 2001. All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug. Both reviewers independently extracted data and assessed trial quality. Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced risk of infection in children with sickle cell disease (SS or Sb0Thal) receiving prophylactic penicillin. For initiation of treatment the odds ratio was 0.37 (95% CI 0.16, 0.86), and for withdrawal OR= 0.49 (95% CI 0.09, 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five. Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.
Feldman, Charles; Abdulkarim, Emad; Alattar, Fatma; Al Lawati, Faryal; Al Khatib, Hisham; Al Maslamani, Muna; Al Obaidani, Idris; Al Salah, Mosaab; Farghaly, Mohamed; Husain, Entesar H; Mokadas, Eiman
Pneumococcal disease has substantial incidence, morbidity and mortality in older adults. Decreased birth rates and longer lifespans indicate that the global population is aging, although rates of aging differ between countries . In 2010, the proportion of the population aged >60 years in the general Arab Region was 7%, and this proportion is expected to rise to 19% by 2050 for the region as a whole ; the United Nations estimates for the individual countries of the Arabian Gulf by 2050 are 25.7%, 24.9%, 20.7%, 26.7% and 10.5% in the Kuwait, Bahrain, Qatar, United Arab Emirates (UAE) and Oman, respectively, which are comparable to the 26.9% predicted for the USA and lower than that predicted in European countries, in which the 2050 estimates are 32.7%, 34.0% and 38.1% for France, the UK and Germany, respectively . Globally and in the Gulf Region, pneumococcal disease is an increasingly important public health burden in the elderly. The burden of pneumococcal disease can be reduced by effective vaccination programs, but the recommendations on pneumococcal vaccination in adults vary widely. The major barriers to vaccine implementation among healthcare professionals are an incomplete awareness of pneumococcal disease and the vaccination options in adults. The Gulf Advocate Group calls for healthcare providers in the countries of the Arabian Gulf (Kuwait, Bahrain, Qatar, United Arab Emirates and Oman) to support awareness and education programs about adult pneumococcal disease, particularly in high-risk groups such as those >65 years of age, those with type 2 diabetes mellitus, hematological malignancy, organ and bone marrow transplantation or chronic kidney or lung diseases and pilgrims undertaking the Hajj to improve pneumococcal disease surveillance and optimize and disseminate recommendations for adult vaccination. The Gulf Advocate Group recommends following the U.S. Centers for Disease Control and Prevention (CDC) guidelines for pneumococcal vaccination [3
Nurhonen, Markku; Cheng, Allen C.; Auranen, Kari
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
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
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.
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.
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
Rodríguez González-Moro, Jose Miguel; Menéndez, Rosario; Campins, Magda; Lwoff, Nadia; Oyagüez, Itziar; Echave, María; Rejas, Javier; Antoñanzas, Fernando
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.
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
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. 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. 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). 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted
Abghari, Pamella F.; Poowuttikul, Pavadee; Secord, Elizabeth
Purpose: Immunoglobulin replacement is the mainstay treatment in patients with humoral immunodeficiencies, yet a handful of patients continue to develop sinopulmonary infections while on therapy. The objective of our study was to compare immunoglobulin G (IgG) pneumococcal antibody levels in patients with humoral immune deficiencies who have been on intravenous immunoglobulin (IVIG) replacement for at least 1 year to those on subcutaneous immunoglobulin (SCIG) therapy for at least 1 year. Methods: A retrospective chart review was completed on 28 patients. These patients’ ages ranged between 1 and 61 years. Pneumococcal serotype titers obtained at least 1 year after initiating therapy were compared between patients on IVIG (19 patients) and SCIG (9 patients). Results: A comparison between the groups demonstrated that SCIG achieved a higher percentage of serotype titers protective for noninvasive disease (≥1.3) and 100% protection for invasive disease (≥0.2). Our data also demonstrated a similar lack of protection (less than 50% ≥1.3) in 9N, 12F, and 23F on IVIG and 4, 9N, 12F, and 23F on SCIG. Conclusions: Our data demonstrated that serotypes 1, 3, 4, 9N, 12F, and 23F exhibited the lowest random IgG means while on IVIG, which was comparable to other published studies that looked at the mean IgG levels. In addition, our retrospective chart review demonstrated a greater number of therapeutic pneumococcal titers with SCIG in comparison to IVIG. PMID:28321436
Iroh Tam, Pui-Ying; Thielen, Beth K; Obaro, Stephen K; Brearley, Ann M; Kaizer, Alexander M; Chu, Haitao; Janoff, Edward N
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
Grogg, Stanley E; Schultz, Jan
In 2015, the Advisory Committee on Immunization Practices issued updated recommendations for the use of 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to immunize adults aged 19 to 64 years with risk factors and all adults aged 65 years or older. Despite these recommendations, rates of vaccination among adults remain low. Federal and state initiatives have been launched to encourage health care providers to incorporate vaccination screening and recommendations in practice. Several resources are available to improve vaccination rates, including implementing electronic medical records; engaging non-physician staff in assessing vaccination history and administering immunizations; adopting standing order protocols; and implementing strong recommendations to patients regarding needed immunizations. However, even in the face of compelling evidence-based research, implementing changes in practice is challenging. The American Osteopathic Association implemented a 2-part Web program called the Call to Action on Pneumococcal Disease. Although some changes in attitudes and intent to change were demonstrated by this initiative, there were no statistically significant increases in self-reported actual adoption of standing order protocols or increases in adult pneumococcal immunization. Nonetheless, some lessons were learned, and these results support the need for ongoing efforts in this area of medicine.
How, Choon How; Phua See Chun, Priscilla; Shafi, Fakrudeen; Jakes, Rupert W
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
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
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.
Emori, Kazumasa; Takeuchi, Nobuhiro; Soneda, Junichi
A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen. PMID:26942021
Emori, Kazumasa; Takeuchi, Nobuhiro; Soneda, Junichi
A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen.
Vila-Corcoles, Angel; Ochoa-Gondar, Olga
Streptococcus pneumoniae remains a major cause of morbidity and mortality throughout the world. To date, after the introduction of routine childhood immunization, elderly people (i.e., persons aged 65 years or older) suffer the greatest burden of pneumococcal disease in developed countries. At present, two anti-pneumococcal vaccines are available for use in adults: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent protein-polysaccharide conjugate vaccine (PCV13). This article reviews current data about the burden of pneumococcal disease in the elderly, as well as evidence for immunogenicity, clinical efficacy, and possible cost-effectiveness of both vaccines. The main advantage of PCV13 is that it may be more effective than PPV23, but a major limitation is that it is directed against strains that are likely to be greatly reduced in the population since its introduction in childhood immunization. The main disadvantage of PPV23 is that it may be less effective than PCV13 against vaccine-type infections but a major advantage is that it may provide protection against ten additional serotypes. To date, expert committees have not changed recommendations for pneumococcal vaccination in adults. However, at present, they are evaluating different alternatives (basically, maintaining PPV23, changing from PPV23 to PCV13 in some groups, or adding PCV13 for all or some target adult population subgroups). Critical data (clinical efficacy reported in ongoing trials and magnitude of indirect effects of pediatric PCV13 programs) needed to make a well-informed decision could be available during 2013. Considering all concerns over indirect effects and replacement strains following the use of polysaccharide-based vaccines, efforts should be directed toward developing vaccines, such as protein-based pneumococcal vaccines, with potential serotype-independent protection. Meanwhile, according to current recommendations, PPV23 should continue to be used for high
Pneumococcal meningitis; Pneumococcus - meningitis ... Pneumococcal meningitis is caused by Streptococcus pneumoniae bacteria (also called pneumococcus, or S pneumoniae ). This type of bacteria is the ...
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.
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
Mook-Kanamori, B B; Valls Serón, M; Geldhoff, M; Havik, S R; van der Ende, A; Baas, F; van der Poll, T; Meijers, J C M; P Morgan, B; Brouwer, M C; van de Beek, D
Mortality and morbidity in patients with bacterial meningitis result from the proinflammatory response and dysregulation of coagulation and fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is activated by free thrombin or thrombin in complex with thrombomodulin, and plays an antifibrinolytic role during fibrin clot degradation, but also has an anti-inflammatory role by inactivating proinflammatory mediators, such as complement activation products. To assess the role of TAFI in pneumococcal meningitis. We performed a prospective nationwide genetic association study in patients with bacterial meningitis, determined TAFI and complement levels in cerebrospinal fluid (CSF), and assessed the function of TAFI in a pneumococcal meningitis mouse model by using Cpb2 (TAFI) knockout mice. Polymorphisms (reference sequences: rs1926447 and rs3742264) in the CPB2 gene, coding for TAFI, were related to the development of systemic complications in patients with pneumococcal meningitis. Higher protein levels of TAFI in CSF were significantly associated with CSF complement levels (C3a, iC3b, and C5b-9) and with more systemic complications in patients with bacterial meningitis. The risk allele of rs1926447 (TT) was associated with higher levels of TAFI in CSF. In the murine model, consistent with the human data, Cpb2-deficient mice had decreased disease severity, as reflected by lower mortality, and attenuated cytokine levels and bacterial outgrowth in the systemic compartment during disease, without differences in the brain compartment, as compared with wild-type mice. These findings suggest that TAFI plays an important role during pneumococcal meningitis, which is likely to be mediated through inhibition of the complement system, and influences the occurrence of systemic complications and inflammation. © 2015 International Society on Thrombosis and Haemostasis.
Jusot, Jean-François; Neill, Daniel R; Waters, Elaine M; Bangert, Mathieu; Collins, Marisol; Bricio Moreno, Laura; Lawan, Katiellou G; Moussa, Mouhaiminou Moussa; Dearing, Emma; Everett, Dean B; Collard, Jean-Marc; Kadioglu, Aras
The Sahel region of West Africa has the highest bacterial meningitis attack and case fatality rate in the world. The effect of climatic factors on patterns of invasive respiratory bacterial disease is not well documented. We aimed to assess the link between climatic factors and occurrence of invasive respiratory bacterial disease in a Sahel region of Niger. We conducted daily disease surveillance and climatic monitoring over an 8-year period between January 1, 2003, and December 31, 2010, in Niamey, Niger, to determine risk factors for bacterial meningitis and invasive bacterial disease. We investigated the mechanistic effects of these factors on Streptococcus pneumoniae infection in mice. High temperatures and low visibility (resulting from high concentrations of airborne dust) were identified as significant risk factors for bacterial meningitis. Dust inhalation or exposure to high temperatures promoted progression of stable asymptomatic pneumococcal nasopharyngeal carriage to pneumonia and invasive disease. Dust exposure significantly reduced phagocyte-mediated bacterial killing, and exposure to high temperatures increased release of the key pneumococcal toxin pneumolysin through increased bacterial autolysis. Our findings show that climatic factors can have a substantial influence on infectious disease patterns, altering density of pneumococcal nasopharyngeal carriage, reducing phagocytic killing, and resulting in increased inflammation and tissue damage and consequent invasiveness. Climatic surveillance should be used to forecast invasive bacterial disease epidemics, and simple control measures to reduce particulate inhalation might reduce the incidence of invasive bacterial disease in regions of the world exposed to high temperatures and increased airborne dust. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Orrskog, Sofia; Rounioja, Samuli; Spadafina, Tiziana; Gallotta, Marilena; Norman, Martin; Hentrich, Karina; Fälker, Stefan; Ygberg-Eriksson, Sofia; Hasenberg, Mike; Johansson, Björn; Uotila, Liisa M.; Gahmberg, Carl G.; Barocchi, Michèle; Gunzer, Matthias; Normark, Staffan; Henriques-Normark, Birgitta
ABSTRACT Pneumococcal pili have been shown to influence pneumococcal colonization, disease development, and the inflammatory response in mice. The role of the pilus-associated RrgA adhesin in pneumococcal interactions with murine and human macrophages was investigated. Expression of pili with RrgA enhanced the uptake of pneumococci by murine and human macrophages that was abolished by antibodies to complement receptor 3 (CR3) and not seen in CR3-deficient macrophages. Recombinant RrgA, but not pilus subunit RrgC, promoted CR3-mediated phagocytosis of coated beads by murine and human macrophages. Flow cytometry showed that purified CR3 binds pneumococcal cells expressing RrgA, and purified RrgA was shown to interact with CR3 and its I domain. In vivo, RrgA facilitated spread of pneumococci from the upper airways and peritoneal cavity to the bloodstream. Earlier onset of septicemia and more rapidly progressing disease was observed in wild-type mice compared to CR3-deficient mice challenged intranasally or intraperitoneally with pneumococci. Motility assays and time-lapse video microscopy showed that pneumococcal stimulation of macrophage motility required RrgA and CR3. These findings, together with the observed RrgA-dependent increase of intracellular survivors up to 10 h following macrophage infection, suggest that RrgA-CR3-mediated phagocytosis promotes systemic pneumococcal spread from local sites. PMID:23269830
Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik
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
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
Rankine-Mullings, Angela E; Owusu-Ofori, Shirley
Persons with sickle cell disease (SCD) are particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review first published in 2002, and previously updated, most recently in 2014. To assess the effects of antibiotic prophylaxis against pneumococcus in children with SCD in relation to:1. incidence of infection;2. mortality;3. drug-related adverse events (as reported in the included studies) to the individual and the community;4. the impact of discontinuing at various ages on incidence of infection and mortality. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform. Additionally, we carried out handsearching of relevant journals and abstract books of conference proceedings.Date of the most recent search: 19 December 2016. All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug. Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the quality of the evidence. Five trials were identified by the searches, of which three trials (880 children randomised) met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with SCD (SS or Sβ0Thal) receiving prophylactic penicillin
Munson, Samantha; Raluy-Callado, Mireia; Lambrelli, Dimitra; Wasiak, Radek; Eriksson, Daniel; Gray, Sharon
This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾ 60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0-1 and ⩾ 60 years. © 2015 the Nordic Societies of Public Health.
MacLennan, Calman A; Martin, Laura B; Micoli, Francesca
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
Smith, Kenneth J.; Raymund, Mahlon; Nowalk, Mary Patricia; Roberts, Mark S.; Zimmerman, Richard K.
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
Tsaban, Gal; Ben-Shimol, Shalom
Pneumococcal diseases are major causes of morbidity among adults, especially those over 50years of age. While pneumococcal conjugated vaccines (PCV's) impact on pneumococcal disease rates among children is well established, the extent of its impact on adult pneumococcal related illness remains unclear. The aim of this systematic literature review was to describe the impact of PCV introduction to childhood national immunization programs worldwide on PCV-naive adult population. A systematic literature search was performed using the PubMed database. The search was limited to articles written in English and published between January 2000 and February 2016. Studies evaluating pneumococcal disease rates in individuals over 5years of age were included. Independent extraction of articles was performed by the two authors. Search terms included: Pneumococcal conjugated vaccine, herd, indirect, adults, and pneumonia. Forty-nine articles meeting the selection criteria were identified, 39 regarding invasive pneumococcal disease (IPD, one on meningitis only), 8 regarding pneumonia, and 2 on both IPD and pneumonia. The majority of reports were from the US, UK and Canada. Considerable variability in the data sources, quality and completeness was observed. While most studies reported either statistically significant reduction or insignificant changes in IPD and pneumonia disease rates in adults following PCV nationwide implementation, few studies reported statistically significant increase in pneumococcal disease rates, these were mainly from countries with low PCV coverage rates and/or inadequate surveillance. Invasive pneumococcal diseases and pneumonia rates among the adult population decreased in most countries following PCV introduction into the NIP. This indirect effect on older population seems to be dependent on PCV coverage rates and time from PCV nationwide implementation. Adults >65years old seem to benefit the most from PCV introduction. Copyright © 2017 Elsevier Ltd
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.
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
Carnalla-Barajas, María Noemí; Soto-Noguerón, Araceli; Sánchez-Alemán, Miguel Angel; Solórzano-Santos, Fortino; Velazquez-Meza, María Elena; Echániz-Aviles, Gabriela
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.
Rozenbaum, Mark H; van Hoek, Albert Jan; Fleming, Douglas; Trotter, Caroline L; Miller, Elizabeth; Edmunds, W John
To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. Economic evaluation using a cohort model from the perspective of healthcare providers. England. People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes. Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios. Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions--that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme--the incremental cost effectiveness ratio was estimated to be more than £30,000 (€37,216; $48,210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates. Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups.
van Hoek, Albert Jan; Fleming, Douglas; Trotter, Caroline L; Miller, Elizabeth; Edmunds, W John
Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. Design Economic evaluation using a cohort model from the perspective of healthcare providers. Setting England. Participants People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes. Main outcome measures Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios. Results Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions—that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme—the incremental cost effectiveness ratio was estimated to be more than £30 000 (€37 216; $48 210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates. Conclusion Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non
Barthelemy, A; Ivanov, S; Fontaine, J; Soulard, D; Bouabe, H; Paget, C; Faveeuw, C; Trottein, F
During influenza A virus (IAV) infection, changes in the lung's physical and immunological defenses predispose the host to bacterial superinfections. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that have beneficial or harmful functions during infection. We investigated the iNKT cells' role in a model of invasive pneumococcal superinfection. The use of Jα18 -/- mice indicated that iNKT cells limited susceptibility to influenza-pneumococcal infection and reduced the lethal synergism. This role did not depend on immune-based anti-bacterial mechanisms. At the time of bacterial exposure, iNKT cells from IAV-experienced mice failed to produce antipneumococcal interferon-γ and adoptive transfer of fresh iNKT cells before Streptococcus pneumoniae challenge did not restore anti-bacterial host defenses. Impaired iNKT cell activation in superinfected animals was related to the IAV-induced immunosuppressive cytokine interleukin-10 (IL-10), rather than to an intrinsic functional defect. IL-10 dampened the activation of iNKT cells in response to pneumococci by inhibiting the production of IL-12 by pulmonary monocyte-derived dendritic cells. Neutralization of IL-10 restored iNKT cell activation and tends to increase resistance to secondary bacterial infection. Overall, iNKT cells have a beneficial role (upstream of bacterial colonization) in controlling influenza-pneumococcal superinfection, although they represent novel targets of immunosuppression at the time of bacterial challenge.
Troldborg, Anne; Deleuran, Bent; Storgaard, Merete
Autosplenectomy is a rare phenomenon in patients with systemic lupus erythematosus (SLE). We present a case of pneumococcal septicaemia in an SLE patient. A CT-scan of the abdomen showed complete autosplenectomy, but a CT scan from years prior showed a normal size spleen. SLE patients have an increased risk of invasive pneumococcal disease and asplenia increases this risk. In Denmark there are no guidelines for vaccination of SLE patients. On the basis of this case report and the guidelines from European League Against Rheumatism we propose that the 23-polyvalent pneumococcal vaccine should be part of the standard regime in the management of SLE.
Pavia, Maria; Bianco, Aida; Nobile, Carmelo G A; Marinelli, Paolo; Angelillo, Italo F
Pneumococcal conjugate bacterial vaccines that are able to prevent invasive disease and mucosal infections have been developed. A meta-analysis of published data from trials on pneumococcal conjugate vaccine was performed to determine the efficacy in reducing the incidence of invasive disease caused by Streptococcus pneumoniae, pneumonia, and acute otitis media in healthy infants younger than 24 months. A systematic search of the literature was conducted. Controlled clinical trials had to compare the protective efficacy of the pneumococcal conjugate vaccine in reducing the incidence of invasive disease caused by S pneumoniae, pneumonia, and acute otitis media in healthy infants with placebo or control vaccines. Information was extracted by using a standardized protocol. The efficacy of pneumococcal conjugate vaccine in the reduction of invasive pneumococcal disease was 89% involving vaccine serotypes in both the intention-to-treat and per-protocol analyses and ranged from 63% to 74% for all serotypes. The efficacy to prevent acute otitis media sustained by vaccine serotypes was 55% in the intention-to-treat and 57% in the per-protocol analyses, whereas it was 29% to prevent otitis involving all serotypes in the per-protocol analysis. Finally, in the intention-to-treat and per-protocol analyses, the efficacy to prevent clinical pneumonia was 6% and 7%, respectively, whereas for the prevention of radiograph-confirmed pneumonia it was 29% and 32%, respectively. The pneumococcal conjugate vaccine produces a significant effect regarding prevention of invasive pneumococcal disease. Results on prevention of otitis or pneumonia have been less striking, but considering the high burden of these diseases in infants, even a low efficacy has potential for tremendous impact on the health of infants in developing and industrialized countries.
Memish, Ziad A; Goubeaud, Anette; Bröker, Michael; Malerczyk, Claudius; Shibl, Atef M
The epidemiology of invasive meningococcal disease varies geographically and in time and the risk of acquiring the disease varies regionally, as well as with living conditions and behavior. An area, in which meningococcal disease outbreaks have frequently occurred, is the "African meningitis belt", where epidemics of meningococcal disease with a peak incidence as high as 100-800/100,000 population/year have been reported. Another risk factor is mass gatherings including the Islamic pilgrimage to Makkah (Mecca), where outbreaks of meningococcal disease have repeatedly occurred. The latest outbreaks occurred during the Hajj pilgrimages of 2000 and 2001, when a shift from serogroup A disease to serogroup W135 occurred. Vaccination against serogroups A, C, W-135 and Y with novel conjugate vaccines may help protect individuals and reduce the spread of bacterial carriage and disease. Individuals who should be vaccinated include travelers to epidemic or hyperendemic areas (as identified by international health authorities), travelers for Umra or Hajj (Hajj pilgrims), travelers to high risk countries or regions (African meningitis belt) during the dry season or countries in sub-Saharan Africa outside the meningitis belt (where outbreak of meningitis has been reported in the preceding 2-3 years), military recruits or deployed military personnel, immunocompromized travelers and high school and college students. This review presents the global epidemiology of meningococcal disease, and discusses prophylaxis options including meningococcal ACWY vaccines. Copyright © 2010. Published by Elsevier Ltd.
Reinert, Philippe; Benkerrou, Malika; de Montalembert, Mariane; Lesprit, Emmanuelle; Abadie, Isabelle; Bernaudin, Françoise; Doit, Catherine; Bingen, Edouard; Tetelboum, Robert; Bonnet, Eric
To evaluate safety and immunogenicity of the pneumococcal 7-valent conjugate vaccine (PCV7) when administered to infants with sickle cell disease (SCD) at 2, 3, and 4 months of age with a booster dose of a 23-valent pneumococcal polysaccharide vaccine (PS-23) at 15 to 18 months of age. This open-label multicenter study in France enrolled 2-month-old infants with SCD. Blood samples for the determination of antibody concentrations to vaccine serotypes were obtained immediately before and 1 month after the primary immunization, and before and 1 month after the PS-23 booster. Local and systemic reactions were recorded on diary cards. Of the 51 infants enrolled, 49 received primary immunization and 46 received the booster dose. After primary immunization > or =95% of the subjects had antibody titers > or =0.35 microg/mL for the 7 serotypes. After boosting, geometric mean concentrations were high for all serotypes, ranging from 6.32 microg/mL (serotype 18C) to 29.49 microg/mL (serotype 4). Except for 1 case after administration of the booster dose, all fevers reported were less than 39 degrees C. No vaccine-related serious adverse events were reported. PCV7 administered at 2, 3, and 4 months of age in infants with SCD was well-tolerated, highly immunogenic, and primed for immune memory as indicated by the dramatic response to the PS-23 dose administered at 15-18 months in this study. However, the current recommended schedule is to boost with the PCV7 at 12-15 months of age and for these high-risk children, to enlarge the protection with a subsequent PS-23 dose at 2 years of age.
Davalos, Long; Terrazas, Yessica; Quintana, Ana; Egoavil, Martha; Sedano, Katherine; Castillo, María E; Reyes, Isabel; Chaparro, Eduardo; Silva, Wilda; Campos, Francisco; Saenz, Andrés; Hernandez, Roger; Águila, Olguita Del; Pinto, Daniel Guillén; Ochoa, Theresa J
To describe the clinical characteristics, lethality, antibiotic susceptibility, and serotype distribution of pneumococcal meningitis in pediatric patients in Lima, Peru. A case series of pneumococcal meningitis in children less than 16 years of age from two prospective, multicenter, passive surveillance studies of invasive pneumococcal diseases held in Lima-Peru from 2006 to 2008 and 2009 to 2011. We report 44 pneumococcal meningitis episodes; 68.2% of them were in children less than 2 years old. The overall case fatality rate was 32.6%; 92.9% of fatal cases were in children less than 2 years of age (p<0.05). Malnutrition was associated with fatal cases (p<0.05). 64.3% of fatal cases died within the first two days. 41.9% of pneumococcal isolates were resistant to penicillin, 23.3% were intermediate resistant to ceftriaxone (none were highly resistant) and 9.3% were resistant to chloramphenicol. The most common serotypes were 6B, 14, 19F and 23F, which accounted for 68.3% of all strains; 84.1% of strains were PCV13 serotypes. Pneumococcal meningitis continues to be a lethal disease, especially in children less than 2 years of age. Since almost two third of lethal cases lead to death within the first 48 hours, prompt diagnosis and management is critical, as well as assurance of immunization with pneumococcal vaccine.
Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive
Kerem, E; Bar Ziv, Y; Rudenski, B; Katz, S; Kleid, D; Branski, D
Necrotizing pneumonia, massive necrosis of lung tissue, is a serious, often fatal, complication of lobar pneumonia. Four children 1.3 to 7.5 yr of age were hospitalized with bacteremic pneumococcal pneumonia. All of them were acutely ill on presentation with arterial desaturation, and they developed anemia and thrombocytosis. Two patients had pleural effusion requiring drainage. A chest CT scan revealed segmental or lobar pulmonary liquification, which led to the diagnosis of necrotizing pneumonia. This finding could be demonstrated early in the course of the disease. Subsequently, all of the patients developed cavitating lesions. With adequate antipneumococcal therapy and/or chest tube drainage, all of the patients recovered completely; however, clinical improvement was prolonged: fever lasted 9 to 20 days, and length of hospitalization was 12 to 26 days. Contrary to that in adults, complete recovery is anticipated in children with bacteremic necrotizing pneumococcal pneumonia, and no invasive investigations are required.
Carreño-Ibáñez, L V; Esteban-Vasallo, M D; Domínguez-Berjón, M F; Astray-Mochales, J; González Del Yerro, C; Iniesta-Fornies, D; Gascón-Sancho, M J; Jiménez-García, R
Patients aged ⩾ 40 years with a diagnosis of chronic obstructive pulmonary disease (COPD; codes R95, R79 and R91 in the International Classification for Primary Care) registered in primary care clinical records in the Autonomous Community of Madrid, Spain. To assess pneumococcal vaccination coverage in patients with COPD and to analyse factors associated with vaccination uptake. Population-based cross-sectional study in which data were collected in September 2010. We found that 93,797 patients (72.0% men and 28.0% women) had COPD. Overall coverage was 65.5% (67.5% men vs. 60.4% women, P < 0.001). In patients aged 40-59 years, coverage was 19.5%, reaching 75.8% in those aged ⩾ 60 years. In patients aged <60 years, uptake was associated with a higher number of comorbidities and appropriate adherence to seasonal influenza and pandemic vaccination schedules. In patients aged ⩾ 60 years, factors associated with uptake in both sexes were older age and appropriate adherence to seasonal influenza vaccination schedules. Factors associated with uptake in men were concomitant comorbidities and pandemic vaccination. Vaccination coverage in individuals aged <60 years with COPD is less than acceptable in Madrid. Coverage was higher in men and in patients with another chronic condition.
Porat, Nurith; Benisty, Rachel; Givon-Lavi, Noga; Trefler, Ronit; Dagan, Ron
The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) followed by PCV13 resulted in a dramatic reduction in carriage and disease rates of Streptococcus pneumoniae (Sp) serotype 6B (Sp6B) and Sp6A. The structural modifications of the capsule of Sp6A and Sp6B to become Sp6C and Sp6D, respectively, raised a concern that eradication of Sp6A/Sp6B by PCV could be accompanied by an increase in Sp6C/Sp6D. This study examines the dynamics and clonal distribution of Sp6C/Sp6D relative to Sp6A/Sp6B during 1999-2014, pre- and post-PCV implementation. Sp were cultured from Blood/CSF and MEF of children <2 years, and from conjunctiva and nasopharynx of children <5 years. PCR was applied for Sp6C and Sp6D identification. Clonality was determined by PFGE and MLST. PCV introduction resulted in decreased carriage rates and conjunctivitis caused by serogroup 6 serotypes. Incidence of Sp6A, Sp6B and Sp6D in otitis media dropped gradually along with PCV7/13 introduction, whereas Sp6C rates increased in the PCV7 period and then decreased following PCV13 implementation. In invasive pneumococcal disease, complete elimination of serogroup 6 was found in the PCV era. Similar clonal composition was found for Sp6C and Sp6D pre- and post-PCV. We conclude that Sp6C and Sp6D do not act as replacement serotypes for Sp6A and Sp6B following vaccination with PCV13. The major Sp6C and Sp6D clones present pre-PCV persisted also post-PCV implementation, suggesting that these clones possess an advantage retained post-vaccination. Copyright © 2016. Published by Elsevier Ltd.
Gertz, Robert E.; McEllistrem, M. Catherine; Boxrud, David J.; Li, Zhongya; Sakota, Varja; Thompson, Terry A.; Facklam, Richard R.; Besser, John M.; Harrison, Lee H.; Whitney, Cynthia G.; Beall, Bernard
Theseven-valent pneumococcal conjugated polysaccharide vaccine PC7V was licensed for use among children in 2000. Since 90 serotypes of pneumococci exist, an increase in nonvaccine serotypes could occur through immune selection for capsular type switching. Eleven hundred sixty-eight invasive isolates (24 serotypes), recovered primarily from pediatric patients (855 isolates = 73%) and 22 reference strains of known multilocus sequence types (STs) were subjected to macrorestriction profiling (pulsed-field gel electrophoresis [PFGE]). The correlation of 187 ST results (including 49 newly discovered STs) with the PFGE data assigned 1,042 (89.2%) study isolates to 46 defined clonal complexes or genetic lineages based on related multilocus STs (BURST). Seventeen clonal complexes were represented by 2 to 10 related allelic profiles (STs), while 33 lineages (including reference strains) consisted of single STs with 4 or fewer allelic identities to other STs found in the study. Expansion of the BURST analysis to a global analysis of all known pneumococcal STs (as of 27 November 2002) reduced the number of single ST lineages from 33 to 8, and the number of multi-ST clonal complexes was reduced from 17 to 13. In this work, we established the basic genetic structure within individual serotypes prior to PC7V use. The resultant database will be useful for detecting potential selective effects of this vaccine in postvaccine surveillance. PMID:12958247
13-valent pneumococcal conjugate vaccine (PCV13) is immunogenic and safe in children 6-17 years of age with sickle cell disease previously vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23): Results of a phase 3 study.
De Montalembert, Mariane; Abboud, Miguel R; Fiquet, Anne; Inati, Adlette; Lebensburger, Jeffrey D; Kaddah, Normeen; Mokhtar, Galila; Piga, Antonio; Halasa, Natasha; Inusa, Baba; Rees, David C; Heath, Paul T; Telfer, Paul; Driscoll, Catherine; Al Hajjar, Sami; Tozzi, Alberto; Jiang, Qin; Emini, Emilio A; Gruber, William C; Gurtman, Alejandra; Scott, Daniel A
A large population of older children with sickle cell disease (SCD) is currently vaccinated with only 23-valent pneumococcal polysaccharide vaccine (PPSV23). In immunocompetent adults, PPSV23 vaccination reduces immune responses to subsequent vaccination with a pneumococcal vaccine. The 13-valent pneumococcal conjugate vaccine (PCV13), which addresses this limitation, may offer an advantage to this population at high risk of pneumococcal disease. Children with SCD 6-17 years of age previously vaccinated with PPSV23 at least 6 months before study enrollment received two doses of PCV13 6 months apart. Anti-pneumococcal polysaccharide immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured before, 1 month after each administration, and 1 year after the second administration. Following each PCV13 administration, IgG GMCs and OPA GMTs significantly increased, and antibody levels after doses 1 and 2 were generally comparable. Antibody levels declined over the year following dose 2. At 1 year after the second administration, OPA GMTs for all and IgG GMCs for most serotypes remained above pre-vaccination levels. Most adverse events were due to vaso-occlusive crises, a characteristic of the underlying condition of SCD. Children with SCD who were previously vaccinated with PPSV23 responded well to 1 PCV13 dose, and a second dose did not increase antibody response. PCV13 antibodies persisted above pre-vaccination levels for all serotypes 1 year after dose 2. Children with SCD may benefit from at least one dose of PCV13. © 2015 Wiley Periodicals, Inc.
Iwanaga, Naoki; Nakamura, Shigeki; Oshima, Kazuhiro; Kajihara, Toshiki; Takazono, Takahiro; Miyazaki, Taiga; Izumikawa, Koichi; Yanagihara, Katsunori; Sugawara, Akihiro; Sunazuka, Toshiaki; Omura, Satoshi; Kohno, Shigeru
Streptococcus pneumoniae (pneumococcus) colonizes mucosal surfaces of the upper respiratory tract (URT), resulting in invasive disease. Macrolides are known for their immunomodulatory effects. We investigated the potency of macrolides to reduce pneumococcal colonization by activating host innate immunity. The kinetics of colonization, cellular response, and inflammatory cytokine levels in the URT were assessed after nasal inoculation of pneumococci. EM900 (a novel 12-membered nonantibiotic macrolide with an immunomodulatory effect) was orally administered throughout the experiment. Survival was evaluated for 10 days. Macrolide-mediated CCL2 production from peritoneal macrophages was determined by enzyme-linked immuosorbent assay. The cell-signaling pathway was analyzed by means of Western blotting and gene silencing assays. Streptococcus pneumoniae was significantly reduced from EM900-treated mice 14 days after pneumococcal inoculation. Macrophage recruitment and Ccl2 messenger RNA expression were promoted. CCL2 production from peritoneal macrophages was significantly induced by macrolides and was dependent on NF-κB phosphorylation through the myeloid differentiation primary-response gene 88- or TIR domain-containing adapter-inducing interferon-β-mediated pathway. Mortality of mice with invasive pneumococcal disease was improved by pretreatment with EM900. Macrolides may inhibit invasive pneumococcal infections by accelerating the clearance of pneumococcal nasopharyngeal colonization via promotion of macrophage-mediated innate immunity. © 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: email@example.com.
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
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.
[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].
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
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
Nurhonen, Markku; Auranen, Kari
Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children <5 years of age by 75%. However, due to replacement through herd effects, the decrease among the older population is predicted to be much less (20–40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the
Cohen, Robert; Biscardi, Sandra; Levy, Corinne
ABSTRACT In 2003, France was the first European country to recommend 7-valent pneumococcal conjugate vaccine (PCV7) for a large proportion of healthy children. With complicated recommendations, the vaccine coverage during the first 4 y of implementation was low, then progressively increased to reach 90% in 2008. The aim of this review was to describe the particular impact of PCVs in a country where the vaccine coverage was initially suboptimal. After PCV7 implementation, the PCV7 serotypes nearly disappeared among pneumococci isolated from meningitis (−73%), other invasive pneumococcal disease (IPD; −90%) and pneumococcal carriage (−97%). Consequently, the rates of penicillin-resistant strains declined. However, because of important serotype replacement, the global effect on the incidence of meningitis (−31%) or other IPD (−14%) was modest and observed only in young children < 2 y old. After PCV13 transition, with immediate high vaccine coverage, the vaccine had an important impact on all pneumococcal disease: reduction of −20% for pneumococcal meningitis, −36% for non-meningitis IPD, −32% for community acquired pneumonia and −15% for S. pneumoniae carriage. These findings underline the complexity of pneumococcal epidemiology and the importance of high and fast vaccination coverage to obtain the optimal effect of PCVs. PMID:26905678
Loubet, Paul; Verger, Pierre; Abitbol, Vered; Peyrin-Biroulet, Laurent; Launay, Odile
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.
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.
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
Ferreira, Daniela M.; Gordon, Stephen B.; Rylance, Jamie
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
Setchanova, Lena Petrova; Alexandrova, Alexandra; Dacheva, Daniela; Mitov, Ivan; Kaneva, Radka; Mitev, Vanio
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.
Prato, Rosa; Fortunato, Francesca; Martinelli, Domenico
The indirect protection of adults as a result of pneumococcal conjugate vaccination of infants has been discussed from different epidemiological points of view. In some countries, including Italy, even after pediatric vaccination, vaccine serotypes are still responsible for most pneumonia and invasive diseases in the elderly. Although the Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) produced encouraging results, it has not showed the efficacy of the 13-valent conjugate vaccine in preventing pneumococcal community-acquired pneumonia regardless of the number of episodes and serotype. Addressing these points by monitoring the direct impact of adult vaccination in real life distinguished from the effects of herd immunity will assist public health decision-making on the most effective adult pneumococcal vaccination strategies.
Holder-Murray, Jennifer; Marsicovetere, Priscilla
Abstract: Surgical management of inflammatory bowel disease is a challenging endeavor given infectious and inflammatory complications, such as fistula, and abscess, complex often postoperative anatomy, including adhesive disease from previous open operations. Patients with Crohn's disease and ulcerative colitis also bring to the table the burden of their chronic illness with anemia, malnutrition, and immunosuppression, all common and contributing independently as risk factors for increased surgical morbidity in this high-risk population. However, to reduce the physical trauma of surgery, technologic advances and worldwide experience with minimally invasive surgery have allowed laparoscopic management of patients to become standard of care, with significant short- and long-term patient benefits compared with the open approach. In this review, we will describe the current state-of the-art for minimally invasive surgery for inflammatory bowel disease and the caveats inherent with this practice in this complex patient population. Also, we will review the applicability of current and future trends in minimally invasive surgical technique, such as laparoscopic “incisionless,” single-incision laparoscopic surgery (SILS), robotic-assisted, and other techniques for the patient with inflammatory bowel disease. There can be no doubt that minimally invasive surgery has been proven to decrease the short- and long-term burden of surgery of these chronic illnesses and represents high-value care for both patient and society. PMID:25989341
Kang, Li-Hua; Liu, Meng-Juan; Xu, Wen-Chun; Cui, Jing-Jing; Zhang, Xue-Mei; Wu, Kai-Feng; Zhang, Qun
Objectives: To investigate the molecular epidemiology of pneumococcal isolates in Chongqing, China. Methods: In this cross-sectional study, 51 invasive Streptococcus pneumoniae (S. pneumoniae) strains were from children with invasive pneumococcal disease (IPD) and 32 carriage strains from healthy children from January 2010 to December 2013 at the Children’s Hospital of Chongqing Medical University, Chongqing, China. Multilocus sequence typing was used to identify the sequence types (STs). Capsular serotypes were determined by multiplex polymerase chain reaction. Drug susceptibility and resistance was determined by minimum inhibitory concentrations. Results: In this study, 11 serotypes were identified among the 83 S. pneumoniae clinical isolates tested. Prevalent serotypes were 19A (20.4%), 6A/B (20.4%), 19F (15.7%), 14 (14.5%), and 23F (10.8%). Serotype 19F was the most frequent carriage strain, and serotype 19A was the most frequent invasive strain. The ST983 was the most prevalent ST for carriage strains, and ST320 was the most prevalent ST for invasive strains. For gene analysis, psaA (99.5%) and piaA (98.6%) were present and much conserved in all pneumococci tested. The cps2A and pcsB genes were more frequent in invasive isolates than carriage strains. Antimicrobial resistance rates of invasive pneumococcal isolates to erythromycin, penicillin, meropenem, cefotaxime, and clindamycin were higher than the carriage isolates from children. Conclusion: Our epidemiological evidence shows that 19A, 6A/B, 19F, 14, and 23F remain the most prevalent serotypes, which can be targeted by PCV13. Genotypes and drug resistance varied between carriage and invasive strains. The PsaA and PiaA may be good protein vaccine candidates. PMID:27052283
Kang, Li-Hua; Liu, Meng-Juan; Xu, Wen-Chun; Cui, Jing-Jing; Zhang, Xue-Mei; Wu, Kai-Feng; Zhang, Qun
To investigate the molecular epidemiology of pneumococcal isolates in Chongqing, China. In this cross-sectional study, 51 invasive Streptococcus pneumoniae (S. pneumoniae) strains were from children with invasive pneumococcal disease (IPD) and 32 carriage strains from healthy children from January 2010 to December 2013 at the Children's Hospital of Chongqing Medical University, Chongqing, China. Multilocus sequence typing was used to identify the sequence types (STs). Capsular serotypes were determined by multiplex polymerase chain reaction. Drug susceptibility and resistance was determined by minimum inhibitory concentrations. In this study, 11 serotypes were identified among the 83 S. pneumoniae clinical isolates tested. Prevalent serotypes were 19A (20.4%), 6A/B (20.4%), 19F (15.7%), 14 (14.5%), and 23F (10.8%). Serotype 19F was the most frequent carriage strain, and serotype 19A was the most frequent invasive strain. The ST983 was the most prevalent ST for carriage strains, and ST320 was the most prevalent ST for invasive strains. For gene analysis, psaA (99.5%) and piaA (98.6%) were present and much conserved in all pneumococci tested. The cps2A and pcsB genes were more frequent in invasive isolates than carriage strains. Antimicrobial resistance rates of invasive pneumococcal isolates to erythromycin, penicillin, meropenem, cefotaxime, and clindamycin were higher than the carriage isolates from children. Our epidemiological evidence shows that 19A, 6A/B, 19F, 14, and 23F remain the most prevalent serotypes, which can be targeted by PCV13. Genotypes and drug resistance varied between carriage and invasive strains. The PsaA and PiaA may be good protein vaccine candidates.
... 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 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 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...
... 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 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...
Donald A. Duerr; Paul A. Mistretta
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.âNewâ nonnative invasive insects and diseases will have serious impacts on southern forests over the next 50 years. Some species such as emerald ash borer...
Feldman, Charles; Anderson, Ronald
Streptococcus pneumoniae is the major bacterial cause of pneumonia, meningitis and otitis media, and continues to be associated with significant morbidity and mortality in individuals both in the developed and developing world. Management of these infections is potentially complicated by the emergence of resistance of this pathogen to many of the commonly used first-line antimicrobial agents. A number of significant risk factors exist that predispose to the occurrence of pneumococcal pneumonia, including lifestyle factors, such as exposure to cigarette smoke, as well as underlying medical conditions, such as HIV infection. Several of these predisposing factors also enhance the risk of bacteraemia. The initial step in the pathogenesis of pneumococcal infections is the occurrence of nasopharyngeal colonization, which may be followed by invasive disease. The pneumococcus has a myriad of virulence factors that contribute to these processes, including a polysaccharide capsule, various cell surface structures, toxins and adhesins, and the microorganism is also an effective producer of biofilm. Antibacterial resistance is emerging in this microorganism and affects all the various classes of drugs, including the β-lactams, the macrolides and the fluoroquinolones. Even multidrug resistance is occurring. Pharmacokinetic/pharmacodynamic parameters allow us to understand the relationship between the presence of antibacterial resistance in the pneumococcus and the outcome of pneumococcal infections treated with the different antibacterial classes. Furthermore, these parameters also allow us to predict which antibacterials are most likely to be effective in the management of pneumococcal infections and the correct dosages to use. Most guidelines for the management of community-acquired pneumonia recommend the use of either a β-lactam/macrolide combination or fluoroquinolone monotherapy for the empirical therapy of more severe hospitalized cases with pneumonia, including the
Jiang, Yiling; Gauthier, Aline; Annemans, Lieven; van der Linden, Mark; Nicolas-Spony, Laurence; Bresse, Xavier
The introduction of routine infant vaccination against pneumococcal disease has resulted in a decreased overall invasive pneumococcal disease incidence in adults but also a change in invasive pneumococcal disease serotypes. This study aimed to assess the cost-effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany in this context. A population-based Markov model was developed. A cohort of adults currently eligible for vaccination was followed until death. Adult vaccination with PPV23 was associated with an incremental cost-effectiveness ratio of €17,065/quality-adjusted life years gained from the third-party payer's perspective. Univariate sensitivity analyses showed that the incremental cost-effectiveness ratio was below €50,000/quality-adjusted life years gained in most test scenarios. The model suggests that adult PPV23 vaccination is cost effective in Germany, due to its broad serotype coverage. This is despite epidemiological changes in Streptococcus pneumoniae serotypes caused by wider use of pneumococcal conjugate vaccines during childhood.
Lee, Chien-Chang; Middaugh, Nicole A.; Howie, Stephen R. C.; Ezzati, Majid
Background A number of epidemiologic studies have observed an association between secondhand smoke (SHS) exposure and pediatric invasive bacterial disease (IBD) but the evidence has not been systematically reviewed. We carried out a systematic review and meta-analysis of SHS exposure and two outcomes, IBD and pharyngeal carriage of bacteria, for Neisseria meningitidis (N. meningitidis), Haemophilus influenzae type B (Hib), and Streptococcus pneumoniae (S. pneumoniae). Methods and Findings Two independent reviewers searched Medline, EMBASE, and selected other databases, and screened articles for inclusion and exclusion criteria. We identified 30 case-control studies on SHS and IBD, and 12 cross-sectional studies on SHS and bacterial carriage. Weighted summary odd ratios (ORs) were calculated for each outcome and for studies with specific design and quality characteristics. Tests for heterogeneity and publication bias were performed. Compared with those unexposed to SHS, summary OR for SHS exposure was 2.02 (95% confidence interval [CI] 1.52–2.69) for invasive meningococcal disease, 1.21 (95% CI 0.69–2.14) for invasive pneumococcal disease, and 1.22 (95% CI 0.93–1.62) for invasive Hib disease. For pharyngeal carriage, summary OR was 1.68 (95% CI, 1.19–2.36) for N. meningitidis, 1.66 (95% CI 1.33–2.07) for S. pneumoniae, and 0.96 (95% CI 0.48–1.95) for Hib. The association between SHS exposure and invasive meningococcal and Hib diseases was consistent regardless of outcome definitions, age groups, study designs, and publication year. The effect estimates were larger in studies among children younger than 6 years of age for all three IBDs, and in studies with the more rigorous laboratory-confirmed diagnosis for invasive meningococcal disease (summary OR 3.24; 95% CI 1.72–6.13). Conclusions When considered together with evidence from direct smoking and biological mechanisms, our systematic review and meta-analysis indicates that SHS exposure may be
Lee, Chien-Chang; Middaugh, Nicole A; Howie, Stephen R C; Ezzati, Majid
A number of epidemiologic studies have observed an association between secondhand smoke (SHS) exposure and pediatric invasive bacterial disease (IBD) but the evidence has not been systematically reviewed. We carried out a systematic review and meta-analysis of SHS exposure and two outcomes, IBD and pharyngeal carriage of bacteria, for Neisseria meningitidis (N. meningitidis), Haemophilus influenzae type B (Hib), and Streptococcus pneumoniae (S. pneumoniae). Two independent reviewers searched Medline, EMBASE, and selected other databases, and screened articles for inclusion and exclusion criteria. We identified 30 case-control studies on SHS and IBD, and 12 cross-sectional studies on SHS and bacterial carriage. Weighted summary odd ratios (ORs) were calculated for each outcome and for studies with specific design and quality characteristics. Tests for heterogeneity and publication bias were performed. Compared with those unexposed to SHS, summary OR for SHS exposure was 2.02 (95% confidence interval [CI] 1.52-2.69) for invasive meningococcal disease, 1.21 (95% CI 0.69-2.14) for invasive pneumococcal disease, and 1.22 (95% CI 0.93-1.62) for invasive Hib disease. For pharyngeal carriage, summary OR was 1.68 (95% CI, 1.19-2.36) for N. meningitidis, 1.66 (95% CI 1.33-2.07) for S. pneumoniae, and 0.96 (95% CI 0.48-1.95) for Hib. The association between SHS exposure and invasive meningococcal and Hib diseases was consistent regardless of outcome definitions, age groups, study designs, and publication year. The effect estimates were larger in studies among children younger than 6 years of age for all three IBDs, and in studies with the more rigorous laboratory-confirmed diagnosis for invasive meningococcal disease (summary OR 3.24; 95% CI 1.72-6.13). When considered together with evidence from direct smoking and biological mechanisms, our systematic review and meta-analysis indicates that SHS exposure may be associated with invasive meningococcal disease. The epidemiologic
Stockmann, Chris; Ampofo, Krow; Pavia, Andrew T; Blaschke, Anne J; Mason, Edward O; Presson, Angela P; Forney, Larry J; Byington, Carrie L
The Red Queen hypothesis is an evolutionary theory that describes the reciprocal coevolution of competing species. We sought to study whether introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) altered pneumococcal serotype dynamics among children with invasive pneumococcal disease (IPD) as predicted by the Red Queen hypothesis. This study examined pneumococcal isolates (n = 641) obtained from children <18 years of age hospitalized with IPD from 1997 to 2014 in Utah. A review of the literature also identified several additional studies conducted in the United States and Europe that were used to test the external generalizability of our Utah findings. Simpson's index was used to quantify pneumococcal serotype diversity. In Utah, the introduction of PCV7 and PCV13 was associated with rapid increases in serotype diversity (P < .001). Serotypes rarely present before vaccine introduction emerged as common causes of IPD. Diversity then decreased (P < .001) as competition selected for the fittest serotypes and new evolutionary equilibriums were established. This pattern was also observed more broadly in the United States, the United Kingdom, Norway, and Spain. This vaccine-driven example of human/bacterial coevolution appears to confirm the Red Queen hypothesis, which reveals a limitation of serotype-specific vaccines and offers insights that may facilitate alternative strategies for the elimination of IPD. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail firstname.lastname@example.org.
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
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
Marks, Laura R.; Parameswaran, G. Iyer
The human nasopharynx is the main reservoir for Streptococcus pneumoniae (the pneumococcus) and the source for both horizontal spread and transition to infection. Some clinical evidence indicates that nasopharyngeal carriage is harder to eradicate with antibiotics than is pneumococcal invasive disease, which may suggest that colonizing pneumococci exist in biofilm communities that are more resistant to antibiotics. While pneumococcal biofilms have been observed during symptomatic infection, their role in colonization and the role of host factors in this process have been less studied. Here, we show for the first time that pneumococci form highly structured biofilm communities during colonization of the murine nasopharynx that display increased antibiotic resistance. Furthermore, pneumococcal biofilms grown on respiratory epithelial cells exhibited phenotypes similar to those observed during colonization in vivo, whereas abiotic surfaces produced less ordered and more antibiotic-sensitive biofilms. The importance of bacterial-epithelial cell interactions during biofilm formation was shown using both clinical strains with variable colonization efficacies and pneumococcal mutants with impaired colonization characteristics in vivo. In both cases, the ability of strains to form biofilms on epithelial cells directly correlated with their ability to colonize the nasopharynx in vivo, with colonization-deficient strains forming less structured and more antibiotic-sensitive biofilms on epithelial cells, an association that was lost when grown on abiotic surfaces. Thus, these studies emphasize the importance of host-bacterial interactions in pneumococcal biofilm formation and provide the first experimental data to explain the high resistance of pneumococcal colonization to eradication by antibiotics. PMID:22645283
Amos, Ben; Kisakye, Annet; Makewa, Douglas; Mudhune, Sandra; Mwamtemi, Hadija; Nansera, Dennis; Ngwiri, Thomas; Wamae, Maranga; English, Mike
In a region with high rates of mortality among children aged <5 years, the underfunded health care systems of sub-Saharan Africa have few resources available to perform surveillance activities that can help determine the causes of morbidity and mortality in the region. At present, there are few examples of attempts to promote public health care surveillance that might inform current debates about how to expand and improve surveillance, particularly for bacterial diseases. Driven by this gap in knowledge, we attempted to explore the successes and failures of the Network for Surveillance of Pneumococcal Disease in the East African Region and to share the experiences of what are essentially non research public-sector hospitals in East Africa, with the hopes that surveillance systems for other diseases, especially those that require complex diagnostic support, may be informed by these experiences. The state of services essential for surveillance and the measures taken to overcome any shortcomings are described, as is the progress made in improving clinical diagnosis, laboratory processing, and data management. For surveillance to play a role in public health care, ministries of health and associated institutions must own and push forward the surveillance agenda, with support from global partners, and take advantage of the developments that have been achieved within the institutions. PMID:19191612
Kostinov, M P; Zhestkov, A V; Protasov, A D; Magarshak, O O; Kostinova, T A
To estimate the indicators of the therapeutic effect of combination vaccination against pneumococcal, Haemophilus influenzae type b infection, and influenza in patients with chronic obstructive pulmonary disease (COPD). Clinical, bacteriological, and immunological studies, by determining the quality of life (QL), were conducted in COPD patients during a year after combination vaccination against pneumococcal, Haemophilus influenza type b infection, and influenza. One year after the vaccination, there were reductions in the number of COPD exacerbations by 3.7 times, in that of antibiotic therapy cycles by 3.4 times, in the levels of inflammatory mediators of interleukins 2 and 8 and interferon-γ, and in the synthesis of IgG antibodies to Streptococcus pneumoniae, Haemophilus influenzae type b, and influenza virus strains as compared to the baseline values. Combination vaccination against bacterial and viral infections substantially improves the major clinical parameters of COPD, positively affecting LQ indicators that generally characterize the therapeutic effect of immunization.
Jiang, Yiling; Gauthier, Aline; Keeping, Sam; Carroll, Stuart
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.
Castiglia, Paolo; Pradelli, Lorenzo; Castagna, Stefano; Freguglia, Veronica; Palù, Giorgio; Esposito, Susanna
ABSTRACT Pneumococcal diseases are associated with a significant clinical and economic burden. The 7-valent pneumococcal conjugate vaccine (PCV-7) has been used for the immunization of newborns against invasive pneumococcal diseases (IPD) in Italy while now, the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are available. The aim of this analysis was to compare the estimated health benefits, cost and cost-effectiveness of immunization strategies vs. non-vaccination in Italy using the concept of overall vaccine effectiveness. A published Markov model was adapted using local data wherever available to compare the impact of neonatal pneumococcal vaccination on epidemiological and economic burden of invasive and non-invasive pneumococcal diseases, within a cohort of newborns from the Italian National Health Service (NHS) perspective. A 18-year and a 5-year time horizon were considered for the base-case and scenario analysis, respectively. PHiD-CV and PCV-13 are associated with the most important reduction of the clinical burden, with a potential marginal advantage of PHiD-CV over PCV-13. Compared with no vaccination, PHiD-CV is found on the higher limit of the usually indicated willingness to pay range (30,000 - 50,000€/quality-adjusted life year [QALY] gained), while the incremental cost-effectiveness ratio (ICER) for PCV-13 is slightly above. Compared with PCV-13, PHiD-CV would provide better health outcomes and reduce costs even at parity price, solely due to its differential effect on the incidence of NTHi acute otitis media (AOM). The analysis on a shorter time horizon confirms the direction of the base-case. PMID:28700264
Castiglia, Paolo; Pradelli, Lorenzo; Castagna, Stefano; Freguglia, Veronica; Palù, Giorgio; Esposito, Susanna
Pneumococcal diseases are associated with a significant clinical and economic burden. The 7-valent pneumococcal conjugate vaccine (PCV-7) has been used for the immunization of newborns against invasive pneumococcal diseases (IPD) in Italy while now, the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are available. The aim of this analysis was to compare the estimated health benefits, cost and cost-effectiveness of immunization strategies vs. non-vaccination in Italy using the concept of overall vaccine effectiveness. A published Markov model was adapted using local data wherever available to compare the impact of neonatal pneumococcal vaccination on epidemiological and economic burden of invasive and non-invasive pneumococcal diseases, within a cohort of newborns from the Italian National Health Service (NHS) perspective. A 18-year and a 5-year time horizon were considered for the base-case and scenario analysis, respectively. PHiD-CV and PCV-13 are associated with the most important reduction of the clinical burden, with a potential marginal advantage of PHiD-CV over PCV-13. Compared with no vaccination, PHiD-CV is found on the higher limit of the usually indicated willingness to pay range (30,000 - 50,000€/quality-adjusted life year [QALY] gained), while the incremental cost-effectiveness ratio (ICER) for PCV-13 is slightly above. Compared with PCV-13, PHiD-CV would provide better health outcomes and reduce costs even at parity price, solely due to its differential effect on the incidence of NTHi acute otitis media (AOM). The analysis on a shorter time horizon confirms the direction of the base-case.
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 ...
French, Neil; Gordon, Stephen B; Mwalukomo, Thandie; White, Sarah A; Mwafulirwa, Gershom; Longwe, Herbert; Mwaiponya, Martin; Zijlstra, Eduard E; Molyneux, Malcolm E; Gilks, Charles F
Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed. In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A. From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P = 0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P = 0.003). The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731.).
Marks, Laura R.; Kong, Yong; Gent, Janneane F.; Roche-Hakansson, Hazeline
Streptococcus pneumoniae is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms in vitro and in vivo. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the S. pneumoniae transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed S. pneumoniae, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of S. pneumoniae pathogenesis. PMID:25135685
Reddinger, Ryan M.; Luke-Marshall, Nicole R.; Sauberan, Shauna L.
ABSTRACT Streptococcus pneumoniae and Staphylococcus aureus are ubiquitous upper respiratory opportunistic pathogens. Individually, these Gram-positive microbes are two of the most common causative agents of secondary bacterial pneumonia following influenza A virus infection, and they constitute a significant source of morbidity and mortality. Since the introduction of the pneumococcal conjugate vaccine, rates of cocolonization with both of these bacterial species have increased, despite the traditional view that they are antagonistic and mutually exclusive. The interactions between S. pneumoniae and S. aureus in the context of colonization and the transition to invasive disease have not been characterized. In this report, we show that S. pneumoniae and S. aureus form stable dual-species biofilms on epithelial cells in vitro. When these biofilms are exposed to physiological changes associated with viral infection, S. pneumoniae disperses from the biofilm, whereas S. aureus dispersal is inhibited. These findings were supported by results of an in vivo study in which we used a novel mouse cocolonization model. In these experiments, mice cocolonized in the nares with both bacterial species were subsequently infected with influenza A virus. The coinfected mice almost exclusively developed pneumococcal pneumonia. These results indicate that despite our previous report that S. aureus disseminates into the lungs of mice stably colonized with these bacteria following influenza A virus infection, cocolonization with S. pneumoniae in vitro and in vivo inhibits S. aureus dispersal and transition to disease. This study provides novel insight into both the interactions between S. pneumoniae and S. aureus during carriage and the transition from colonization to secondary bacterial pneumonia. PMID:29317512
Haber, Michael; Barskey, Albert; Baughman, Wendy; Barker, Lawrence; Whitney, Cynthia G; Shaw, Kate M; Orenstein, Walter; Stephens, David S
Invasive pneumococcal disease in older children and adults declined markedly after introduction in 2000 of the pneumococcal conjugate vaccine for young children. An empirical quantitative model was developed to estimate the herd (indirect) effects on the incidence of invasive disease among persons >or=5 years of age induced by vaccination of young children with 1, 2, or >or=3 doses of the pneumococcal conjugate vaccine, Prevnar (PCV7), containing serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. From 1994 to 2003, cases of invasive pneumococcal disease were prospectively identified in Georgia Health District-3 (eight metropolitan Atlanta counties) by Active Bacterial Core surveillance (ABCs). From 2000 to 2003, vaccine coverage levels of PCV7 for children aged 19-35 months in Fulton and DeKalb counties (of Atlanta) were estimated from the National Immunization Survey (NIS). Based on incidence data and the estimated average number of doses received by 15 months of age, a Poisson regression model was fit, describing the trend in invasive pneumococcal disease in groups not targeted for vaccination (i.e., adults and older children) before and after the introduction of PCV7. Highly significant declines in all the serotypes contained in PCV7 in all unvaccinated populations (5-19, 20-39, 40-64, and >64 years) from 2000 to 2003 were found under the model. No significant change in incidence was seen from 1994 to 1999, indicating rates were stable prior to vaccine introduction. Among unvaccinated persons 5+ years of age, the modeled incidence of disease caused by PCV7 serotypes as a group dropped 38.4%, 62.0%, and 76.6% for 1, 2, and 3 doses, respectively, received on average by the population of children by the time they are 15 months of age. Incidence of serotypes 14 and 23F had consistent significant declines in all unvaccinated age groups. In contrast, the herd immunity effects on vaccine-related serotype 6A incidence were inconsistent. Increasing trends of non
El Mdaghri, N; Jilali, N; Belabbes, H; Jouhadi, Z; Lahssoune, M; Zaid, S
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.
Discrimination between Legionnaires' Disease and Pneumococcal Pneumonia Based on the Clinical and Laboratory Features: A Quantitative Approach Using the Modified Winthrop-University Hospital Weighted Point System.
Yamakuchi, Hiroki; Hamada, Yohei; Urakami, Tosiharu; Aoki, Yosuke
Objective Legionnaires' disease (LD) is a common form of lobar pneumonia, but the optimum diagnostic modality has long been a subject of debate due to incomplete sensitivity and specificity. A delay in the initiation of specific therapy for LD is associated with increased mortality. The decision to treat a patient for Legionella must be made quickly. The purpose of this study was to evaluate the ability of the modified Winthrop-University Hospital WUH system to identify LD while discriminating against pneumococcal pneumonia at the time of hospitalization for community-acquired pneumonia. Methods Five patients with LD and 13 patients with pneumococcal pneumonia were retrospectively analyzed. Results The WUH system identified 4 of 5 patients with LD (sensitivity, 80%) while excluding legionellosis in 12 of 13 patients with pneumococcal pneumonia (specificity, 92%). The positive and negative likelihood ratios were 10.4 and 0.2. The area under the receiver operating characteristic curve was 0.969. Conclusion The WUH system is useful for obtaining a rapid presumptive clinical diagnosis of LD. Further investigation with a larger number of patients is strongly recommended.
Discrimination between Legionnaires' Disease and Pneumococcal Pneumonia Based on the Clinical and Laboratory Features: A Quantitative Approach Using the Modified Winthrop-University Hospital Weighted Point System
Yamakuchi, Hiroki; Hamada, Yohei; Urakami, Tosiharu; Aoki, Yosuke
Objective Legionnaires' disease (LD) is a common form of lobar pneumonia, but the optimum diagnostic modality has long been a subject of debate due to incomplete sensitivity and specificity. A delay in the initiation of specific therapy for LD is associated with increased mortality. The decision to treat a patient for Legionella must be made quickly. The purpose of this study was to evaluate the ability of the modified Winthrop-University Hospital WUH system to identify LD while discriminating against pneumococcal pneumonia at the time of hospitalization for community-acquired pneumonia. Methods Five patients with LD and 13 patients with pneumococcal pneumonia were retrospectively analyzed. Results The WUH system identified 4 of 5 patients with LD (sensitivity, 80%) while excluding legionellosis in 12 of 13 patients with pneumococcal pneumonia (specificity, 92%). The positive and negative likelihood ratios were 10.4 and 0.2. The area under the receiver operating characteristic curve was 0.969. Conclusion The WUH system is useful for obtaining a rapid presumptive clinical diagnosis of LD. Further investigation with a larger number of patients is strongly recommended. PMID:28250292
Pugès, Mathilde; Biscay, Pascal; Barnetche, Thomas; Truchetet, Marie-Élise; Richez, Christophe; Seneschal, Julien; Gensous, Noémie; Lazaro, Estibaliz; Duffau, Pierre
The aim was to assess the immunogenicity and the impact on disease activity of pneumococcal and influenza vaccines in SLE patients. We conducted a systematic literature review and meta-analysis of studies comparing the humoral response of either pneumococcal (serotype 23F) or influenza (AH1N1, AH3N2 and B strains) vaccines between SLE patients and healthy controls, assessed by a seroconversion or a seroprotection rate 3-6 weeks after vaccination. The impact on disease activity was assessed by the comparison of the SLEDAI score before and 3-8 weeks after vaccination. Odds ratios (ORs), risk ratios and their 95% CIs were pooled using the generic inverse variance method. Twenty studies were included, three for pneumococcal vaccine and 17 for influenza vaccine, gathering 1665 SLE patients and 826 healthy controls. For pneumococcal vaccination, no significant difference was observed, either for seroconversion rate between SLE patients and controls or for the SLEDAI score. For influenza vaccination, the response against AH1N1 was significantly reduced in SLE patients, with a lower rate of seroconversion (OR = 0.38; 95% CI: 0.27, 0.54; P < 0.00001, I(2) = 39%) and seroprotection (OR = 0.36; 95% CI: 0.28, 0.47; P < 0.00001, I(2) = 25%). For AH3N2, only seroprotection rate was significantly lower in SLE patients (OR = 0.26; 95% CI: 0.14, 0.50; P < 0.0001, I(2) = 21%). For B strain, neither seroconversion nor seroprotection rates were significantly different. Influenza vaccine did not modify the SLEDAI score. The immunogenicity of influenza vaccine in SLE patients depends on the viral strains. A reduced immunogenicity against influenza A is noted, while the immunogenicity against the B strain is preserved. The pneumococcal vaccine against 23F serotype has a preserved immunogenicity. These vaccines have no impact on the SLEDAI score. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions
Boccalini, Sara; Bechini, Angela; Levi, Miriam; Tiscione, Emila; Gasparini, Roberto; Bonanni, Paolo
Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been differently implemented in the Italian regions in the past years, reaching overall low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012, indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Italian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly. Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact of an adult pneumococcal vaccination program in Italy. Particularly, different immunization scenarios were modeled: vaccination of 65 y-olds (1 cohort strategy), simultaneous vaccination of people aged 65 and 70 y (double cohort strategy) and, lastly, immunization of people aged 65, 70 and 75 y (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the 5 y of the program. In addition, the administration of a PPV23 dose one year after PCV13 was evaluated, in order to verify the economic impact of the supplemental serotype coverage in elderly people. The mathematical model valued the clinical impact of PCV13 vaccination on the number of bacteraemic pneumococcal pneumonia (BPP) and pneumococcal meningitis (PM) cases, and related hospitalizations and deaths. Although PCV13 is not yet formally indicated for the prevention of pneumococcal CAP by the European Medicine Agency (differently from FDA, whose
Miller, Elizabeth; Andrews, Nicholas J; Waight, Pauline A; Slack, Mary Pe; George, Robert C
The seven-valent pneumococcal conjugate vaccine (PCV7) has reduced vaccine-type (VT) invasive pneumococcal disease but increases in non-vaccine-type (NVT) disease have varied between countries. We assess the effect of the PCV7 vaccination on VT and NVT disease in England and Wales. The study cohort was the population of England and Wales from July, 2000, to June, 2010. We calculated incidence rate ratios (IRRs) to compare incidences of VT and NVT disease before (2000-06) and after (2009-10) the introduction of PCV7. We used data from the national surveillance database. Cases included in our analysis were restricted to those confirmed by culture linked with isolates referred for serotyping at the national reference centre by laboratories in England and Wales. We adjusted for potential bias from missing data (serotype and age of patient) and changes in case ascertainment rates during the study period. 5809 cases of invasive pneumococcal disease were reported in 2009-10, giving an incidence of 10·6 per 100,000 population in 2009-10, which, when compared with the adjusted average annual incidence of 16·1 in 2000-06, gives an overall reduction of 34% (95% CI 28-39). VT disease decreased in all age groups, with reductions of 98% in individuals younger than 2 years and 81% in those aged 65 years or older. NVT disease increased by 68% in individuals younger than 2 years and 48% in those aged 65 years or older, giving an overall reduction in invasive pneumococcal disease of 56% in those younger than 2 years and 19% in those aged 65 years or older. After vaccine introduction, more NVT serotypes increased in frequency than decreased, which is consistent with vaccine-induced replacement. Key serotypes showing replacement were 7F, 19A, and 22F. Increases in NVT invasive pneumococcal disease were not associated with antimicrobial resistance. Despite much serotype replacement, a substantial reduction in invasive pneumococcal disease in young children can be achieved with PCV7
Brouwer, Matthijs C.; Baas, Frank; van der Ende, Arie; van de Beek, Diederik
It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05–64.1; p = 0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39–3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis. PMID:23741476
Galante, Julieta; Augustovski, Federico; Colantonio, Lisandro; Bardach, Ariel; Caporale, Joaquin; Marti, Sebastian Garcia; Kind, Paul
To estimate and compare EuroQol instrument (EQ-5D) health states' values for pneumococcal and human papillomavirus (HPV) diseases in Argentina, Chile, and the United Kingdom. Twelve vignettes were designed, pilot-tested, and administered to a convenience sample in a cross-sectional design to elicit descriptive EQ-5D state data. Country-specific EQ-5D time-trade-off-based weights were used to map these descriptive health states into local country preference weights. Descriptive analysis is reported and intercountry differences for each condition were compared using repeated measures analysis of variance. Seventy-three subjects completed the survey. Pneumococcal disease-related health states mean values ranged from -0.331 (sepsis, Chile) to 0.727 (auditive sequelae, Argentina). HPV-related conditions ranged from 0.152 (cervical cancer, United Kingdom) to 0.848 (cervical intraepithelial neoplasia 1, Argentina). Chile had consistently the lowest mean values in pneumococcal states and in one HPV state, whereas those of the United Kingdom were the lowest in most HPV states. Argentina had the highest mean values in both diseases. Differences in country-specific values for each health state were statistically (P < 0.001) significant except for six health states in which differences between Chilean and United Kingdom weights were nonsignificant. Utility values for most conditions differed statistically relevantly among analyzed countries, even though the same health states' descriptive set was valued for each. These results reflect the difference in social weights among different countries, which could be attributed to either different population values or valuation study methodologies. They stress the importance of using local preference weights for context-specific decision making. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Olarte, Liset; Barson, William J; Barson, Ryan M; Lin, Philana Ling; Romero, José R; Tan, Tina Q; Givner, Laurence B; Bradley, John S; Hoffman, Jill A; Hultén, Kristina G; Mason, Edward O; Kaplan, Sheldon L
The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis (PM) in US children is unknown. We compared the serotype distribution, antibiotic susceptibility, hospital course, and outcomes of children with PM 3 years before and 3 years after the introduction of PCV13. We identified patients ≤ 18 years of age with PM at 8 children's hospitals in the United States. Pneumococcal isolates were collected prospectively. Serotyping and antibiotic susceptibility were performed in a central laboratory. Clinical data were abstracted from medical records. Patients were divided into 3 subgroups: pre-PCV13 (2007-2009), transitional year (2010), and post-PCV13 (2011-2013). Categorical variables were analyzed by the χ(2) test and continuous variables by the Mann--Whitney U test. During the study period, 173 of 1207 episodes (14%) of invasive pneumococcal disease were identified as PM; 76 of 645 (12%) were during 2007-2009 and 69 of 394 (18%) during 2011-2013 (50% increase; P = .03). The proportion of PCV13 serotype cases decreased from 54% in 2007-2009 to 27% in 2011-2013 (P = .001). Non-PCV13 serotype cases represented 73% of the isolates in 2011-2013. Isolates with ceftriaxone minimum inhibitory concentration ≥ 1 µg/mL decreased (13% to 3%) from 2007-2009 to 2011-2013 (P = .03). No significant differences were identified for hospital course or outcome, with the exception that a greater proportion of patients had subdural empyema and hemiparesis in 2011-2013. After the introduction of PCV13, the number of cases of PM in children remained unchanged compared with 2007-2009, although the proportion of PCV13 serotypes decreased significantly. Serotype 19A continued to be the most common serotype in 2011-2013. Antibiotic resistance decreased significantly. Morbidity and case-fatality rate due to PM remain substantial. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved
Henken, Stefanie; Bohling, Jennifer; Martens-Lobenhoffer, Jens; Paton, James C.; Ogunniyi, A. David; Briles, David E.; Salisbury, Vyvyan C.; Wedekind, Dirk; Bode-Böger, Stefanie M.; Welsh, Thomas; Bange, Franz C.; Welte, Tobias; Maus, Ulrich A.
Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to ∼70% or ∼60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease. PMID:19917756
Pletz, Mathias W
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.
Xu, Qingfu; Pryharski, Karin; Pichichero, Michael E
Currently licensed serotype-based pneumococcal vaccines are effective in preventing invasive pneumococcal diseases, but less effective in preventing non-bacteremic pneumonia and acute otitis media (AOM). We previously reported that a trivalent pneumococcal protein recombinant vaccine (PPrV) protected against pneumonia in a murine model. Here we evaluated PPrV protection against AOM in an infant murine model. C57BL/6J mice were intramuscularly vaccinated at 1-3weeks of age with monovalent pneumococcal histidine triad protein D (PhtD), or pneumococcal choline binding protein A (PcpA), or detoxified pneumolysin (PlyD1), or trivalent vaccine, and transtympanically challenged at 7-8weeks of age with 1×102CFU of pneumococcal strain BG7322 (6A) or 1×104CFU of pneumococcal nontypeable strain 0702064MEF. Serum IgG titers were determined by ELISA. At 24 and 48h post infection (hpi), animals were sacrificed and middle ear fluid (MEF) samples were collected to determine pneumococcal CFUs. We found that vaccination of infant mice with monovalent and trivalent pneumococcal proteins elicited significant serum IgG antibody responses to corresponding component proteins. Vaccination with PhtD reduced BG7322 bacterial burdens in MEF at both 24 (p=0.05) and 48hpi (p=0.16). Vaccination with PcpA significantly reduced the bacterial burdens in MEF at both 24 (p=0.02) and 48hpi (p=0.004), and PlyD1 significantly reduced bacterial burden in MEF at 48hpi (p=0.02). Vaccination with trivalent PPrV (PhtD, PcpA and PlyD1) significantly reduced Spn burdens in MEF at both 24 (p=0.001) and 48hpi (p<0.0001). Similar reductions of bacterial burdens were found when the vaccinated animals were challenged with a non-typeable Spn strain. Vaccinated mice had significantly milder inflammatory cytokine levels (IL-1β, IL-6, TNF-α, MIP-2 and KC) in middle ears at 24hpi (all p values<0.05). Trivalent PPrV confers protection against pneumococcal AOM in an infant murine model. Copyright © 2016 Elsevier Ltd
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.
Black, Carla L; Williams, Walter W; Warnock, Rob; Pilishvili, Tamara; Kim, David; Kelman, Jeffrey A
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).
Loubet, Paul; Kernéis, Solen; Groh, Matthieu; Loulergue, Pierre; Blanche, Philippe; Verger, Pierre; Launay, Odile
Immunocompromised patients are at increased risk for severe influenza and invasive pneumococcal diseases. Population-specific vaccine recommendations are thus warranted. This study aimed to estimate the prevalence and predictors of influenza and pneumococcal vaccine uptake in a large cohort of patients with secondary immune deficiency. An anonymous online survey was submitted to the members of 11 French associations of immunocompromised patients. The questionnaire included questions concerning underlying disease, care and treatment, flu and pneumococcal vaccine uptake, attitudes and knowledge about vaccination. Factors associated with vaccine uptake were assessed by multivariate logistic regression. Among the 10,897 solicited patients, 3653 agreed to participate (33.5%): 75% were female, 20% aged 65+, 79% were followed for an autoimmune disease, 13% were solid organ recipients or waiting for transplantation and 8% were treated for hematological malignancies. 3109 (85%) participants were treated with immunosuppressive therapy. Self-reported vaccine uptake was 59% (95%CI [57-60]) against seasonal influenza and 49% (95%CI [47-50]) against pneumococcal diseases. Better knowledge of and favorable attitudes toward vaccination were positively associated with vaccine uptake while being treated with a biological therapy was negatively associated. Despite specific recommendations regarding immunocompromised patients, influenza and pneumococcal vaccination rates do not reach recommended levels. Targeted information campaigns on vaccination toward these populations should be implemented to improve vaccine coverage and thus reduce the burden of infections. Copyright © 2015. Published by Elsevier Ltd.
Grzesiowski, Pawel; Aguiar-Ibáñez, Raquel; Kobryń, Aleksandra; Durand, Laure; Puig, Pierre-Emmanuel
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
Ciruela, Pilar; Martínez, Ana; Izquierdo, Conchita; Hernández, Sergi; Broner, Sonia; Muñoz-Almagro, Carmen; Domínguez, Àngela
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 10 ( 5) 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.
Ciruela, Pilar; Martínez, Ana; Izquierdo, Conchita; Hernández, Sergi; Broner, Sonia; Muñoz-Almagro, Carmen; Domínguez, Àngela; of Catalonia Study Group, the Microbiological Reporting System
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
Engelen-Lee, Joo-Yeon; Brouwer, Matthijs C; Aronica, Eleonora; van de Beek, Diederik
Delayed cerebral thrombosis (DCT) is a devastating cerebrovascular complication in patients with excellent initial recovery of pneumococcal meningitis. The aetiology is unknown, but direct bacterial invasion, activation of coagulation or post-infectious immunoglobulin deposition has been suggested. We studied histopathology of 4 patients with pneumococcal meningitis complicated by DCT. Results were compared with 8 patients who died of pneumococcal meningitis without DCT and 3 non-meningitis control cases. Furthermore, we evaluated vascular immunoglobulin depositions (IgA, IgG and IgM) and the presence of pneumococcal capsules by immunofluorescence. Patients who died after pneumococcal meningitis showed inflammation in the meninges and blood vessels with extensive infarction and thrombosis. We did not observe gross differences between DCT and non-DCT patients, except that 2 of 4 DCT patients had a basilar artery aneurysm compared to none of the non-DCT patients. We observed high density of IgM and IgG deposition in meningitis cases as compared to controls, but no difference between DCT and non-DCT patients. Immunofluorescence staining of pneumococci demonstrated the presence of bacterial capsules in the meninges of all meningitis patients, even 35 days after the initiation of antibiotic treatment. The aetiology of DCT complicating pneumococcal meningitis seems to be of multifactorial aetiology and includes vascular inflammation, thromboembolism of large arteries and infectious intracranial aneurysms. Pneumococcal cell wall components can be observed for weeks after pneumococcal meningitis and may be a source of resurging inflammation after the initial immunosuppression by dexamethasone.
Castañeda-Orjuela, Carlos; Alvis-Guzmán, Nelson; Paternina, Angel José; De la Hoz-Restrepo, Fernando
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.
Kong, Il Gyu; Sato, Ayuko; Nochi, Tomonori; Takahashi, Haruko; Sawada, Shinichi; Mejima, Mio; Kurokawa, Shiho; Okada, Kazunari; Sato, Shintaro; Briles, David E.; Kunisawa, Jun; Inoue, Yusuke; Yamamoto, Masafumi; Akiyoshi, Kazunari
To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection. PMID:23460513
Argondizzo, Ana Paula Corrêa; Rocha-de-Souza, Cláudio Marcos; de Almeida Santiago, Marta; Galler, Ricardo; Reis, Joice Neves; Medeiros, Marco Alberto
Streptococcus pneumoniae is a colonizer of the human nasopharynx, which accounts for most of the community-acquired pneumonia cases and can cause non-invasive and invasive diseases. Current available vaccines are serotype-specific and the use of recombinant proteins associated with virulence is an alternative to compose vaccines and to overcome these problems. In a previous work, we describe the identification of proteins in S. pneumoniae by reverse vaccinology and the genetic diversity of these proteins in clinical isolates. It was possible to purify a half of 20 selected proteins in soluble form. The expression of these proteins on the pneumococcal cells surface was confirmed by flow cytometry. We demonstrated that some of these proteins were able to bind to extracellular matrix proteins and were recognized by sera from patients with pneumococcal meningitis infection caused by several pneumococcal serotypes. In this context, our results suggest that these proteins may play a role in pneumococcal pathogenesis and might be considered as potential vaccine candidates.
Has the licensing of respiratory quinolones for adults and the 7-valent pneumococcal conjugate vaccine (PCV-7) for children had herd effects with respect to antimicrobial non-susceptibility in invasive Streptococcus pneumoniae?
Fenoll, A; Aguilar, L; Granizo, J J; Giménez, M J; Aragoneses-Fenoll, L; Mendez, C; Tarragó, D
The aim of the study was to analyse the evolution of antibiotic non-susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine (PCV-7) for immunization of children. All invasive pneumococci received in the Reference Laboratory (January 2000-August 2007; n = 12 957 isolates) were serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and the manufacturer, respectively. In 2000-07, PCV-7 distribution (doses/1000 inhabitants =59 months age/year) increased from 0.0 to 411.90, and antibiotic consumption (DDD/1000 inhabitants/day) was maintained for beta-lactams ( approximately 16), decreased for macrolides (from 4.4 to 2.7) and increased for respiratory fluoroquinolones (from 0.3 to 2.7). The increase in PCV-7 distribution correlated with a decrease in PCV-7 serotypes prevalence among invasive isolates in children (r = -0.976; P < 0.001) and adults (r = -0.905; P = 0.002). This decrease in PCV-7 serotypes correlated with a decrease in penicillin non-susceptibility in children (r = 0.929; P < 0.001) and adults (r = 0.905; P = 0.002) and with erythromycin non-susceptibility in children (r = 0.833; P = 0.010). Penicillin/erythromycin non-susceptibility in 2000 was significantly higher in paediatric versus adult isolates (penicillin: 51.4% versus 29.2%; erythromycin: 39.5% versus 20.4%), but similar in 2006-07 (20% to 24%). The increase in respiratory quinolones consumption correlated with the increase in levofloxacin non-susceptibility in adults (r = 0.926; P = 0.008) but not in children, with different non-susceptibility rates in 2007 (1.6% versus 0.0%; P = 0.013). This ecological analysis suggests that PCV-7 vaccination in children had a herd effect in adults, but consumption of respiratory quinolones in adults had no effect on pneumococcal susceptibility to levofloxacin in
Reddinger, Ryan M; Luke-Marshall, Nicole R; Sauberan, Shauna L; Hakansson, Anders P; Campagnari, Anthony A
Streptococcus pneumoniae and Staphylococcus aureus are ubiquitous upper respiratory opportunistic pathogens. Individually, these Gram-positive microbes are two of the most common causative agents of secondary bacterial pneumonia following influenza A virus infection, and they constitute a significant source of morbidity and mortality. Since the introduction of the pneumococcal conjugate vaccine, rates of cocolonization with both of these bacterial species have increased, despite the traditional view that they are antagonistic and mutually exclusive. The interactions between S. pneumoniae and S. aureus in the context of colonization and the transition to invasive disease have not been characterized. In this report, we show that S. pneumoniae and S. aureus form stable dual-species biofilms on epithelial cells in vitro When these biofilms are exposed to physiological changes associated with viral infection, S. pneumoniae disperses from the biofilm, whereas S. aureus dispersal is inhibited. These findings were supported by results of an in vivo study in which we used a novel mouse cocolonization model. In these experiments, mice cocolonized in the nares with both bacterial species were subsequently infected with influenza A virus. The coinfected mice almost exclusively developed pneumococcal pneumonia. These results indicate that despite our previous report that S. aureus disseminates into the lungs of mice stably colonized with these bacteria following influenza A virus infection, cocolonization with S. pneumoniae in vitro and in vivo inhibits S. aureus dispersal and transition to disease. This study provides novel insight into both the interactions between S. pneumoniae and S. aureus during carriage and the transition from colonization to secondary bacterial pneumonia. IMPORTANCE In this study, we demonstrate that Streptococcus pneumoniae can modulate the pathogenic potential of Staphylococcus aureus in a model of secondary bacterial pneumonia. We report
Jonczyk, Magda S.; Simon, Michelle; Kumar, Saumya; Fernandes, Vitor E.; Sylvius, Nicolas; Mallon, Ann-Marie; Denny, Paul; Andrew, Peter W.
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. PMID
Caceres, Diana C; Ortega-Barria, Eduardo; Nieto, Javier; DeAntonio, Rodrigo
Colombia introduced mass pneumococcal conjugate vaccination at the end of 2011. Using 2005-2015 surveillance data, we conducted a retrospective interrupted time-series analysis. A significant trend towards reduced monthly was observed in the post-vaccination period (2012-2015) compared with the expected rate, reaching in 2015 a reduction of 90.5% of pneumococcal meningitis. This trend was not observed for control diseases.
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Piao, Zhenyu; Akeda, Yukihiro; Takeuchi, Dan; Ishii, Ken J; Ubukata, Kimiko; Briles, David E; Tomono, Kazunori; Oishi, Kazunori
An increase in the appearance of nonvaccine serotypes in both children and adults with invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine represents a limitation of this vaccine. In this study, we generated three recombinant pneumococcal surface protein A (PspA) proteins comprising PspA families 1 and 2, and we examined the reactivity of antisera raised in mice immunized with a PspA fusion protein in combination with CpG oligonucleotides plus aluminum hydroxide gel. The protective effects of immunization with PspA fusion proteins against pneumococcal challenge by strains with five different PspA clades were also examined in mice. Flow cytometry demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA-specific IgG to all five challenge strains with different clades. PspA2+4- or PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade 3. Immunization with PspA3+2 afforded significant protection against pneumococcal challenge by five strains with different clades in mice, but immunization with PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three PspA fusion proteins was examined in 68 clinical isolates from adult patients with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding capacity for clinical isolates expressing clades 1-4, but not clade 5. Our results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical isolates and cross-protection against pneumococcal challenge in mice. Copyright © 2014 Elsevier Ltd. All rights reserved.
Ordóñez, Jaime E; Orozco, John Jairo
Pneumococcal diseases in children under five years are common and preventable. In Colombia there are two pneumococcal conjugate vaccines (PCV) that have proved clinical efficacy. The aim was to estimate the cost-effectiveness of 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in terms of prevention of Invasive Pneumococcal Diseases (IPD), radiologically-confirmed pneumonia, and their related mortality, as well as, acute otitis media (AOM) in a cohort of newborns in Colombia. We developed an analytical decision tree model with national data including the distribution of pneumococcal serotypes in Colombia between 2009 and 2013. A simulation of vaccination of 90% of newborns in Colombia took place with a time horizon of 5 years. The analysis was done from the Colombian health system perspective. Vaccines efficacy parameters were measured as life-years gained (LYG) and avoided morbidity by pneumococcal diseases; they were determined by a systematic review of literature. A health insurance company provided the costs. A probabilistic and a univariate sensitivity analysis for epidemiological, efficacy and cost parameters were done. After 5 years projection, PCV13 would prevent 437 deaths due to pneumococcal infections versus 321 that would be prevented by PCV10, compared to no vaccination. PCV13 would generate 25 396 LYG, and PCV10 would generate 18 708 LYG. Medical costs avoided would be US$ 19 479 395 for PCV13 and US$ 13 703 271 for PCV10. Compared to no vaccination, PCV13 and PCV10 were cost-effective, with an incremental cost-effectiveness ratio (ICER) of US$ 489.26 and US$ 813.41 per additional LYG, respectively; besides, PCV13 was dominant over PCV10 due to lower costs and better outcomes. PCV13 is a cost-saving strategy compared with PCV10, as part of a universal coverage vaccination program in Colombian children under one year. PCV13 is expected to lead to a greater decrement in infant mortality from pneumococcal diseases, and a higher cost saving by preventing
Witzenrath, Martin; Pache, Florence; Lorenz, Daniel; Koppe, Uwe; Gutbier, Birgitt; Tabeling, Christoph; Reppe, Katrin; Meixenberger, Karolin; Dorhoi, Anca; Ma, Jiangtao; Holmes, Ashleigh; Trendelenburg, George; Heimesaat, Markus M; Bereswill, Stefan; van der Linden, Mark; Tschopp, Jürg; Mitchell, Timothy J; Suttorp, Norbert; Opitz, Bastian
Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and sepsis. Pneumococci can be divided into >90 serotypes that show differences in the pathogenicity and invasiveness. We tested the hypotheses that the innate immune inflammasome pathway is involved in fighting pneumococcal pneumonia and that some invasive pneumococcal types are not recognized by this pathway. We show that human and murine mononuclear cells responded to S. pneumoniae expressing hemolytic pneumolysin by producing IL-1β. This IL-1β production depended on the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Some serotype 1, serotype 8, and serotype 7F bacteria, which have previously been associated with increased invasiveness and with production of toxins with reduced hemolytic activity, or bacterial mutants lacking pneumolysin did not stimulate notable IL-1β production. We further found that NLRP3 was beneficial for mice during pneumonia caused by pneumococci expressing hemolytic pneumolysin and was involved in cytokine production and maintenance of the pulmonary microvascular barrier. Overall, the inflammasome pathway is protective in pneumonia caused by pneumococci expressing hemolytic toxin but is not activated by clinically important pneumococcal sequence types causing invasive disease. The study indicates that a virulence factor polymorphism may substantially affect the recognition of bacteria by the innate immune system.
Payeras, Antoni; Villoslada, Aroa; Garau, Margarita; Salvador, Ma Neus; Gallegos, Ma Carmen
To describe the distribution of vaccine and non-vaccine pneumococcal serotypes from adult patients for different clinical scenarios, after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV-13) for children. This was a prospective study of pneumococcal infections in adult patients (January 2010 to April 2014) in Hospital Son Llàtzer, Mallorca (Spain). Two different periods of time were compared, the first before (first period) and the second after (second period) the introduction of PCV-13. Information related to clinical characteristics, outcomes of infection, pneumococcal serotypes, and antibiotic susceptibility was collected. We studied 407 episodes (371 patients), 201 in the first period and 206 in the second period. The majority of patients were male; the median patient age was 68 (range 15-99) years. Infections due to PCV-13 serotypes decreased from 59.7% to 47.6% (p=0.014), mainly serotypes 3, 7, 18C, 19F, and 23F. In the second period, PCV-13 serotypes were the cause of pneumonia in 58.2% of cases and in 40.8% of invasive infections, but these serotypes were not related with any outcome variable. No differences in hospital or intensive care unit admission, severity, or mortality were observed between the two periods. Susceptibility to penicillin (98.2% vs. 95.1%, p=0.03) and amoxicillin (96.5% vs. 91%, p=0.007) was slightly higher in the first period. Although a reduction in infections due to vaccine serotypes was observed, close to half of infections in adult patients were caused by PCV-13 serotypes. Even after pediatric vaccination with PCV-13, vaccine serotypes were still responsible for most pneumonia and invasive disease, underscoring the importance of implementing current guidelines and extending vaccination to other risk groups. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Alari, Anna; Chaussade, Hélène; Domenech De Cellès, Matthieu; Le Fouler, Lénaig; Varon, Emmanuelle; Opatowski, Lulla; Guillemot, Didier; Watier, Laurence
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
Schurder, Juliet; Goulenok, Tiphaine; Jouenne, Romain; Dossier, Antoine; Van Gysel, Damien; Papo, Thomas; Sacre, Karim
Our study aimed to analyze the risk factors associated with the occurrence and severity of pneumococcal infection (PI) in systemic lupus erythematosus (SLE) patients. Medical records of all SLE patients admitted in our department from January 2005 to December 2014 were retrospectively reviewed. SLE patients were separated in 2 groups according to whether they had PI or not. Medical records of all consecutive patients (with and without SLE) admitted in our department for PI over the same period of time were also reviewed. Clinical characteristics associated with PI occurrence and severity were analyzed in SLE patients. One hundred and ninety SLE patients (42.2+14.9 years; 87.4% females) were hospitalized over a 10-year period. PI was the reason for admission in 6 (3.2%) patients, including 5 cases of invasive infection. With a follow-up of 2112.8 patient-years for the total cohort, incidence of invasive PI in SLE was of 236/100,000 patient-years. PI occurred at a younger age (43.5+14.9 versus 65.3+18.7 years, P<0.01) and were more severe, with a higher frequency of invasive infection (P<0.001) and higher need for ICU admission (P<0.05) in SLE as compared to non SLE patients. Risk factors associated with PI in SLE patients were a serum gammaglobulin level<5g/L (P<0.01) and a past history of lupus nephritis (P<0.05), only. Steroids (P<0.001) and immunosuppressive drugs (P<0.05) were associated with infection severity. SLE is a disease of high susceptibility for invasive pneumococcal infections. Our study points to the need for vaccination against Streptococcus pneumoniae in SLE. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
Menéndez, Rosario; España, Pedro Pablo; Pérez-Trallero, Emilio; Uranga, Ane; Méndez, Raul; Cilloniz, Catia; Marimón, José María; Cifuentes, Isabel; Méndez, Cristina; Torres, Antoni
Streptococcus pneumoniae serotypes distribution in community-acquired pneumonia (CAP) requiring hospitalization in adults after introduction of PCV13 in children is not well known. Our aim was to evaluate the distribution of serotypes in pneumococcal pneumonia according to risk factors and comorbidity conditions after the introduction of PCV13 in children in 2010. A prospective study from 2011 to 2014 was performed in immunocompetent adults hospitalized with CAP in 3 Spanish hospitals. Microbiological confirmation was obtained using a serotype specific urinary antigen detection test (UAD test), Binax Now and conventional cultures. 1258 adults were enrolled and pneumococcal pneumonia (invasive disease in 17.7%) was confirmed in 368 (29.3%) and 17.6% of the any-cause CAP were caused by PVC13 serotypes (3.5% PCV7 serotypes). Around 60% of pneumococcal CAP were caused by PCV13 serotypes (74.6% in invasive episodes vs 57.4% in non-invasive ones). The most prevalent serotypes in invasive disease were 1, 3, 7F, 19A and 14. No significant differences were observed in the distribution of PCV13 serotypes across the study periods. Regarding comorbidity, the rate of PCV13 serotypes was similar among them, and it was slightly higher in those with no underlying conditions. Serotypes included in PCV13 caused a significant proportion of CAP in adults with underlying conditions and in healthy adults, with no significant changes in cases due to PCV7 or PCV13 from 2011 to 2014, suggesting an insufficient indirect protection from childhood vaccination. Strategies for implementing pneumococcal vaccination of adults are encouraged to reduce the incidence of pneumococcal episodes. Copyright © 2017 Elsevier Ltd. All rights reserved.
Rezai, Mohammad Sadegh; Ghaffari, Javad; Mahdavi, Mohammadreza; Bahari, Amir; Ala, Shahram
Background: Pneumococcal vaccine provides protection against invasive pneumococcal disease in population at risk. This study was conducted to compare the antibody response to 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in patients with thalassemia major. Methods: A randomized cross-over clinical trial was performed on 50 asplenic patients with thalassemia major who referred to thalassemia center at Bouali Sina Hospital, Sari, Iran from 2013 to 2014. Patients were divided into two equal groups. The first group received 13-valent pneumococcal conjugate vaccine (PCV) injected into the deltoid muscle at first and received 23-valent polysaccharide vaccine (PPV) by the same way two months later. The second group received PPV vaccine at first and PCV13 two months later. Levels of serum antibody were checked and measured by enzyme-linked immunosorbent assay (ELISA) before vaccination, and then 8 weeks after the first injection and 2 months after the second injection in all patients. Each time 0.5-ml dose of the vaccine was injected. Results: Of the 50 patients, three cases were excluded due to lack of cooperation and avoidance of vaccination. From 47 patient participants, 28 (59.6%) were males and 19 (40.4%) were females with age ranged between 20 to 44 years (average age of 29.6±1.4 years). Pneumococcal IgG levels in a group that used PCV before PPV (Group A) increased from 114.5±87.7 to 1049±720 U/ml (p=0.0001) and in another group that used PPV before PCV (Group B) increased from 115±182.2 to 1497.3±920.3 U/ml (P=0.0001). Conclusion: It can be concluded that PCV vaccine before PPV can be more effective in asplenic thalassemia major patients as a booster dose. PMID:28503278
Guchev, I A; Klochkov, O I; Sinopalnikov, A I
Pneumococcal pneumonia and other diseases caused by pneumococci still remain the main factors of high morbidity and mortality rates throughout the world. Pneumococci as the leading pathogens of community-acquired pneumonia (CAP), acute otitis media and sinusitis also cause a number of other serious systemic disorders including invasive infections with high mortality in spite of the antimicrobial resistance status and adequate antimicrobials choice. Pneumococcal infections are responsible for 5-35% or more of community-acquired pneumonias. The burden of pneumonia (up to 100-200 per thousand) is recorded among military recruits in training centers. Since the specific environment of the soldiers could be carrected, their health protection requires medical surveillance. For these reasons, polysaccharide and more immunogenic conjugated pneumococcal vaccines were developed. There is now an urgent need to understand whether such vaccines are effective in military conscripts. Controversy about the effectiveness and value of the polysaccharide (PPV-23) vaccine as a CAP morbidity restriction measure still persists. There were implemented plenty of metaanalyses of pneumococcal vaccines in adults. Some of them showed that the vaccine was effective against bacteremic pneumococcal pneumonia in 'low risk' healthy adults and elders. There have been a number of poor quality observational studies in Russia where 'all pneumonia cases' were considered as an endpoint. It remains controversial whether these observational studies provide adequate evidence to justify the use of the polysaccharide vaccine in the groups of healthy young men for whom it is being advocated. In our analysis we found weak evidence supporting pneumococcal vaccination with PPV-23 for this group. Nevertheless, favorable tendency was found to immunize. It is the reason for a trail to find pharmacoepidemiological support for vaccination by novel conjugated vaccines with better immunogenicity.
Newall, A T; Reyes, J F; McIntyre, P; Menzies, R; Beutels, P; Wood, J G
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
Earnshaw, Stephanie R; McDade, Cheryl L; Zanotti, Giovanni; Farkouh, Raymond A; Strutton, David
Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 10-valent pneumococcal conjugate vaccine (PCV10) are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi). We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs) in Canada. A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars) were presented. In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only) than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination) were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public health and economic benefits relative to PCV10.
... Educators Search English Español Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth / For Parents / Your Child's Immunizations: ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, ...
Sherwin, Robert L; Gray, Sharon; Alexander, Ronika; McGovern, Paul C; Graepel, Jay; Pride, Michael W; Purdy, Jay; Paradiso, Peter; File, Thomas M
Streptococcus pneumoniae causes a substantial proportion of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United States. Limited data are available regarding the pneumococcal serotypes causing CAP and HCAP. Adults aged ≥ 50 years presenting to participating US hospitals with radiographically confirmed pneumonia between February 2010 and September 2011 were screened for inclusion. S. pneumoniae was identified using microbiological cultures, BinaxNOW® S. pneumoniae assay, or urine antigen detection (UAD) assay capable of detecting 13-valent pneumococcal conjugate vaccine (PCV13)-associated serotypes. Among 710 subjects enrolled, the median age was 65.4 years; 54.2% of subjects were male, 22.4% of radiographically confirmed pneumonia cases were considered HCAP, and 96.6% of subjects were hospitalized. S. pneumoniae was detected in 98 subjects (13.8%) by any test, and PCV13-associated serotype(s) were identified by UAD in 78 (11.0%). Serotype 19A was most prevalent, followed by 7F/A, 3, and 5. Serotypes associated with 7-valent pneumococcal conjugate vaccine (PCV7) accounted for 25% of UAD-positive isolates. Pneumococcal serotypes causing noninvasive pneumonia in adults may differ significantly from those causing invasive disease, with PCV7-associated serotypes overrepresented. Serotype 5, rarely seen in contemporary surveillance of invasive disease in the United States, substantially contributed to the observed cases of S. pneumoniae-positive CAP or HCAP.
Cohen, Robert; Cohen, Jérémie François; Chalumeau, Martin; Levy, Corinne
The high level of effectiveness of pneumococcal conjugate vaccines (PCVs) was demonstrated initially in high-income countries (HICs). However, because the burden of pneumococcal diseases (PDs) is greater in non-high-income countries (NHICs) than HICs, the assessment of these vaccines in this latter setting is crucial. Areas covered: PubMed was used to search for literature related to the effectiveness of PCVs. Several studies described the effectiveness of PCVs in NHICs, and we compare the impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and pneumonia in HICs and NHICs. Expert commentary: Implementation of PCVs has been effective in both HICs and NHICs. The decline in overall incidence of PD is due to the disappearance of most vaccine serotypes, which is straightforward and comparable across the different settings. As expected, the decrease in overall incidence of PD was eroded in part by the increasing incidence of IPD due to non-vaccine serotypes. We need to continue a multi-faceted surveillance of IPD and carriage.
Ruiz-Camps, Isabel; Jarque, Isidro
Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper. Copyright © 2014. Published by Elsevier Espana.
Al-Tawfiq, Jaffar A; Memish, Ziad A
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. PMID:26176306
Aronoff, David M.; Mulla, Zuber D.
To describe the clinical features of individuals hospitalized for postpartum invasive group A Streptococcus (GAS) infection, a retrospective, population-based study of hospitalized patients in the state of Florida was conducted. Cases of postpartum invasive GAS infection (occurring within 42 days of delivery) were compared to women with other manifestations of invasive GAS disease with respect to their age at the time of admission. Four cases of postpartum invasive GAS infection were detected in this population, yielding a prevalence of 1.6% (4/257) of postpartum disease in this invasive GAS infection database. Patients presented a median of 4 days (mean of 9 days) after delivery with signs and symptoms of infection. Three cases were complicated by bacteremia and one patient had streptococcal toxic shock syndrome. Each patient received multiple antibiotics and survived. No patients received intravenous immunoglobulin. For comparison, a secondary retrospective investigation of a large hospital discharge dataset obtained from the Florida Agency for Health Care Administration was assessed for patients with puerperal GAS infections. This method yielded an additional three cases, whose clinical and demographic characteristics were summarized. These data highlight that postpartum invasive GAS infection continues to complicate pregnancy, though the frequency has decreased markedly over the past century. PMID:19125207
Peruski, A H; Kludt, P; Patel, R S; DeMaria, A
Invasive meningococcal disease (IMD) reported to the Massachusetts Department of Public Health from 1988 to 2011 was reviewed. The average annual incidence of IMD/100 000 decreased from 1·57 [95% confidence interval (CI) 1·42-1·73] for 1988-1991 to 0·22 (95% CI 0·17-0·29) for 2008-2011. The pattern of decreasing incidence over time differed by age group. There was a decrease in IMD/100 000 in the 0-4 years age group after 1991 from 10·92 (95% CI 8·08-14·70) in 1991 to 5·76 (95% CI 3·78-8·72) in 1992. Incidence in the 0-4 years age group remained below 5/100 000 per year on average thereafter. A substantial reduction in incidence in all age groups was observed between 2000 and 2009, which began before the introduction of conjugate meningococcal vaccine in 2005. Marked reductions in incidence of IMD in Massachusetts, and elsewhere, deserve further investigation with respect to potential factors that go beyond the introduction and deployment of improved meningococcal vaccines.
Zhang, Xu-Hao; Leeuwenkamp, Oscar; Oh, Kyu-Bin; Lee, Young Eun; Kim, Chul-Min
Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) can cause invasive pneumococcal diseases (IPD), pneumonia, and acute otitis media (AOM). Both the 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are included in the National Immunization Program for infants in Korea. This study aimed to evaluate the cost-effectiveness of the 3+1 schedule of PHiD-CV versus that of PCV-13 for National Immunization Program in Korea. A published Markov model was adapted to evaluate the cost-effectiveness of vaccinating the 2012 birth cohort with PHiD-CV vs. PCV-13 from the Korean government perspective over 10 y. Best available published data were used for epidemiology, vaccine efficacy and disutilities. Data on incidence and direct medical costs were taken from the national insurance claims database. Sensitivity analyses were conducted to explore the robustness of the results. PHiD-CV was projected to prevent an additional 195,262 cases of pneumococcal diseases and NTHi-related diseases vs. PCV-13, with a substantially greater reduction in NTHi-related AOM and a comparable reduction in IPD and community-acquired pneumonia. Parity-priced PHiD-CV generated a health gain of about 844 quality-adjusted life years and a total cost-saving of approximately 4 million United States Dollars (USD) over 10 y. 93% of probabilistic simulations found PHiD-CV 3+1 to be the dominant vaccine option. Compared to PCV-13, PHiD-CV was projected to provide similar prevention against IPD and community-acquired pneumonia but would prevent more cases of AOM. Parity-priced PHiD-CV was anticipated to generate substantial cost-savings and health benefits vs. PCV-13 in Korea.
Bast, Darrin J; Yue, M; Chen, X; Bell, D; Dresser, L; Saskin, R; Mandell, L A; Low, D E; de Azavedo, Joyce C S
Surface temperature measured by an infrared temperature-scanning thermometer was used to evaluate disease severity and predict imminent death in a murine model of pneumococcal pneumonia. We showed that a decrease in temperature was associated with increasing severity of disease and concomitant histological changes and also that a temperature of 30 degrees C or less was a predictor of death. Furthermore, viable bacterial counts in the lungs of mice euthanized at a temperature of < or = 30 degrees C were not significantly different from those seen in the lungs of mice allowed to die without intervention. These data support temperature change as a more subtle indicator of outcome than death and demonstrate that this could be used as a reliable end point for euthanasia. To test the utility of our model in a drug trial, we examined the efficacies of moxifloxacin and levofloxacin by using temperature as a measure of disease severity prior to and during treatment. Regardless of the antibiotic used, mice assessed as moderately ill (temperature > or = 32 degrees C) at the start of treatment had better clinical and bacteriological outcomes than mice assessed as severely ill (temperature < 32 degrees C). However, moxifloxacin offered better protection and greater bacterial clearance than did levofloxacin in all infected mice independent of disease severity. This model not only allows a more subtle evaluation of drug efficacy but also ensures a better degree of standardization and a more humane approach to drug efficacy studies involving animals.
Andrade, Ana Lucia S; Franco, Cáritas M; Lamaro-Cardoso, Juliana; André, Maria Cláudia DPB; Oliveira, Leandro LG; Kipnis, André; Rocha, Cristyane GBB; Andrade, João G; LA Alves, Sueli; Park, In H; Nahm, Moon H; Almeida, Samanta G; Brandileone, Maria Cristina C
Objectives We have recently found a high prevalence of non-typeable pneumococcal isolates (NTPn) circulating in day-care centers in Central Brazil, besides serotype 14 isolates. We therefore examined the genetic relationship among NTPn and serotype 14 from carriage and invasive pneumococcal isolates obtained from children attending emergency rooms enrolled in a population-based surveillance. Methods The isolates were characterized by Quellung reaction serotyping, PCR for the presence of pneumolysin and the loci for a capsule gene (cpsA) and the type 14 gene (cps14H) in all NTPn, and by multilocus sequence typing and pulsed field gel electrophoresis. Results 87.2% of the isolates were clustered into nine clusters. The major cluster included 41 pneumococcal serotype 14 (28 carriage and 13 invasive isolates) and two NTPn related to the global pneumococcal clone Spain 9V-3. Overall, 95.4% of the NTPn carriage strains were genetically related to carriage or invasive strains expressing serotype 14. A dominant NTPn lineage was found, that grouped 14 pneumococcal strains. Almost half of the multidrug-resistant isolates grouped into the NTPn cluster. Conclusion These findings provide baseline data to assess the impact of the pneumococcal vaccination on the molecular epidemiology of S. pneumoniae. Changes in frequency of NTPn isolates and also genetic changes should be carefully monitored post vaccination, to detect potential vaccine-escape or replacement disease by capsule switched strains, especially in areas where colonization with NTPn has been frequently observed. PMID:20637229
Conley, Amy K; Watling, James I; Orrock, John L
Risk models for vector-borne diseases rely on accurate quantification of the relationship between vector abundance and habitat, but this relationship can be obscured if habitats are modified by invasive species in ways that alter vector behavior but are undetectable in remotely sensed data. At a forest in eastern Missouri we assessed whether the presence of an invasive shrub, Amur honeysuckle, Lonicera maackii, affects oviposition by treehole mosquitoes, Aedes triseriatus, a primary vector of La Crosse virus in the United States. Oviposition significantly decreased with increasing density of L. maackii. Moreover, our results indicate that L. maackii may hinder the efficacy of models that use remotely sensed data to predict vector abundance: there was a strong relationship between landscape composition around plots and oviposition, but only in plots not invaded by L. maackii. Overlooking potentially important but cryptic effects of invasive plants on habitat selection by vectors may undermine accurate forecasting of disease risk.
Nyasulu, Peter; Cohen, Cheryl; De Gouveia, Linda; Feldman, Charles; Klugman, Keith P; von Gottberg, Anne
Pneumococcal disease is a major global cause of morbidity and mortality. This study evaluated risk factors for mortality in children with pneumococcal meningitis and other invasive pneumococcal diseases (IPD). The study population included patients <15 years of age with laboratory-confirmed IPD and available outcome data between January 1, 2003 and December 31, 2005 as reported to a national laboratory-based surveillance program. Meningitis was defined by having pneumococcus identified from cerebrospinal fluid culture, while other IPD included patients with pneumococci identified from other normally sterile site specimens. Risk factors for mortality were evaluated using multivariable logistic regression. A total of 2251 patients with IPD were reported from sentinel sites: 581 with laboratory-confirmed meningitis and 1670 with other IPD. The case-fatality ratio was 35% (205/581) among meningitis cases and 18% (300/1670) among other IPD cases (P < 0.001). Among individuals with available human immunodeficiency virus (HIV) status data, HIV coinfection was less likely among patients with meningitis compared with other IPD (74% [244/328] vs. 82% [880/1067] P < 0.001). On multivariable analysis, HIV-infected status (odds ratio [OR]: 5.34, 95% confidence interval [CI]: 2.32-12.29), Pitt bacteremia score ≥4 (OR: 3.08, 95% CI: 1.21-7.83) and age group <1 year (OR: 2.58, 95% CI: 1.21-5.51) were independent predictors of death among patients with meningitis. Among children with other IPD, malnutrition was an independent predictor of death while HIV infection was not independently associated with increased risk of death. Pneumococcal meningitis is associated with a high case-fatality ratio among South African children and this is increased by HIV coinfection. Increasing access to antiretroviral therapy and a catch-up program for pneumococcal conjugate vaccine among HIV-infected and malnourished children could reduce this excess mortality.
Gomez, Jorge Alberto; Tirado, Juan Carlos; Navarro Rojas, Aldo Amador; Castrejon Alba, Maria Mercedes; Topachevskyi, Oleksandr
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
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
Jayasinghe, Sanjay; Chiu, Clayton; Menzies, Rob; Lehmann, Deborah; Cook, Heather; Giele, Carolien; Krause, Vicki; McIntyre, Peter
High incidence and serotype diversity of invasive pneumococcal disease (IPD) in Indigenous children in remote Australia led to rapid introduction of 7-valent conjugate pneumococcal vaccine (7vPCV) at 2, 4 and 6 months in 2001, followed by 23-valent polysaccharide pneumococcal vaccine (23vPPV) in the second year of life. All other Australian children were offered 3 doses of 7vPCV without a booster from 2005. This study evaluated the impact of the unique pneumococcal vaccine schedule of 7vPCV followed by the 23vPPV booster among Indigenous Australian children. Changes in IPD incidence derived from population-based passive laboratory surveillance in Indigenous children <5 years eligible for 23vPPV were compared to non-Indigenous eligible for 7vPCV only from the pre-vaccine introduction period (Indigenous 1994-2000; non-Indigenous 2002-2004) to the post-vaccine period (2008-2010 in both groups) using incidence rate ratios (IRRs) stratified by age into serotype groupings of vaccine (7v and 13vPCV and 23vPPV) and non-vaccine types. Vaccine coverage was assessed from the Australian Childhood Immunisation Register. At baseline, total IPD incidence per 100,000 was 216 (n=230) in Indigenous versus 55 (n=1993) in non-Indigenous children. In 2008-2010, IRRs for 7vPCV type IPD were 0.03 in both groups, but for 23v-non7v type IPD 1.2 (95% CI 0.8-1.8) in Indigenous versus 3.1 (95% CI 2.5-3.7) in non-Indigenous, difference driven primarily by serotype 19A IPD (IRR 0.6 in Indigenous versus 4.3 in non-Indigenous). For non-7vPCV type IPD overall, IRR was significantly higher in those age-eligible for 23vPPV booster compared to those younger, but in both age groups was lower than for non-Indigenous children. These ecologic data suggest a possible "serotype replacement sparing" effect of 23vPPV following 7vPCV priming, especially for serotype 19A with supportive evidence from other immunogenicity and carriage studies. Applicability post 10vPCV or 13v PCV priming in similar settings
Isolated congenital asplenia (ICA) is a rare and life-threatening condition that predisposes patients to severe bacterial infections. Most of the reported cases are familial and the mode of inheritance is usually autosomal dominant. Here, we report a case of sporadic isolated asplenia and review the literature while focusing on sporadic cases. We report the case of an 11-month-old female infant who developed fulminant pneumococcal meningitis. The pneumococcal vaccine-unimmunized patient was hospitalized with fever, irritability, and purpura, and was diagnosed as having meningitis, septic shock, and disseminated intravascular coagulation. Streptococcus pneumoniae was isolated from both cerebrospinal fluid and blood. She was successfully treated with prompt antibiotic therapy. During hospitalization, abdominal ultrasonography and computed tomography findings, scintigraphy results, and Howell-Jolly body-containing red blood cells indicated the presence of asplenia without any visceroarterial anomalies. Moreover, the findings of peripheral blood smears and spleen ultrasonographic examinations of her parents were normal. Majority of sporadic ICA cases were detected only after the onset of overwhelming infection and had a high mortality. In cases of severe invasive pneumococcal disease, a systematic search for Howell-Jolly bodies on blood smears and the presence of asplenia on abdominal imaging are essential for detecting ICA even in the absence of any family history. After the diagnosis of ICA, patient and parent education, vaccinations, antibiotic prophylaxis, and prompt empiric treatment of febrile episode should be provided.
Hung, Te-Yu; Kotecha, Rishi S; Blyth, Christopher C; Steed, Sarah K; Thornton, Ruth B; Ryan, Anne L; Cole, Catherine H; Richmond, Peter C
Children receiving immunosuppressive treatment for cancer are at high risk for invasive pneumococcal disease. The 13-valent pneumococcal conjugate vaccine (PCV13) can prevent pneumococcal disease in healthy children; however, there is an absence of literature regarding the benefit of PCV13 in immunocompromised children with cancer. A prospective, open-label cohort study recruited children between ages 1 and 18 years who were receiving active immunosuppressive therapy (AIT) or were within 12 months after completing immunosuppressive therapy (CIT). Blood samples were taken before and 4 weeks after the administration of single-dose PCV13. Serotype-specific immunoglobulin G antibody titers were measured, and titers ≥0.35 μg/mL were considered protective. Solicited side effects were recorded in a 7-day diary after vaccination. Eighty-five children were recruited. At baseline, ≤50% had protective antibody titers against Streptococcus pneumoniae for 10 serotypes in the AIT group and for 8 serotypes in the CIT group. Postvaccination, ≥70% had protective antibody titers for 9 and 11 serotypes in the AIT and CIT groups, respectively. Both groups had comparable responses to PCV7 serotypes, whereas a significantly higher proportion in the CIT group achieved protective antibody titers to PCV13 serotypes. There was a low rate of serious adverse events (3.5%). A single-dose of PCV13 is safe and immunogenic in children diagnosed with cancer. All children who are receiving therapy for cancer should receive a single dose of PCV13 as soon as possible after diagnosis, regardless of prior PCV exposure. The current data support the recommendation for an additional dose of PCV13 after the completion of immunosuppressive therapy to provide additional protection against invasive pneumococcal disease. Cancer 2017;123:4215-4223. © 2017 American Cancer Society. © 2017 American Cancer Society.
Porchia, Barbara Rita; Bonanni, Paolo; Bechini, Angela; Bonaccorsi, Gugliemo; Boccalini, Sara
Pneumococcal infection is a public health concern that disproportionately affects the young, the elderly, and the immunocompromised. There is an open debate on the implementation of polysaccharide and/or conjugate vaccines for pneumococcal diseases in adults and the elderly in many countries. The aim of this paper is to systematically review the economic profile of pneumococcal vaccines in adults in terms of costs and benefits. Areas covered: The search for economic studies on pneumococcal vaccination was carried out in Pubmed, Embase, Scopus, and the HTA and NHS EED databases and through a manual search in journals dealing with economic evaluations. We included original articles and reviews with economic evaluation of polysaccharide 23-valent (PPV23) and/or conjugate pneumococcal vaccine 13-valent (PCV13) use in adults, the elderly, and at-risk groups to provide a systematic review of economical evaluation. Expert commentary: Pneumococcal vaccination is strongly recommended for all adults, especially subjects at risk and the elderly. Pneumococcal vaccination with PCV13 or PPV23 in adults is good value for money and should be a priority for the decision-makers. The main issue is how vaccination could be offered.
Yamataka, Atsuyuki; Miyano, Go; Takeda, Masahiro
Transanal pull-through (TAPT) is the procedure of choice for treating Hirschsprung disease and should be performed with laparoscopic assistance using the anorectal line (ARL) to ensure optimum postoperative bowel function (POBF). The dentate line (DL) has traditionally been used as the landmark for commencing dissection during TAPT, but we prefer the ARL because the DL is too subjective and can be associated with risk for injury to delicate sensory innervation required for normal defecation in the anal transition zone. An intact anal transition zone and total excision of the posterior rectal cuff are crucial for normal defecation. Objective assessment of POBF is essential for thorough follow-up and early detection of potential late complications that may arise. Copyright © 2017 Elsevier Inc. All rights reserved.
Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki
We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed.
Stawasz, Andrew; Johnson, Sydney T.; Sato, Reiko; Bloom, David E.
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
Cafiero-Fonseca, Elizabeth T; Stawasz, Andrew; Johnson, Sydney T; Sato, Reiko; Bloom, David E
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
Muller, Martha; Obert, Caroline; Burnham, Corinna; Mann, Beth; Li, Yimei; Hayden, Randall T; Pestina, Tamara; Persons, Derek; Camilli, Andrew
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
Poletti, Venerino; Chilosi, Marco; Olivieri, Dario
The diagnosis of infiltrative diffuse lung disease may require invasive procedures after all noninvasive tools have failed. The clinical context in which these diseases develop and the radiological patterns are crucial for defining the timing and the methods to be used. Immunocompromised hosts are usually acutely ill with fever, cough, shortness of breath, and often with progressive hypoxemia. In this context a prompt diagnosis is necessary to decrease mortality. Bronchoalveolar lavage [especially in cases that show ground-glass attenuation or alveolar opacification in high-resolution CT scan (HRCT)] is the most important invasive procedure allowing the identification of infectious agents, neoplastic elements and characteristic cytological and phenotypical profiles (for drug injury) in the majority of cases. Less frequently transbronchial lung biopsy, transbronchial needle aspiration and biopsy or surgical lung biopsy are necessary. In immunocompetent patients the clinical spectrum of diffuse lung disease is quite broad. Furthermore, in the last two decades HRCT, used in conjunction with clinical and other noninvasive investigative modalities, has increased the accuracy of diagnosis for some diseases without the need of surgical biopsy. Also in these patients bronchoalveolar lavage, frequently in combination with transbronchial lung biopsy, is sufficient to achieve a definitive diagnosis in the majority of cases. Surgical lung biopsy is, however, still relevant in cases with idiopathic interstitial pneumonias. In this article invasive diagnostic procedures in patients with diffuse lung infiltrates are discussed from the perspective of their clinical context and their imaging characteristics. Copyright 2004 S. Karger AG, Basel
Crump, John A; Heyderman, Robert S
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: email@example.com.
Haraldsson, Gunnsteinn; Erlendsdóttir, Helga; Haraldsson, Ásgeir; Kristinsson, Karl G.
Background Information on pneumococcal serotype distribution before vaccination is a prerequisite for evaluation of vaccine effect. The aim was to investigate the prevalence of pneumococcal serotypes isolated from middle ear (ME), lower respiratory tract (LRT) and from invasive disease (IPD) in Iceland prior to implementation of ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV-10) into the infant vaccination program (April 2011). Methods and findings All isolates cultured 2007–2011 from ME, LRT and IPD identified as pneumococci were serotyped and tested for susceptibility at the Clinical Microbiology Department, Landspitali University Hospital that serves approximately 85% of the Icelandic population. Pneumococcal isolates were 1711 and 1616 (94.4%) were available for serotyping and included. Isolates belonging to PHiD-CV10 serotypes (VTs) were 1052 (65.1%). Isolates from ME were 879 (54.4%), with 639 (72.7%) from 0–1 year old patients and 651 of VTs (74%). Isolates from LRT were 564 (34.9%), with 292 (51.8%) from ≥65 years old patients, and 300 (53.2%) of VTs. IPD isolates were 173 (10.7%), although more evenly distributed according to age than isolates from the other sites most were from adults and the youngest age group,101 (58.4%) isolates were of VTs. The most common serotype was 19F, 583 (36.1%). Its prevalence was highest in ME, 400 (45.5%), 172 (30.5%) in LRT and 11 isolates (6.4%), in IPD. Penicillin non-susceptible isolates were 651 (40.3%), mainly belonging to VTs, 611 (93.9%), including 535 (82.2%) of 19F. Conclusions Multiresistant isolates of serotype 19F were highly prevalent, especially from ME of young children but also from LRT of adults. Serotype 14 was the most common serotype in IPD. The rate of VTs was high and almost all PNSP were of VTs. There was great difference in vaccine coverage between sampling sites, also reflecting difference in vaccine coverage by age groups. PMID:28125588
Hjálmarsdóttir, Martha Á; Quirk, Sigríður Júlía; Haraldsson, Gunnsteinn; Erlendsdóttir, Helga; Haraldsson, Ásgeir; Kristinsson, Karl G
Information on pneumococcal serotype distribution before vaccination is a prerequisite for evaluation of vaccine effect. The aim was to investigate the prevalence of pneumococcal serotypes isolated from middle ear (ME), lower respiratory tract (LRT) and from invasive disease (IPD) in Iceland prior to implementation of ten-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV-10) into the infant vaccination program (April 2011). All isolates cultured 2007-2011 from ME, LRT and IPD identified as pneumococci were serotyped and tested for susceptibility at the Clinical Microbiology Department, Landspitali University Hospital that serves approximately 85% of the Icelandic population. Pneumococcal isolates were 1711 and 1616 (94.4%) were available for serotyping and included. Isolates belonging to PHiD-CV10 serotypes (VTs) were 1052 (65.1%). Isolates from ME were 879 (54.4%), with 639 (72.7%) from 0-1 year old patients and 651 of VTs (74%). Isolates from LRT were 564 (34.9%), with 292 (51.8%) from ≥65 years old patients, and 300 (53.2%) of VTs. IPD isolates were 173 (10.7%), although more evenly distributed according to age than isolates from the other sites most were from adults and the youngest age group,101 (58.4%) isolates were of VTs. The most common serotype was 19F, 583 (36.1%). Its prevalence was highest in ME, 400 (45.5%), 172 (30.5%) in LRT and 11 isolates (6.4%), in IPD. Penicillin non-susceptible isolates were 651 (40.3%), mainly belonging to VTs, 611 (93.9%), including 535 (82.2%) of 19F. Multiresistant isolates of serotype 19F were highly prevalent, especially from ME of young children but also from LRT of adults. Serotype 14 was the most common serotype in IPD. The rate of VTs was high and almost all PNSP were of VTs. There was great difference in vaccine coverage between sampling sites, also reflecting difference in vaccine coverage by age groups.
Crump, John A.; Heyderman, Robert S.
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. PMID:26449937
i Editor: Wayne M. Meyers CoEd itors: Adolfo Firpo Douglas J. Wear Topics on The paThology of proTozoan and invasive arThropod diseases Armed...samples often consist of fibers, keratin, scabs, hairs, food particles or flies. Most patients see numerous health care providers and fiercely reject...they defecate infective para- sites that the host self -inoculates by inadvertently scratch- ing or rubbing the parasite-laden fecal material into the
Payeras, Antoni; Villoslada, Aroa; Garau, Margarita; Borras, María; Pareja, Antonio; Beingolea, David; García-Gasalla, Mercedes; Gallegos, M del Carmen; Alonso-Villaverde, Carlos José
To describe clinical features, complications, serotypes and antibiotic resistance in pneumococcal pneumonia in our environment after the generalization of the heptavalent conjugate vaccine (PCV-7) in paediatrics. Prospective study of episodes of pneumococcal pneumonia, with positive cultures in patients treated in the emergency department from January 2006 to February 2010. We studied 346 episodes in 320 patients, 335 belonged to 309 adult patients, 221 (71.5%) males, median age 68 years (range 16-94), and 11 episodes to patients<15 years. Two-hundred and thirty seven (68.5%) episodes were community acquired. Bacteraemia was present in 130 (37.6%) cases, with a tendency towards an increased risk in patients < 65 years (OR=1.56, 95% CI 0.96- 2.56, P=.07). Thirteen (3.8%) patients developed empyema and 33 (9.5%) septic shock. The mean age of patients with empyema was lower (P=.03). In the multivariate analysis were related to the presence of bacteraemia: a history of chronic respiratory disease (OR=0.45, 95% CI 0.25-0.81, P=.008), positive urinary antigen (OR 2.02, 95% CI 1 13-3.62, P=.01) and pleural effusion (OR=3.86, 95% CI 1.79-8.35, P=.001). Shock was associated with Fine IV-V stage (OR=23.6, 95% CI 4.96-112.82, P<.001), age < 65 years (OR=4.47, 95% CI 1.75-11.39, P=.002) and pleural effusion (OR=4.15, 95% CI 1.65 to 10.41, P=.002). Increased mortality risk was associated with presence of any complication (OR=6.6, 95% CI 1.5-27.2, P=.009) and specifically septic shock (OR=3.3, 95% CI 1.06-10.3, P=.04). Most serotypes obtained were not included in the VNC-7. Pneumococcal pneumonia after generalisation of PCV-7 is mainly related to non-vaccine serotypes. Younger patients without respiratory disease are at increased risk of bacteraemia, empyema, and septic shock, the latter being associated with a higher mortality. Copyright © 2010 Elsevier España, S.L. All rights reserved.
Quindós, Guillermo; Eraso, Elena; López-Soria, Leyre M; Ezpeleta, Guillermo
Diagnosis of invasive mycoses is a difficult challenge due to the limitations and low sensitivity of traditional microbiology methods which lead to diagnostic and therapeutic delays. The aim of this review is to summarise the state of the art of the molecular diagnosis of invasive fungal disease and to clarify its current role in the clinical practice. Conventional microbiological methods could be complemented with molecular methods in the rapid and definitive identification of fungal isolates. Biomarkers (β-glucan, galactomannan) are very useful in immunocompromised patients and have been included as probable invasive mycoses by the EORTC/MSG. Nucleic acid detection is currently used as a complementary tool for diagnosis. However, PCR can be very useful in mould invasive mycoses. Finally, the combined detection using biomarkers can improve the diagnosis. However, their applicability in the microbiology laboratory is not so easy and further studies are required for the appropriate evaluation of its clinical usefulness. Copyright © 2011 Elsevier España, S.L. All rights reserved.
Flasche, Stefan; Givon-Lavi, Noga; Dagan, Ron
Pneumococcal conjugate vaccines (PCVs) have substantially reduced the burden of pneumococcal disease, including the incidence of otitis media (OM). However, in most countries, no surveillance exists to monitor the change in pneumococcal OM incidence after the introduction of PCVs. We explored whether measuring pneumococcal carriage was a useful surrogate for monitoring postvaccination changes in the incidence of pneumococcal OM. The 7-valent PCV was introduced to Israel's national immunization program in July 2009 and gradually replaced by the 13-valent PCV starting in November 2010. Each day since 2009, nasopharyngeal swabs have been obtained from the first 4 Bedouin children and the first 4 Jewish children who were younger than 5 years old and attended a pediatric emergency room in southern Israel. During the same time, OM surveillance in southern Israel included all children younger than 2 years of age who were diagnosed with OM and had undergone a middle-ear fluid culture. The relative change in the prevalence of vaccine-serotype (VT) pneumococcal carriage was predictive of the relative change in incidence of OM due to VT pneumococcus. However, the serotype replacement observed in non-VT carriage is not paralleled in the incidence of OM due to non-VT pneumococcus. This could indicate that there are more complex mechanisms of the immune response involved in preventing initial and consecutive episodes of OM, which has been changed through declining prevalence of the most virulent serotypes as a result of vaccination. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
Kumar K L, Ravi; Ganaie, Feroze; Ashok, Vandana
Globally, Streptococcus pneumoniae is estimated to be responsible for 1 to 2 million deaths annually, in extremes of age. Serotypic distribution of pneumococci varies with age, time, and geographical area. Limited data is available on serotypic prevalence and antimicrobial susceptibility patterns of pneumococci in India. To assess resistance trends to different groups of antimicrobials and serotypic prevalences of invasive pneumococci. A prospective, hospital based study was conducted for two years, at a tertiary care medical college hospital in south Bangalore. Forty invasive pneumococcal isolates from children who were ≤5 years, with a clinical and radiological diagnosis of invasive pneumococcal disease, (IPD) were evaluated. Qualitative typing/grouping was performed by doing the capsular reaction test (Neufeld test). Antimicrobial susceptibility was tested by Minimum Inhibitory Concentration method using automated microdilution procedure. The predominant invasive pneumococcal serotypes were serogroups/types (SGTs) 6 (25%) and 14 (17.5%). 35%, 77.5% and 15% of isolates were resistant to Penicillin, Trimethoprim/Sulfamethoxazole (TMP-SMX) and Ceftriaxone respectively. Intermediate and high level resistances to penicillin were seen in 22.5% and 12.5% of S. pneumoniae isolates correspondingly. Multidrug resistance was observed in 20% of strains. This study reported presence of high level drug resistance in invasive pneumococcal isolates which were obtained from children. The serogroup/type distribution in our study and those in other Indian studies were not even. This calls for monitoring of resistance and mapping of serotype distribution.
Barichello, Tatiana; Collodel, Allan; Generoso, Jaqueline S; Simões, Lutiana R; Moreira, Ana Paula; Ceretta, Renan A; Petronilho, Fabrícia; Quevedo, João
Pneumococcal meningitis is a severe infectious disease of the central nervous system (CNS) and a significant cause of morbidity and mortality worldwide. The inflammatory reaction to the disease contributes to neuronal injury and involves the meninges, the subarachnoid space and the brain parenchymal vessels. Bacterial pathogens may reach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors, triggering an inflammatory cascade. This in turn produces cytokines and chemokines, increases adhesion molecule expression and attracts leukocytes from the blood. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier permeability. In spite of effective antibacterial treatments, approximately one third of survivors suffer from long-term sequelae, such as hearing loss, cerebral palsy, seizures, hydrocephaly or cognitive impairment. This review summarizes the information on targets of adjuvant treatments of acute pneumococcal meningitis. Copyright © 2014 Elsevier B.V. All rights reserved.
Thorrington, Dominic; Andrews, Nick; Stowe, Julia; Miller, Elizabeth; van Hoek, Albert Jan
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
Shrestha, Sourya; Foxman, Betsy; Dawid, Suzanne; Aiello, Allison E; Davis, Brian M; Berus, Joshua; Rohani, Pejman
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.
Shrestha, Sourya; Foxman, Betsy; Dawid, Suzanne; Aiello, Allison E.; Davis, Brian M.; Berus, Joshua; Rohani, Pejman
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 carriage and antibiotic susceptibility patterns from two cross-sectional colonization surveys among children aged <5 years prior to the introduction of 10-valent pneumococcal conjugate vaccine - Kenya, 2009-2010.
Kobayashi, Miwako; Conklin, Laura M; Bigogo, Godfrey; Jagero, Geofrey; Hampton, Lee; Fleming-Dutra, Katherine E; Junghae, Muthoni; Carvalho, Maria da Gloria; Pimenta, Fabiana; Beall, Bernard; Taylor, Thomas; Laserson, Kayla F; Vulule, John; Van Beneden, Chris; Kim, Lindsay; Feikin, Daniel R; Whitney, Cynthia G; Breiman, Robert F
Pneumococci are spread by persons with nasopharyngeal colonization, a necessary precursor to invasive disease. Pneumococcal conjugate vaccines can prevent colonization with vaccine serotype strains. In 2011, Kenya became one of the first African countries to introduce the 10-valent pneumococcal conjugate vaccine (PCV10) into its national immunization program. Serial cross-sectional colonization surveys were conducted to assess baseline pneumococcal colonization, antibiotic resistance patterns, and factors associated with resistance. Annual surveys were conducted in one urban and one rural site during 2009 and 2010 among children aged <5 years. To reflect differences in vaccine target population, recruitment was age-stratified in Kibera, whereas a simple random sample of children was drawn in Lwak. Nasopharyngeal swabs were collected from eligible children. Pneumococci were isolated and serotyped. Antibiotic susceptibility testing was performed using the 2009 isolates. Antibiotic nonsusceptibility was defined as intermediate susceptibility or resistance to ≥1 antibiotics (i.e., penicillin, chloramphenicol, levofloxacin, erythromycin, tetracycline, cotrimoxazole, and clindamycin); multidrug resistance (MDR) was defined as nonsusceptibility to ≥3 antibiotics. Weighted analysis was conducted when appropriate. Modified Poisson regression was used to calculate factors associated with antibiotic nonsusceptibility. Of 1,087 enrolled (Kibera: 740, Lwak: 347), 90.0% of these were colonized with pneumococci, and 37.3% were colonized with PCV10 serotypes. There were no differences by survey site or year. Of 657 (of 730; 90%) isolates tested for antibiotic susceptibility, nonsusceptibility to cotrimoxazole and penicillin was found in 98.6 and 81.9% of isolates, respectively. MDR was found in 15.9% of isolates and most often involved nonsusceptibility to cotrimoxazole and penicillin; 40.4% of MDR isolates were PCV10 serotypes. In the multivariable model, PCV10 serotypes
Skoczyńska, Anna; Waśko, Izabela; Kuch, Alicja; Kadłubowski, Marcin; Gołębiewska, Agnieszka; Foryś, Małgorzata; Markowska, Marlena; Ronkiewicz, Patrycja; Wasiak, Katarzyna; Kozińska, Aleksandra; Matynia, Bożena; Hryniewicz, Waleria
Background Neisseria meningitidis is a leading etiologic agent of severe invasive disease. The objective of the study was to characterise invasive meningococcal disease (IMD) epidemiology in Poland during the last decade, based on laboratory confirmed cases. Methods The study encompassed all invasive meningococci collected between 2002 and 2011 in the National Reference Centre for Bacterial Meningitis. The isolates were re-identified and characterised by susceptibility testing, MLST analysis, porA and fetA sequencing. A PCR technique was used for meningococcal identification directly from clinical materials. Results In the period studied, 1936 cases of IMD were confirmed, including 75.6% identified by culture. Seven IMD outbreaks, affecting mostly adolescents, were reported; all were caused by serogroup C meningococci of ST-11. The highest incidence was observed among children under one year of age (15.71/100,000 in 2011). The general case fatality rate in the years 2010–2011 was 10.0%. Meningococci of serogroup B, C, Y and W-135 were responsible for 48.8%, 36.6%, 1.2% and 1.2% of cases, respectively. All isolates were susceptible to third generation cephalosporins, chloramphenicol, ciprofloxacin, and 84.2% were susceptible to penicillin. MLST analysis (2009–2011) revealed that among serogroup B isolates the most represented were clonal complexes (CC) ST-32CC, ST-18CC, ST-41/44CC, ST-213CC and ST-269CC, and among serogroup C: ST-103CC, ST-41/44CC and ST-11CC. Conclusions The detection of IMD in Poland has changed over time, but observed increase in the incidence of the disease was mostly attributed to changes in the surveillance system including an expanded case definition and inclusion of data from non-culture diagnostics. PMID:23977184
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
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.
Lehmann, Birthe A; Eilers, Renske; Mollema, Liesbeth; Ferreira, José; de Melker, Hester E
Increasing life expectancy results in a larger proportion of older people susceptible to vaccine preventable diseases (VPDs). In the Netherlands, influenza vaccination is routinely offered to people aged 60 years and older. Vaccination against pneumococcal disease, herpes zoster and pertussis is rarely used. These vaccines will be evaluated by the Dutch Health Council and might be routinely offered to older people in the near future. Possible expansion of the program depends partly on the willingness of general practitioners (GPs) to endorse additional vaccinations. In this study, we assessed predictors of GPs' attitude and intention to vaccinate people aged 60 years and older. GPs (N = 12.194) were invited to fill in an online questionnaire consisting of questions about social cognitive factors that can influence the willingness of GPs to vaccinate people aged 60 years and older, including underlying beliefs, practical considerations of adding more vaccines to the national program, demographics, and GPs' patient population characteristics. The questionnaire was filled in by 732 GPs. GPs were positive both about vaccination as a preventive tool and the influenza vaccination program, but somewhat less positive about expanding the current program. Prediction analysis showed that the intention of GPs to offer additional vaccination was predicted by their attitude towards offering additional vaccination, towards vaccination as a preventive tool, towards offering vaccination during an outbreak and on GPs opinion regarding suitability to offer additional vaccination (R 2 = 0.60). The attitude of GPs towards offering additional vaccination was predicted by the perceived severity of herpes zoster and pneumonia, as well as the perceived incidence of herpes zoster. Severity of diseases was ranked as important argument to recommend vaccination, followed by effectiveness and health benefits of vaccines. Providing GPs with evidence-based information about the severity
Pemán, Javier; Quindós, Guillermo
Invasive fungal infections have become a major cause of morbimortality in intensive care patients, persons suffering from cancer or immune deficiencies, and other diseases with impaired immunity. Candida albicans remains the most frequent fungal pathogen, but advances in the diagnosis, prevention and treatment of invasive candidiasis are leading to important etiological changes. Among the emerging invasive mycoses, are those caused by filamentous fungi, such as Aspergillus, Lomentospora/Scedosporium, Fusarium or the Mucorales. Invasive aspergillosis is difficult to diagnose, and although there are diagnostic tools available, their use is not widespread, and their effectiveness vary depending on the group of patients. Clinical suspicion in high-risk patients, radiological diagnosis and the use of biomarkers, such as 1,3-β-D-glucan and galactomannan, can be of great help. However, diagnostic resources are limited in other mycoses, but radiology, pathological studies and the microbiological diagnosis can be useful. The high mortality of these mycoses requires early empirical antifungal treatment in many cases. Voriconazole is the first choice for treatment of the majority of aspergillosis, scedosporiasis, fusariosis and other hyalohyphomycoses. The treatment of mucormycoses, Lomentospora prolificans infections or mycoses by dematiaceous fungi are more complicated. Amphotericin B is active against many mucoralean fungi, but the combination of two or more antifungal agents could be a therapeutic alternative in many amphotericin B-refractory mycoses. Current clinical challenges include improving the diagnosis and the treatment of these mycoses, along with improving the adequate prevention in patients at high risk of suffering from them. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.
Kara, Soner Sertan; Polat, Meltem; Tapisiz, Anıl; Nar Otgun, Selin; Tezer, Hasan
Pneumococci are one of the most common causes of bacterial meningitis in children. It's also responsible for the other invasive pneumococcal diseases (IPD) including bacteremia and pneumonia worldwide. Unvaccinated children are more prone to IPD. Although IPD tend to have a higher prevalence under 2 years of age and in children with primary/secondary immunodeficiencies, and various predisposing factors, older age groups with no underlying diseases also experience IPD. In this report, a pediatric case diagnosed with meningitis due to Streptococcus pneumoniae serotype 35F with no underlying condition and no history of pneumococcal vaccination was presented. An 11-year-old male patient was admitted to the hospital with the complaints of high (39.4°C) fever, headache, vomiting and sleepiness. On the basis of findings from physical examination and laboratory results, the patient was prediagnosed as bacterial meningitis and empirical ceftriaxone and vancomycin therapy was initiated. The cerebrospinal fluid culture of the patient yielded penicillin-susceptible pneumococci and the isolate was identified as serotype 35F by quellung reaction. Vancomycin treatment discontinued depending on the culture result, and the patient fully recovered with 14-days of ceftriaxone therapy without any complications during his follow-ups. Although effective antibiotics are available for IPD, vaccination is indispensable considering the high mortality rates. Seven serotypes (1, 5, 6A, 6B, 14, 19F, 23F) which are currently included in the vaccine, were the most common serotypes related to IPD globally. After mass infant vaccination has been introduced, invasive pneumococcal diseases due to the vaccine serotypes have tended to decrease in both vaccinated young children and non-vaccinated age groups due to herd immunity. Nevertheless, non-vaccine serotypes (NVTs) have emerged as the agents of IPD as a result of serotype replacement. 13-valent pneumococcal conjugate vaccine (PCV13) was
Campins Martí, Magda
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.
Ghadieh, Alexandra S; Hamadeh, Ghassan N; Mahmassani, Dina M; Lakkis, Najla A
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.
Giese, Coralie; Mereckiene, Jolita; Danis, Kostas; O'Donnell, Joan; O'Flanagan, Darina; Cotter, Suzanne
The World Health Organization (WHO), and European Agencies recommend influenza vaccination for individuals at-risk due to age (≥65 years), underlying diseases, pregnancy and for health care workers (HCWs) in Europe. Pneumococcal vaccine is recommended for those at-risk of pneumococcal disease. In Ireland, vaccination uptake among at-risk adults is not routinely available. In 2013, we conducted a national survey among Irish residents ≥18 years of age, to estimate size and vaccination coverage of at-risk groups, and identify predictive factors for influenza vaccination. We used computer assisted telephone interviews to collect self-reported information on health, vaccination status, attitudes towards vaccination. We calculated prevalence and prevalence ratios (PR) using binomial regression. Overall, 1770 individuals participated. For influenza, among those aged 18-64 years, 22% (325/1485) [95%CI: 17%-20%] were at-risk; 28% [95%CI: 23%-33%] were vaccinated. Among those aged ≥65 years, 60% [95%CI: 54%-66%] were vaccinated. Influenza vaccine uptake among HCWs was 28% [95%CI: 21%-35%]. For pneumococcal disease, among those aged 18-64 years, 18% [95%CI: 16%-20%] were at-risk; 16% [95%CI: 12%-21%] reported ever-vaccination; among those aged ≥65 years, 36% [95%CI: 30%-42%] reported ever-vaccination. Main reasons for not receiving influenza vaccine were perceptions of not being at-risk, or not thinking of it; and among HCWs thinking that vaccination was not necessary or they were not at-risk. At-risk individuals were more likely to be vaccinated if their doctor had recommended it (PR 3.2; [95%CI: 2.4%-4.4%]) or they had access to free medical care or free vaccination services (PR 2.0; [95%CI: 1.5%-2.8%]). Vaccination coverage for both influenza and pneumococcal vaccines in at-risk individuals aged 18-64 years was very low. Influenza vaccination coverage among individuals ≥65 years was moderate. Influenza vaccination status was associated with GP vaccination
Lu, Shay; Tsai, Jeng-Dau; Tsao, Ten-Fu; Liao, Pei-Fen; Sheu, Ji-Nan
Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.
Lu, Shay; Tsai, Jeng-Dau; Tsao, Ten-Fu; Liao, Pei-Fen; Sheu, Ji-Nan
Streptococcus pneumoniae is a common cause of infectious diseases in children that may lead to life-threatening complications. Acute purulent pericarditis is an uncommon complication of S. pneumoniae in the antibiotic era. A healthy 4-year-old girl was admitted with pneumonia and pleural effusion. She had received one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age. She rapidly developed necrotizing pneumonia, complicated by bronchopleural fistula presenting as subcutaneous emphysema and pneumothorax and acute purulent pericarditis. S. pneumoniae serotype 19A was subsequently identified from blood, empyema and pericardial fluid cultures. After appropriate antibiotic therapy and a right lower lobectomy, her condition stabilized and she promptly recovered. This case highlights two rare potential clinical complications of pneumococcal disease in a child: necrotizing pneumonia and acute purulent pericarditis. This is the first report of a child who received just one catch-up dose of 13-valent pneumococcal conjugate vaccine at 2 years of age, as per the United States' Advisory Committee on Immunization Practice's recommendations, but who still developed severe invasive pneumococcal disease with life-threatening complications caused by S. pneumoniae serotype 19A.
Vilanova, J C; Luna, A
Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.
Ohkoshi, Yasuo; Sato, Toyotaka; Wada, Takayuki; Fukushima, Yukari; Murabayashi, Hiromi; Takakuwa, Yasunari; Nishiyama, Kaoru; Honda, Hiroyuki; Shiraishi, Tsukasa; Kuronuma, Koji; Takahashi, Hiroki; Nakajima, Chie; Suzuki, Yasuhiko; Yokota, Shin-Ichi
Multidrug-resistant Streptococcus pneumoniae strains were isolated from blood and sputum of a patient with disseminated intravascular coagulation in Sapporo city, Japan. These antibiograms were only susceptible to vancomycin, linezolid, daptomycin, some carbapenems, and some fluoroquinolones. Identical antibiograms, serotypes (19F), and sequence types (ST10017) suggested a shared origin of these isolates. Only one ST10017 strain has been isolated in the same city in Japan previously (2014), and the 2014 isolate is still susceptible to macrolides. The whole genome of the blood-derived isolate was sequenced. The strain harbored resistance mutations in parC, gyrA, pbp1a, pbp2a, pbp2b, and pbp2x, and harbored the resistance genes, ermB and tetM. The nucleotide sequences of parC and pbp2x genes of strain MDRSPN001 were clearly different from those of other S. pneumoniae strains and were similar to those of oral streptococci strains. These findings suggest that strain MDRSPN001 has been rapidly and drastically evolving multidrug resistance by gene replacement and accumulation of genes originating from other strains, such as oral streptococci, Streptococcus mitis. Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Lloyd, Adam; Patel, Nishma; Scott, David A; Runge, Claus; Claes, Christa; Rose, Markus
In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost-effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease.
Hirose, Tatiane E; Maluf, Eliane M C P; Rodrigues, Cristina O
To evaluate the possible effects of the introduction of the pneumococcal conjugate 10-valent vaccine schedule in the state of Parana on pneumococcal meningitis cases and to assess the distribution of serotypes among cases. Cross-sectional study with retrospective data collection of cases of pneumococcal meningitis in the state of Paraná reported to Sistema de Informação de Agravos de Notificação (SINAN), from 1998 to 2011. A total of 1,339 cases of pneumococcal meningitis were analyzed; 1,205 cases from the pre-vaccine period (1998-2009) were compared to 134 cases from the post-vaccine period (2010-2011). Descriptive and comparative statistical analyses (chi-squared test and prevalence ratio) were performed using JMP 5.1.2 statistical software (JMP Statistical Discovery, North Carolina, USA) and EPI INFO 6 (Centers for Disease Control and Prevention, Georgia, EUA). There was a significant reduction in the mean rates of incidence and mortality in the general population. The analysis of cases in the pre- and post-vaccination periods in the age groups covered by vaccination (younger than 2 years) showed significant reductions in incidence rates (6.01 cases/100,000 to 2.49 cases/100,000 individuals) and mortality (1.85 cases/100,000 population to 0.47 cases/100,000 population), while the mean lethality rate did not change significantly. There was a significant reduction in cases whose serotypes are included in the vaccine (80.7% to 53.3%). Even after a short time of use, the 10-valent pneumococcal conjugate vaccine has already had a significant impact in reducing the incidence and mortality of meningitis cases among infants, as well as the reduction of cases whose serotypes are included in the vaccine. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
Talbird, Sandra E; Ismaila, Afisi S; Taylor, Thomas N
This paper estimated the clinical impact of routine vaccination of infants with a new 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the 7-valent pneumococcal conjugate vaccine (PCV-7) and no vaccination in Canada using a new steady-state, population-based model. A deterministic, compartmental model was developed to simulate the effect of vaccination for a 1-year time period for a steady-state population, allowing for the incorporation of herd and replacement effects across all age groups. Annual clinical outcomes in the steady-state year for a population of 32.9 million were calculated for all three vaccination strategies. The no vaccination strategy was included for the purpose of validating the model. The model estimated that PHiD-CV prevented more cases of disease and more deaths than PCV-7 and no vaccination, with the largest incremental impact on acute otitis media (AOM). Compared with PCV-7, vaccination with PHiD-CV was estimated to prevent an additional 10 cases of invasive disease, 416 cases of pneumonia, 155,757 cases of AOM, 8943 myringotomy procedures, and 6 deaths nationwide. For the comparison between PCV-7 and no vaccination, the model estimated a 36.8% reduction in invasive disease; this result was similar to other models and a recent observational study in Canada, providing preliminary validation of the model. Copyright © 2010 Elsevier Ltd. All rights reserved.
Klugman, K P
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
Rashid, Harunor; Abdul Muttalif, Abdul Razak; Mohamed Dahlan, Zuraimi Bin; Djauzi, Samsuridjal; Iqbal, Zafar; Karim, Hj Matnoh; Naeem, Syed Muhammad; Tantawichien, Terapong; Zotomayor, Ricardo; Patil, Shilpa; Schmitt, Heinz-Josef
Hajj is the annual pilgrimage to Mecca in the Kingdom of Saudi Arabia, and is one of the largest mass gathering events in the world. Acute respiratory tract infections are very common during Hajj, primarily as a result of close contact among pilgrims, intense congestion, shared accommodation and air pollution. A number of vaccines are (or have been) recommended for Hajj pilgrims in recent years. Several additional vaccines could significantly reduce the morbidity and mortality at Hajj and should be considered in health recommendations for pilgrims. Pneumococcal vaccines (particularly for those aged >65 years) are widely available, and have been shown to reduce the burden of disease associated with Streptococcus pneumoniae infection. Importantly, a considerable percentage of Hajj pilgrims have pre-existing illnesses or are elderly, both important risk factors for pneumococcal infection. While there are substantial gaps that need to be addressed regarding our knowledge of the exact burden of disease in Hajj pilgrims and the effectiveness of pneumococcal vaccination in this population, S. pneumoniae may be an important cause of illness among this group of travelers. It can be assumed that the majority of pneumococcal serotypes circulating during Hajj are included in the existing pneumococcal vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.
Alexander M. Evans
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...
Todd A. Crowl; Thomas O. Crist; Robert R. Parmenter; Gary Belovsky; Ariel E. Lugo
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...
Reduction of Streptococcus pneumoniae in upper respiratory tract cultures and a decreased incidence of related acute otitis media following introduction of childhood pneumococcal conjugate vaccines in a Swedish county.
Littorin, Nils; Ahl, Jonas; Uddén, Fabian; Resman, Fredrik; Riesbeck, Kristian
The effect of pneumococcal conjugate vaccines (PCV) on invasive pneumococcal disease is frequently reported, but the impact on upper respiratory tract infections in a clinical setting is less documented. Our aim in this 5-year observational study was to investigate serotype changes in a large number of Streptococcus pneumoniae upper respiratory tract isolates following sequential introduction of PCV7 and pneumococcal Haemophilus influenza protein D conjugate vaccine (PHiD-CV10) in a Swedish county. All bacterial isolates from the upper respiratory tract (nasopharynx, sinus or middle ear fluid) from patients with respiratory tract infections referred to a clinical microbiology laboratory prior to (2 years 2007-2008; n = 1566) and after introduction of PCV (3 years 2011-2013; n = 1707) were prospectively collected. Microbiological findings were compared between the two periods, and information from clinical referrals was recorded in order to explore changes in incidence of pneumococcal acute otitis media (AOM). Pneumococcal serotypes covered by PHiD-CV10 decreased from 45 to 12 % prior to and after immunization (p < 0.001), respectively. Despite non-PHiD-CV10 serotypes increased from 49 to 80 %, a significant decline of 35 % in the absolute incidence of pneumocococal isolates (p < 0.001) was observed. Finally, the frequency of complicated AOM caused by S. pneumoniae decreased by 32 % (p < 0.001). After introduction of PCV in 2009, we have observed a significantly decreased number of pneumococcal isolates in the upper respiratory tract, a shift to non-PHiD-CV10 serotypes, and a reduction of complicated AOM. Our findings may have implications for future vaccine design.
Dicko, Alassane; Odusanya, Olumuyiwa O; Diallo, Abdoulbaki I; Santara, Gaoussou; Barry, Amadou; Dolo, Amagana; Diallo, Aminata; Kuyinu, Yetunde A; Kehinde, Omolara A; François, Nancy; Borys, Dorota; Yarzabal, Juan P; Moreira, Marta; Schuerman, Lode
Pneumonia is still the leading cause of death among children in Africa, and pneumococcal serotypes 1 and 5 are frequently isolated from African children with invasive pneumococcal disease below the age of 5 years. The immunogenicity, safety and reactogenicity of 3-dose primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in infants in Mali and Nigeria. In an open, randomized, controlled study, 357 infants received DTPw-HBV/Hib and OPV primary vaccination with (PHiD-CV group) or without (control group) PHiD-CV co-administration at 6, 10 and 14 weeks of age. Pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured and adverse events (AEs) recorded. One month post-dose 3, ≥ 97.2% of PHiD-CV-vaccinated infants had an antibody concentration ≥ 0.2 μg/mL for each vaccine pneumococcal serotype except for 6B (82.0%) and 23F (87.6%) versus < 10% in the control group except for serotypes 14 (35.7%) and 19F (22.5%). For each vaccine serotype, ≥ 93.3% of PHiD-CV recipients had an OPA titre ≥ 8, except for serotypes 1 (87.6%) and 6B (85.4%), compared to < 10% in the control group, except for serotypes 7F (42.9%), 9V (24.1%) and 14 (24.5%). Anti-protein D geometric mean antibody concentrations were 3791.8 and 85.4 EL.U/mL in the PHiD-CV and control groups, respectively. Overall incidences of solicited and unsolicited AEs were similar between groups. In sub-Saharan African infants, PHiD-CV was immunogenic for all vaccine pneumococcal serotypes and protein D. Vaccine tolerability was generally comparable between the PHiD-CV and control groups. ClinicalTrials.gov identifier: NCT00678301.
González, Roser; Armadans, Lluís; Martínez, Xavier; Moraga, Fernando; Campins, Magda
The public health system in Catalonia only funds pneumococcal vaccination in paediatrics for children at-risk. The aim of this study was to determine pneumococcal vaccination coverage and its association with age, sociodemographic factors and other variables. Descriptive cross-sectional study of children aged between 2 months and 15 years old assigned to primary care centres in Catalonia and with diseases that are included for pneumococcal vaccine in the official vaccination program. The information on vaccination status and study variables were obtained from data registered in the electronic medical records in the primary care centres. An analysis was made of the association between pneumococcal vaccination and demographic and medical variables using bivariate analysis and a multiple logistic regression model. The adjusted odds ratio (aOR), with a confidence interval of 95%, was used to measure the relationships. Pneumococcal vaccination coverage was 47.7%. Variables which predicted pneumococcal vaccination were: age (aOR: 9.2 [7.9-10.7] in children 2 months-2 years old; aOR 8.1 [7.0-9.3] in children 3-5 years; aOR: 4.6 [4.0-5.2] in children 6-10 years), Spanish nationality (aOR: 3.9 [3.5-4.3]), correct immunisation according to systematic immunisation schedule (aOR: 2.5 [2.1-3.0]), and number of risk conditions (aOR: 3.2 [2.5-4.1] in children with 2 or more conditions). Pneumococcal vaccination coverage in children with risk conditions is low in Catalonia. Strategies need to be implemented to increase coverage. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Croucher, Nicholas J; Goldblatt, David; Nosten, François; Parkhill, Julian; Turner, Claudia
Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance. PMID:28742023
Feasey, Nicholas A; Dougan, Gordon; Kingsley, Robert A; Heyderman, Robert S; Gordon, Melita A
Summary Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20–25%. The clinical presentation of invasive non-typhoidal salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and respiratory symptoms are common, and features of enterocolitis are often absent. The most important risk factors are HIV infection in adults, and malaria, HIV, and malnutrition in children. A distinct genotype of Salmonella enterica var Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa, and might have adapted to cause invasive disease in human beings. Multidrug-resistant ST313 has caused epidemics in several African countries, and has driven the use of expensive antimicrobial drugs in the poorest health services in the world. Studies of systemic cellular and humoral immune responses in adults infected with HIV have revealed key host immune defects contributing to invasive non-typhoidal salmonella disease. This emerging pathogen might therefore have adapted to occupy an ecological and immunological niche provided by HIV, malaria, and malnutrition in Africa. A good understanding of the epidemiology of this neglected disease will open new avenues for development and implementation of vaccine and public health strategies to prevent infections and interrupt transmission. PMID:22587967
Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio
Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis.
Riccò, Matteo; Vezzosi, Luigi; Odone, Anna; Signorelli, Carlo
Background and aims of the work: Invasive Meningococcal Disease (IMD) represents a global health threat, and occupational settings have the potential to contribute to its spreading. Therefore, here we present the available evidences on the epidemiology of IMD on the workplaces. The following key words were used to explore PubMed: Neisseria meningitidis, meningococcus, meningococcal, invasive meningococcal disease, epidemiology, outbreaks, profession(al), occupation(al). We identified a total of 12 IMD cases among healthcare workers (HCW), 44 involving biological laboratory workers (BLW), 8 among school personnel, and eventually 27 from other settings, including 3 large industrial working populations. Eventual prognosis of BLW, particularly the case/fatality ratio, was dismal. As clustered in time and space, data about school cases as well as industrial cases seem to reflect community rather than occupational outbreaks. In general, we identified a common pattern for HCW and BLW, i.e. the exposure to droplets or aerosol containing N meningitidis in absence of appropriate personal protective equipment (PPE) and/or microbiological safety devices (MSD) (e.g. cabinets). Post-exposure chemoprophylaxis (PEC) was rarely reported by HCW (16.7%) workers, and never by BLW. Data regarding vaccination status were available only for a case, who had failed requested boosters. The risk for occupational transmission of IMD appears relatively low, possibly as a consequence of significant reporting bias, with the exception of HCW and BLW. Improved preventive measures should be implemented in these occupational groups, in order to improve the strict use of PPE and MSD, and the appropriate implementation of PEC.
Mueller, Sebastian; Seitz, Helmut Karl; Rausch, Vanessa
Alcoholic liver disease (ALD) is the most common liver disease in the Western world. For many reasons, it is underestimated and underdiagnosed. An early diagnosis is absolutely essential since it (1) helps to identify patients at genetic risk for ALD; (2) can trigger efficient abstinence namely in non-addicted patients; and (3) initiate screening programs to prevent life-threatening complications such as bleeding from varices, spontaneous bacterial peritonitis or hepatocellular cancer. The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis (AH). The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on a combination of laboratory, clinical and imaging findings. It is not widely conceived that conventional screening tools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca. 40% of manifest alcoholic liver cirrhosis. Non-invasive methods such as transient elastography (Fibroscan), acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholic cirrhosis. Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca. 95% of patients. The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels. Other non-invasive methods such as controlled attenuation parameter, serum levels of M30 or M65, susceptometry or breath tests are under current evaluation to assess the degree of steatosis, apoptosis and iron overload in these patients. Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. PMID:25356026
... the United States.Treatment of pneumococcal infections with penicillin and other drugs is not as effective as ... Anyone who has ever had a life-threatening allergic reaction to a dose of this vaccine, to an ...
Ao, Trong T; Feasey, Nicholas A; Gordon, Melita A; Keddy, Karen H; Angulo, Frederick J; Crump, John A
Nontyphoidal Salmonella is a major cause of bloodstream infections worldwide, and HIV-infected persons and malaria-infected children are at increased risk for the disease. We conducted a systematic literature review to obtain age group-specific, population-based invasive nontyphoidal Salmonella (iNTS) incidence data. Data were categorized by HIV and malaria prevalence and then extrapolated by using 2010 population data. The case-fatality ratio (CFR) was determined by expert opinion consensus. We estimated that 3.4 (range 2.1-6.5) million cases of iNTS disease occur annually (overall incidence 49 cases [range 30-94] per 100,000 population). Africa, where infants, young children, and young adults are most affected, has the highest incidence (227 cases [range 152-341] per 100,000 population) and number of cases (1.9 [range 1.3-2.9] million cases). An iNTS CFR of 20% yielded 681,316 (range 415,164-1,301,520) deaths annually. iNTS disease is a major cause of illness and death globally, particularly in Africa. Improved understanding of the epidemiology of iNTS is needed.
Ao, Trong T.; Feasey, Nicholas A.; Gordon, Melita A.; Keddy, Karen H.; Angulo, Frederick J.
Nontyphoidal Salmonella is a major cause of bloodstream infections worldwide, and HIV-infected persons and malaria-infected and malnourished children are at increased risk for the disease. We conducted a systematic literature review to obtain age group–specific, population-based invasive nontyphoidal Salmonella (iNTS) incidence data. Data were categorized by HIV and malaria prevalence and then extrapolated by using 2010 population data. The case-fatality ratio (CFR) was determined by expert opinion consensus. We estimated that 3.4 (range 2.1–6.5) million cases of iNTS disease occur annually (overall incidence 49 cases [range 30–94] per 100,000 population). Africa, where infants, young children, and young adults are most affected, had the highest incidence (227 cases [range 152–341] per 100,000 population) and number of cases (1.9 [range 1.3–2.9] million cases). An iNTS CFR of 20% yielded 681,316 (range 415,164–1,301,520) deaths annually. iNTS disease is a major cause of illness and death globally, particularly in Africa. Improved understanding of the epidemiology of iNTS is needed. PMID:25860298
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
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.
Cross, P.C.; Lloyd-Smith, James O.; Johnson, P.L.F.; Getz, W.M.
The epidemic potential of a disease is traditionally assessed using the basic reproductive number, R0. However, in populations with social or spatial structure a chronic disease is more likely to invade than an acute disease with the same R0, because it persists longer within each group and allows for more host movement between groups. Acute diseases ‘perceive’ a more structured host population, and it is more important to consider host population structure in analyses of these diseases. The probability of a pandemic does not arise independently from characteristics of either the host or disease, but rather from the interaction of host movement and disease recovery timescales. The R* statistic, a group-level equivalent of R0, is a better indicator of disease invasion in structured populations than the individual-level R0.
Luo, Fang; Annane, Djillali; Orlikowski, David; He, Li; Yang, Mi; Zhou, Muke; Liu, Guan J
Acute respiratory failure is a common life-threatening complication of acute onset neuromuscular diseases, and may exacerbate chronic hypoventilation in patients with neuromuscular disease or chest wall disorders. Standard management includes oxygen supplementation, physiotherapy, cough assistance, and, whenever needed, antibiotics and intermittent positive pressure ventilation. Non-invasive mechanical ventilation (NIV) via nasal, buccal or full-face devices has become routine practice in many centres. The primary objective of this review was to compare the efficacy of non-invasive ventilation with invasive ventilation in improving short-term survival in acute respiratory failure in people with neuromuscular disease and chest wall disorders. The secondary objectives were to compare the effects of NIV with those of invasive mechanical ventilation on improvement in arterial blood gas after 24 hours and lung function measurements after one month, incidence of barotrauma and ventilator-associated pneumonia, duration of mechanical ventilation, length of stay in the intensive care unit and length of hospital stay. We searched the following databases on 11 September 2017: the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We also searched conference proceedings and clinical trials registries. We planned to include randomised or quasi-randomised trials with or without blinding. We planned to include trials performed in children or adults with acute onset neuromuscular diseases or chronic neuromuscular disease or chest wall disorders presenting with acute respiratory failure that compared the benefits and risks of invasive ventilation versus NIV. Two review authors reviewed searches and independently selected studies for assessment. We planned to follow standard Cochrane methodology for data collection and analysis. We did not identify any trials eligible for inclusion in the review. Acute respiratory failure is a life-threatening complication of
Pickren, Elizabeth; Crane, Brad
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.
Geno, K. Aaron; Gilbert, Gwendolyn L.; Song, Joon Young; Skovsted, Ian C.; Klugman, Keith P.; Jones, Christopher; Konradsen, Helle B.
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
... A Hepatitis B HPV (Human Papillomavirus) Influenza (Flu) Measles Meningococcal Disease Mumps Pertussis (Whooping Cough) Pneumococcal Disease Rubella (German Measles) Shingles (Herpes Zoster) Tetanus (Lockjaw) Professional Resources Adult ...
Background Nowadays, there are two vaccination strategies in Colombia to prevent pneumococcal diseases in people over 50 years. Our aim is to estimate cost-effectiveness of pneumococcal conjugate vaccine 13-valent (PCV13) versus pneumococcal polysaccharide vaccine 23-valent (PPSV23) to prevent pneumococcal diseases and their related mortality in people over 50 years old in Colombia. Methods A Markov model was developed with national data, including pneumococcal serotypes distribution in Colombia between 2005 and 2010. Vaccination of a cohort was simulated and a five year time horizon was assumed. Analysis was done from a perspective of a third party payer. Direct costs were provided by a national insurance company; sensitive univariate and probabilistic analysis were done for epidemiological and clinical effectiveness parameters and costs. Results PCV13 avoids 3 560 deaths by pneumococcal infections versus PPSV23 and 4 255 deaths versus no vaccine. PCV13 prevents 79 633 cases by all-cause pneumonia versus PPSV23 and 81 468 cases versus no vaccine. Total costs (healthcare and vaccines costs) with PCV13 would be U.S. $ 97,587,113 cheaper than PPSV23 and it would save U.S. $ 145,196,578 versus no vaccine. Conclusion PCV13 would be a cost-saving strategy in the context of a mass vaccination program in Colombia to people over 50 years old because it would reduce burden of disease and specific mortality by pneumococcal diseases, besides, it saves money versus PPSV23. PMID:24679135
Daudin, M; Tattevin, P; Lelong, B; Flecher, E; Lavoué, S; Piau, C; Ingels, A; Chapron, A; Daubert, J-C; Revest, M
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.
Rodgers, Gail L; Arguedas, Adriano; Cohen, Robert; Dagan, Ron
Acute otitis media (AOM) is the most common infection following pneumococcal colonization of the upper respiratory tract. Streptococcus pneumoniae causes 30-60% of AOM cases worldwide. However, not all pneumococcal serotypes cause disease and an association exists with nasopharyngeal colonization by certain serotypes and their propensity to cause AOM. This review examines the global serotype distribution relationship between pneumococcal serotypes and AOM in children aged <18 years and demonstrates that the most common pneumococcal serotypes causing AOM globally are 3, 6A, 6B, 9V, 14, 19A, 19F, and 23F.
Loo, Jennifer D; Conklin, Laura; Deloria Knoll, Maria; Fleming-Dutra, Katherine E; Park, Daniel E; Kirk, Jennifer; Johnson, T Scott; Goldblatt, David; O'Brien, Katherine L; Whitney, Cynthia G
Streptococcus pneumoniae causes a considerable amount of morbidity and mortality in children <5. However, pneumococcal conjugate vaccines (PCVs) can prevent much of this burden. Until recently, PCVs were mostly available only in developed countries using a variety of dosing schedules. As more lower income countries make decisions to introduce PCV into their national immunization programs, an optimal schedule with which to administer PCV has become a key policy question. We performed a systematic review of English literature published from 1994 to 2010 on the effects of PCV dosing schedules on immunogenicity, nasopharyngeal carriage, invasive pneumococcal disease and pneumonia. Data were independently double abstracted and cleaned for analysis. Descriptive analyses were performed. We identified 12,980 citations from the literature search (12,976) and secondary means (44). Double review of titles and abstracts yielded 769 articles that underwent full data abstraction. Of these, 350 were further analyzed and are presented in separate reports in this supplement. This article presents the methods utilized in our systematic review. Because of the heterogenity of the study methods of the reports identified by this review, we did not conduct formal meta-analyses. However, these methods allow us to present a full landscape of the literature on PCV dosing schedules.
Background: Streptococcus pneumoniae causes a considerable amount of morbidity and mortality in children <5. However, pneumococcal conjugate vaccines (PCVs) can prevent much of this burden. Until recently, PCVs were mostly available only in developed countries using a variety of dosing schedules. As more lower income countries make decisions to introduce PCV into their national immunization programs, an optimal schedule with which to administer PCV has become a key policy question. Methods: We performed a systematic review of English literature published from 1994 to 2010 on the effects of PCV dosing schedules on immunogenicity, nasopharyngeal carriage, invasive pneumococcal disease and pneumonia. Data were independently double abstracted and cleaned for analysis. Descriptive analyses were performed. Results: We identified 12,980 citations from the literature search (12,976) and secondary means (44). Double review of titles and abstracts yielded 769 articles that underwent full data abstraction. Of these, 350 were further analyzed and are presented in separate reports in this supplement. Conclusions: This article presents the methods utilized in our systematic review. Because of the heterogenity of the study methods of the reports identified by this review, we did not conduct formal meta-analyses. However, these methods allow us to present a full landscape of the literature on PCV dosing schedules. PMID:24336060
Luthander, Joachim; Bennet, Rutger; Giske, Christian G; Nilsson, Anna; Eriksson, Margareta
This study explored the incidence and aetiology of bloodstream infections after patients received the pneumococcal conjugate vaccination and a risk-based intrapartum antibiotic prophylaxis against early onset sepsis caused by group B streptococcus. We also monitored clinically relevant antimicrobial resistance. We studied 3986 positive blood cultures from children up to 17 years of age at a paediatric hospital in Stockholm, Sweden, using data from medical records before and after the initiatives, to reduce early onset sepsis, were introduced in 2007 and 2008. Bloodstream infections caused by Streptococcus pneumoniae declined by 42% overall (5.6 to 3.2/100 000) and by 62% in previously healthy children under 36 months of age (24.2 to 9.2/100 000). Early onset sepsis caused by group B streptococcus declined by 60% (0.5 to 0.2/1000 live born children). Bacterial meningitis caused by these bacteria decreased by 70%. Staphylococcus aureus and various Gram-negative bacteria became the dominant pathogens, in both previously healthy children and those with underlying disease. Overall, antimicrobial resistance remained low between the two 5-year study periods. Pneumococcal conjugate vaccination and risk-based intrapartum antibiotic prophylaxis against group B streptococcus effectively decreased the incidence of bloodstream infections. Empirical antibiotic therapy should target Staphylococcus aureus in both community and hospital-acquired invasive bacterial infections. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.
Familial isolated congenital asplenia: a rare, frequently hereditary dominant condition, often detected too late as a cause of overwhelming pneumococcal sepsis. Report of a new case and review of 31 others.
Gilbert, Brigitte; Menetrey, Céline; Belin, Valérie; Brosset, Philippe; de Lumley, Lionel; Fisher, Alain
Congenital isolated asplenia may arise as a minor form of situs abnormalities or result from an unrelated specific defect of spleen development. It is a rare life-threatening condition and pneumococcal sepsis is often the first sign of the disease. We report on the case of a deceased 11-month-old girl and her father who developed recurrent pneumococcal meningitis. The fatal evolution in the girl was due to Streptococcus pneumoniae serotype 23 with intermediate penicillin sensitivity 4 h after amoxicillin (100 mg/kg i.v.) administration. Establishing the diagnosis of congenital isolated asplenia in the case of pneumococcal sepsis can be achieved by performing two easy and non-invasive investigations: searching for Howell-Jolly bodies on blood smears and performing ultrasound examination of the abdomen to look for the spleen. In the case of congenital isolated asplenia, use of appropriate prophylaxis could save the lives of affected children. Our review of the literature yielded 31 cases of congenital isolated asplenia. Thirteen were sporadic and 18 were familial cases involving eight families. in the case of Streptococcus pneumoniae sepsis, a systematic search for Howell-Jolly bodies on blood smears and ultrasound examination of the abdomen for the presence of asplenia should be mandatory to detect isolated congenital asplenia. If asplenia is found, potentially life-saving antibiotic prophylaxis and pneumococcal vaccination should be initiated.
Geneidy, Morsy R; El-Dahshan, Tarek A; Metwally, Karima M
Vaccination remains the primary preventive strategy in the elderly against Streptococcus pneumoniae and influenza infections. However, the effectiveness of vaccines decreases with increasing age and among patients. This study evaluated the opportunistic parasites infecting vaccinated and non-vaccinated pneumococcal children. The result showed that Invasive children (4%) had bacternrmid, septicemid and pneumococcal but no meningitis while the non-invasive ones (86%) had community acquired freunonia and otitis media. The non-vaccinated children were at risk of Ascaris lumbricoides, Ancylostoma duodenale, Trichuris trichura, Schistosoma mansoni, S. haematobium, bancroftian microfilaria, Enterobius vermicularis, Hymenolepis nana, Giadia lamblia, Entaemeba histolytica and Trichomonas vaginalis.
Barberán, José; Mensa, José
Invasive pulmonary aspergillosis (IPA) is a common infection in immunocompromised patients with hematological malignancies or allogenic stem cell transplantation, and is less frequent in the context of chronic obstructive pulmonary disease (COPD). Mucociliary activity impairment, immunosuppression due to the inhibition of alveolar macrophages and neutrophils by steroids, and receiving broad-spectrum antibiotics, play a role in the development of IPA in COPD patients. Colonized patients or those with IPA are older, with severe CODP stage (GOLD≥III), and have a higher number of comorbidities. The mortality rate is high due to the fact that having a definitive diagnosis of IPA in COPD patients is often difficult. The main clinical and radiological signs of IPA in these types of patients are non-specific, and tissue samples for definitive diagnosis are often difficult to obtain. The poor prognosis of IPA in COPD patients could perhaps be improved by faster diagnosis and prompt initiation of antifungal treatment. Some tools, such as scales and algorithms based on risk factors of IPA, may be useful for its early diagnosis in these patients. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.
Belkhir, L; Rodriguez-Villalobos, H; Vandercam, B; Marot, J C; Cornu, O; Lambert, M; Yombi, J C
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).
Oligbu, Godwin; Hsia, Yingfen; Folgori, Laura; Collins, Sarah; Ladhani, Shamez
Pneumococcal conjugate vaccines (PCVs) are highly effective in preventing pneumococcal invasive disease (IPD) due to serotypes included in the vaccines. The risk of vaccine-type IPD in immunised children (i.e. vaccine failure) has not been systematically assessed in countries with established PCV programmes. We undertook a systematic review of the English literature published from January 2000 to April 2016 to evaluate the vaccine schedule, risk factors, serotype distribution, clinical presentation and outcomes of vaccine failure in children vaccinated with the 7-valent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) vaccines. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles. We identified 1742 potential studies and included 20 publications involving 7584 participants in children aged ⩽5year-olds: 5202 received 2 doses followed by a booster in 10 studies, (68.6%), 64 (0.8%) received 3 doses without a booster in 2 studies, and 2318 received a 3+1 schedule (30.6%) in 8 studies. A total of 159 vaccine failure cases were identified, representing 2.1% [95% CI: 1.8-2.4%] of the reported IPD cases. Most studies did not report clinical characteristics or outcomes. Among eight studies reporting comorbidities, 33/77 patients (42.9%) had an underlying condition. The main serotypes associated with vaccine failure were 19F (51/128 cases with known serotype; 39.8%), 6B (33/128; 25.8%), and 4 (10/128; 7.8%). Only five studies reported patient outcomes, with a crude case fatality rate of 2.4% (2/85; 95%CI: 0.3-8.5%). Pneumococcal conjugate vaccines have been implemented in national immunisation programmes for more than a decade, yet there are only a few studies reporting vaccine failure. PCV failure is rare, irrespective of vaccine or schedule. Co-morbidity prevalence was high amongst vaccine failure cases but case fatality rate was relatively low. There is a need for more systematic reporting vaccine failure cases in countries
Walter, Katharine S; Pepin, Kim M; Webb, Colleen T; Gaff, Holly D; Krause, Peter J; Pitzer, Virginia E; Diuk-Wasser, Maria A
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. © 2016 The Author(s).
Waye, Arianna; Chuck, Anderson W; Jacobs, Philip; Tyrrell, Gregory; Kellner, James D
Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children and the elderly. In 2002, Alberta introduced a pneumococcal universal immunization program for children, using Pfizer's Prevnar 7, a 7-valent pneumococcal conjugate vaccine (PCV7). In this study, we explored the impact of the immunization program on the burden of disease and related health care costs in Alberta, in the context of serotype replacement. Using surveillance data from Alberta, we examined the change in costs averted as a result of a decline in invasive pneumococcal disease (IPD) cases caused by PCV7 serotypes, as well as the increase in costs due to serotype replacement. We also calculated the magnitude of positive externalities (indirect effects) in terms of costs averted. We found that following the introduction of PCV7 (2003-2008), the number of cases of IPD caused by vaccine serotypes declined significantly across all ages. Non-PCV7 IPD cases, on the other hand, increased. Net costs were averted as a result of the implementation of PCV7 universal vaccination in Alberta, after accounting for serotype replacement. On the basis of the analysis of serotype-specific pneumococcal data, the impact of the Prevnar public immunization program on direct health costs averted in Alberta as a result of reducing IPD cases caused by PCV7 strains amounted to $5.5 million (in 2008 Canadian dollars). However, the unintended effects of serotype replacement resulted in costs incurred of nearly $1.9 million. As a result, on net, the total cost savings for Alberta amounted to about $3.6 million. Irrespective of serotype replacement, the PCV7 immunization program has had a positive impact in terms of health benefits, which translates into health service costs averted.
Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J
The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular
Coskun-Ari, Fatma Filiz; Guldemir, Dilek; Durmaz, Riza
The life-threatening illnesses caused by Streptococcus pneumoniae have been declined significantly after the use of pneumococcal conjugate vaccines. Continuous monitoring of the vaccine serogroups/types is necessary to follow the changing epidemiology of invasive pneumococcal diseases. Recently, the sequential multiplex PCR approach, which uses several different sets of reactions, has been commonly adopted for determining capsular serogroups/types of S. pneumoniae isolates. In our study, we focused on development of a one-step multiplex PCR assay detecting all 1, 3, 4, 5, 6A/B, 7F, 9V, 14, 18C, 19A, 19F and 23F serogroups/types targeted by PCV13. The content of multiplex PCR mix and the cycling conditions were optimized in a manner that allowed rapid and accurate serotyping of a pneumococcal isolate by performing only a single amplification reaction. In our study of 182 clinical isolates, the one-step multiplex PCR assay exhibited 100% sensitivity and specificity, suggesting that its utilization can significantly reduce the use of traditional antiserum method requiring expensive reagents. PMID:23226519
Jewell, Brenda; Danila, Richard N.; Boxrud, David; Beall, Bernard; Van Beneden, Chris; Lynfield, Ruth
Nursing home residents are at high risk for invasive group A streptococcal (GAS) disease, and clusters of cases in nursing homes are common.To characterize the epidemiologic features of invasive GAS disease in nursing homes, we conducted active, statewide, population- and laboratory-based surveillance in Minnesota from April 1995 through 2006. Of 1,858 invasive GAS disease cases, 134 (7%) occurred in nursing home residents; 34 of these cases were identified as part of 13 clusters. Recognizing cases of GAS disease in nursing homes posed challenges. Measures to ensure identification of case-patients as residents of specific nursing homes need to be included in standard guidelines for the prevention and control of invasive GAS disease in this setting. PMID:18439360
Immunogenicity and Safety of 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Administered to Children With Sickle Cell Disease Between 8 Weeks and 2 Years of Age: A Phase III, Open, Controlled Study.
Sirima, Sodiomon B; Tiono, Alfred; Gansané, Zakaria; Siribié, Mohamadou; Zongo, Angèle; Ouédraogo, Alphonse; François, Nancy; Strezova, Ana; Dobbelaere, Kurt; Borys, Dorota
Immunogenicity, safety and reactogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in children with sickle cell disease (SCD), who are at increased risk for infections. In this phase III, open-label, single-center, controlled study in Burkina Faso (NCT01175083), children with SCD (S) or without SCD (NS) were assigned to 6 groups (N = 300): children 8-11 weeks of age (<6 months; <6S and <6NS groups) received 3 primary doses and a booster dose of PHiD-CV coadministered with routine childhood vaccines; children 7-11 months of age (7-11S and 7-11NS groups) received 2 primary doses and a booster dose of PHiD-CV; children 12-23 months of age (12-23S and 12-23NS groups) received 2 catch-up doses of PHiD-CV. Pneumococcal antibody responses were measured using 22F-inhibition enzyme-linked immunosorbent assay and functional opsonophagocytic activity. Responses to other antigens were measured by enzyme-linked immunosorbent assay. Adverse events were recorded. One month postprimary vaccination, for each vaccine serotype ≥98% of infants in the <6S and <6NS groups had antibody concentrations ≥0.2 µg/mL, except for 6B (≥85%) and 23F (≥89%). Immune responses to PHiD-CV after age-appropriate vaccination in children <2 years did not appear influenced by SCD. All infants were seroprotected/seropositive for diphtheria, tetanus and Bordetella pertussis antigens postprimary and booster vaccination. Safety and reactogenicity profiles were similar in children with or without SCD. PHiD-CV was immunogenic with an acceptable safety profile in children with and without SCD starting vaccination at 8 weeks to 23 months of age.
Janoir, Claire; Cohen, Robert; Levy, Corinne; Bingen, Edouard; Lepoutre, Agnès; Gutmann, Laurent; Varon, Emmanuelle
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
Zhen, Li; Pan, Min; Han, Jin; Yang, Xin; Ou, Yan-Mei; Liao, Can; Li, Dong-Zhi
To evaluate the efficacy of the sonographic cardiothoracic ratio (CTR) in early pregnancy for the prediction of fetal haemoglobin (Hb) Bart's disease. Over a 1.5-year period at a Chinese tertiary obstetric centre, women at risk of Hb Bart's disease were given the option of a non-invasive approach to exclude an affected pregnancy between 11 weeks and 13 weeks and 6 days of gestation, with a routine rescan after a 2-week interval. The fetal CTR, a sonographic marker, was assessed, and invasive testing followed in cases of fetal cardiomegaly. The diagnosis of fetal Hb Bart's disease was based on DNA analysis from chorionic villus sampling. Of 154 at-risk cases studied, five cases (four at 11 weeks of gestation) were subjected to direct invasive testing because of an unsatisfactory scan. Of the remaining 149 cases, non-invasive ultrasound examinations were performed successfully. Thirty-four (22.8%) affected pregnancies were revealed, including one picked up on rescan. The sensitivity and specificity of the non-invasive approach were 97.1% and 100%, respectively. The need for an invasive test was reduced by 74.7%, and all affected pregnancies except one were diagnosed before 14 weeks of gestation. CTR can differentiate reliably between pregnancies with and without Hb Bart's disease. This non-invasive approach for the exclusion of Hb Bart's disease can be used in early pregnancy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Aquarius, Annelies E; Denollet, Johan; Hamming, Jaap F; De Vries, Jolanda
Social support may influence the seeking of appropriate treatment. We examined social support and peripheral arterial disease (PAD) severity as determinants of treatment for PAD in younger and older patients. Consecutive PAD patients (N=203) completed the Perceived Social Support Scale. Treadmill-walking distance and ankle-brachial pressure index (ABPI) were measured. The main outcome was invasive treatment for PAD in the year following diagnosis. During follow-up, 48% of the patients underwent invasive treatment for PAD. Younger patients (
Morpeth, Susan C.; Ramadhani, Habib O.; Crump, John A.
Invasive non-Typhi Salmonella (NTS) is endemic in sub-Saharan Africa where it is a leading cause of bloodstream infection. Host risk factors have been established, but little is known about environmental reservoirs and predominant modes of transmission so prevention strategies are underdeveloped. While foodborne transmission from animals to humans predominates in high-income countries, it has been postulated that anthroponotic transmission both within and outside healthcare facilities may be important in sub-Saharan Africa. Antimicrobial resistance to ampicillin, trimethoprim-sulphamethoxazole and chloramphenicol is common; wider use of alternative agents may be warranted for empiric therapy. Vaccine development targeting the leading invasive NTS serotypes Typhimurium and Enteritidis shows promise. The clinical presentation of NTS bacteremia is non-specific and in the absence of blood culture may be confused with other febrile illnesses such as malaria. Much work remains to understand and control invasive NTS in sub-Saharan Africa. PMID:19591599
Taitel, Michael; Cohen, Ed; Duncan, Ian; Pegus, Cheryl
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
Arias-Constantí, Vanessa; Trenchs-Sainz de la Maza, Victoria; Sanz-Marcos, Nuria Elvira; Guitart-Pardellans, Carmina; Gené-Giralt, Amadeu; Luaces-Cubells, Carles
The last years an increase of severe cases of invasive disease (ID) due to Streptococcus pyogenes or streptococcus b-hemolytic group A (SGA) had been detected. The aim of this study was to analyze the epidemiology and the clinical features of ID due to SGA in a tertiary Pediatric Hospital. Retrospective study in a Pediatric hospital, of all in-patients with final diagnosis of ID due to SGA during 6 years (2009-2014). To consider ID, SGA had to be isolated in sterile samples; in patients with fascitis necroticans in skin samples or in any sample in patients with the diagnostic of Streptococcal Toxic Shock Syndrome (STSS). The SSTS was defined as hypotension and at least 2 of these criteria: renal failure, hepatic failure, acute respiratory distress, tissue necrosis or desquamative erythematous rash. Demographic data, type of infection, risk factors, clinical presentation, analytical data at admission, treatment, need for admission to a pediatric intensive care unit, microbiological data, hospital stay and evolution were collected. Fifty-two (52) cases were included (12/10,000 of all inpatients); 3 years-old was the medium age (p25-75: 1.4-6.9 years); 28 (53.8%) were boys. Fourteen patients (26.9%) had risk factors. Fever was the major symptom (51 patients, 98.1%). The skin lesions were the most frequent clinical manifestations found (21; 40.4%). In 50 (96%) cases, SGA was isolated in at least one sterile sample. Skin and soft tissue infections were diagnosed in 14 patients (26.9%), 14 (26.9%) pneumonias, 12 (23.1%) bones and joints infections, 10 (19.2%) SSTS, 6 (11.5%) occult bacteremia, 4 (7.7%) meningitis and 2 (3.8%) sepsis. Surgery was required in 18 cases (34.6%) and 17 patients (32.7%) needed intensive care. The medium hospital stay was 9.5 days (p25-75: 8-15 days). Three patients presented sequels and one patient died. The ID due to SGA was a rare but serious reason for hospital admission. Skin and soft tissue infections, and pleuroneumonia were the most
Sundaram, Neisha; Chen, Cynthia; Yoong, Joanne; Luvsan, Munkh-Erdene; Fox, Kimberley; Sarankhuu, Amarzaya; La Vincente, Sophie; Jit, Mark
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
Kambiré, Dinanibè; Soeters, Heidi M; Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Sangaré, Lassana; Yaméogo, Issaka; Sawadogo, Guetawendé; Ouédraogo, Abdoul-Salam; Ouangraoua, Soumeya; McGee, Lesley; Srinivasan, Velusamy; Aké, Flavien; Congo-Ouédraogo, Malika; Ky Ba, Absatou; Whitney, Cynthia G; Novak, Ryan T; Van Beneden, Chris
We evaluate early impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in Burkina Faso. Nationwide surveillance gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination, and strains serotyped using PCR. We compared incidence (cases per 100,000) in the early post-PCV13 period (2014 and 2015) to average pre-PCV13 incidence (2011-2013). In 2015, age-specific pneumococcal meningitis incidences were 8.7 (<1 year), 2.4 (1-4 years), 6.5 (5-14 years), and 2.6 (≥15 years). Compared to 2011-2013, PCV13-serotype incidence among all ages decreased by 32% (95%CI: 23%-39%), with significant decreases among children aged <1 year (76%; 95%CI: 64%-84%) and 1-4 years (58%, 95%CI: 40%-71%). Among all ages, incidence of PCV13 serotypes besides serotype 1 decreased (68%; 95%CI: 59%-75%), but serotype 1 incidence did not. Incidence of non-PCV13 serotypes also decreased (47%; 95%CI: 29%-60%). Among children aged <1 year, serotypes 12F/12A/12B/44/46 (17%), 1 (12%), and 5 (10%) predominated. Following PCV13 introduction, PCV13-serotype meningitis incidence in young children significantly decreased. PCV13 impact on serotype 1 and disease in older children and adults requires continued monitoring. Published by Elsevier Ltd.
Prozorovskiĭ, S T; Parikov, M A; Tsoĭ, V G; Shneĭder, Iu A
The authors discuss specific using minimally invasive surgical technique of ablation of the saphenous vein trunks by a modified Oesch PIN stripper method proposed by the authors. An experience with surgical treatment of 245 patients with varicose veins using the same modified technique is analyzed. Postoperative complications and medium-term results are evaluated.
Siegel, Steven J.; Roche, Aoife M.; Weiser, Jeffrey N.
Summary Much of the mortality attributed to influenza virus is due to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae. However, mechanisms underlying this co-infection are incompletely understood. We find that prior influenza infection enhances pneumococcal colonization of the murine nasopharynx, which in-turn promotes bacterial spread to the lungs. Influenza accelerates bacterial replication in vivo, and sialic acid, a major component of airway glycoconjugates, is identified as the host-derived metabolite that stimulates pneumococcal proliferation. Influenza infection increases sialic acid and sialylated mucin availability, and enhances desialylation of host glycoconjugates. Pneumococcal genes for sialic acid catabolism are required for influenza to promote bacterial growth. Decreasing sialic acid availability in vivo by genetic deletion of the major airway mucin Muc5ac or mucolytic treatment limits influenza-induced pneumococcal replication. Our findings suggest that higher rates of disease during co-infection could stem from influenza-provided sialic acid, which increases pneumococcal proliferation, colonization and aspiration. PMID:25011108
Conklin, Laura M; Bigogo, Godfrey; Jagero, Geofrey; Hampton, Lee; Junghae, Muthoni; da Gloria Carvalho, Maria; Pimenta, Fabiana; Beall, Bernard; Taylor, Thomas; Plikaytis, Brian; Laserson, Kayla F; Vulule, John; Van Beneden, Chris; Whitney, Cynthia G; Breiman, Robert F; Feikin, Daniel R
Streptococcus pneumoniae is a leading cause of pneumonia, meningitis and sepsis in developing countries, particularly among children and HIV-infected persons. Pneumococcal oropharyngeal (OP) or nasopharyngeal (NP) colonization is a precursor to development of invasive disease. New conjugate vaccines hold promise for reducing colonization and disease. Prior to introduction of 10-valent pneumococcal conjugate vaccine (PCV10), we conducted a cross-sectional survey among HIV-infected parents of children <5 years old in rural Kenya. Other parents living with an HIV-infected adult were also enrolled. After broth enrichment, NP and OP swabs were cultured for pneumococcus. Serotypes were identified by Quellung. Antimicrobial susceptibility was performed using broth microdilution. We enrolled 973 parents; 549 (56.4%) were HIV-infected, 153 (15.7%) were HIV-uninfected and 271 (27.9%) had unknown HIV status. Among HIV-infected parents, the median age was 32 years (range 15-74) and 374/549 (68%) were mothers. Pneumococci were isolated from 237/549 (43.2%) HIV-infected parents and 41/153 (26.8%) HIV-non-infected parents (p = 0.0003). Colonization with PCV10 serotypes was not significantly more frequent in HIV-infected (12.9%) than HIV-uninfected parents (11.8%; p = 0.70). Among HIV-infected parents, cooking site separate from sleeping area and CD4 count >250 were protective (OR = 0.6; 95% CI 0.4, 0.9 and OR = 0.5; 95% CI 0.2, 0.9, respectively); other associations were not identified. Among 309 isolates tested from all parents, 255 (80.4%) were penicillin non-susceptible (MIC ≥0.12 μg/ml). Prevalence of pneumococcal colonization is high among HIV-infected parents in rural Kenya. If young children are the pneumococcal reservoir for this population, PCV10 introduction may reduce vaccine-type colonization and disease among HIV-infected parents through indirect protection.
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
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
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
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.
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
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
Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial.
O'Grady, Kerry-Ann F; Grimwood, Keith; Cripps, Allan; Mulholland, Edward K; Morris, Peter; Torzillo, Paul J; Wood, Nicholas; Smith-Vaughan, Heidi; Revell, Amber; Wilson, Andrew; Van Asperen, Peter; Richmond, Peter; Thornton, Ruth; Rablin, Sheree; Chang, Anne B
Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW₁₃₅) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ≥6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ≥6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children
Kariuki, Samuel; Gordon, Melita A.; Feasey, Nicholas; Parry, Christopher M
Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20–30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50–75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. PMID:25912288
Kariuki, Samuel; Gordon, Melita A; Feasey, Nicholas; Parry, Christopher M
Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness estimated at nearly 3.4 million cases and over 600,000 deaths annually especially in resource-limited settings. Invasive non-typhoidal Salmonella (iNTS) infections are particularly important in immunosuppressed populations especially in sub-Saharan Africa, causing a mortality of 20-30% in vulnerable children below 5 years of age. In these settings, where routine surveillance for antimicrobial resistance is rare or non-existent, reports of 50-75% multidrug resistance (MDR) in NTS are common, including strains of NTS also resistant to flouroquinolones and 3rd generation cephalosporins. Typhoid (enteric) fever caused by Salmonella Typhi and Salmonella Paratyphi A remains a major public health problem in many parts of Asia and Africa. Currently over a third of isolates in many endemic areas are MDR, and diminished susceptibility or resistance to fluoroquinolones, the drugs of choice for MDR cases over the last decade is an increasing problem. The situation is particularly worrying in resource-limited settings where the few remaining effective antimicrobials are either unavailable or altogether too expensive to be afforded by either the general public or by public health services. Although the prudent use of effective antimicrobials, improved hygiene and sanitation and the discovery of new antimicrobial agents may offer hope for the management of invasive salmonella infections, it is essential to consider other interventions including the wider use of WHO recommended typhoid vaccines and the acceleration of trials for novel iNTS vaccines. The main objective of this review is to describe existing data on the prevalence and epidemiology of antimicrobial resistant invasive Salmonella infections and how this affects the management of these infections, especially in endemic developing countries. Copyright © 2015. Published by Elsevier Ltd.
Berman, Melissa; Dubé, Eve; Quach, Caroline
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.
Vintiñi, Elisa; Villena, Julio; Raya, Raul
Most studies of Lactococcus lactis as delivery vehicles of pneumococcal antigens are focused on the effectiveness of mucosal recombinant vaccines against Streptococcus pneumoniae in animal models. At present, there are three types of pneumococcal vaccines: capsular polysaccharide pneumococcal vaccines (PPV), protein-polysaccharide conjugate pneumococcal vaccines (PCV) and protein-based pneumococcal vaccines (PBPV). Only PPV and PCV have been licensed. These vaccines, however, do not represent a definitive solution. Novel, safe and inexpensive vaccines are necessary, especially in developing countries. Probiotic microorganisms such as lactic acid bacteria (LAB) are an interesting alternative for their use as vehicles in pneumococcal vaccines due to their GRAS (Generally Recognized As Safe) status. Thus, the adjuvanticity of Lactococcus lactis by itself represents added value over the use of other bacteria, a question dealt with in this review. In addition, the expression of different pneumococcal antigens as well as the use of oral and nasal mucosal routes of administration of lactococcal vaccines is considered. The advantages of nasal live vaccines are evident; nonetheless, oral vaccines can be a good alternative when the adequate dose is used. Another point addressed here is the use of live versus inactivated vaccines. In this sense, few researchers have focused on inactivated strains to be used as vaccines against pneumoccoccus. The immunogenicity of live vaccines is better than the one afforded by inactivated ones; however, the probiotic-inactivated vaccine combination has improved this matter considerably. The progress made so far in the protective immune response induced by recombinant vaccines, the successful trials in animal models and the safety considerations of their application in humans suggest that the use of recombinant vaccines represents a good short-term option in the control of pneumococcal diseases. PMID:21326831
Pini-Prato, Alessio; Faticato, Maria Grazia; Barabino, Arrigo; Arrigo, Serena; Gandullia, Paolo; Mazzola, Cinzia; Disma, Nicola; Montobbio, Giovanni; Mattioli, Girolamo
The incidence of paediatric inflammatory bowel disease (PIBD) has dramatically increased in the last 20 years. Although first reported in mid 1970s’, diagnostic laparoscopy has started to be routinely adopted in paediatric surgical practice since late 1990s’. Minimally invasive surgery was first limited to diagnostic purposes. After 2002 it was also applied to the radical treatment of PIBD, either Crohn’s disease (CD) or Ulcerative colitis. During the last decade minimally invasive approaches to PIBD have gained popularity and have recently became the “gold standard” for the treatment of such invalidating and troublesome chronic diseases. The authors describe and track the historical evolution of minimally invasive surgery for PIBD and address all available opportunities, including most recent advancements such as robotic surgery, single port approaches and minimally invasive treatment of perianal fistulising CD. A systematic review of all series of PIBD treated with minimally invasive approaches published so far is provided in order to determine the incidence and type of patients’ complications reported up to present days. The authors also describe their experience with minimally invasive surgery for PIBD and will report the results of 104 laparoscopic procedures performed in a series of 61 patients between January 2006 and December 2014. PMID:26525138
Schouten, Marcel; de Boer, J Daan; Kager, Liesbeth M; Roelofs, Joris J T H; Meijers, Joost C M; Esmon, Charles T; Levi, Marcel; van 't Veer, Cornelis; van der Poll, Tom
Pneumococcal pneumonia is a frequent cause of gram-positive sepsis and has a high mortality. The endothelial protein C receptor (EPCR) has been implicated in both the activation of protein C (PC) and the anti-inflammatory actions of activated (A)PC. The aim of this study was to determine the role of the EPCR in murine pneumococcal pneumonia and sepsis. Wild-type (WT), EPCR knockout (KO) and Tie2-EPCR mice, which overexpress EPCR on the endothelium, were infected intranasally (pneumonia) or intravenously (sepsis) with viable Streptococcus pneumoniae and euthanised at 24 or 48 hours after initiation of the infection for analyses. Pneumonia did not alter constitutive EPCR expression on pulmonary endothelium but was associated with an influx of EPCR positive neutrophils into lung tissue. In pneumococcal pneumonia EPCR KO mice demonstrated diminished bacterial growth in the lungs and dissemination to spleen and liver, reduced neutrophil recruitment to the lungs and a mitigated inflammatory response. Moreover, EPCR KO mice displayed enhanced activation of coagulation in the early phase of disease. Correspondingly, in pneumococcal sepsis EPCR KO mice showed reduced bacterial growth in lung and liver and attenuated cytokine release. Conversely, EPCR-overexpressing mice displayed higher bacterial outgrowth in lung, blood, spleen and liver in pneumococcal sepsis. In conclusion, EPCR impairs antibacterial defense in both pneumococcal pneumonia and sepsis, which is associated with an enhanced pro-inflammatory response.
Bruce, Michael G.; Bruden, Dana; Zulz, Tammy; Reasonover, Alisa; Hurlburt, Debby; Hennessy, Thomas
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
Chaguza, Chrispin; Cornick, Jennifer E; Andam, Cheryl P; Gladstone, Rebecca A; Alaerts, Maaike; Musicha, Patrick; Peno, Chikondi; Bar-Zeev, Naor; Kamng'ona, Arox W; Kiran, Anmol M; Msefula, Chisomo L; McGee, Lesley; Breiman, Robert F; Kadioglu, Aras; French, Neil; Heyderman, Robert S; Hanage, William P; Bentley, Stephen D; Everett, Dean B
Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in clade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine serotype in clade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in clade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines
Shi, Bibo; Grimm, Lars J.; Mazurowski, Maciej A.; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.
Predicting the risk of occult invasive disease in ductal carcinoma in situ (DCIS) is an important task to help address the overdiagnosis and overtreatment problems associated with breast cancer. In this work, we investigated the feasibility of using computer-extracted mammographic features to predict occult invasive disease in patients with biopsy proven DCIS. We proposed a computer-vision algorithm based approach to extract mammographic features from magnification views of full field digital mammography (FFDM) for patients with DCIS. After an expert breast radiologist provided a region of interest (ROI) mask for the DCIS lesion, the proposed approach is able to segment individual microcalcifications (MCs), detect the boundary of the MC cluster (MCC), and extract 113 mammographic features from MCs and MCC within the ROI. In this study, we extracted mammographic features from 99 patients with DCIS (74 pure DCIS; 25 DCIS plus invasive disease). The predictive power of the mammographic features was demonstrated through binary classifications between pure DCIS and DCIS with invasive disease using linear discriminant analysis (LDA). Before classification, the minimum redundancy Maximum Relevance (mRMR) feature selection method was first applied to choose subsets of useful features. The generalization performance was assessed using Leave-One-Out Cross-Validation and Receiver Operating Characteristic (ROC) curve analysis. Using the computer-extracted mammographic features, the proposed model was able to distinguish DCIS with invasive disease from pure DCIS, with an average classification performance of AUC = 0.61 +/- 0.05. Overall, the proposed computer-extracted mammographic features are promising for predicting occult invasive disease in DCIS.
MacLennan, Calman A; Msefula, Chisomo L; Gondwe, Esther N; Gilchrist, James J; Pensulo, Paul; Mandala, Wilson L; Mwimaniwa, Grace; Banda, Meraby; Kenny, Julia; Wilson, Lorna K; Phiri, Amos; MacLennan, Jenny M; Molyneux, Elizabeth M; Molyneux, Malcolm E; Graham, Stephen M
Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0-15 years) and 52/256 children (20%; 95%CI 15-25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71-82%), 123/240 (51%; 95%CI 45-58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36-49%) had an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8-35.1), dyspnea (OR 4.2; 95%CI 1.5-12.0) and HIV infection (OR 3.3; 95%CI 1.1-10.2) were independent risk factors for inpatient mortality. Invasive Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children.
Vila-Córcoles, Angel; Ochoa-Gondar, Olga; Satué, Eva; de Diego, Cinta; Vila-Rovira, Marc; Jariod, Manel
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.
Grau, I; Ardanuy, C; Schulze, M H; Liñares, J; Pallares, R
Polymicrobial bacteraemia involving Streptococcus pneumoniae and other bacteria (e.g. Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Haemophilus influenza, viridans streptococci, Salmonella spp.) occurred in 3.4% of our pneumococcal bacteraemia cases. Compared with 308 controls (monomicrobial bacteraemia), the 77 polymicrobial cases included more males (83 vs 62%, p = 0.001), had serious underlying diseases (100 vs 80%, p < 0.001), abdominal infection (18 vs 5%, p < 0.001), nosocomial infection (33 vs 8%, p < 0.001), shock (40 vs 13%, p < 0.001), and higher mortality (52 vs 18%, p < 0.001). Clinicians must be aware that some patients with pneumococcal bacteraemia may have other bacteria in their blood, which would confer higher mortality and may lead to inappropriate or incomplete antibiotic therapy.
Moberley, Sarah; Licciardi, Paul V; Balloch, Anne; Andrews, Ross; Leach, Amanda J; Kirkwood, Marie; Binks, Paula; Mulholland, Kim; Carapetis, Jonathan; Tang, Mimi L K; Skull, Sue
Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3μg/ml but <4.0μg/ml; or a post-vaccination antibody concentration >4.0μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose. All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of serotypes with a positive response. Indigenous participants demonstrated a
A rapid test for an infectious disease that can be used at point-of-care at a physician's office, a pharmacy, or in the field is critical for the prompt and appropriate therapeutic intervention. Ultimately by treating infections early on will decrease transmission of the pathogen. In contrast to metabolic diseases or cancer where multiple biomarkers are required, infectious disease targets (e.g. antigen, antibody, nucleic acid) are simple and specific for the pathogen causing the disease. Our laboratory has focused on three major infectious disease; HIV, Tuberculosis, and Malaria. These diseases are pandemic in much of the world thus putting natives, tourists and military personnel at risk for becoming infected, and upon returning to the U.S., transmitting these diseases to their contacts. Our devices are designed to detect antigens, antibodies or nucleic acids in blood or saliva samples in less than 30 minutes. An overview describing the current status of each of the three diagnostic platforms is presented. These microfluidic point-of-care devices will be relatively inexpensive, disposable, and user friendly.
Kohler, Sylvia; Voß, Franziska; Gómez Mejia, Alejandro; Brown, Jeremy S; Hammerschmidt, Sven
Streptococcus pneumoniae (pneumococcus) has evolved sophisticated strategies to survive in several niches within the human body either as a harmless commensal or as a serious pathogen causing a variety of diseases. The dynamic interaction between pneumococci and resident host cells during colonization of the upper respiratory tract and at the site of infection is critical for bacterial survival and the development of disease. Pneumococcal lipoproteins are peripherally anchored membrane proteins and have pivotal roles in bacterial fitness including envelope stability, cell division, nutrient acquisition, signal transduction, transport (as substrate-binding proteins of ABC transporter systems), resistance to oxidative stress and antibiotics, and protein folding. In addition, lipoproteins are directly involved in virulence-associated processes such as adhesion, colonization, and persistence through immune evasion. Conversely, lipoproteins are also targets for the host response both as ligands for toll-like receptors and as targets for acquired antibodies. This review summarizes the multifaceted roles of selected pneumococcal lipoproteins and how this knowledge can be exploited to combat pneumococcal infections. © 2016 Federation of European Biochemical Societies.
Klaile, Yvonne; Schlack, Katrin; Boegemann, Martin; Steinestel, Julie; Schrader, Andres Jan; Krabbe, Laura-Maria
Bladder cancer (BC) is a frequent type of carcinoma with an estimated incidence of approximately 100,000 men and women each year in the European Union (EU) with an associated mortality of 30,000 of these patients. In more than 70% the disease is diagnosed in a non-muscle invasive stage with the chance of minimally invasive, local treatment only, which might be required repetitively due to high rate of recurrence. In contrast, muscle invasive or metastatic stages need multimodal treatment strategies including surgical treatment and chemotherapy (CTX) in neoadjuvant (NAC), adjuvant, or palliative settings. Therapy recommendations and guidelines mainly refer to the most common histological type of BC, pure urothelial carcinoma (UC). However, BC can be classified as urothelial and non-UC. Non-urothelial BC and variants of UC account for up to 25% of all BCs. Further discrimination can be made into epithelial and non-epithelial non-UC. Most of the non-UCs are of epithelial origin (approximately 90%) including squamous-cell carcinoma, adenocarcinoma and small-cell carcinoma. Non-epithelial tumors are rare and include variants as sarcoma, carcinosarcoma, paraganglioma, melanoma and lymphoma. Even though it is unclear whether the prognosis of non-urothelial cancer truly differs from that of UC, there is evidence that additional variant histology might prognosticate an impaired prognosis. Accordingly, aggressive behavior and often advanced stages at primary presentation are frequently observed in non-UC arguing for radical and sometimes different treatment strategies as compared to pure UC. This review aims to summarize the available data for the most common histological variants of non-urothelial BC.
Buschmann, Ivo R; Voskuil, Michiel; van Royen, Niels; Hoefer, Imo E; Scheffler, Klaus; Grundmann, Sebastian; Hennig, Jürgen; Schaper, Wolfgang; Bode, Christoph; Piek, Jan J
Our current knowledge regarding the efficacy of factors stimulating collateral artery growth in the peripheral circulation primarily stems from models in small animals. However, experimental models in large sized animals are a prerequisite for extrapolation of growth factor therapy to patients with peripheral atherosclerotic obstructive disease. Therefore, we have developed a novel porcine femoral artery ligation model using non-invasive and invasive evaluation techniques. In 12 young farm pigs and nine older minipigs, a ligation of the superficial femoral artery was performed. Using an intra-arterial catheter, phosphate buffered saline (PBS) was administered with a first-pass over the collateral vascular bed. Directly after ligation as well as after 2 weeks of continuous infusion of PBS, perfusion of the leg was measured using various flow and pressure parameters. Using a pump driven extracorporal system, collateral conductance was determined under maximal vasodilatation. Conductance decreased after acute ligation to similar levels in both young farm pigs as well as the older minipigs (both 9.3% of normal perfusion) and recovered after 2 weeks to a higher value in farm pigs compared with minipigs (22.4 vs. 12.7% of normal; P<0.05). Angiography using both X-ray and magnetic resonance imaging was performed to visualize the formed collateral arteries. To the best of our knowledge this is the first in vivo pig model for hemodynamic assessment of growth of collateral arteries in the peripheral circulation, that is suitable for evaluation of arteriogenic effects of growth factors or genes.
Everett, Dean B.; Mukaka, Mavuto; Denis, Brigitte; Gordon, Stephen B.; Carrol, Enitan D.; van Oosterhout, Joep J.; Molyneux, Elizabeth M.; Molyneux, Malcolm; French, Neil; Heyderman, Robert S.
Objective To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis. Methods Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection. Results 4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = −0.91; p<0.001). Conclusion During 2004–2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes. PMID:21423577
Sobanjo-ter Meulen, Ajoke; Vesikari, Timo; Malacaman, Edgardo A; Shapiro, Steven A; Dallas, Michael J; Hoover, Patricia A; McFetridge, Richard; Stek, Jon E; Marchese, Rocio D; Hartzel, Jonathan; Watson, Wendy J; Musey, Luwy K
Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) in children has led to significant reduction in pneumococcal disease in children and adults. However, diseases caused by serotypes not included in PCV7 have increased. A 15-valent pneumococcal conjugate vaccine (PCV15) containing serotypes in PCV7 and 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in toddlers 12 to 15 months of age. Ninety toddlers who completed an infant series with PCV7 received a single dose of either aluminum-adjuvanted PCV15, nonadjuvanted PCV15, or PCV7. Injection-site and systemic adverse events (AEs) were collected for 14 days postvaccination and serious AEs (SAEs) were collected for 30 days postvaccination. Solicited AEs included local (pain/tenderness, swelling, nodule and redness) and systemic (fatigue, arthralgia and myalgia) AEs. Serotype-specific immunoglobulin G (IgG) and opsonophagocytic (OPA) responses were measured immediately prior and 30 days postvaccination. Incidences of local and systemic AEs were comparable across vaccine groups. The majority of reported events, regardless of vaccine received, were transient and of mild to moderate intensity. No clinically significant differences were observed when comparing duration and severity of AEs. No vaccine-related SAEs or discontinuations from the study due to AEs were reported. Pneumococcal IgG concentrations and OPA titers increased postvaccination, with appreciable fold rises for all serotypes. Antibody levels were comparable between both PCV15 formulations and generally comparable to PCV7 for the shared serotypes. Both formulations of PCV15 display acceptable safety profiles and induce IgG and OPA responses to all vaccine serotypes.
van Hoek, Albert Jan; Miller, Elizabeth
Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years. A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results. The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust. Vaccinating
Mesk, Mohammed; Mahdjoub, Tewfik; Gourbière, Sébastien; Rabinovich, Jorge E; Menu, Frédéric
Demographic processes and spatial dispersal of Triatoma dimidiata, a triatomine species vector of Chagas disease, are modeled by integrodifference equations to estimate invasion capacity of this species under different ecological conditions. The application of the theory of orthogonal polynomials and the steepest descent method applied to these equations, allow a good approximation of the abundance of the adult female population and the invasion speed. We show that: (1) under the same mean conditions of demography and dispersal, periodic spatial dispersal results in an invasion speed 2.5 times larger than the invasion speed when spatial dispersal is continuous; (2) when the invasion speed of periodic spatial dispersal is correlated to adverse demographic conditions, it is 34.7% higher as compared to a periodic dispersal that is correlated to good demographic conditions. From our results we conclude, in terms of triatomine population control, that the invasive success of T. dimidiata may be most sensitive to the probability of transition from juvenile to adult stage. We discuss our main theoretical predictions in the light of observed data in different triatomines species found in the literature. Copyright © 2016 Elsevier Ltd. All rights reserved.
Teatero, Sarah; Ferrieri, Patricia; Fittipaldi, Nahuel
To further understand the emergence of serotype IV group B Streptococcus (GBS) invasive disease, we used whole-genome sequencing to characterize 3 sequence type 468 strains isolated from neonates in Minnesota, USA. We found that strains of tetracycline-resistant sequence type 468 GBS have acquired virulence genes from a putative clonal complex 17 GBS donor by recombination.
de Soárez, Patrícia Coelho; Sartori, Ana Marli Christovam; Freitas, Angela Carvalho; Nishikawa, Álvaro Mitsunori; Novaes, Hillegonda Maria Dutilh
Objective 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. Methods 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. Results 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. Conclusion 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. PMID:26114297
Lower respiratory tract infections are among the most important causes of childhood mortality worldwide, more than 2 million children die due to pneumonia every year. A number of infections caused by the main pathogens related to pneumonia can be prevented through vaccination ( S. pneumoniae, H. influenzae type-b, morbilli, pertussis, influenza). In the last decade, after the introduction of the 7-valent pneumococcal conjugated vaccine (PCV), the epidemiological background of childhood pneumonia has changed. Recently, several studies have been performed to collect data and evidences about the efficacy of PCV against noninvasive pneumococcal diseases (e.g. pneumonia, otitis media). These investigations showed 10-50% decrease of all pneumonia cases, 10-30% decrease of radiologically diagnosed pneumonia, and 50-70% decrease of the incidence of pneumococcal pneumonia in children. The aim of this review was to determine the role of the PCV in the prevention of childhood pneumonia according to the medical literature, and to summarize the efforts of global organizations (WHO, UNICEF, GAVI) in the fight against pneumonia in children.
Cernuschi, Tania; Schwalbe, Nina; Jones, Andrew; Berndt, Ernst R; McAdams, Susan
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
Reyes, Luis F.; Restrepo, Marcos I.; Hinojosa, Cecilia A.; Soni, Nilam J.; Shenoy, Anukul T.; Gilley, Ryan P.; Gonzalez-Juarbe, Norberto; Noda, Julio R.; Winter, Vicki T.; de la Garza, Melissa A.; Shade, Robert E.; Coalson, Jacqueline J.; Giavedoni, Luis D.; Anzueto, Antonio; Orihuela, Carlos J.
Rationale Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. Objective To develop a non-human primate model of pneumococcal pneumonia. Methods Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Results Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. Conclusions We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes. PMID:27855182
Montes, M; Ardanuy, C; Tamayo, E; Domènech, A; Liñares, J; Pérez-Trallero, E
The incidence, clinical manifestations, and circulating clones involved in Streptococcus pyogenes invasive disease was analyzed in two regions of Spain between 1998 and 2009. The annual average incidence of invasive disease was 2 episodes per 100,000 inhabitants (3.1 for children and 1.9 for adults). The most frequent clinical manifestations were cellulitis (41.3%), bacteremia without focus (19.0%), streptococcal toxic shock syndrome (12.6%), and pneumonia (7.7%). Among 247 invasive isolates analyzed, the most prevalent clones were emm1/ST28 (27.9%), emm3/ST15-406 (9.8%), and emm4/ST39 (6.5%). The emm1/ST28 clone was the only clone detected each year throughout the study period and was associated with more than one third of all fatal outcomes. When invasive isolates were compared with 1,189 non-invasive isolates, the emm1/ST28 clone was significantly associated with invasive disease. The speA and ssa genes were more frequent among invasive emm1 and emm4 isolates, respectively. Forty-two (17%) invasive isolates were resistant to erythromycin (21 harbored the mef gene and 21 the ermB or ermA genes). Twenty-two (8.9%) isolates had reduced susceptibility to ciprofloxacin (minimum inhibitory concentration [MIC] 2-8 μg/mL) and 32 (13%) were tetracycline-resistant (tetM or tetO gene). In conclusion, the emm1 type was overrepresented among invasive cases and was associated with high mortality rates.
Cross, Paul C; Johnson, Philip L F; Lloyd-Smith, James O; Getz, Wayne M
Early theoretical work on disease invasion typically assumed large and well-mixed host populations. Many human and wildlife systems, however, have small groups with limited movement among groups. In these situations, the basic reproductive number, R0, is likely to be a poor predictor of a disease pandemic because it typically does not account for group structure and movement of individuals among groups. We extend recent work by combining the movement of hosts, transmission within groups, recovery from infection and the recruitment of new susceptibles into a stochastic model of disease in a host metapopulation. We focus on how recruitment of susceptibles affects disease invasion and how population structure can affect the frequency of superspreading events (SSEs). We show that the frequency of SSEs may decrease with the reduced movement and the group sizes due to the limited number of susceptible individuals available. Classification tree analysis of the model results illustrates the hierarchical nature of disease invasion in host metapopulations. First, the pathogen must effectively transmit within a group (R0>1), and then the pathogen must persist within a group long enough to allow for movement among the groups. Therefore, the factors affecting disease persistence--such as infectious period, group size and recruitment of new susceptibles--are as important as the local transmission rates in predicting the spread of pathogens across a metapopulation.
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
Marcial, José M; Pérez, Reynerio; Vargas, Pedro; Franqui-Rivera, Hilton
Peripheral arterial disease (PAD) is a significant cause of morbidity and mortality worldwide. Lifestyle changes, like the cessation of the use of tobacco as well as a modification of dietary and exercise habits, can be the most cost-effective interventions in patients with PAD. Smocking cessation is the most important intervention, since it increases survival in these patients. Antiplatelet therapy is an essential component in the treatment of peripheral arterial disease (PAD) of the lower extremities. In addition to delaying arterial obstructive progression, these agents are most usefull in reducing adverse cardiovascular events such as non-fatal myocardial infarction (MI), stroke and vascular death. Mainstay of treatment continues to be aspirin monotherapy (75-325mg daily). Current treatment for lower extremity PAD is directed towards the relief of symptoms and improvement in QoL. The two agents which have consistently been found to be most efficient in achieving these goals are cilostazol and naftidrofuryl oxalate. Naftidrofuryl oxalate may emerge as the most efficient and cost-effective treatment for symptom relief.
Allan, Brian F.; Dutra, Humberto P.; Goessling, Lisa S.; Barnett, Kirk; Chase, Jonathan M.; Marquis, Robert J.; Pang, Genevieve; Storch, Gregory A.; Thach, Robert E.; Orrock, John L.
Despite the ubiquity of invasive organisms and their often deleterious effects on native flora and fauna, the consequences of biological invasions for human health and the ecological mechanisms through which they occur are rarely considered. Here we demonstrate that a widespread invasive shrub in North America, Amur honeysuckle (Lonicera maackii), increases human risk of exposure to ehrlichiosis, an emerging infectious disease caused by bacterial pathogens transmitted by the lone star tick (Amblyomma americanum). Using large-scale observational surveys in natural areas across the St. Louis, Missouri region, we found that white-tailed deer (Odocoileus virginianus), a preeminent tick host and pathogen reservoir, more frequently used areas invaded by honeysuckle. This habitat preference translated into considerably greater numbers of ticks infected with pathogens in honeysuckle-invaded areas relative to adjacent honeysuckle-uninvaded areas. We confirmed this biotic mechanism using an experimental removal of honeysuckle, which caused a decrease in deer activity and infected tick numbers, as well as a proportional shift in the blood meals of ticks away from deer. We conclude that disease risk is likely to be reduced when honeysuckle is eradicated, and suggest that management of biological invasions may help ameliorate the burden of vector-borne diseases on human health. PMID:20937859
Chandesris, M-O; Hot, A; Dannaoui, E; Bougnoux, M-E; Viard, J-P; Dupont, B; Lortholary, O
Coccidioidomycosis is an endemic mycosis in the southwest of United States resulting from the inhalation of arthrospores present in desert soil. The authors present a case of uncomplicated pulmonary coccidioidomycosis in a healthy woman, acquired during a recent trip to California. The initial clinical presentation first suggested a diagnosis of community-acquired pneumonia, then of tuberculosis. The diagnosis was finally reached with blood tests and mycological culture of broncho-alveolar lavage fluid. The final identification of Coccidioides immitis was made by molecular analysis. Clinical resolution of the infection was obtained after three months of posaconazole treatment. Coccidioidomycosis is a major cause of pneumonia. Its diagnosis requires specific investigation such as mycological culture, histology, blood tests and molecular biology helps to identify the species. The progression of the disease as well as the associated immunocellular deficit are strictly correlated with the onset of complications and late relapses despite an adequate initial treatment using antifungal molecules and/or surgery.
Duval, Linda; George, Cheryl; Hedrick, Nellie; Woodruff, Sandra; Kleinpeter, Myra A
Vaccinations are available for primary prevention of many infections in adults. Morbidity and mortality from invasive diseases such as influenza and Streptococcus pneumoniae (pneumococcus) remain high and may be largely preventable by vaccination of high-risk adults, including dialysis patients. The current 23-valent vaccine-efficacious, with a low adverse event profile-is widely available. Revaccination is also recommended in patients with immunocompromising conditions, including chronic kidney disease. Despite having many opportunities to be vaccinated, adult hemodialysis and peritoneal dialysis patients are often missed During the recent H1N1 influenza outbreak, we conducted a performance improvement project to increase the vaccination rates for pneumococcal pneumonia, hepatitis B, and influenza, with a special focus on prevention. The project included an education phase, baseline assessment of vaccination rates, intervention, and a follow-up assessment of vaccination rates. The geographic jurisdiction of ESRD Network 13 encompasses the states of Arkansas, Louisiana, and Oklahoma. At the beginning of the network-wide project, the documented state-specific rates for influenza immunization were below the average influenza immunization rates for adults reported by Centers for Disease Control and Prevention and far below its target for adults. Our improvement project incorporated educational interventions to improve patient acceptance of vaccinations, educational interventions to improve staff participation in quality improvement activities, and improved techniques of quality improvement data collection and analysis by participants. During this project, the immunization rates for hepatitis B and pneumococcal pneumonia were also reviewed. At project's conclusion, improvement was demonstrated in all three focus areas, with statistically significant improvements noted in both influenza and pneumococcus vaccination rates. The use of educational interventions to improve
Jenney, Adam; Kado, Joseph; Good, Michael F.; Batzloff, Michael; Waqatakirewa, Lepani; Mullholland, E. Kim; Carapetis, Jonathan R.
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
Capinha, César; Larson, Eric R; Tricarico, Elena; Olden, Julian D; Gherardi, Francesca
Climate change will require species to adapt to new conditions or follow preferred climates to higher latitudes or elevations, but many dispersal-limited freshwater species may be unable to move due to barriers imposed by watershed boundaries. In addition, invasive nonnative species may expand into new regions under future climate conditions and contribute to the decline of native species. We evaluated future distributions for the threatened European crayfish fauna in response to climate change, watershed boundaries, and the spread of invasive crayfishes, which transmit the crayfish plague, a lethal disease for native European crayfishes. We used climate projections from general circulation models and statistical models based on Mahalanobis distance to predict climate-suitable regions for native and invasive crayfishes in the middle and at the end of the 21st century. We identified these suitable regions as accessible or inaccessible on the basis of major watershed boundaries and present occurrences and evaluated potential future overlap with 3 invasive North American crayfishes. Climate-suitable areas decreased for native crayfishes by 19% to 72%, and the majority of future suitable areas for most of these species were inaccessible relative to native and current distributions. Overlap with invasive crayfish plague-transmitting species was predicted to increase. Some native crayfish species (e.g., noble crayfish [Astacus astacus]) had no future refugia that were unsuitable for the modeled nonnative species. Our results emphasize the importance of preventing additional introductions and spread of invasive crayfishes in Europe to minimize interactions between the multiple stressors of climate change and invasive species, while suggesting candidate regions for the debatable management option of assisted colonization. © 2013 Society for Conservation Biology.
Bar-Zeev, Naor; Kapanda, Lester; King, Carina; Beard, James; Phiri, Tambosi; Mvula, Hazzie; Crampin, Amelia C.; Mwansambo, Charles; Costello, Anthony; Parashar, Umesh; Tate, Jacqueline E.; Verani, Jennifer R.; Whitney, Cynthia G.; Heyderman, Robert S.; Cunliffe, Nigel A.; French, Neil
Background Pneumonia and gastroenteritis are leading causes of vaccine-preventable childhood morbidity and mortality. Malawi introduced pneumococcal conjugate and rotavirus vaccines to the immunisation programme in 2011 and 2012, respectively. Evaluating their effectiveness is vital to ensure optimal implementation and justify sustained investment. Methods/Design A national evaluation platform was established to determine vaccine effectiveness and impact in Malawi. Impact and effectiveness against vaccine-type invasive pneumococcal disease, radiological pneumonia and rotavirus gastroenteritis are investigated using before-after incidence comparisons and case-control designs, respectively. Mortality is assessed using a prospective population cohort. Cost-effectiveness evaluation is nested within the case-control studies. We describe platform characteristics including strengths and weaknesses for conducting vaccine evaluations. Discussion Integrating data from individual level and ecological methods across multiple sites provides comprehensive information for policymakers on programme impact and vaccine effectiveness including changes in serotype/genotype distribution over time. Challenges to robust vaccine evaluation in real-world conditions include: vaccination ascertainment; pre-existing rapid decline in mortality and pneumococcal disease in the context of non-vaccine interventions; and the maintenance of completeness and quality of reporting at scale and over time. In observational non-randomised designs ascertainment of vaccine status may be biased particularly in infants with fatal outcomes. In the context of multiple population level interventions targeting study endpoints attribution of reduced incidence to vaccine impact may be flawed. Providing evidence from several independent but complementary studies will provide the greatest confidence in assigning impact. Welcome declines in disease incidence and in child mortality make accrual of required sample sizes
Bar-Zeev, Naor; Kapanda, Lester; King, Carina; Beard, James; Phiri, Tambosi; Mvula, Hazzie; Crampin, Amelia C; Mwansambo, Charles; Costello, Anthony; Parashar, Umesh; Tate, Jacqueline E; Verani, Jennifer R; Whitney, Cynthia G; Heyderman, Robert S; Cunliffe, Nigel A; French, Neil
Pneumonia and gastroenteritis are leading causes of vaccine-preventable childhood morbidity and mortality. Malawi introduced pneumococcal conjugate and rotavirus vaccines to the immunisation programme in 2011 and 2012, respectively. Evaluating their effectiveness is vital to ensure optimal implementation and justify sustained investment. A national evaluation platform was established to determine vaccine effectiveness and impact in Malawi. Impact and effectiveness against vaccine-type invasive pneumococcal disease, radiological pneumonia and rotavirus gastroenteritis are investigated using before-after incidence comparisons and case-control designs, respectively. Mortality is assessed using a prospective population cohort. Cost-effectiveness evaluation is nested within the case-control studies. We describe platform characteristics including strengths and weaknesses for conducting vaccine evaluations. Integrating data from individual level and ecological methods across multiple sites provides comprehensive information for policymakers on programme impact and vaccine effectiveness including changes in serotype/genotype distribution over time. Challenges to robust vaccine evaluation in real-world conditions include: vaccination ascertainment; pre-existing rapid decline in mortality and pneumococcal disease in the context of non-vaccine interventions; and the maintenance of completeness and quality of reporting at scale and over time. In observational non-randomised designs ascertainment of vaccine status may be biased particularly in infants with fatal outcomes. In the context of multiple population level interventions targeting study endpoints attribution of reduced incidence to vaccine impact may be flawed. Providing evidence from several independent but complementary studies will provide the greatest confidence in assigning impact. Welcome declines in disease incidence and in child mortality make accrual of required sample sizes difficult, necessitating large
Msefula, Chisomo L.; Gondwe, Esther N.; Gilchrist, James J.; Pensulo, Paul; Mandala, Wilson L.; Mwimaniwa, Grace; Banda, Meraby; Kenny, Julia; Wilson, Lorna K.; Phiri, Amos; MacLennan, Jenny M.; Molyneux, Elizabeth M.; Molyneux, Malcolm E.; Graham, Stephen M.
Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0–15 years) and 52/256 children (20%; 95%CI 15–25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71–82%), 123/240 (51%; 95%CI 45–58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36–49%) had an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8–35.1), dyspnea (OR 4.2; 95%CI 1.5–12.0) and HIV infection (OR 3.3; 95%CI 1.1–10.2) were independent risk factors for inpatient mortality. Invasive Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children
Tashani, Mohamed; Barasheed, Osamah; Azeem, Mohammad; Alfelali, Mohammad; Badahdah, Al-Mamoon; Bokhary, Hamid; Almasri, Nedal; Alshehri, Jassir; Matbouly, Ghassan; Kalantan, Nadeen; Heron, Leon; Ridda, Iman; Haworth, Elizabeth; Asghar, Atif; Rashid, Harunor; Booy, Robert
The uptake of the pneumococcal vaccine is suboptimal in Australia and remains unknown among Australian Hajj pilgrims, many of whom are eligible because of age or underlying disease and at particular risk because of travel and activities at Hajj. Pneumococcal vaccination uptake was examined over three consecutive years (2011 to 2013) through anonymous self-administered cross sectional surveys among Australian pilgrims who assembled in Mina valley, Mecca, Saudi Arabia. Respectively, 158, 513 and 219 pilgrims were recruited in 2011, 2012 and 2013; their mean ages were 43.8 (SD±13), 43 (SD±13.5) and 42.6 (SD±12.3) years; males accounted for 67 (42.4%), 325 (63.4%) and 172 (78.5%). Pneumococcal vaccine uptake rates were 28.5% (45/158), 28.7% (147/513) and 14.2% (31/219); among the pilgrims with 'at risk' conditions the pneumococcal vaccine uptake rates were 15 (30.6%), 43 (45.3%) and 9 (29%) respectively. According to our surveys, the pneumococcal vaccine uptake among Australian pilgrims is low. Further research is needed to explore the reasons through a validated study.
Background Non-invasive prenatal testing of trisomy 21 (T21) is being actively investigated using fetal-specific epigenetic markers (EPs) that are present in maternal plasma. Recently, 12 EPs on chromosome 21 were identified based on tissue-specific epigenetic characteristics between placenta and blood, and demonstrated excellent clinical performance in the non-invasive detection of fetal T21. However, the disease-specific epigenetic characteristics of the EPs have not been established. Therefore, we validated the disease-specific epigenetic characteristics of these EPs for use in non-invasive detection of fetal T21. Methods We performed a high-resolution tiling array analysis of human chromosome 21 using a methyl-CpG binding domain-based protein (MBD) method with whole blood samples from non-pregnant normal women, whole blood samples from pregnant normal women, placenta samples of normal fetuses, and placenta samples of T21 fetuses. Tiling array results were validated by bisulfite direct sequencing and qPCR. Results Among 12 EPs, only four EPs were confirmed to be hypermethylated in normal placenta and hypomethylated in blood. One of these four showed a severe discrepancy in the methylation patterns of T21 placenta samples, and another was located within a region of copy number variations. Thus, two EPs were confirmed to be potential fetal-specific markers based on their disease-specific epigenetic characteristics. The array results of these EPs were consisted with the results obtained by bisulfite direct sequencing and qPCR. Moreover, the two EPs were detected in maternal plasma. Conclusions We validated that two EPs have the potential to be fetal-specific EPs which is consistent with their disease-specific epigenetic characteristics. The findings of this study suggest that disease-specific epigenetic characteristics should be considered in the development of fetal-specific EPs for non-invasive prenatal testing of T21. PMID:24397966
Lorente Antoñanzas, Reyes; Varona Malumbres, Juan Luis; Antoñanzas Villar, Fernando; Rejas Gutiérrez, Javier
To estimate the 5-year clinical and economic impact of a pneumococcal vaccination program on immunocompetent population aged 65-year-old in Spain. A 5 year dynamic model based on differential equations was built for the conceptualization of the burden of pneumococcal disease (PD) on a 65 year-old cohort. A 36.5% of the cohort was vaccinated with an expected efficacy rate of 52.5% as observed in the CAPITA study. The serotype vaccination coverage used was 63.4% (CAPA study), the incidence of pneumococcal disease was 162.2 per 100,000 cases per year (CMBD 2010-2013) and a rate of vaccinated subjects previously from the start of the model of 0.99%. The study used the perspective of The National Health System, and included the costs associated to PD and the conjugate vaccine laboratory selling price. In a 5 years-period, the vaccination with 13-valent pneumococcal conjugate vaccine is expected to avoid 10,360 cases of pneumococcal disease (7,411 in-patient pneumonias) and 699 deaths (14,736 Life Years Gained) in the 65 year old cohort. Vaccination costs of 36.5 million euros would be completely offset by medical cost reduction of 41.5 million euros, yielding to a net saving of 3.8 million constant euros (4.9 million undiscounted). PCV13 vaccination targeting the cohort of 65 year-old immunocompetent Spanish adults is expected to result in net savings for the National Health System, while decreasing disease burden and averting a substantial number of related deaths.
Ciapponi, Agustín; Elorriaga, Natalia; Rojas, Juan Ignacio; Romano, Marina; Martí, Sebastián García; Bardach, Ariel; Ruvinsky, Silvina
Pneumococcal meningitis and bacteremia pose a significant disease burden in Latin America and the Caribbean (LAC). To perform a systematic review of studies of pediatric pneumococcal meningitis and non-pneumonia, non-meningitis pneumococcal bacteremia in LAC, we conducted an exhaustive search from 2000 to 2010 in electronic databases and grey literature. Pairs of independently selected reviewers assessed the quality and extracted the studies' data. A STROBE-based checklist was used to assess the risk of bias in observational studies. Meta-analyses were performed. Of 1218 retrieved studies, 39 were included. In children <5 years, the pooled 95% confidence interval (CI) percentage of pneumococcal etiology out of cases studied with cerebrospinal fluid/blood cultures was 6.0% (95% CI: 3.3-9.5) for meningitis and 8.0% (95% CI: 5.3-12.4) for bacteremia. The incidences per 100,000 children were 4.7 (95% CI: 3.2-6.1) and 3.9 (95% CI: 2.0-5.9) for pneumococcal meningitis and non-pneumonia, non-meningitis bacteremia, respectively. The mortality was 8.3 (95% CI: 0.0-21.0) and 0.5 (95% CI: 0.3.0-0.6)/100,000 for meningitis and sepsis, respectively. The case fatality ratio was 33.2% (95% CI: 21.3-46.2) for meningitis and 29.0% (95% CI: 21.9-36.8) for sepsis. The pooled serotype distribution from SIREVA surveillance data showed that 14, 5, 6B (for meningitis) and 14, 6B, 19F (for bacteremia) were the most frequent serotypes, all included in licensed vaccines. Pneumococcal meningitis and bacteremia are important causes of morbidity and mortality in LAC children <5 years of age. This systematic review provided evidence about the burden of pneumococcal disease and the serotype distribution to assess the impact the pneumococcal vaccines and to assist decision makers in the region.
Chao, Yashuan; Marks, Laura R; Pettigrew, Melinda M; Hakansson, Anders P
Streptococcus pneumoniae (the pneumococcus) is a common colonizer of the human nasopharynx. Despite a low rate of invasive disease, the high prevalence of colonization results in millions of infections and over one million deaths per year, mostly in individuals under the age of 5 and the elderly. Colonizing pneumococci form well-organized biofilm communities in the nasopharyngeal environment, but the specific role of biofilms and their interaction with the host during colonization and disease is not yet clear. Pneumococci in biofilms are highly resistant to antimicrobial agents and this phenotype can be recapitulated when pneumococci are grown on respiratory epithelial cells under conditions found in the nasopharyngeal environment. Pneumococcal biofilms display lower levels of virulence in vivo and provide an optimal environment for increased genetic exchange both in vitro and in vivo, with increased natural transformation seen during co-colonization with multiple strains. Biofilms have also been detected on mucosal surfaces during pneumonia and middle ear infection, although the role of these biofilms in the disease process is debated. Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, changes in the microflora, inflammation, or other host assaults trigger active release of pneumococci from biofilms. These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and broth-grown, planktonic bacteria, resulting in a significantly increased virulence in vivo. In this review we discuss the properties of pneumococcal biofilms, the role of biofilm formation during pneumococcal colonization, including their propensity for increased ability to exchange genetic material, as well as mechanisms involved in transition from asymptomatic biofilm colonization to dissemination and disease of otherwise sterile sites. Greater understanding of pneumococcal biofilm
Chao, Yashuan; Marks, Laura R.; Pettigrew, Melinda M.; Hakansson, Anders P.
Streptococcus pneumoniae (the pneumococcus) is a common colonizer of the human nasopharynx. Despite a low rate of invasive disease, the high prevalence of colonization results in millions of infections and over one million deaths per year, mostly in individuals under the age of 5 and the elderly. Colonizing pneumococci form well-organized biofilm communities in the nasopharyngeal environment, but the specific role of biofilms and their interaction with the host during colonization and disease is not yet clear. Pneumococci in biofilms are highly resistant to antimicrobial agents and this phenotype can be recapitulated when pneumococci are grown on respiratory epithelial cells under conditions found in the nasopharyngeal environment. Pneumococcal biofilms display lower levels of virulence in vivo and provide an optimal environment for increased genetic exchange both in vitro and in vivo, with increased natural transformation seen during co-colonization with multiple strains. Biofilms have also been detected on mucosal surfaces during pneumonia and middle ear infection, although the role of these biofilms in the disease process is debated. Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, changes in the microflora, inflammation, or other host assaults trigger active release of pneumococci from biofilms. These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and broth-grown, planktonic bacteria, resulting in a significantly increased virulence in vivo. In this review we discuss the properties of pneumococcal biofilms, the role of biofilm formation during pneumococcal colonization, including their propensity for increased ability to exchange genetic material, as well as mechanisms involved in transition from asymptomatic biofilm colonization to dissemination and disease of otherwise sterile sites. Greater understanding of pneumococcal biofilm
Voss, S; Gámez, G; Hammerschmidt, S
Microorganisms have evolved elaborate strategies to adhere to host cells and to evade the host complement and immune attack, ensuring survival in various host niches and dissemination into sterile parts of the human body. Streptococcus pneumoniae (the pneumococcus) is not only a commensal of the human respiratory tract but also the etiological agent of severe and life-threatening diseases. Pneumococcal attachment to mucosal surfaces is a highly dynamic process requiring the contact of pneumococcal surface-exposed proteins with soluble or immobilized host factors. These avid interactions may trigger proteolytic cascades or result in engagement of cell surface receptors and intracellularly associated signaling machineries for subsequent uptake of pneumococci into host cells. In the present review, the intimate communication of S. pneumoniae molecules recognizing adhesive matrix molecules (microbial surface components recognizing adhesive matrix molecules) with their host counterparts and their individual role in pneumococcal colonization is discussed. © 2012 John Wiley & Sons A/S.
Craven, Melanie; Egan, Charlotte E.; Dowd, Scot E.; McDonough, Sean P.; Dogan, Belgin; Denkers, Eric Y.; Bowman, Dwight; Scherl, Ellen J.; Simpson, Kenneth W.
Background and Aims Understanding the interplay between genetic susceptibility, the microbiome, the environment and the immune system in Crohn’s Disease (CD) is essential for developing optimal therapeutic strategies. We sought to examine the dynamics of the relationship between inflammation, the ileal microbiome, and host genetics in murine models of ileitis. Methods We induced ileal inflammation of graded severity in C57BL6 mice by gavage with Toxoplasma gondii, Giardia muris, low dose indomethacin (LDI;0.1 mg/mouse), or high dose indomethacin (HDI;1 mg/mouse). The composition and spatial distribution of the mucosal microbiome was evaluated by 16S rDNA pyrosequencing and fluorescence in situ hybridization. Mucosal E. coli were enumerated by quantitative PCR, and characterized by phylogroup, genotype and pathotype. Results Moderate to severe ileitis induced by T. gondii (day 8) and HDI caused a consistent shift from >95% Gram + Firmicutes to >95% Gram - Proteobacteria. This was accompanied by reduced microbial diversity and mucosal invasion by adherent and invasive E. coli, mirroring the dysbiosis of ileal CD. In contrast, dysbiosis and bacterial invasion did not develop in mice with mild ileitis induced by Giardia muris. Superimposition of genetic susceptibility and T. Gondii infection revealed greatest dysbiosis and bacterial invasion in the CD-susceptible genotype, NOD2−/−, and reduced dysbiosis in ileitis-resistant CCR2−/− mice. Abrogating inflammation with the CD therapeutic anti-TNF-α-mAb tempered dysbiosis and bacterial invasion. Conclusions Acute ileitis induces dysbiosis and proliferation of mucosally invasive E. coli, irrespective of trigger and genotype. The identification of CCR2 as a target for therapeutic intervention, and discovery that host genotype and therapeutic blockade of inflammation impact the threshold and extent of ileal dysbiosis are of high relevance to developing effective therapies for CD. PMID:22848538
Early diagnosis and timely treatment are critical in Invasive Fungal Disease (IFD) caused by filamentous fungi in immunocompromised patients. Clinical features of IFD are nonspecific; therefore, images (CT scan), direct microscopic examination, staining and cultures of clinical samples and galactomannan determination in blood or BAL, are substantial. This guideline provides recommendations on transport and sample processing, including stains and culture media requirements. It also describes clues for diagnosis of major genera and species of Aspergillus.
Goldstone, Andrew B; Woo, Y Joseph
The treatment of mitral valve disease remains dynamic; surgeons and patients must now choose between many different surgical options when addressing mitral regurgitation and mitral stenosis. Notably, advances in imaging and surgical instrumentation allow surgeons to perform less invasive mitral valve surgery that spares the sternum. With favorable long-term data now emerging, we compare the benefits and risks of thoracoscopic mitral valve surgery with that through conventional sternotomy or surgery that is robot-assisted.
... 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 ...
Martinón-Torres, Federico; Wysocki, Jacek; Center, Kimberly J; Czajka, Hanna; Majda-Stanislawska, Ewa; Omeñaca, Felix; Concheiro-Guisan, Ana; Gimenez-Sanchez, Francisco; Szenborn, Leszek; Blázquez-Gamero, Daniel; Moreno-Galarraga, Laura; Giardina, Peter C; Sun, Gang; Gruber, William C; Scott, Daniel A; Gurtman, Alejandra
Premature infants have lower short-term immune responses to vaccination than term infants, but patterns of antibody persistence in preterm infants over longer periods are not well established. This study assessed the persistence of antibody response to the 13-valent pneumococcal conjugate vaccine (PCV13) in formerly preterm versus term infants. In total, 100 preterm and 100 term infants received PCV13 with routine vaccines at ages 2, 3, 4 and 12 months. Serotype-specific anticapsular immunoglobulin G (IgG)-binding antibodies and opsonophagocytic activity were determined 1 and 2 years after the last PCV13 dose. At 1 and 2 years after the last vaccination (toddler dose), IgG geometric mean concentrations (GMCs) for all serotypes had declined from levels measured 1 month after the toddler dose but remained above pretoddler dose levels. IgG GMCs were significantly lower in preterm than term subjects for a majority of serotypes at both follow-up time points. IgG GMCs increased in both groups for some serotypes from the 1-year to 2-year follow-up, whereas others declined. Opsonophagocytic activity results supported the IgG results. The routine (3 + 1) vaccination schedule is likely to offer long-term protection against invasive pneumococcal disease in preterm infants and should be initiated regardless of gestational age or weight at birth, without delay of the toddler dose.
Sanvictores, Diozele Hazel M; Lucero, Marilla G; Nohynek, Hanna; Tallo, Veronica L; Tanskanen, Antti; Nillos, Leilani T; Williams, Gail
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.
Sanchez-Pernaute, Rosario; Jenkins, Bruce G.; Isacson, Ole
Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders.
Ishiguro, Takashi; Kagiyama, Naho; Uozumi, Ryuji; Odashima, Kyuto; Kurashima, Kazuyoshi; Morita, Satoshi; Takayanagi, Noboru
Comorbidity is known to be associated with the severity and mortality of pneumonia. The severity of each underlying disease varies, and performance status, which is known to be a prognostic factor of malignant diseases, reflects the overall patient condition as affected by his/her comorbidity and underlying diseases of various severity. We investigated whether premorbid patients' performance status is associated with the severity and mortality of pneumococcal pneumonia. This retrospective study assessed these factors in hospitalized patients suffering from pneumococcal pneumonia from 2002 to 2015. We included 424 patients aged 68.9 ± 14.1 years in the study, of which 68.9% were men. A multivariate analysis found that advanced age (≥65 years), diabetes mellitus, and poor performance status were independent factors associated with severity, whereas old pulmonary tuberculosis, poor performance status, pneumococcal bacteremia, and severe pneumonia were independent factors that were associated with non-survival. Poor performance status was associated with the severity and mortality of pneumococcal pneumonia. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Pemán, Javier; Quindós, Guillermo
Invasive candidiasis is the most common invasive fungal disease causing an unacceptably high mortality. Candida albicans remains the predominant origin, but an epidemiological shift has been described in the last decades. Some species of Candida have emerged as an important cause of severe candidaemia and can exhibit reduced susceptibility to the current antifungal agents. Candida parapsilosis has been associated with candidaemia in neonates and young adults, whereas Candida glabrata, Candida tropicalis, and Candida krusei are most frequently isolated in blood cultures from older patients (>65 years). Other yeasts are becoming important causes of invasive mycoses, such as Cryptococcus, Trichosporon, Malassezia, Geotrichum or Saprochaete/Magnusiomyces. Cryptococcosis is more relevant as a cause of meningitis in HIV-infected people, but cryptococcal infections are also a clinical challenge in transplant recipients. Diagnosis remains an important problem, causing unacceptable delays in starting a correct and direct treatment. However, there are some new approaches that can help in the prompt and specific diagnosis of invasive yeast infections, such as in situ hybridisation using PNA-FISH probes, causal agent identification in blood cultures using MALDi-TOF MS, or new and rapid nucleic acids detection assays. Copyright © 2015 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.
Iroh Tam, Pui-Ying; Sadoh, Ayebo E; Obaro, Stephen K
Pneumonia causes an enormous burden of childhood disease globally, particularly in low- and middle-income countries. Pneumococcus is the most common bacterial aetiology of pneumonia; however, antimicrobials are limited and may not adequately address the local epidemiology of the region. To undertake a review and meta-analysis of pneumonia studies in sub-Saharan Africa to evaluate antimicrobial susceptibility patterns in childhood pneumonia. Articles published in PubMed and Google between 2006 and 2016 which evaluated antimicrobial susceptibility profiles of pneumococcal pneumonia in children in sub-Saharan Africa were identified. The source of specimens, pathogens and antimicrobial susceptibility data were extracted. Pooled analysis of susceptible isolates was conducted using random effects models. Children from 15 studies and 1634 isolates were included in the meta-analysis. In cases of childhood pneumonia, the mean overall proportion of penicillin susceptibility from invasive specimens of Streptococcus pneumoniae was 85.7% (95% CI 80.1-91.3), and of trimethoprim-sulfamethoxazole was 21.0% (95% CI 5.1-36.9). Compared with all S. pneumoniae specimens, penicillin susceptibility was 68.6% (95% CI 59.6-77.5) and that of trimethoprim-sulfamethoxazole was 26.3% (95% CI 14.1-38.6). A high level of heterogeneity was detected, reflecting the paucity of data available. The establishment of national and regional diagnostic platforms to monitor antimicrobial susceptibility profiles for pneumonia as well as other invasive diseases will provide data with which to assess the relevance and adaptation of antimicrobial prescribing recommendations.
McNeil, Shelly A; Qizilbash, Nawab; Ye, Jian; Gray, Sharon; Zanotti, Giovanni; Munson, Samantha; Dartois, Nathalie; Laferriere, Craig
Background. Routine vaccination against Streptococcus pneumoniae is recommended in Canada for infants, the elderly, and individuals with chronic comorbidity. National incidence and burden of all-cause and pneumococcal pneumonia in Canada (excluding Quebec) were assessed. Methods. Incidence, length of stay, and case-fatality rates of hospitalized all-cause and pneumococcal pneumonia were determined for 2004-2010 using ICD-10 discharge data from the Canadian Institutes for Health Information Discharge Abstract Database. Population-at-risk data were obtained from the Statistics Canada census. Temporal changes in pneumococcal and all-cause pneumonia rates in adults ≥65 years were analyzed by logistic regression. Results. Hospitalization for all-cause pneumonia was highest in children <5 years and in adults >70 years and declined significantly from 1766/100,000 to 1537/100,000 per year in individuals aged ≥65 years (P < 0.001). Overall hospitalization for pneumococcal pneumonia also declined from 6.40/100,000 to 5.08/100,000 per year. Case-fatality rates were stable (11.6% to 12.3%). Elderly individuals had longer length of stay and higher case-fatality rates than younger groups. Conclusions. All-cause and pneumococcal pneumonia hospitalization rates declined between 2004 and 2010 in Canada (excluding Quebec). Direct and indirect effects from pediatric pneumococcal immunization may partly explain some of this decline. Nevertheless, the burden of disease from pneumonia remains high.
Pereira, Jorge; Porto-Figueira, Priscilla; Cavaco, Carina; Taunk, Khushman; Rapole, Srikanth; Dhakne, Rahul; Nagarajaram, Hampapathalu; Câmara, José S.
Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases. PMID:25584743
Lee, Irwin H.; Roberts, Rebecca; Shah, Rajal B.
Purpose: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer. Methods and Materials: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage). Results: For the overall population, PNI was associated with a significantly increased frequency of upgrading andmore » of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation. Conclusions: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy.« less
Rubio, Nicolás Agustín; Puia, Sebastian; Toranzo, Silvia; Brusca, María Isabel
In the last few years unusual microorganisms have been isolated from subgingival biofilm, as possible initiators or contributors to periodontal disease, especially in patients who show no improvement during treatment. To study the Candida invasion of the connective tissue in relation to subgingival biofilm presence. A total of 55 immunocompetent patients of both sexes, between 21 and 55 years of age, non-smokers, without previous antimicrobial treatment, suffering periodontal diseases, were studied. Soft tissues, supragingival and subgingival plaque samples, and periodontal pocket biopsies were taken. Microscopic studies, cultures, assimilation profiles, and DNA amplifications were performed. In 35% of the samples, different species of Candida were isolated in cultures, especially Candida albicans. Hyphae invasions in the connective tissue were observed, in association with anaerobic microorganisms (Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans) in patients with periodontitis. Different species of Candida could be part of the periodontal plaque and could play an important role in the adherence to soft tissues, allowing deep invasion. They also could infect gingival pockets in patients with gingivitis, even in healthy locations, playing a commensal or opportunist role. Copyright © 2011 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.
Wang, Yan; Hou, Jin-Lin
Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine.
Whitlock, Matthew C.; Hundley, W. Gregory
With advancements in technology and a better understanding of human cardiovascular physiology, research as well as clinical care can go beyond dimensional anatomy offered by traditional imaging and investigate aortic functional properties and the impact disease has on this function. Linking the knowledge of the histopathological changes with the alterations in aortic function observed on noninvasive imaging results in a better understanding of disease pathophysiology. Translating this to clinical medicine, these noninvasive imaging assessments of aortic function are proving to be able to diagnosis disease, better predict risk, and assess response to therapies. This review is designed to summarize the various hemodynamic measures that can characterize the aorta, the various non-invasive techniques, and applications for various disease states. PMID:26381770
Dangor, Ziyaad; Lala, Sanjay G; Cutland, Clare L; Koen, Anthonet; Jose, Lisa; Nakwa, Firdose; Ramdin, Tanusha; Fredericks, Joy; Wadula, Jeannette; Madhi, Shabir A
Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0-6 days of life, EOD) and late-onset (7-89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women. A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age. We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24-9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94-386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44-49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17-10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44-120.95) greater in cases (13.2%) than controls (0.4%). The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting.
Dangor, Ziyaad; Lala, Sanjay G.; Cutland, Clare L.; Koen, Anthonet; Jose, Lisa; Nakwa, Firdose; Ramdin, Tanusha; Fredericks, Joy; Wadula, Jeannette; Madhi, Shabir A.
Introduction Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis. We aimed to evaluate the burden of invasive early-onset (0–6 days of life, EOD) and late-onset (7–89 days, LOD) GBS disease and subsequent neurological sequelae in infants from a setting with a high prevalence (29.5%) of HIV among pregnant women. Methods A case-control study was undertaken at three secondary-tertiary care public hospitals in Johannesburg. Invasive cases in infants <3 months age were identified by surveillance of laboratories from November 2012 to February 2014. Neurodevelopmental screening was done in surviving cases and controls at 3 and 6 months of age. Results We identified 122 cases of invasive GBS disease over a 12 month period. Although the incidence (per 1,000 live births) of EOD was similar between HIV-exposed and HIV-unexposed infants (1.13 vs. 1.46; p = 0.487), there was a 4.67-fold (95%CI: 2.24–9.74) greater risk for LOD in HIV-exposed infants (2.27 vs. 0.49; p<0.001). Overall, serotypes Ia, Ib and III constituted 75.8% and 92.5% of EOD and LOD, respectively. Risk factors for EOD included offensive draining liquor (adjusted Odds Ratio: 27.37; 95%CI: 1.94–386.50) and maternal GBS bacteriuria (aOR: 8.41; 95%CI: 1.44–49.15), which was also a risk-factor for LOD (aOR: 3.49; 95%CI: 1.17–10.40). The overall case fatality rate among cases was 18.0%. The adjusted odds for neurological sequelae at 6 months age was 13.18-fold (95%CI: 1.44–120.95) greater in cases (13.2%) than controls (0.4%). Discussion The high burden of invasive GBS disease in South Africa, which is also associated with high case fatality rates and significant neurological sequelae among survivors, is partly due to the heightened risk for LOD in infants born to HIV-infected women. An effective trivalent GBS conjugate vaccine targeted at pregnant women could prevent invasive GBS disease in this setting. PMID:25849416
Recent advances of the measurement of bone turn over markers contribute to non-invasive assessment of bone-metabolic disorders. We can detect the cause of the metabolic disorders with bone turn over markers and hormonal profiles more easily than before. Today, we can diagnose and treat metabolic bone diseases without invasive procedure such as bone biopsy.
Wahid, S T; Nag, S; Bilous, R W; Marshall, S M; Robinson, A C
To document uptake of influenza and pneumococcal vaccination in diabetic patients attending secondary care in the Northern Region, and to explore influencing factors. Diabetic patients attending out-patients in Middlesbrough, Gateshead and Newcastle were questioned from October 1999 to March 2000. Physicians inquired about influenza and pneumococcal vaccination status using a standardized questionnaire. Data collected included age, year of diagnosis, duration of diabetes, type of diabetes, and the presence of other recognized indications for vaccination. Two hundred and sixty-eight diabetic patients, 42% (113/268) with Type 1 diabetes, 34% (91/268) with ischaemic heart disease, 10% (26/268) with chronic pulmonary disease (CPD) and 10% (27/268) with chronic renal disease, were questioned. Thirty-five percent (93/268) of patients received both influenza and pneumococcal vaccines, 24% (64/268) received only influenza vaccine, and none received pneumococcus vaccine alone. Most vaccinees received advice about influenza and pneumococcal vaccination from their general practitioner (90% (142/157) and 87% (81/93), respectively). A large number of non-vaccinees were unaware of the need for influenza and pneumococcal vaccination (69% (76/111) and 91% (159/175), respectively). Using multiple logistic regression co-existing CPD increased the odds of receiving influenza (odds ratio (OR) (95% confidence interval (CI)) = 1.99 (1.07-14.12)) or pneumococcal (OR = 3.77 (1.69-21.76)) vaccination. Furthermore, each 1-year increase in age increased the chance of receiving influenza or pneumococcal vaccination by 22% (OR = 1.22 (1.09-1.67) and 29% (OR = 1.29 (1.07-1.72)), respectively. Vaccination rates in these diabetic patients are unsatisfactory. Secondary care health professionals might increase rates by raising the topic in consultations. Diabet. Med. 18, 599-603 (2001)
Saidi, Trust; Douglas, Tania S
The treatment of rheumatic heart disease presents a medical and surgical challenge, particularly in developing countries, where the disease is prevalent. Most of these countries find it prohibitively expensive to import heart valve prostheses that are required for treatment and are largely manufactured in the United States and Europe. Even if the valves were available, the absence of facilities to conduct open-heart surgery for valve replacement results in many people from developing countries dying needlessly of the disease. To address this problem, transcatheter aortic valve implantation, an emerging, minimally invasive, treatment strategy for rheumatic heart disease, has been proposed. Areas covered: This paper reviews the literature on current valve technologies in use globally, and focuses on a minimally invasive transcatheter aortic valve implantation device and aortic valve prosthesis that have been developed by Strait Access Technologies Holdings in South Africa. Expert commentary: This new technology holds the potential of making available heart valve replacements to millions of patients in the developing world who would otherwise have no recourse to treatment.
Nita-Lazar, Mihai; Banerjee, Aditi; Feng, Chiguang; Amin, Mohammed N.; Frieman, Matthew B.; Chen, Wilbur H.; Cross, Alan S.; Wang, Lai-Xi; Vasta, Gerardo R.
The continued threat of worldwide influenza pandemics, together with the yearly emergence of antigenically drifted influenza A virus (IAV) strains, underscore the urgent need to elucidate not only the mechanisms of influenza virulence, but also those mechanisms that predispose influenza patients to increased susceptibility to subsequent infection with Streptococcus pneumoniae. Glycans displayed on the surface of epithelia that are exposed to the external environment play important roles in microbial recognition, adhesion, and invasion. It is well established that the IAV hemagglutinin and pneumococcal adhesins enable their attachment to the host epithelia. Reciprocally, the recognition of microbial glycans by host carbohydrate-binding proteins (lectins) can initiate innate immune responses, but their relevance in influenza or pneumococcal infections is poorly understood. Galectins are evolutionarily conserved lectins characterized by affinity for β-galactosides and a unique sequence motif, with critical regulatory roles in development and immune homeostasis. In this study, we examined the possibility that galectins expressed in the airway epithelial cells might play a significant role in viral or pneumococcal adhesion to airway epithelial cells. Our results in a mouse model for influenza and pneumococcal infection revealed that the murine lung expresses a diverse galectin repertoire, from which selected galectins, including galectin 1 (Gal1) and galectin 3 (Gal3), are released to the bronchoalveolar space. Further, the results showed that influenza and subsequent S. pneumoniae infections significantly alter the glycosylation patterns of the airway epithelial surface and modulate galectin expression. In vitro studies on the human airway epithelial cell line A549 were consistent with the observations made in the mouse model, and further revealed that both Gal1 and Gal3 bind strongly to IAV and S. pneumoniae, and that exposure of the cells to viral neuraminidase or
Traverso, F; Sparo, M; Rubio, V; Sáez Nieto, J A
Streptococcus pyogenes causes a variety of common human diseases, including pharyngitis, scarlet fever and impetigo. Nevertheless, the past decades have witnessed a worldwide resurgence in invasive disease and streptococcal toxic shock syndrome (STSS). The objective of the present study is to evaluate the genetic diversity, virulence gene distribution (spe, sme and ssa genes) and susceptibility pattern of 10 S. pyogenes isolates causing invasive disease and STSS. The isolates were recovered from blood cultures of hospitalized patients at Hospital Santamarina and Nueva Clínica Chacabuco, Tandil, Buenos Aires, Argentina between 12/2000-04/2005. Two pulse field gel electrophoretic patterns predominated. The most frequent one included 5 characteristic isolates of emm1-T1 type, toxin gene profile speA, speB, speF, speG and smeZ. The second pattern included 2 characteristic isolates of emm3-TNT type (speB, speF, speG). The other 3 isolates corresponded to types emm49-TNT (speB, speC, speF, speG), emm75-T25 (speB, speF, speG) and emm83-TNT (speB, speF, speG, ssa, smeZ). All isolates were susceptible to penicillin, cefotaxime, erythromycin, clindamycin, chloramphenicol, tetracycline and rifampicin. The data from the present study demonstrated genetic diversity among the strains. Types emm1 and emm3 were prevalent in invasive disease. The empirical treatment with the combination of penicillin and clindamicin is still valid.
Coimbra, Roney S; Voisin, Veronique; de Saizieu, Antoine B; Lindberg, Raija LP; Wittwer, Matthias; Leppert, David; Leib, Stephen L
Background Pneumococcal meningitis is associated with high mortality (~30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy. PMID
Kong, Yujia; Zhang, Wei; Jiang, Zhiwei; Wang, Ling; Li, Chanjuan; Li, Yanping; Xia, Jielai
Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. Vaccines have become the most effective way to prevent pneumococcal infections. This phase III trial was designed to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years. We conducted a randomized, double-blinded, active-controlled, multicenter trial in which 1660 healthy population (>2 years of age) were randomly assigned in a 1 : 1 ratio to receive 2 intramuscular doses of either the treatment vaccine or the active control vaccine, PNEUMOVAX 23. The surveillance period was 30 days. The primary end point was the 2-fold increase rate of anti-pneumococcal antibody for all 23 included serotypes in each group. In the intention-to-treat cohort, the 2-fold increase rate of anti-pneumococcal antibody for 23 included serotypes varied from 62.47% to 97.01% in the treatment group, and from 51.49% to 95.77% in the control group. According to −10% non-inferiority margin and 95% confidence intervals of rate difference, almost all included serotypes of the treatment group reached non-inferiority to control group except for serotype 6B, the lower limit of rate difference of which was −10.00%, equal to the non-inferiority margin. The 2-fold increase rates of anti-pneumococcal antibody were significantly higher in the treatment group for serotype 2, 3, 4, 10A, 11A and 20. Furthermore, for all 23 serotypes, IgG geometric mean concentrations (GMCs) at day 30 were significantly higher in treatment group for serotype 2, 3, 4, 9V, 10A, 11A, 15B, 18C, 19A, 22F and 33F. Higher geometric mean fold increase (GMFI) were also observed in the treatment group correspondingly. Serious adverse events occurred in 3 of 830 participants in the treatment group (0.36%) and 2 of 830 participants in the control group (0.24%). No death occurred during the trial. The frequencies of both solicited and
Filippiadis, Dimitrios; Mavrogenis, Andreas F; Mazioti, Argyro; Palialexis, Konstantinos; Megaloikonomos, Panayiotis D; Papagelopoulos, Panayiotis J; Kelekis, Alexis
Skeletal-related events in patients with metastatic bone disease include intractable severe pain, pathologic fracture, spinal cord and nerve compression, hypercalcemia and bone marrow aplasia. In patients with breast cancer, the skeleton is the most frequent site for metastases. Treatment options for metastatic bone disease in these patients include bisphosphonates, chemotherapeutic agents, opioids, hormonal therapy, minimally invasive/interventional and surgical techniques. Interventional oncology techniques for breast cancer patients with bone metastases include diagnostic (biopsy) and therapeutic (palliative and curative) approaches. In the latter, percutaneous ablation, augmentation and stabilization are included. The purpose of this article is to describe the basic concepts of biopsy, ablation, embolization and peripheral skeleton augmentation techniques in patients with metastatic bone disease from breast carcinoma. The necessity for a tailored approach applying different techniques for different cases and locations will be addressed.
Parra, Eliana L.; Ramos, Viviana; Sanabria, Olga; Moreno, Jaime
In Colombia, a laboratory-based surveillance of invasive Streptococcus pneumoniae isolates as part of SIREVA II PAHO has been conducted since 1994. This study describes the serotype distribution, antimicrobial resistance, and genetic relationships of pneumococcal isolates recovered in Colombia from 2005 to 2010. In this study, demographic data of invasive S. pneumoniae isolates were analyzed, and antimicrobial susceptibility patterns were determined. Pulse field gel electrophoresis (n = 629) and multilocus sequence typing (n = 10) were used to determine genetic relationship of isolates with minimal inhibitory concentration to penicillin ≥0.125 µg/mL. A total of 1775 isolates of S. pneumoniae were obtained. Fifteen serotypes accounted for 80.7% of isolates. Serotype 14 (23.1%) was the most frequent in the general population. Penicillin resistance was 30.7% in meningitis and 9.0% in non-meningitis. Clones Spain6BST90, Spain9VST156, Spain23FST81, and Colombia23FST338 were associated to isolates. Additionally, serotype 6A isolates were associated with ST460 and ST473, and 19A isolates with ST276, ST320, and ST1118. In conclusion, the surveillance program provided updated information of trends in serotype distribution, antimicrobial resistance and the circulation of clones in invasive pneumococcal diseases. These results could be helpful to understand the epidemiology of S. pneumoniae in Colombia, and provide a baseline to mea