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International Journal of Infectious... Feb 2022Streptococcus pneumoniae is one of the most important causes of diseases leading to child mortality, especially in low- and lower-middle-income countries. This review... (Review)
Review
OBJECTIVES
Streptococcus pneumoniae is one of the most important causes of diseases leading to child mortality, especially in low- and lower-middle-income countries. This review aims to describe the prevalence of carriage of S. pneumoniae and the impact of vaccination among children aged under five years in low- and lower-middle-income countries since 2012.
METHOD
The study is a systematic review of the literature. Relevant publications were searched in PubMed and screened systematically for information on the prevalence of carriage of S. pneumoniae among children aged under five years. 149 publications were identified, and 20 were included in the review.
RESULTS
The prevalence of S. pneumoniae ranged between 26.7% - 90.7%. The prevalence of vaccine-type carriage ranged between 4.4% - 57.6% but generally decreased in countries after the introduction of PCV, with a reduction of 15.6% - 65.7%. Half of the post- pneumococcal conjugate vaccine (PCV) studies reported a vaccine-type carriage rate below 15%.
CONCLUSION
Vaccine-type-carriage has decreased in most countries with the introduction of PCV. Still, coverage is only moderate, and carriage rates of S. pneumoniae vary significantly between countries. Continuous monitoring of carriage is needed to evaluate the effect of the further introduction of PCV10 and PCV13.
Topics: Carrier State; Child; Developing Countries; Humans; Infant; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34800691
DOI: 10.1016/j.ijid.2021.11.021 -
Journal of Microbiology, Immunology,... Feb 2022A number of pneumococcal carriage studies in children have been conducted in recent years. However, summary data of carriage prevalence and serotype distribution from... (Meta-Analysis)
Meta-Analysis Review
Carriage of Streptococcus pneumoniae in children under five years of age prior to pneumococcal vaccine introduction in Southeast Asia: A systematic review and meta-analysis (2001-2019).
A number of pneumococcal carriage studies in children have been conducted in recent years. However, summary data of carriage prevalence and serotype distribution from South East Asia Region (SEAR) are limited. This may lead to the misconception that Streptococcus pneumoniae vaccine-types are uncommon in the region. Systematic reviews of pneumococcal carriage and the distribution of serotypes are critically important for evidence-based decision-making. We aimed to summarize published data on the serotype prevalence of S. pneumoniae carried in the nasopharynx of children under 5 years of age in SEAR. We performed a systematic review and meta-analysis for relevant studies on S. pneumoniae carriage conducted prior to PCV program implementation from online journal databases published between January 2001 to December 2019. The pooled prevalence of S. pneumoniae in healthy children under 5 years of age in SEAR was 36.0% (95% CI 34.2%-37.8%), and ranged from 68.0% (95% CI: 61.9%-74.0%) in Cambodia to 7.6% (95% CI: 5.7%-9.6%) in Malaysia. Serotypes 6A/B, 23F and 19F were the most common serotypes in children <5 years, accounting for 12.9% (95% CI: 9.4%-16.3%), 9.3% (95% CI: 5.9%-12.8%) and 10.1% (95% CI: 6.6%-13.5%) of isolates, respectively. Vaccine policy makers should take these results into account when making decisions on pneumococcal conjugate vaccine programs implementation. Given the paucity of data, collection of more extensive and updated information of S. pneumoniae serotype epidemiology in children under five years in SEAR is also very important for future studies.
Topics: Cambodia; Carrier State; Child; Child, Preschool; Humans; Infant; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34511388
DOI: 10.1016/j.jmii.2021.08.002 -
The Lancet. Microbe Sep 2021Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial...
BACKGROUND
Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation.
METHODS
We did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer). Population-based studies of invasive pneumococcal disease or nasopharyngeal colonisation were eligible for inclusion. As primary outcome measures, we extracted the proportions of isolates that were non-susceptible or resistant to penicillin, macrolides, sulfamethoxazole-trimethoprim, third-generation cephalosporins, and tetracycline from each study. Where available, we also extracted data on pneumococcal serotypes. We estimated changes in the proportion of isolates with reduced susceptibility or resistance to each antibiotic class using random-effects meta-regression models, adjusting for study-level and region-level heterogeneity, as well as secular trends, invasive or colonising isolate source, and countries' per-capita gross domestic product.
FINDINGS
From 4910 studies screened for inclusion, we extracted data from 559 studies on 312 783 paediatric isolates. Susceptibility of isolates varied substantially across regions both before and after implementation of any PCV product. On average across all regions, we estimated significant absolute reductions in the proportions of pneumococci showing non-susceptibility to penicillin (11·5%, 95% CI 8·6-14·4), sulfamethoxazole-trimethoprim (9·7%, 4·3-15·2), and third-generation cephalosporins (7·5%, 3·1-11·9), over the 10 years after implementation of any PCV product, and absolute reductions in the proportions of pneumococci resistant to penicillin (7·3%, 5·3-9·4), sulfamethoxazole-trimethoprim (16·0%, 11·0-21·2), third-generation cephalosporins (4·5%, 0·3-8·7), macrolides (3·6%, 0·7-6·6) and tetracycline (2·0%, 0·3-3·7). We did not find evidence of changes in the proportion of isolates non-susceptible to macrolides or tetracycline after PCV implementation. Observed changes in penicillin non-susceptibility were driven, in part, by replacement of vaccine-targeted serotypes with non-vaccine serotypes that were less likely to be non-susceptible.
INTERPRETATION
Implementation of PCVs has reduced the proportion of circulating pneumococci resistant to first-line antibiotic treatments for pneumonia. This effect merits consideration in assessments of vaccine impact and investments in coverage improvements.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Child; Drug Resistance, Bacterial; Humans; Macrolides; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Regression Analysis; Streptococcus pneumoniae; Sulfamethoxazole; Tetracycline; Trimethoprim; Vaccines, Conjugate
PubMed: 34485957
DOI: 10.1016/S2666-5247(21)00064-1 -
The Journal of Infectious Diseases Sep 2021The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently,...
BACKGROUND
The meningitis belt of sub-Saharan Africa has traditionally experienced large outbreaks of meningitis mainly caused by Neisseria meningitidis. More recently, Streptococcus pneumoniae has been recognized as a cause of meningitis outbreaks in the region. Little is known about the natural history and epidemiology of these outbreaks, and, in contrast to meningococcal meningitis, there is no agreed definition for a pneumococcal meningitis epidemic. The aim of this analysis was to systematically review and understand pneumococcal meningitis outbreaks in Africa between 2000 and 2018.
METHODS
Meningitis outbreaks were identified using a systematic literature review and analyses of meningitis surveillance databases. Potential outbreaks were included in the final analysis if they reported at least 10 laboratory-confirmed meningitis cases above baseline per week with ≥50% of cases confirmed as pneumococcus.
RESULTS
A total of 10 potential pneumococcal meningitis outbreaks were identified in Africa between 2000 and 2018. Of these, 2 were classified as confirmed, 7 were classified as possible, and 1 was classified as unlikely. Three outbreaks spanned more than 1 year. In general, the outbreaks demonstrated lower peak attack rates than meningococcal meningitis outbreaks and had a predominance of serotype 1. Patients with pneumococcal meningitis tended to be older and had higher case fatality rates than meningococcal meningitis cases. An outbreak definition, which includes a weekly district-level incidence of at least 10 suspected cases per 100 000 population per week, with >10 cumulative confirmed cases of pneumococcus per year, would have identified all 10 potential outbreaks.
CONCLUSIONS
Given the frequency of and high case fatality from pneumococcal meningitis outbreaks, public health recommendations on vaccination strategies and the management of outbreaks are needed. Improved laboratory testing for S. pneumoniae is critical for early outbreak identification.
Topics: Africa South of the Sahara; Disease Outbreaks; Humans; Meningitis, Meningococcal; Meningitis, Pneumococcal; Public Health Surveillance; Streptococcus pneumoniae
PubMed: 34469561
DOI: 10.1093/infdis/jiab105 -
Vaccine Aug 2021Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule... (Review)
Review
BACKGROUND
Streptococcus pneumoniae is one of the most common bacterial pathogens of infants and young children. Antibody responses against the pneumococcal polysaccharide capsule are the basis of vaccine-mediated protection. We examined the relationship between the dose of polysaccharide in pneumococcal conjugate vaccines (PCVs) and immunogenicity.
METHODS
A systematic search of English publications that evaluated the immunogenicity of varying doses of pneumococcal conjugate vaccines was performed in Medline and Embase (Ovid Sp) databases in August 2019. We included only articles that involved administration of pneumococcal conjugate vaccine in humans and assessed the immunogenicity of more than one serotype-specific saccharide dose. Results were synthesised descriptively due to the heterogeneity of product valency, product content and vaccine schedule.
RESULTS
We identified 1691 articles after de-duplication; 9 studies met our inclusion criteria; 2 in adults, 6 in children and 1 in both. Doses of polysaccharide evaluated ranged from 0.44 mcg to 17.6 mcg. In infants, all doses tested elicited IgG geometric mean concentrations (GMCs) above the established correlate of protection (COP; 0.35 mcg/ml). A month after completion of the administered vaccine schedule, 95% confidence intervals of only three out of all the doses evaluated had GMCs that crossed below the COP. In the adult studies, all adults achieved GMCs that would be considered protective in children who have received 3 standard vaccine doses.
CONCLUSION
For some products, the mean antibody concentrations induced against some pneumococcal serotypes increased with increasing doses of the polysaccharide conjugate, but for other serotypes, there were no clear dose-response relationships or the dose response curves were negative. Fractional doses of polysaccharide which contain less than is included in currently distributed formulations may be useful in the development of higher valency vaccines, or dose-sparing delivery for paediatric use.
Topics: Adult; Antibodies, Bacterial; Child; Child, Preschool; Humans; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34340858
DOI: 10.1016/j.vaccine.2021.07.033 -
Clinical Infectious Diseases : An... Apr 2022Vaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To...
Vaccine-Preventable Disease Incidence Based on Clinically, Radiologically, and Etiologically Confirmed Outcomes: Systematic Literature Review and Re-analysis of Pneumococcal Conjugate Vaccine Efficacy Trials.
BACKGROUND
Vaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes with radiologically/etiologically confirmed outcomes.
METHODS
We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator).
RESULTS
Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 (95% CI not calculable), 2.1 (1.5-3.0), and 3.7 (1.0-10.2); the VPDI ratios comparing clinically defined with radiologically confirmed pneumonia ranged from not calculable to 2.7 (1.2-10.4); the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) with laboratory-confirmed IPD was 3.8 (95% CI not calculable). Among adults, the ratio comparing clinically defined with radiologically confirmed pneumonia was 1.9 (-6.0 to 9.1) and with vaccine serotype-confirmed pneumonia was 2.9 (.5-7.8).
CONCLUSIONS
While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine's public health value.
Topics: Adult; Child; Humans; Incidence; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Vaccine Efficacy; Vaccine-Preventable Diseases; Vaccines, Conjugate
PubMed: 34313721
DOI: 10.1093/cid/ciab649 -
Clinical and Experimental Vaccine... May 2021This systematic review and meta-analysis aims to quantify the impact of vaccination on the incidence and prevalence of nonsusceptible infections and investigates the... (Review)
Review
This systematic review and meta-analysis aims to quantify the impact of vaccination on the incidence and prevalence of nonsusceptible infections and investigates the impact of vaccination programs on serotype replacement. We searched a comprehensive set of databases. Identified studies were assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and resulting evidence was analyzed using random-effect meta-analyses. Nineteen studies on pneumococcal conjugate vaccines (PCV) met our inclusion criteria. PCV decreases the incidence of nonsusceptible pneumococcal infections (PIs) by 56.91% (95% confidence interval [CI], -50.90% to -62.91%) and the probability of carriage of nonsusceptible pneumococcal bacteria by 28.10% (95% CI, -13.25% to -42.95%). The effect of PCV on PIs becomes higher when only serotypes specifically targeted by the vaccine are taken into account (-80.98%; 95% CI, -70.34% to -91.52%), while it becomes lower when all the PIs, including both susceptible and nonsusceptible PIs, are considered (-48.30%; 95% CI, -31.55% to -65.08%). The effect of PCV is found greater in populations with high prevalence of human immunodeficiency virus and for PCV covering a higher number of serotypes. Findings from this study suggest that vaccination programs may be an effective tool to prevent the spread of PIs and may play a significant role in tackling antimicrobial resistance.
PubMed: 34222121
DOI: 10.7774/cevr.2021.10.2.81 -
Human Vaccines & Immunotherapeutics Oct 2021The aim was to summarize pneumococcal disease burden data among adults in Southern Europe and the potential impact of vaccines on epidemiology. Of 4779 identified... (Meta-Analysis)
Meta-Analysis
The aim was to summarize pneumococcal disease burden data among adults in Southern Europe and the potential impact of vaccines on epidemiology. Of 4779 identified studies, 272 were selected. Invasive pneumococcal disease (IPD) incidence was 15.08 (95% CI 11.01-20.65) in Spain versus 2.56 (95% CI 1.54-4.24) per 100,000 population in Italy. Pneumococcal pneumonia incidence was 19.59 (95% CI 10.74-35.74) in Spain versus 2.19 (95% CI 1.36-3.54) per 100,000 population in Italy. Analysis of IPD incidence in Spain comparing pre-and post- PCV7 and PCV13 periods unveiled a declining trend in vaccine-type IPD incidence (larger and statistically significant for the elderly), suggesting indirect effects of childhood vaccination programme. Data from Portugal, Greece and, to a lesser extent, Italy were sparse, thus improved surveillance is needed. Pneumococcal vaccination uptake, particularly among the elderly and adults with chronic and immunosuppressing conditions, should be improved, including shift to a higher-valency pneumococcal conjugate vaccine when available.
Topics: Adult; Aged; Europe; Greece; Humans; Incidence; Infant; Italy; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Portugal; Spain; Vaccines, Conjugate
PubMed: 34106040
DOI: 10.1080/21645515.2021.1923348 -
Scientific Reports Jun 2021Risk factors associated with mortality in invasive pneumococcal disease remain unclear. The present work is a meta-analysis of studies that enrolled only patients with... (Meta-Analysis)
Meta-Analysis
Risk factors associated with mortality in invasive pneumococcal disease remain unclear. The present work is a meta-analysis of studies that enrolled only patients with invasive pneumococcal disease and reported on mortality. Potentially eligible reports were identified from PubMed, CHAHL, and Web of Science, comprising 26 reports in total. Overall mortality for invasive pneumococcal disease was reported as 20.8% (95% confidence interval (CI) 17.5-24%). Factors associated with mortality were age (odds ratio (OR) 3.04, 95% CI 2.5-3.68), nursing home (OR 1.62, 95% CI 1.13-2.32), nosocomial infection (OR 2.10, 95% CI 1.52-2.89), septic shock (OR 13.35, 95% CI 4.54-39.31), underlying chronic diseases (OR 2.34, 95% CI 1.78-3.09), solid organ tumor (OR 5.34, 95% CI 2.07-13.74), immunosuppressed status (OR 1.67, 95% CI 1.31-2.14), and alcohol abuse (OR 3.14, 95% CI 2.13-4.64). Mortality rates with invasive pneumococcal disease remained high, and these findings may help clinicians provide appropriate initial treatment for this disease.
Topics: Adult; Aged; Chronic Disease; Female; Humans; Immunocompromised Host; Male; Middle Aged; Observational Studies as Topic; Odds Ratio; Pneumococcal Infections; Prognosis; Risk Factors; Shock, Septic; Streptococcus pneumoniae
PubMed: 34088948
DOI: 10.1038/s41598-021-91234-y -
Human Vaccines & Immunotherapeutics Dec 2022In 2010, a 10-valent pneumococcal non-typeable protein D conjugate vaccine (PHiD-CV) was introduced in the Brazilian national immunization program; the 3 + 1 dose...
In 2010, a 10-valent pneumococcal non-typeable protein D conjugate vaccine (PHiD-CV) was introduced in the Brazilian national immunization program; the 3 + 1 dose schedule was replaced by a 2 + 1 dose schedule in 2016. This systematic review presents the latest published evidence (2015-2020) on the impact after 10-year use of PHiD-CV in Brazil from a total of 29 publications. Overall, the PHiD-CV program had a positive impact on the morbidity and mortality associated with invasive pneumococcal disease (IPD), pneumonia and acute otitis media (AOM) in children <5 years-old. A reduction in the vaccine-type invasive disease was observed in all-ages; suggesting indirect protection unvaccinated older children and adults. The occurrence of non-vaccine type disease was evidenced in some studies. Higher vaccination coverage is required at national and state level for sustained population impact. Given the change in the vaccination schedule and the dynamics of pneumococcal disease epidemiology, continuous surveillance is warranted.GSK Study identifier: HO-18-19438.
Topics: Adolescent; Brazil; Child; Child, Preschool; Humans; Infant; Otitis Media; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 33735585
DOI: 10.1080/21645515.2021.1879578