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Effectiveness of pneumococcal conjugate vaccines against invasive pneumococcal disease among children under five years of age in Africa: A systematic review.

ABSTRACT: BACKGROUND:Despite the widespread implementation of the pneumococcal conjugate vaccine, Streptococcus pneumoniae remains the leading cause of severe pneumonia associated with mortality among children less than 5 years of age worldwide, with the highest mortality rates recorded in Africa and Asia. However, information on the effectiveness and prevalence of vaccine serotypes post-roll out remains scarce in most African countries. Hence, this systematic review aimed to describe what is known about the decline of childhood invasive pneumococcal disease post-introduction of the pneumococcal conjugate vaccine in Africa. METHODS:This systematic review included articles published between 2009 and 2018 on the implementation of the pneumococcal conjugate vaccine in Africa. We searched PubMed, Scopus and African Index Medicus for articles in English. Studies on implementation programmes of pneumococcal conjugate vaccine 10/13, with before and after data from different African countries, were considered eligible. The review followed the procedures published in PROSPERO (ID = CRD42016049192). RESULTS:In total, 2,280 studies were identified through electronic database research, and only 8 studies were eligible for inclusion in the final analysis. Approximately half (n = 3) of these studies were from South Africa. The overall decline in invasive pneumococcal disease ranged from 31.7 to 80.1%. Invasive pneumococcal diseases caused by vaccine serotypes declined significantly, the decline ranged from 35.0 to 92.0%. A much higher decline (55.0-89.0%) was found in children below 24 months of age. Of all vaccine serotypes, the relative proportions of serotypes 1, 5 and 19A doubled following vaccine roll out. INTERPRETATION:Following the introduction of the pneumococcal conjugate vaccine, a significant decline was observed in invasive pneumococcal disease caused by vaccine serotypes. However, data on the effectiveness in this region remain scarce, meriting continued surveillance to assess the effectiveness of pneumococcal vaccination to improve protection against invasive pneumococcal disease.

SUBMITTER: Ngocho JS

PROVIDER: S-EPMC6380553 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effectiveness of pneumococcal conjugate vaccines against invasive pneumococcal disease among children under five years of age in Africa: A systematic review.

Ngocho James Samwel JS Magoma Best B Olomi Gaudencia Alois GA Mahande Michael Johnson MJ Msuya Sia Emmanueli SE de Jonge Marien Isaäk MI Mmbaga Blandina Theophil BT

PloS one 20190219 2

<h4>Background</h4>Despite the widespread implementation of the pneumococcal conjugate vaccine, Streptococcus pneumoniae remains the leading cause of severe pneumonia associated with mortality among children less than 5 years of age worldwide, with the highest mortality rates recorded in Africa and Asia. However, information on the effectiveness and prevalence of vaccine serotypes post-roll out remains scarce in most African countries. Hence, this systematic review aimed to describe what is know ...[more]

PMID: 30779801

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Project description:IntroductionThe widespread implementation of pneumococcal conjugate vaccines (PCVs) has significantly reduced the burden of pneumococcal disease around the world. Although licensed 10-valent (PCV10) and 13-valent (PCV13) vaccines have considerably reduced mortality and morbidity, a sizeable disease burden attributable to serotypes not contained in these PCVs remains. This study aimed to estimate the annual clinical and economic burden of pneumococcal disease attributable to licensed (PCV10 and PCV13) and investigational PCVs, notably 15-valent (PCV15) and 20-valent (PCV20) vaccines, in 13 countries in children under 5 years of age.MethodsA decision-analytic model was created to aggregate total cases [inclusive of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM)], deaths, and direct costs in each country of interest [stratified by PCV10/PCV13 countries, depending on national immunization programs (NIPs)] over 1 year, using up to the three most recent years of available serotype coverage data. Data inputs were sourced from local databases, surveillance reports, and published literature.ResultsIn 5 PCV10 NIPs (Austria, Finland, Netherlands, New Zealand, Sweden), most remaining PCV20-type disease was due to PCV13-unique serotypes (30-85%), followed by PCV20-unique (9-50%), PCV15-unique (4-15%), and PCV10-unique (2-14%) serotypes. In 8 PCV13 NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, United Kingdom), most remaining PCV20-type disease was caused by PCV20-unique serotypes (16-69%), followed by PCV13-unique (11-54%), PCV15-unique (2-33%), and PCV10-unique serotypes (3-19%). Across all countries, PCV20 serotypes caused 3000 to 345,000 cases of disease and cost between $1.3 and $44.9 million USD annually with variability driven by population size, NIP status, and epidemiologic inputs. In aggregate, PCV20 serotypes caused 1,234,000 cases and $213.5 million in annual direct medical costs in children under 5 years of age.ConclusionDespite the success of PCV10 and PCV13 in reducing pneumococcal disease, a substantial clinical and economic burden remains due to serotypes contained in investigational vaccines.

Project description:BackgroundThe study objective was to determine the carriage and serotype distribution of Streptococcus pneumoniae among children in Accra, Ghana, five years after the introduction of the pneumococcal conjugate vaccine (PCV-13) in 2012.MethodsNasopharyngeal swab samples were collected from 410 children below 5?years of age in Accra, Ghana, from September to December, 2016. Pneumococcal isolates were identified by optochin sensitivity and bile solubility. Serotyping was performed using the latex agglutination kit and Quellung reaction. The isolates were furthermore tested for antimicrobial susceptibility for different antimicrobials, including penicillin (PEN). Twelve isolates including seven non-typeable (NT) isolates were characterized using whole-genome sequencing analysis (WGS).ResultsThe overall carriage prevalence was found to be 54% (95% CI, 49-59%), and 20% (95% CI, 49-59%) of the children were carrying PCV-13 included serotypes, while 37% (95% CI, 33-42%) of the children were carrying non-PCV-13 serotypes. Based on the serotype distribution, 33% of all observed serotypes were included in PCV-13 while 66% were non-PCV-13 serotypes. The dominating non-PCV-13 serotypes were 23B, 16F, and 11A followed by PCV-13 serotypes 23F and 19F. The PCV-13 covers the majority of resistant isolates in Accra. A proportion of 22.3% of the isolates showed intermediate resistance to penicillin G, while only one isolate showed full resistance. Forty-five isolates (20.5%) were defined as multidrug-resistant (MDR) as they were intermediate/resistant to three or more classes of antimicrobials. Of the seven NT isolates characterized by WGS, four showed highest match to genotype 38, while the remaining three showed highest match to genotype 14. Four MDR serotype 19A isolates were found to be MLST 320.ConclusionPCV-13 introduced in Ghana did not eliminate PCV-13 covered serotypes, and the carriage rate of 54% in this study is similar to carriage studies from pre PCV-13 period. However, the penicillin non-susceptible isolates have been reduced from 45% of carriage isolates before PCV-13 introduction to 22.3% of the isolates in this study. Continuous monitoring of serotype distribution is important, and in addition, an evaluation of an alternative vaccination schedule from 3?+?0 to 2?+?1 will be important to consider.

Project description: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 among patients tested by PCR or culture methods; however trends of non-vaccine serotypes/serogroups differed between the two groups. Misclassifications of serotypes/serogroups, affecting the use of non-vaccine serotypes as a control group, may have occurred due to the low performance of the serotyping assay among lytA-positive cases with high Ct-values. Until PCR methods improve further, culture methods should continue to be used to monitor the effects of PCV vaccination programs on IPD incidence.

Project description:IntroductionUse of the 13-valent pneumococcal conjugate vaccine in nonimmunocompromised adults aged ≥65 years is controversial. Higher-valency conjugate vaccines (15-valent and 20-valent ) are under development; their potential cost effectiveness in older adults is unknown, particularly when potential indirect (herd immunity) effects from childhood vaccination are considered.MethodsA Markov model estimated the cost effectiveness of current U.S. recommendations and alternative strategies using currently available and in-development pneumococcal conjugate vaccines in seniors. Separately, strategies using a hypothetical 20-valent vaccine adding the 7 most common disease-causing non-13-valent vaccine serotypes were considered. Sensitivity analyses were performed and alternative scenarios were examined. Data were gathered and the analyses were performed in 2020.ResultsIn analyses considering only existing and in-development vaccines, sole 20-valent vaccine use cost $172,491/quality-adjusted life year gained compared with current U.S. recommendations under baseline assumptions (equal serotype effectiveness and no childhood vaccination indirect effects). Strategies using 15-valent vaccine were more costly and less effective. When 13-valent/20-valent vaccines were assumed ineffective against pneumococcal serotype 3 and 15-valent vaccine was fully effective, 15-valent vaccine cost $237,431/quality-adjusted life year gained. With indirect effects considered, 15-valent or 20-valent vaccine cost >$449,000/quality-adjusted life year gained. When adding hypothetical 20-valent vaccine under baseline assumptions, hypothetical 20-valent vaccine cost $139,348/quality-adjusted life year gained.ConclusionsIn-development pneumococcal conjugate vaccines may be economically unreasonable in older adults, regardless of serotype effectiveness assumptions, particularly when considering potential indirect effects from use of those vaccines in children. Adult vaccines containing high-risk serotypes not contained in childhood vaccines may be more promising.

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

Project description:INTRODUCTION:Africa harbours a high burden of pneumococcal disease, with associated high mortality rates. Despite 34 countries introducing the pneumococcal conjugate vaccine, which reduces the risk of pneumococcal carriage (a prerequisite for disease) of some of the most pathogenic pneumococcal serotypes, it remains uncertain whether they will achieve the sustained direct or indirect protection necessary to reduce pneumococcal carriage to levels sufficient to interrupt transmission and disease. We will therefore summarise the available data on the impact of the pneumococcal conjugate vaccine in reducing vaccine serotype carriage and pneumococcal pneumonia in Africa between 2000 and 2019. METHODS AND ANALYSIS:Using a predetermined search strategy, we will conduct a comprehensive search of PubMed, MEDLINE database, the Excerpta Medica Database, the ISI Web of Science (Science Citation Index), Scopus and the African Index Medicus to identify published studies reporting the prevalence of Streptococcus pneumoniae carriage (vaccine type and non-vaccine type), incidence rates of pneumococcal pneumonia and mortality among children, adults and HIV-infected (all-ages) pre-pneumococcal conjugate vaccine (PCV) and post-PCV introduction (published between 1st January 2000 and 31st December 2019) in African countries that have introduced PCVs (PCV7/PCV10/PCV13) in their routine national immunisation programme. The studies retained and data extracted will be assessed for bias using prevalidated tools and checklists. Heterogeneity across studies will be assessed using the ?2 test on Cochrane Q statistic. A random effect meta-analysis will be used to estimate the overall prevalence of pneumococcal carriage and incidence of pneumococcal pneumonia across studies with similar characteristics. Results will be reported in compliance with the Meta-Analysis Of Observational Studies in Epidemiology guidelines. The protocol has been prepared in accordance to the 2015 guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses. ETHICS AND DISSEMINATION:This systematic review will not require ethical approval as we will be using already published data. The final manuscript will be submitted for publication in a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER:CRD42019130976.

Dataset Information

Effectiveness of pneumococcal conjugate vaccines against invasive pneumococcal disease among children under five years of age in Africa: A systematic review.

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Effectiveness of pneumococcal conjugate vaccines against invasive pneumococcal disease among children under five years of age in Africa: A systematic review.

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