Effectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study

Cohen, Cheryl; Mollendorf, Claire von; Gouveia, Linda de; Lengana, Sarona; Meiring, Susan; Quan, Vanessa; Nguweneza, Arthermon; Moore, David P.; Reubenson, Gary; Moshe, Mamokgethi; Madhi, Shabir А.; Eley, Brian; Hallbauer, Ute; Finlayson, Heather; Varughese, Sheeba; O'Brien, Katherine L.; Zell, Elizabeth R.; Klugman, Keith P.; Whitney, Cynthia G.; Gottberg, Anne von

doi:10.1016/s2214-109x(17)30043-8

Cited by 50 publications

(45 citation statements)

References 18 publications

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“…Regardless, PCV7 caused >85% reduction in IPD in South Africa, crucially in HIV-infected individuals [5]. Consistent with findings in high-income countries [6], higher-valent PCVs appears to be highly effective in reducing VT serotypes in carriage (>65%) and IPD (>80%) in Africa[7–9].…”

Section: Introductionmentioning

confidence: 67%

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Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data

Chaguza

Heinsbroek

Gladstone

et al. 2018

Preprint

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36Pneumococcal conjugate vaccines (PCV) have reduced pneumococcal diseases glob-37 ally. Despite this, much remains to be learned about their effect on pathogen pop-38 ulation structure. Here we undertook whole genome sequencing of 660 pneumococ-39 cal strains from asymptomatic carriers to investigate population restructuring in 40 pneumococcal strains sampled before and after PCV13 introduction in a previously 41 vaccine-naïve setting. We show substantial decreasing frequency of vaccine-type (VT) 42 strains and their strain diversity post-vaccination in the vaccinated but not unvacci-43 nated age groups indicative of direct but limited or delayed indirect effect of vaccina-44 tion. Clearance of identical VT serotypes associated with multiple lineages occurred 45 regardless of their genetic background. Interestingly, despite the increasing frequency 46 of non-vaccine type (NVT) strains through serotype replacement, the serotype diver-47 sity was not fully restored to the levels observed prior to vaccination implying lim-48 ited serotype replacement. The frequency of antibiotic resistant strains was low and 49 remained largely unchanged post-vaccination but intermediate-penicillin-resistant 50 lineages were reduced in the post vaccine population. Significant perturbations marked 51 by changing frequency of accessory genes associated with diverse functions especially 52 mobile genetic elements and bacteriocin activity were detected. This phylogenomic 53 analysis demonstrates early vaccine-induced pneumococcal population restructuring 54 not only at serotype but also accessory genome level. 55 Author summary 56 Different formulations of PCVs have been effective in reducing the invasive pneu-57 mococcal disease burden globally. Clinical trials have started to indicate high im-58 pact and effectiveness of PCV13 in Sub Saharan Africa (SSA) but there is limited 59 understanding of how the introduction of PCVs alters the population structure of 60 pneumococcal strains at serotype and genomic level. Here we investigated this using 61 pneumococcal strains sampled pre-and post-PCV13 introduction from a previously 62 vaccine naïve setting in Northern Malawi. Our findings reveal decrease in frequency 63 of VT serotypes and their associated lineages in the largely vaccinated under-five 64 population but not older individuals indicating a direct but limited or delayed in-65 direct protection. The diversity of serotypes also decreased post-vaccination in VT 66 strains in the under-fives but there was no change in NVT strains suggesting incom-67 plete serotype replacement. At the genomic level, logistic regression revealed chang-68 ing frequency of accessory genes largely associated with mobile genetic elements but 69 2 such changes did not include any antibiotic resistance genes. These findings show 70 significant perturbations at serotype and accessory genome level in carried pneumo-71 coccal population after two years from PCV13 introduction but the pneumococcal 72 population was still perturbed and had not returned to a new e...

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Section: Introductionmentioning

confidence: 67%

“…In addition to reducing IPD [2, 8, 9], PCV has an added benefit of reducing VT carriage [10]. However, the impact on overall carriage rate and density is not substantial [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data

Chaguza

Heinsbroek

Gladstone

et al. 2018

Preprint

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“…Disappointingly, introduction of the broader vaccine did not further improve ear health. The vaccine efficacy for prevention of invasive disease has been proven [58, 59]. Although thoroughly studied regarding several aspects, including OM, there is at present a lack of knowledge on the specific effects of PCV on rAOM.…”

Section: Preventionmentioning

confidence: 99%

Recurrent Acute Otitis Media: What Are the Options for Treatment and Prevention?

Granath

2017

Curr Otorhinolaryngol Rep

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Purpose of ReviewTo survey current strategies for treatment and prevention of recurrent acute otitis media (rAOM).Recent FindingsTreatment with systemic antibiotics is required in recurrent episodes of acute otitis media. A cautious attitude is recommended due to antibiotic resistance. Antibiotics also provide effective prophylaxis for rAOM. Topical treatment with ear drops is recommended in rAOM with otorrhea from tympanostomy tubes. Pneumococcal conjugated vaccines seem to have a moderate reductive effect on overall otitis media. The effect on rAOM is still unclear. Different administrations of immunoglobulins have not been effective against rAOM. Breastfeeding had a protective effect against rAOM. A recommendation against cigarette smoke exposure as a measure to prevent otitis seems warranted. An effect for adenoidectomy in children <2 years old with rAOM has been suggested. There is a strong genetic connection with rAOM. Probiotics and nasal spray with Streptococci might offer future opportunities as prophylaxis. Too little is known about complimentary treatments to give any recommendations.SummarySystemic antibiotics are still needed as treatment against episodes of AOM in rAOM children. There are several preventive measures that can be taken to reduce the burden of AOM but they all have a small-moderate effect. Systemic antibiotics provide effective prophylaxis in rAOM, but must be used with extreme caution due to the emerging antibiotic resistance.

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“…Studies in sub-Saharan Africa have reported varied measures of vaccine effectiveness and impact. Overall, there is overwhelming evidence of effectiveness against invasive pneumococcal disease with significant decline in disease after introduction of the vaccine (25–29).…”

Section: Introductionmentioning

confidence: 99%

Estimating the impact of pneumococcal conjugate vaccines on childhood pneumonia in sub-Saharan Africa: A systematic review

Onwuchekwa

Edem

Williams

et al. 2019

Preprint

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BackgroundThe impact of pneumococcal conjugate vaccine introduction in reducing the incidence of childhood pneumonia has not been well documented in sub-Saharan Africa. Many studies evaluating vaccine impact have used invasive pneumococcal disease or pneumococcal pneumonia as an outcome.ObjectiveTo estimate the impact of routine administration of 10-valent and 13-valent PCV on the incidence of pneumonia in children under five years of age in sub-Saharan Africa.Data sourcesA systematic review was conducted between 16 and 31 July 2019. The review was registered on PROSPERO with registration number CRD42019142369. The literature search was conducted in indexed databases including Medline and Embase, grey literature databases and online libraries of two universities. Manual search of the references of included studies was performed to identify additional relevant studies. The search strategy combined pneumococcal conjugate vaccine, pneumonia and child as search concepts.Study selectionStudies investigating the impact of 10- or13-valent PCV on childhood pneumonia in a sub-Saharan African country were eligible for inclusion. Case-control, cohort, pre-post and time-series study designs were eligible for inclusion. Exclusion criteria were use of 7- or 9-valent PCV, systematic review studies, clinical trials and record publication prior to 2009.Data extractionIndependent data extraction was conducted. Key variables include year study conducted, type of study design, type of PCV used and year of introduction, reported PCV coverage, outcome measure evaluated and the effect measure.Data synthesisEight records were included in the final analysis, 6 records were pre-post or time-series studies, 1 was a case-control study and 1 report combined pre-post and case-control studies. Vaccine impact measured as percentage reduction in risk (%RR) of clinical pneumonia was mostly small and non-significant. The risk reduction was more significant and consistent on radiological and pneumococcal pneumonia. Vaccine effectiveness reported in case-control studies was mostly non-significant.ConclusionEvidence of the positive impact of routine infant pneumococcal vaccination on pneumonia in sub-Saharan Africa is weak. There is a need for more research in this area to evaluate the influence of pathogen or serotype replacement in pneumonia after PCV introduction. Ongoing surveillance is also required to establish the long term trend in pneumonia epidemiology after PCV introduction.

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Effectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study

Abstract: Gavi, The Vaccine Alliance.

Cited by 50 publications

References 18 publications

Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data

Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data

Recurrent Acute Otitis Media: What Are the Options for Treatment and Prevention?

Estimating the impact of pneumococcal conjugate vaccines on childhood pneumonia in sub-Saharan Africa: A systematic review

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