High residual prevalence of vaccine-serotypeStreptococcus pneumoniaecarriage after introduction of a pneumococcal conjugate vaccine in Malawi: a prospective serial cross-sectional study

Abstract

BackgroundThere are concerns that pneumococcal conjugate vaccines (PCV) in sub-Saharan Africa sub-optimally interrupt vaccine-serotype (VT) carriage and transmission, thus limiting vaccine-induced direct and indirect protection. We assessed carriage in vaccinated children and unvaccinated populations targeted for indirect protection, between 4 and 7 years after Malawi's November 2011 introduction of PCV13 using a 3+0 schedule. MethodsWe conducted sequential prospective nasopharyngeal carriage surveys between 2015 and 2018 among healthy PCV-vaccinated and PCV-unvaccinated children, and HIV-infected adults. VT and NVT carriage risk by age was analysed by non-linear regression. ResultsAmong PCV-vaccinated children, there was a 24% relative reduction in carriage, from a mean 21.1% to 16.1%; 45% reduction among older PCV-unvaccinated children, from 27.5% to 15.2%; 41.4% reduction among adults, from 15.2% to 8.9%. Using carriage data from children 3.6 to 10 years of age, VT carriage probability declined with age, with a similar prevalence half-life among PCV-vaccinated (3.34 years) and children. ConclusionCompared to high-income settings, the 3+0 schedule in Malawi has led to a sub-optimal reduction in pneumococcal carriage prevalence. This is likely due to recolonisation of vaccinated children with waning vaccine-induced immunity, resulting in insufficient indirect protection of unvaccinated populations. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns is required.

Determinants of high residual post-PCV13 pneumococcal vaccine type carriage in Blantyre, Malawi: a modelling study

“…A deterministic, ordinary-differential equations (ODE) model ( Figure 1a) was developed to fit VT carriage levels as reported in the cross-sectional observational study in Blantyre (Figure 1d) 22 . Fitting was implemented using a Bayesian Markov chain Monte Carlo (bMCMC) approach developed and used by us in other modelling studies [37][38][39] , including informative priors for duration of carriage ( Figure 1b, Table S1) and uninformative uniform priors for vaccine efficacy (individuallevel protection against carriage) and transmission potential.…”

“…For simplicity, routine vaccination was implemented at birth with coverage (ρ) at 92.5% 22 , and catch-up (k) implemented as a one-off transfer of a proportion of individuals from the unvaccinated susceptibles with 0 (<1) years of age (S 0 ) to the vaccinated susceptible class with the same age (S v 0 ) with coverage of 60% 22 . We assumed the vaccine to reduce the risk of infection (colonization) of vaccinated individuals by a proportion ζ (between 0 and 1, with ζ=1 equating to no risk).…”

“…With high routine coverage (~90%) and a small catch-up campaign of young children, PCV13 was expected to quickly reduce carriage as previously reported in developed countries. However, recently published data on nasopharyngeal carriage as measured in a cross-sectional observational study in Blantyre (Southern Malawi), four to seven years after PCV13 introduction (2015)(2016)(2017)(2018), has shown that vaccine impact (VT carriage reduction) has been slower than expected and heterogeneous across age-groups 22 . Epidemiological mathematical models have previously been employed successfully to improve our understanding of pneumococcal dynamics 5,9,[23][24][25][26][27] , as well as having contributed to explain, estimate and project PCV impact 8,11,28 .…”

“…Observed VT carriage levels are presented in Figure 1d (and Table S7). Further details on collection, processing and observations, have been previously described in detail 22 .…”

Pneumonia in the developing world: Characteristic features and approach to management

“…Whilst pneumococcal conjugate vaccine (PCV) is known to be effective in HIV‐positive patients, it remains to be seen whether the significant reductions in vaccine‐serotype pneumococcal disease observed in adults in high‐income countries following the introduction of universal infant immunization with PCV are replicated in high HIV burden settings . HIV‐infected adults remain an important reservoir for carriage of pneumococci even after several years of antiretroviral therapy (ART) and apparent immune reconstitution . ART, however, markedly reduces the risk of pneumonia in HIV‐infected patients and early initiation improves survival .…”