High residual carriage of vaccine-serotype Streptococcus pneumoniae after introduction of pneumococcal conjugate vaccine in Malawi

Abstract

There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi's 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3-5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6-8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with high-income settings, there is high residual VT carriage 3.6-7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.

Fig. 1. Recruitment flow diagram.

Among school-goers (6–10 years old), the number reported as screened does not include parents/guardians who did not come to the school after written invitation. Overall, 3781 letters of invitation were sent to parents/guardians during recruitment of school-goers. Of these, 1493 (39.5%) came to the school to be further informed of the study and consider their child’s participation. Reasons for not accepting the invitation were not routinely collected. A total 1427 school-goers were recruited. Among children recruited from household (18 weeks to 5 years old), study teams maintained a diary of number of homes visited (i.e. knocked on gate/door of main house). An average of 7.2 household were approached for every child screened. Reasons for failing to screen-at-household included, (i) no one home, (ii) someone home but no age-eligible child home, and (iii) age-eligible child home but no parent/guardian available.

Fig. 2. S. pneumoniae carriage prevalence per survey, stratified by study group.

Surveys 1–7 spanned a time of 3.6–7.1 years after the 12 November 2011 introduction of PCV into Malawi’s EPI program. Younger children (4–8 weeks up to 2 years of age; cells a–c) were recruited starting survey 4 or 5. Prevalence of non-carriers is calculated by 1 − (NVT + VT). Aggregated sample size for each study group: a n = 346 children 4–8 weeks old (PCV-unvaccinated), b n = 566 children 18 weeks to 1 year old (PCV vaccinated), c n = 499 children 2 years old (PCV vaccinated), d n = 2565 children 3–7 years old (PCV vaccinated), e n = 1402 children 3–10 years old (PCV-unvaccinated), f n = 1770 HIV-infected adults on ART (PCV-unvaccinated). Refer to Supplementary Tables 3 and 4 for the sample sizes used in calculating per-survey VT and NVT prevalence data and error bars in this figure. 95% confidence interval error bars are shown. The confidence interval bounds are calculated by exponentiating the bounds in the logit scale.

Fig. 3. Distribution of vaccine-serotype (VT) carriage, aggregated across study period and stratified by study group.

Proportion of VT carriage attributed to individual VTs across all surveys, stratified by study group. The denominator for each serotype is the total VT isolates in each study group.

Fig. 4. Modelling the relationship between a child’s probability of VT carriage and age.

Estimated probabilities and pointwise 95% confidence intervals (shaded regions) of the probability of an individual child’s vaccine-serotype (VT) carriage as a function of a child’s age (years), for an unvaccinated child (red line) and a vaccinated child (blue line). The fitted line for unvaccinated children includes the range of the empiric data. The fitted line for vaccinated children is left censored at 3.6 years old and extrapolated beyond the oldest vaccinated child (7.9 years old). The model shows significantly different estimated probabilities of VT carriage for an individual (distance between lines), while the estimated population-level half-life of VT carriage (derived from individual carriage probability data; refer to Table 3 in manuscript) translates to very similar estimates among PCV-vaccinated (3.34 years) and PCV-unvaccinated (3.26 years) children.