Moisi, J. | bioRxiv Science

bioRxiv2018

Impact of 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya

Background10-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10 and 14 weeks of age, was introduced in Kenya in January 2011, accompanied by a catch-up campaign in Kilifi County for children <5 years. Coverage with [≥]2 PCV10 doses in children 2-11 months was 80% in 2011 and 84% in 2016; coverage with [≥]1 dose in children 12-59 months was 66% and 87%, respectively.\n\nMethodsClinical and microbiological surveillance for invasive pneumococcal disease (IPD) among admissions of all ages at Kilifi County Hospital was linked to the Kilifi Health and Demographic Surveillance System from 1999-2016. We calculated the incidence rate ratio (IRR) comparing the pre-vaccine and post-vaccine eras, adjusted for confounding, and reported percent reduction in IPD as 1-IRR. Annual cross-sectional surveys of nasopharyngeal carriage were conducted from 2009-2016.\n\nFindingsSurveillance identified 667 IPD cases in 3,211,403 person-years of observation. IPD incidence in children <5 years fell sharply in 2011 following PCV10 introduction, and remained low (PCV10-type IPD: 60{middle dot}8 vs 3{middle dot}2/100,000 [92% reduction; 95%CI: 78, 97]; overall IPD: 81{middle dot}6 vs 15{middle dot}3/100,000 [68% reduction; 95%CI: 40, 83]; 1999-2010 vs 2012-2016). PCV10-type IPD also declined significantly in unvaccinated age groups (<2 months, 5-14 years, [≥]15 years), with estimated reductions of 100%, 74%, and 81%, respectively. There was no significant change in the incidence of non-PCV10 type IPD. In children aged <5 years, PCV10-type carriage declined by 74% and non-PCV10-type carriage increased by 71%.\n\nInterpretationIntroduction of PCV10 in Kenya resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. These findings suggest that routine infant PCV10 immunization programmes with catch-up campaigns will provide substantial direct and indirect protection in low-income settings in tropical Africa.

epidemiology↗

bioRxiv2018

Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the United States, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identify a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939-1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.\n\nAuthor SummaryStreptococcus pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and otitis media. Despite inclusion in the most recent pneumococcal conjugate vaccine, PCV13, serotype 3 remains epidemiologically important globally. We investigated the persistence of serotype 3 using whole-genome sequencing data form 301 isolates collected among 24 countries from 1993-2014. Through phylogenetic analysis, we identified three distinct lineages within a single clonal complex, CC180, and found one has recently emerged and grown in prevalence. We then compared genomic difference among lineages as well as variations in pneumococcal vaccine use among sampled countries. We found that the recently emerged lineage, termed Clade II, has a higher prevalence of antibiotic resistance compared to other lineages, diverse surface protein antigens, and a higher rate of recombination, a process by which bacteria can uptake and incorporate genetic material from its surroundings. Differences in vaccine use among sampled countries did not appear to be associated with the emergence of Clade II. We highlight the need to routine, representative sampling of bacterial isolates from diverse geographic areas and show the utility of genomic data in resolving epidemiological differences within a pathogen population.

evolutionary biology↗