Phylogeography and resistome of pneumococcal meningitis in West Africa before and after vaccine introduction

Abstract

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S. pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.

Keywords: West and Central Africa; antibiotic resistance; genomic epidemiology; paediatric meningitis; pneumococcus.

Fig. 1.

Distribution of the major S. pneumoniae serotypes and genotypes among isolates from suspected paediatric meningitis cases pre- and post-PCV introduction in West and Central Africa grouped by sub-region. (a) A map of West Africa including Cameroon with pie charts showing the distribution of the main serotypes. (b) A map with pie charts showing the distribution of the main STs. (c) A stacked column plot showing the proportion of isolates bearing non-vaccine serotypes, PCV7 serotypes and additional PCV13 serotypes before and after the introduction of PCV. (d) A bar graph showing the change in prevalence of the most common serotypes before and after PCV introduction in the Western and Central sub-regions.

Fig. 2.

Phylogeny of S. pneumoniae genotypes causing paediatric meningitis in West and Central Africa, and a scatter plot showing accessory genome similarity. (a) A phylogenetic tree annotated with branches coloured by serotype, with metadata rings to show sub-region of origin, vaccine era and vaccine type with ST displayed as text on the outer ring. (b) A panini accessory genome scatter plot where each point, representing one isolate, is coloured by serotype, and distances between points are proportional to accessory genome similarity. The panini plot is by major serotypes (in bold) and the STs that demonstrate geographical clustering.

Fig. 3.

Trends in the presence and absence of antibiotic-resistance genotypes in the context of sub-region and PCV introduction period. (a) A column plot showing the proportion of genomes bearing antibiotic-resistance genes among serotypes, which were grouped according to whether they were PCV7 serotypes, additional PCV13 serotypes or non-vaccine serotypes. (b) A column plot showing the proportion of isolates bearing antibiotic-resistance among isolates from the pre-and post-PCV introduction periods in each sub-region. Note that only two isolates from the Eastern sub-region in the pre-PCV introduction period were available.

Fig. 4.

Antibiotic resistance and resistance genotype patterns in the context of the whole genome phylogeny. A phylogenetic tree with branches coloured by serotype and metadata blocks corresponding to sub region, vaccine introduction period, phenotypic antibiotic resistance patterns and presence of antibiotic resistance genes for penicillin (PBP, OX), chloramphenicol (cat, C), erythromycin (mef/ermB, E), co-trimoxazole (folP/ folA, SXT), tetracycline (tetM, TE) and cefotaxime (CTX).