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

Madikay Senghore, Peggy-Estelle Tientcheu, Archibald Kwame Worwui, Sheikh Jarju, Catherine Okoi, Sambou M S Suso, Ebenezer Foster-Nyarko, Chinelo Ebruke, Mohamadou Sonko, Mamdou Hama Kourna, Joseph Agossou, Enyonam Tsolenyanu, Lorna Awo Renner, Daniel Ansong, Bakary Sanneh, Catherine Boni Cisse, Angeline Boula, Berthe Miwanda, Stephanie W Lo, Rebecca A GladstoneStephanie Schwartz, Paulina Hawkins, Lesley McGee, Keith P Klugman, Robert F Breiman, Stephen D Bentley, Jason M Mwenda, Brenda Anna Kwambana-Adams, Martin Antonio

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalMicrobial Genomics
Volume7
Issue number7
DOIs
Publication statusPublished - 30 Jul 2021

Bibliographical note

Data statement: All supporting data, code and protocols have been provided within the article or through supplementary data files. One supplementary figure and two supplementary tables are available with the online version of this article.

Funding information
This work was supported by the World Health Organization Regional Office for Africa. The GAVI, The Vaccine Alliance provided funding to the World Health Organization to support new vaccines sentinel surveillance implemented by the national governments and support for Regional Reference laboratory at the Medical Research Council Unit, The Gambia.

Keywords

  • Adolescent
  • Africa, Western/epidemiology
  • Antitubercular Agents/pharmacology
  • Child
  • Child, Preschool
  • Drug Resistance, Multiple, Bacterial/genetics
  • Genome, Bacterial/genetics
  • Heptavalent Pneumococcal Conjugate Vaccine/immunology
  • Humans
  • Infant
  • Infant, Newborn
  • Meningitis, Pneumococcal/epidemiology
  • Microbial Sensitivity Tests
  • Pneumococcal Vaccines/immunology
  • Streptococcus pneumoniae/drug effects
  • Whole Genome Sequencing

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