Recent and convergent reversion to serotype Ogawa in the AFR12 sublineage of Vibrio cholerae O1 El Tor in Cameroon

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Abstract

Since 1971, Cameroon has experienced several outbreaks of cholera due to strains of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage originating from South Asia. Over the last six years, more than 26,000 cholera cases have been reported. The aim of this study was to perform a genomic characterisation of the V. cholerae O1 isolates collected during recent cholera outbreaks in Cameroon. We investigated the virulence, antimicrobial resistance (AMR) signatures and phylogenetic relationships between 164 clinical V. cholerae isolates representative of the successive outbreaks that were collected between 2018 and 2023. A phylogenomic analysis of more than 1,700 7PET genomes —including 45 from isolates collected in Cameroon between 1971 and 2011 — was performed to place the recent 7PET strains in a broader phylogenetic context. We found that all the recent Cameroonian isolates studied belonged to genomic wave 3 of the 7PET lineage. They clustered together within the AFR12 sublineage (which was identified for the first time in Cameroon in 2009 and with contemporary isolates from other countries in the same region). Serotyping and genome analysis revealed a reversion from serotype Inaba (all isolates between 2018 and 2019) to Ogawa (all isolates between 2021 and 2023) in two different strains originating from different regions of Cameroon. Finally, the AFR12 isolates studied here were less resistant to antimicrobial drugs than the AFR12 isolates identified in Cameroon between 2009 and 2011 due to a 10-kb deletion in the integrative conjugative element conferring multidrug resistance, ICE Vch Ind5, resulting in the loss of four antimicrobial resistance (AMR) genes ( strA , strB , floR and sul2 ). Our findings confirm the complementarity between traditional microbiological methods and microbial genomics for monitoring circulating 7PET strains and tracking their evolution development and that of AMR in particular.

IMPACT STATEMENT

The number of cholera cases has fallen since the beginning of 2024 (only 49 cases reported up to July 28), but Cameroon, in Central Africa, experienced a number of cholera epidemics between 2018 and 2023, with 26,411 cholera cases in total and 735 deaths (case fatality rate: 2.8%). We performed a phenotypic and genomic analysis of 164 V. cholerae O1 isolates representative of the successive outbreaks that were collected from 2018 to 2023 from seven of the 10 regions of Cameroon, which revealed that these isolates were very similar and closely related to other West African isolates. All belonged to the same pandemic lineage thought to have been introduced into West Africa from South Asia in 2007. The strains of this lineage have become less resistant to antimicrobial drugs over time, due to a single genetic event (i.e., deletion of a region of the bacterial chromosome containing several antimicrobial resistance genes) and have reverted to the Ogawa serotype (the original serotype of wild-type strains). Neither of these changes were anticipated. Furthermore, our findings support the hypothesis that the causal agent of cholera is permanently circulating in the countries around the Lake Chad basin and those of West Africa. They stress the importance of combining a genomic approach with traditional microbiology for the epidemiological surveillance of cholera. Furthermore, transborder collaborative efforts are strongly advised to ensure effective cholera control in this region.

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