Continued T12 transmission and shared antibiotic resistance during 2018-2023 Vibrio cholerae outbreaks in Cameroon

Abstract

Seventh pandemic Vibrio cholerae was first identified in Cameroon in 1971, causing several sporadic disease clusters with few cases. More recent years have seen larger cholera outbreaks, but the mechanism behind these periodic outbreaks is poorly understood, and it is unclear the degree to which antibiotic resistant strains contribute to disease burden and spread. We used whole genome sequencing to characterize 13 V. cholerae isolates from the 2018-2019, 2020, and 2021-2023 cholera epidemics in Cameroon. All these isolates belonged to the T12 lineage, and most showed the same antimicrobial resistance (AMR) pattern regardless of year. This suggests that cholera outbreaks in Cameroon are, at least in part, a continuation of the outbreaks previously reported in 2018 and as far back as 2012. This finding has important implications for cholera management since it suggests the ongoing presence of pathogenic cholera even in years with few reported cases. Similarly, the AMR results suggest the need for new treatment approaches, as resistance to many common antibiotics was found even within our limited sample set. As such, whole genome sequencing should be implemented in low-income countries such as Cameroon to improve disease surveillance and to detect and predict pathogen antibiotic resistance profiles.

Fig 1. Spatial distribution of V. cholerae isolates selected for sequencing.

Blue: high quality genomes included in downstream analyses; white: sequenced isolates that did not produce high quality genomes (see also S2 Data). The number of cholera cases reported between 18 May 2018 – 17 October 2023 are shown in shades of red (S1 Data). Map created with R raster package. Shapefile source: https://gadm.org/maps/CMR.html.

Fig 2. Maximum likelihood tree of the V. cholerae T12 lineage.

Sequences generated in this study form two distinct T12 sub-clusters and are shown in bright blue. Previously generated sequences from Cameroon are shown in white, and other previously generated sequences from the T12 lineage are colored by the country in which the isolate was collected. Groups of newly generated sequences are labeled by the regions in Cameroon the corresponding isolates were collected in, and sequences with some degree of resistance to doxycycline (see S5 Data) are indicated by a red asterisk. Scale bar: nucleotide substitutions per site. Full V. cholerae O1 tree including other lineages: S1 Fig.

Fig 3. AMR-associated genes identified in V. cholerae core genome.

Blue = gene presence; gray = gene absence. Isolates to the left of the dotted line also underwent antibiotic resistance testing in the laboratory, and the results of these assays are presented in S5 Data. The top six genes shown were also observed in Cameroonian samples from a similar timeframe [14].