The seventh cholera pandemic arrived in Africa during 1970, and the related cholera strain, Vibrio cholerae O1 biotype El Tor (7PET), has since become endemic in many countries in Africa (1–3). As of March 20, 2023, at least 24 countries globally reported ongoing cholera cases. Several countries in southeastern Africa, in particular Malawi and Mozambique, were experiencing outbreaks. In addition, outbreaks were spreading regionally, including to Tanzania, Zambia, Zimbabwe, and South Africa. The largest active cholera outbreak on the continent was in Malawi: 54,841 cases and 1,684 deaths reported during February 28, 2022–March 20, 2023 (4).

South Africa is not considered endemic for cholera; previous outbreaks have typically been associated with importation events. However, cholera remains under active surveillance in South Africa. The National Institute for Communicable Diseases is notified of all suspected cases. All V. cholerae isolates are submitted to the Centre for Enteric Diseases, which provides further laboratory investigation, including phenotypic and genotypic characterization (Appendix 1) (5). Ethics approval was obtained from the Human Research Ethics Committee, University of the Witwatersrand, Johannesburg, South Africa (protocol reference no. M210752).

As of February 28, 2023, a total of 6 cholera cases in South Africa had been laboratory confirmed by the Centre for Enteric Diseases; fecal samples were collected from patients February 1–23, 2023. All cases occurred in Gauteng Province (Table); 3 case-patients were female (19–44 years of age) and 3 male (23–41 years of age). Cases 1–3 were imported or import-related cases. Case-patients 1 and 2 (sisters) left Johannesburg on January 15, 2023, and traveled together to Chinsapo, Lilongwe, Malawi, in one of the districts reporting active outbreaks, where they stayed until their departure on January 29, 2023. Both women reported onset of symptoms within 12 hours of departure during the bus trip back to Johannesburg. Case-patient 3 was a close household contact of case-patient 1. Case-patients 4–6 acquired infection locally and were classified as indigenous cases; none had travelled or had any link to the imported or import-related cases or to one another. We identified isolates associated with all 6 cases as V. cholerae O1 serotype Ogawa and all were PCR-positive for the cholera toxin–producing gene.

We used whole-genome sequencing, comparative genomics, and phylogenetic analysis to further characterize the isolates (Appendix 2 Tables 1, 2). The 6 V. cholerae O1 isolates had similar genomic features, including the toxin-coregulated pilus gene subunit A gene variant, tcpA^CIRS101, a deletion (ΔVC_0495-VC_0512) within the vibrio seventh pandemic island II (VSP-II), and an SXT/R391 integrating conjugating element called ICEVchInd5, encoding resistance to streptomycin (strAB), sulfonamides (sul2), trimethoprim (dfrA1), and trimethoprim/sulfamethoxazole (dfrA1 and sul2) and resistance or intermediate resistance to chloramphenicol (floR). The isolates also had mutations of VC_0715 (resulting in the R169C substitution) and VC_A0637 (resulting in the premature stop codon Q5Stop) conferring nitrofuran resistance, and of the DNA gyrase, gyrA (S83I), and topoisomerase IV, parC (S85L) genes, conferring resistance to nalidixic acid and decreased susceptibility to ciprofloxacin (3,6). The isolates also had a specific nonsynonymous single-nucleotide variant (SNV) in the vprA gene (VC_1320) (resulting in the D89N substitution), conferring susceptibility to polymyxins (6).

Figure

Figure. Maximum-likelihood phylogeny of Vibrio cholerae O1 El Tor isolates collected in South Africa, 2023, compared with 1,443 reference seventh pandemic V. choleraeEl Tor (7PET) genomic sequences....

To place these 6 isolates into a global phylogenetic context, we constructed a maximum-likelihood phylogeny of 1,443 genomes (Appendix 2 Table 3) with 10,679 SNVs evenly distributed over the nonrepetitive, nonrecombinant core genome. All isolates from South Africa clustered together (median pairwise distance of 4 [range 0–8] core-genome SNVs) in the 7PET lineage wave 3 clade, containing isolates carrying the ctxB7 allele (Figure) (6). However, those isolates did not belong to any of the sublineages previously found in Africa (AFR1 and AFR3–AFR 14) (Figure) (3,6,7); instead, they tightly grouped with genomes of south Asia variants, suggesting that the 2022–2023 cholera outbreak in Malawi and cases in South Africa in our study were associated with a newly imported 7PET strain, sublineage AFR15, from south Asia. All but 1 of the closest genomes were either collected locally and identified in Pakistan during June–December 2022 or detected within the framework of cholera surveillance in the United States or Australia (8).

In conclusion, we show that isolates from cases in South Africa, which have been linked to the 2022–2023 cholera outbreak in Malawi, belong to the seventh pandemic El Tor sublineage AFR15. Those cases did not result from resurgence of a strain previously circulating in any region of Africa but were caused by a cholera agent newly introduced into Africa from south Asia. This finding offers valuable information to all public health authorities in Africa. Genomic microbial surveillance and cross-border collaborations have a key role to play in identifying new cholera introductions, areas prone to cholera importation, and the main routes of cholera circulation. All of these elements are key to better understanding cholera epidemiology in Africa.

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