Genomic epidemiology of the cholera outbreak in Malawi 2022-2023

Since early 2022, in the aftermath of two extreme weather events, Malawi experienced its largest ever cholera outbreak, with over 58,000 reported cases and 1,761 deaths as of May 2023. We generated 49 high-quality, near-complete Vibrio cholerae genomes in Malawi from isolates collected between December 2022 and March 2023 from all three regions of Malawi. Using phylogenetic methods with 2159 publicly available genomes, we present evidence suggesting that the Malawi outbreak strains originated from the Pakistan outbreak, the estimated most recent ancestor of this lineage, named T15, was during the Pakistan floods, and once introduced into Malawi was exacerbated by major floods between June and October 2022. The extreme weather events and humanitarian crises in Malawi provided the environment for the spread of V. cholerae, and the subsequent movement of large numbers of people may have facilitated its spread to susceptible populations in areas relatively unaffected by cholera for over a decade. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement CERI and the CLIMADE program are supported by grants from the Rockefeller Foundation (HTH 017), the African Society for Laboratory Medicine, the SAMRC South African mRNA Vaccine Consortium (SAMVAC), the South African Department of Science and Innovation (SA DSI). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The CLIMADE initiative is approved by the Stellenbosch University Health Research Ethics Committee (BES-2023-24266). The sequencing of V. cholerae outbreak isolates in Malawi was approved by the Public Health Institute of Malawi and Malawi Ministry of Health National Health Sciences Research Committee. Isolates were anonymized and did not contain any personal identifiers. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Raw reads of the isolates that were successfully sequenced have been made publicly available and deposited at the Short Read Archive (SRA) of GenBank, Bioproject: PRJNA967700.