Genomic insights into the 2022-2023 Vibrio cholerae outbreak in Malawi

Malawi is experiencing its deadliest Vibrio cholerae (Vc) outbreak following devastating cyclones, with >58,000 cases and >1,700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022- 2023 Vc outbreak isolates. Our results demonstrate the predominance of ST69 seventh cholera pandemic El Tor (7PET) strains expressing O1 Ogawa ([~]80%) serotype followed by Inaba ([~]16%) and typical non-outbreak-associated non-O1/non-ST69 serotypes ([~]4%). Phylogenetic reconstruction of the current and historical Vc isolates from Malawi, together with global Vc isolates, suggested the Malawi outbreak strains originated from Asia. The unique antimicrobial resistance and virulence profiles of the 2022-2023 isolates, notably the acquisition of ICEGEN/ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTX{varphi} prophage, which caused ctxB3 to ctxB7 genotype shift, support the importation hypothesis. These data suggest that the recent importation of ctxB7 O1 strains, coupled with climatic changes, may explain the magnitude of the cholera outbreak in Malawi.