Cholera

BackgroundCholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology.MethodsFrom a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics.ResultsWe identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks.ConclusionsThis study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored.

Since 2016, Yemen has been experiencing the largest cholera outbreak in modern history. Multidrug resistance (MDR) emerged among Vibrio cholerae isolates from cholera patients in 2018. Here, to characterize circulating genotypes, we analysed 260 isolates sampled in Yemen between 2018 and 2019. Eighty-four percent of V. cholerae isolates were serogroup O1 belonging to the seventh pandemic El Tor (7PET) lineage, sub-lineage T13, whereas 16% were non-toxigenic, from divergent non-7PET lineages. Treatment of severe cholera with macrolides between 2016 and 2019 coincided with the emergence and dominance of T13 subclones carrying an incompatibility type C (IncC) plasmid harbouring an MDR pseudo-compound transposon. MDR plasmid detection also in endemic non-7PET V. cholerae lineages suggested genetic exchange with 7PET epidemic strains. Stable co-occurrence of the IncC plasmid with the SXT family of integrative and conjugative element in the 7PET background has major implications for cholera control, highlighting the importance of genomic epidemiological surveillance to limit MDR spread.

The current circulating pandemic El Tor biotype of Vibrio cholerae has persisted for over sixty years and is characterized by its acquisition of two unique genomic islands called the Vibrio Seventh Pandemic Islands 1 and 2 (VSP-I and VSP-II). However, the functions of most of the genes on VSP-I and VSP-II are unknown and the advantages realized by El Tor through these two islands are not clear. Recent studies have broadly implicated these two mobile genetic elements with phage defense. Still, protection against phage infection through these islands has not been observed directly in any V. cholerae El Tor biotype. Here we report the isolation of a circulating phage from a cholera patient stool sample and demonstrate that propagation of this phage in its native host is inhibited by elements in both VSP-I and VSP-II, providing direct evidence for the role of these genomic islands in phage defense. Moreover, we show that these defense systems are regulated by quorum sensing and active only at certain cell densities. Finally, we have isolated a naturally occurring phage variant that is resistant to the defense conferred by the VSP islands, illustrating the countermeasures used by phages to evade these defense mechanisms. Together, this work demonstrates a functional role for the VSPs in V. cholerae and highlights the key regulatory and mechanistic insights that can be gained by studying anti-phage systems in their native contexts.

Cholera remains a significant public health burden in many countries in sub-Saharan Africa, though the exact mechanisms of bacterial emergence and spread remain largely undefined. We generated genomic data from 763 Vibrio cholerae O1 isolates predominantly collected between 2019-2024 to create the largest dataset of V. cholerae genomes sequenced locally in Africa. This dataset enabled us to interrogate recent patterns of spread, including the rapid circulation of the AFR15 lineage associated with unusually large outbreaks in Southern Africa. We provide evidence for the movement of the AFR15 lineage into new African Union Member States and confirm previously observed differences in V. cholerae transmission dynamics in West versus East Africa, though cross-border transmission is prevalent on both sides of the continent. Despite observed differences, evolutionary processes are similar across lineages and we find no evidence for significant changes in antimicrobial resistance genotypes. Overall, our findings emphasize the importance of regionally coordinated cross-border surveillance and interventions, while also demonstrating the critical role of locally generated genomic data in understanding the spread of cholera in Africa.