Although much focus is placed on cholera epidemics, the greatest burden occurs in settings in which cholera is endemic, including areas of South Asia, Africa and now Haiti1,2. Dhaka, Bangladesh is a megacity that is hyper-endemic for cholera, and experiences two regular seasonal outbreaks of cholera each year3. Despite this, a detailed understanding of the diversity of Vibrio cholerae strains circulating in this setting, and their relationships to annual outbreaks, has not yet been obtained. Here we performed whole-genome sequencing of V. cholerae across several levels of focus and scale, at the maximum possible resolution. We analyzed bacterial isolates to define cholera dynamics at multiple levels, ranging from infection within individuals, to disease dynamics at the household level, to regional and intercontinental cholera transmission. Our analyses provide a genomic framework for understanding cholera diversity and transmission in an endemic setting.
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This research was supported in part by NIAID grants R01 AI106878 to E.T.R., F.Q., S.B.C., F.C., A.I.K., Y.A.B. and R.C.C., R01 AI103055 to J.B.H., F.Q. and R.C.L., U01 AI058935 to S.B.C., F.Q., E.T.R., R.C.L. and J.B.H., U01 AI077883 to E.T.R. and F.Q., the Fogarty International Center-NIH D43 grant TW005572 to M.I.U. and T.R.B., as well as K43 TW010362 to T.R.B. This work was supported by the Wellcome Trust (grant 098051) to N.R.T. M.J.D. is supported by a Wellcome Trust Sanger Institute PhD Studentship. R.C.C. was supported by the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program (grant 72424). We thank A. J. Page, J. Keane and the sequencing teams at the Wellcome Trust Sanger Institute. This work was supported by the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) which is grateful to the Governments of Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support.
The authors declare no competing interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Integrated supplementary information
Supplementary Figure 1 Maximum likelihood phylogeny showing the relationships between Vibrio cholerae isolates.
Three isolates sampled in Dhaka, shown in green, do not belong to the 7th Pandemic El Tor (7PET) lineage. The location and date of isolation for each isolate are listed. V. metoecus and Vibrio sp. RC586 were used as outgroups for the phylogeny.
The diarrheal disease surveillance system at icddr,b enrolls every fiftieth individual for full analysis. The different panels discriminate between O1 serotypes and the O139 serogroup.
a, Pairwise comparison of SNVs shared across households ordered from least to greatest variation within a single household. b, Pairwise variation across individuals sampled more than once. c, Pairwise variability within technical replicates.
Supplementary Figure 4 Phylogenies of isolates sampled from individuals over the course of an infection.
Each panel depicts the relatedness of samples from the same individual. The scale is the number of SNVs per site.
The phylogenetic relatedness of the isolates from this individual is shown in the top diagram. The bottom panel shows the coverage of reads mapped to the CTXϕ region of the reference genome N16961 for samples from day 2 and day 4.
The tips are colored according to the geographic origin of the isolates. The nodes are in the same order as in Fig. 5.
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Domman, D., Chowdhury, F., Khan, A.I. et al. Defining endemic cholera at three levels of spatiotemporal resolution within Bangladesh. Nat Genet 50, 951–955 (2018). https://doi.org/10.1038/s41588-018-0150-8
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