Epidemiologic and Genomic Surveillance of Vibrio cholerae and Effectiveness of Single-Dose Oral Cholera Vaccine, Democratic Republic of the Congo

Abstract

We conducted 4 years of epidemiologic and genomic surveillance of single-dose effectiveness of a killed whole-cell oral cholera vaccine (kOCV) and Vibrio cholerae transmission in the Democratic Republic of the Congo. We enrolled 1,154 patients with diarrhea; 342 of those had culture-confirmed cholera. We performed whole-genome sequencing on clinical and water V. cholerae isolates from 200 patient households, which showed annual bimodal peaks of V. cholerae clade AFR10e infections. A large clonal cholera outbreak occurred 14 months after a kOCV campaign of >1 million doses, likely because of low (9%) vaccine coverage in informal settlements. Clinical and water isolates collected in the same household were closely related, suggesting person-to-person and water-to-person transmission. Single-dose kOCV vaccine effectiveness 24 months after vaccination was 59.8% (95% CI 19.7%-79.9%), suggesting modest single-dose kOCV protection. kOCV campaigns combined with water, sanitation, and hygiene programs should be used to reduce cholera in disease-endemic settings worldwide.

Keywords: Democratic Republic of the Congo; PICHA7; Preventative Intervention for Cholera for 7 Days program; Vibrio cholerae; bacteria; cholera; enteric infections; epidemiology; surveillance; vaccines; whole-genome sequencing.

Figure 1

Location of patients with diarrhea and the corresponding healthcare facilities where they sought treatment in a surveillance study of Vibrio cholerae and effectiveness of single-dose oral cholera vaccine, Democratic Republic of the Congo, 2020–2024. A total of 115 healthcare facilities and 1,098 households of patients with diarrhea are shown; 56 patient households had missing Global Positioning System coordinates.

Figure 2

Phylogenetic analysis of Vibrio cholerae seventh pandemic El Tor (7PET) isolates collected during study of V. cholerae transmission and effectiveness of single-dose oral cholera vaccine, Democratic Republic of the Congo. A) Maximum-likelihood tree of 255 7PET V. cholerae genomes sampled in Bukavu during 2020–2023. Node colors indicate sample type. Associated colored metadata indicate sampling year and inferred serotypes according to genome analysis. Scale bar indicates nucleotide substitutions per site. B) Minimum spanning tree of 255 7PET V. cholerae genomes sampled in Bukavu during 2020–2023. Node colors indicate sample type. Isolates with 0 single-nucleotide polymorphism differences between each other are collapsed into single node. Node sizes are scaled according to the number of samples. Scale bar indicates single-nucleotide polymorphisms.

Figure 3

Pairwise comparisons of SNPs in surveillance study of Vibrio cholerae and effectiveness of single-dose killed oral cholera vaccine (kOCV), Democratic Republic of the Congo. A) Violin plot showing distribution of pairwise SNP differences from all isolates collected during the study, those from the same household, and those pre-kOCV and post-kOCV campaign. Density curves indicate frequency of data points. Inside each density plot, horizontal white lines within boxes indicate medians; box tops and bottoms indicate upper (third) and lower (first) quartiles; and whiskers indicate minimum and maximum values. Number of pairwise comparisons for each category is as follows: all samples, n = 32,385; same household, n = 99; pre-kOCV campaign, n = 6,205; and post-kOCV campaign, n = 10,296. B) SNP differences per household. Pairwise SNP differences are relative to the first sample in the household. Node colors indicate sample type; stems connect samples to their household. ID, identification; SNP, single-nucleotide polymorphism.

Figure 4

Phylogenetic analysis of Vibrio cholerae strains in study of V. cholerae transmission and effectiveness of single-dose killed oral cholera vaccine, DRC. Maximum-likelihood phylogenetic trees were prepared to compare V. cholerae seventh pandemic El Tor (7PET) isolates. A) Globally representative phylogeny of 1,428 7PET strains; 5 representative isolates from this study (red) were placed within the larger context of those 7PET strains. Tree was rooted on the A6 strain. Branch colors indicate geographic origin of the strain. B) Phylogeny of the T10/AFR10 lineage of V. cholerae. Colors indicate different V. cholerae lineages. Representative isolates from this study (n = 46; red) were placed within the context of 221 T10/AFR10 lineage strains. Tree was rooted on the reference strain N16961. Scale bars indicate nucleotide substitutions per site. DRC, Democratic Republic of the Congo.