Effectiveness of a single dose of oral cholera vaccine: findings from epidemiological and genomic surveillance of Vibrio Cholerae in the Democratic Republic of the Congo (PICHA7 Program)

Abstract

This study investigated whole-cell oral cholera vaccine (kOCV) single-dose effectiveness and transmission dynamics of Vibrio cholerae through 4 years of epidemiological and genomic surveillance in Democratic Republic of the Congo (DRC). Whole genome sequencing was performed on clinical and water V. cholerae strains from 200 patient households and found annual bimodal peaks of V. cholerae clade AFR10e. 1154 diarrhea patients were enrolled with 342 culture confirmed cholera patients. A large clonal cholera outbreak occurred 18 months after a kOCV campaign of >1 million doses of Euvichol-Plus, likely because of low vaccine coverage in informal settlements (9%). Clinical and water V. cholerae strains in the same household were more closely related than different households suggesting both person-to-person and water-to-person transmission. Single-dose kOCV vaccine effectiveness in the first 24 month after vaccination was 56.9% (95% CI: 18.6%-77.2%), suggesting a single-dose provided modest protection against medically attended cholera during the 24 months post-vaccination.

Figure 1.. Four-Year Epidemological Surveillance of Bacterial Culture Confirmed Cholera Patients from 115 Health Facilities in Bukavu City of South Kivu Province of the Democratic Republic of the Congo from March 2020 to March 2024.

A total of 1154 diarrhea patients were screened at 115 health facilities and 342 cholera patients were confirmed by bacterial culture. A preventative oral killed whole-cell cholera vaccine (kOCV) campaign was conducted in December 2021 and April 2022.

Figure 2.. Map of diarrhea patients positive for V. cholerae by bacterial culture and health facilities where cholera patient surveillance was conducted between 2020–2024 in Bukavu, Democratic Republic of the Congo.

Red cross indicates healthcare facilities (N=115) and black dots indicate diarrhea patient households (N=1098) (56 patient households were missing GPS coordinates).

Figure 3.. Phylogenetic analyses describing the relationships of the 255 7PET strains.

A. Maximum likelihood phylogeny of the 255 7PET V. cholerae genomes sampled in Bukavu from 2020 to 2023. The nodes are colored according to sample type. The associated colored metadata corresponds to year of sampling and inferred serotyping results based on genome analysis. Not all strains have serotype data as indicated. B. Minimum spanning tree of 255 genomes. Strains that have zero SNP differences between them are collapsed into a single node. Node sizes scale with number of samples. The nodes are colored according to sample type.

Figure 4.. Pairwise comparisons of SNPs.

(A) Boxplots of pairwise SNP differences. Boxplots depict the distribution of pairwise SNP differences for all strains, those from the same household, and those from the same individual. Each plot shows the median, and interquartile range. The 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) Stem plots of the SNP differences per household. Pairwise SNP differences are relative to the first sample in the household. Nodes are colored by sample type and stems connect all samples to their given household.

Figure 5.. Maximum likelihood phylogenetic trees of seventh pandemic strains.

(A) Globally representative phylogeny of 1,428 7PET strains. Five representative strains from this DRC study were placed within the larger context of 1,423 7PET strains. The tree was rooted on A6 strain. The branches are colored according to geographic origin of the strain. (B) Phylogeny of the T10/AFR10 lineage. Representative strains from this DRC study (n=46) were placed within the context of 221 T10/AFR10 lineage strains. The tree was rooted on the reference strain N16961.