Unravelling Cholera's Footprints in India: A Data-Driven Investigation of its Burden, Risk, and Strain Variability

Cholera continues to pose a public health challenge in India; however, existing evidence on Vibrio cholerae prevalence, strain diversity, and cross-border transmission risk remains fragmented and methodologically inconsistent. This limits the development of targeted and evidence-based control strategies. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, we conducted a systematic review and meta-analysis to derive pooled national and regional prevalence estimates of V. cholerae in India. To elucidate pathogen diversity beyond epidemiological burden, pan-genome analysis of V. cholerae genomes was undertaken to characterize strain-level genetic variation and evolutionary clustering. Additionally, a scenario tree-based quantitative risk assessment was applied to estimate the probability of cholera risk in India from neighbouring endemic countries. The meta-analysis estimated a pooled national prevalence of 7% (95% CI 4-11%), with substantial regional heterogeneity and higher detection through PCR-based detection showing a higher prevalence (9%) than culture methods (7%). Pan-genome analysis revealed marked genetic divergence among circulating strains 4295STDY6534200 (Bangladesh, 2013) and mvav6203 (China, 2000), forming distinct evolutionary clusters. Quantitative risk assessment estimated mean transmission probabilities from Bangladesh at 1.04 × 10^-6 and China at 9.35 × 10⁻1a higher mean probability of cholera introduction from Bangladesh (1.04 × 10^-6) than from China (9.35 × 10^-10). Sensitivity analysis identified false-negative diagnostics and inadequate water and sanitation as the most influential risk drivers (Spearman's ρ = 0.83). V. cholerae remains a significant public health concern in India. This study provides a comprehensive and unified assessment of cholera burden, strain variability, and transmission risk in India. The findings highlight critical intervention priorities, including strengthening genomic surveillance, improving diagnostic accuracy, and enhancing WASH (Water, Sanitation, and Hygiene) infrastructure, to support region-specific and cross-border cholera control strategies.

The online version contains supplementary material available at https://doi.org/10.1007/s12088-026-01549-5.