Real-world effectiveness of oral cholera vaccine amid fragility: A case-control study from Eastern Sudan, 2024

• Reactive vaccination was vital in outbreak control amid fragility. • OCV cut cholera infection risk by 93% in Kassala, Sudan. • Poor hygiene and street food strongly increased infection risk. • Overcrowding and exposure at funerals fuelled transmission. • Lasting control needs WASH, hygiene, and risk communication. Cholera is a serious public health threat, especially in fragile conflict-affected areas. Reactive oral cholera vaccine (rOCV) during outbreaks is a key response strategy recommended by the World Health Organization. Sudan implemented a large-scale reactive campaign during 2024 cholera outbreak in Kassala State. This unmatched case-control study was conducted between 6–26 October 2024 in Kassala locality, targeted by the national OCV campaign using Euvichol–Plus. Data were collected through structured interviews using a pre-tested questionnaire, and analysed in Epi Info 7 with logistic regression to estimate vaccine effectiveness and identify predictors of infection. The mean age was significantly lower in cases (30.6 years, SD = 20.8, p < 0.001). Cases had bigger households and multiple families per household (p < 0.001). Only 42.5% of cases used soap after defecation vs 97.5% of controls (OR = 0.018), while 57% used only water (OR = 52.9). Street food consumption (OR = 4.04), funeral exposure (OR = 13.3), and family history (OR = 124.4) were strong predictors. OCV reduced infection odds by 93% (aOR = 0.07, 95% CI: 0.037 -0.13, p < 0.001). Findings reaffirm OCV effectiveness but emphasize the need for sustainable investment in WASH, hygiene promotion, and risk communication in fragile settings.