Effectiveness of the TYPHIBEV® (Vi-CRM197 conjugate) vaccine introduction in Nepal: A test-negative, case-control study

Objectives: We aimed to evaluate the effectiveness of TYPHIBEV®, which was introduced through a catch-up campaign and routine immunization in Nepal, in preventing blood culture-confirmed typhoid fever among children.MethodsWe conducted a test-negative, case-control study where typhoid test-positive cases were defined as vaccine-eligible pediatric patients who tested positive for Salmonella Typhi by blood culture at participating health facilities and test-negative controls were vaccine-eligible patients who tested negative for S. Typhi on blood cultures. We matched by age, location, date of blood culture, and surveillance site. We used conditional logistic regression to calculate odds ratios(OR), and vaccine effectiveness was calculated as 1-OR.ResultsBetween October 1, 2022 and December 31, 2024, 40 typhoid cases and 113 matched, test-negative controls were enrolled. Both cases and controls were similar in sociodemographic characteristics and water, sanitation and hygiene-related living conditions. Among 39 cases and 108 controls with known vaccine status, 20 cases (51%) and 91 controls (84%) had received TCV. Vaccine effectiveness was 89% (95% CI: 65–97%) and was lower among children <5 years (72%, 95% CI: −203–97%) compared with those 5–15 years (98%, 95% CI: 80–100%). Vaccine effectiveness estimates did not significantly differ when restricted to participants with documented vaccination status.ConclusionsThe findings indicate that TYPHIBEV® was highly effective in preventing typhoid fever over a 30-month follow-up period following national introduction, with effectiveness estimates comparable to those observed for Typbar-TCV®.