Statistical analysis
non-typhoid fever, non-typhoid illness, typhoid-negative, typhoid, typhoid fever
TYPHOID FEVER, TYPHOID
In the randomised controlled trial per-protocol analysis, vaccine efficacy against blood culture-confirmed typhoid fever up to Sept 30, 2021, was calculated as (1 – incidence rate ratio [IRR]) × 100%, where IRR is the ratio of the incidence rate in the Vi-TT group to that in the MenA group, as described in the study protocol and the published 18–24-month analysis.In each of the three test-negative design samples, vaccine effectiveness against typhoid fever was calculated as (1 – odds ratio [OR]) × 100%, where OR is the relative odds of Vi-TT vaccination in cases compared with controls. The Woolf approximation method was used to compute 95% CIs for the ORs. All randomised trial participants were used to test the core assumption of the test-negative design, that Vi-TT has no effect on non-typhoid fever. Vaccine efficacy against non-typhoid illness was calculated as (1 – RR) × 100%, where RR is the relative risk of participants or specimens testing negative for typhoid in the Vi-TT group compared with the MenA group. Three methods were used (participant-based with or without censoring and specimen-based analysis).Instead of using all available controls, a matched test-negative design was simulated to examine the effect of matching key study variables on vaccine efficacy estimates. A matched test-negative design is preferable because it improves the comparability between cases and controls and requires data collection on fewer individuals. Mahalanobis multivariate-distance nearest-neighbour matching without replacement was used to match each typhoid-positive specimen with three typhoid-negative specimens (To examine the effect of vaccine misclassification on test-negative design vaccine effectiveness estimation, we assumed that poor vaccination records affected both cases and controls equally. Different probabilities of misclassifying vaccinated individuals as unvaccinated and misclassifying unvaccinated individuals as vaccinated were considered (To examine the effect of blood culture sensitivity in detecting typhoid fever on vaccine effectiveness estimation, the test-negative design specimen-based method was used.A data and safety management board oversaw the randomised controlled trial, but not the present study. All analyses were done using Stata/SE version 17.