Sample size calculation
infectious disease, typhoid fever, typhoid
INFECTIOUS DISEASE, CNS INFECTIONS, TYPHOID FEVER, TYPHOID
The sample size was calculated using a simulation approach as outcome is an infectious disease that affects the probability of further infections in that cluster. The required number of participants was sampled from the VDSS 2021 dataset so that the simulation used the empirical distributions of age and household size in the study area (to explore potential sample sizes larger than the VDSS dataset, we replicated it before sampling). The ‘households’ were subsequently set within clusters of the required size, these clusters were randomised, and the discrete-time (one-month blocks) simulation began. We made conservative assumptions about the population proportion under 30 (47% assumed), typhoid incidence rate in the control arm (190 per 100,000 per year across all age groups combined), vaccine uptake (as low as 75%), and 70% reduction in risk due to vaccination. Further details of the simulations are provided in Additional file The simulation model reflected several important features of the trial but considered cluster membership to be constant throughout the 2 years of the trial and so did not represent the anticipated in- and out-migration.Through this trial, we will test the null hypothesis of no vaccine effect on the incidence rate of blood culture-confirmed typhoid fever among participants. The sample size required to achieve this was determined to be 60 clusters of approximately 2800 individuals each. This will provide our trial with > 90% power for both total and overall vaccine effects. It will also provide some power to demonstrate the vaccine’s effectiveness above specific margins.