Background: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe
Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations
eligible for interventions using novel typhoid conjugate vaccines.
Methods: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation
surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or
≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate.
Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level
was estimated using a Bayesian mixture model.
Findings: 27 866 (33·8%) of 82491 participants who met inclusion criteria were recruited. Blood cultures were
performed for 27544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%)
of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per
100000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315,
95% credible interval 254–390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility.
Interpretation: High disease incidence (ie, 100 per 100 000 person-years of observation) recorded in four countries,
the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains
strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with
measures designed to improve clean water, sanitation, and hygiene practices.