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Nontyphoidal Salmonella is a major cause of bloodstream infections worldwide, and HIV-infected persons and malaria-infected and malnourished children are at increased risk for the disease. We conducted a systematic literature review to obtain age group–specific, population-based invasive nontyphoidal Salmonella (iNTS) incidence data. Data were categorized by HIV and malaria prevalence and then extrapolated by using 2010 population data. The case-fatality ratio (CFR) was determined by expert opinion consensus. We estimated that 3.4 (range 2.1–6.5) million cases of iNTS disease occur annually (overall incidence 49 cases [range 30–94] per 100,000 population). Africa, where infants, young children, and young adults are most affected, had the highest incidence (227 cases [range 152–341] per 100,000 population) and number of cases (1.9 [range 1.3–2.9] million cases). An iNTS CFR of 20% yielded 681,316 (range 415,164–1,301,520) deaths annually. iNTS disease is a major cause of illness and death globally, particularly in Africa. Improved understanding of the epidemiology of iNTS is needed.

To determine the prevalence of invasive nontyphoid salmonellosis and typhoid fever in Malawi and South Africa, we compared case frequency and patient age distribution. Invasive nontyphoid salmonellosis showed a clear bimodal age distribution; the infection developed in women at a younger age than in men. Case frequency for typhoid fever was lower than for salmonellosis.