Editorial Commentary: Out of Africa: Links Between Invasive Nontyphoidal Salmonella Disease, Typhoid Fever, and Malaria

Abstract

The report by Biggs et al in the current issue of Clinical Infectious Diseases provides important insight into relationships between the 2 main forms of invasive Salmonella disease and the major childhood infectious disease burden in sub-Saharan Africa—malaria. It is the latest in a series of carefully conducted clinical studies from Tanzania from the research groups of John Crump and Hugh Reyburn. The study combines blood culture and clinical data from 2 major hospitals located some 250 km apart in very different settings: the Kilimanjaro Christian Medical Centre (KCMC), at 890 m at the foot of Mount Kilimanjaro in Moshi, where malaria transmission is low and seasonal, and Teule Hospital, at 96 m near the coast in Muheza, where malaria transmission is intensive and perennial. Invasive Salmonella disease can be divided broadly into enteric fever, principally caused by Salmonella enterica serovars Typhi and Paratyphi A, and invasive nontyphoidal Salmonella (iNTS) disease, mainly caused by Salmonella Typhimurium and Enteritidis. Enteric fever is a particular problem in Southeast Asia [1], where iNTS disease is relatively uncommon. By contrast, iNTS disease is responsible for a much larger disease burden than enteric fever in sub-Saharan Africa, causing >100 000 deaths a year. In many African countries, nontyphoidal Salmonella (NTS) is the commonest cause of bacteremia [2], although in recent years, there has been a growing number of reports of invasive disease caused by S. Typhi in the region. It is currently uncertain what is driving the evolving epidemiology of invasive Salmonella disease in sub-Saharan Africa. The sites in Tanzania where this study was conducted represent 2 locations in Africa where both iNTS disease and typhoid can be studied. The authors investigated bacteremia among febrile children admitted to both hospitals. There was no difference in the isolation rates of Streptococcus pneumoniae and Escherichia coli, 2 commonly isolated bacterial pathogens, between the sites. However, bacteremia at Teule Hospital was twice as common as at KCMC and this difference is due to the higher incidence of iNTS disease at Teule. Half of all pathogenic isolates from that site were NTS, whereas only 1 case of NTS bacteremia was detected at KCMC. In contrast, S. Typhi accounted for 3% of culture isolates at Teule and a third at KCMC. These findings suggest the presence of a factor that exerts a strong influence on the 2 types of invasive Salmonella disease. Malaria is the obvious candidate. Malaria parasites were present in more than half of febrile children admitted at Teule, but only 2% at KCMC. Threequarters of iNTS disease cases at Teule were associated with malaria or recent malaria. By multivariate analysis, iNTS disease was significantly associated with younger age, recent malaria, acute severe