Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa

Abstract

Invasive strains of non-typhoidal salmonellae have emerged as a prominent cause of bloodstream infection in African adults and children, with an associated case fatality of 20-25%. The clinical presentation of invasive non-typhoidal salmonella disease in Africa is diverse: fever, hepatosplenomegaly, and respiratory symptoms are common, and features of enterocolitis are often absent. The most important risk factors are HIV infection in adults, and malaria, HIV, and malnutrition in children. A distinct genotype of Salmonella enterica var Typhimurium, ST313, has emerged as a new pathogenic clade in sub-Saharan Africa, and might have adapted to cause invasive disease in human beings. Multidrug-resistant ST313 has caused epidemics in several African countries, and has driven the use of expensive antimicrobial drugs in the poorest health services in the world. Studies of systemic cellular and humoral immune responses in adults infected with HIV have revealed key host immune defects contributing to invasive non-typhoidal salmonella disease. This emerging pathogen might therefore have adapted to occupy an ecological and immunological niche provided by HIV, malaria, and malnutrition in Africa. A good understanding of the epidemiology of this neglected disease will open new avenues for development and implementation of vaccine and public health strategies to prevent infections and interrupt transmission.

Figure 1

Map of Africa showing results of a meta-analysis of studies investigating the cause of bloodstream infection in febrile adults and children in Africa Reproduced from Reddy and colleagues. BSI=bloodstream infection.

Figure 2

Clinical features of invasive non-typhoidal salmonella disease in adults and children in Africa

Figure 3

Features of host adaptation in salmonellae and effects on clinical syndrome in the host

Figure 4

Three key defects that contribute to the pathogenesis of invasive non-typhoidal salmonellae in HIV-positive people Arrows show routes of dissemination of salmonellae.

Figure 5

Radial phylogram showing the phylogenetic relations of Salmonella enterica var Typhimurium (S Typhimurium) sequence types (STs) The S Typhimurium sequence types (red or yellow circles) are rooted to Salmonella enterica var Typhi (S Typhi) (blue circle) and Salmonella enterica var Paratyphi A (S Paratyphi A) (green circle). Genetic distance is calculated as the number of single nucleotide polymorphisms per base and is indicated as a solid black line. The length of this line is proportional to the degree of genetic divergence. S Typhimurium sequence types from various worldwide locations outside sub-Saharan Africa (red) and from sub-Saharan AfrIca (yellow) are shown.