Invasive Nontyphoidal Salmonella Disease in Africa

Abstract

Nontyphoidal salmonellae (NTS) are a major cause of invasive (iNTS) disease in sub-Saharan Africa, manifesting as bacteremia and meningitis. Available epidemiological data indicate that iNTS disease is endemic in much of the region. Antimicrobial resistance is common and case fatality rates are high. There are well-characterized clinical associations with iNTS disease, including young age, HIV infection, malaria, malnutrition, anemia, and sickle cell disease. However, the clinical presentation of iNTS disease is often with fever alone, so clinical diagnosis is impossible without blood culture confirmation. No vaccine is currently available, making this a priority area for global health research. Over the past ten years, it has emerged that iNTS disease in Africa is caused by distinct pathovars of Salmonella Typhimurium, belonging to sequence type ST313, and Salmonella Enteritidis. These are characterized by genome degradation and appear to be adapting to an invasive lifestyle. Investigation of rare patients with primary immunodeficiencies has suggested a key role for interferon gamma–mediated immunity in host defense against NTS. This concept has been supported by recent population-based host genetic studies in African children. In contrast, immunoepidemiological studies from Africa indicate an important role for antibody for protective immunity, supporting the development of antibody-inducing vaccines against iNTS disease. With candidate O-antigen–based vaccines due to enter clinical trials in the near future, research efforts should focus on understanding the relative contributions of antibody and cell-mediated immunity to protection against iNTS disease in humans.

Non-typhoidal Salmonella bloodstream infections in Kisantu, DR Congo: Emergence of O5-negative Salmonella Typhimurium and extensive drug resistance

“…Local outbreaks impacted the serotype distribution [32,33,43]. In line with previous reports from sub-Saharan African countries also consistently ranked Salmonella Typhimurium as the predominant serotype (representing 43-88% of NTS); the proportion of Salmonella Enteritidis (representing 10-50% of NTS) and other less frequent serotypes varied between countries [44]. Similar to the results presented in this study, the Typhimurium-to-Enteritidis ratio varied between 1:1 to 1:8 between countries [44].…”

Salmonella Virulence and Immune Escape

“…The iNTS disease burden in Africa is especially caused due to urbanization with large populations living in crowded and insanitary conditions with poor access to potable water [62][63][64]. iNTS is more common amongst people with an impaired immunity, and typically represents a febrile systemic illness and lower respiratory tract disease, commonly attributable to co-infections with HIV or malaria [50,60,65,66].…”

Salmonella Typhimurium encoded cold shock protein E is essential for motility and biofilm formation

“…S. Typhimurium is a host generalist which has a wide variety of hosts and, hence its successful propagation is dependent on its ability to adjust to multiple lifestyles relative to the environment. One of the major concerns of Salmonella infection is the rise in invasive nontyphoidal salmonellae (iNTS) in under-developed nations [18]. In Sub-Saharan Africa, iNTS disease is caused by two distinct lineages of S. Typhimurium ST313, both carrying MDR-encoding Tn21 elements on plasmid pSLT and the prophages, BTP1 and BTP5 [19].…”