Severe Typhoid in Africa Program (DRC site) (SETA)

Invasive Salmonella infections (typhoidal and non-typhoidal) cause a huge burden of illness, especially in sub-Saharan Africa. Unlike the case in the northern hemisphere, Salmonella causes so-called invasive infection, mostly presenting as bloodstream infections (BSI). While typhoidal Salmonella infection is strongly associated with hygienic factors, invasive non-typhoid Salmonella (iNTS) infection appears to be predominantly associated with host-related factors including malnutrition and malaria in children, and HIV in adults. Together typhoid fever and invasive non-typhoid Salmonella accounts for over 1/3 of all isolated pathogens causing BSI among febrile patients at various sites across sub-Saharan Africa. Incidence rates are over 100/100,000 person years of observation for both typhoid fever and invasive non-Typhoidal Salmonella in many settings, especially in children < 5 years old.Given the high public health burden and difficult control of invasive salmonellosis, vaccine strategies to contain both typhoid fever and iNTS infections have been put forward. However, the mechanisms of immune response to invasive salmonellosis are not well understood. While a safe and effective parental TF Vi polysaccharide (Vi-PS) vaccine exists, the vaccine does not elicit an adequate immune response in children < 2 years of age, the time period at which typhoid fever burden starts to affect children. Conversely, there is currently no vaccine available against iNTS as the development is more complicated by the immunocompromised nature of susceptible patients, the limited knowledge of the immune mechanisms underlying natural infection and other factors. Furthermore, data on disease severity and complications, long-term disease outcome as well as carriage and transmission of invasive salmonellosis are still lacking. To improve our understanding of the epidemiology of invasive salmonellosis, there is a need for detailed knowledge about the true burden of disease. Epidemiological data are important to assist clinical management in high prevalence areas. In addition, a better understanding of serotype distribution and immunologic response to natural infection is of great value for vaccine studies and for the development of prevention strategies. Studies about community-based incidence of invasive salmonellosis from Africa are rare, and mostly originate from East Africa.The SETA study is performed at multiple surveillance sites in Africa and Asia (so-called SETA surveillance network); the network is funded by the Bill and Melinda Gates Foundation and International Vaccine Institute (IVI) is sponsor. IVI collaborates with ITM for the study setup in DR Congo which is one of the seven participating countries in sub-Saharan Africa under study. The SETA study will provide quantitative descriptions of incidence, severity, long-term disease outcomes, complications, and sequelae. It is also designed to assess the mechanisms of immune response to typhoid fever and invasive non-Typhoidal Salmonella and data on other febrile diseases diagnosed in the program.

Project type:PhD project