Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas.
In: Park, Se Eun, Toy, Trevor, Espinoza, Ligia Maria Cruz, Panzner, Ursula, Mogeni, Ondari D., Im, Justin, Poudyal, Nimesh, Pak, Gi Deok, Seo, Hyeongwon, Chon, Yun, Schutt-Gerowitt, Heidi, Mogasale, Vittal orcid:0000-0003-0596-8072 , Ramani, Enusa, Dey, Ayan orcid:0000-0002-0718-7336 , Park, Ju Yeong, Kim, Jong-Hoon, Seo, Hye Jin, Jeon, Hyon Jin, Haselbeck, Andrea, Conway Roy, Keriann, MacWright, William, Adu-Sarkodie, Yaw, Owusu-Dabo, Ellis, Osei, Isaac, Owusu, Michael, Rakotozandrindrainy, Raphael, Soura, Abdramane Bassiahi, Kabore, Leon Parfait, Teferi, Mekonnen, Okeke, Iruka N., Kehinde, Aderemi, Popoola, Oluwafemi, Jacobs, Jan, Metila, Octavie Lunguya, Meyer, Christian G., Crump, John A., Elias, Sean, Maclennan, Calman A., Parry, Christopher M., Baker, Stephen, Mintz, Eric D., Breiman, Robert F., Clemens, John D. and Marks, Florian (2019). The Severe Typhoid Fever in Africa Program: Study Design and Methodology to Assess Disease Severity, Host Immunity, and Carriage Associated With Invasive Salmonellosis. Clin. Infect. Dis., 69. S. S422 - 13. CARY: OXFORD UNIV PRESS INC. ISSN 1537-6591
Background. Invasive salmonellosis is a common community-acquired bacteremia in persons residing in sub-Saharan Africa. However, there is a paucity of data on severe typhoid fever and its associated acute and chronic host immune response and carriage. The Severe Typhoid Fever in Africa (SETA) program, a multicountry surveillance study, aimed to address these research gaps and contribute to the control and prevention of invasive salmonellosis. Methods. A prospective healthcare facility-based surveillance with active screening of enteric fever and clinically suspected severe typhoid fever with complications was performed using a standardized protocol across the study sites in Burkina Faso, the Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Defined inclusion criteria were used for screening of eligible patients for enrollment into the study. Enrolled patients with confirmed invasive salmonellosis by blood culture or patients with clinically suspected severe typhoid fever with perforation were eligible for clinical follow-up. Asymptomatic neighborhood controls and immediate household contacts of each case were enrolled as a comparison group to assess the level of Salmonella-specific antibodies and shedding patterns. Healthcare utilization surveys were performed to permit adjustment of incidence estimations. Postmortem questionnaires were conducted in medically underserved areas to assess death attributed to invasive Salmonella infections in selected sites. Results. Research data generated through SETA aimed to address scientific knowledge gaps concerning the severe typhoid fever and mortality, long-term host immune responses, and bacterial shedding and carriage associated with natural infection by invasive salmonellae. Conclusions. SETA supports public health policy on typhoid immunization strategy in Africa.