SETA-PLUS

Background

Typhoid fever (TF) and invasive non-typhoidal Salmonella (iNTS) are major causes of illness and death worldwide. TF causes about 21.7 million cases and 217,000 deaths annually, while iNTS causes about 3.4 million cases and 681,000 deaths. The highest burden is seen in areas with poor access to safe water and sanitation. Although some information exists on factors linked to mortality for TF and iNTS, recent comprehensive data, especially from sub-Saharan Africa (sSA), is lacking.

The “Typhoid Surveillance in Africa Program” (TSAP), conducted between 2010 and 2014, provided the first standardized multi-country data for sSA. It showed high TF and iNTS incidence in children under 15, with both diseases accounting for over a third of all invasive bacterial infections in febrile patients. TF was most common in children aged 2–15 years, while iNTS mostly affected children under 5.

Vaccination against TF is possible with the WHO-prequalified typhoid conjugate vaccine (TCV), which works in children under 2 years old and offers longer protection than the older polysaccharide vaccine. No licensed vaccine exists for iNTS, though candidates are in development.

The Severe Typhoid in Africa (SETA) Plus Program builds on TSAP to collect updated data on TF, iNTS, and other febrile illnesses in sSA, including Ghana. Ghana is also part of the Typhoid Vaccine in Ghana (TyVEGHA) study under the THECA project, a large-scale TCV effectiveness trial aiming to vaccinate 22,500 children in Asante Akim North District. SETA Plus surveillance will support TyVEGHA by providing baseline and follow-up data.

Objective

To estimate the burden and severity of invasive Salmonella infections, including TF, paratyphoid fever (PF), and iNTS, to guide prevention and control strategies in sSA, particularly vaccination programs.

Expected Outcomes

1. Population-based adjusted incidence of invasive Salmonella infections.
2. Facility-based incidence of severe invasive Salmonella infections.
3. Incidence of complications of severe TF, including intestinal perforation, encephalopathy, and hepatitis.
4. Population-based adjusted mortality rate of invasive Salmonella Typhi infections.
5. Evidence for TCV effectiveness and its impact on population-level disease prevention.
6. Prevalence of antimicrobial resistance markers among Salmonella isolates.
7. Validation of a new rt-PCR assay for diagnosing invasive Salmonella infections in selected sites.

The SETA Plus program, with its integration into TyVEGHA, is expected to deliver comprehensive, multi-year surveillance data to fill existing knowledge gaps in sSA and guide vaccine policy and deployment.

Funding Partners:  TyVEGHA is part of broader efforts under the Typhoid Conjugate Vaccine Introduction in Africa (THECA) and it’s funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) alongside International Vaccine Institute (IVI) and Bill and Melinda Gates Foundation