Effectiveness of Malaria Vaccines in Reducing the Risk of Invasive Non-typhoidal Salmonella Disease

International Vaccine Institute10,000 enrolled

Overview

The goal of this observational study is to learn about the impact of malaria vaccination on the risk of invasive non-typhoidal Salmonella disease in children below the age of 5. Eligible participants residing in the Kisantu Health Zone (DRC) and presenting fever are enrolled in healthcare facilities and tested for malaria and iNTS. Using a case-control (test-negative) design, the researchers will look at the malaria vaccination status of participants with and without iNTS infection to determine if the malaria vaccine protects against iNTS.

* This study builds on existing febrile illnesses surveillance in the Kisantu Health Zone, which enrolls patients presenting to participating healthcare facilities with fever.(See specific eligibility criteria) * For participants eligible to receive the malaria vaccine (6-24 months) and included in the study at the surveillance sites (presenting with fever), malaria vaccination status is ascertained with the Expanded Program of Immunization (EPI) card, Alternatively, a dedicated vaccination registration database that was set-up in the study catchment area is searched. The study team can also visit participants' house to verify the EPI vaccination card. R21/Matrix-M malaria vaccine was rolled out in the Kisantu Health Zone as part of the Expanded Program on Immunizations (DRC Ministry of Public Health) on 29th of October 2024. * The laboratory diagnosis of iNTS uses automated blood culture method. Malaria diagnosis is confirmed with microscopic examination of blood smears. Malaria Rapid Diagnostic Tests (mRDTs) are also performed for all participants for routine clinical management and rapid treatment guidance at the healthcare facility level. For laboratory-confirmed iNTS cases, malaria parasitemia and species specification is confirmed by Polymerase Chain Reaction (PCR). * All participants with positive blood culture to iNTS and/or a confirmed malaria parasitemia receive antibacterial and/or antimalarial treatment in accordance with national guidelines. Hospitalized cases with confirmed iNTS, with or without malaria co-infection, are followed until hospital discharge or death. Participants with a positive blood culture for iNTS and discharged after enrollment are followed every 7 to 9 days until disease resolution (defined as no fever in the past 24 hours), death, or up to 21 days post-enrollment to assess symptom severity, hospitalization, and disease outcome.

Study Type

OBSERVATIONAL

Enrollment

Outcomes

Primary Outcomes

Blood culture-confirmed iNTS disease (including malaria co-infections) in participants who received complete malaria vaccination vs. unvaccinated participants.

Among individuals seeking care for symptoms consistent with clinical malaria/iNTS, those who have received the full recommended regimen of the R21/Matrix-M malaria vaccine will have a 1.00 - 0.38 or lower odds of blood-culture confirmed iNTS.