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

• 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.

Inclusion criteria

• Patients of all ages currently living in the catchment area of the health center presenting to healthcare facility with objective fever of at least 38.0°C tympanic or 37.5 °C axillary OR
• Patients of all ages currently living in the catchment area of the health center presenting to healthcare facility with reported fever ≥3 consecutive days within 7 days of presentation