Invasive Non-Typhoidal Salmonella Disease, Malaria, Malaria Vaccine
Conditions
Keywords
Malaria, Vaccine effectiveness, iNTS, Invasive Non-Typhoidal Salmonella Disease, DRC, Democratic Republic of Congo, Malaria vaccine, Effectiveness, R21/Matrix-M
Brief summary
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.
Detailed description
* 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.
Interventions
BIOLOGICALR21/Matrix-M malaria vaccine
R21/Matrix-M malaria vaccination was introduced by DRC Ministry of Public Health in the Expanded Program on Immunizations on 29th of October 2024. Children aged 6 months to 24 months are eligible to receive the vaccine. Vaccination follows a 4 doses schedule: a first dose administered between 6 and 11 months of age, a second dose one month after the first dose, a third dose one month after the second dose and a booster dose seven months after the third dose.
Sponsors
International Vaccine Institute
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. 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 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood culture-confirmed iNTS disease (including malaria co-infections) in participants who received complete malaria vaccination vs. unvaccinated participants. | At presentation (enrollment) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood culture-confirmed iNTS disease (including malaria co-infections) in participants who received any dose of malaria vaccine vs. unvaccinated participants. | At presentation (enrollment) | Among individuals seeking care for symptoms consistent with clinical malaria/iNTS, those who have received any dose of the R21/Matrix-M malaria vaccine will have a 1.00 - 0.19 or lower odds of blood-culture confirmed iNTS. |
| Culture-confirmed iNTS disease (including malaria co-infections) in participants with at least one severity feature and who received complete malaria vaccination vs. unvaccinated participants. | At presentation (enrollment) | Among individuals seeking care for symptoms consistent with clinical malaria/iNTS and meeting the definition for severe disease at first presentation to the enrolling healthcare facility, those who have received the full recommended regimen of the R21/Matrix-M malaria vaccine will have a 1.00 - 0.57 or lower odds of blood-culture confirmed iNTS. |
| Blood culture-confirmed iNTS disease (including malaria co-infections) in participants with at least one severity feature and who received any dose of the malaria vaccine vs. unvaccinated participants. | At presentation (enrollment) | Among individuals seeking care for symptoms consistent with clinical malaria/iNTS and meeting the definition for severe disease at first presentation to the enrolling healthcare facility, those who have received any dose of the R21/Matrix-M malaria vaccine will have a 1.00 - 0.38 or lower odds of blood-culture confirmed iNTS. |
| mRDT, blood smear and/or PCR-confirmed malaria disease, including severe malaria cases, with or without culture-confirmed iNTS disease, in participants who received complete malaria vaccination vs. unvaccinated participants | At presentation (enrollment) | 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 - 0.75 or lower odds of test-positive malaria infection. |
| Impact of vaccination using R21/Matrix-M on the incidence of culture-confirmed iNTS and mRDT, blood smear and/or PCR confirmed malaria co-infection (before/after) | 2 years | Among individuals seeking care for symptoms consistent with clinical malaria/iNTS (age-cohorts exposed to R21/Matrix-M vaccination program), relative rate of healthcare-ascertained, laboratory-confirmed malaria-iNTS co-infections 1-year-after versus before the introduction of the program will be 1.00 - 0.38 or lower. |
Countries
Democratic Republic of the Congo
Contacts
CONTACTBirkneh Tadesse, MD, PHD
CONTACTCamille Dauvergne, PharmD, M.S.c
PRINCIPAL_INVESTIGATOROctavie Lunguya
Institut National de Recherche Biomedicale
Outcome results
None listed