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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Age-eligible children who received the R21/Matrix-M Malaria Vaccine. | Depending on the study objective, participants who received at least the three primary doses of the R21/Matrix-M vaccine will be considered for analysis (complete vaccination - primary objective) or participants who received either the first or first two doses of R21/Matrix-M vaccine (incomplete vaccination - secondary objectives) shall be considered for analysis. |
| |
| Age-eligible children who were not vaccinated against malaria. | Unvaccinated participants will be defined as not meeting the definitions for complete nor incomplete vaccination by time of enrollment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| R21/Matrix-M malaria vaccine | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At presentation (enrollment) |
| Measure | Description | Time Frame |
|---|---|---|
| Blood culture-confirmed iNTS disease (including malaria co-infections) in participants who received any dose of malaria vaccine vs. unvaccinated participants. | 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. | At presentation (enrollment) |
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Inclusion Criteria:
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Though only children 6-24 months of age are eligible to receive R21/Matrix-M, patients of all age groups presenting with fever at participating sites will be monitored for malaria and iNTS.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Birkneh Tadesse, MD, PHD | Contact | +821098041348 | Birkneh.Tadesse@ivi.int | |
| Camille Dauvergne, PharmD, M.S.c | Contact | +821091480309 | Camille.Dauvergne@ivi.int |
| Name | Affiliation | Role |
|---|---|---|
| Octavie Lunguya | Institut National de Recherche Biomedicale | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut National de Recherche Biomedicale (INRB) | Recruiting | Kinshasa | Democratic Republic of the Congo |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26933028 | Background | von Kalckreuth V, Konings F, Aaby P, Adu-Sarkodie Y, Ali M, Aseffa A, Baker S, Breiman RF, Bjerregaard-Andersen M, Clemens JD, Crump JA, Cruz Espinoza LM, Deerin JF, Gasmelseed N, Sow AG, Im J, Keddy KH, Cosmas L, May J, Meyer CG, Mintz ED, Montgomery JM, Olack B, Pak GD, Panzner U, Park SE, Rakotozandrindrainy R, Schutt-Gerowitt H, Soura AB, Warren MR, Wierzba TF, Marks F. The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies. Clin Infect Dis. 2016 Mar 15;62 Suppl 1(Suppl 1):S9-S16. doi: 10.1093/cid/civ693. | |
| 36442498 |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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Blood specimen
|
| 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. | 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. | At presentation (enrollment) |
| 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. | 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. | At presentation (enrollment) |
| 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 | 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. | At presentation (enrollment) |
| 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) | 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. | 2 years |
| Background |
| Liang Y, Driscoll AJ, Patel PD, Datta S, Voysey M, French N, Jamka LP, Henrion MYR, Ndeketa L, Laurens MB, Heyderman RS, Gordon MA, Neuzil KM. Typhoid conjugate vaccine effectiveness in Malawi: evaluation of a test-negative design using randomised, controlled clinical trial data. Lancet Glob Health. 2023 Jan;11(1):e136-e144. doi: 10.1016/S2214-109X(22)00466-1. Epub 2022 Nov 25. |
| 28182657 | Background | Bornstein K, Hungerford L, Hartley D, Sorkin JD, Tapia MD, Sow SO, Onwuchekwa U, Simon R, Tennant SM, Levine MM. Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa. PLoS Negl Trop Dis. 2017 Feb 9;11(2):e0005283. doi: 10.1371/journal.pntd.0005283. eCollection 2017 Feb. |
| 38310910 | Background | Datoo MS, Dicko A, Tinto H, Ouedraogo JB, Hamaluba M, Olotu A, Beaumont E, Ramos Lopez F, Natama HM, Weston S, Chemba M, Compaore YD, Issiaka D, Salou D, Some AM, Omenda S, Lawrie A, Bejon P, Rao H, Chandramohan D, Roberts R, Bharati S, Stockdale L, Gairola S, Greenwood BM, Ewer KJ, Bradley J, Kulkarni PS, Shaligram U, Hill AVS; R21/Matrix-M Phase 3 Trial Group. Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial. Lancet. 2024 Feb 10;403(10426):533-544. doi: 10.1016/S0140-6736(23)02511-4. Epub 2024 Feb 1. |
| 29248635 | Background | Nyirenda TS, Mandala WL, Gordon MA, Mastroeni P. Immunological bases of increased susceptibility to invasive nontyphoidal Salmonella infection in children with malaria and anaemia. Microbes Infect. 2018 Oct-Nov;20(9-10):589-598. doi: 10.1016/j.micinf.2017.11.014. Epub 2017 Dec 15. |
| 23601932 | Background | van Santen S, de Mast Q, Swinkels DW, van der Ven AJ. The iron link between malaria and invasive non-typhoid Salmonella infections. Trends Parasitol. 2013 May;29(5):220-7. doi: 10.1016/j.pt.2013.03.006. Epub 2013 Apr 16. |
| 24548672 | Background | Church J, Maitland K. Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review. BMC Med. 2014 Feb 19;12:31. doi: 10.1186/1741-7015-12-31. |
| 26180063 | Background | Crump JA, Sjolund-Karlsson M, Gordon MA, Parry CM. Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections. Clin Microbiol Rev. 2015 Oct;28(4):901-37. doi: 10.1128/CMR.00002-15. |
| 26933016 | Background | Park SE, Pak GD, Aaby P, Adu-Sarkodie Y, Ali M, Aseffa A, Biggs HM, Bjerregaard-Andersen M, Breiman RF, Crump JA, Cruz Espinoza LM, Eltayeb MA, Gasmelseed N, Hertz JT, Im J, Jaeger A, Parfait Kabore L, von Kalckreuth V, Keddy KH, Konings F, Krumkamp R, MacLennan CA, Meyer CG, Montgomery JM, Ahmet Niang A, Nichols C, Olack B, Panzner U, Park JK, Rabezanahary H, Rakotozandrindrainy R, Sampo E, Sarpong N, Schutt-Gerowitt H, Sooka A, Soura AB, Sow AG, Tall A, Teferi M, Yeshitela B, May J, Wierzba TF, Clemens JD, Baker S, Marks F. The Relationship Between Invasive Nontyphoidal Salmonella Disease, Other Bacterial Bloodstream Infections, and Malaria in Sub-Saharan Africa. Clin Infect Dis. 2016 Mar 15;62 Suppl 1(Suppl 1):S23-31. doi: 10.1093/cid/civ893. |
| 26933027 | Background | Krumkamp R, Kreuels B, Sarpong N, Boahen KG, Foli G, Hogan B, Jaeger A, Reigl L, Zeeb H, Marks F, Adu-Sarkodie Y, May J. Association Between Malaria and Invasive Nontyphoidal Salmonella Infection in a Hospital Study: Accounting for Berkson's Bias. Clin Infect Dis. 2016 Mar 15;62 Suppl 1:S83-9. doi: 10.1093/cid/civ950. |
| 38485477 | Background | Kim JH, Tack B, Fiorino F, Pettini E, Marchello CS, Jacobs J, Crump JA, Marks F; Vacc-iNTS Consortium. Examining geospatial and temporal distribution of invasive non-typhoidal Salmonella disease occurrence in sub-Saharan Africa: a systematic review and modelling study. BMJ Open. 2024 Mar 14;14(3):e080501. doi: 10.1136/bmjopen-2023-080501. |
| D000079426 |
| Vector Borne Diseases |