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

NCT07416461 | Recruiting

• 1 other identifier: 2025-002
• Study Type: observational
• Target: 10,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Invasive Non-Typhoidal Salmonella Disease; Malaria; Malaria Vaccine

Keywords

Malaria; Vaccine effectiveness; iNTS; Invasive Non-Typhoidal Salmonella Disease; DRC; Democratic Republic of Congo; Malaria vaccine; Effectiveness; R21/Matrix-M

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Blood culture-confirmed iNTS disease (including malaria co-infections) in participants who received any dose of malaria vaccine vs. unvaccinated participants.

  At presentation (enrollment)

• 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)

• 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)

• 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)

• 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

Study Arms (2)

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.

Biological: R21/Matrix-M malaria vaccine

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.

Interventions

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.

Age-eligible children who received the R21/Matrix-M Malaria Vaccine.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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.

You may qualify if:

• 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

Sponsors & Collaborators

• International Vaccine Institute: lead

Study Sites (1)

Institut National de Recherche Biomedicale (INRB)

Kinshasa, Democratic Republic of the Congo

RECRUITING

Related Publications (11)

• 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.

  PMID: 26933028 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.

  PMID: 36442498 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.

  PMID: 28182657 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.

  PMID: 38310910 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.

  PMID: 29248635 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.

  PMID: 23601932 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.

  PMID: 24548672 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.

  PMID: 26180063 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.

  PMID: 26933016 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.

  PMID: 26933027 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.

  PMID: 38485477 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood specimen

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Octavie Lunguya

  Institut National de Recherche Biomedicale

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Birkneh Tadesse, MD, PHD

CONTACT

+821098041348; Birkneh.Tadesse@ivi.int

Camille Dauvergne, PharmD, M.S.c

CONTACT

+821091480309; Camille.Dauvergne@ivi.int

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2026
• First Posted: February 18, 2026
• Study Start: October 27, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

DE (1)