Assessing Vaccine Effectiveness of R21/Matrix-M Across Malaria Transmission Settings (AVERT) (AVERT)

August 3, 2026 updated by: Clinton Health Access Initiative Inc.

Real-World Effectiveness of the R21/Matrix-M Malaria Vaccine in Children in Burkina Faso and Uganda

The AVERT study is a prospective observational test-negative case control study evaluating the real-world effectiveness of the R21/Matrix-M malaria vaccine among children younger than 5 years in Burkina Faso and Uganda. Children who seek outpatient care with suspected malaria and are eligible for the national R21/Matrix-M vaccination program will be enrolled. Malaria infection will be determined by blood smear microscopy. Children with a positive microscopy result will be classified as cases and children with a negative result as controls. Vaccination history, including the number and timing of doses, will be obtained primarily from vaccination cards or other written records. Vaccine effectiveness will be estimated by comparing the odds of vaccination among cases and controls.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

R21/Matrix-M has been introduced through national immunization programs, but its effectiveness under routine conditions may differ from efficacy observed in clinical trials because children may receive different numbers of doses, doses may be delayed, protection may wane, and malaria transmission and other prevention measures vary across settings.

AVERT will use a prospective test-negative case-control design at approximately 22 outpatient health facilities in moderate- to high-transmission areas of Burkina Faso and Uganda. Consecutive children younger than 5 years who meet country definitions for suspected malaria, are eligible for R21/Matrix-M vaccination, and have caregiver consent will be enrolled. All participants will undergo malaria testing as part of routine care, with study blood smear microscopy used to assign case or control status. A structured caregiver questionnaire will collect demographic, clinical, residential, socioeconomic, health-care access, and malaria-prevention information. R21/Matrix-M dose number and vaccination dates will be verified primarily from vaccination cards, individual health records, or facility vaccination registers.

Cases and controls will be matched, when feasible, by geographic area and calendar time. Conditional or standard logistic regression will estimate adjusted odds ratios comparing vaccinated and unvaccinated children, and vaccine effectiveness will be calculated as (1 - adjusted odds ratio) x 100%. Analyses will be conducted separately by country and will assess effectiveness by dose, time since vaccination, dose spacing, transmission intensity, sex, and use of seasonal malaria chemoprevention, insecticide-treated nets, and indoor residual spraying. A health-system-perspective economic evaluation will estimate incremental cost per uncomplicated clinical malaria case averted.

Study Type

Observational

Enrollment (Estimated)

20000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Burkina Faso
    • Boucle Mouhoun
      • Boromo, Boucle Mouhoun, Burkina Faso
        • Recruiting
        • Boromo urbain 1
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Boromo, Boucle Mouhoun, Burkina Faso
        • Recruiting
        • Ouahabou
        • Contact:
    • Hauts-Bassins Region
      • Houndé, Hauts-Bassins Region, Burkina Faso
        • Recruiting
        • Béréba
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Houndé, Hauts-Bassins Region, Burkina Faso
        • Recruiting
        • Dohoun
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Houndé, Hauts-Bassins Region, Burkina Faso
        • Recruiting
        • Kari
        • Contact:
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recruiting
        • Déguélin
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recruiting
        • Karangasso-Vigué
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recruiting
        • Sourmousso
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Karangasso-Vigué, Hauts-Bassins Region, Burkina Faso
        • Recruiting
        • Wara
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
    • Oubri
      • Zorgo, Oubri, Burkina Faso
        • Recruiting
        • Mankarga T
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Zorgo, Oubri, Burkina Faso
        • Recruiting
        • Mankarga V3
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
      • Zorgo, Oubri, Burkina Faso
        • Recruiting
        • Mankarga V6
        • Contact:
          • Halidou Tinto, PhD
          • Phone Number: +226 25 40 92 12
          • Email: tintoh@crun.bf
  • Uganda
    • Acholi
      • Kitgum, Acholi, Uganda
        • Not yet recruiting
        • Kitgum-Matidi HCIII
        • Contact:
      • Kitgum, Acholi, Uganda
        • Not yet recruiting
        • Namokora HCIV
        • Contact:
      • Omoro, Acholi, Uganda
        • Not yet recruiting
        • Lalogi HCIV
        • Contact:
    • Bunyoro
      • Kikube, Bunyoro, Uganda
        • Not yet recruiting
        • Rwenyawawa HCIII
        • Contact:
    • Busoga
      • Kaliro, Busoga, Uganda
        • Not yet recruiting
        • Nawaikoke HCIII
        • Contact:
      • Mayuge, Busoga, Uganda
        • Not yet recruiting
        • Kigandalo HCIV
        • Contact:
    • Karamoja
      • Moroto, Karamoja, Uganda
        • Not yet recruiting
        • Nadunget HCIII
        • Contact:
    • Lango
      • Otuke, Lango, Uganda
        • Not yet recruiting
        • Orum HCIV
        • Contact:
      • Oyam, Lango, Uganda
        • Not yet recruiting
        • Otwal HCIII
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Children younger than 5 years who reside in the catchment areas of selected health facilities in R21/Matrix-M implementation districts in Burkina Faso or Uganda, are age-eligible for vaccination under the relevant national schedule, and present for outpatient care with suspected malaria. Participants are recruited from health facilities in moderate- to high-transmission settings.

Description

Inclusion Criteria:

  • Residence in an area where R21/Matrix-M is implemented and within the catchment area of a selected study facility.
  • Younger than 5 years and eligibleto receive R21/Matrix-M under the national vaccination schedule at rollout.
  • Meets the country definition of suspected malaria, generally axillary temperature of at least 37.5 degrees Celsius or a history of fever within the previous 24 hours, and is undergoing malaria testing.
  • Written informed consent provided by an adult caregiver aged 18 years or older.

Exclusion Criteria:

  • Caregiver is unable or unwilling to provide informed consent.
  • Severe non-malaria illness at presentation that would interfere with study participation.
  • Repeat presentation within the protocol-defined exclusion window after a previous enrollment: within 14 days after a microscopy-positive visit; or more than 7 but fewer than 14 days after a microscopy-negative visit. A microscopy-negative visit followed by a positive diagnosis within 7 days will be reclassified as positive rather than treated as a new enrollment.
  • Documented receipt of any RTS,S malaria vaccine dose.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Suspected malaria cases that test positive using microscopy
Eligible children with suspected malaria whose enrollment blood smear microscopy result is positive for P. falciparum infection
Biological: R21/Matris-M Malaria vaccine
R21/Matrix-M vaccination received through routine national immunization programs. The study will record the number and dates of doses received. Children will be classified as having received 0, 1, 2, 3, or 4 eligible doses, with prespecified grouped classifications used if individual dose categories are underpowered. Doses given fewer than 14 days before malaria testing will not count toward the primary exposure classification.
Suspected malaria cases that test negative using microscopy
Eligible children with suspected malaria whose enrollment blood smear microscopy result is negative for P. falciparum infection
Biological: R21/Matris-M Malaria vaccine
R21/Matrix-M vaccination received through routine national immunization programs. The study will record the number and dates of doses received. Children will be classified as having received 0, 1, 2, 3, or 4 eligible doses, with prespecified grouped classifications used if individual dose categories are underpowered. Doses given fewer than 14 days before malaria testing will not count toward the primary exposure classification.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-specific effectiveness of R21/Matrix-M against microscopy-confirmed clinical malaria
Time Frame: At the enrollment illness episode, during the approximately 7- to 8-month study recruitment period
Adjusted vaccine effectiveness will be calculated as (1 - adjusted odds ratio) x 100%. The odds ratio will compare the odds of each documented R21/Matrix-M dose category among microscopy-positive malaria cases with the odds among microscopy-negative controls, using children with 0 doses as the primary reference group. Prespecified grouped dose categories will be used if individual dose categories do not have adequate statistical power.
At the enrollment illness episode, during the approximately 7- to 8-month study recruitment period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness of R21/Matrix-M by time since vaccination
Time Frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Adjusted vaccine effectiveness will be estimated by categorical and/or continuous time since the most recent eligible vaccine dose, including interactions between dose and time.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by malaria transmission intensity
Time Frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Dose-specific vaccine effectiveness will be compared across prespecified malaria transmission levels within each country.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification of vaccine effectiveness by sex
Time Frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Dose-specific vaccine effectiveness will be estimated using vaccination-by-sex interaction terms and sex-stratified analyses.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effect modification by other malaria prevention interventions
Time Frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Dose-specific vaccine effectiveness will be assessed in relation to seasonal malaria chemoprevention, insecticide-treated net use, and indoor residual spraying using interaction analyses.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effectiveness according to vaccine dose timing
Time Frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Among vaccinated children, effectiveness will be compared for on-time and late vaccination and in analyses restricted to doses spaced 3 to 5 weeks apart. A late dose is defined as a dose received at least 2 weeks after the scheduled date.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Effectiveness of the fourth dose relative to the three-dose primary series
Time Frame: At the enrollment illness episode, during the approximately 7- to 8-month recruitment period
Adjusted vaccine effectiveness of 4 doses compared with 3 doses will be estimated using the odds of microscopy-confirmed malaria.
At the enrollment illness episode, during the approximately 7- to 8-month recruitment period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinton Health Access Initiative Inc.

Collaborators

University of California, San Francisco
Institut de Recherche en Sciences de la Sante, Burkina Faso
Ministry of Health, Uganda
Ministry of Health, Burkina Faso
Infectious Diseases Research Collaboration, Uganda

Investigators

  • Principal Investigator: Isabel Rodriguez-Barraquer, MD, PhD, University of California, San Francisco
  • Principal Investigator: Halidou Tinto, PhD, Institut de Recherche en Sciences de la Santé (Burkina Faso)
  • Principal Investigator: Joaniter Nankabirwa, MD, PhD, Infectious Diseases Research Collaboration, Kampala, Uganda

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 14, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

August 3, 2026

First Submitted That Met QC Criteria

August 3, 2026

First Posted (Actual)

August 6, 2026

Study Record Updates

Last Update Posted (Actual)

August 6, 2026

Last Update Submitted That Met QC Criteria

August 3, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVERT-2026-01
  • INV-097482 (Other Grant/Funding Number: Gates Foundation)
  • 2026-06-05 (Other Grant/Funding Number: Givewell)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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