Clinical performance of novel malaria rapid diagnostic tests for the detection of malaria infections with pfhrp2/3 gene deletions in Ethiopia
| ISRCTN | ISRCTN11071786 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11071786 |
| Sponsor | Program for Appropriate Technology in Health |
| Funder | Bill and Melinda Gates Foundation |
- Submission date
- 02/12/2025
- Registration date
- 08/12/2025
- Last edited
- 08/12/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Infections and Infestations
Plain English summary of protocol
Background and study aims
Malaria rapid diagnostic tests (RDTs) usually detect a protein called histidine rich protein 2 (HRP2). However, some Plasmodium falciparum malaria parasites have hrp2/3 gene deletions, which can cause these tests to give false negative results. This leads to missed diagnoses, untreated cases, and continued disease spread. New RDTs are needed to address this challenge. The goal of this study is to evaluate two new RDTs — the STANDARD Q hs-Malaria P.f Ag and the STANDARD Q hs-Malaria P.f/P.v Ag — for their ability to detect P. falciparum infections with hrp2/3 deletions.
Who can participate?
Patients aged 5 years or older attending clinics in Ethiopia who either have a fever (suspected malaria) or are confirmed positive for P. falciparum malaria by microscopy but negative by an HRP2-based screening RDT.
What does the study involve?
For suspected malaria patients, finger-prick blood will be collected for the routine malaria test at the clinic (microscopy or RDT) and the two new RDTs. For confirmed cases enrolled by screening, fingerprick blood will be collected for the new RDTs. All participants will have venous blood (from the arm) drawn for laboratory use. In the laboratory, the study will repeat the new RDTs, conduct additional comparator tests, and conduct the gold standard reference test for malaria. All clinical management of study participants will follow the standard of care for malaria diagnosis in Ethiopia. Venous blood will undergo confirmatory testing, including identifying genetic variation, sequencing of Plasmodium genes and quantifying antigens. Specimens will be stored frozen for testing of additional RDTs in the future.
What are the possible benefits and risks of participating?
There are minimal risks associated with participation in this study, mainly related to blood sample collection, such as slight pain or bruising. Participation will not benefit individuals personally, but what is learned from this study may help others in the future who need testing for malaria.
Where is the study run from?
This study is being conducted by Addis Ababa University Aklilu Lemma Institute of Health Research (Ethiopia). Recruitment will take place in Oromia Region of Ethiopia at Haro Adi Health Center.
When is the study starting and how long is it expected to run for?
The study will recruit from October 2025 to Q1 2026.
Who is funding the study?
Bill and Melinda Gates Foundation (USA)
Who is the main contact?
1. Lemu Golassa, Principal Investigator, lemu.golassa@aau.et
2. Stephanie Zobrist, Co-Investigator and Sponsor Representative, szobrist@path.org
3. Miraf Mesfin, Co-Investigator and Sponsor Representative, mmesfin@path.org
Contact information
Principal investigator
Aklilu Lemma Institute of Health Research, Sefere-Selam Campus
Addis Ababa
1176
Ethiopia
| Phone | +251 (0)911371981 |
|---|---|
| lemu.golassa@aau.edu.et |
Scientific
437 N 34th St
Seattle
98103
United States of America
| Phone | +1 (0)(206) 285-3500 |
|---|---|
| szobrist@path.org |
Public
Bole Medhanialem - MOENCO Road, Street No-03,711, Woreda-03, H.No-2317, Bole Sub City
Addis Ababa
493 Code 1110
Ethiopia
| Phone | +251 (0)912 914862 |
|---|---|
| mmesfin@path.org |
Study information
| Primary study design | Observational |
|---|---|
| Observational study design | Cross sectional study |
| Scientific title | Clinical performance evaluation of novel malaria rapid diagnostic tests for the detection of malaria infections with pfhrp2/3 gene deletions among febrile individuals in Ethiopia |
| Study acronym | ETH-mRDT |
| Study objectives | Primary objective is to assess the sensitivity of the SD Biosensor P.f combo and P.f/P.v combo RDTs for the detection of P. falciparum infections containing hrp2 and/or hrp3 gene deletions. Secondary objectives 1. To assess the sensitivity and specificity [altogether referred to hereafter as “diagnostic accuracy”] of the SD Biosensor P.f combo and P.f/P.v combo RDTs in intended use settings for detecting P. falciparum infections in capillary and venous whole blood samples collected prospectively from patients with confirmed or suspected malaria. 2. To assess the diagnostic accuracy of comparator tests (microscopy and the Rapigen BIOCREDIT Pf/Pv [pLDH/pLDH] test) in intended use settings for detecting P. falciparum infections in capillary and venous whole blood samples collected prospectively from patients with symptoms suggestive of malaria. 3. To establish a repository of frozen specimens for the evaluation of RDTs for their performance against P.falciparum specimens with known hrp2/hrp3 gene deletion status. |
| Ethics approval(s) |
1. Approved 04/04/2025, Aklilu Lemma Institute of Health Research- Institutional Research Ethics Review Committee (ALIHR-IRERC) (Aklilu Lemma Institute of Health Research Institutional Review Board, PO Box 1176, Sefere-Selam Campus, Addis Ababa, 1000, Ethiopia; +251 (0)112763091; aklilu.lemma@aau.edu.et), ref: ALIHR IRERC/185/2017/25 2. Approved 15/04/2025, WIRB Copernicus Group (1019 39th Ave. SE, Suite 120, Puyallup, 98374, United States of America; +1 (0)360-252-2447; clientcare@wcgclinical.com), ref: 1391503 3. Approved 09/09/2025, National Research Ethics Review Board (PO Box 1367, Arada Sub-City, Addis Ababa, 1000, Ethiopia; +251 (0)111553133; info@moe.gov.et), ref: 8/246/84/25 |
| Health condition(s) or problem(s) studied | Malaria |
| Intervention | Index tests/investigational product: 1. STANDARD Q hs-Malaria P.f Ag Test 2. STANDARD Q hs-Malaria P.f/P.v Ag Test Comparator tests: 1. Light microscopy: standard of care and research-grade 2. Standard of care RDT, if applicable 3. Comparator RDT: Rapigen BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) 4. An HRP-2 based RDT for screening Reference test: 1. Real-time polymerase chain reaction (PCR) assay for quantification and species identification 2. Speciation of all malaria, P.vivax, P.falciparum Confirmatory tests: 1. Research use only assay for quantification of malaria antigens 2. PCR testing for HRP2/HRP3 gene deletion in P. falciparum infections |
| Intervention type | Device |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | STANDARD Q hs-Malaria P.f Ag Test, STANDARD Q hs-Malaria P.f/P.v Ag Test |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) | |
| Completion date | 30/01/2026 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 5 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 200 |
| Key inclusion criteria | Inclusion criteria for cross sectional component: 1. Aged 5 years of age or older 2. Presenting at the study site with fever or a history of fever during the preceding 48 hours 3. Freely agreeing to participate by providing informed consent (and assent, as applicable) Inclusion criteria for screening component: 1. Aged 5 years of age or older 2. Presenting at the study site with fever or a history of fever during the preceding 48-hours 3. Confirmed P. falciparum malaria positive by microscopy 4. Negative for P. falciparum malaria on a WHO-recommended HRP2-based RDT 5. Freely agreeing to participate by providing informed consent (and assent, as applicable) |
| Key exclusion criteria | Presence of symptoms and signs of severe illness and/or central nervous system infections as defined by WHO guidelines |
| Date of first enrolment | 06/10/2025 |
| Date of final enrolment | 30/01/2026 |
Locations
Countries of recruitment
- Ethiopia
Study participating centres
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not expected to be made available |
| IPD sharing plan |
Editorial Notes
03/12/2025: Study's existence confirmed by Aklilu Lemma Institute of Health Research- Institutional Research Ethics Review Committee (ALIHR-IRERC).
