Phase 3 evaluation of an innovative simple molecular test for the diagnosis of malaria in different endemic and health settings in sub-Saharan Africa (DIAGMAL)

• DOI: 10.1371/journal.pone.0272847
• Publication Date: 2022-09-01T17:36:22Z
• Authors: Francois Kiemde; Halidou Tinto; Jane Carter; Toussaint Rouamba; Daniel Valia; Lesong Conteh; Elisa Sicuri; Bryony Simmons; Bakri Nour; Davis Mumbengegwi; Asrat Hailu; Stephen Munene; Albadawi Talha; Mulugeta Aemero; Paul Meakin; René Paulussen; Scott Page; Norbert van Dijk; Petra Mens; Henk Schallig
• Keywords: Veterinary medicine; Protozoan Proteins; Test (biology); Rapid diagnostic test; Diagnostic accuracy; Pediatrics; Study Protocol; 0302 clinical medicine; Pathology; Malaria, Falciparum; Internal medicine; Immunology and Microbiology; Public health; Gold standard (test); Q; R; Life Sciences; Diagnostic test; 3. Good health; Environmental health; Telecommunications; Medicine; Science; Malaria Parasite; Plasmodium falciparum; Global health; Antigens, Protozoan; Challenges and Innovations in Bioinformatics Education; Real-Time Polymerase Chain Reaction; Diagnosis of malaria; Sensitivity and Specificity; 03 medical and health sciences; Biochemistry, Genetics and Molecular Biology; Health Sciences; Humans; Intensive care medicine; Global Impact of Arboviral Diseases; Biology; Molecular Biology; Diagnostic Tests, Routine; Public Health, Environmental and Occupational Health; Paleontology; Kenya; Transmission (telecommunications); Computer science; Malaria; Tick-Borne Diseases and Pathogens Transmission; Parasitology

Background Rapid Diagnostic Tests (RDTs) have become the cornerstone for the management of malaria in many endemic settings, but their use is constrained for several reasons: (i) persistent malaria antigen (histidine-rich protein 2; HRP2) leading to false positive test results; (ii) hrp2 deletions leading to false negative PfHRP2 results; and (iii) limited sensitivity with a detection threshold of around 100 parasites/μl blood (pLDH- and HRP2-based) leading to false negative tests. Microscopy is still the gold standard for malaria diagnosis, and allows for species determination and quantitation, but requires trained microscopists, maintained microscopes and has detection limit issues. Consequently, there is a pressing need to develop and evaluate more sensitive and accurate diagnostic tests. To address this need we have developed a direct on blood mini PCR-NALFIA test that combines the benefits of molecular biology with low infrastructural requirements and extensive training.

Methods This is a Phase 3 diagnostic evaluation in 5 African countries. Study sites (Sudan, Ethiopia, Burkina, Kenya and Namibia) were selected to ensure wide geographical coverage of Africa and to address various malaria epidemiological contexts ranging from high transmission to near elimination settings with different clinical scenarios and diagnostic challenges. Study participants will be enrolled at the study health facilities after obtaining written informed consent. Diagnostic accuracy will be assessed following the WHO/TDR guidelines for the evaluation of diagnostics and reported according to STARD principles. Due to the lack of a 100% specific and sensitive standard diagnostic test for malaria, the sensitivity and specificity of the new test will be compared to the available diagnostic practices in place at the selected sites and to quantitative PCR as the reference test.

Discussion This phase 3 study is designed to validate the clinical performance and feasibility of implementing a new diagnostic tool for the detection of malaria in real clinical settings. If successful, the proposed technology will improve the diagnosis of malaria. Enrolment started in November 2022 (Kenya) with assessment of long term outcome to be completed by 2023 at all recruitment sites.

Trial registration Pan African Clinical Trial Registry (www.pactr.org) PACTR202202766889963 on 01/02/2022 and ISCRTN (www.isrctn.com/) ISRCTN13334317 on 22/02/2022.