TY - JOUR
T1 - Phase 3 Evaluation of an Innovative Simple Molecular Test for the Diagnosis of Malaria and Follow-Up of Treatment Efficacy in Pregnant Women in Sub-Saharan Africa (Preg-Diagmal)
AU - Kiemde, Francois
AU - van Dijk, Norbert
AU - Tinto, Halidou
AU - Muhindo-Mavoko, Hypolite
AU - Valia, Daniel
AU - Kaboré, Berenger
AU - Kabalu, Japhet
AU - Maketa, Vivi
AU - Mens, Petra
AU - Schallig, Henk
N1 - Funding Information: The work received financial support from the European & Developing Countries Clinical Trials Partnership (EDCTP) as part of the EDCTP2 programme supported by the European Union (grant numbers RIA2017MC-2022-PyraPreg, and RIA2018D-2496-DIAGMAL). FK is a recipient of a Career Developing Fellowship (CDF) from EDCTP (TMA2019CDF-2697) and VM also received a CDF from EDCTP (TMA2019CDF-2699). The funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Publisher Copyright: © 2022 by the authors.
PY - 2022/9/1
Y1 - 2022/9/1
N2 - The malaria parasite Plasmodium falciparum (Pf) can sequester in the placenta resulting in low density of peripheral parasitemia and consequently in false negative malaria diagnosis (by microscopy) in pregnant women. Moreover, the use of rapid diagnostic tests (RDTs) in diagnostic strategies, including those for the detection of a malaria infection during pregnancy, is constrained by either persistent malaria antigen (histidine-rich protein 2; HRP2) after successful treatment, leading to false positive test results, or by false negative results as previously mentioned due to parasite sequestration (which is further exacerbated due to the low limited of detection [LoD] of conventional RDTs) or to HRP2 deletion. Recently, a direct blood polymerase chain reaction combined with a nucleic acid lateral flow immunoassay (dbPCR-NALFIA) has been developed, which circumvents these challenges and has demonstrated its diagnostic potential in phase 1 and 2 studies. The PREG-DIAGMAL trial presented in this manuscript will assess the diagnostic performance of dbPCR-NALFIA for the diagnostic of malaria in pregnant women and its potential to monitor treatment efficacy in these subjects. The work is ancillary embedded in an ongoing EDCTP funded trial, the PyraPreg project (PACTR202011812241529) in which the safety and efficacy of a newly registered Artemisinin-Based Combination (Pyronaridine-Artesunate) is being evaluated in pregnant women. This is a Phase 3 diagnostic evaluation conducted in 2 African countries: Democratic Republic of the Congo (DRC) and Burkina Faso. Pregnant women fulfilling the inclusion criteria of the PyraPreg study will be also invited to participate in the PREG-DIAGMAL study. 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 practice in place at the selected settings (microscopy and/or RDT) and to quantitative PCR as the reference test. This phase 3 diagnostic study is designed towards the evaluation of the performance of a new diagnostic tool for the screening of malaria and the monitoring of treatment in pregnant women under real conditions life. If successful, the dbPCR-NALFIA could be a valuable tool to add to the diagnostic arsenal for malaria, in particular during pregnancy. Trial registration: Pan African Clinical Trial Registry database (PACTR202203780981413). Registered on 17 March 2022.
AB - The malaria parasite Plasmodium falciparum (Pf) can sequester in the placenta resulting in low density of peripheral parasitemia and consequently in false negative malaria diagnosis (by microscopy) in pregnant women. Moreover, the use of rapid diagnostic tests (RDTs) in diagnostic strategies, including those for the detection of a malaria infection during pregnancy, is constrained by either persistent malaria antigen (histidine-rich protein 2; HRP2) after successful treatment, leading to false positive test results, or by false negative results as previously mentioned due to parasite sequestration (which is further exacerbated due to the low limited of detection [LoD] of conventional RDTs) or to HRP2 deletion. Recently, a direct blood polymerase chain reaction combined with a nucleic acid lateral flow immunoassay (dbPCR-NALFIA) has been developed, which circumvents these challenges and has demonstrated its diagnostic potential in phase 1 and 2 studies. The PREG-DIAGMAL trial presented in this manuscript will assess the diagnostic performance of dbPCR-NALFIA for the diagnostic of malaria in pregnant women and its potential to monitor treatment efficacy in these subjects. The work is ancillary embedded in an ongoing EDCTP funded trial, the PyraPreg project (PACTR202011812241529) in which the safety and efficacy of a newly registered Artemisinin-Based Combination (Pyronaridine-Artesunate) is being evaluated in pregnant women. This is a Phase 3 diagnostic evaluation conducted in 2 African countries: Democratic Republic of the Congo (DRC) and Burkina Faso. Pregnant women fulfilling the inclusion criteria of the PyraPreg study will be also invited to participate in the PREG-DIAGMAL study. 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 practice in place at the selected settings (microscopy and/or RDT) and to quantitative PCR as the reference test. This phase 3 diagnostic study is designed towards the evaluation of the performance of a new diagnostic tool for the screening of malaria and the monitoring of treatment in pregnant women under real conditions life. If successful, the dbPCR-NALFIA could be a valuable tool to add to the diagnostic arsenal for malaria, in particular during pregnancy. Trial registration: Pan African Clinical Trial Registry database (PACTR202203780981413). Registered on 17 March 2022.
KW - Plasmodium
KW - db-PCR-NALFIA
KW - diagnosis
KW - malaria
KW - pregnant women
KW - rapid diagnostic test
UR - http://www.scopus.com/inward/record.url?scp=85138602310&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/tropicalmed7090219
DO - https://doi.org/10.3390/tropicalmed7090219
M3 - Article
C2 - 36136630
SN - 2414-6366
VL - 7
JO - Tropical Medicine and Infectious Disease
JF - Tropical Medicine and Infectious Disease
IS - 9
M1 - 219
ER -