Yannick Bazitama Munyeku1,2,3,4, Alain Abera Musaka5,6, Medard Ernest7,8, Chris Smith9,10, Paul Mankadi Mansiangi11, Richard Culleton12,13,14,15. 1. Direction Des Laboratoires de Santé, Ministère de La Santé, Kinshasa, Democratic Republic of the Congo. ymunyeku@gmail.com. 2. Institut National de Recherche Biomédicale (INRB), Laboratoire de Virologie Clinique, Kinshasa, Democratic Republic of the Congo. ymunyeku@gmail.com. 3. Graduate School of Tropical Medicine and Global Health (TMGH), Nagasaki University, Nagasaki, Japan. ymunyeku@gmail.com. 4. Malaria Unit, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. ymunyeku@gmail.com. 5. Division Provinciale de La Santé du Kwilu, Kwilu, Democratic Republic of the Congo. 6. Institut Supérieur Des Techniques Médicales (ISTM), Kikwit, DR, Congo. 7. Malaria Unit, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. 8. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA. 9. Graduate School of Tropical Medicine and Global Health (TMGH), Nagasaki University, Nagasaki, Japan. 10. Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. 11. Kinshasa School of Public Health, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo. 12. Graduate School of Tropical Medicine and Global Health (TMGH), Nagasaki University, Nagasaki, Japan. culleton.richard.oe@ehime-u.ac.jp. 13. Malaria Unit, Department of Pathology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. culleton.richard.oe@ehime-u.ac.jp. 14. Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki, Japan. culleton.richard.oe@ehime-u.ac.jp. 15. Division of Molecular Parasitology, Proteo-Science Centre, Ehime University, Toon, Japan. culleton.richard.oe@ehime-u.ac.jp.
Abstract
BACKGROUND: Malaria rapid diagnostic tests have become a primary and critical tool for malaria diagnosis in malaria-endemic countries where Plasmodium falciparum Histidine Rich Protein 2-based rapid diagnostic tests (PfHRP2-based RDTs) are widely used. However, in the last decade, the accuracy of PfHRP2-based RDTs has been challenged by the emergence of P. falciparum strains harbouring deletions of the P. falciparum histidine rich protein 2 (pfhrp2) gene, resulting in false-negative results. In the Democratic Republic of Congo (D.R. Congo), little is known about the prevalence of the pfhrp2 gene deletion among P. falciparum isolates infecting symptomatic patients, especially in low to moderate transmission areas where pfhrp2 deletion parasites are assumed to emerge and spread. Here we determine the local prevalence and factors associated with pfhrp2 gene deletions among symptomatic malaria patients in the Kwilu Province of the D.R. Congo. METHODS: We used secondary data from a prospective health facility-based cross-sectional study conducted in 2018. Blood was collected for microscopy, PfHRP2-RDT, and spotted onto Whatman filter paper for downstream genetic analysis. Genomic DNA was extracted and used to perform PCR assays for the detection and confirmation of pfhrp2 gene deletions. Fischer's exact and the Kruskal-Wallis tests were applied to look for associations between potential explanatory variables and the pfhrp2 gene deletion with a level of statistical significance set at P < 0.05. RESULTS: Of the 684 enrolled symptomatic patients, 391 (57.7%) were female. The majority (87.7%) reported the presence of mosquito breeding sites within the household's compound, and fever was the most reported symptom (81.6%). The overall prevalence of the pfhrp2 gene deletion was 9.2% (95% CI: 6.7%-12.1%). The deletion of the pfhrp2 gene was associated with health zone of origin (P = 0.012) and age (P = 0.019). Among false-negative PfHRP2-RDT results, only 9.9% were due to pfhrp2 gene deletion. CONCLUSIONS: P. falciparum isolates with pfhrp2 gene deletions are relatively common among symptomatic patients in Kwilu province. Further investigations are needed to provide enough evidence for policy change. Meanwhile, the use of RDTs targeting PfHRP2 and parasite lactate dehydrogenase (pLDH) antigens could limit the spread of deleted isolates.
BACKGROUND:Malaria rapid diagnostic tests have become a primary and critical tool for malaria diagnosis in malaria-endemic countries where Plasmodium falciparumHistidine Rich Protein 2-based rapid diagnostic tests (PfHRP2-based RDTs) are widely used. However, in the last decade, the accuracy of PfHRP2-based RDTs has been challenged by the emergence of P. falciparum strains harbouring deletions of the P. falciparumhistidine rich protein 2 (pfhrp2) gene, resulting in false-negative results. In the Democratic Republic of Congo (D.R. Congo), little is known about the prevalence of the pfhrp2 gene deletion among P. falciparum isolates infecting symptomatic patients, especially in low to moderate transmission areas where pfhrp2 deletion parasites are assumed to emerge and spread. Here we determine the local prevalence and factors associated with pfhrp2 gene deletions among symptomatic malariapatients in the Kwilu Province of the D.R. Congo. METHODS: We used secondary data from a prospective health facility-based cross-sectional study conducted in 2018. Blood was collected for microscopy, PfHRP2-RDT, and spotted onto Whatman filter paper for downstream genetic analysis. Genomic DNA was extracted and used to perform PCR assays for the detection and confirmation of pfhrp2 gene deletions. Fischer's exact and the Kruskal-Wallis tests were applied to look for associations between potential explanatory variables and the pfhrp2 gene deletion with a level of statistical significance set at P < 0.05. RESULTS: Of the 684 enrolled symptomatic patients, 391 (57.7%) were female. The majority (87.7%) reported the presence of mosquito breeding sites within the household's compound, and fever was the most reported symptom (81.6%). The overall prevalence of the pfhrp2 gene deletion was 9.2% (95% CI: 6.7%-12.1%). The deletion of the pfhrp2 gene was associated with health zone of origin (P = 0.012) and age (P = 0.019). Among false-negative PfHRP2-RDT results, only 9.9% were due to pfhrp2 gene deletion. CONCLUSIONS:P. falciparum isolates with pfhrp2 gene deletions are relatively common among symptomatic patients in Kwilu province. Further investigations are needed to provide enough evidence for policy change. Meanwhile, the use of RDTs targeting PfHRP2 and parasite lactate dehydrogenase (pLDH) antigens could limit the spread of deleted isolates.
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