Evolution and spread of Plasmodium falciparum mutations associated with resistance to sulfadoxine-pyrimethamine in central Africa: a cross-sectional study.

Autor:	Guémas E; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse, CNRS UMR5051, INSERM UMR 1291, UPS, Toulouse, France; Département de Parasitologie et Mycologie, CHU Toulouse, Toulouse, France; LAAS-CNRS, Université de Toulouse, CNRS, UPS, Toulouse, France., Coppée R; Université Paris Cité and Sorbonne Paris Nord, INSERM, IAME, Paris, France., Ménard S; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse, CNRS UMR5051, INSERM UMR 1291, UPS, Toulouse, France., du Manoir M; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse, CNRS UMR5051, INSERM UMR 1291, UPS, Toulouse, France., Nsango S; Faculté de Médecine et des Sciences Pharmaceutiques, Université de Douala, Douala, Cameroon; Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroon., Makaba Mvumbi D; Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo; Institute for Medical Immunology, Université Libre de Bruxelles, Brussells, Belgium., Nakoune E; Institut Pasteur de Bangui, Bangui, Central African Republic., Eboumbou Moukoko CE; Faculté de Médecine et des Sciences Pharmaceutiques, Université de Douala, Douala, Cameroon; Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroon., Bouyou Akotet MK; Département de Parasitologie Mycologie Médecine Tropicale, Faculté de Médecine de l'Université des Sciences de la Santé, Libreville, Gabon; Centre de Recherche Biomédicale en Pathogènes Infectieux et Pathologies Associées, CREIPA, Université des Sciences de la Santé, Libreville, Gabon., Mirabeau TY; Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Health Sciences, Niger Delta University, Wilberforce Island, Nigeria., Manguin S; Hydro Sciences Montpellier, Université de Montpellier, CNRS, IRD, Montpellier, France., Malekita Yobi D; Department of Basic Sciences, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo., Akiana J; Laboratoire National de Santé Publique, Université Marien Ngouabi, Brazzaville, Republic of the Congo., Kouna LC; Unité d'Evolution Epidémiologie et Résistances Parasitaires, Centre Interdisciplinaire de Recherches Médicales de Franceville, Franceville, Gabon; Département de Parasitologie-Mycologie, Université des Sciences de la Santé, Libreville, Gabon., Mawili Mboumba DP; Département de Parasitologie Mycologie Médecine Tropicale, Faculté de Médecine de l'Université des Sciences de la Santé, Libreville, Gabon; Centre de Recherche Biomédicale en Pathogènes Infectieux et Pathologies Associées, CREIPA, Université des Sciences de la Santé, Libreville, Gabon., Voumbo-Matoumona DF; Laboratoire National de Santé Publique, Université Marien Ngouabi, Brazzaville, Republic of the Congo; Unité d'Evolution Epidémiologie et Résistances Parasitaires, Centre Interdisciplinaire de Recherches Médicales de Franceville, Franceville, Gabon; Département de Parasitologie-Mycologie, Université des Sciences de la Santé, Libreville, Gabon., Otam AL; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse, CNRS UMR5051, INSERM UMR 1291, UPS, Toulouse, France., Rubbo PA; Institut Pasteur de Bangui, Bangui, Central African Republic., Lombart JP; Institut Pasteur de Bangui, Bangui, Central African Republic., Kwanai E; Coordination diocésaine de la Santé, Diocèse de Maroua-Mokolo, Maroua, Cameroon., Cohen O; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse, CNRS UMR5051, INSERM UMR 1291, UPS, Toulouse, France., Iriart X; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse, CNRS UMR5051, INSERM UMR 1291, UPS, Toulouse, France; Département de Parasitologie et Mycologie, CHU Toulouse, Toulouse, France., Ayong L; Malaria Research Unit, Centre Pasteur du Cameroun, Yaoundé, Cameroon., Lekana-Douki JB; Unité d'Evolution Epidémiologie et Résistances Parasitaires, Centre Interdisciplinaire de Recherches Médicales de Franceville, Franceville, Gabon; Département de Parasitologie-Mycologie, Université des Sciences de la Santé, Libreville, Gabon., Ariey F; INSERM U1016, Institut Cochin, Laboratoire de Parasitologie-Mycologie, Hôpital Cochin, AP-HP, Université Paris Cité, Paris, France., Berry A; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université de Toulouse, CNRS UMR5051, INSERM UMR 1291, UPS, Toulouse, France; Département de Parasitologie et Mycologie, CHU Toulouse, Toulouse, France. Electronic address: berry.a@chu-toulouse.fr.
Jazyk:	angličtina
Zdroj:	The Lancet. Microbe [Lancet Microbe] 2023 Dec; Vol. 4 (12), pp. e983-e993. Date of Electronic Publication: 2023 Oct 18.
DOI:	10.1016/S2666-5247(23)00211-2
Abstrakt:	Background: Efficacy of sulfadoxine-pyrimethamine, the malaria chemoprophylaxis used in pregnant women, and in children when combined with amodiaquine, is threatened by the accumulation of mutations in the Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes. Data on the prevalence of resistant alleles in central Africa and the new pfdhps I431V mutation, particularly associated with other mutations to form the pfdhps vagKgs allele, are scarce. We explored the frequency and geographical distribution of pfdhps and pfdhfr mutations in central Africa in 2014-18, and assessed the evolutionary origin of the vagKgs allele. Methods: Samples were collected at 18 health-care centres in seven countries (Angola, Cameroon, Central African Republic, Democratic Republic of the Congo, Gabon, Nigeria, and Republic of the Congo) from patients who showed possible symptoms of malaria between March 1, 2014, and Oct 31, 2018. Samples that were positive for P falciparum were transported to a laboratory in Toulouse, France, and genotyped. The frequency of pfdhfr and pfdhps mutations was studied in 1749 samples. Microsatellites in pfdhps flanking regions and whole-genome analysis compared with parasite genomes from the data-sharing network MalariaGEN were performed on samples carrying the vagKgs allele. Findings: Mapping of the prevalence of single nucleotide polymorphisms and corresponding alleles of pfdhfr and pfdhps showed a substantial spread of alleles associated with sulfadoxine-pyrimethamine resistance in central Africa during the 2014-18 period, especially an increase going west to east in pfdhps alleles carrying the K540E and A581G mutations. A high prevalence of the pfdhps I431V mutation was observed in Cameroon (exceeding 50% in the northern region) and Nigeria. Genomic analysis showed a recent African emergence and a clonal expansion of the most frequent pfdhps vagKgs allele. Interpretation: Reduced sulfadoxine-pyrimethamine efficacy due to increased resistance is a worrying situation, especially because the malaria transmission level is high in central Africa. Although the resistance phenotype remains to be confirmed, the emergence and spread of the vagKgs allele in west and central Africa could challenge the use of sulfadoxine-pyrimethamine. Funding: Toulouse Institute for Infectious and Inflammatory Diseases. Competing Interests: Declaration of interests We declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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