Efficacy of dihydroartemisinin/piperaquine in patients with non-complicated Plasmodium falciparum malaria in Yaoundé, Cameroon.

Autor:	Mairet-Khedim M; Malaria Translational Research Unit, Pasteur International Unit, Pasteur International Network, Phnom Penh, Cambodia and Paris, France.; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse, CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France.; Structural Microbiology Unit, Institut Pasteur, CNRS UMR 3528, 25 rue du Docteur Roux, 75724 Paris 15, France., Nsango S; Department of Biological Sciences, Faculté de Médecine et des Sciences Pharmaceutiques, Université de Douala, Douala, Cameroon.; Malaria Research Unit, Centre Pasteur du Cameroon, Yaoundé, Cameroon., Ngou C; Malaria Research Unit, Centre Pasteur du Cameroon, Yaoundé, Cameroon.; MIVEGEC, IRD, CNRS, Univ. Montpellier, Montpellier, France., Menard S; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse, CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France., Roesch C; Malaria Translational Research Unit, Pasteur International Unit, Pasteur International Network, Phnom Penh, Cambodia and Paris, France.; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia., Khim N; Malaria Translational Research Unit, Pasteur International Unit, Pasteur International Network, Phnom Penh, Cambodia and Paris, France.; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia., Srun S; Malaria Translational Research Unit, Pasteur International Unit, Pasteur International Network, Phnom Penh, Cambodia and Paris, France.; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia., Iriart X; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse, CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France.; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse F-31300, France., Lanot T; Laboratoire de Pharmacocinétique et Toxicologie, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse F-31300, France., Otam L; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse, CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France.; Département des Sciences Biomédicales, Faculté des Sciences, Université de Ngaoundéré, Ngaoundéré, Cameroon., Abega F; Dispensaire de Nkol-Eton, BP894, Yaounde, Cameroon., Ayong L; Malaria Research Unit, Centre Pasteur du Cameroon, Yaoundé, Cameroon., Morlais I; MIVEGEC, IRD, CNRS, Univ. Montpellier, Montpellier, France., Gandia P; Laboratoire de Pharmacocinétique et Toxicologie, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse F-31300, France.; INTHERES, Université de Toulouse, INRA, ENVT, BP 87614, 31076 Toulouse Cedex 3, France., Witkowski B; Malaria Translational Research Unit, Pasteur International Unit, Pasteur International Network, Phnom Penh, Cambodia and Paris, France.; Malaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia., Berry A; Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse, CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France.; Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse F-31300, France.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2021 Oct 11; Vol. 76 (11), pp. 3037-3044.
DOI:	10.1093/jac/dkab281
Abstrakt:	Background: Dihydroartemisinin/piperaquine is increasingly used for the treatment of uncomplicated Plasmodium falciparum malaria in Africa. The efficacy of this combination in Cameroon is poorly documented, while resistance to dihydroartemisinin/piperaquine readily spreads in Southeast Asia. Objectives: This study evaluated the clinical efficacy of dihydroartemisinin/piperaquine in Cameroon, as well as the molecular profile and phenotypic susceptibility of collected isolates to dihydroartemisinin and piperaquine. Patients and Methods: Dihydroartemisinin/piperaquine efficacy in 42 days was followed-up for 138 patients presenting non-complicated falciparum malaria. Piperaquine concentration was determined at day 7 for 124 patients. kelch13 gene polymorphisms (n = 150) and plasmepsin2 gene amplification (n = 148) were determined as molecular markers of resistance to dihydroartemisinin and piperaquine, respectively. Parasite susceptibility to dihydroartemisinin and piperaquine was determined using validated in vitro survival assays. Results: The efficacy of dihydroartemisinin/piperaquine treatment was 100% after PCR correction. The reinfections were not associated with a variation of piperaquine concentration at day 7. Ninety-six percent (144/150) of the samples presented a WT allele of the kelch13 gene. Two percent (3/150) presented the non-synonymous mutation A578S, which is not associated with resistance to dihydroartemisinin. No duplication of the plasmepsin2 gene was observed (0/148). All the samples tested in vitro by survival assays (n = 87) were susceptible to dihydroartemisinin and piperaquine. Conclusions: Dihydroartemisinin/piperaquine has demonstrated excellent therapeutic efficacy with no evidence of emerging artemisinin or piperaquine resistance in Yaoundé, Cameroon. This observation suggests that dihydroartemisinin/piperaquine could be a sustainable therapeutic solution for P. falciparum malaria if implemented in areas previously free of artemisinin- and piperaquine-resistant parasites, unlike Southeast Asia. (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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