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


Journal

The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617

Informations de publication

Date de publication:
11 10 2021
Historique:
received: 26 04 2021
accepted: 12 07 2021
pubmed: 29 8 2021
medline: 15 12 2021
entrez: 28 8 2021
Statut: ppublish

Résumé

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. 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. 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. 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. 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.

Sections du résumé

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.

Identifiants

pubmed: 34453535
pii: 6359119
doi: 10.1093/jac/dkab281
doi:

Substances chimiques

Antimalarials 0
Artemisinins 0
Quinolines 0
artenimol 6A9O50735X
piperaquine A0HV2Q956Y

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3037-3044

Informations de copyright

© 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.

Auteurs

Mélissa 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.

Sandrine 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.

Christelle Ngou (C)

Malaria Research Unit, Centre Pasteur du Cameroon, Yaoundé, Cameroon.
MIVEGEC, IRD, CNRS, Univ. Montpellier, Montpellier, France.

Sandie Menard (S)

Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse, CNRS UMR5051, INSERM UMR1291, UPS, Toulouse, France.

Camille 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.

Nimol 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.

Sreynet 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.

Xavier 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.

Thomas Lanot (T)

Laboratoire de Pharmacocinétique et Toxicologie, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse F-31300, France.

Laure 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.

Francis Abega (F)

Dispensaire de Nkol-Eton, BP894, Yaounde, Cameroon.

Lawrence Ayong (L)

Malaria Research Unit, Centre Pasteur du Cameroon, Yaoundé, Cameroon.

Isabelle Morlais (I)

MIVEGEC, IRD, CNRS, Univ. Montpellier, Montpellier, France.

Peggy 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.

Benoit 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.

Antoine 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.

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