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Ex vivo RSA and Pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017

Authors :
Yade, Mamadou Samb
Dièye, Baba
Coppée, Romain
Mbaye, Aminata
Diallo, Mamadou Alpha
Diongue, Khadim
Bailly, Justine
Mama, Atikatou
Fall, Awa
Thiaw, Alphonse Birane
Ndiaye, Ibrahima Mbaye
Ndiaye, Tolla
Gaye, Amy
Tine, Abdoulaye
Diédhiou, Younouss
Mbaye, Amadou Mactar
Doderer-Lang, Cécile
Garba, Mamane Nassirou
Bei, Amy Kristine
Ménard, Didier
Ndiaye, Daouda
Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)
Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137))
Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord
Centre de Recherche et de Formation en Infectiologie de Guinée [Conakry, Guinée] (CERFIG)
Université Gamal Abdel Nasser de Conakry
Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261)
Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité)
Institut Cochin (IC UM3 (UMR 8104 / U1016))
Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Hôpital Cochin [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Université de Sherbrooke (UdeS)
Dynamique des interactions hôte pathogène (DIHP)
Université de Strasbourg (UNISTRA)
Yale School of Public Health (YSPH)
Harvard T.H. Chan School of Public Health
CHU Strasbourg
Biologie de Plasmodium et Vaccins - Malaria Parasite Biology and Vaccines
Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions
Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
The work was supported by the International Centers of Excellence for Malaria Research (ICEMR), West Africa (U19AI089696) and the Université Cheikh Anta Diop de Dakar. The study was also supported by the Institut Pasteur, Paris, the French Government (Agence Nationale de la Recherche), Laboratoire d’Excellence (LabEx) 'French Parasitology Alliance for Health Care' (ANR-11-LABX-0024-PARAFRAP), the Cochin institute (ANR Chrono ANR-19-CE35-0009) and the University of Strasbourg through the Programme IdEX 2022 (DM).
ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011)
ANR-19-CE35-0009,Chrono,Résistance à l'artémisinine et cycle cellulaire de Plasmodium falciparum(2019)
Source :
Malaria Journal, Malaria Journal, 2023, 22 (1), pp.167. ⟨10.1186/s12936-023-04588-1⟩
Publication Year :
2023
Publisher :
Research Square Platform LLC, 2023.

Abstract

Background Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur. Methods Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach. Results All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively. Conclusion The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.

Details

ISSN :
14752875
Database :
OpenAIRE
Journal :
Malaria Journal, Malaria Journal, 2023, 22 (1), pp.167. ⟨10.1186/s12936-023-04588-1⟩
Accession number :
edsair.doi.dedup.....cefe801e595e370ba22e45ab365710cb
Full Text :
https://doi.org/10.21203/rs.3.rs-2538775/v1