Accès ouvert

Plasmodium falciparum Kelch13 polymorphisms identified after treatment failure with artemisinin- based combination therapy in Niger

Article scientifique 2022 Anglais

Résumé

Abstract Background: Artemisinin-based combination therapy (ACT) is the most effective treatment for malaria, and has significantly reduced morbimortality. Polymorphisms associated with the Plasmodium falciparum kelch gene (Pfkelch13) propeller domains have been associated with delayed parasite clearance even with ACT treatment. Methods: The Pfkelch13gene was sequenced from P. falciparum infected patients (n=159) with uncomplicated malaria in Niger.An adequate clinical and parasitological response (ACPR) was reported in 155 patients. Four (n=4) patients had treatment failure (TF) that were not reinfections - two of which had late parasitological failures (LPF) and two had late clinical failures (LCF). Results: Thirteen single nucleotide polymorphisms (SNPs) were identified of which eight were non synonymous (NSY) (C469R, T508S, S515T, A578S, I465V, I437V, E506L, N197D), and five were synonymous (SY) (H298H, H385H, P443P, P715P, L514L). Six SNP (C469R, H298H, E506L, N197D, H385H, P715P) were present before ACT treatment, while seven mutations (C469R, T508S, S515T, L514L, P443P, I437V, I465V) were selected by Artemether lumefantrine (AL) - five of which were non synonymous (C469R, T508S, S515T, I437V, I465V). Artesunate amodiaquine (ASAQ) has selected any mutation. One sample presented three cumulatively non-synonymous SNPs - C469R, T508S, S515T. This study demonstrates intra host selection of Pfkelch13 gene NS by AL. Conclusions: The study highlights the importance of LCF and LPF parasites in the selection of resistance to ACT. Further studies using gene editing are required to confirm the potential implication of resistance to ACT with the most common S515T and T508S mutations. It would also be important to elucidate the role of cumulative mutations. GenBank accession numbers: MZ364160, MZ364-213

Citer ce document

Arzika, I., Lobo, N., Tidjani, I., Houzé, S., Hubert, V., Mahamadou, B., Adéhossi, E., Sarr, D., Mahmud, O., Laminou, I. (2022). Plasmodium falciparum Kelch13 polymorphisms identified after treatment failure with artemisinin- based combination therapy in Niger. https://doi.org/10.21203/rs.3.rs-2390016/v1

Accès au document

Voir sur le dépôt source

Ce document est hébergé sur son dépôt institutionnel d'origine.

Auteur(s)

Ibrahima Issa Arzika Neil F. Lobo Ilagouma Amadou Tidjani Sandrine Houzé Véronique Hubert Boubacar Mahamadou Eric Adéhossi Demba Sarr Ousman Mahmud Ibrahim Maman Laminou

Statistiques

Consultations : 1

Téléchargements : 0