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Detection of Plasmodium falciparum K13 Propeller A569G Mutation after Artesunate-amodiaquine Treatment Failure in Niger | Chapter 04 | Advances and Trends in Biotechnology and Genetics Vol. 2

Background: Artemisinin (ART) resistance is a problem that may compromise the elimination of malaria. It is associated with point mutations in the kelch gene PF3D7_1343700 or K13 propeller (pfk13). A recent worldwide map of pfk13 polymorphisms revealed more than 100 non-synonymous (NS) mutations. However, it remains unclear whether these mutations are the result of drug pressure or the expression of a natural polymorphism, because of the scarcity of in-vivo selection of pfK13 mutations data in Africa.

This survey evaluates the association between mutations in PfK13 and the response to treatment with artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) at Gaya, Niger. Mutations in PfK13 before and after treatment were analyzed and used as evidence for the selection of drug resistance following drug pressure.

A total of 161 DNA from patients included in a therapeutic efficacy survey comparing AL vs ASAQ at Gaya sentinel site in 2011 were amplified and sequenced. Five SNPs were identified including 3 non-synonymous (NS) mutations (R528K, A569G and V637I) and 2 synonymous (SY) mutations (C469C and Q613Q). Four SNPs were observed prior to artemisinin-based Combination Therapy (ACT) including 2 NS (R528K and V637I) and 2 SY (C469C and Q613Q) mutations. One NS mutation was selected by ASAQ (PfK13A569G) whereas AL treatment did not select any mutation.

This study suggests that the mutation pfk13A569G is selected by ASAQ. Further mutagenesis studies (CRISPR/Cas9 or Z-Finger Nuclease) will be needed to confirm if pfk13A569G confers resistance to artemisinin.

Author(s) Details

Ibrahim Maman Laminou
Centre de Recherche Médicale et Sanitaire-Niamey, Niger.

Moustapha Mahamane Lamine
Université Cheick Anta Diop de Dakar, Sénégal.

Ibrahim Arzika
Centre de Recherche Médicale et Sanitaire-Niamey, Niger.

Boubacar Mahamadou
Centre de Recherche Médicale et Sanitaire-Niamey, Niger.

D. Gora
Université Cheick Anta Diop de Dakar, Sénégal.

A. Dieye
Université Cheick Anta Diop de Dakar, Sénégal.

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