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Selection of Pfcrt 76T and Pfmdr1 86Y Mutant Plasmodium falciparum after Treatment of Uncomplicated Malaria with Artesunate-Amodiaquine in Republic of Guinea

2021; American Society of Parasitologists; Volume: 107; Issue: 5 Linguagem: Inglês

10.1645/19-199

1937-2345

Abdoul Habib Béavogui, Elisabeth Y. Diawara, Mahamoud Sama Chérif, Alexandre Délamou, Nouhoum Diallo, Aliou Traoré, Pascal Millimouno, Daouda Camara, Malick Minkael Sylla, Almamy Amara Touré, Alpha Diallo, Sekou Touré, Amadou Hamidou Togo, Gnepou Camara, Karifa Kourouma, Issaka Sagara, Alhassane Dicko, Abdoulaye Djimdé,

Computational Drug Discovery Methods

The use of Amodiaquine monotherapy is associated with the selection of molecular markers of Plasmodium falciparum resistance to chloroquine (pfcrt and pfmdr1). The decrease in sensitivity and the emergence of P. falciparum resistant to artemisinin-based combination therapy have been reported. Therefore, it is important to assess the impact of treatment of uncomplicated malaria with Artesunate-Amodiaquine (AS+AQ) on molecular markers of antimalarial resistance. We used standard World Health Organization (WHO) protocols to determine the in vivo efficacy of the combination (AS+AQ). In total, 170 subjects were included in the study. The molecular analysis focused on 168 dried blood spots. The aims were to determine the frequency of pfcrt 76T and pfmdr1 86Y mutations and the rates of reinfection using polymorphism markers msp1, msp2, and microsatellite markers (CA1, Ta87, TA99). Nested-PCR was used, followed in some cases by a restriction digestion. The level of P. falciparum clinical response was 92.9% (156/168) of Adequate Clinical and Parasitological Response (ACPR) before molecular correction and 97.0% (163/168) after molecular correction (P = 0.089). The frequency of mutation point pfcrt 76T was 76.2% (128/168) before treatment and 100% (7/7) after treatment (P = 0.1423). For the pfmdr1 mutation, the frequency was 28% (47/168) before treatment and 60% (6/10) after treatment (P = 0.1124). The rate of pfcrt 76T + pfmdr1 86Y was 22% (37/168) before and 50% (6/12) after treatment (P = 0.1465). Despite the presence of AS in the combination, AS+AQ selects for pfcrt 76T and pfmdr1 86Y mutant P. falciparum in Guinea.