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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
Journal of Parasitology ( IF 1.0 ) Pub Date : 2021-09-28 , DOI: 10.1645/19-199
Abdoul H Beavogui 1, 2 , Elisabeth Y Diawara 1 , Mahamoud S Cherif 1, 3 , Alexandre Delamou 1, 4 , Nouhoum Diallo 5 , Aliou Traore 5 , Pascal Millimouno 1 , Daouda Camara 1 , Malick M Sylla 1 , Almamy A Toure 1 , Mamadou S Diallo 1 , Sekou Toure 5 , Amadou Togo 5 , Gnepou Camara 1 , Karifa Kourouma 1 , Issaka Sagara 5 , Alhassane Dicko 5 , Abdoulaye Djimde 5
Affiliation  

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.



中文翻译:

几内亚共和国青蒿琥酯-阿莫地喹治疗单纯性疟疾后 PFCRT 76T 和 PFMDR1 86Y 突变恶性疟原虫的选择

使用阿莫地喹单药治疗与选择恶性疟原虫对氯喹耐药的分子标志物(pfcrt 和 pfmdr1)有关。敏感性下降和恶性疟原虫的出现已有报道对青蒿素为基础的联合治疗耐药。因此,评估青蒿琥酯-阿莫地喹 (AS+AQ) 治疗单纯性疟疾对抗疟分子标志物的影响非常重要。我们使用标准的世界卫生组织 (WHO) 协议来确定组合 (AS+AQ) 的体内功效。总共有 170 名受试者被纳入研究。分子分析集中在 168 个干血点上。目的是使用多态性标记msp1msp2和微卫星标记(CA1、Ta87、TA99)确定 pfcrt 76T 和 pfmdr1 86Y 突变的频率和再感染率。使用嵌套 PCR,在某些情况下使用限制性消化。恶性疟原虫水平分子校正前临床反应为充分临床和寄生虫学反应(ACPR)的92.9%(156/168),分子校正后为97.0%(163/168)(P =0.089)。突变点pfcrt 76T的频率在治疗前为76.2%(128/168),治疗后为100%(7/7)(P =0.1423)。对于 pfmdr1 突变,治疗前的频率为 28% (47/168),治疗后的频率为 60% (6/10) ( P = 0.1124)。治疗前 pfcrt 76T + pfmdr1 86Y 的发生率为 22% (37/168) 和治疗后的 50% (6/12) ( P = 0.1465)。尽管组合中存在 AS,但 AS+AQ在几内亚选择 pfcrt 76T 和 pfmdr1 86Y 突变体恶性疟原虫

更新日期:2021-09-28
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