Prevalence of Plasmodium falciparum delayed clearance associated polymorphisms in adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1) genes in Ghanaian isolates.
Prevalence of Plasmodium falciparum delayed clearance associated polymorphisms in adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1) genes in Ghanaian isolates.
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DOI：
10.1186/s13071-018-2762-3
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发表时间：
2018-03-12
影响因子：
3.2
通讯作者：
Duah NO
中科院分区：
文献类型：
--
作者：
Adams T;Ennuson NAA;Quashie NB;Futagbi G;Matrevi S;Hagan OCK;Abuaku B;Koram KA;Duah NO
据报道，一些非洲国家使用以青蒿素为基础的联合疗法(ACTS)延迟了恶性疟原虫的清除。两个基因的单核苷酸多态(SNPs)，恶性疟原虫适应蛋白复合体2 u亚单位(Pfap2u)和泛素特异性蛋白水解酶1(Pfubp1)，被认为与肯尼亚使用ACT的延迟清除和英国的反复输入性疟疾有关。在加纳使用ACT超过12年的情况下，本研究调查了加纳恶性疟原虫临床分离株pfap2u和pfubp1中SNPs的患病率，为该国抗疟疾耐药性监测提供基线数据。使用了2015-2016年间在贝戈罗、开普敦和纳夫隆戈三个哨所的医院收集的9岁以下患有简单疟疾的儿童的滤纸血迹。从120份标本中提取寄生虫DNA，然后进行套式聚合酶链式反应(NPCR)。Sanger测序检测和鉴定pfap2u和pfubp1基因的SNPs。共有11.1%(9/81)的分离株同时携带两种基因的野生型。在67个分离株中检测到164个pfap2u突变，在72个分离株中检测到271个pfubp1突变。大多数突变为非同义突变：pfap2u突变78%(128/164)，pfubp1突变92.3%(250/271)。5个独特的样本总共有215个pfap2亩SNPs，每个样本的SNPs在15到63个之间。与ART抗性相关的基因包括pfap2muS160N(7.4%，6/81)、pfubp1 E1528D(7.4%，6/81)和D1525E(4.9%，4/81)。3个不同生态类型的研究点间SNPs的分布差异无统计学意义(pfap2：χ2=6.905，df=2，P=0.546；pfubp1：χ2=4.883，df=2，P=0.769)。检测到与ACT延迟清除寄生虫有关的pfap2u和pfubp1基因类型，是加纳逐渐出现抗药性的证据。这些结果将作为监测和选择随时间推移的药物压力的基因型别的基线数据。在ACT敏感性研究中，必须监测加纳分离株中的pfap2muS160N、pfubp1 E1528D和D1525E，特别是当ACTS，特别是AL的治愈率低于100%时。本文的在线版本(10.1186/s13071-0182762-3)包含补充材料，可供授权用户使用。
Plasmodium falciparum delayed clearance with the use of artemisinin-based combination therapy (ACTs) has been reported in some African countries. Single nucleotide polymorphisms (SNPs) in two genes, P. falciparum adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1), have been linked to delayed clearance with ACT use in Kenya and recurrent imported malaria in Britain. With over 12 years of ACT use in Ghana, this study investigated the prevalence of SNPs in the pfap2mu and pfubp1 in Ghanaian clinical P. falciparum isolates to provide baseline data for antimalarial drug resistance surveillance in the country. Filter paper blood blots collected in 2015–2016 from children aged below 9 years presenting with uncomplicated malaria at hospitals in three sentinel sites Begoro, Cape Coast and Navrongo were used. Parasite DNA was extracted from 120 samples followed by nested polymerase chain reaction (nPCR). Sanger sequencing was performed to detect and identify SNPs in pfap2mu and pfubp1 genes. In all, 11.1% (9/81) of the isolates carried the wildtype genotypes for both genes. A total of 164 pfap2mu mutations were detected in 67 isolates whilst 271 pfubp1 mutations were observed in 72 isolates. The majority of the mutations were non-synonymous (NS): 78% (128/164) for pfap2mu and 92.3% (250/271) for pfubp1. Five unique samples had a total of 215 pfap2mu SNPs, ranging between 15 and 63 SNPs per sample. Genotypes reportedly associated with ART resistance detected in this study included pfap2mu S160N (7.4%, 6/81) and pfubp1 E1528D (7.4%, 6/81) as well as D1525E (4.9%, 4/81). There was no significant difference in the prevalence of the SNPs between the three ecologically distinct study sites (pfap2mu: χ2 = 6.905, df = 2, P = 0.546; pfubp1: χ2 = 4.883, df = 2, P = 0.769). The detection of pfap2mu and pfubp1 genotypes associated with ACT delayed parasite clearance is evidence of gradual nascent emergence of resistance in Ghana. The results will serve as baseline data for surveillance and the selection of the genotypes with drug pressure over time. The pfap2mu S160N, pfubp1 E1528D and D1525E must be monitored in Ghanaian isolates in ACT susceptibility studies, especially when cure rates of ACTs, particularly AL, is less than 100%. The online version of this article (10.1186/s13071-018-2762-3) contains supplementary material, which is available to authorized users.
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影响因子：
3.3
作者：
Ouattara, Amed;Kone, Aminatou;Djimde, Abdoulaye A.
通讯作者：
Djimde, Abdoulaye A.
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影响因子：
4.9
作者：
Henriques G;van Schalkwyk DA;Burrow R;Warhurst DC;Thompson E;Baker DA;Fidock DA;Hallett R;Flueck C;Sutherland CJ
通讯作者：
Sutherland CJ
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
3
作者：
Golassa L;Kamugisha E;Ishengoma DS;Baraka V;Shayo A;Baliraine FN;Enweji N;Erko B;Aseffa A;Choy A;Swedberg G
通讯作者：
Swedberg G
影响因子：
7
作者：
Ng, PC;Henikoff, S
通讯作者：
Henikoff, S