Molecular markers of chloroquine resistance in Plasmodium falciparum in Sri Lanka: frequency before revision of the antimalarial drug policy
Molecular markers of chloroquine resistance in Plasmodium falciparum in Sri Lanka: frequency before revision of the antimalarial drug policy
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斯里兰卡恶性疟原虫氯喹耐药性分子标记：抗疟药物政策修订前的频率
DOI：
10.1179/136485909x435067
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发表时间：
2009
影响因子：
--
通讯作者：
N. D. Silva
中科院分区：
文献类型：
--
作者：
H. Hapuarachchi;S. Abeysundara;M. Dayanath;A. Manamperi;W. Abeyewickreme;N. D. Silva
耐药性现在是控制人类疟疾的一个主要障碍，有报道称除青蒿素衍生物外，临床上对所有常用的抗疟药物都存在广泛的耐药性（WHO，2008）。在斯里兰卡，虽然恶性疟原虫对氯喹 (CQ) 的耐药性于 1984 年首次被记录，并且最近发现某些流行地区 50% 的恶性疟原虫感染表现出这种耐药性（Handunnetti 等，1996 年；Hapuarachchi 等，2004 年），但直到 2008 年，CQ 仍然是所有无并发症疟疾感染的一线治疗方法。抗疟药耐药性的检测对于遏制其出现和传播至关重要。分子标记的检测已成为记录此类耐药性的流行工具，因为与传统的体内和体外测定相比，它通常更容易在社区水平上进行，并且更省力。对与耐药性相关的分子标记的流行程度的评估可用于识别最需要体内评估的群落（Plowe，2003）。恶性疟原虫中最常用的 CQ 抗性标记是寄生虫的 CQ 抗性转运蛋白 (pfcrt) 和多重耐药性 1 (pfmdr1) 基因的变体。恶性疟原虫的多项体外和体内研究结果证实了 pfcrt 突变与 CQ 抗性之间的关联（Fidock 等，2000；Labbé 等，2001；Maguire 等，2001）。在已报道的突变中，密码子 76 (K76T) 的甘氨酸-苏氨酸取代目前被认为是预测 CQ 抗性最合适的分子标记，因为它在 CQ 抗性寄生虫中出现的频率很高，并且与 CQ 抗性密切相关（Djimdé 等，2001）。尽管 pfmdr1 在 CQ 耐药中的确切作用仍存在争议，但有人认为突变 N86Y、Y184F、S1034C、D1042N 和 D1246Y 可能各自在调节 CQ 耐药水平中发挥潜在作用 (Reed et al., 2000)。
Drug resistance is now a major obstacle in the control of human malaria, with reports of widespread clinical resistance against all the commonly used antimalarial drugs except the artemisinin derivatives (WHO, 2008). In Sri Lanka, although resistance of Plasmodium falciparum to chloroquine (CQ) was first documented in 1984 and 50% of P. falciparum infections in certain endemic areas were recently found to show such resistance (Handunnetti et al., 1996; Hapuarachchi et al., 2004), CQ remained the first-line therapy for all uncomplicated malarial infections until 2008. The detection of antimalarial resistance is of vital importance for containment of its emergence and spread. The detection of molecular markers has become a popular tool for the recording of such resistance since, compared with conventional in-vivo and in-vitro assays, it is often easier to perform at community level, and less laborious. Evaluation of the prevalence of the molecular markers associated with resistance can be used to identify communities that are most in need of in-vivo assessments (Plowe, 2003). The most commonly used markers for CQ resistance in P. falciparum are variants of the parasite’s CQ resistance transporter (pfcrt) and multiple drug resistance 1 (pfmdr1) genes. The results of several in-vitro and in-vivo studies of P. falciparum have confirmed the association between mutations in pfcrt and CQ resistance (Fidock et al., 2000; Labbé et al., 2001; Maguire et al., 2001). Of the reported mutations, the lycine-tothreonine substitution at codon 76 (K76T) is currently considered the most appropriate molecular marker for predicting CQ resistance, given its high frequency in CQresistant parasites and strong association with CQ resistance (Djimdé et al., 2001). Although the exact role of pfmdr1 in CQ resistance is still controversial, it has been suggested that mutations N86Y, Y184F, S1034C, D1042N and D1246Y may each play a potential role in modulating the level of CQ resistance (Reed et al., 2000).
影响因子：
16
作者：
Fidock, DA;Nomura, T;Wellems, TE
通讯作者：
Wellems, TE
影响因子：
6.4
作者：
Dorsey, G;Kamya, MR;Rosenthal, PJ
通讯作者：
Rosenthal, PJ