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在卡塔尔,对输入性恶性疟原虫疟疾中氯喹药物耐药标记物(PfCRT 和 PfMDR1)进行分子监测。

Molecular surveillance of chloroquine drug resistance markers (Pfcrt and Pfmdr1) among imported Plasmodium falciparum malaria in Qatar.

机构信息

a Department of Microbiology and Immunology, Weill Cornell Medicine - Qatar, Cornell University , Qatar Foundation - Education City , Doha , Qatar.

b National Institute for Research in Tribal Health, Indian Council of Medical Research , Jabalpur , India.

出版信息

Pathog Glob Health. 2018 Mar;112(2):57-62. doi: 10.1080/20477724.2017.1399234. Epub 2017 Nov 10.

Abstract

Imported malaria has been a great challenge for public health in Qatar due to influx of large number of migrant workers. Antimalarial drug resistance has emerged as one of the greatest challenges facing malaria control today. Monitoring parasite haplotypes that predict susceptibility to major antimalarial can guide treatment policies. This study aimed to determine molecular drug resistance pattern in imported malaria cases in Qatar. Blood samples from the uncomplicated P. falciparum malaria patients were collected at Hamad General Hospital, HMC, Doha, Qatar. The samples were further confirmed by nested-polymerase chain reaction (PCR) for P. falciparum. Molecular markers of chloroquine (Pfcrt and Pfmdr1) were analyzed by using nested PCR- RFLP method to determine the key point mutations associated with chloroquine (CQ) drug resistance. A total 118 blood samples were positive for P. falciparum. Overall, by RFLP, 72% harboured wild type allele (N86) of Pfmdr1 gene. The prevalence of Pfcrt mutant (T76), WT (K76) and mixed alleles (K76T) was 63.6% (n = 75), 22.9% (n = 27) and 13.5% (n = 16), respectively. Mean parasitaemia level was higher among the wild type alleles of Pfcrt gene as compared to the mixed/mutant alleles whereas mixed alleles of Pfmdr1 gene having high parasitaemia. Molecular surveillance strategy based on imported malaria cases can be used to detect and track CQ drug-resistant malaria. The data presented here might be helpful for enrichment of molecular surveillance of antimalarial resistance and will be useful for developing and updating antimalarial guidance for non-immune imported cases in Qatar.

摘要

输入的疟疾由于大量移民工人的涌入,一直是卡塔尔公共卫生的一大挑战。抗疟药物耐药性的出现是当今疟疾控制面临的最大挑战之一。监测预测对主要抗疟药物敏感性的寄生虫单倍型可以指导治疗政策。本研究旨在确定卡塔尔输入性疟疾病例的分子药物耐药模式。在卡塔尔多哈的哈马德综合医院(HMC)采集无并发症恶性疟原虫疟疾患者的血样。进一步通过巢式聚合酶链反应(PCR)对恶性疟原虫进行确认。采用巢式 PCR-RFLP 法分析氯喹(Pfcrt 和 Pfmdr1)的分子标记物,以确定与氯喹(CQ)耐药相关的关键突变点。共有 118 份血样对恶性疟原虫呈阳性。总体而言,通过 RFLP,72%的Pfmdr1 基因携带野生型等位基因(N86)。Pfcrt 突变体(T76)、野生型(K76)和混合等位基因(K76T)的流行率分别为 63.6%(n=75)、22.9%(n=27)和 13.5%(n=16)。与混合/突变等位基因相比,Pfcrt 基因野生型等位基因的平均寄生虫血症水平更高,而 Pfmdr1 基因的混合等位基因则具有较高的寄生虫血症水平。基于输入性疟疾病例的分子监测策略可用于检测和跟踪 CQ 耐药性疟疾。这里提供的数据可能有助于丰富抗疟药物耐药性的分子监测,并将有助于为卡塔尔非免疫输入性病例制定和更新抗疟指导方针。

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