Al-Hamidhi Salama, Mahdy Mohammed A K, Al-Hashami Zainab, Al-Farsi Hissa, Al-mekhlafi Abdulsalam M, Idris Mohamed A, Beja-Pereira Albano, Babiker Hamza A
Malar J. 2013 Jul 15;12:244. doi: 10.1186/1475-2875-12-244.
Despite evident success of malaria control in many sites in the Arabian Peninsula, malaria remains endemic in a few spots, in Yemen and south-west of Saudi Arabia. In addition to local transmission, imported malaria sustains an extra source of parasites that can challenge the strengths of local control strategies. This study examined the genetic diversity of Plasmodium falciparum in Yemen and mutations of drug resistant genes, to elucidate parasite structure and distribution of drug resistance genotypes in the region.
Five polymorphic loci (MSP-2, Pfg377 and three microsatellites on chromosome 8) not involved in anti-malarial drug resistance, and four drug resistant genes (pfcrt, pfmdr1, dhfr and dhps) were genotyped in 108 P. falciparum isolates collected in three sites in Yemen: Dhamar, Hodeidah and Taiz.
High diversity was seen in non-drug genes, pfg377 (He = 0.66), msp-2 (He = 0.80) and three microsatellites on chr 8, 7.7 kb (He = 0.88), 4.3 kb (He = 0.77) and 0.8 kb (He = 0.71). There was a high level of mixed-genotype infections (57%), with an average 1.8 genotypes per patient. No linkage disequilibrium was seen between drug resistant genes and the non-drug markers (p < 0.05). Genetic differentiation between populations was low (most pair-wise FST values <0.03), indicating extensive gene flow between the parasites in the three sites.
The high diversity of P. falciparum in Yemen is indicative of a large parasite reservoir, which represents a challenge to control efforts. The presence of two distinct pfcrt genotype, CVIET and SVMNT, suggests that chloroquine resistance can possibly be related to a migratory path from Africa and Asia. The absence of the triple mutant dhfr genotype (IRN) and dhps mutations supports the use of artesunate + sulphadoxine-pyrimethamine as first-line therapy. However, the prevalent pfmdr1 genotype NFSND [21%] has previously been associated with tolerance/resistance response to artemisinin combination therapy (ACT). Regular surveys are, therefore, important to monitor spread of pfmdr1 and dhfr mutations and response to ACT.
尽管阿拉伯半岛许多地区在疟疾控制方面取得了显著成效，但也门和沙特阿拉伯西南部的一些地区疟疾仍然流行。除了本地传播外，输入性疟疾维持着额外的寄生虫来源，这可能对当地控制策略的力度构成挑战。本研究调查了也门恶性疟原虫的遗传多样性和耐药基因的突变情况，以阐明该地区寄生虫的结构和耐药基因型的分布。
对在也门三个地点（达马尔、荷台达和塔伊兹）收集的108株恶性疟原虫分离株，对5个与抗疟药物耐药性无关的多态性位点（MSP-2、Pfg377和8号染色体上的三个微卫星）以及4个耐药基因（pfcrt、pfmdr1、dhfr和dhps）进行基因分型。
在非耐药基因中观察到高度多样性，Pfg377（He = 0.66）、MSP-2（He = 0.80）以及8号染色体上的三个微卫星，7.7 kb（He = 0.88）、4.3 kb（He = 0.77）和0.8 kb（He = 0.71）。混合基因型感染水平较高（57%），每位患者平均有1.8种基因型。耐药基因与非耐药标记之间未观察到连锁不平衡（p < 0.05）。群体间的遗传分化较低（大多数成对FST值<0.03），表明三个地点的寄生虫之间存在广泛的基因流动。
也门恶性疟原虫的高度多样性表明存在大量寄生虫库，这对控制工作构成挑战。两种不同的pfcrt基因型CVIET和SVMNT的存在表明，氯喹耐药性可能与来自非洲和亚洲的迁徙路径有关。三重突变dhfr基因型（IRN）和dhps突变的缺失支持将青蒿琥酯+磺胺多辛-乙胺嘧啶作为一线治疗药物。然而，普遍存在的pfmdr1基因型NFSND [21%]此前已与对青蒿素联合疗法（ACT）的耐受性/耐药反应相关。因此，定期调查对于监测pfmdr1和dhfr突变的传播以及对ACT的反应很重要。
