Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania
Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania
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DOI：
10.1186/1475-2875-13-264
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发表时间：
2014-07-09
期刊：
影响因子：
3
通讯作者：
Alifrangis, Michael
中科院分区：
文献类型：
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作者：
Kavishe, Reginald A.;Paulo, Petro;Alifrangis, Michael
背景：抗疟疾耐药性是世界范围内的一个主要公共卫生问题。据报道，在采用基于青蒿素的联合疗法 (ACT) 后，东南亚的疟原虫对 ACT 的敏感性降低。在坦桑尼亚，蒿甲醚-本芴醇 (ALu) 是治疗单纯性疟疾的推荐一线药物。本研究调查了坦桑尼亚与疟原虫对 ALu 耐受性增加相关的恶性疟原虫多药耐药性蛋白 1 单核苷酸多态性 (SNP) 的分布。方法：通过手指刺破法从 2010 年 6 月至 2011 年 8 月期间在坦桑尼亚大陆六个地区的医疗机构就诊的患者身上采集的滤纸和快速诊断试纸上总共 687 个恶性疟原虫阳性干血点，并进行了分析。使用过。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术检测Pfmdr1 SNPs N86Y、Y184F和D1246Y。结果：Pfmdr1多态性区域分布存在差异。坦噶地区突变等位基因的患病率异常高，而姆贝亚地区野生型等位基因的患病率最高。单倍型 YFY 在坦噶最为普遍 (29.6%)，而 NYD 单倍型在所有其他地区最为普遍。排除 Tanga 和 Mbeya，四种最常见的 Pfmdr1 单倍型在其余四个区域之间没有变化 (X-2 = 2.3，p = 0.512)。 NFD单倍型是所有地区第二常见的单倍型，范围为17% - 26%。结论：这是第一个全国范围内与ACT耐药相关的Pfmdr1突变的调查。 Pfmdr1 密码子 86、184 和 1246 处的个体突变分布在整个坦桑尼亚地区有所不同。常见 Pfmdr1 单倍型的分布存在总体同质性，反映出坦桑尼亚严格执行 ALu 政策，其中 NFD 单倍型的总体患病率在其他单倍型中为 17% 至 26%。随着 ALu 继续作为一线药物，该单倍型预计将继续上升，因此需要继续进行药物警戒研究，以监测药物对寄生虫清除的任何延迟。
Background: Resistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malaria parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu) is the recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania.Methods: A total of 687 Plasmodium falciparum positive dried blood spots on filter paper and rapid diagnostic test strips collected by finger pricks from patients attending health facilities in six regions of Tanzania mainland between June 2010 and August 2011 were used. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect Pfmdr1 SNPs N86Y, Y184F and D1246Y.Results: There were variations in the distribution of Pfmdr1 polymorphisms among regions. Tanga region had exceptionally high prevalence of mutant alleles, while Mbeya had the highest prevalence of wild type alleles. The haplotype YFY was exclusively most prevalent in Tanga (29.6%) whereas the NYD haplotype was the most prevalent in all other regions. Excluding Tanga and Mbeya, four, most common Pfmdr1 haplotypes did not vary between the remaining four regions (X-2 = 2.3, p = 0.512). The NFD haplotype was the second most prevalent haplotype in all regions, ranging from 17% - 26%.Conclusion: This is the first country-wide survey on Pfmdr1 mutations associated with ACT resistance. Distribution of individual Pfmdr1 mutations at codons 86, 184 and 1246 varies throughout Tanzanian regions. There is a general homogeneity in distribution of common Pfmdr1 haplotypes reflecting strict implementation of ALu policy in Tanzania with overall prevalence of NFD haplotype ranging from 17 to 26% among other haplotypes. With continuation of ALu as first-line drug this haplotype is expected to keep rising, thus there is need for continued pharmacovigilance studies to monitor any delayed parasite clearance by the drug.