Kavishe Reginald A, Paulo Petro, Kaaya Robert D, Kalinga Akili, van Zwetselaar Marco, Chilongola Jaffu, Roper Cally, Alifrangis Michael
Kilimanjaro Christian Medical University College and Kilimanjaro Clinical Research Institute, Moshi, Tanzania.
Malar J. 2014 Jul 9;13:264. doi: 10.1186/1475-2875-13-264.
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.
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.
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 (χ² = 2.3, p = 0.512). The NFD haplotype was the second most prevalent haplotype in all regions, ranging from 17% - 26%.
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.
抗疟药物耐药性是全球主要的公共卫生问题。在采用以青蒿素为基础的联合疗法（ACT）后，有报告称东南亚疟原虫对ACT的敏感性降低。在坦桑尼亚，蒿甲醚-本芴醇（ALu）是治疗非复杂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蛋白1单核苷酸多态性（SNP）的分布情况。
使用了2010年6月至2011年8月期间从坦桑尼亚大陆六个地区的医疗机构就诊患者手指采血收集的687份滤纸干血斑和快速诊断试纸条上的恶性疟原虫阳性样本。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测Pfmdr1 SNP N86Y、Y184F和D1246Y。
各地区Pfmdr1多态性的分布存在差异。坦噶地区突变等位基因的患病率异常高，而姆贝亚野生型等位基因的患病率最高。单倍型YFY在坦噶地区最为普遍（29.6%），而NYD单倍型在所有其他地区最为普遍。排除坦噶和姆贝亚地区，其余四个地区四种最常见的Pfmdr1单倍型没有差异（χ² = 2.3，p = 0.512）。NFD单倍型在所有地区都是第二普遍的单倍型，范围在17% - 26%之间。
这是首次在全国范围内对与ACT耐药性相关的Pfmdr1突变进行的调查。密码子86、184和1246处的单个Pfmdr1突变在坦桑尼亚各地区的分布有所不同。常见Pfmdr1单倍型的分布总体上具有同质性，这反映了坦桑尼亚严格实施ALu政策，NFD单倍型在其他单倍型中的总体患病率在17%至26%之间。随着继续将ALu作为一线药物，预计这种单倍型会持续上升，因此需要继续进行药物警戒研究，以监测该药物导致的寄生虫清除延迟情况。
