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首页> 外文期刊>Malaria Journal >Molecular surveillance for drug-resistant Plasmodium falciparum in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies
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Molecular surveillance for drug-resistant Plasmodium falciparum in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies

机译：缅甸/缅甸三个边界地区临床和亚临床人群中耐药恶性疟原虫的分子监测：横断面数据和耐药研究的系统评价

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Background Confirmation of artemisinin-delayed parasite clearance in Plasmodium falciparum along the Thai-Myanmar border has inspired a global response to contain and monitor drug resistance to avert the disastrous consequences of a potential spread to Africa. However, resistance data from Myanmar are sparse, particularly from high-risk areas where limited health services and decades of displacement create conditions for resistance to spread. Subclinical infections may represent an important reservoir for resistance genes that confer a fitness disadvantage relative to wild-type alleles. This study estimates the prevalence of resistance genotypes in three previously unstudied remote populations in Myanmar and tests the a priori hypothesis that resistance gene prevalence would be higher among isolates collected from subclinical infections than isolates collected from febrile clinical patients. A systematic review of resistance studies is provided for context. Methods Community health workers in Karen and Kachin States and an area spanning the Indo-Myanmar border collected dried blood spots from 988 febrile clinical patients and 4,591 villagers with subclinical infection participating in routine prevalence surveys. Samples positive for P. falciparum 18 s ribosomal RNA by real-time PCR were genotyped for P. falciparum multidrug resistance protein (pfmdr1) copy number and the pfcrt K76T polymorphism using multiplex real-time PCR. Results Pfmdr1 copy number increase and the pfcrt K76 polymorphism were determined for 173 and 269 isolates, respectively. Mean pfmdr1 copy number was 1.2 (range: 0.7 to 3.7). Pfmdr1 copy number increase was present in 17.5%, 9.6% and 11.1% of isolates from Karen and Kachin States and the Indo-Myanmar border, respectively. Pfmdr1 amplification was more prevalent in subclinical isolates (20.3%) than clinical isolates (6.4%, odds ratio 3.7, 95% confidence interval 1.1 - 12.5). Pfcrt K76T prevalence ranged from 90-100%. Conclusions Community health workers can contribute to molecular surveillance of drug resistance in remote areas of Myanmar. Marginal and displaced populations under-represented among previous resistance investigations can and should be included in resistance surveillance efforts, particularly once genetic markers of artemisinin-delayed parasite clearance are identified. Subclinical infections may contribute to the epidemiology of drug resistance, but determination of gene amplification from desiccated filter samples requires further validation when DNA concentration is low.
机译：背景确认泰国-缅甸边境沿线恶性疟原虫中青蒿素延迟的寄生虫清除率激发了全球对遏制和监测耐药性的反应，以防止潜在的扩散到非洲的灾难性后果。但是，缅甸的抵抗数据很少，特别是在高风险地区，那里有限的医疗服务和数十年的流离失所为抵抗扩散创造了条件。亚临床感染可能代表了重要的抗性基因库，这些抗性基因相对于野生型等位基因具有适应性劣势。这项研究估计了缅甸三个以前未被研究的偏远人群中耐药基因型的流行，并检验了一个先验假设，即从亚临床感染中分离出的菌株中耐药基因的流行率要高于从发热临床患者中分离出的菌株。有针对性的抗性研究的系统综述。方法克伦邦和克钦邦以及印度-缅甸边境地区的社区卫生工作者收集了988名发热临床患者和4,591名亚临床感染村民的干血斑，参加了常规患病率调查。使用实时荧光定量PCR对恶性疟原虫18 s核糖体RNA阳性的样本进行基因分型，确定恶性疟原虫多药抗性蛋白（pfmdr1）的拷贝数和pfcrt K76T多态性。结果分别确定了173和269株菌株的Pfmdr1拷贝数增加和pfcrt K76多态性。 pfmdr1的平均副本数为1.2（范围：0.7至3.7）。来自克伦邦和克钦邦以及印度-缅甸边境的分离株分别有17.5％，9.6％和11.1％的Pfmdr1拷贝数增加。在亚临床分离株中（20.3％）Pfmdr1扩增比临床分离株（6.4％，比值比3.7，95％置信区间1.1-12.5）更为普遍。 Pfcrt K76T患病率为90-100％。结论社区卫生工作者可以为缅甸偏远地区的耐药性分子监测做出贡献。在先前的抗药性调查中代表性不足的边缘人群和流离失所者可以而且应该纳入抗药性监测工作中，尤其是一旦确定了青蒿素延迟的寄生虫清除的遗传标记。亚临床感染可能是造成耐药性流行病学的原因，但是当DNA浓度低时，要确定从干燥过滤器样品中扩增出的基因需要进一步验证。

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