High sensitivity detection of Plasmodium species reveals positive correlations between infections of different species, shifts in age distribution and reduced local variation in Papua New Guinea.
High sensitivity detection of Plasmodium species reveals positive correlations between infections of different species, shifts in age distribution and reduced local variation in Papua New Guinea.
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DOI：
10.1186/1475-2875-8-41
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发表时间：
2009-03-11
期刊：
影响因子：
3
通讯作者：
Zimmerman PA
中科院分区：
文献类型：
--
作者：
Mueller I;Widmer S;Michel D;Maraga S;McNamara DT;Kiniboro B;Sie A;Smith TA;Zimmerman PA
当通过标准光学显微镜(LM)诊断时，疟疾流行率在不同地点之间可能存在显著差异，甚至在局部范围内也是如此，在恶性疟原虫、间日疟原虫和疟疾共同流行的地区，混合物种感染始终低于预期。高通量分子物种诊断分析的发展现在能够在大范围现场和干预研究中对疟疾感染进行基于聚合酶链式反应的常规监测，并提高了社区内和社区之间物种分布的分辨率。这项研究报告了巴布亚新几内亚塞皮克中部地区15个村庄中所有四种人类疟疾感染和混合感染的流行率的差异，这些感染是通过光镜和聚合酶后连接酶检测反应-荧光微球(LDR-FMA)试验诊断的。与LM诊断相比，LDR-FMA的恶性疟原虫、间日疟原虫、疟疾和卵形疟原虫的感染率显著升高(p<；0.001)。疟疾原虫(3.9%比13.4%)和卵形疟原虫(0.0%比4.8%)的增长尤为明显。与LM诊断表明混合感染存在显著缺陷相反，LDR-FMA检测到的混合感染明显超出预期(p<；0.001)。在LDR-FMA诊断的恶性疟(7-9岁占47.5%，LDR-FMA：10-19岁占74.2%)和间日疟(LM：4-6岁占24.2%，LDR-FMA：7-9岁占50.9%)感染的高发年龄组，但未诊断出疟疾感染(10-19岁占7.7%，LDR-FMA：21.6%)。除了被诊断为恶性疟原虫的物种外，所有物种的患病率都存在显著的地域差异，在LDR-FMA中这种差异的程度大于被诊断为恶性疟原虫的感染(总体上，84.4%对37.6%)。驱虫蚊帐(ITN)覆盖率也是影响疟原虫种群感染率地理差异的主要因素，LDR-FMA和LM(恶性疟原虫除外)的感染率差异分别在60.6%-74.5%和81.8%-90.0%之间。本研究表明，分子诊断的应用揭示了疟疾风险的模式，这些模式与标准LM获得的模式显著不同。这些结果为疟疾控制和根除战略的设计提供了相关的见解。
When diagnosed by standard light microscopy (LM), malaria prevalence can vary significantly between sites, even at local scale, and mixed species infections are consistently less common than expect in areas co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae. The development of a high-throughput molecular species diagnostic assay now enables routine PCR-based surveillance of malaria infections in large field and intervention studies, and improves resolution of species distribution within and between communities. This study reports differences in the prevalence of infections with all four human malarial species and of mixed infections as diagnosed by LM and post-PCR ligase detection reaction – fluorescent microsphere (LDR-FMA) assay in 15 villages in the central Sepik area of Papua New Guinea. Significantly higher rates of infection by P. falciparum, P. vivax, P. malariae and Plasmodium ovale were observed in LDR-FMA compared to LM diagnosis (p < 0.001). Increases were particularly pronounced for P. malariae (3.9% vs 13.4%) and P. ovale (0.0% vs 4.8%). In contrast to LM diagnosis, which suggested a significant deficit of mixed species infections, a significant excess of mixed infections over expectation was detected by LDR-FMA (p < 0.001). Age of peak prevalence shifted to older age groups in LDR-FMA diagnosed infections for P. falciparum (LM: 7–9 yrs 47.5%, LDR-FMA: 10–19 yrs 74.2%) and P. vivax (LM: 4–6 yrs 24.2%, LDR-FMA: 7–9 yrs 50.9%) but not P. malariae infections (10–19 yrs, LM: 7.7% LDR-FMA: 21.6%). Significant geographical variation in prevalence was found for all species (except for LM-diagnosed P. falciparum), with the extent of this variation greater in LDR-FMA than LM diagnosed infections (overall, 84.4% vs. 37.6%). Insecticide-treated bednet (ITN) coverage was also the dominant factor linked to geographical differences in Plasmodium species infection prevalence explaining between 60.6% – 74.5% of this variation for LDR-FMA and 81.8% – 90.0% for LM (except P. falciparum), respectively. The present study demonstrates that application of molecular diagnosis reveals patterns of malaria risk that are significantly different from those obtained by standard LM. Results provide insight relevant to design of malaria control and eradication strategies.