冈比亚无症状儿童中恶性疟原虫在旱季的流行情况，以及对诊断方法的比较评估。
Dry season prevalence of Plasmodium falciparum in asymptomatic gambian children, with a comparative evaluation of diagnostic methods.
机构信息
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Ashworth Laboratories, Kings Buildings, Charlotte Auerbach Rd, Edinburgh, EH9 3FL, UK.
Medical Research Council Unit in The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.
出版信息
Malar J. 2022 Jun 7;21(1):171. doi: 10.1186/s12936-022-04184-9.
BACKGROUND
Subclinical infection with Plasmodium falciparum remains highly prevalent, yet diagnosing these often low-density infections remains a challenge. Infections can be subpatent, falling below the limit of detection for conventional thick-film microscopy and rapid diagnostic testing (RDT). In this study, the prevalence of subclinical P. falciparum infections in school-aged children was characterised at the start of the dry season in the Upper River Region of The Gambia in 2017/2018, with a goal to also compare the utility of different diagnostic tools.
METHODS
In a cross-sectional survey of children living in 29 villages on the south bank of the Gambia river (median age of 10 years), matched microscopy, rapid diagnostic test (RDT, detecting histidine-rich protein 2) and polymerase chain reaction (PCR, targeting either 18S rRNA or var gene acidic terminal sequence) were used to determine the prevalence of patent and subpatent infections and to compare the performance of the different diagnostic methods.
RESULTS
The prevalence of var gene acidic terminal sequence (varATS) qPCR-detectable infections was 10.2% (141/1381) with a median density of 3.12 parasites/µL. Malaria prevalence was highly heterogeneous across the region, ranging from < 1% to ~ 40% prevalence in different village clusters. Compared to varATS, 18S rRNA PCR detected fewer low-density infections, with an assay sensitivity of 50% and specificity of 98.8%. Parasite prevalence in the cohort was 2.9% by microscopy and 1.5% by RDT. Compared to varATS qPCR, microscopy and RDT had sensitivities of 11.5% and 9.2%, respectively, although both methods were highly specific (> 98%). Samples that were positive by all three tests (varATS qPCR, RDT and microscopy) had significantly higher parasite densities (median = 1705 parasites/µL) than samples that were positive by varATS qPCR only (median = 2.4 parasites/µL).
CONCLUSIONS
The majority of subclinical malaria infections in school-aged children were of extremely low parasite density and detectable only by ultra-sensitive PCR analysis. Understanding the duration of these low density infections, their physiological impact and their contribution to sustained parasite transmission is necessary to inform malaria elimination strategies.
背景
间日疟原虫亚临床感染仍然高度流行，但诊断这些通常低密度感染仍然是一个挑战。感染可能是亚临床的，低于常规厚涂片显微镜检查和快速诊断检测 (RDT) 的检测下限。在这项研究中，2017/2018 年在冈比亚河上流域的 29 个村庄进行了学龄儿童亚临床间日疟原虫感染的横断面调查，目的是比较不同诊断工具的效用。
方法
在对居住在冈比亚河南岸 29 个村庄的儿童（中位数年龄为 10 岁）的横断面调查中，匹配显微镜检查、快速诊断检测（RDT，检测组氨酸丰富蛋白 2）和聚合酶链反应（PCR，针对 18S rRNA 或 var 基因酸性末端序列）用于确定专利和亚临床感染的流行率，并比较不同诊断方法的性能。
结果
var 基因酸性末端序列 (varATS) qPCR 检测到的感染率为 10.2%（141/1381），中位数密度为 3.12 个/µL。疟疾的流行率在该地区高度异质，不同村庄群的流行率从<1%到~40%不等。与 varATS 相比，18S rRNA PCR 检测到的低密度感染较少，检测灵敏度为 50%，特异性为 98.8%。该队列的寄生虫患病率为显微镜检查 2.9%，RDT 为 1.5%。与 varATS qPCR 相比，显微镜检查和 RDT 的敏感性分别为 11.5%和 9.2%，尽管两种方法的特异性均>98%。通过所有三种检测方法（varATS qPCR、RDT 和显微镜检查）呈阳性的样本的寄生虫密度明显高于仅通过 varATS qPCR 呈阳性的样本（中位数=2.4 个/µL）。
结论
学龄儿童亚临床疟疾感染大多数为极低的寄生虫密度，仅通过超灵敏 PCR 分析才可检测到。了解这些低密度感染的持续时间、生理影响及其对持续寄生虫传播的贡献，对于制定疟疾消除策略是必要的。
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