Detection of asymptomatic Leishmania infection in Bangladesh by novel antigen and antibody diagnostic tools shows strong association with PKDL patients

Detection of asymptomatic Leishmania infection in Bangladesh by novel antigen and antibody diagnostic tools shows strong association with PKDL patients
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通过新型抗原和抗体诊断工具检测孟加拉国无症状利什曼原虫感染,结果显示与 PKDL 患者存在密切关联

DOI:
10.1101/2020.05.26.20113431
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发表时间:
2020
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通讯作者:
Owen S
Owen S
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作者:
Owen S

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背景在印度次大陆(ISC),无症状利什曼病感染人数超过临床感染人数,那里的疾病宿主是人为的。检测到活动性无症状感染的诊断方法可能有助于ISC的内脏利什曼病(VL)消除运动。方法/主要发现在2016年9月至2018年3月期间,对孟加拉国流行区720户家庭及其邻近276名VL接触者和黑热病后皮肤利什曼病(PKDL)指数病例的血液和尿样进行了定量聚合酶链式反应(QPCR)、环路介导的等温扩增(LAMP)、直接凝集试验(DAT)和利什曼抗原ELISA检测。在指示病例的720名接触者中,通过qPCR(1.0%)、LAMP(2.1%)、DAT(3.9%)和利什曼病毒抗原ELISA法(3.3%)的联合检测,69名参与者(9.6%)检出无症状感染。4种诊断试验全部阳性者仅1例(0.1%)。使用科恩的kappa(K)统计量计算出测试之间的一致性很差,然而利什曼抗原ELISA和DAT结合起来通过一次以上的测试捕获了所有参与者的阳性。我们发现强有力的证据表明,指示病例是pkdl病例(OR1.94,p=0.009),尤其是黄斑性pkdl(OR2.12,p=0.004)与至少四种tests.Conclusions/SignificanceLeishmaniaantigen中的一种呈阳性之间存在关联。发展RDT格式的抗原检测测试将有利于消除运动。作者概述感染寄生虫的杜氏利什曼原虫可导致无症状感染,只有约5%的无症状转化为内脏利什曼病,这是感染的临床表现。血清学检测到抗利什曼抗体,因此不能区分既往感染和活动性感染。分子检测和检测利什马尼亚病毒抗原的方法可以检测到活动性感染。自2005年签署谅解备忘录以来,印度、尼泊尔和孟加拉国一直致力于消除内脏利什曼病。在像孟加拉国这样的消灭环境中,疾病宿主是人为性的,相对简单的检测,如利什曼抗原ELISA,需要非侵入性的尿样,与血清学相结合,可能对监测和监测利什曼传播是有益的。将抗原测试发展为现场兼容的快速诊断测试将进一步有利于消除运动。
BackgroundAsymptomaticLeishmaniainfections outnumber clinical infections on the Indian sub-continent (ISC) where disease reservoirs are anthroponotic. Diagnostics which detect active asymptomatic infection, which are suitable for monitoring and surveillance, may be of benefit to the visceral leishmaniasis (VL) elimination campaign on the ISC.Methodology/Principal FindingsQuantitative polymerase chain reaction (qPCR), loop mediated isothermal amplification (LAMP), the direct agglutination test (DAT), and theLeishmaniaantigen ELISA were carried out on blood and urine samples collected from 720 household and neighbouring contacts of 276 VL and post kala-azar dermal leishmaniasis (PKDL) index cases, with no symptoms or history of VL and PKDL, in endemic regions of Bangladesh between September 2016 and March 2018. Of the 720 contacts of index cases, asymptomatic infection was detected in 69 (9.6%) participants by a combination of qPCR (1.0%), LAMP (2.1%), DAT (3.9%), andLeishmaniaantigen ELISA (3.3%). Only 1 (0.1%) participant was detected positive by all 4 diagnostic tests. Poor agreement between tests was calculated using Cohen’s kappa (k) statistics, however theLeishmaniaantigen ELISA and DAT in combination capture all participants positive by more than one test. We find strong evidence for association between the index case being a PKDL case (OR 1.94, p = 0.009), specifically macular PKDL (OR 2.12, p = 0.004) and being positive for at least one of the four tests.Conclusions/SignificanceLeishmaniaantigen ELISA detects active asymptomatic infection, requires a non-invasive sample, and therefore may be of benefit for monitoring transmission and surveillance in an elimination setting in combination with serology. Development of an antigen detection test in RDT format would be of benefit to the elimination campaign.Author summaryInfection with the parasiteLeishmania donovanican lead to an asymptomatic infection with only around 5% of asymptomatics converting to visceral leishmaniasis the clinical manifestation of the infection. Serological assays detect anti-Leishmaniaantibodies and therefore cannot distinguish between past and active infection. Molecular assays and those which detectLeishmaniaantigens detect active infection. Since the signing of a memorandum of understanding in 2005, visceral leishmaniasis has been targeted for elimination in India, Nepal and Bangladesh. In an elimination setting such as Bangladesh, where disease reservoirs are anthroponotic, a relatively simple test such as theLeishmaniaantigen ELISA which requires a non-invasive urine sample, may be of benefit in combination with serology for surveillance and monitoring ofLeishmaniatransmission. Development of an antigen test into a field compatible rapid diagnostic test would be of further benefit to the elimination campaign.
孟加拉国一个高度流行的村庄内脏利什曼病和无症状利什曼病感染的流行病学。
DOI: --
发表时间: 2007
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DOI: --
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期刊: Clinical Diagnostic Laboratory Immunology
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