The Diagnostic Accuracy of Serologic and Molecular Methods for Detecting Visceral Leishmaniasis in HIV Infected Patients: Meta-Analysis

BackgroundHuman visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising. ObjectiveThis work is a comprehensive systematic review and meta-analysis to evaluate the accuracy of serologic and molecular tests for VL diagnosis specifically in HIV-infected patients. MethodsTwo independent reviewers searched PubMed and LILACS databases. The quality of studies was assessed by QUADAS score. Sensitivity and specificity were pooled separately and compared with overall accuracy measures: diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). ResultsThirty three studies recruiting 1,489 patients were included. The following tests were evaluated: Immunofluorescence Antibody Test (IFAT), Enzyme linked immunosorbent assay (ELISA), immunoblotting (Blot), direct agglutination test (DAT) and polimerase chain reaction (PCR) in whole blood and bone marrow. Most studies were carried out in Europe. Serological tests varied widely in performance, but with overall limited sensitivity. IFAT had poor sensitivity ranging from 11% to 82%. DOR (95% confidence interval) was higher for DAT 36.01 (9.95–130.29) and Blot 27.51 (9.27–81.66) than for IFAT 7.43 (3.08–1791) and ELISA 3.06 (0.71–13.10). PCR in whole blood had the highest DOR: 400.35 (58.47–2741.42). The accuracy of PCR based on Q-point was 0.95; 95%CI 0.92–0.97, which means good overall performance. ConclusionBased mainly on evidence gained by infection with Leishmania infantum chagasi, serological tests should not be used to rule out a diagnosis of VL among the HIV-infected, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Considering the available evidence, tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup.

背景 人类内脏利什曼病（Human visceral leishmaniasis, VL）是一种潜在致死性疾病，现已成为HIV感染者中重要的机会性感染病症。对于免疫功能低下的患者，血清学检测手段被认为并非VL诊断的精准方法，而分子检测技术则展现出尤为可观的应用前景。
目的 本研究为一项全面的系统综述与荟萃分析，旨在专门评估血清学及分子检测手段在HIV感染者VL诊断中的准确性。
方法 由两名独立研究者检索PubMed与LILACS数据库。采用QUADAS量表对纳入研究的质量进行评估。分别合并计算敏感度与特异度，并与诊断比值比（diagnostic odds ratio, DOR）、对称综合受试者工作特征曲线（symmetric summary receiver operating characteristic, sROC）等整体准确性评价指标进行对比。
结果 共纳入33项研究，累计招募1489名受试者。本研究评估的检测手段包括：免疫荧光抗体试验（Immunofluorescence Antibody Test, IFAT）、酶联免疫吸附试验（Enzyme linked immunosorbent assay, ELISA）、免疫印迹试验（immunoblotting, Blot）、直接凝集试验（direct agglutination test, DAT），以及全血与骨髓标本中的聚合酶链反应（polimerase chain reaction, PCR）。多数研究在欧洲开展。血清学检测的性能差异显著，但整体敏感度有限。IFAT的敏感度极差，介于11%至82%之间。直接凝集试验（DAT）与免疫印迹试验（Blot）的诊断比值比（95%置信区间）分别为36.01（9.95~130.29）与27.51（9.27~81.66），均高于IFAT的7.43（3.08~1791）与ELISA的3.06（0.71~13.10）。全血标本聚合酶链反应（PCR）检测的诊断比值比最高，达400.35（58.47~2741.42）。基于Q值点的PCR检测准确率为0.95，95%置信区间为0.92~0.97，整体性能优异。
结论 主要基于婴儿利什曼原虫查加斯亚种（Leishmania infantum chagasi）感染的相关研究证据，血清学检测手段不应被用于排除HIV感染者的VL诊断，但当结合临床病例定义时，即使低滴度的阳性检测结果仍具备诊断价值。综合现有证据，基于DNA检测的手段具有极高的敏感度，可为VL的诊断流程提供重要支持。