Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negative tuberculosis in HIV-infected patients.

Bronchoalveolar lavage enzyme-linked immunospot for diagnosis of smear-negative tuberculosis in HIV-infected patients.
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DOI:
10.1371/journal.pone.0039838
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Huang L
Huang L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cattamanchi A;Ssewenyana I;Nabatanzi R;Miller CR;Den Boon S;Davis JL;Andama A;Worodria W;Yoo SD;Cao H;Huang L

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外周血干扰素-γ释放试验(IGRAs)诊断活动性肺结核(TB)的灵敏度和特异性欠佳。然而,据报道,局部免疫反应的评估可以提高结核病诊断的准确性。我们招募了在乌干达坎帕拉Mulago医院住院的咳嗽持续时间≥2周的HIV感染成人,并在两次痰抗酸杆菌涂片阴性后转诊进行支气管镜检查。我们使用外周血和支气管肺泡灌洗(BAL)液单核细胞进行了基于ELISPOT的IGRA(T-SPOT.TB®,Oxford Immunotec,Oxford,UK),并使用分枝杆菌培养结果作为参考标准确定了IGRA的准确性。纳入了94例具有配对外周血和BAL IGRA结果的HIV感染患者。研究人群年轻(中位年龄34岁[IQR 28-40岁]),患有晚期HIV/AIDS(中位CD 4 + T淋巴细胞计数60个细胞/μl [IQR 22-200个细胞/μl])。BAL液中不确定IGRA结果的比例高于外周血标本(34% vs. 14%,差异20%,95% CI 7- 33%,p = 0.002)。  BAL IGRA对TB诊断的敏感性中等(73%,95% CI 50-89%),但特异性较差(48%,95% CI 32-64%)。当对外周血进行IGRA时,敏感性相似(75%,95% CI 57-89%),特异性较高(78%,95% CI 63-88%)。BAL IGRA在高HIV/TB负担环境中对涂片阴性TB的诊断表现不佳。需要进一步研究以检查在高HIV/TB负担环境中BAL IGRA对活动性TB的不确定结果的大部分和低特异性的原因。
Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis. We enrolled HIV-infected adults with cough ≥2 weeks’ duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard. 94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28–40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22–200 cells/µl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7–33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50–89%) but poor specificity (48%, 95% CI 32–64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57–89%) and specificity was higher (78%, 95% CI 63–88%) when IGRA was performed on peripheral blood. BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.
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