Epicentre, Paris, France.
Médecins Sans Frontières, Lilongwe, Malawi.
PLoS Med. 2019 Apr 30;16(4):e1002792. doi: 10.1371/journal.pmed.1002792. eCollection 2019 Apr.
Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB.
We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results.
LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.
目前的指南建议在出现结核病（TB）症状和体征的 HIV 阳性、门诊患者中，仅在病情严重或 CD4 计数≤100 个/μl 时使用侧向流动尿液脂阿拉伯甘露聚糖检测（LAM）。我们评估了在 CD4<200 个/μl 的 HIV 阳性、门诊患者中纳入 LAM 对 TB 诊断算法的诊断效果，以及在未使用其他诊断工具诊断且未接受 TB 治疗的 LAM 阳性患者中的死亡率风险。
我们进行了一项前瞻性观察性研究，包括在马拉维和莫桑比克的 6 个卫生机构就诊的出现结核病症状和体征且 CD4<200 个/μl 的 HIV 阳性成年患者。2015 年 9 月 18 日至 2016 年 10 月 27 日在马拉维，2014 年 12 月 3 日至 2016 年 8 月 22 日在莫桑比克连续纳入患者。所有患者均进行了临床检查和 LAM、胸部 X 线、痰显微镜检查和 Xpert MTB/RIF 检测（Xpert）。对部分患者进行了痰培养。诊断效果定义为实验室确诊结核病患者中检测结果阳性的比例。在纳入的 456 例患者中，中位年龄为 36 岁（IQR 31-43），中位 CD4 计数为 50 个/μl（IQR 21-108）。45%（205/456）的患者经实验室确诊为结核病。LAM、显微镜检查和 Xpert 的诊断效果分别为 82.4%（169/205）、33.7%（69/205）和 40.0%（84/205）。总的来说，50.2%（103/205）的实验室确诊结核病患者仅通过 LAM 进行诊断。总体而言，在包含显微镜检查和 Xpert 的诊断算法中，使用 LAM 分别将算法的检测效果提高了 38.0%（78/205）和 34.6%（71/205），特别是在 CD4 为 100-199 个/μl 的患者中，分别提高了 27.5%（14/51）和 29.4%（15/51）。未通过其他工具诊断且未接受 TB 治疗的 LAM 阳性患者的死亡率风险显著高于接受治疗的 LAM 阳性患者（调整后的风险比 2.57，95%CI 1.27-5.19，p=0.009）。尽管研究地点的结核病诊断条件与其他资源有限的地区相似，但 LAM 的附加值可能取决于显微镜检查或 Xpert 结果的可用性。
LAM 对识别出现结核病症状和体征且免疫功能严重受损（包括 CD4 计数为 100-199 个/μl）的 HIV 阳性患者中的结核病具有诊断价值。在这项研究中，LAM 使一半的确诊结核病患者得到诊断；如果没有 LAM，这些患者可能会被漏诊。LAM 能够快速识别和治疗结核病，从而可能降低这些患者的总体死亡率风险。
