Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.
University of Basel, Basel, Switzerland.
PLoS One. 2020 Mar 4;15(3):e0229875. doi: 10.1371/journal.pone.0229875. eCollection 2020.
In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania.
We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death.
We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31-46) and a median CD4+ cell count of 229/μl (IQR 94-421) at baseline. During the median follow-up of 1.25 years (IQR 0.46-2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2-22.6) and 5.8/1000 py (95% CI 4.0-8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14-2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15-3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08-0.27); p <0.001].
Extrapulmonary tuberculosis was a frequent manifestation in this cohort of PLHIV. The diagnosis of EPTB in the absence of histopathology and mycobacterial culture remains challenging even with availability of Xpert® MTB/RIF. Patients with EPTB had increased rates of mortality and LTFU despite early recognition of the disease after enrollment.
在撒哈拉以南非洲，艾滋病毒感染者（PLHIV）中肺外结核病（EPTB）的诊断和管理仍然是一个主要挑战。本研究旨在描述坦桑尼亚农村地区 PLHIV 中 EPTB 的流行病学特征和不良预后的危险因素。
我们纳入了 2013 年至 2017 年期间参加 Kilombero 和 Ulanga 抗逆转录病毒队列（KIULARCO）的年龄大于 18 岁的 PLHIV。我们通过前瞻性收集的临床和微生物学数据来评估结核病的诊断。我们计算了患病率和发病率，并使用 Cox 回归分析评估了 EPTB 中与随访丢失（LTFU）和死亡相结合的终点相关的危险因素。
我们纳入了 3129 名受试者（64.5%为女性），中位年龄为 38 岁（四分位距[IQR] 31-46），基线时 CD4+细胞计数中位数为 229/μl（IQR 94-421）。在中位随访 1.25 年（IQR 0.46-2.85）期间，574 名（18.4%）受试者被诊断为结核病，其中 175 名（30.5%）有肺外表现。在 483 名患有肺结核（PTB 和 EPTB）的患者中，有 178 名（36.9%）患者的 AFB 染色或 Xpert® MTB/RIF 检测到微生物证据，在 175 名患有肺外表现的患者中，有 28 名（16.0%）患者检测到微生物证据。PTB 和 EPTB 的发病率密度分别为 17.9/1000 人年（95%CI 14.2-22.6）和 5.8/1000 人年（95%CI 4.0-8.5）。1058 名（33.8%）患者出现死亡和 LTFU 的联合终点，EPTB 亚组中最常见（47.2%）。与 PTB 相比，EPTB 患者在诊断为结核病后死亡/LTFU 的复合结局发生率更高[风险比（HR）1.63，（1.14-2.31）；p=0.006]。EPTB 患者死亡/LTFU 的调整后 HR（95%CI）在年龄大于 45 岁的患者中显著增加[HR 1.95，（1.15-3.3）；p=0.013]，而 ART 使用具有保护作用[HR 0.15，（0.08-0.27）；p<0.001]。
在本队列的 PLHIV 中，肺外结核病是一种常见的表现。即使 Xpert® MTB/RIF 可用，在没有组织病理学和分枝杆菌培养的情况下，EPTB 的诊断仍然具有挑战性。尽管在入组后早期发现了疾病，但 EPTB 患者的死亡率和 LTFU 率仍较高。
