Chronic Diseases Clinic of Ifakara, Ifakara Health Institute, Ifakara, Tanzania.
Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences (MUHAS), Dar-es-Salaam, Tanzania.
J Acquir Immune Defic Syndr. 2019 Feb 1;80(2):205-213. doi: 10.1097/QAI.0000000000001899.
Cryptococcal antigen (CrAg) screening in persons with advanced HIV/AIDS is recommended to prevent death. Implementing CrAg screening only in outpatients may underestimate the true CrAg prevalence and decrease its potential impact. Our previous 12-month survival/retention in CrAg-positive persons not treated with fluconazole was 0%.
HIV testing was offered to all antiretroviral therapy-naive outpatients and hospitalized patients in Ifakara, Tanzania, followed by laboratory-reflex CrAg screening for CD4 <150 cells/μL. CrAg-positive individuals were offered lumbar punctures, and antifungals were tailored to the presence/absence of meningitis. We assessed the impact on survival and retention-in-care using multivariate Cox-regression models.
We screened 560 individuals for CrAg. The median CD4 count was 61 cells/μL (interquartile range 26-103). CrAg prevalence was 6.1% (34/560) among individuals with CD4 ≤150 and 7.5% among ≤100 cells/μL. CrAg prevalence was 2.3-fold higher among hospitalized participants than in outpatients (12% vs 5.3%, P = 0.02). We performed lumbar punctures in 94% (32/34), and 31% (10/34) had cryptococcal meningitis. Mortality did not differ significantly between treated CrAg-positive without meningitis and CrAg-negative individuals (7.3 vs 5.4 deaths per 100 person-years, respectively, P = 0.25). Independent predictors of 6-month death/lost to follow-up were low CD4, cryptococcal meningitis (adjusted hazard ratio 2.76, 95% confidence interval: 1.31 to 5.82), and no antiretroviral therapy initiation (adjusted hazard ratio 3.12, 95% confidence interval: 2.16 to 4.50).
Implementing laboratory-reflex CrAg screening among outpatients and hospitalized individuals resulted in a rapid detection of cryptococcosis and a survival benefit. These results provide a model of a feasible, effective, and scalable CrAg screening and treatment strategy integrated into routine care in sub-Saharan Africa.
在晚期 HIV/AIDS 患者中进行隐球菌抗原 (CrAg) 筛查，以预防死亡。仅在门诊患者中实施 CrAg 筛查可能会低估真正的 CrAg 患病率，并降低其潜在影响。我们之前对未经氟康唑治疗的 CrAg 阳性患者的 12 个月生存/保留率为 0%。
在坦桑尼亚伊法卡拉，为所有接受抗逆转录病毒治疗的门诊和住院患者提供 HIV 检测，随后对 CD4<150 个细胞/μL 的患者进行实验室反射性 CrAg 筛查。CrAg 阳性者接受腰椎穿刺，根据是否存在脑膜炎来调整抗真菌药物。我们使用多变量 Cox 回归模型评估对生存和保留在护理中的影响。
我们对 560 人进行了 CrAg 筛查。中位 CD4 计数为 61 个细胞/μL（四分位距 26-103）。CD4≤150 个细胞/μL 的人群中 CrAg 患病率为 6.1%（34/560），而 CD4≤100 个细胞/μL 的人群中 CrAg 患病率为 7.5%。住院患者的 CrAg 患病率是门诊患者的 2.3 倍（12%比 5.3%，P=0.02）。我们对 94%（32/34）的患者进行了腰椎穿刺，其中 31%（10/34）患有隐球菌性脑膜炎。治疗后的 CrAg 阳性无脑膜炎患者和 CrAg 阴性患者的死亡率无显著差异（分别为每 100 人年死亡/失访 7.3 例和 5.4 例，P=0.25）。6 个月死亡/失访的独立预测因素是低 CD4、隐球菌性脑膜炎（校正后的危险比 2.76，95%置信区间：1.31 至 5.82）和未开始抗逆转录病毒治疗（校正后的危险比 3.12，95%置信区间：2.16 至 4.50）。
在门诊和住院患者中实施实验室反射性 CrAg 筛查可快速检测隐球菌病并带来生存获益。这些结果为在撒哈拉以南非洲将 CrAg 筛查和治疗策略纳入常规护理提供了一种可行、有效且可扩展的模式。
