巴西对艾滋病患者进行隐球菌抗原血症筛查、抢先治疗和随访的前瞻性队列研究。
Prospective cohort of AIDS patients screened for cryptococcal antigenaemia, pre-emptively treated and followed in Brazil.
机构信息
Institute of Tropical Pathology and Public Health of Federal University of Goiás-Goiânia, Goiás, Brazil.
Infectious Disease Unit, Clinical Hospital of Federal University of Goiás-Goiânia, Goiás, Brazil.
出版信息
PLoS One. 2019 Jul 25;14(7):e0219928. doi: 10.1371/journal.pone.0219928. eCollection 2019.
BACKGROUND
Cryptococcal meningitis has a high morbidity and mortality among AIDS population. Cryptococcal antigen (CrAg) detection is considered an independent predictor for meningitis and death. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts <100-200 cells/μl. Its implementation is still limited in low-middle-income countries. We aimed to estimate the prevalence and predictors of CrAg positivity in PLHAs. We also evaluated outcomes among those who were CrAg-positive.
METHODS
Prospective cohort conducted at an infectious diseases hospital, in Brazil. Adults with CD4 <200 cells/μl, without previous cryptococcal disease and regardless of symptoms, were enrolled from 2015 to 2018. CrAg tests were performed by LFA. Lumbar puncture was done in CrAg+ individuals and pre-emptive therapy was offered for those without meningitis.
RESULTS
Of 214 individuals recruited, 88% were antiretroviral experienced, of which only 11.6% with viral suppression. Overall, CrAg prevalence was 7.9% (95% CI, 4.7-12.4). In CD4 ≤100 cells/μl group it was 7.5% (95% CI, 4.1-12.6) and 9.1% (95% CI, 3.4-19.0) in the group with CD4 101 to 199 cells/μl (p = 0.17). Prevalence in asymptomatic subjects was 5.3% (95% CI, 1.4-13.1). One among 17 CrAg+ participants had documented meningoencephalitis and no subclinical meningitis was detected. Adherence to pre-emptive treatment was 68.7% (11/16). There were no statistically significant differences in sociodemographic, clinical or laboratory characteristics to predict CrAg positivity. No case of cryptococcal disease was diagnosed among CrAg + subjects, followed by a median of 12 months.
CONCLUSIONS
CrAg screening for severely immunosuppressed PLHAs in Brazil yielded a prevalence of 7.9%. No difference was found in the prevalence of CrAg stratified by CD4 values (CD4 <100 versus CD4 101-199 cells/μl). No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4 <200 cells/μl in similar settings.
背景
隐球菌性脑膜炎在艾滋病患者中发病率和死亡率较高。隐球菌抗原（CrAg）检测被认为是脑膜炎和死亡的独立预测因素。自 2011 年以来，世界卫生组织建议对 CD4 计数<100-200 个/μl 的艾滋病毒/艾滋病患者（PLHAs）进行 CrAg 筛查。但其在中低收入国家的实施仍然有限。我们旨在评估 PLHAs 中 CrAg 阳性的患病率和预测因素。我们还评估了 CrAg 阳性患者的结局。
方法
在巴西的一家传染病医院进行前瞻性队列研究。纳入 2015 年至 2018 年期间 CD4<200 个/μl、无隐球菌病史且无任何症状的成年人。通过 LFA 进行 CrAg 检测。CrAg+个体进行腰椎穿刺，并对无脑膜炎者进行预防性治疗。
结果
在 214 名入组患者中，88%为抗逆转录病毒经验丰富者，其中仅 11.6%的患者病毒得到抑制。总体而言，CrAg 阳性率为 7.9%（95%CI，4.7-12.4）。在 CD4≤100 个/μl 组中为 7.5%（95%CI，4.1-12.6），在 CD4 为 101-199 个/μl 组中为 9.1%（95%CI，3.4-19.0）（p=0.17）。无症状患者的患病率为 5.3%（95%CI，1.4-13.1）。17 名 CrAg+参与者中有 1 名患有确诊的脑膜脑炎，未发现亚临床脑膜炎。预防性治疗的依从率为 68.7%（11/16）。CrAg 阳性的预测因素在社会人口统计学、临床或实验室特征方面无统计学差异。CrAg+患者中未诊断出隐球菌病，中位随访时间为 12 个月。
结论
在巴西对严重免疫抑制的 PLHAs 进行 CrAg 筛查，其阳性率为 7.9%。按 CD4 值分层（CD4<100 与 CD4 为 101-199 个/μl），CrAg 阳性率无差异。无临床或实验室因素可预测 CrAg 阳性，这支持在类似情况下对 CD4<200 个/μl 的 PLHAs 实施普遍的 CrAg 筛查的必要性。
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