Context descriptions of included studies.

Background
The World Health Organization (WHO) recommended cryptococcal antigen (CrAg) screening for people presenting with advanced HIV disease (AHD) and for those with positive CrAg without evidence of meningitis to initiate preemptive antifungal medication. Data on the implementation of WHO recommendations regarding CrAg screening is limited. We estimated pooled prevalence of CrAg screening uptake, cryptococcal antigenemia, lumbar puncture, cryptococcal meningitis and initiation of preemptive antifungal medication from available eligible published studies conducted in Africa.
Methods
PubMed, Cochrane Library and Embase were searched for articles published between January 2011 and December 2023. CrAg uptake was defined as percentage of eligible people (CD4 ≤ 200 cells/mm3 or WHO stage III/IV) who received cryptococcal antigen testing. Stratified analysis to compare uptake and cryptococcal antigenemia between studies that involved multiple vs single sites was performed. Using random effects models, we computed the pooled estimate of CrAg screening uptake, cryptococcal antigenemia, lumbar puncture, cryptococcal meningitis, preemptive antifungals treatment and 95% confidence intervals (CIs).
Results
Ten studies with 18,820 individuals with AHD were analyzed. Overall, the pooled estimate of CrAg screening uptake was 57.1% (95% CI: 41.4–72.7). CrAg screening uptake was significantly lower among studies that involved multiple sites compared to those that involved single site, (47.3% vs 73.3%; p<0.001). Overall, the pooled prevalence of cryptococcal antigenemia was 9.6% (95% CI:6.4–12.9). Cryptococcal antigenemia was significantly lower among studies that involved multiple sites compared to those that involved single site, (9.1% vs 10.4%; p<0.001). Among those who tested positive for CrAg, 84.6% (95% CI: 54.1–99.0) received preemptive antifungal treatment, though nearly 25% did not undergo lumbar puncture, highlighting gaps in diagnostic follow-up. Six studies evaluated CrAg positive patients with lumbar puncture and the overall prevalence of lumbar puncture was 74.9% (48.0–94.8). The overall prevalence of cryptococcal meningitis was 58.1% (46.6–69.6).
Conclusions
Not screening for CrAg among people with AHD and failure to initiate antifungal medications among eligible patients with cryptococcal antigenemia presents a significant missed opportunity. Emphasis on improving CrAg screening is critical given its proven cost-effective benefits.

背景
世界卫生组织（World Health Organization, WHO）推荐对罹患晚期HIV疾病（advanced HIV disease, AHD）的患者，以及隐球菌抗原（cryptococcal antigen, CrAg）检测呈阳性但无脑膜炎证据的人群启动预防性抗真菌药物治疗。目前针对WHO隐球菌抗原筛查推荐方案的实施现状，相关研究数据较为匮乏。本研究针对非洲地区已发表的符合纳入标准的相关研究，对隐球菌抗原筛查覆盖率、隐球菌抗原血症发生率、腰椎穿刺操作率、隐球菌性脑膜炎患病率以及预防性抗真菌药物启动率进行了合并效应量估计。

方法
检索PubMed、Cochrane图书馆及Embase数据库中2011年1月至2023年12月发表的相关文献。隐球菌抗原筛查覆盖率定义为符合纳入标准（CD4细胞计数≤200个/mm³或WHO疾病分期Ⅲ/Ⅳ期）的人群中接受隐球菌抗原检测的比例。本研究开展分层分析，对比多中心研究与单中心研究之间的筛查覆盖率及隐球菌抗原血症发生率差异。采用随机效应模型，计算隐球菌抗原筛查覆盖率、隐球菌抗原血症发生率、腰椎穿刺操作率、隐球菌性脑膜炎患病率、预防性抗真菌药物治疗率及其95%置信区间（confidence intervals, CIs）的合并效应量。

结果
本研究共纳入10项符合标准的研究，涉及18820名晚期HIV疾病患者。整体而言，隐球菌抗原筛查覆盖率的合并效应量为57.1%（95%CI：41.4%~72.7%）。多中心研究的筛查覆盖率显著低于单中心研究（47.3% vs 73.3%；p<0.001）。整体隐球菌抗原血症的合并患病率为9.6%（95%CI：6.4%~12.9%），多中心研究的隐球菌抗原血症发生率显著低于单中心研究（9.1% vs 10.4%；p<0.001）。在隐球菌抗原检测阳性的患者中，84.6%（95%CI：54.1%~99.0%）接受了预防性抗真菌治疗，但近25%的患者未接受腰椎穿刺检查，凸显出诊断随访环节存在的缺口。另有6项研究对隐球菌抗原阳性患者开展了腰椎穿刺检查，整体腰椎穿刺操作率为74.9%（95%CI：48.0%~94.8%）。隐球菌性脑膜炎的整体患病率为58.1%（95%CI：46.6%~69.6%）。

结论
对晚期HIV疾病患者未开展隐球菌抗原筛查，以及对隐球菌抗原血症阳性的符合指征患者未启动抗真菌药物治疗，均属于重大的医疗错失机遇。鉴于隐球菌抗原筛查已被证实具有成本效益优势，强化该筛查工作的推广至关重要。