Charles River Medical Group, Harare, Zimbabwe.
Unit of Internal Medicine, Department of Primary Health Care Sciences, University of Zimbabwegrid.13001.33, Harare, Zimbabwe.
Microbiol Spectr. 2022 Aug 31;10(4):e0107522. doi: 10.1128/spectrum.01075-22. Epub 2022 Aug 4.
Cryptococcal disease (CD) is a leading cause of mortality among individuals with advanced HIV disease (AHD). Screening with serum cryptococcal antigen (sCrAg) lateral flow assay (LFA) enables early detection of subclinical disease but requires venipuncture and laboratory processing. Clinic-based point of care (POC) CrAg screening tests using urine or fingerprick whole blood could facilitate early diagnosis of CD. We evaluated the diagnostic performance of POC clinic-based fingerprick whole blood and urine CrAg compared to the gold standard laboratory sCrAg LFA in screening for CD among asymptomatic individuals with CD4 counts of <200 cells/μL in Harare, Zimbabwe. sCrAg positive participants who consented to a lumbar puncture also had cerebrospinal fluid (CSF) CrAg testing and titers for CSF-positive specimens. A total of 1,333 individuals were screened, and over half (56.6%) were males. The median (interquartile range) CD4 count was 27.5 (11-46) cells/μL. We found a sensitivity of 63.8% (95% CI: 54.8-72.1) and specificity of 84.0% (95% CI: 81.7-86.0) for urine CrAg, and a sensitivity of 48.0% (95% CI: 39.1-57.1) and specificity of 99.5% (95% CI: 98.9-99.8) was found for fingerprick whole blood. The sensitivity of both POC CrAg tests increased in individuals with sCrAg titers of ≥1:160, CD4 count of <50 cells/μL and disseminated central nervous system (CNS) disease. Clinic-based POC urine and fingerprick whole blood CrAg testing performed better in screening for CD among AHD patients with CNS disease. More sensitive assays to identify AHD patients with asymptomatic CD are needed. Cryptococcal disease (CD) remains a leading cause of morbidity and mortality among individuals with advanced HIV disease (AHD). Identifying point of care (POC) approaches to screening for CD in asymptomatic individuals is important to guide therapeutic management. We evaluated the use of POC fingerprick whole blood and urine testing for cryptococcal disease in patients with AHD as compared with laboratory-based serum antigen testing. POC fingerprick whole blood and urine testing had low sensitivity and specificity in asymptomatic individuals with AHD. Most analysis has focused on evaluating test performance in symptomatic individuals. Here we show that POC testing with whole blood and urine samples should not be used to screen for asymptomatic CD in AHD.
隐球菌病（CD）是晚期 HIV 疾病（AHD）患者死亡的主要原因。血清隐球菌抗原（sCrAg）侧向流动检测（LFA）筛查可早期发现亚临床疾病，但需要静脉穿刺和实验室处理。基于诊所的即时护理（POC）CrAg 筛查试验使用尿液或指尖全血，可以促进 CD 的早期诊断。我们评估了 POC 基于诊所的指尖全血和尿液 CrAg 与实验室 sCrAg LFA 相比，在筛查津巴布韦哈拉雷 CD4 计数<200 个/μL 的无症状个体中 CD 的诊断性能。同意腰椎穿刺的 sCrAg 阳性参与者也进行了脑脊液（CSF）CrAg 检测和 CSF 阳性标本的滴度检测。共有 1333 人接受了筛查，其中一半以上（56.6%）为男性。中位（四分位距）CD4 计数为 27.5（11-46）个/μL。我们发现尿液 CrAg 的敏感性为 63.8%（95%CI：54.8-72.1），特异性为 84.0%（95%CI：81.7-86.0），指尖全血的敏感性为 48.0%（95%CI：39.1-57.1），特异性为 99.5%（95%CI：98.9-99.8）。在 sCrAg 滴度≥1:160、CD4 计数<50 个/μL 和播散性中枢神经系统（CNS）疾病的个体中，两种 POC CrAg 检测的敏感性均增加。基于诊所的 POC 尿液和指尖全血 CrAg 检测在筛查 AHD 伴 CNS 疾病患者的 CD 方面表现更好。需要更敏感的检测方法来识别无症状 CD 的 AHD 患者。隐球菌病（CD）仍然是晚期 HIV 疾病（AHD）患者发病率和死亡率的主要原因。确定用于无症状个体的 CD 筛查的即时护理（POC）方法对于指导治疗管理非常重要。我们评估了在 AHD 患者中，与基于实验室的血清抗原检测相比，使用 POC 指尖全血和尿液检测对 CD 的诊断效果。在无症状的 AHD 患者中，POC 指尖全血和尿液检测的敏感性和特异性均较低。大多数分析都集中在评估有症状个体的检测性能上。在这里，我们表明 POC 检测不应用于筛查 AHD 中的无症状 CD。
