Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
J Clin Microbiol. 2021 Jul 19;59(8):e0086021. doi: 10.1128/JCM.00860-21.
A newly developed cryptococcal antigen (CrAg) semiquantitative (SQ) lateral flow assay (LFA) provides a semiquantitative result in a rapid one-step test instead of performing serial dilutions to determine CrAg titer. We prospectively compared the diagnostic performance of the CrAgSQ assay (IMMY) with the CrAg LFA (IMMY) on cerebrospinal fluid (CSF) samples collected from persons with HIV-associated meningitis. The CrAgSQ grades (1+ to 5+) were compared with CrAg LFA titers and quantitative CSF fungal cultures. Among 87 participants screened for HIV-associated meningitis, 60 had cryptococcal meningitis (59 CrAg positive [CrAg] by LFA and 1 false negative due to prozone with CrAg LFA titer of 1:1,310,000 and culture positivity), and 27 had no cryptococcal meningitis by CrAg LFA or culture. The CrAgSQ on CSF had 100% (60/60) sensitivity and 100% specificity (27/27). CSF CrAg titers ranged from 1:5 to 1:42 million. CrAgSQ grades of 1+, 2+, 3+, 4+, and 5+ corresponded to median CrAg LFA titers of 1:<10, 1:60, 1:7,680, 1:81,920, and 1:1,474,000, respectively. CSF CrAgSQ grades 3+ or higher were always CSF culture positive. Mortality at 14 days for those with low CrAgSQ grade (1+ to 3+) was 5% (1/22) versus 21% (8/38) with high CrAgSQ grades (4+ to 5+) ( = 0.084). The CrAgSQ demonstrates excellent diagnostic performance, maintaining both the sensitivity and specificity of the CrAg LFA, and counters false-negative prozone effects. The CrAgSQ assay reading is more complex but does provide useful clinical information about disease burden and probability of culture positivity in a single rapid diagnostic test.
一种新开发的隐球菌抗原（CrAg）半定量（SQ）侧向流动检测（LFA）在一步快速检测中提供半定量结果，而不是进行连续稀释以确定 CrAg 滴度。我们前瞻性地比较了 CrAgSQ 检测（IMMY）与 CrAg LFA（IMMY）在 HIV 相关脑膜炎患者脑脊液（CSF）样本中的诊断性能。CrAgSQ 级（1+到 5+）与 CrAg LFA 滴度和定量 CSF 真菌培养进行比较。在筛查 HIV 相关脑膜炎的 87 名参与者中，60 名患有隐球菌性脑膜炎（59 名 LFA 阳性[CrAg]，1 名因 CrAg LFA 滴度为 1:1,310,000 且培养阳性而出现前区带效应的假阴性），27 名 CrAg LFA 或培养均未患有隐球菌性脑膜炎。CSF 中的 CrAgSQ 具有 100%（60/60）的敏感性和 100%（27/27）的特异性。CSF CrAg 滴度范围为 1:5 至 1:420 万。CrAgSQ 级 1+、2+、3+、4+和 5+分别对应于中位数 CrAg LFA 滴度 1:<10、1:60、1:7,680、1:81,920 和 1:1,474,000。CSF CrAgSQ 级 3+或更高者的 CSF 培养总是阳性。CrAgSQ 低级别（1+至 3+）患者的 14 天死亡率为 5%（1/22），而 CrAgSQ 高级别（4+至 5+）患者的死亡率为 21%（8/38）（=0.084）。CrAgSQ 表现出出色的诊断性能，保持了 CrAg LFA 的敏感性和特异性，并对抗假阴性前区带效应。CrAgSQ 检测的读数更为复杂，但在单次快速诊断检测中提供了有关疾病负担和培养阳性概率的有用临床信息。
