Blood cryptococcal antigen (CrAg) titers >160 are associated with concurrent subclinical cryptococcal meningitis (CM). When lumbar puncture (LP) is not immediately available in a CrAg screening program, semi-quantitative CrAg assays may provide risk stratification for CM. Two semi-quantitative assays (SQ [Immuno-Mycologics, Norman, OK, USA] and CryptoPS [Biosynex, Strasbourg, France]) were evaluated against a qualitative lateral flow assay (LFA) using 194 plasma samples from a cohort of HIV-seropositive individuals with CD4 counts <100 cells/μl. We compared SQ and CryptoPS results to titers for LFA-positive samples. Among patients with LP, we examined the association between semi-quantitative CrAg results and CM. We used a Cox proportional hazards model to determine the association between SQ score and mortality. Of 194 participants, 60 (31%) had positive LFA results, of whom 41 (68%) had a titer of ≤160 and 19 (32%) a titer >160. Fifty individuals with antigenemia had an LP; a clinically useful SQ score that identified all ten cases of subclinical CM was ≥3 (100% sensitivity, 55% specificity). Patients with an SQ score of 3 or 4 also had a 2.2-fold increased adjusted hazards of 6-month mortality (95% CI: 0.79–6.34; p = 0.13) versus those with score of <3. Nine of ten patients with subclinical CM had a strong-positive CryptoPS result versus 10/40 without subclinical CM (p < 0.001). Semi-quantitative assays offered a sensitive though not specific means of gauging the risk of concurrent CM in this patient population. Lay summary We evaluated two single-step laboratory tests that can quantify the amount of cryptococcal antigen in plasma of patients with advanced HIV disease and could thus gauge the risk of concurrent cryptococcal meningitis and subsequent mortality. These tests are not a substitute for a lumbar puncture.

中文翻译：

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半定量隐球菌抗原导致血浆与亚临床隐球菌脑膜炎和晚期 HIV 患者死亡率的关联

血隐球菌抗原(CrAg)滴度＞160与并发的亚临床隐球菌脑膜炎(CM)有关。当腰椎穿刺 (LP) 不能立即用于 CrAg 筛查计划时，半定量 CrAg 检测可能会为 CM 提供风险分层。使用来自 HIV 血清反应阳性队列的 194 个血浆样本，针对定性侧向流动分析 (LFA) 评估了两种半定量分析（SQ [Immuno-Mycologics, Norman, OK, USA] 和 CryptoPS [Biosynex, Strasbourg, Fr​​ance]） CD4 计数＜100 个细胞/μl 的个体。我们将 SQ 和 CryptoPS 结果与 LFA 阳性样本的滴度进行了比较。在 LP 患者中，我们检查了半定量 CrAg 结果与 CM 之间的关联。我们使用 Cox 比例风险模型来确定 SQ 评分与死亡率之间的关联。在 194 名参与者中，60 人 (31%) 的 LFA 结果阳性，其中 41 人 (68%) 的滴度≤160，19 人 (32%) 的滴度 > 160。50 名抗原血症患者有 LP；确定所有 10 例亚临床 CM 的临床有用 SQ 评分≥3（100% 敏感性，55% 特异性）。SQ 评分为 3 或 4 的患者与评分＜3 的患者相比，6 个月死亡率的调整后风险也增加了 2.2 倍（95% CI：0.79-6.34；p = 0.13）。10 名患有亚临床 CM 的患者中有 9 人具有强阳性 CryptoPS 结果，而没有亚临床 CM 的患者为 10/40（p < 0.001）。半定量分析提供了一种敏感但非特异性的方法来衡量该患者群体中并发 CM 的风险。总结 我们评估了两项单步实验室测试，这些测试可以量化晚期 HIV 疾病患者血浆中隐球菌抗原的数量，从而可以衡量并发隐球菌性脑膜炎和随后死亡的风险。这些测试不能替代腰椎穿刺。