Departments of Global Health, University of Washington, Seattle, USA.
Medicine, University of Washington, Seattle, USA.
Sci Rep. 2019 Feb 25;9(1):2687. doi: 10.1038/s41598-018-37478-7.
Since rapid cryptococcal antigen lateral flow assays (CrAg LFA) may expedite treatment of HIV-associated cryptococcal infections, we sought to validate clinic-based CrAg LFA testing. Among newly-diagnosed HIV-infected adults in South Africa, a trained nurse performed clinic-based testing of urine, fingerprick capillary and venous whole blood with rapid CrAg LFA (Immy Diagnostics, Norman, USA). We performed matched laboratory-based serum cryptococcal antigen testing with an enzyme immunoassay (EIA). We assessed diagnostic accuracy using EIA as the gold-standard, and performed additional validation testing on serum and among hospitalized adults with cryptococcal meningitis. Among 5,618 participants enrolled, 1,296 were HIV-infected and screened for cryptococcal antigenemia. Overall CrAg prevalence by serum EIA was 3.6% (95% CI 2.0-6.0%) for adults with CD4 < 200 cells/mm, and 5.7% (95% CI 2.8-10.2%) for adults with CD4 < 100 cells/mm. Using expanded screening guidelines (CD4 < 200 cells/mm), CrAg LFA testing of venous whole blood, fingerprick capillary blood, and urine had diagnostic sensitivities of 46% (95% CI 19-75%), 38% (95% CI 14-68%), and 54% (95% CI 25-81%), and specificities of 97%, 97%, and 86%, respectively. When tested on serum samples, CrAg LFA had sensitivity of 93% (95% CI 66-100%) and specificity of 100% (95% CI 88-100%). All venous and fingerprick whole blood CrAg LFA tests were positive among 30 hospitalized adults with cryptococcal meningitis. Two independent readers had strong agreement for all LFA results (p < 0.0001). When performed at the point-of-care by trained nurses, CrAg LFA testing was feasible, had the highest accuracy on serum specimens, and may accelerate treatment of HIV-associated cryptococcal infections.
由于快速 cryptococcal 抗原侧向流动检测（CrAg LFA）可以加快治疗与 HIV 相关的 cryptococcal 感染，我们试图验证基于临床的 CrAg LFA 检测。在南非新诊断出的 HIV 感染成年人中，一名受过训练的护士使用快速 CrAg LFA（Immy Diagnostics，美国诺曼）对尿液、指尖毛细血管和静脉全血进行基于临床的检测。我们使用酶联免疫吸附试验（EIA）进行了匹配的基于实验室的血清 cryptococcal 抗原检测。我们使用 EIA 作为金标准评估诊断准确性，并在血清中以及 cryptococcal 脑膜炎住院成年人中进行了额外的验证测试。在纳入的 5618 名参与者中，有 1296 名 HIV 感染者接受了 cryptococcal 抗原血症筛查。使用扩展的筛查指南（CD4<200 个细胞/mm），血清 EIA 检测到的成人总体 CrAg 患病率为 3.6%（95%CI 2.0-6.0%），而 CD4<100 个细胞/mm 的成人患病率为 5.7%（95%CI 2.8-10.2%）。使用静脉全血、指尖毛细血管血和尿液进行 CrAg LFA 检测，其诊断灵敏度分别为 46%（95%CI 19-75%）、38%（95%CI 14-68%）和 54%（95%CI 25-81%），特异性分别为 97%、97%和 86%。当在血清样本上进行测试时，CrAg LFA 的灵敏度为 93%（95%CI 66-100%），特异性为 100%（95%CI 88-100%）。30 名 cryptococcal 脑膜炎住院患者的所有静脉和指尖全血 CrAg LFA 检测均为阳性。两名独立读者对所有 LFA 结果的一致性很强（p<0.0001）。当由经过培训的护士在护理点进行时，CrAg LFA 检测是可行的，在血清标本上具有最高的准确性，并可能加速治疗与 HIV 相关的 cryptococcal 感染。
