Abstract
Cryptococcosis is one of the most common opportunistic infections in both immunocompetent and immunocompromised hosts. Although the cryptococcal antigen (CrAg) lateral flow assay (LFA) has been widely used in clinical settings due to its high sensitivity and specificity, the diagnostic value of a low CrAg LFA titers remains unclear. In this study, we performed a retrospective analysis of 149 HIV-negative patients with low CrAg LFA titers (≤1:10) in a Chinese tertiary hospital from January 2013 to December 2017, to evaluate the diagnostic value of low CrAg LFA titers in serum and cerebrospinal fluid (CSF) at different thresholds. Sensitivity and specificity of low CrAg LFA titers in patients with definitive diagnoses of cryptococcosis were 39.6% (95% CI, 29.7–50.1%) and 100% (95% CI, 69.2–100%), respectively, at a threshold of 1:10 in serum. A sensitivity of 72.9% (95% CI, 62.9–81.5%) and a decreased specificity of 70.0% (95% CI, 34.8–93.3%) were observed at a threshold of 1:5 in serum. No false-positive cases were identified in patients with low CrAg titers in CSF and all positive predictive values (PPVs) were 100%. Among the cases with low serum CrAg titers, lumbar puncture was performed in 97 patients and positive CSF CrAg titers were reported in 6 patients. In conclusion, the results of this study imply that low CrAg LFA titer, either in serum or CSF, is crucial for early diagnosis of cryptococcosis in HIV-negative patients, and lumbar puncture is recommended to be performed routinely for CSF testing when a positive low serum titer is reported. Cryptococcal meningitis should be considered seriously when the CSF CrAg titer is positive.
Highlights
Cryptococcosis is a life-threatening mycosis that primarily occurs in individuals with significant immunologic impairment, including those who have HIV infection, solid organ transplantation, hematological malignancy, and other diseases that affect cellular immunity (Pappas2013, La Hoz & Pappas 2013)
Study design and population This was a retrospective study conducted using patient samples from January 2013 to December 2017 obtained in the Huashan Hospital, a tertiary hospital in Shanghai, to evaluate the diagnostic value of low cryptococcal antigen (CrAg) lateral flow assay (LFA) titers (≤ 1:10)
Patient characteristics A total of 840 unique patients with 4496 positive specimens were screened, and 149 patients that had low CrAg titers (≤ 1:10) in serum and/or cerebrospinal fluid (CSF) were included in this study (Fig. 1)
Summary
Cryptococcosis is a life-threatening mycosis that primarily occurs in individuals with significant immunologic impairment, including those who have HIV infection, solid organ transplantation, hematological malignancy, and other diseases that affect cellular immunity (Pappas2013, La Hoz & Pappas 2013). Cryptococcosis is a life-threatening mycosis that primarily occurs in individuals with significant immunologic impairment, including those who have HIV infection, solid organ transplantation, hematological malignancy, and other diseases that affect cellular immunity Due to the use of mAbs, CrAg LFA is highly sensitive and specific for the detection of cryptococcosis in HIV-positive patients. In a large validation study in Africa, the CrAg LFA was performed in 832 HIV-positive patients, and the assay sensitivity of 99.3% and specificity of 99.1% were reported using cerebrospinal fluid (CSF) (Boulware et al 2014). A satisfactory median sensitivity and specificity of 100% (95% CI, 95.6–100%) and 99.5% (95% CI, 95.7–100%), respectively, were reported for serum specimens from HIV-infected individuals in a review including seven abstracts and two full-length articles (Vijayan et al 2013). As most comparative investigations have been conducted primarily using samples from HIV-positive patients, little is known about the relative diagnostic accuracy in HIV-negative individuals
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