Polymerase chain reaction negative cryptococcal meningitis.

A 61-year-old male with subacute headache was found to have cryptococcal meningitis despite a negative BioFire FilmArray meningitis/encephalitis panel. This case underscores the importance of liberal cryptococcal antigen testing, and that a negative FilmArray panel is inadequate in excluding cryptococcal meningitis, particularly in a HIV-negative host.

HIV-associated disseminated cryptococcosis-An unusual clinical and diagnostic picture with successful cure by single dose liposomal amphotericin B treatment.

BACKGROUND: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection. METHODS AND RESULTS: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine. CONCLUSION: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals.

Isolated cryptococcal pleural effusion in a heart transplant recipient: A case report and literature review of pleural fluid adenosine deaminase levels.

Isolated cryptococcal pleural effusion is rare as the initial clinical presentation in opportunistic cryptococcal infection. We describe a 59-year-old male heart transplantation recipient who presented with a mononuclear-leukocyte-predominant exudative pleural effusion, with adenosine deaminase levels (ADA) of 37 IU/L and focal pleural nodularity on computed tomography. A thorough evaluation, including pleural fluid culture, cryptococcal antigen, and histological examination, led to the diagnosis of cryptococcal pleural effusion. Antifungal therapy with fluconazole of 400 mg/day showed clinical and radiological improvement. A literature review identified six cases of cryptococcal pleural effusion that reported pleural fluid ADA levels. All cases, including the present one, involved immunocompromised hosts and exhibited a mononuclear-leukocyte-predominant exudate. High pleural fluid ADA levels were observed in approximately half of these cases. The pleural fluid cryptococcal antigen test was an important diagnostic tool for early diagnosis. In an era where immunocompromised hosts are increasing, cryptococcal infection should be considered as a potential aetiology in immunosuppressed patients with an exudative pleural effusion of unknown cause, even if ADA levels are elevated.

Performance of Cryptococcal Antigen Lateral Flow Assay in Bronchoalveolar Lavage Fluid in HIV-Negative Patients.

OBJECTIVE: We presented the performance of cryptococcal antigen lateral flow assay test using bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population. METHODS: From January 2019 to June 2022, cryptococcal antigen was detected in both serum and BALF samples from 113 patients with suspected pulmonary cryptococcosis. RESULTS: 49 patients were finally diagnosed with pulmonary cryptococcosis. The sensitivity of cryptococcal antigen lateral flow assay test in serum and BALF specimens from confirmed cases was 90.0% and 96.0%, respectively, and the specificity was 87.3% and 95.5%, respectively. When the diameter of the lung lesion was less than 15 mm, the antigen positivity rate of BALF was higher than that of serum. Moreover, the result of the cryptococcal antigen test was associated with the lymphocytes count of BALF. CONCLUSION: Our data demonstrate that cryptococcal antigen Lateral Flow Assay for BALF specimens might contribute to the early diagnosis of pulmonary cryptococcosis.

Diagnosis and management of cryptococcal meningitis in HIV-infected adults.

SUMMARYCryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity. These tests have led to improved diagnostic accuracy and are essential for screening campaigns to reduce the burden of cryptococcosis. In the last 5 years, several high-quality, multisite clinical trials have led to innovations in therapeutics that have allowed for simplified regimens, which are better tolerated and result in less intensive monitoring and management of medication adverse effects. One trial found that a shorter, 7-day course of deoxycholate amphotericin B is as effective as the longer 14-day course and that flucytosine is an essential partner drug for reducing mortality in the acute phase of disease. Single-dose liposomal amphotericin B has also been found to be as effective as a 7-day course of deoxycholate amphotericin B. These findings have allowed for simpler and safer treatment regimens that also reduce the burden on the healthcare system. This review provides a detailed discussion of the latest evidence guiding the clinical management and special circumstances that make cryptococcal meningitis uniquely difficult to treat.

Cryptococcal pneumonia and meningitis in a renal transplant recipient with a false negative serum cryptococcal antigen due to postzone phenomenon.

Cryptococcal infection can cause significant morbidity and mortality in immunocompromised patients. We present a patient who was diagnosed with cryptococcal meningitis and pulmonary disease in the setting of a history of renal transplantation. The diagnosis was made based on growth of Cryptococcus neoformans in blood cultures and identification of cryptococcal antigen (CrAg) in cerebral spinal fluid (CSF) using a lateral flow assay (LFA). Our case is unique since the initial serum CrAg was falsely negative due to excess cryptococcal antigen preventing the formation of antigen-antibody complexes, referred to as the postzone phenomenon. This phenomenon has been reported on CSF samples but rarely reported on serum samples in patients without an HIV diagnosis.

Retrospective analysis of pulmonary cryptococcosis and extrapulmonary cryptococcosis in a chinese tertiary hospital.

Cryptococcosis is an invasive fungal disease with increased morbidity in China over the past two decades. Cryptococci can infect immunocompromised hosts as well as immunocompetent ones. In this study, we reviewed data of 71 inpatients with cryptococcosis at Ningbo First Hospital from May 2010 to May 2020 and compared the clinical profiles of pulmonary cryptococcosis (PC) and extrapulmonary cryptococcosis (EPC). Of 71 patients (38 males, 33 females), 70 were non-HIV. The annual inpatient population increased dramatically, especially in the PC group. PC was confirmed in 77.46% (55/71) of cases by pathology. The rest were EPC including intracranial infection (15.49%, 11/71) and cryptococcemia (7.04%, 5/71). Compared with PC, a larger proportion of EPC patients were found to have immunocompromised conditions judged by predisposing factors (p < 0.01), or detectable humoral or cellular immunodeficiency. Fever and headache were more common in EPC patients (p < 0.001). Patients with EPC had lower serum sodium level (p = 0.041), lower monocyte counts (p = 0.025) and higher C-reactive protein (p = 0.012). In our study, the sensitivity of cryptococcus antigen detection for EPC was 100% regardless of sample type, while serum lateral flow assay (LFA) tested negative in 25% (5/20) of PC. Immunocompromised hosts are more likely to suffer from EPC than PC.

The incidence of histoplasmosis and cryptococcal antigenemia among patients attending a large HIV clinic in Trinidad.

Our aim was to determine the incidence disseminated histoplasmosis and cryptococcal antigenemia among 280 patients with a CD4<350 cells/mm3 attending a large HIV clinic in Trinidad over the period November 2021-June 2022. Sera were screened for cryptococcal antigen (CrAg) using the Immy CrAg Immunoassay (EIA) and the Immy CrAg lateral flow assay (LFA). Urine was screened for Histoplasma antigen using the Immy EIA and the Optimum Imaging Diagnostics (OIDx) LFA. For the purposes of analysis, it was assumed, that all patients with positive urine Histoplasma antigen tests by both EIA and LFA and those with a single positive urine Histoplasma antigen test and clinical features of disseminated histoplasmosis were true positives. The incidence of probable disseminated histoplasmosis and cryptococcal antigenemia were 6.4% (18/280) and 2.5% (7/280) respectively. The sensitivity and specificity of the Immy Histoplasma EIA were 100% (95% CI, 81.5%-100%) and 98.5% (95% CI, 96.1% - 99.6%) respectively as compared to the OIDx Histoplasma LFA of 88.9% (95% CI, 65.3% - 98.6%) and 93.9% (95% CI, 90.3% - 96.5%) respectively, with substantial agreement between the 2 test kits (Kappa value = 0.763; 95% CI 0.685, 0.841). Testing for disseminated histoplasmosis in HIV patients is important in endemic areas.

Preemptive Therapy in Cryptococcosis Adjusted for Outcomes.

Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, early diagnosis and appropriate treatment are important. OBJECTIVES: The aim of the study was to understand the development of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow assay (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. MATERIALS AND METHODS: A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material, and pulmonary tomography imaging. RESULTS: Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia, and 50 had preemptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with preemptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. CONCLUSION: Preemptive therapy avoided progression to meningitis in CrAg LFA-positive patients. Preemptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended.

Cryptococcal meningoencephalitis: Risk factors associated to death in a hospital in Northeastern Brazil.

INTRODUCTION: Cryptococcosis is an opportunistic systemic mycosis caused by pathogenic encapsulated yeasts of the genus Cryptococcus. The objective of the present study was to evaluate the risk factors associated with death of patients diagnosed with meningitis due to Cryptococcus spp. METHODS: This retrospective cohort study included patients admitted to the São José Hospital (SJH) with Cryptococcal Meningoencephalitis (CM) who were diagnosed between 2010 and 2018. Data collection was carried out by reviewing the patients' medical records. Death during hospitalization was considered the primary outcome. RESULTS: From 2010 to 2018, 21,519 patients were admitted to the HSJ, 124 of whom were hospitalized due to CM. The CM incidence rate was 5.8 cases/103 hospitalizations. We included 112 patients in the study. Male patients were the most affected (82.1%), and the median age was 37 years [IQR: 29-45]. HIV coinfection occurred in 79.4% of the patients. Fever (65.2%) and headache (88.4%) were the most frequent symptoms. Greater cellularity in the CSF was the most related factor to CM in non-HIV individuals (p < 0.05). Death during hospitalization occurred in 28.6% (n = 32) of the patients. The independent risk factors associated with death during the hospitalization were women (p = 0.009), age > 35 years (p = 0.046), focal neurological deficits (p = 0.013), altered mental status (p = 0.018) and HIV infection (p = 0.040). The twelve-month survival was lower in HIV-positive patients (p < 0.05). CONCLUSION: Early diagnosis, optimal treatment, and clinical follow-up strategies, especially in HIV patients, should be prioritized.

Cryptococcal infection causing longitudinal extensive transverse myelitis in an immunocompetent individual: Case report and literature review.

Cryptococcal CNS infections in immunocompetent individuals are occasionally reported in literature. The spinal manifestations of cryptococcal CNS infections are epidural abscess, chronic arachnoiditis, intramedullary granuloma, myelitis and vasculitis. We report a rare case of CNS cryptococcal infection presenting as a longitudinal extensive transverse myelitis (LETM) in an immunocompetent male. This report highlights cryptococcus as an important etiology among infectious causes in acute LETM patients in-spite of the immunocompetent status of the patient and the utility of CRAG (cryptococcal antigen) for diagnosis in such patients. We also present a literature review of all reported cases of cryptococcal myelitis.

Diagnostic performance of the IMMY cryptococcal antigen lateral flow assay on serum and cerebrospinal fluid for diagnosis of cryptococcosis in HIV-negative patients: a systematic review.

BACKGROUND: The incidence of cryptococcosis amongst HIV-negative persons is increasing. Whilst the excellent performance of the CrAg testing in people living with HIV is well described, the diagnostic performance of the CrAg LFA has not been systematically evaluated in HIV-negative cohorts on serum or cerebrospinal fluid. METHODS: We performed a systematic review to characterise the diagnostic performance of IMMY CrAg® LFA in HIV-negative populations on serum and cerebrospinal fluid. A systematic electronic search was performed using Medline, Embase, Global Health, CENTRAL, WoS Science Citation Index, SCOPUS, Africa-Wide Information, LILACS and WHO Global Health Library. Studies were screened and data extracted from eligible studies by two independent reviewers. A fixed effect meta-analysis was used to estimate the diagnostic sensitivity and specificity. RESULTS: Of 447 records assessed for eligibility, nine studies met our inclusion criteria, including 528 participants overall. Amongst eight studies that evaluated the diagnostic performance of the IMMY CrAg® LFA on serum, the pooled median sensitivity was 96% (95% Credible Interval (CrI) 68-100%) with a pooled specificity estimate of 96% (95%CrI 84-100%). Amongst six studies which evaluated the diagnostic performance of IMMY CrAg® LFA on CSF, the pooled median sensitivity was 99% (95%CrI 95-100%) with a pooled specificity median of 99% (95%CrI 95-100%). CONCLUSIONS: This review demonstrates a high pooled sensitivity and specificity for the IMMY CrAg® LFA in HIV-negative populations, in keeping with findings in HIV-positive individuals. The review was limited by the small number of studies. Further studies using IMMY CrAg® LFA in HIV-negative populations would help to better determine the diagnostic value of this test.

Impact of prior cryptococcal antigen screening on in-hospital mortality in cryptococcal meningitis or fungaemia among HIV-seropositive individuals in South Africa: a cross-sectional observational study.

OBJECTIVES: We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital. METHODS: We compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/µL and laboratory-confirmed CM/fungaemia from 2017-2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre-COVID-19: before March 2020 vs. COVID-19: after March 2020). RESULTS: Overall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69-0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47-0.87]; p = 0.005) compared with before (OR, 0.95 [0.76-1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51-0.96]; p = 0.03). DISCUSSION: Previous CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier.

Digital Platform for Automatic Qualitative and Quantitative Reading of a Cryptococcal Antigen Point-of-Care Assay Leveraging Smartphones and Artificial Intelligence.

Cryptococcosis is a fungal infection that causes serious illness, particularly in immunocompromised individuals such as people living with HIV. Point of care tests (POCT) can help identify and diagnose patients with several advantages including rapid results and ease of use. The cryptococcal antigen (CrAg) lateral flow assay (LFA) has demonstrated excellent performance in diagnosing cryptococcosis, and it is particularly useful in resource-limited settings where laboratory-based tests may not be readily available. The use of artificial intelligence (AI) for the interpretation of rapid diagnostic tests can improve the accuracy and speed of test results, as well as reduce the cost and workload of healthcare professionals, reducing subjectivity associated with its interpretation. In this work, we analyze a smartphone-based digital system assisted by AI to automatically interpret CrAg LFA as well as to estimate the antigen concentration in the strip. The system showed excellent performance for predicting LFA qualitative interpretation with an area under the receiver operating characteristic curve of 0.997. On the other hand, its potential to predict antigen concentration based solely on a photograph of the LFA has also been demonstrated, finding a strong correlation between band intensity and antigen concentration, with a Pearson correlation coefficient of 0.953. The system, which is connected to a cloud web platform, allows for case identification, quality control, and real-time monitoring.

Cryptococcal meningitis in people living with human immunodeficiency virus in Nepal: Perspectives from resource limited setting.

Early diagnosis of cryptococcal meningitis among people living with HIV (PLHIV) is crucial for its therapeutic success. The objective of this study was to diagnose cryptococcal meningitis in PLHIV cases using the available laboratory techniques for its confirmation in resource limited setting. This cross-sectional prospective study was conducted among 72 PLHIV with clinical suspicion of meningitis. Each cerebrospinal fluid (CSF) sample received at the National Public Health Laboratory, Kathmandu was processed for India ink staining, cryptococcal antigen lateral flow assay, and fungal culture following standard protocols. The laboratory-confirmed cryptococcal meningitis cases were between 24 and 69 years of age (median age 39 years) with 87.5% (12/14) of cases being male. Cryptococcus was detected in 22.22% (16/72) by any of the three tests, 19.44% (14/72) by cryptococcal antigen lateral flow assay, 16.66% (12/72) by India ink staining, and 8.33% (6/72) by culture. High percentage of cryptococcal meningitis among PLHIV warrants early microbiological diagnosis for better case management. Cryptococcal antigen detection immunoassay should be the priority test for laboratory diagnosis of cryptococcal meningitis in PLHIV. Alternatively, very simple and economic India ink staining of CSF specimens could be used in resource limited settings.

Cryptococcal antigenemia in people living with HIV and AIDS.

AIM: To assess the prevalence of cryptococcal antigenemia among people living with HIV/AIDS (PLHA) with CD4 ≤100/mm3. DESIGN: This observational study was performed on PLHA with laboratory-confirmed CD4 ≤100/mm3. All PLHA were recruited irrespective of their duration of HIV diagnosis, antiretroviral therapy (ART) naïve, or ART failure. METHODS: The prevalence of cryptococcal antigen (CrAg) was assessed in 102 PLHA, with CD4 ≤100/mm3, using a latex agglutination test on serum samples. All the subjects were followed up for 3 months. RESULTS: Amongst 102 PLHA, 62 (60.8%) and 40 (39.2%) patients were ART-naïve and ART failures, respectively, with 2.9% (n = 3) having clinical features of meningitis and 6.8% (n = 7) patients being asymptomatic CrAg-positive. At the 3 month follow-up, total mortality was 10.8%, of which 33.3% and 8.8% were among CrAg-positive and negative patients (p = 0.05). Mortality in asymptomatic and meningitis symptomatic CrAg-positive patients was 1.03% (n = 1) and 2.06% (n = 2), respectively. Of note, five patients were lost to follow-up. CONCLUSION: Cryptococcal antigenemia is common among patients with CD4 ≤100/mm3 who were either ART naïve or had treatment failure. Asymptomatic patients who underwent pre-emptive therapy demonstrated good clinical outcomes.

Hidden in plain sight: urinary Cryptococcus neoformans missed by routine diagnostics in a patient with acute leukemia.

Cryptococcuria is a rare manifestation of localized cryptococcal disease. We present a case of Cryptococcus neoformans urinary tract infection in an immunocompromised host missed by routine laboratory workup. The patient had negative blood cultures, a negative serum cryptococcal antigen (CrAg), and "non-Candida yeast" growing in urine culture that was initially dismissed as non-pathogenic. The diagnosis was ultimately made by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) from a repeat urine culture after transfer to a tertiary care center. Cryptococcus should be considered in the differential of refractory urinary tract infections growing non-Candida yeast.

Fatal cryptococcal meningitis in the Non-HIV infected: A case report.

Cryptococcal meningitis (CM) is underreported in the immunocompetent, the disease being more commonly associated with advanced human immunodeficiency virus (HIV) disease. We report the diagnosis, management, and eventual fatal outcome of CM in a non-HIV-infected man. Late presentation, delayed diagnosis, difficulties in accessing medications, and raised intracranial pressure (ICP) were contributory to his demise. Detailed history, a high index of suspicion, and laboratory workup coupled with prompt antifungal therapy and aggressive ICP management are essential for better outcomes.

Investigation of CryptoPS LFA-positive sera in patients at risk of cryptococcosis.

Cryptococcal antigen (CrAg) is a capsule polysaccharide antigen that can be detected in the fluids of patients with cryptococcal infections. Cryptococcal Antigen Latex Agglutination System (CALAS), enzyme-linked immunosorbent assays (EIA), and lateral flow assay (LFA) are the main methods available. Two main commercial LFA kits are available: CryptoPS (Biosynex, Illkirch Graffenstaden, France) and CrAg LFA (IMMY, Inc. USA). In our lab, we prospectively used CryptoPS as a screening tool in serum for confirmed positive results with CALAS. We investigated the rigor of the CryptoPS test in serum in a multicentric evaluation over 3 years. To improve the specificity of CryptoPS in serum, we additionally implemented and evaluated a pretreatment protocol before CryptoPS testing. A total of 43 serum samples collected from 43 patients were investigated. We found that the CryptoPS assay is hampered by a high rate of false-positive results in serum with a high rate of CryptoPS-positive but CrAg LFA-negative and CALAS-negative sera in patients with no proof of Cryptococcus infection (n = 29). Using a simple pretreatment procedure (5 min incubation at 100°C and centrifugation) we were able to reverse false-positive results, suggesting that there could be interferent material present in the serum. Pretreatment also impacted the CryptoPS results (negative result) in two patients with the cryptococcal disease, one with isolated antigenemia and one with cryptococcal meningitis. Comparing the titers obtained with CALAS and CrAg LFA, we noticed that the titer obtained with CrAg LFA was almost 10-fold higher than those with CALAS. This study showed that Biosynex CryptoPS in serum could give false-positive results even in the absence of cryptococcal disease. These could be reduced by applying an easy pretreatment procedure to the serum before testing, with little but existing impact on the sensitivity.

Lateral flow assays are useful to detect the cryptococcal antigen in human fluids. We investigated CryptoPS-positive results and observed that true false-positive results occurred. The false-positive results can be reduced by applying an easy pretreatment procedure.

Diagnostic Accuracy of Point of Care Cryptococcal Antigen Lateral Flow Assay in Fingerprick Whole Blood and Urine Samples for the Detection of Asymptomatic Cryptococcal Disease in Patients with Advanced HIV Disease.

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. IMPORTANCE 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.