Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid.
Ontology highlight
ABSTRACT:
SUBMITTER: Kabanda T
PROVIDER: S-EPMC3864499 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
Publications
Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid.
Kabanda Taseera T Siedner Mark J MJ Klausner Jeffrey D JD Muzoora Conrad C Boulware David R DR
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20130924 1
The cryptococcal antigen (CRAG) lateral flow assay (LFA) had 100% sensitivity and specificity on cerebrospinal fluid samples. Pretreatment LFA titers correlated with quantitative cultures (R(2) = 0.7) and predicted 2- and 10-week mortality. The CRAG LFA is an accurate diagnostic assay for CSF and should be considered for point-of-care diagnosis of cryptococcal meningitis. ...[more]
Similar Datasets
Project description:BackgroundThe 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.MethodsWe 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.ResultsOf 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%).ConclusionsThis 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.
| S-EPMC10080957 | biostudies-literature
Project description:BACKGROUND:Cryptococcal antigen (CrAg) screening at the point of care could improve cryptococcal meningitis prevention where laboratory resources are limited. We evaluated the accuracy of Immunomycologics (IMMY, Norman, OK) CrAg lateral flow assay (LFA) using different techniques at point of care. SETTING:Two tertiary-level hospitals in Johannesburg and a community health clinic in Soweto, South Africa. METHODS:A case-control diagnostic validation study and a prospective clinic-based implementation study using the IMMY CrAg LFA on finger-prick blood. Accuracy, using direct application of LFA to sample, or pipette to transfer sample to diluent, and reading after 10 and 20 minutes, was compared with laboratory-based plasma testing. RESULTS:The validation study tested 64 CrAg-positive and 152 CrAg-negative patients with no symptoms or signs of meningitis, identified by routine laboratory screening, recruited by convenience sampling. Consecutively diagnosed HIV-infected adults (n = 654) were included in the implementation study. Sensitivity was 82% and 20% when the LFA was read 10 minutes after direct application to finger-prick blood in the validation and implementation studies, respectively. Using a pipette to transfer blood and reading after 20 minutes improved sensitivity to 100%, while retaining 100% specificity, in both studies. CONCLUSIONS:Although the IMMY CrAg LFA performs well when applied directly to finger-prick blood for diagnosing cryptococcal meningitis, this technique may not provide adequate volume to detect low concentrations of CrAg when screening asymptomatic patients. Using a pipette to transfer larger volumes of blood to diluent before CrAg LFA testing and reading results after 20 minutes is a more reliable point-of-care method.
| S-EPMC6381996 | biostudies-literature
Project description: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.
| S-EPMC7325107 | biostudies-literature
Project description:ObjectivesCryptococcosis remains a severe global health concern, underscoring the urgent need for rapid and reliable diagnostic solutions. Point-of-care tests (POCTs), such as the cryptococcal antigen semi-quantitative (CrAgSQ) lateral flow assay (LFA), offer promise in addressing this challenge. However, their subjective interpretation poses a limitation. Our objectives encompass the development and validation of a digital platform based on Artificial Intelligence (AI), assessing its semi-quantitative LFA interpretation performance, and exploring its potential to quantify CrAg concentrations directly from LFA images.MethodsWe tested 53 cryptococcal antigen (CrAg) concentrations spanning from 0 to 5000 ng/ml. A total of 318 CrAgSQ LFAs were inoculated and systematically photographed twice, employing two distinct smartphones, resulting in a dataset of 1272 images. We developed an AI algorithm designed for the automated interpretation of CrAgSQ LFAs. Concurrently, we explored the relationship between quantified test line intensities and CrAg concentrations.ResultsOur algorithm surpasses visual reading in sensitivity, and shows fewer discrepancies (p < 0.0001). The system exhibited capability of predicting CrAg concentrations exclusively based on a photograph of the LFA (Pearson correlation coefficient of 0.85).ConclusionsThis technology's adaptability for various LFAs suggests broader applications. AI-driven interpretations have transformative potential, revolutionizing cryptococcosis diagnosis, offering standardized, reliable, and efficient POCT results.
| S-EPMC11365246 | biostudies-literature
Project description:BackgroundCryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.MethodsWe screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard.ResultsThe saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001).ConclusionThere was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis.
| S-EPMC4117530 | biostudies-literature
Project description:Robust population pharmacokinetic (PK) data for fluconazole are scarce. The variability of fluconazole penetration into the central nervous system (CNS) is not known. A fluconazole PK study was conducted in 43 patients receiving oral fluconazole (usually 800 mg every 24 h [q24h]) in combination with amphotericin B deoxycholate (1 mg/kg q24h) for cryptococcal meningitis (CM). A four-compartment PK model was developed, and Monte Carlo simulations were performed for a range of fluconazole dosages. A meta-analysis of trials reporting outcomes of CM patients treated with fluconazole monotherapy was performed. Adjusted for bioavailability, the PK parameter means (standard deviation) were the following: clearance, 0.72 (0.24) liters/h; volume of the central compartment, 18.07 (6.31) liters; volume of the CNS compartment, 32.07 (17.60) liters; first-order rate constant from the central to peripheral compartment, 12.20 (11.17) h-1, from the peripheral to central compartment, 18.10 (8.25) h-1, from the central to CNS compartment, 35.43 (13.74) h-1, and from the CNS to central the compartment, 28.63 (10.03) h-1 Simulations of the area under concentration-time curve resulted in median (interquartile range) values of 1,143.2 (range, 988.4 to 1,378.0) mg · h/liter in plasma (AUCplasma) and 982.9 (range, 781.0 to 1,185.9) mg · h/liter in cerebrospinal fluid (AUCCSF) after a dosage of 1,200 mg q24h. The mean simulated ratio of AUCCSF/AUCplasma was 0.89 (standard deviation [SD], 0.44). The recommended dosage of fluconazole for CM induction therapy fails to attain the pharmacodynamic (PD) target in respect to the wild-type MIC distribution for C. neoformans The meta-analysis suggested modest improvements in both CSF sterility and mortality outcomes with escalating dosage. This study provides the pharmacodynamic rationale for the long-recognized fact that fluconazole monotherapy is an inadequate induction regimen for CM.
| S-EPMC6125572 | biostudies-literature
Project description:Cryptococcus is the leading cause of AIDS-related meningitis in sub-Saharan Africa. The clinical implications of a sterile cerebrospinal fluid (CSF) culture among individuals diagnosed with cryptococcal meningitis using CSF cryptococcal antigen (CrAg) are unclear. We prospectively enrolled 765 HIV-positive Ugandans with first-episode cryptococcal meningitis from November 2010 to May 2017. All persons were treated with amphotericin-based induction therapy. We grouped participants by tertile of baseline CSF quantitative Cryptococcus culture burden and compared clinical characteristics, CSF immune profiles, and 18-week mortality. We found 55 (7%) CSF CrAg-positive participants with sterile CSF cultures. Compared to the non-sterile groups, participants with sterile CSF cultures had higher CD4 counts, lower CSF opening pressures, and were more frequently receiving ART. By 18 weeks, 47% [26/55] died in the sterile culture group versus 35% [83/235] in the low culture tertile, 46% [107/234] in the middle tertile, and 56% [135/241] in the high tertile (p < 0.001). The sterile group had higher levels of CSF interferon-gamma (IFN-γ), IFN-α, interleukin (IL)-6, IL-17, G-CSF, GM-CSF, and chemokine CXCL2 compared with non-sterile groups. Despite persons with sterile CSF cultures having higher CD4 counts, lower CSF opening pressures, and CSF cytokine profiles associated with better Cryptococcus control (e.g., IFN-γ predominant), mortality was similar to those with higher fungal burdens. This unexpected finding challenges the traditional paradigm that increasing CSF fungal burdens are associated with increased mortality but is consistent with a damage-response framework model.
| S-EPMC9866844 | biostudies-literature
Project description:Cryptococcal meningitis is a leading cause of meningitis in sub-Saharan Africa. Given the need for rapid point-of-care testing, we evaluated the diagnostic performance of the Dynamiker cryptococcal antigen (CrAg) lateral flow assay (LFA). We assessed the diagnostic performance of the Dynamiker CrAg LFA compared to the IMMY CrAg LFA as the reference standard. We tested 150 serum, 115 plasma, and 100 cerebrospinal fluid (CSF) samples from HIV patients with symptomatic meningitis and 113 serum samples from patients with suspected asymptomatic cryptococcal antigenemia. Compared to the IMMY CrAg LFA, sensitivity of Dynamiker CrAg LFA was 98% in serum, 100% in plasma, 100% in CSF from symptomatic patients and 96% in serum from asymptomatic patients. Specificity was 66% in serum, 61% in plasma, and 91% in CSF from symptomatic patients, and 86% in serum from asymptomatic patients. The positive predictive value was 85% in serum, 82% in plasma, and 96% in CSF from symptomatic patients, and 69% in serum from asymptomatic patients. The negative predictive value was 94% in serum, 100% in plasma, and 100% in CSF from symptomatic patients, and 99% in serum from asymptomatic patients. The interassay reproducibility was 100% across the four sample types with no observed discordant results when Dynamiker CrAg LFA was tested in duplicate. However, a high number of false positives were observed on serum of symptomatic patients (11%), serum of asymptomatic patients (11%) and plasma of symptomatic patients (14%). The Dynamiker CrAg LFA had excellent sensitivity but poor specificity, particularly when tested on serum and plasma.
| S-EPMC8106724 | biostudies-literature
Project description:BackgroundCryptococcus neoformans is the most common cause of adult meningitis in sub-Saharan Africa. The cryptococcal antigen (CRAG) lateral flow assay (LFA) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (CSF). We evaluated the accuracy of the CRAG LFA using fingerstick whole blood compared with serum/plasma and CSF for diagnosing meningitis.MethodsFrom August 2013 to August 2014, CRAG LFA (IMMY, Norman, Oklahoma) tests were performed on fingerstick whole blood, plasma/serum, and CSF in 207 HIV-infected adults with suspected meningitis in Kampala, Uganda. Venous blood was also collected and centrifuged to obtain serum and/or plasma. CSF was tested after lumbar puncture.ResultsOf 207 participants, 149 (72%) had fingerstick CRAG-positive results. There was 100% agreement between fingerstick whole blood and serum/plasma. Of the 149 fingerstick CRAG-positive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG. Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and culture, of whom 8 had CSF abnormalities (n = 3 lymphocytic pleocytosis, n = 5 elevated protein, n = 4 increased opening pressure). No persons with cryptococcal meningitis had negative fingersticks.ConclusionsThe 100% agreement between whole blood, serum, and plasma CRAG LFA results demonstrates that fingerstick CRAG is a reliable bedside diagnostic test. Using point-of-care CRAG testing simplifies screening large numbers of patients and enables physicians to prioritize on whom to measure CSF opening pressure using manometers.
| S-EPMC4503809 | biostudies-literature
Project description:Higher cryptococcal antigen (CrAg) titers are strongly associated with mortality risk in individuals with HIV-associated cryptococcal disease. Rapid tests to quantify CrAg levels may provide important prognostic information and enable treatment stratification. We performed a laboratory-based validation of the IMMY semiquantitative cryptococcal antigen (CrAgSQ) lateral flow assay (LFA) against the current gold standard CrAg tests. We assessed the diagnostic accuracy of the CrAgSQ in HIV-positive individuals undergoing CrAg screening, determined the relationship between CrAgSQ scores and dilutional CrAg titers, assessed interrater reliability, and determined the clinical correlates of CrAgSQ scores. A total of 872 plasma samples were tested using both the CrAgSQ LFA and the conventional IMMY CrAg LFA, of which 692 were sequential samples from HIV-positive individuals undergoing CrAg screening and an additional 180 were known CrAg-positive plasma samples archived from prior studies. Interrater agreement in CrAgSQ reading was excellent (98.17% agreement, Cohen's kappa 0.962, P < 0.001). Using the IMMY CrAg LFA as a reference standard, CrAgSQ was 93.0% sensitive (95% confidence interval [CI] 80.9% to 98.5%) and 93.8% specific (95% CI, 91.7% to 95.6%). After reclassification of discordant results using CrAg enzyme immunoassay testing, the sensitivity was 98.1% (95% CI, 90.1% to 100%) and specificity 95.8% (95% CI, 93.9% to 97.2%). The median CrAg titers for semiquantitative score categories (1+ to 4+) were 1:10 (interquartile range [IQR], 1:5 to 1:20) in the CrAgSQ 1+ category, 1:40 (IQR, 1:20 to 1:80) in the CrAgSQ 2+ category, 1:640 (IQR, 1:160 to 1:2,560) in the CrAgSQ 3+ category, and 1:5,120 (IQR, 1:2,560 to 1:30,720) in the CrAgSQ 4+ category. Increasing CrAgSQ scores were strongly associated with 10-week mortality. The IMMY CrAgSQ test had high sensitivity and specificity compared to the results for the IMMY CrAg LFA and provided CrAg scores that were associated with both conventional CrAg titers and clinical outcomes.
| S-EPMC7448662 | biostudies-literature