scholarly journals Evaluation of a cryptococcal antigen lateral flow assay test for rapid detection of cryptococcal infection in HIV-negative patients in Ibadan, Nigeria

2021 ◽  
Vol 22 (1) ◽  
pp. 93-96
Author(s):  
S.A. Fayemiwo ◽  
O.B. Makanjuola ◽  
J. Nwaokenye ◽  
M.O. Owolabi

Background: A number of studies have been conducted in Nigeria on the prevalence of cryptococcal infections mostly on HIV-infected patients using culture, India ink and/or latex agglutination tests. These tests are either laborious, time-consuming and expensive or have low sensitivity, thus limiting their use. Cryptococcal antigen lateral flow assays (LFA) were introduced in the last decade as rapid user-friendly tests for diagnosis. In this study, we sought to determine the diagnostic accuracy of an LFA kit for the detection of cryptococcal antigen in the serum of HIV-negative patients with or without cerebrovascular accident (CVA) or stroke in University College Hospital, Ibadan, Nigeria.Methodology: The diagnostic accuracy of Dynamiker CrAg LFA was tested against BiosynexR CryptoPS on serum samples of 100 HIV-negative patients with and without stroke. Samples were tested and results interpreted in accordance with the manufacturer’s instructions. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios of the Dynamiker CrAg LFA were calculated by comparing with the BiosynexR CryptoPS as ‘gold standard’.Results: Overall, a total of 98 valid patient sample results were analysed; 17 samples (17.3%) were positive with Dynamiker CrAg LFA cryptococcal antigen and 16 samples (16.3%) were positive with BiosynexR CryptoPS. The sensitivity, specificity, PPV and NPV of Dynamiker CrAg LFA compared to the BiosynexR CryptoPS were 100%, 98.8%, 94.1% and 100% respectively, while the positive and negative likelihood ratios were 82 and 0 respectively.Conclusion: In comparison to the BiosynexR CryptoPS, the Dynamiker CrAg LFA is a highly sensitive and specific test for the detection of cryptococcal antigen in serum. The test kit should be considered as a screening device for cryptococcal infection both in outreach and clinical settings, especially in antiretroviral therapy (ART) centres. Keywords: Cryptococcus; evaluation; lateral flow assay; HIV-negative; stroke

2020 ◽  
Vol 59 (1) ◽  
pp. e02307-20
Author(s):  
Mark W. Tenforde ◽  
Timothée Boyer-Chammard ◽  
Charles Muthoga ◽  
Leabaneng Tawe ◽  
Thandi Milton ◽  
...  

ABSTRACTHigh cryptococcal antigen (CrAg) titers in blood are associated with subclinical meningitis and mortality in CrAg-positive individuals with advanced HIV disease (AHD). We evaluated a novel semiquantitative lateral flow assay (LFA), CryptoPS, that may be able to identify individuals with high CrAg titers in a cohort of AHD patients undergoing CrAg screening. In a prospective cohort of patients with AHD (CD4 cell count, ≤200/μl) receiving CD4 count testing, whole blood was tested for CrAg by CryptoPS and the IMMY LFA; the two assays were conducted by two different operators, each blind to the results of the other assay. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CryptoPS were assessed against the IMMY LFA as a reference. CryptoPS low-titer (T1 band) and high-titer (T2 band) results were compared with IMMY LFA titers obtained through serial dilution. A total of 916 specimens were tested. The sensitivity of the CryptoPS assay was 61.0% (25/41) (95% confidence interval [95% CI], 44.5 to 75.8%), its specificity was 96.6% (845/875) (95% CI, 95.1 to 97.7%), its PPV was 45.5% (95% CI, 32.0 to 59.4%), and its NPV was 98.1% (95% CI, 97.0 to 98.9%). All (16/16) CryptoPS false-negative results were obtained for samples with IMMY titers of ≤1:160. Of 29 patients (30 specimens) who tested positive by CryptoPS but negative by the IMMY LFA, none developed cryptococcal meningitis over 3 months of follow-up without fluconazole. Median CrAg titers were 1:20 (interquartile range [IQR], 0 to 1:160) in CryptoPS T1-positive samples and 1:2,560 (IQR, 1:1,280 to 1:10,240) in T2-positive samples. We conclude that the diagnostic accuracy of the CryptoPS assay was suboptimal in the context of CrAg screening, with poor sensitivity at low CrAg titers. However, the CryptoPS assay reliably detected individuals with high titers, which are associated with poor outcomes.


2020 ◽  
Vol 58 (11) ◽  
Author(s):  
Matthew A. Hevey ◽  
Ige A. George ◽  
Adriana M. Rauseo ◽  
Lindsey Larson ◽  
William Powderly ◽  
...  

ABSTRACT Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed in 227 patients with cryptococcosis. Of 141 HIV-negative patients, 107 had LA testing and 34 had LFA testing. In patients with disseminated disease, serum CrAg sensitivity by LA was 78.1% compared to 82.6% for LFA. In patients with localized pulmonary disease, serum CrAg sensitivity was 23.5% compared to 90.9% for LFA. Of 86 people living with HIV (PLWH), 76 had LA testing, and 10 had LFA testing. Serum CrAg sensitivity for LA was 94.7% compared to 100% for LFA in patients with disseminated disease. We noted a significant improvement in sensitivity from LA testing to LFA testing, predominantly in those with localized pulmonary disease. However, both LFA and LA appear to be less sensitive in HIV-negative patients than previously described in PLWH.


2015 ◽  
Vol 61 (3) ◽  
pp. 464-467 ◽  
Author(s):  
Darlisha A. Williams ◽  
Tadeo Kiiza ◽  
Richard Kwizera ◽  
Reuben Kiggundu ◽  
Sruti Velamakanni ◽  
...  

Author(s):  
Richard Kwizera ◽  
Denis Omali ◽  
Kiiza Tadeo ◽  
John Kasibante ◽  
Morris K. Rutakingirwa ◽  
...  

Background: 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). Methods: 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, 100 cerebrospinal fluid (CSF) samples from HIV patients with symptomatic meningitis and 113 serum samples from patients with suspected asymptomatic cryptococcal antigenemia. Results: 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, 91% in CSF from symptomatic patients, and 86% in serum from asymptomatic patients. The positive predictive value was 85% in serum, 82% in plasma, 96% in CSF from symptomatic patients, and 69% in serum from asymptomatic patients. The negative predictive value was 94% in serum, 100% in plasma, 100% in CSF from symptomatic patients, and 99% in serum from asymptomatic patients. The inter-assay 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%). Conclusion: The Dynamiker CrAg-LFA had excellent sensitivity but poor specificity, particularly when tested on serum and plasma.


2015 ◽  
Vol 54 (2) ◽  
pp. 460-463 ◽  
Author(s):  
Anupop Jitmuang ◽  
Anil A. Panackal ◽  
Peter R. Williamson ◽  
John E. Bennett ◽  
John P. Dekker ◽  
...  

The cryptococcal antigen lateral flow assay (CrAg LFA) was evaluated for the diagnosis of cryptococcosis in HIV-negative patients. The sensitivity was excellent, suggesting that this assay can replace conventional testing based on latex agglutination (LA). CrAg LFA and LA titers were correlated but were not directly comparable, with implications for conversion between assays.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Adriana Sánchez-García ◽  
René Rodríguez-Gutiérrez ◽  
Leonardo Mancillas-Adame ◽  
Victoria González-Nava ◽  
Alejandro Díaz González-Colmenero ◽  
...  

Introduction. The triglyceride and glucose (TyG) index has been described as a biochemical marker of insulin resistance (IR); however, its diagnostic accuracy remains uncertain. Objective. To summarize the evidence assessing the diagnostic accuracy of the TyG index regarding IR. Methods. A comprehensive search in MEDLINE, EMBASE, Web of Science, and Scopus was performed without any language restriction. Studies assessing the diagnostic accuracy of the TyG index against the hyperinsulinemic-euglycemic clamp (HIEC) or any other IR biochemical were assessed independently and in duplicate. Diagnostic accuracy measures (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios) were extracted independently and in duplicate. The QUADAS-2 tool was used to assess the risk of bias of independent studies. Results. We identified 15 eligible studies with 69,922 participants and an overall quality of low to moderate. The TyG index was evaluated by HIEC and HOMA as reference tests. The highest achieved sensitivity was 96% using HIEC, and the highest specificity was of 99% using HOMA-IR, with a cutoff value of 4.68. AUC values varied from 0.59 to 0.88. Cutoff values for IR were variable between studies, limiting its comparability. Conclusion. In this systematic review, we found moderate-to-low quality evidence about the usefulness of the TyG index as a surrogate biochemical marker of IR. Due to the lack of a standardized IR definition and heterogeneity between studies, further validation and standardized cutoff values are needed to be used in clinical practice.


Author(s):  
Ling-Yu Guo ◽  
Phyllis Schneider ◽  
William Harrison

Purpose This study provided reference data and examined psychometric properties for clausal density (CD; i.e., number of clauses per utterance) in children between ages 4 and 9 years from the database of the Edmonton Narrative Norms Instrument (ENNI). Method Participants in the ENNI database included 300 children with typical language (TL) and 77 children with language impairment (LI) between the ages of 4;0 (years;months) and 9;11. Narrative samples were collected using a story generation task, in which children were asked to tell stories based on six picture sequences. CD was computed from the narrative samples. The split-half reliability, concurrent criterion validity, and diagnostic accuracy were evaluated for CD by age. Results CD scores increased significantly between ages 4 and 9 years in children with TL and those with LI. Children with TL produced higher CD scores than those with LI at each age level. In addition, the correlation coefficients for the split-half reliability and concurrent criterion validity of CD scores were all significant at each age level, with the magnitude ranging from small to large. The diagnostic accuracy of CD scores, as revealed by sensitivity, specificity, and likelihood ratios, was poor. Conclusions The finding on diagnostic accuracy did not support the use of CD for identifying children with LI between ages 4 and 9 years. However, given the attested reliability and validity for CD, reference data of CD from the ENNI database can be used for evaluating children's difficulties with complex syntax and monitoring their change over time. Supplemental Material https://doi.org/10.23641/asha.13172129


2012 ◽  
Vol 15 (1) ◽  
pp. 12 ◽  
Author(s):  
Levent Sahiner ◽  
Ali Oto ◽  
Kudret Aytemir ◽  
Tuncay Hazirolan ◽  
Musturay Karcaaltincaba ◽  
...  

<p><b>Background:</b> The aim of this study was to investigate the diagnostic accuracy of 16-slice multislice, multidetector computed tomography (MDCT) angiography for the evaluation of grafts in patients with coronary artery bypass grafting (CABG).</p><p><b>Methods:</b> Fifty-eight consecutive patients with CABG who underwent both MDCT and conventional invasive coronary angiography were included. The median time interval between the 2 procedures was 10 days (range, 1-32 days). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MDCT for the detection of occluded grafts were calculated. The accuracy of MDCT angiography for detecting significant stenoses in patent grafts and the evaluability of proximal and distal anastomoses were also investigated.</p><p><b>Results:</b> Optimal diagnostic images could not be obtained for only 3 (2%) of 153 grafts. Evaluation of the remaining 150 grafts revealed values for sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the MDCT angiography procedure for the diagnosis of occluded grafts of 87%, 97%, 94%, 93%, and 92%, respectively. All of the proximal anastomoses were optimally visualized. In 4 (8%) of 50 patent arterial grafts, however, the distal anastomotic region could not be evaluated because of motion and surgical-clip artifacts. The accuracy of MDCT angiography for the detection of significant stenotic lesions was relatively low (the sensitivity, specificity, PPV, and NPV were 67%, 98%, 50%, and 99%, respectively). The number of significant lesions was insufficient to reach a reliable conclusion, however.</p><p><b>Conclusion:</b> Our study showed that MDCT angiography with 16-slice systems has acceptable diagnostic performance for the evaluation of coronary artery bypass graft patency.</p>


Author(s):  
Kristin R V Harrington ◽  
Yun F (Wayne) Wang ◽  
Paulina A Rebolledo ◽  
Zhiyong Liu ◽  
Qianting Yang ◽  
...  

Abstract Background Cryptococcus neoformans is a major cause of morbidity and mortality among HIV-infected persons worldwide, and there is scarce recent data on cryptococcal antigen (CrAg) positivity in the U.S. We sought to determine the frequency of cryptococcal disease and compare the performance of a CrAg lateral flow assay (LFA) versus latex agglutination (LA) test. Methods All patients from Grady Health System in Atlanta who had a serum or cerebrospinal fluid (CSF) sample sent for CrAg testing as part of clinical care from November 2017 – July 2018 were included. Percent positivity and test agreement were calculated. Results Among 467 patients, 557 diagnostic tests were performed; 413 on serum and 144 on CSF. Mean age was 44 years, most were male (69%) and had HIV (79%). Twenty-four (6.4%, CI95% = 4.1, 9.4) patients were serum CrAg positive, and eight (5.8%, CI95% = 2.6, 11.2) individuals tested positive for CSF CrAg. While overall agreement between the LA and LFA was substantial to high for CSF (κ= 0.71, CI95% = 0.51, 0.91) and serum (κ= 0.93, CI95% = 0.86, 1.00), respectively, there were important discrepancies. Five patients had false-positive CSF LA tests which affected clinical care, and four patients had discordant serum tests. Conclusions We found a moderately high proportion of cryptococcal disease and important discrepancies between the LA test and LFA. Clinical implications of these findings include accurate detection of serum CrAg and averting unnecessary treatment of meningitis with costly medications associated with high rates of adverse events.


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