Evaluation of Fingerstick Cryptococcal Antigen Lateral Flow Assay in HIV-Infected Persons: A Diagnostic Accuracy Study: Figure 1.

Abstract Objective To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (real time assessment of community transmission 2—React 2). Design Diagnostic accuracy study. Setting Laboratory analyses were performed in the United Kingdom at Imperial College, London and university facilities in London. Research clinics for finger prick sampling were run in two affiliated NHS trusts. Participants Sensitivity analyses were performed on sera stored from 320 previous participants in the React 2 programme with confirmed previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Specificity analyses were performed on 1000 prepandemic serum samples. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger prick testing. Interventions Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 serum samples from participants with confirmed SARS-CoV-2 infection and 500 prepandemic serum samples, respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger prick sensitivity of the LFIA currently used in React 2 seroprevalence studies (84%). These LFIAs were then further evaluated through finger prick testing on participants with confirmed previous SARS-CoV-2 infection: two LFIAs (Surescreen, Panbio) were evaluated in clinics in June-July 2020 and the third LFIA (AbC-19) in September 2020. A spike protein enzyme linked immunoassay and hybrid double antigen binding assay were used as laboratory reference standards. Main outcome measures The accuracy of LFIAs in detecting immunoglobulin G (IgG) antibodies to SARS-CoV-2 compared with two reference standards. Results The sensitivity and specificity of seven new LFIAs that were analysed using sera varied from 69% to 100%, and from 98.6% to 100%, respectively (compared with the two reference standards). Sensitivity on finger prick testing was 77% (95% confidence interval 61.4% to 88.2%) for Panbio, 86% (72.7% to 94.8%) for Surescreen, and 69% (53.8% to 81.3%) for AbC-19 compared with the reference standards. Sensitivity for sera from matched clinical samples performed on AbC-19 was significantly higher with serum than finger prick at 92% (80.0% to 97.7%, P=0.01). Antibody titres varied considerably among cohorts. The numbers of positive samples identified by finger prick in the lowest antibody titre quarter varied among LFIAs. Conclusions One new LFIA was identified with clinical performance suitable for potential inclusion in seroprevalence studies. However, none of the LFIAs tested had clearly superior performance to the LFIA currently used in React 2 seroprevalence surveys, and none showed sufficient sensitivity and specificity to be considered for routine clinical use.

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

African Journal of Clinical and Experimental Microbiology ◽

10.4314/ajcem.v22i1.12 ◽

2021 ◽

Vol 22 (1) ◽

pp. 93-96

Author(s):

S.A. Fayemiwo ◽

O.B. Makanjuola ◽

J. Nwaokenye ◽

M.O. Owolabi

Keyword(s):

Diagnostic Accuracy ◽

Predictive Value ◽

Lateral Flow ◽

Lateral Flow Assay ◽

Likelihood Ratios ◽

Cryptococcal Antigen ◽

Cryptococcal Infection ◽

Test Kit ◽

Sensitivity Specificity ◽

Hiv Negative

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

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Diagnostic Accuracy of the Biosynex CryptoPS Cryptococcal Antigen Semiquantitative Lateral Flow Assay in Patients with Advanced HIV Disease

Journal of Clinical Microbiology ◽

10.1128/jcm.02307-20 ◽

2020 ◽

Vol 59 (1) ◽

pp. e02307-20

Author(s):

Mark W. Tenforde ◽

Timothée Boyer-Chammard ◽

Charles Muthoga ◽

Leabaneng Tawe ◽

Thandi Milton ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Predictive Value ◽

High Titer ◽

False Negative ◽

Lateral Flow ◽

Lateral Flow Assay ◽

Hiv Disease ◽

Cd4 Cell Count ◽

Cryptococcal Antigen ◽

Advanced Hiv Disease

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.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study

Wellcome Open Research ◽

10.12688/wellcomeopenres.17231.1 ◽

2021 ◽

Vol 6 ◽

pp. 358

Author(s):

Alexandra Cann ◽

Candice Clarke ◽

Jonathan Brown ◽

Tina Thomson ◽

Maria Prendecki ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Diagnostic Accuracy ◽

Natural Infection ◽

Protein Detection ◽

Lateral Flow ◽

Antibody Responses ◽

Spike Protein ◽

Diagnostic Accuracy Study ◽

Extensive Evaluation ◽

Accuracy Study

Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.

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SARS-CoV-2 Antibody Lateral Flow Assay for antibody prevalence studies following vaccine roll out: a Diagnostic Accuracy Study

10.1101/2021.07.14.21260488 ◽

2021 ◽

Author(s):

Alexandra H C Cann ◽

Candice L Clarke ◽

Jonathan C Brown ◽

Tina Thomson ◽

Maria Prendecki ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Natural Infection ◽

Protein Detection ◽

Imperial College ◽

Lateral Flow ◽

Antibody Responses ◽

Spike Protein ◽

Diagnostic Accuracy Study ◽

Extensive Evaluation ◽

Accuracy Study

Background Lateral flow immunoassays (LFIAs) have the potential to deliver affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of SARS-CoV-2 vaccine. Methods This is a prospective diagnostic accuracy study. Setting Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Laboratory analyses were performed across Imperial College London sites and university facilities. Participants Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following SARS-CoV-2 vaccine booster, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination, and 21 day follow up. A total of 186 paired samples were collected. Interventions During the participants visit, capillary blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG were detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. Main outcome measures The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay. Results Using the threshold value for positivity on serological testing of ≥7.10 BAU/ml, the overall performance of the test produces an estimate of sensitivity of 91.94% (95% CI 85.67% to 96.06%) and specificity of 93.55% (95% CI 84.30% to 98.21%) using the Abbott assay as reference standard. Conclusions Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveys, but does not meet criteria for individual testing.

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