A Patient with Immunocompetent Cryptococcal Meningitis Showing Repetitive False-Negative Immunoassay for Cryptococcal Antigen

Introduction: A newly developed cryptococcal antigen (CrAg) semi-quantitative (SQ) lateral flow assay (LFA) provides a semi-quantitative result in a rapid, one-step test instead of performing serial dilutions to determine CrAg titer. Methodology: We prospectively compared the diagnostic performance of the CrAgSQ assay (IMMY) with the CrAg LFA (IMMY) on cerebrospinal fluid (CSF) samples collected from persons with HIV-associated meningitis. The CrAgSQ grades (1+ to 5+) were compared with CrAg LFA titers and quantitative CSF fungal cultures. Results: Among 87 participants screened for HIV-associated meningitis, 60 had cryptococcal meningitis (59 CrAg+ by LFA and 1 false negative due to prozone with CrAg LFA titer of 1:1,310,000 and culture positivity), and 27 had no cryptococcal meningitis by CrAg LFA or culture. The CrAgSQ on CSF had 100% (60/60) sensitivity and 100% specificity (27/27). CSF CrAg titers ranged from 1:5 to 1:42 million. CrAgSQ grade of 1+, 2+, 3+, 4+, and 5+ corresponded to median CrAg LFA titers of 1:<10, 1:60, 1:7,680, 1:81,920, and 1:1,474,000, respectively. CSF CrAgSQ 3+ or higher were always CSF culture positive. Mortality at 14 days for those with low CrAgSQ grade (1+ to 3+) was 5% (1/22) versus 21% (8/38) with high CrAgSQ grades (4+ to 5+) (P=.084). Conclusion: The CrAgSQ demonstrates excellent diagnostic performance, maintaining both the sensitivity and specificity of the CrAg LFA, and counters false negative prozone effects. The CrAgSQ assay reading is more complex but does provide useful clinical information about disease burden and probability of culture positivity in a single rapid diagnostic test.

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Evaluation of Clinical Profile, Diagnostic Tests, And Prognosis of Cryptococcal Meningitis in HIV Infected Patients in Western India

Infectious Disorders - Drug Targets ◽

10.2174/1567201817666200516160432 ◽

2020 ◽

Vol 20 ◽

Author(s):

Deepak Kumar ◽

Suresh Bishnoi ◽

Durga Shankar Meena ◽

Gopal Krishana Bohra ◽

Naresh Midha ◽

...

Keyword(s):

Prognostic Factors ◽

Clinical Features ◽

Cryptococcal Meningitis ◽

Fatal Outcome ◽

Clinical Profile ◽

Western India ◽

Antigen Test ◽

Cryptococcal Antigen ◽

India Ink ◽

Csf Examination

Background: Cryptococcal meningitis is a dreaded complication in HIV infected patients. It was associated with high mortality and morbidity before the advent of Highly Active Anti-Retroviral Therapy. A study was planned in our institute to evaluate the clinical profile, laboratory findings, and prognostic factors for survival in these patients. Settings and Design: A prospective hospital-based observational study, conducted in the Department of Medicine at a tertiary care centre in western Rajasthan. Method and Material: HIV infected patients presenting with clinical features of meningitis, and positive CSF culture for Cryptococcus were included in our study. All cases underwent detailed clinical history, physical examinations and relevant laboratory investigations including CD4 count and CSF examination. Results: 48 HIV infected cryptococcal meningitis patients were analysed, and the most common presenting clinical features were headache (85.42%), and fever (72.92%), followed by neck stiffness (62.50%). CSF examination was also done for Cryptococcal Antigen test which was reactive in all cases (100%), and India ink staining was positive in 43 cases (89.58%). Significant fatal outcome was associated with patients presenting with altered sensorium, loss of consciousness, cranial nerve palsy and CD4 cell count of less than 100. Similarly, on laboratory and imaging diagnosis, cryptococcal antigen test (>3+reactive), fundus examination (papilloedema) and abnormal CT/MRI brain imaging were associated with poor survival. Conclusion: Cryptococcal meningitis is a potentially lethal infection in immunocompromised individuals and should be diagnosed early with high clinical suspicion as around 10% of the cases may not be detected on India ink staining and a large proportion (75%) of cases may have normal imaging at initial evaluation. Early diagnosis, watchful eye on prognostic factors and treatment is vital to improve outcome in these patients.

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Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India – A Prospective Cohort Study

Current HIV Research ◽

10.2174/1570162x18666200827113816 ◽

2020 ◽

Vol 18 ◽

Author(s):

Rajendra Bhati ◽

Pramendra Sirohi ◽

Bharat Sejoo ◽

Deepak Kumar ◽

Gopal K Bohra ◽

...

Keyword(s):

Cryptococcal Meningitis ◽

Morbidity And Mortality ◽

People Living With Hiv ◽

Cryptococcal Antigen ◽

North West ◽

Cryptococcal Disease ◽

Increased Risk ◽

Living With Hiv ◽

Inflammatory Syndrome

Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and pre-emptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. Method and material: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. Results: A total of 116 patients were analysed. Asymptomatic cryptococcal antigenemia was detected in 5.17% patients and it correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Conclusion: Serum cryptococcal positivity is correlated with increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

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Evaluation of a Novel Point-of-Care Cryptococcal Antigen Test on Serum, Plasma, and Urine From Patients With HIV-Associated Cryptococcal Meningitis

Clinical Infectious Diseases ◽

10.1093/cid/cir613 ◽

2011 ◽

Vol 53 (10) ◽

pp. 1019-1023 ◽

Cited By ~ 192

Author(s):

J. N. Jarvis ◽

A. Percival ◽

S. Bauman ◽

J. Pelfrey ◽

G. Meintjes ◽

...

Keyword(s):

Cryptococcal Meningitis ◽

Point Of Care ◽

Antigen Test ◽

Cryptococcal Antigen

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Cost-Effectiveness Analysis of the Implementation of Cryptococcal Antigen Lateral Flow Assay for the Diagnosis of Cryptococcal Meningitis in Symptomatic People Living With Human Immunodeficiency Virus in Brazil

Value in Health Regional Issues ◽

10.1016/j.vhri.2021.09.006 ◽

2022 ◽

Vol 29 ◽

pp. 53-59

Author(s):

Cid Manso de Mello Vianna ◽

Gabriela Bittencourt Gonzalez Mosegui

Keyword(s):

Human Immunodeficiency Virus ◽

Cost Effectiveness ◽

Cryptococcal Meningitis ◽

Cost Effectiveness Analysis ◽

Lateral Flow ◽

Lateral Flow Assay ◽

Cryptococcal Antigen ◽

Effectiveness Analysis ◽

Immunodeficiency Virus

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LATERAL FLOW ASSAY FOR CRYPTOCOCCAL ANTIGEN: AN IMPORTANT ADVANCE TO IMPROVE THE CONTINUUM OF HIV CARE AND REDUCE CRYPTOCOCCAL MENINGITIS-RELATED MORTALITY

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652015000700008 ◽

2015 ◽

Vol 57 (suppl 19) ◽

pp. 38-45 ◽

Cited By ~ 46

Author(s):

Jose E. VIDAL ◽

David R. BOULWARE

Keyword(s):

Cerebrospinal Fluid ◽

Cryptococcal Meningitis ◽

Capsular Polysaccharide ◽

Lateral Flow ◽

Lateral Flow Assay ◽

World Health ◽

Hiv Care ◽

Analytical Sensitivity ◽

Symptomatic Infection ◽

Cryptococcal Antigen

SUMMARYAIDS-related cryptococcal meningitis continues to cause a substantial burden of death in low and middle income countries. The diagnostic use for detection of cryptococcal capsular polysaccharide antigen (CrAg) in serum and cerebrospinal fluid by latex agglutination test (CrAg-latex) or enzyme-linked immunoassay (EIA) has been available for over decades. Better diagnostics in asymptomatic and symptomatic phases of cryptococcosis are key components to reduce mortality. Recently, the cryptococcal antigen lateral flow assay (CrAg LFA) was included in the armamentarium for diagnosis. Unlike the other tests, the CrAg LFA is a dipstick immunochromatographic assay, in a format similar to the home pregnancy test, and requires little or no lab infrastructure. This test meets all of the World Health Organization ASSURED criteria (Affordable, Sensitive, Specific, User friendly, Rapid/robust, Equipment-free, and Delivered). CrAg LFA in serum, plasma, whole blood, or cerebrospinal fluid is useful for the diagnosis of disease caused by Cryptococcusspecies. The CrAg LFA has better analytical sensitivity for C. gattii than CrAg-latex or EIA. Prevention of cryptococcal disease is new application of CrAg LFA via screening of blood for subclinical infection in asymptomatic HIV-infected persons with CD4 counts < 100 cells/mL who are not receiving effective antiretroviral therapy. CrAg screening of leftover plasma specimens after CD4 testing can identify persons with asymptomatic infection who urgently require pre-emptive fluconazole, who will otherwise progress to symptomatic infection and/or die.

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