A comparative evaluation of three methods for the rapid diagnosis of cryptococcal meningitis (CM) among HIV-infected patients in Northern Malawi

Abstract

<jats:p>IntroductionCryptococcal meningitis (CM) is the most common systemic fungal infection in patients with HIV infection. Rapid diagnosis and timely initiation of antifungal therapy are key to reducing mortality rate associated with CM. This study aims to evaluate the ability of four different diagnostic tests (Gram stain, India ink, and two types of commercial lateral flow assay [LFA]) to identify CM-positive patients and to compare the sensitivity and specificity of these tests.MethodsThis was a prospective cross-sectional study on diagnostic tests accuracy conducted in Northern Malawi. The target population was HIV-infected adult patients presenting with features of meningitis. Four types of diagnostic tests were conducted: India ink, Gram stain, and two types of commercial lateral flow assay (LFA) (Immy, Inc., OK, USA and Dynamiker Biotechnology (Tianjin) Co., Ltd), Singapore). Culture was conducted as the reference standard.ResultsA total of 265 samples were collected. The rate of positive CM detection ranged from 6.4% (using India ink) to 14.3% (using LFA). India ink exhibited the lowest sensitivity of 54.8% (95% confidence interval [CI]: 36.0%–72.7%), followed by Gram stain (61.3%; 95% CI: 42.2%–78.2%). The Dynamiker LFA exhibited the highest sensitivity of 100.0% (95% CI: 90.0%–100.0%) but a lower specificity (97.0%; 93.9%–98.8%) compared to the Immy LFA (98.3%; 95% CI: 95.7%–99.5%). ConclusionLFA diagnostic methods have the potential to double the detection rate of CM-positive patients in resource-limited countries such as Malawi. As such, LFAs should be considered to become the main diagnostic tests used for CM diagnostics in these countries. Our data indicate that LFAs may be the best method for diagnosing CM and exhibits the highest diagnostic accuracy as it has shown that it outperforms cell culture, the current gold standard. </jats:p>

Clinical Characteristics and Risk Factors for Mortality in Cryptococcal Meningitis: Evidence From a Cohort Study

“…Despite requiring a long detection time, CSF culture is considered the gold standard in CM diagnosis. India ink stain is a rapid and economical diagnostic method for CM but it is limited by low sensitivity (18). To our acknowledge, there is no available data to show the number of times that either of these tests needs to be replicated.…”

Sequential infection of Epstein‐Barr virus and cryptococcal encephalitis after umbilical cord blood transplantation in a child with X‐linked adrenoleukodystrophy

“…12,13 The sensitivity and specificity of the India ink test range from 50%-86% and 94%-100%. 11,[14][15][16] However, from reports compared to culture, India ink (PPV range 86%-98%, NPV range 48%-80%) had poor predictive value. 14,17 For the false negative cases which cannot get the positive results by the conventional diagnostic methods, molecular methods for detection cryptococcus have been reported that may improve laboratory diagnosis.…”

“…The sensitivity and specificity of LAT are 92%‐98.8% and 93%‐98% for cryptococcal ME with the PPV and NPV of 90%‐97% and 93%‐100%, respectively 12,13 . The sensitivity and specificity of the India ink test range from 50%‐86% and 94%‐100% 11,14‐16 …”

Invasive fungal infections in liver diseases

“…Currently, the lateral flow assay is the most commonly used diagnostic method to detect cryptococcal antigens with high sensitivity (93%–100%) and specificity (93%–98%) in both blood and CSF. 77 , 78 Of note, false-positive serum cryptococcal antigen can occur in the setting of infection due to the fungus Trichosporon asahii . 79 …”