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5 diagnostic approaches for cryptococcal meningitis in non-HIV-infected patients

June 09 2016

Cryptococcal meningitis (CM) is a fungal illness often associated with HIV positive patients; however, an increasing percentage of CM cases in non-HIV-infected individuals, particularly in China, Japan and Taiwan have been identified (e.g. Yuchong et al. 2012). Diagnosis of CM is perceived to be more difficult in HIV negative patients; this could be both due to physicians overlooking the possibility of CM, and the potentially lower fungal burden in non-HIV-infected patients, leading to low sensitivity in common diagnostic tests. It is therefore very important to evaluate a variety of diagnostic approaches in this patient population.

Chen et al. (2016) have verified five conventional and molecular approaches in 58 HIV negative CM patients, including: India ink staining, culture, a newly developed loop-mediated isothermal amplification (LAMP), the lateral flow assay (LFA) of cryptococcal antigen detection, and a qPCR assay. In HIV-infected patients, India ink staining and culture both have lower sensitivity. They also rely on experienced technicians and are time consuming.
LFA on the other hand, is affordable, robust and rapid. However, the performance of this test is unknown in non-HIV infected patients. Molecular techniques may be an alternative rapid diagnostic technique. For example, the LAMP technology has been shown to provide accurate, cost effective and rapid DNA amplification in 1 hour (Notomi et al. 2000).

 
Testing for cryptococcal antigens with a Lateral Flow assay

85 clinical CSF specimens were collected from 58 confirmed non-HIV-infected CM patients, from Shangai Changzheng Hospital and Shanghai Huashan Hospital. Positive detection of CM was significantly higher from the LFA (97.6%) compared to both culture (70.6%) and India ink (35.3%). These levels of detection may be due to the high percentage of patients on antifungal drug therapy. The detection rates of the LAMP (87.1%) and the qPCR (80.0%) were significantly higher than both culture and India ink methods.

LFA testing fulfils the WHO ASSURED criteria (affordable, sensitive, specific, user-friendly, robust and rapid) even in resource-limited regions and is widely used in HIV-infected CM patients.

This study indicates that LFA is the optimal test for non-HIV-infected patients, due to its high rates of detection and because most non-HIV-infection CM patients are also from resource limited areas. Molecular diagnostic techniques have the potential to be used as alternatives in the future, although they require more efficient protocols for the extraction of DNA from clinical CSF specimens.

Chen et al. 2016

Notomi et al. 2000

Yuchong et al. 2012