Abstract
Cryptococcosis diagnosis has been recently improved by the use of rapid cryptococcal antigen testing with lateral flow assays, which have proved sensitive and specific. Using “test and treat” screening strategies for cryptococcal disease with these tests has been showed effective in reducing cryptococcal meningitis (CM) in HIV-infected patients. Recommended induction, consolidation, and maintenance therapeutic strategy for CM is widely unavailable and/or expensive in low and middle-income settings. New therapeutic strategies, mostly using reduced duration, have recently shown acceptable outcome or are currently tested. Diagnostic and therapeutic guidelines for cryptococcal disease in limited resources countries are undergoing a paradigmatic shift.
Highlights
The diagnosis of cryptococcal meningitis (CM) and more broadly, disseminated cryptococcosis, is made by direct examination of a pelleted biological fluid using India ink with the typical observation of rounded cells measuring about 3-10 μm in diameter surrounded a thick capsule represented as a clear halo
Thereafter, we summarise the main studies and clinical trials which have helped to improve cryptococcosis outcome and survival in the last decades
Amphotericin B with flucytosine - The use of flucytosine combined with amphotericin B for CM therapy was already observed in a study in 1979, before the HIV pandemic, where authors concluded that the combination therapy allowed more rapid sterilisation of the cerebrospinal fluid (p < 0.001) and less nephrotoxicity
Summary
The diagnosis of cryptococcal meningitis (CM) and more broadly, disseminated cryptococcosis, is made by direct examination of a pelleted biological fluid using India ink with the typical observation of rounded cells measuring about 3-10 μm in diameter surrounded a thick capsule represented as a clear halo Sensitivity of this technique is around 86% (Kambugu et al 2008, Boulware et al 2014b) but can be lower in HIV-negative patients in association with a low fungal burden (Dromer et al 2007). 2|6 Cryptococcosis: diagnosis and treatment Timothée Boyer Chammard et al. Pre-ART CrAg screening and pre-emptive therapy In HIV-infected patients with advanced AIDS disease, the prevalence of CrAg positivity ranged from 2-21%, with a median of 6% (IQR: 5-7) (Temfack et al, unpublished observations). In CrAg positive patients who received preemptive fluconazole initiated at 800 mg/day, there was a significant decrease in the relative risk of developing CM (from 21.4-6%) and of incident mortality (Temfack et al, unpublished observations)
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