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Guidelines for Diagnosing, Preventing and Managing Cryptococcal Disease Among Adults, Adolescents and Children Living with HIV [Internet]. Geneva: World Health Organization; 2022.

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Guidelines for Diagnosing, Preventing and Managing Cryptococcal Disease Among Adults, Adolescents and Children Living with HIV [Internet].

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5RESEARCH NEEDS

Further research is needed to assess the value of cryptococcal antigen screening at CD4 cell count thresholds between 100 and 200 cells/mm3, which has been suggested to save costs if carried out in inpatient settings.

High cryptococcal antigen titres (>160) in blood have been found to predict subclinical meningitis. It has been suggested that blood titres could be used to predict meningitis in settings in which lumbar puncture cannot be performed or in which providing lumbar puncture for everyone screening cryptococcal antigen–positive is operationally challenging; the feasibility of this approach should be further investigated in a diversity of settings. Second-generation cryptococcal antigen lateral-flow assays that can give a high or low cryptococcal antigen result need to be evaluated as part of this approach.

Research could help improve the understanding of how to manage relapse or treatment non-response in public health settings, since the current course of action would be referral to a tertiary care centre. In tertiary care settings, intrathecal and intraventricular administration of amphotericin B have been attempted successfully, but further research is needed to establish safety and tolerability (74). Managing space-occupying lesions among people with a positive serum cryptococcal antigen test, the concurrent treatment of HIV-associated TB and cryptococcal meningitis and the best approach for treating immune reconstitution inflammatory syndrome are other research needs.

WHO has issued a Prequalification Expression of Interest for sustained-release flucytosine to simplify inpatient and outpatient treatment of cryptococcal infections. The role of azoles other than fluconazole, notably voriconazole and isavuconazole, as well as novel oral antifungal agents (such as oral encochleated amphotericin B) for the treatment and prophylaxis of cryptococcosis could benefit from further study.

There remains a need to better understand the prevalence of cryptococcal disease among children and the best diagnostic approach to enable the timely identification of disease.

WHO recommends a package of interventions for people presenting with advanced HIV disease, and implementation science research is encouraged on the feasibility and impact of cryptococcal antigen screening delivered together with other components of an advanced ART package (such as tuberculosis lipoarabinomannan assay and tuberculosis prophylaxis).

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Bookshelf ID: NBK581833
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