Background Cryptococcosis remains one of the four commonest invasive fungal infections world-wide. In 2014, there were an estimated 220,000 new cases of cryptococcal meningitis per annum, predominantly in African HIV- infected populations , with 180,000 deaths1 and an unknown incidence of debility/chronic sequelae. Acute management with induction and initial consolidation therapy is relatively well defined, especially in HIV-infected patients, and must be accompanied by close control of intracranial pressure. Post-acute (chronic) management is less well-defined.
Aims To highlight issues to consider and approaches to management of post-acute (chronic) neuro-cryptococcosis and its sequelae. For the purpose of this presentation, chronicity will be defined as greater than one-month post-initiation of antifungal therapy.
Key points
- Neurocryptococcosis is a meningo-encephalitis with a different pathogenesis from bacterial meningitis – invading the CNS initially via transit across cortical post-capillary venules.
- In apparently healthy hosts, cryptococcomas and obstructive hydrocephalus or more common than in immunocompromised (especially HIV-positive) hosts, and in C gattii infection (especially with concurrent with pulmonary lesions).
- Mortality correlates with delayed sterilisation of CSF, cryptococcomas, high and/or prolonged raised intracranial pressure, obstructive hydrocephalus and hyper-inflammatory syndromes. These sequelae/complications should be ruled out in cases with prolonged positive CSF cultures (> 1 month) and when clinically indicated. Although fluconazole MICs do not correlate directly with clinical outcomes, they are recommended in cases of persistent infection.
- IRIS can, uncommonly, occur in the presence of positive cryptococcal cultures.
- Cerebral cryptococcomas: Extension of induction therapy is recommended. Adjunctive surgery may be needed if lesions are large and accessible. Adjunctive corticosteroids are recommended if there is surrounding oedema and mass effect (having excluded IRIS).
- The risk of IRIS is inversely proportional to the degree of host immunosuppression. Corticosteroids are of some therapeutic benefit, but dose reductions must be slow.
- Predicting which patients are likely to have a complicated course, treating sequelae or complications rapidly and monitoring for at least 12 months leads to better outcomes.