Clinical and epidemiological features of Cryptococcus neoformans var. gattii meningitis in Papua New Guinea
In the Central Province of Papua New Guinea (PNG) the annual incidence of Cryptococcus neoformans meningitis was calculated at 42.8 cases/million. Men were most frequently affected (2,2:1). In immunocompetent patients 95% of cerebrospinal fluid (CSF) isolates were var. gattii. Var. neoformans infection was associated with immunosuppression (p=0.009). In a cohort of 88 immunocompetent patients visual loss occurred in 52.6% of survivors and was associated with post-papilloedema optic atrophy in 60.9%. Progression to optic atrophy was associated with an abducens palsy (p=0.049) and high CSF cryptococcal antigen titres (p=0.036). Raised intracranial pressure (RICP) was not associated with visual loss. In survivors who had received corticosteroids visual deterioration was reduced (p=0.007) and blindness was less frequent (p=0.018), perhaps due to reduced immune-mediated optic nerve dysfunction. Mortality (34.1%) was associated with male sex (p=0.025), older age (p=0.0.39), altered consciousness (p<0.001), convulsions (p=0.002), and raised systolic blood pressure (p=0.017). RICP was common (81%) but did not predict outcome. Mortality may be reduced by lowering intracranial pressure in those with poor prognostic signs. Cell mediated immunity, assessed by an intradermal multi-test device, was similar in 37 cured, healthy patients and matched controls, although male patients had higher compound scores than controls (p=0.041). Male scores were higher in both patients (p=0.002) and controls (p=0.017). Three of four patients tested pre-treatment were anergic but survivors showed improved responsiveness post-treatment.