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Immune reconstitution inflammatory syndrome, relapse of cryptococcal meningitis and fluconazole resistance: case report A 35-year-old man with HIV/AIDS and cryptococcal meningitis (CM) developed immune reconstitution inflammatory syndrome (IRIS), a relapse of CM and a fluconazole-resistant strain of Cryptococcus neoformans during treatment with antiretrovirals, fluconazole and prednisolone. He later died. The man presented in April 2008 with a new diagnosis of HIV/AIDS and CM. After induction with amphotericin B, he received consolidation therapy with fluconazole 400 mg/day for 8 weeks [route not stated], followed by 200mg daily. Twenty-four days after his diagnosis, he started receiving zidovudine, lamivudine and efavirenz [dosages and routes not stated]. After 12 weeks of antiretrovirals, he presented with photophobia, headache, neck pain and vomiting. Lumbar puncture revealed an elevated opening pressure, a CSF WBC count of 110 cells/µL and a CSF protein level of 100 mg/dL. Tests also showed an increased CD4 count and a decreased HIV viral load. He was diagnosed with IRIS. The man received prednisolone 60 mg/day for 7 days [route not stated], then decreased by 10 mg/week over 6 weeks. His symptoms showed marked improvement. However, approximately 14 days later, C. neoformans was identified from CSF cultures. He was unable to be contacted, and continued fluconazole 200 mg/day. After 26 weeks of antiretrovirals, he presented with headache, malaise, anorexia and lethargy. His CSF protein levels and CD4 counts had increased, and CSF cultures showed increased C. neoformans growth. He declined admission, and received fluconazole 800 mg/day for 14 days, then 400mg daily for 8 weeks, for a CM relapse. After 31 weeks of antiretrovirals, he presented with similar symptoms, as well as behavioural changes, uncoordinated speech, disorientation, visual hallucinations, poor concentration, inattentiveness, staggered gait and urinary incontinence. Brain CT revealed a parietal cystic mass with hydrocephalus. He received albendazole, without improvement. After 36 weeks of antiretrovirals, he was admitted with progressive symptoms and worsening hydrocephalus. He was scheduled to undergo ventriculoperitoneal shunt placement; however, he died prior to surgery [cause of death not stated]. Autopsy findings included disseminated fungal organisms in the parietal lobe, consistent with C. neoformans. Retrospective analysis of stored cryptococcal isolates determined that the relapsed strain was identical to the strain from his initial diagnosis; however, further tests showed that fluconazole resistance had developed by the 26-week relapse. Author comment: "The management of CM-IRIS with corticosteroids may increase the risk of persistent C. neoformans infection and complications which may further increase the risk of recurrent IRIS." Musubire AK, et al. Challenges in diagnosis and management of cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings. African Health Sciences 12: 226-230, No. 2, Jun