A 12-year-old boy presented to the Kilimanjaro Christian Medical Centre (KCMC) referral hospital in Moshi, Tanzania, with complaints of 8 days of headache associated with photophobia, neck pain, and vomiting (Figure 1). Eleven weeks earlier, he was admitted at the regional government hospital for similar complaints when he was diagnosed with HIV and treated presumptively (cerebral spinal fluid [CSF] evaluation negative; Table 1) for cryptococcal meningitis (CM) initially with 800 mg intravenous (IV) fluconazole (induction therapy) then transitioned to oral 400 mg (consolidation therapy) according to Tanzanian National Guidelines. Cryp-tococcal antigen (CrAg) lateral flow assay (LFA) was unavailable. He also received trimethoprim/sulfamethoxazole prophylaxis and IV ceftriaxone for possible bacterial meningitis. Three weeks after CM treatment, his clinical status improved and he began antiretroviral therapy (ART) with abacavir, lamivudine, and efavirenz. One month after starting ART and receiving fluconazole consolidation therapy, this patient reported no vomiting, resolution of his headache, and weight gain. Seven weeks after starting ART, he had a relapse of his original presenting symptoms (headache and vomiting) leading to presentation at KCMC.
At KCMC, he was slightly tachypneic (respiratory rate = 28 breaths/min), normocardic (heart rate = 87 beats/min), afebrile (temperature = 36.2 C), with an oxygen saturation of 99%. He was severely malnourished (weight = 23 kg; height = 136 cm; body mass index = 12.4 kg/m2; Z = -3) and had a deduced Glasgow Coma Score of 14. He had a positive Kerning's and Brudzinski's sign, papilledema, and mild ataxia. CSF analysis demonstrated a white blood cell count of 6 x 106 cells/L, no organisms on gram stain, and India Ink and CSF CrAg were positive. Urea and creatinine measurements remained unremarkable throughout admission. He received IV fluconazole (240 mg) daily until discharge, prophylactic trimethoprim/sulfamethoxazole, and continuation of his ART. Therapeutic lumbar punctures removing 15 to 25 cc of fluid were performed weekly. Opening pressure was not documented, but was noted to be "high" in one of the procedure notes. The therapeutic lumbar punctures offered relief for a few days, but symptoms of severe headache quickly returned. Acetazolamide was started to reduce intracranial pressure and daily prednisone was initiated for presumed immune reconstitution inflammatory syndrome (IRIS). His CD4 level was not available at the time of KCMC admission, but prior to initiating ART he had a CD4 count of 65 cells/microL. At this admission, his viral load was fully suppressed (HIV RNA <20 copies/mL). Once stabilized, he was discharged home with CM consolidation therapy (fluconazole 400 mg daily), ART, and an oral prednisone taper.
One week after discharge, he was readmitted to KCMC with similar complaints of headache and vomiting. Fundoscopy showed papilledema. CSF was CrAg-positive and Gene Xpert was negative for tuberculosis. After 2 weeks, his clinical condition still had not improved, so IV amphotericin B was added to his fluconazole regimen while his steroids were tapered. Despite escalation in management, his condition continued to deteriorate and he died soon after.