Cryptococcal Meningitis- HIV In Children

Cryptococcal meningitis occurs less frequently among HIV infected children (1%) than adults ^{(40, 41, 42)}

Clinical features: Patients present with fever, headache and altered mental status. HIV infected children between 6-12 years of age those with severe immunosuppression are prone. Neck stiffness and focal neurological deficit is rare.

Diagnosis: - CSF analysis with India ink preparation is a must. Cryptococcal antigen on CSF should be sent in centers where facilities are available. In cryptococcal meningitis, CSF pressure should be measured as CSF cell count, glucose and protein may be virtually normal but opening pressure may be elevated.

CSF antigen detection may be negative in culture positive cryptococcal meningitis; high titers of antigen (prozone effect), low levels of antigen or nonencapsulated organisms ^{(43, 44)}. However, cryptococcal antigen titers in CSF are helpful in evaluation response to therapy. A CSF titer of > 1:8 after completion of therapy indicate treatment failure or relapse (45). Fungal cultures from CSF or blood may be useful especially for susceptibility testing in patients with refractory disease.

Treatment: Cryptococcal meningitis is a severe infection and initial treatment consists of a combination of amphotericin B (0.7-1.5 mg/kg/day) plus flucytosine (100 mg/kg/day in 4 divided doses) for a minimum of 2 weeks. In India, flucytosine is not available and amphotericin B alone can be used. Liposomal Amphotericin B (3-5 mg/kg/day) is found to be useful ^{(46, 47)}. After successful initial therapy, consolidation therapy with fluconazole (5-6 mg/kg/do IV or orally BD) for a minimum of 8-10 weeks is recommended ^{(48, 49)}. If fluconazole cannot be given, itraconazole can be used as an alternative (2-5 mg/kg/dose BD). In refractory cryptococcal meningitis, intrathecal or intraventricular amphotericin B can be used.
For elevated intracranial pressure, serial lumbar punctures to relieve CSF pressure may be required.

Prophylaxis
Secondary prophylaxis: - After successful treatment of cryptococcal meningitis, secondary prophylaxis should be given life-long, Fluconazole (3-6 mg/kg/day, max: 200 mg) may be effective. For adolescents receiving ART, maintenance fluconazole may be stopped if immune reconstitution occurs and CD4 count increases to between 100-200 cells ^{(50, 51)}. Safety of discontinuation of secondary prophylaxis in children has not been studied extensively.
Primary prophylaxis: - Antifungal prophylaxis is not to be used routinely to prevent cryptococcosis because of rarity of the disease, lack of survival benefit, possibility of drug interaction and potential development of antifungal drug resistance.