Management of cryptococcal meningitis in AIDS: the need for specific studies in developing countries.

Cryptococcosis is a deadly opportunistic infection caused by an encapsulated yeast, Cryptococcocus neoformans. The major predisposing factor is the profound cellular immune defect caused by HIV infection. Despite major advances in the treatment of HIV infection with HAART, cryptococcosis is still diagnosed in Western countries, especially in patients who have limited acess to health care [1, 2]. In sub-Saharan Africa and Southeast Asia, cryptococcosis remains a major concern [3, 4], representing the third most common cause of hospital admission and the cause of 44% of HIV infection–related deaths in South Africa [5]. Meningitis is diagnosed in ∼90% of HIV-infected patients who have cryptococcosis [3, 6], and C. neoformans currently represents the first or second microorganism that causes meningitis in adults in several African countries [7, 8]. Recent data obtained by the French Cryptococcosis Study Group [6] have suggested that the observation of any evidence of cryptococcosis on the basis of positive antigen detection, the presence of encapsulated yeasts during direct examination or histological analysis, and/ or the isolation of C. neoformans from any body site should be immediately followed by sampling and culture of CSF, blood, and urine samples and by serum antigen titration, to evaluate fungal burden and to optimize induction treatment. On the basis of the results of several carefully conducted clinical trials, the 2000 Infectious Diseases Society of America guidelines for the management of cryp-tococcal meningitis [9] recommends a combination of amphotericin B (AmB; 0.7–1 mg/kg/day or a lipid formulation in the case of renal impairment) and oral flucytosine (100 mg/kg/day) for 2 weeks, followed by fluconazole (400 mg/day) for a minimum of 8 weeks. The proposal to add flucytosine to AmB therapy was made on the basis of the results of the study by van der Horst et al. [10], which showed that 2 weeks of combination therapy was an independent factor that was associated with CSF sterilization. In addition, during the pre-HAART era, Saag et al. [11] demonstrated that the best predictive factor for relapse was the lack of flucytosine administration during the initial 2 weeks of therapy. Since then, the results of several studies have reinforced the potential value of flu-cytosine in combination for the management of cryptococcal meningitis in HIV-infected patients. Brouwer et al. [12], in a study performed in Thailand, elegantly pointed out that clearance of cryptococci from the CSF occurred significantly more quickly with AmB plus flucytosine than with AmB alone, …