Treatment of cryptococcal meningitis in resource limited settings.
OBJECTIVE
Cryptococcal meningitis most commonly occurs in advanced HIV. Although diminishing in the developed world with antiretroviral therapy (ART), it remains a major problem in resource-limited settings. ART rollout will improve long-term HIV survival if opportunistic infections are effectively treated. Considering cryptococcal meningitis in that context, this review addresses excess morbidity and mortality in developing countries, treatment in areas of limited drug availability and challenges posed by combined anticryptococcal and HIV therapy.


RESULTS
From Early Fungicidal Activity (EFA) studies, amphotericin B-flucytosine is best induction therapy but often unavailable; high dose amphotericin B monotherapy may be feasible in some settings. Where fluconazole is the only option, higher doses are more fungicidal. Serum cryptococcal antigen testing may identify patients at highest disease risk and primary prophylaxis is effective; the clinical role of such interventions needs to be established. Timing of ART introduction remains controversial; early initiation risks Immune Reconstitution Disease (IRD) delays may increase mortality.


CONCLUSIONS
Amphotericin B based treatment is appropriate where possible. More studies are needed to optimize fluconazole monotherapy doses. Other research priorities include management of raised intracranial pressure, appropriate ART initiation and IRD treatment. Studies should focus on developing countries where problems are greatest.
Sloan
Derek J
DJ
School of Clinical Sciences, University Clinical Departments, University of Liverpool, Liverpool, UK. djsloan@liverpool.ac.uk
Dedicoat
Martin J
MJ
Lalloo
David G
DG
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000821:virology; D000666:Amphotericin B / Q000191:economics / Q000627:therapeutic use; D000935:Antifungal Agents / Q000191:economics* / Q000627:therapeutic use*; D003906:Developing Countries; D015725:Fluconazole / Q000191:economics / Q000627:therapeutic use; D015658:HIV Infections / Q000382:microbiology; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000191:economics* / Q000821:virology
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole