Cryptococcus a major problem in Africa: treatment options needed

A community based study of 1,372 people living with HIV monitored intensively at two clinics in Entebbe, Uganda, between October 1995 and January 1999, has identified cryptococcus as one of their most serious health risks.

In the absence of widespread access to antiretrovirals, the UK and Ugandan researchers suggest cryptococcus vaccine development as the best strategy to pursue, with antifungal drugs as an alternative. Their findings are likely to be valid for most African countries, raising yet again the question of whether and how such treatments can be delivered.

The study was set up as a double-blinded trial of a pneumococcal vaccine; there was extremely limited access to medical treatment during the study. One third of the people enrolled died during the study, of whom 77 were diagnosed with Cryptococcus.

The median survival after diagnosis with Cryptococcus was 26 days, despite the fact that only a minority (18%) showed classic symptoms of meningitis. Headache and other neurological problems were, however, very common. The best diagnosis was provided by a serum cryptococcal antigen test, which the researchers also applied to everyone with CD4 counts below 50, to make sure they weren't simply picking up people with advanced HIV disease.

Seventy five of those diagnosed had a CD4 count below 200 at the time; 68 showed HIV disease at WHO clinical stages 3 or 4, which would be a more practical criterion for any effort to target preventive treatment or improved monitoring, given that CD4 counts are still generally unaffordable.

This Ugandan report matches previously reported Thai experience - where 15-20% of people with AIDS develop cryptococcal disease. It is approximately double the rate of Cryptococcus reported from the USA, before the introduction of antiretroviral drugs.

US studies of primary prophylaxis for Cryptococcus showed that although a weekly adult dose of 400mg of fluconazole could greatly reduce the rate of the disease, and could almost match daily treatment with 200mg, this had no significant impact on survival. There were also concerns about fungal infections becoming resistant to this drug. US public health service guidelines therefore don't recommend primary prophylaxis for cryptococcus.

In contrast, Thai guidelines now do recommend prophylactic use of fluconazole in people with HIV whose CD4 counts are below 100. Given the greater risk of Cryptococcus in Thailand than in the USA, this may be a good example of how such guidelines should vary, based on local epidemiology and risks.

Another key factor in Thailand's policy is the availability of generic fluconazole, manufactured and sold very cheaply by the Government Pharmaceutical Organisation, a division of the Ministry of Public Health.

Pfizer has responded to criticisms of the high price it charges for branded fluconazole by launching a partnership drug donation programme which is now on offer to 50 of the poorest and most heavily HIV-affected countries, for the treatment of cryptococcal meningitis and/or oesophageal candida. The company says this is not limited by time or funds. Whether they could extend it to cover everyone with HIV in Africa who falls into WHO clinical stages 3 and 4, even if they wanted to, remains to be seen.