New Hope in the Treatment of Meningitis in AIDS Patients

3 million people died of AIDS in 2003, with 2.3 million people dying in Sub-Saharan Africa alone. One of the most common causes of death in AIDS patients is a very difficult to treat form of meningitis, caused by a yeast-like organism, Cryptococcus neoformans. Unlike drugs for bacterial meningitis, current treatments for cryptococcal meningitis are relatively weak and work by controlling the infection in the cerebrospinal fluid surrounding the brain. This often takes several weeks to work. 20-40 per cent of patients deteriorate and die because of this slow response to treatment and many others are left blind. In research published today in the Lancet, Dr Tom Harrison from the Department of Cellular and Molecular Medicine at St George's Hospital Medical School, and a team of researchers have found a new much more powerful way to test the activity of new drug combinations.

Progress in testing new drugs and combinations of drugs has been extremely slow due to the large number of patients needed for drug trials that rely on looking for a difference in clinical endpoints such as rate of survival.

Dr Harrison and colleagues from St George's Hospital Medical School, doctors from Thailand and doctors from the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme in Bangkok have found that by accurately quantifying the number of yeast cells in cerebrospinal fluid, before and during treatment, they were able to calculate, for the first time, the rate at which the infection was killed. Clear differences in the rate of killing with different drug combinations were seen despite the small size of the study. The most effective treatment was a combination of 2 drugs, amphotericin B and flucytosine.

Dr Harrison commented that "The technique can now be used to rapidly test the activity of other drug dosages and combinations. Only the best drug regimes need then be tested in larger trials to show differences in clinical outcome." He also pointed out that "by speeding up the progress of research, the study raises the real prospect of an improved outlook for these patients. The results are particularly timely, given the expanding access to antiretroviral treatment for HIV in many areas of the developing world. Antiretroviral drugs offer the chance of a good long-term prognosis for these patients provided they survive the acute cryptococcal meningitis.

Cryptococcal Meningitis is a disease that has received relatively little attention and funding, but in three separate studies in Africa cryptococcal meningitis was responsible for 13per cent, 17per cent, and 44 per cent of all deaths in HIV-infected patients. This compares with TB, for which treatment is more widely available and effective, which caused six per cent, five per cent and 13 per cent of deaths, respectively.