Experts aim to halve the number of deaths from cryptococcal meningitis by changing drug treatment programmes after the results of a new medical trial.

ACTA trial


Cryptococcal meningitis, a fungal infection and the commonest form of meningitis in many parts of Africa, is responsible for more than 180,000 deaths per year worldwide, mainly in HIV-infected patients. Current treatment is difficult and mortality rates in Africa in routine care are in the region of 70% - higher than for the Ebola virus infection.

Now an international team led by Professor Tom Harrison at the Centre for Global Health in the Institute of Infection and Immunity at St George’s, University of London, has published results of their Advancing Cryptococcal Treatment for Africa (ACTA) Trial which shows relatively simple changes can save tens of thousands of lives a year.

The internationally recommended treatment is two weeks of the drug amphotericin B plus flucytosine; but amphotericin needs intravenous administration and close laboratory monitoring because of serious side effects including anaemia and renal impairment. In addition, the drug flucytosine is not currently available in most of the world because of its cost and the fact that the drug is not used for any other major infection.

The result is that most centres across Africa and elsewhere have relied on an alternative drug, fluconazole. However this is less effective, with mortality as high as 75% at one year.

The 5-year trial has demonstrated two new treatment plans that are either as good as or better than the internationally recommended approach.

The first is a two-week oral combination of high-dose fluconazole plus flucytosine, which saved as many lives as the current gold standard so, if implemented, could halve the number of deaths from the condition.

The second is a shorter, and therefore safer and more practical, one-week course of amphotericin B plus flucytosine. This one-week programme proved to be superior to the current gold standard with mortality rates as low as 24%, compared to 38%.

Professor Tom Harrison said: “We are calling for the generic manufacture and widespread availability of the drug flucytosine, and plan large-scale programmes of implementation with partner countries and international agencies that could result in the mortality from this dreaded infection being halved.

“It’s been a long hard slog and meant work over a 15-year period but we now have the results that could mark the beginning of widely available life-saving treatment for this disease which currently claims the lives of tens of thousands of people each year.”

The St George’s team worked with partners at Liverpool School of Tropical Medicine, The Institute Pasteur, and hospitals in Malawi, Zambia, Cameroon and Tanzania for the study whose results were announced at the International AIDS Society meeting in Paris on July 24.

The trial, funded by the UK Medical Research Council and the ANRS (the French national agency for research on AIDS and viral hepatitis), is the largest conducted to date, including over 700 participants, on the treatment of cryptococcal meningitis.

Read more about the Centre for Global Health.

Related:

Cryptococcal meningitis should be classified as a ‘neglected tropical disease’, researchers say

ACTA: Developing novel treatments for HIV-associated cryptococcal meningitis in Africa.

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