Dexamethasone, a cheap steroid, is being tested alongside antifungal drugs to see if it can cut the high death rate from cryptococcal meningitis, a brain infection that kills people with HIV. This matters because current antifungal treatment alone fails most patients. The body's own immune response to the yeast causes dangerous inflammation and pressure inside the skull, which can damage brain tissue or trigger strokes. Steroids like dexamethasone reduce that harmful inflammation and are already used successfully in other forms of meningitis, such as bacterial and tuberculous meningitis. The trial is being conducted in Africa and Asia, where the vast majority of cases occur. If the trial succeeds, the impact could be immediate and practical. Dexamethasone is cheap, safe, and widely available, meaning it could be added to standard antifungal treatment in the poorest regions of the world without requiring expensive new infrastructure. This would give clinicians a simple, affordable tool to lower the death rate from a disease that currently kills most of those it infects.
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Cryptococcal meningitis is a brain infection due to a yeast called Cryptococcus neoformans. It is important because it is a major cause of death in people infected with HIV. There are over 600 000 deaths each year, and most of these occur in poorer countries in Africa and Asia. Even if patients receive treatment with antifungal drugs, the death rate remains high - about 55% of people with disease in Asia and 70% in Africa will die within 3 months of diagnosis. A combination of antifungal drugs is given to kill the yeast, but researchers have been unable to improve on the antifungal treatment combination that has been recommended for the past 10 years. This is despite extensive research. We believe that new approaches are needed to try and improve outcome in this disease. The features of infectious diseases are the result of not only the infectious agent, but also the way our bodies respond to them. When our bodies? immune systems fight infection, this causes inflammation which can sometimes make disease worse. When people have cryptococcal meningitis, there is inflammation and raised pressure in the brain. The inflammation can result in parts of the brain dying (a stroke). The raised pressure leads to the brain getting squeezed (compressed) against the inside of the skull. This can impair the blood supply and can directly damage the brain tissue itself. These processes can lead to death. Steroids are drugs that can reduce inflammation, and are frequently used to lower raised pressure in brain diseases. They have been found to be useful in other forms of meningitis, such as acute bacterial meningitis and tuberculous meningitis. These diseases share some features with cryptococcal meningitis. We want to test whether giving dexamethasone, a steroid, alongside antifungal therapy, can reduce the death rate in people with cryptococcal meningitis. Dexamethasone is cheap, safe, and widely available, and if successful is a treatment that would be affordable and practical for the majority of patients around the world with this disease. We want to do this study in Africa and Asia, because this is where most people with cryptococcal meningitis live.
Anatoli Kamali (Co-Investigator)Camilla Rothe (Co-Investigator)Chau Tran Thi Hong (Co-Investigator)Cuong Do (Co-Investigator)Darma Imran (Co-Investigator)David Lalloo (Co-Investigator)Halima Dawood (Co-Investigator)Hanh Doan Thi Hong (Co-Investigator)Jeremy Day (Principal Investigator)Kinh Nguyen Van (Co-Investigator)Marcel Wolbers (Co-Investigator)Mayfong Mayxay (Co-Investigator)Robert Heyderman (Co-Investigator)Wirongrong Chierakul (Co-Investigator)
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