Daniel O’Brien reflects on the challenges of treating cryptococcal meningitis in developing countries.
Being a doctor in the era of bringing antiretroviral treatment (ART) to HIV-infected populations in resource-limited settings has been inspirational and rewarding. During my time involved with the treatment of AIDS in Africa, Asia, Eastern Europe and the Caribbean, I have experienced some of my proudest moments. This includes sitting in on peer-support group meetings and seeing the joy, vitality and hope of people who without ART would have been dead. For a physician it is like curing cancer – people who have been slowly dying, often in terrible pain and distress, no longer able to support family and friends and often feeling a burden to them, to then see them regain health and strength, and renew life with their family and community, is truly amazing and heart-warming to witness.
But despite the great progress over the past decade, many challenges remain. Foremost among these is the significant burden of disease and high mortality that result from the opportunistic infections that take hold when immune systems fail. Of course if HIV could be diagnosed and treated earlier before significant immune suppression develops, if drugs were more readily available to prevent these diseases, if diagnostic tools allowed more accurate and easier diagnosis of these conditions, then their impact would be significantly lessened. Further significant gains could also be made if treatments for these conditions were more available, more effective, less toxic and cheaper in resource-limited settings.
Cryptococcal meningitis is high on the list of diseases that need to be better prevented, diagnosed and treated. Even in resource-rich environments it is difficult to manage, but in resource-limited settings it is devastating. In the HIV/AIDS programmes of Médecins Sans Frontières (MSF) globally it is a major cause of disease and is associated with the highest mortality rate of all opportunistic infections. Almost every day in my work in MSF hospital wards in countries afflicted by high HIV prevalence I would come across a patient desperately unwell or even unconscious whilst suffering from cryptococcal meningitis. Under very difficult conditions we would administer treatment but sadly often to no avail.
In some situations less effective treatments such as fluconazole alone have to be used as more effective treatments such as amphotericin B and 5-flucytoseine are not available, too expensive or not feasible or safe to administer. Often the diagnosis can be uncertain due to a lack of diagnostic tools to confirm it. On many occasions I have pondered what a difference it would make to have culture and sensitivity services available when assessing a deteriorating patient with cryptococcal meningitis to help distinguish between apparent treatment failure due to inadequate therapy, drug resistance or immune reconstitution disease. Then there are the enormous difficulties in trying to diagnose and treat the dreaded and often fatal disease complication of raised intracranial pressure that requires repeated lumbar punctures and monitoring of pressures often without the tools to do so. But at least in MSF programmes our access to treatment and care was likely better than in many others – for many patients and health-care staff the possibilities for treatment and care are much worse.
It is encouraging to see research published in PLOS Medicine that highlights the constraints of treating cryptococcal meningitis in resource-limited settings, and provides evidence for cost-effective strategies to address them. However more research is urgently required to determine the optimum treatment for cryptococcal meningitis under field conditions in resource-limited settings that considers its effectiveness, toxicity and ease of acquisition, distribution and administration. In addition efforts are required to improve access to the best drug treatments, early HIV diagnosis, earlier initiation of ART, and the tools to diagnose and prevent cryptococcal meningitis in order to impact on its significant associated morbidity and mortality. Programme planners, governments, donors and international organizations urgently need to make these things a reality if health-care workers in these settings are to avoid the frustration of watching patients suffer and die of cryptococcal meningitis and to realize the gains that life-saving ART can bring to the HIV-infected people under their care.
Daniel O’Brien is a specialist advisor with the Manson Unit, MSF-UK focusing on HIV/AIDS, tuberculosis and Buruli ulcer. He is also an Infectious Diseases specialist with Geelong and Royal Melbourne Hospitals, Australia and Clinical Associate Professor with the University of Melbourne, Australia.
Rajasingham et al. (2012) Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis. PLOS Medicine
Farlow (2012) The Challenges and Possibilities of Reducing Deaths from Cryptococcal Meningitis in Sub-Saharan Africa. PLOS Medicine