Fungal Infections
Cryptococcal Meningitis – Global Public Health Challenges and Opportunities
Eszter Deak and Benjamin J Park Mycotic Diseases Branch, Division of Foodborne, Waterborne, and Environmental Diseases, US Centers for Disease Control and Prevention
Abstract
Cryptococcal meningitis is the leading cause of meningitis in much of sub-Saharan Africa due to HIV/AIDS. Delayed or misdiagnosis due to inadequate lab capacity and limited access to treatment are primary reasons that Cryptococcus remains an important source of mortality, despite the availability of antiretroviral drugs. This review discusses the clinical aspects and epidemiology of cryptococcal meningitis and highlights the public health challenges and opportunities encountered by public health officials in resource-limited settings.
Keywords Cryptococcal meningitis, Cryptococcus, CrAg, Cryptococcal antigen, Public health, HIV, AIDS, fluconazole
Disclosure: The findings and conclusions in this presentation/report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Acknowledgements: This information is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the Centers for Disease Control and Prevention. It does not represent and should not be construed to represent any agency determination or policy. Received: 12 January 2011 Accepted: 10 April 2011 Citation: European Infectious Disease, 2011;5(2):83–7 Correspondence: Benjamin J Park, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS C-09, Atlanta, GA 30333, US. E:
bpark1@cdc.gov
Cryptococcal meningitis was once perceived as a rare infection in immunocompetent hosts. An expanding population with acquired immunosuppression due to corticosteroids, cytotoxic treatments and immunosuppressive therapies contributed to a rise in cryptococcal disease. However, the epidemiology of cryptococcal infection underwent a dramatic change during the HIV epidemic, when the global incidence of cryptococcal meningitis soared.1–6
Today, it is one of the
most important AIDS-related opportunistic infections, particularly in the developing world. Introduction of combination antiretroviral therapy (ART) significantly decreased the incidence of cryptococcal disease in North America and Western Europe.3,7–9
However, in resource-limited
countries, such as those in sub-Saharan Africa that are still highly affected by the HIV/AIDS epidemic, Cryptococcus is currently a leading cause of meningitis and mortality.2,10–15
The epidemiology and public health issues related to cryptococcal disease continue to evolve. Management of cryptococcal meningitis presents numerous challenges for public health officials, especially in less developed countries where access to ART and antifungal drugs is still very limited. Complications of elevated intracranial pressure, commonly associated with cryptococcal meningitis, result in high morbidity and mortality. As ART becomes more readily available to the less developed countries through public health initiatives, management of immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningitis also becomes a concern. This review will examine clinical aspects of cryptococcal meningitis and will discuss the epidemiology and public health issues surrounding Cryptococcus infection. It will touch upon the occurrence of cryptococcosis in non-HIV populations, but primary focus will be devoted to HIV-associated cryptococcosis and the public health challenges this disease poses.
© TOUCH BRIEFINGS 2011
Clinical Aspects Cryptococcus neoformans, the primary aetiological agent causing cryptococcal meningitis, is an encapsulated yeast that is distributed worldwide and is ubiquitous in the environment, commonly in soil and bird droppings.16
Cryptococcus gattii, a recently emerging infection in the US Pacific Northwest, also causes meningitis; although, the geographical distribution of this organism appears to be more limited.17–19
Signs and Symptoms
Cryptococcosis presents clinically with a number of different syndromes. The fungus is acquired through inhalation and can cause a primary respiratory illness.20,21
However, disseminated disease in the form of
meningitis is the most frequent manifestation of cryptococcal infection, particularly in HIV-infected populations who have CD4 cell counts <100 cells/µl. Cryptococcal meningitis is associated with headache, fever, malaise, generalised pain, nausea and vomiting; severe cases may have neck stiffness, altered mental status, photophobia and focal neurological deficits. Because many symptoms are nonspecific and development is subacute, diagnosis of cryptococcal meningitis is often delayed.22
In
addition, patients with advanced HIV are likely to be co-infected with other opportunistic organisms, especially tuberculosis, due to the failed immune response resulting from reduced CD4 cell counts.23–27
Elevated intracranial pressure (>20 cm H2O) is often observed in patients with cryptococcal meningitis. Raised intracranial pressure,
responsible for many of the signs, symptoms and mortality associated with cryptococcal meningitis, is thought to occur as a result of inhibited cerebrospinal fluid reabsorption (CSF) due to an abundance of organisms and capsular polysaccharide.28
Serum protein is often mildly elevated, glucose levels are normal or slightly low and white 83
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