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Preventing Deaths Due to Cryptococcus with Targeted Screening

What is cryptococcal meningitis?

Cryptococcal meningitis is an infection caused by the fungus Cryptococcus after it has spread from the lungs to the brain. Inflammation of the covering around the brain is called meningitis. Meningitis can be caused by a variety of organisms, including bacteria, viruses, and fungi. The symptoms of meningitis include headache, fever, neck pain, nausea and vomiting, sensitivity to light, and altered mental status (which can range from confusion to coma).

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Why is cryptococcal meningitis a problem?

Globally, most cryptococcal meningitis cases occur among people with HIV/AIDS. As the HIV/AIDS epidemic emerged in the 1980s, approximately 5%-10% of all AIDS patients were affected by Cryptococcus. However, the prevalence of cryptococcal disease began to decline with the introduction of new antifungal treatments and later, antiretroviral treatment (ART) in 1996. The widespread availability of ART in developed countries has helped prevent many HIV patients from reaching the immunocompromised state in which they are most vulnerable to Cryptococcus.

Although the number of cryptococcal infections has declined in developed areas of the world, cryptococcal meningitis is still a major problem in developing countries where access to healthcare is limited. CDC and collaborating researchers recently estimated the global burden of cryptococcal meningitis, and found that approximately 1 million new cases occur each year, resulting in 625,000 deaths.

Global burden of HIV-related cryptococcal meningitis

Map of Global burden of Human Immunodeficiency Virus-related cryptococcal meningitis.

Adapted from BJ Park et al., AIDS 2009;23:525-530

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The majority of cryptococcal meningitis cases occur in areas of the world with the highest numbers of people living with HIV/AIDS. Throughout much of sub-Saharan Africa, Cryptococcus is now the most common cause of meningitis. Cryptococcal meningitis is therefore one of the leading causes of death in HIV/AIDS patients, and in sub-Saharan Africa, it may kill more people each year than tuberculosis.

Causes of death in sub-Saharan Africa, excluding HIV/AIDS

Graph of Causes of death in sub-Saharan Africa, excluding Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome

Adapted from BJ Park et al., AIDS 2009;23:525-530

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How can cryptococcal meningitis be prevented?

Primary prophylaxis

One possible approach is to give an antifungal medication to all HIV–infected patients with low CD4+ T-cell counts (i.e., patients with advanced HIV) in order to prevent them from getting cryptococcal meningitis. This approach is known as "primary prophylaxis." Even though fluconazole is less expensive than amphotericin B (the type of antifungal medication that patients need after cryptococcal meningitis develops), primary prophylaxis for cryptococcal meningitis has not been shown to prevent death in most settings.

Targeted screening to prevent deaths

A second approach to combating the global burden of cryptococcal meningitis is known as "targeted screening." Research suggests that Cryptococcus is able to live in the body undetected, especially when a person's immune system is weaker than normal. A targeted screening program would test HIV-infected patients for cryptococcal antigen (an indicator of cryptococcal infection) before they begin taking antiretroviral treatment (ART). A patient who tests positive for cryptococcal antigen can take oral fluconazole, which is free of cost in many areas of the world, to help the body fight the fungus before the patient starts ART. This would prevent them from developing severe cryptococcal infection, as well as complications from their cryptococcal infection.

A new method for detecting cryptococcal antigen has recently been developed. This test is a "dipstick" test, and is simple to use on a small sample of serum (a component of blood ). The test accurately detects silent, as well as active, cryptococcal infections 95% of the time. In addition, the test is inexpensive (it costs less than $2 per test) and the results are ready in just 10 minutes.

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What is CDC doing to address the public health burden of cryptococcal meningitis?

CDC is assisting areas of the world where the prevalence of cryptococcal infections is high (such as sub-Saharan Africa and Southeast Asia) to implement targeted cryptococcal screening programs. Because many of the countries in these areas do not always have the resources to reliably detect Cryptococcus as the underlying cause of meningitis, CDC is also helping these countries build their laboratory capacity. In the future, it is hopeful that the new cryptococcal antigen dipstick test will work on urine, and possibly a finger-prick of blood, so that people in remote areas of the world will be able to use the test even if there are no advanced laboratories nearby.

CDC's call to action is to equip half of all HIV clinics in Africa and Asia to perform Cryptococcus testing and treatment, which could save 50,000 to 100,000 lives every year. Early identification of cryptococcal-infected patients in resource-limited settings may lead to more timely treatment, reduced mortality due to cryptococcal meningitis, and overall improved quality of life.

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