Life-saving blood test for fungal meningitis, a leading cause of AIDS-related deaths in developing countries

"The ability to quickly identify yeast infection in patients is expected to help in significantly reducing cryptococcal meningitis deaths in resource-limited countries such as those in sub-Saharan Africa," said Tom Kozel, professor of microbiology at the University of Nevada School of Medicine. "Cryptococcosis is a rare form of meningitis among otherwise healthy individuals, but an estimated 600,000 lives are lost to this infection each year in patients with AIDS. Many of these lives could be saved through early diagnosis."

If successful, the new field test to detect cryptococcal antigen will use a drop of blood from a finger-stick or a urine sample to immediately identify the presence of the disease so treatment can begin instantly, rather than having to wait for results to be processed at a lab. The point-of-care product is the result of a collaboration between Kozel and Sean Bauman, president and CEO of IMMY. The product is being developed under a licensing agreement established through the University's Technology Transfer Office and IMMY.

"We developed several antibodies to the fungus with the support of research funded by the National Institutes of Health," Kozel said. "IMMY needed an antibody that worked well with their idea for this new noninvasive procedure to introduce in developing countries where deaths are skyrocketing from HIV-related cryptococcal meningitis. We found fairly quickly that one of ours works very well."

Kozel developed the antibody used for the Cryptococcus test in his lab at the University of Nevada, Reno. Bauman commercialized the technology to make it available at low cost to patients in developing countries through IMMY, a market leader in diagnostics for fungal infections.

"One of the stipulations in our agreement for the licensing of the product with IMMY is to have this crucial test available at low cost," Ryan Heck, director of the University's Technology Transfer Office, said. "Dr. Bauman had already begun to make this happen on several avenues."

IMMY is using the antibody now for testing in Africa, but only through the traditional, time-consuming and expensive methods of venipuncture (blood draw) or spinal tap for cerebrospinal fluid. The team is working to get additional funding for studies needed to further develop and validate the new point-of-care product to make it readily available to patients.

We have submitted a version of the test that is designed for use with serum from a venipuncture or cerebrospinal fluid to the FDA for approval. We have received the CE mark, which allows sales in EU countries and many developing world countries," Bauman said. "We are already manufacturing and distributing the diagnostic for this use."

Modification of the test to a point-of-care format and clinical validation will be a major step toward meeting the World Health Organization's Global Access health requirements.

"With the point-of-care product, a health-care provider can give the test, observe the results and administer the first dose of oral medication, all within a few minutes," Kozel, who has been conducting AIDS research for more than 25 years, said. "Studies have shown early identification and treatment are essential to beat the disease; a late diagnosis means antifungal therapy will likely fail in resource-limited countries. Most patients in that setting are not diagnosed until they are very sick, and then it's too late."

Antifungals used to treat cryptococcosis are available for free or at low cost in regions such as sub-Saharan Africa. However, early diagnosis is crucial for successful drug therapy. Bauman saw this need and the staggering numbers of preventable deaths occurring in third-world countries, particularly in Africa, and decided to do something about it.

"As many as one in 10 AIDS patients in countries with limited infrastructure or resources may develop cryptococcal meningitis," Kozel said. "If we can diagnose early and begin treatment, we can save an amazing number of lives."