Cryptococcus is a fungus that is found in soil around the globe and produces spores that can be inhaled. People can get Cryptococcus early in life but never know it. If a person's immune system is weakened (for example, by HIV or use of powerful immunosuppressive drugs), Cryptococcus can cause a life-threatening infection called cryptococcal meningitis. Cryptococcosis is a devastating disease in countries with limited resources. Cryptococcosis kills 200,000 people each year; most are in sub-Saharan Africa.
Deaths due to cryptococcosis can be prevented through early diagnosis and treatment. Drugs to treat cryptococcosis are available at little or no cost to resource-limited countries. The barrier to treatment is early diagnosis of patients who are infected with the yeast - early diagnosis enables effective treatment. Previous diagnostic tests i) required a highly invasive and painful spinal tap, ii) could only be done in settings with advanced infrastructure, and iii) were expensive.
The goal of this project was an immunoassay for detection of cryptococcal antigens (CrAg) in a drop of blood. Such a test needed to meet the WHO ASSURED (Affordable, Sensitive, Specific, User-friendly, Rapid, Equipment free, and Deliverable) criteria for diagnostics for use in the developing world. This goal has been achieved by production of a lateral flow immunoassay (LFI) in a collaborative effort between the UNR Diagnostics Discovery Laboratory and Immuno-Mycologics (IMMY), a private sector partner that is focused on diagnostics for fungal disease. The Diagnostics Discovery team developed third-generation monoclonal antibodies that detect infection found across the globe; IMMY translated this discovery into a commercially viable test.
The CrAg LFI is cleared by the FDA for use with serum and cerebral spinal fluid. In December, 2011, the WHO recommended the CrAg LFI for early diagnosis of cryptococcal meningitis in all AIDS patients globally (Rapid advice: diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. A CDC factsheet recently issued a call to action to equip HIV clinics in Africa and Asia to perform Cryptococcus testing and treatment. This could save 50,000-100,000 lives each year.
Investigator: Thomas Kozel, Ph.D. (Principal investigator)
Grant support: Work that led to production of the mAbs used in the CrAg LFA was supported by NIH grant R01 AI014209, Cryptococcal polysaccharide - phagocytosis inhibition, 1975-2010.