NIAID-supported research for fungal diseases includes studying the basic biology of the organisms that cause these diseases to developing vaccines and better ways to diagnose, treat, and prevent infection.
Candida are yeast that can be found on the skin, mucous membranes, and in the intestinal tract. Overgrowth of these yeasts can cause symptoms to develop. For example, candidiasis that develops in the mouth or throat is called “thrush” or oropharyngeal candidiasis. Candidiasis in the vagina is typically referred to as a “yeast infection.” For people with certain risk factors, overgrowth of these fungi can cause invasive candidiasis—a serious infection that can affect the blood, heart, brain, eyes, bones and other parts of the body. Candidemia, a bloodstream infection with Candida, is the most common form of invasive candidiasis and frequently affects hospitalized patients. There are more than 20 species of Candida yeasts that can cause human infection, but most infections are caused by Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Candida auris is a newly emerging fungal species that is difficult to identify and is often resistant to multiple antifungal drugs.
NIAID-supported researchers are developing genetic tools to determine the cause of drug resistance, to understand how Candida becomes an invasive pathogen, and to identify new medications for treating infection. NIAID support has also led to the development of assays to rapidly detect candidemia and an experimental vaccine to protect against Candida infection.
Cryptococcus fungi are found in the soil throughout the world and are often associated with bird droppings. There are two main species that cause disease: Cryptococcus neoformans and C. gattii. These fungi rarely cause infections in healthy individuals but can be very serious for individuals with compromised immune systems, such as those with HIV/AIDS. Infection generally occurs when someone breathes in the fungus. The most common sites of infection are the lungs and nervous system. In sub-Sharan Africa, cryptococcal meningitis is the most common cause of meningitis in adults and is a leading cause of death in people with HIV/AIDS.
NIAID-supported researchers have sequenced the genomes of multiple species of Cryptococcus to determine how they target the brain and why some clinical strains cause severe disease, while others do not. Additional NIAID-supported research is focused on identifying new fungal pathways that can be targeted for drug development; understanding how the immune response resolves Cryptococcal infection; and developing a vaccine to protect people at risk of Cryptococcal infection.
Aspergillus is a common mold (a type of fungus) found indoors and outdoors. People breathe in numerous Aspergillus spores every day without becoming sick. However, people with weakened immune systems or lung diseases are at-risk for developing health problems caused by Aspergillus. There are many types of aspergillosis, ranging from mild to serious disease. For example, Aspergillus can cause inflammation in the lungs (allergic bronchopulmonary aspergillosis) or sinuses (allergic Aspergillus sinusitis) without causing infection. Invasive aspergillosis is an uncommon, serious infection of the lung or other body systems and is a major cause of mortality in immunocompromised individuals.
NIAID-supported researchers are identifying the fungal pathways responsible for human infection and determining how the immune system responds to and clears Aspergillus infections. Drug resistance is an emerging concern for Aspergillus, and NIAID is supporting research to determine the cause of increasing resistance and to identify new antifungal therapeutics to treat aspergillosis. Aspergillosis can be difficult to diagnose; therefore, NIAID is supporting research to rapidly detect lung infections through breath-based diagnostics.
Coccidioidomycosis (Valley Fever)
Coccidioidomycosis, also called Valley Fever, is an infection caused by the fungi Coccidioides immitis and C. posadasii. These soil-dwelling fungi are found in arid, desert-like conditions throughout the southwestern United States (primarily Arizona, California, Nevada, New Mexico, Texas and Utah), Mexico, Central and South America. The fungi were recently found in south-central Washington. Infection generally occurs by breathing Coccidioides spores into the lungs and, unlike most serious fungal diseases, healthy people are at risk for Coccidioides infection. In the United States, the highest incidence of infection has occurred in California and Arizona. These states reported more than 11,000 cases of Valley Fever in 2016. It is estimated that Valley Fever causes 15 to 30% of community-acquired pneumonia. However, due to low testing rates, Valley Fever may be under-reported. Valley Fever can range from a self-limiting, mild, flu-like disease to severe disseminated infection that can require life-long therapy.
NIAID-supported researchers are using genomics to understand why some strains of Coccidioides are more infectious than other strains and why some individuals are more susceptible to the most severe form of the disease, disseminated coccidioidomycosis. NIAID also supports the development of rapid diagnostics to identify infected individuals, novel therapeutics to treat the disease, and several vaccine approaches to prevent Valley Fever.
Currently, there is no vaccine to prevent Valley fever, despite consistent efforts since the 1960s. Because Valley fever infection usually provides protective immunity from reinfection, a safe and effective vaccine is generally expected to provide durable immunity. A vaccine against Coccidioides infection could contribute to the public health of the residents of the affected areas in the United States and other countries. In order to more broadly protect against Coccidioides infection, the NIAID Strategic Plan for Research to Develop a Valley Fever Vaccine reflects the benchmarks the National Institute of Allergy and Infectious Diseases believes necessary to develop a Valley fever vaccine.
Histoplasmosis is caused by the fungus Histoplasma capsulatum. This fungus is found in soil that contains large amounts of bird or bat droppings. Histoplasma can be found throughout the world, but in the United States, it is mainly found in the central and eastern states, particularly along the Ohio and Mississippi River valleys. People develop infection after breathing in microscopic fungal spores, particularly during activities that disturb contaminated soil. In healthy people, the disease is usually self-limiting and is characterized by mild flu-like symptoms. In people with weakened immune systems, histoplasmosis can be severe and require long term antifungal treatment to resolve the disease.
NIAID-supported researchers are identifying the pathways necessary for the fungi to establish infection and the human immune factors that are required to clear the infection. NIAID also supports the development of rapid assays to detect Histoplasma infection.
Blastomycosis is an infection caused by the fungus Blastomyces dermatitidis. This fungus is found in moist soil and decomposing material, such as wood and leaves. Blastomyces can be found in Canada, particularly around the Saint Lawrence River, and in areas of the United States surrounding the Ohio and Mississippi River valleys and the Great Lakes. The fungus causes infection mainly in the lungs through inhalation of fungal spores. Most people who breathe in the fungal spores do not become sick, but some will develop flu-like symptoms. In individuals with weakened immune systems, Blastomyces can cause serious infection that can spread beyond the lungs to other body systems, such as the skin, bones, and central nervous system.
NIAID-supported researchers are determining how the fungus alters the immune system to establish infection in healthy individuals and how a protein from Blastomyces can help improve the activity of vaccines.
Pneumocystis pneumonia, called PCP, is caused by the fungus Pneumocystis jirovecii. The fungus is spread through the air, from person to person. PCP is extremely rare in healthy people, but the fungus that causes the disease can live in their lungs without causing symptoms. Individuals with weakened immune systems, such as people with HIV/AIDS, cancer patients, and people with inflammatory or autoimmune diseases taking certain medications that weaken the immune system, are at greatest risk for serious PCP infections requiring treatment.
NIAID-supported researchers are developing new diagnostics and therapies to treat PCP.