Cryptococcus neoformans Infection
Cryptococcus neoformans Infection
Cryptococcus neoformans is a yeast that is the sole species of the genus capable of causing mycotic (fungal) disease. There are three versions of C. neoformans, based on differences in the capsule that surrounds the yeast, in the use of various sugars as nutrients, and in the shape of the environmentally resilient structures called spores that can be produced by the yeast. C. neoformans variety neoformans causes most of the cryptococcal infections in humans.
C. neoformans causes cryptococcosis. The infection begins in the lungs following the inhalation of the microorganism, particularly the small form of the organism called a basidiospore. These spores are smaller than the growing (vegetative) form of the yeast, and so can penetrate deeper into the very small air passages (alveoli) of the lung. In the warm and moist conditions of the lung, the basidiospores can increase in size and normal growth of the yeast can resume.
When the yeast begins to grow, a capsule that is usually only minimally produced by the spores is exuberantly produced. Like the capsule produced by some bacteria, the capsule of C. neoformans is made of sugars. The capsule helps shield the yeast from the immune response of the host, in particular the engulfing (phagocytosis) and breakdown of the yeast by a type of immune cell called a macrophage.
C. neoformans is equipped with enzymes known as proteases, which degrade proteins, as well as enzymes that destroy phospholipids. Both proteins and phospholipids are important components of the cell wall that surrounds cells. This causes the destruction of host cells, which makes it easier for C. neoformans to enter the host cells and to invade tissue.
Evidence from laboratory studies indicates that C. neoformans is not only capable of evading the host's immune response, but may also actively impair the response. This would explain the observation that people who survive a bout of cryptococcal meningitis can continue to have a malfunctioning immune system afterward.
Most commonly, C. neoformans causes the form of meningitis called cryptococcal meningitis. (Meningitis can also be caused by bacteria or viruses.) People who are immunocompromised—their immune system is not functioning properly due to infection with, for example, the human immunodeficiency virus (HIV) or deliberate suppression to lessen the rejection of a transplanted organ—can are at particular risk for a potentially fatal infection with C. neoformans. The yeast can become more widely distributed in the body. This can produce inflammation and damage of the nerves in the brain (meningitis); and infections of the eye (conjunctivitis), ear (otitis), heart (myocarditis), liver (hepatitis), and bone (arthritis). Prior to the explosion of the number of cases of AIDS and the more routine use of immunosuppressant drugs, C. neoformans infections were rare.
C. neoformans is found all over the world. It is a natural inhabitant of some plants, fruits, and birds such as pigeons and chickens. The microbe is often transferred to humans via bird feces. As the feces dry, the yeast spores can be wafted into the air to be subsequently inhaled.
Treatment for cryptococcal meningitis usually includes anti-fungal drugs such as fluconazole. Often a compound called amphotericin B is also administered. It is usually given intravenously, which produces a higher concentration of the drug throughout the body. This is important since the infection can quickly become widespread. The treatment has a variety of potential side effects, including fever, chills, headache, nausea with vomiting, diarrhea, kidney damage, and a decrease in the number of red blood cells due to the inhibition of bone marrow. Fewer red blood cells means less oxygen and iron is capable of being transported throughout the body, a condition called anemia. Also, some people can have an allergic reaction to the drug.
Amphotericin B is available as a liposome preparation; that is, the drug is packaged inside a sphere made of lipid. The liposomes can also contain proteins that recognize target proteins in the patient. This allows the drug to be more specifically targeted to a site within the body, rather than applying the drug generally.
Prospects for recovery are good if the infection is identified and treated while it is still confined to the lungs. However, spread of the infection beyond the lungs, especially to the central nervous system, is a serious complication, and can threaten the life of someone who is immunocompromised.
WORDS TO KNOW
BASIDIOSPORE: A fungal spore of Basidomycetes. Basidomycetes are classified under the Fungi kingdom as belonging to the phylum Mycota (i.e., Basidomycota or Basidiomycota), class Mycetes (i.e., Basidomycetes). Fungi are frequently parasites that decompose organic material from their hosts, such as those growing on rotten wood, although some may cause serious plant diseases such as smuts (Ustomycetes) and rusts (Teliomycetes). Some live in a symbiotic relationship with plant roots (Mycorrhizae). A cell type termed basidium is responsible for sexual spore formation in Basidomycetes, through nuclear fusion followed by meiosis, thus forming haploid basidiospores.
IMMUNOCOMPROMISED: A reduction of the ability of the immune system to recognize and respond to the presence of foreign material.
MYCOTIC: Mycotic means having to do with or caused by a fungus. Any medical condition caused by a fungus is a mycotic condition, also called a mycosis.
Other the past several decades, the prevalence of cryptococcal illness on Vancouver Island on Canada's west coast has been increasing. Researchers from the United States Centers for Disease Control and Prevention and Health Canada who have been studying the illnesses have concluded that the increasingly temperate climate of the region is favoring the expansion of the yeast into a region that it formerly did not occupy. With regions of the world expected to warm over the next century, the geographic range of C. neoformans may increase.
As about 85% of cases of cryptococcosis in the United States occur among HIV-positive people, finding an affordable and readily available prevention strategy for persons whose immune system is already weakened is an important challenge for researchers. Globally, the increase in AIDS has made many more people vulnerable to C. neoformans infection.
Black, Jacquelyn G. Pigeons: The Fascinating Saga of the World's Most Revered and Reviled Bird. New York: Grove Press, 2006.
Blechman, Andrew D. Microbiology: Principles and Explorations. New York: John Wiley & Sons, 2004.
Centers for Disease Control and Prevention. “Cryptococcosis” <http://www.cdc.gov/ncidod/dbmd/diseaseinfo/cryptococcosis_t.htm> (accessed March 8, 2007).