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Fungal Pathogens in Humans.

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Sarah Wagg 010404720 March 3, 2003 Fungal Pathogens in Humans Introduction Though there are well over seventy thousand true fungal species that inhabit this planet, very few of these cause diseases in humans, called mycoses. Many more fungal diseases are associated with various plants and other animals. Mycoses in humans can range from superficial infections to deep-seated systemic infections that are life threatening. The superficial mycoses follow a similar pattern to most bacterial and viral diseases: incubation period is relatively short, onset of disease is sudden and symptoms decrease in severity over time, often with spontaneous healing. Deep-seated mycoses, however, show similarities to aberrant bacterial diseases such as leprosy and tuberculosis: incubation is short, onset of symptoms is varied, and symptoms increase in severity, often resulting in death (Ainsworth 1952). The types of mycoses can be broken into three major groups: cutaneous infections (affecting the outer layers of skin), subcutaneous infections (affecting the tissue below the skin) and systemic (affecting multiple organs in the body). These infections differ from one another in severity of symptoms and mode of transmission, and cause a wide variety of diseases in humans. This paper does not attempt to cover all human mycoses, but rather those that are interesting from a mycologist's perspective. Cutaneous Infections Cutaneous fungal infections are those that involve the outer layers of the skin and cause an inflammatory or allergic response. Most cutaneous infections are caused by specialized fungi that thrive on keratinised tissues such as skin, hair, and nails (Kendrick 2000). These organisms are a taxonomically related group of fungi called the dermatophytes. There are approximately forty species of dermatophytes grouped into three genera: Epidermophyton, Microsporum and Trichophyton. Those with sexual stages have teleomorphs in Nannizzia or Arthroderma (Cole and Hoch 1991). Dermatophytes are also classified on the basis of the environment in which they are often found. Geophillic strains are able to grow and strive in soil, surviving with a saprophytic mechanism, but these can also be isolated from the hair of some animals. ...read more.


Again, there have been no deaths associated with this infection, as it is not likely to spread to other regions of the body. Systemic Infections Systemic infections result from inhalation of spores produced by the fungi that often live in soil or rotting vegetation. Unlike subcutaneous diseases, these infections have the ability to spread to several organs in the body. The systemic infection Histoplasmosis is caused by the ascomycete Histoplasma Capsulatum. It is endemic in specific geographical areas, such as the Ohio and Mississippi River valleys (Kern 1985). Infection is established after the inhalation of microconidia and hyphae. After this, most people (approximately 90%) do not show any symptoms. Those that do become ill complain of mild, non-specific symptoms such as fever, chills, headache, chest pain, weight loss and arthritis. Occasionally, the lung infection can become chronic, and the fungus forms small nodules in the lungs called histoplasmomas (Campbell and Stewart 1980). These nodules degrade the outer layers of the lung, and often resemble tuberculosis in appearance and symptomatology. Inflammation of the membranes covering the heart (pericarditis) and fibrosis of major blood vessels are also associated with this disease (Klein 2000). Though there have been reported cases of spontaneous recovery of chronic pulmonary histoplasmosis, prognosis is rather grim-many chronic patients die within a few weeks to a few months (Ainsworth 1952). An interesting aspect of Histoplasma is that it lives a double life: one as a soil-dwelling mycelial saprobe and another as a pathogenic yeast living in mammalian tissues. This mycelial form is found in soil enriched with bird and bat droppings, and produces infections spores (Klein 2000). When the soil is disturbed, spores are inhaled into the respiratory tract, and the temperature change from twenty-five degrees Celsius to the mammalian body temperature of thirty-seven degrees Celsius stimulates the growth of the yeast form (Magrini and Goldman 2001). In an attempt to destroy the foreign yeast, the host's macrophages and other cells of the reticulo-endothelial system engulf them (Klein 2000). ...read more.


One of the key genes responsible for filamentous growth is TUP1, first isolated from Saccaromyces cerevisiae, which until 1992, was not thought to have a filamentous form at all (Hoffman 1992). By isolating and disrupting TUP1, researchers have observed constitutive filamentous growth. This discovery leads to possible modes of treatment, perhaps by supplementing an infected individual with a compound that stimulates transcription of TUP1, in hopes to prevent filamentous growth (Braun and Johnson 1997). Treatment of Human Mycoses There are several drugs available to treat fungal infections in humans. Until quite recently, however, diseases such as Histoplasmosis, Aspergillosis, and Blastomycosis were almost always fatal (Kendrick 2000). Nyastatin, produced in 1950, was one of the first successes in treatment of superficial and oesophageal candidiasis (Kendrick 2000). Amphotericin and Ketoconazole are useful in treating deep-seated systemic mycoses, but have several unpleasant side effects, and should only by administered as a last resort. Dermatophyte infections can also be treated using Canestin, Griseofluvin, Tolnaftate, and most recently, Terbinafine, with relatively mild side effects (McClellan et al. 1999). Some mycoses can also be prevented by diet and lifestyle changes. For example, candidiasis can be prevented by keeping skin dry and wearing loose clothing, as fungal growth is encouraged by moist conditions. Also, several studies have shown that eating yoghurt every day will restore the natural flora of lactobacilli in the body, preventing yeast infections (Lewis 1992). Conclusions Despite the array of possible mycoses with which humans have been afflicted, severe systemic and subcutaneous diseases are still quite rare in North America. Due to the increasing number of immunocompromised individuals, however, rare fungal diseases once found only in other animals are causing complications and death in these people. The ability of kingdom Eumycota to thrive in both saprophytic and parasitic environments and change its morphology has contributed greatly to the success of fungi on Earth. As we continue to observe the evolution of saprophytic fungi to parasitic organisms, we must expect to see more mycoses affecting humans-we simply present an environment too ideal to pass up. ...read more.

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