FUNGI AS HUMAN PATHOENS

Fungi as Human Pathogens

Introduction
Fungi that are pathogens are usually plant pathogenic Fungi. There are comparatively few species that are pathogenic to animals, especially mammals. According to Hawksworth (1992), there are approximate a little 1.5 million described species of fungi. A little more than 400 of these species are known to cause disease in animals, and far fewer of these species will specifically cause disease in people. Many of the latter will only be superficial types of diseases that are more of a cosmetic than a health problem. Thus, there are not many species of fungi that are pathogenic to human that will be fatal. The study of Fungi as animal and human pathogens is medical mycology. There is also such a thing as veterinary mycology, but the types of diseases that are found in your pets often are the same as those that are found in people. Because of the rarity of human diseases caused by Fungi, most people have little, if any, knowledge of such diseases.
The diseases of warm-blooded animals caused by fungi are known as mycoses (sing.=mycosis). Although such diseases are relatively few, the fungi that cause them have a wide host as well as geographical range. Most of these diseases are not fatal, but once contracted, they may forever be a source of constant irritation and can lead to permanent scaring, which is why they are not such a pretty sight to view.
The successful treatment of fungal diseases is more difficult than those caused by bacteria. Because bacteria are prokaryotes, the makeup of their cells are very different than our own eukaryotic cells and pharmaceutical products, such as antibiotics, are able to successfully destroy bacteria without harming our cells, tissues and organs. However, because fungi are eukaryotes, finding a treatment that will kill the fungus and not harm our own cells is more difficult. Thus, most chemical treatments are also toxic us as well as the fungus. The most widely used drug for treating systemic mycosis and other fungal infections that do not respond to other drugs is Amphotericin B. Azole drugs are also widely used, but these only inhibited fungal growth and do not kill the fungus.

History on the Theory of Human Diseases
The history human diseases tells a story that parallels and overlaps that of plant diseases. Early man viewed disease as a work of demons, and in many tribal societies, the exorcism of demons was the job of the shaman, witch doctor, sorcerer, etc. With the development of agriculture and civilization, more elaborate stories came about. For example, the Greeks tell of the myth about Pandora opening a box given to her by Zeus and releasing a host of plagues on mankind. However, they also created Aesculapius, the god of healing and medicine who had two daughters, Hygeia and Panacea, who were goddesses of health.
During the 4th Century B.C., Aristotle introduced the theory that life could arise abiologically, i.e. without parents. This is the theory of spontaneous generation, a theory that survived well into the 1800s. 
As early as 350 B.C., Hippocrates developed a theory that was not based on superstition and myth. His Humoral Theorysuggested that diseases were the result of disproportionate relationship of body humors or fluids: blood, yellow bile, black bile and phlegm (saliva). In order to have good health, each body humor must maintain a certain proportion with the other body fluids. An individual's humors may become unbalanced when they becomes ill, with the changing of the season, over-eating, etc., and the balance in their humors must be adjusted to bring them back into balance. Adjustments were often made by inducing an individual to vomit or to draw out "bad blood" by cutting an artery or vein. Thus, arose the practice of blood letting, which along with hair cuts, shaves and enemas, was carried out in barber shops. Even today, barbershops still utilize the red and white striped pole display as a means of letting the public know that it is a hair cutting establishment. However, meaning of this barbershop symbol has nothing to do with hair cutting. The red strip is to indicate the blood that is bled, the white corresponds to the tourniquet used to dilate the veins. 
Roman scholar, Marcus Terentius Varro (116BC -27BC ) suspected that disease was caused by little animals in the air. However, because of the dark age that followed, science progressed little until the 1500s. In 1546, Girolamo Fracastoro gave the first description of typhus and suggested that this disease could be contracted from one person to another through direct contact or individuals coming in contact with inanimate objects referred to as fomite, i.e., linen, eating utensils, clothing, etc.
In 1688, Francesco Redi, a Florentine scientist, was the first to challenge the idea of spontaneous generation. It was thought that maggots and flies arose spontaneously, from rotting animal flesh. Redi protected the rotted animal flesh from the air and other to sources of visible infection and observed that maggots and flies did not arise from the protected meat. His conclusion was that flies and maggots were present in the unprotected meat, but absent in the protected meat, because it served as a nesting area for the eggs of the flies as well as a food source once the eggs hatched. For a detailed description and illustration of Redi's experiment, see Lecture 02.
In 1674, Anton Van Leeuwenhoek became the first person to see and describe various microorganisms. He would continue to describe observations of anything that he could place under the microscope until just before his death in 1723.
You should also recall that Anton de Bary's demonstration that the Potato Blight was caused by Phytophthora infestants came a year earlier than Pasteur's Germ Theory.  However, the demonstration that fungi could cause disease in people preceded even de Bary. In 1835, Agostino Bassi discovered that a disease of silkworms known as muscardine could be transferred from silk worm to silk worm and was caused by a fungus, Beauvaria bassiana, a species that was later named for Bassi in honor of his discovery. The fungus grows on the silk worm, covering it with white mycelium, eventually killing it. This is a significant problem in the silk industry since one infected silkworm can spread the fungus to all of the other silkworms. It was shortly after that, in 1841, David Gruby demonstrated for the first time that a fungus infection of the scalp, called favus, was caused by a fungus (in Rippon, 1988). The disease is characterized by thick yellow crusts over the hair follicles. At a time before the use of agar media, Gruby isolated the fungus causing favus, from infected individuals, grew the fungus on slices of potatoes and was able to reproduced the favus disease by carrying out inoculation experiments on healthy tissue. This experiment demonstrated, for the first time, that a microorganism was the cause of a human disease (remember Koch's Postulate?). However, Gruby's research in this areas has mostly been ignored, possibly due to strong anti-Semitic feelings, in medicine, at that time (Rippon, 1988).

Slow Knowledge of Medical Mycology Advancement
It would appear that with the knowledge gained from the research of Bassi and Gruby that in the study of diseases,  the knowledge of fungal diseases should have progressed more rapidly than bacterial diseases. However, that is obviously not the case. Bacterial diseases are by far more well known. There are several reasons for this disparity in knowledge. Relative to bacterial diseases, fungal diseases are infrequent and while some mycoses can be severe to fatal, there have not been epidemics of such diseases as we have found in bacteria. For example, bubonic plague was responsible for approximately a third of the population of Europe, between 1346-1350 and 40% of the population of Constantinople, in 1542, and while other diseases such as tuberculosis, malaria, dysentery epidemics were not as severe, they, too, have caused numerous deaths. The combination of the severity, frequency and the epidemics that have occurred in bacterial diseases have, undoubtedly, driven the progress in the study of bacterial diseases. Another problem that slowed the progress of fungal diseases, and one that should not be estimated, is the understanding of species concept in fungi. By 1890 Sabouraud began publishing large numbers of articles on fungus disorders of the skin which eventually culminated in an enormous contribution to the field of medical mycology. However, Sabouraud had difficulty understanding variations in forms fungi can often exhibit. Some species of fungi can take on several forms, a phenomenon known as pleomorphism. Thus, some of Sabouraud's published species as well as those of his contemporaries were merely different forms of existing species. This resulted in hundreds of species being described that would later be determined to represent already published species. Some of these species were based on careful observations where only slight variations in the form of the fungus was thought to represent new species, but some newly described species were also based on inaccurate and incomplete observations. The complication of nomenclature and classification of fungi also slowed progress. This was a problem, at that time, since doctors, were not trained in either mycology nor the systems of naming and classification of organisms. It would not be until 1934 that species concepts of dermatophytes would be redefined by Chester Emmons, according to the Rules of Botanical Nomenclature, and current mycological standards of spore morphology and the structures on/in which they were borne. However, with the means of mass producing penicillin in the early 1940s and discovery of other antibiotics, many of the very serious bacterial diseases were being controlled. Although, to some extent, there have are chemical means of controlling some fungal diseases, they are by no means always successful ones.

What Kind of Fungi Are We Talking About?
There are a number of diseases that specifically cause human diseases. However, fungi can vary in their host specificity. 
The majority of most human pathogenic fungi appear to be soil inhabiting species where they live as saprobes, but given the appropriate conditions, i.e. if the person is not healthy, an open wound is present, direct injection of fungus into your system, a particular life-style, AIDS, etc., they will aggressively attack people. Thus, many fungal infections may be due to opportunistic fungi (=facultative parasites) rather than fungi that specifically cause human diseases. For example Coprinus cinereus, a common mushroom has been recorded as causing endocarditis (Speller and MacIver, 1970), Ustilago maydis, the corn smut is known to cause skin lesions (Review by Lacaz, et al., 1996) and Schizophyllum commune, a wood decomposing fungus that has documented to cause several different types of infections, including meningitis and lung disorder (Reviewed in Kern and Uecker, 1986). These types of fungi can be more harmful than obligate parasites since a facultative parasite is not dependent on a live organism and have not evolved with any particular host, they aggressively attack their hosts, and there is a greater probability that they will kill their hosts than an obligate parasite. However, normally these types of fungi will not cause human mycoses unless their immune system have somehow become compromised.

Left Image: Coprinus cinereus, from Jason Stajich, http://farm3.static.flickr.com/2269/1904556823_950594c954.jpg. Middle Image: Ustilago maydis. Right Image: Schizophyllum commune, from http://en.wikipedia.org/wiki/File:Spaltbl%C3%A4ttlinge.jpg.

We often come in contact with fungi during our everyday routines, some which are potentially pathogenic to human and others not. We may be exposed simply by walking by construction areas where the soil has been disturbed and scattered into the wind by the machinery, we are constantly exposed while we are hiking, jogging, hunting or fishing. During recreation when we injure ourselves, such as with puncture wound, abrasions, burns or even by inhalation of a large number of harmful spores. Fortunately, most of us have an immune system that will protect us from such infections by fungi, but some individuals will contract fungal diseases from such injuries.
So, what kind of fungi can be human pathogens? Probably all fungi can potentially be harmful, in this respect, if your immune system has been compromised. Fortunately, for most of us, this is not a problem and the probability of contracting a serious fungal disease is low relative to bacterial or viral diseases. However, in recent years, it has become more of a problem with the rising number of people with compromised immune systems such as people with AIDS, organ transplants, diabetes and treatment for various forms of cancer. 
Some Fungal Human Pathogens
In discussing fungal diseases, the most convenient way of classifying them is to categorize them according to the type of infection that has occurred: 1. Superficial infections, are caused by fungi that attack the skin or its appendages (nail, feathers and hair). Some examples of these infection include ringworms, jock-itch and athlete's foot. These fungi are known as dermatophytes. 2. Systemic infections, diseases that occur deep within the tissues, involving vital organs and/or the nervous system, and which may be fatal, but may also be chronic. Entry into the body is usually through inhalation of spores or open wounds. Blood circulation or respiratory system may then transmit fungus throughout body and additional infection of internal organ may occur. These fungi, are usually saprotrophic fungi, growing in the soil. A third, Intermediate infection, is sometimes also recognize and is intermediate between the two just discussed. The infection will occur below the skin, but will remain localized
Superficial Infections
The superficial mycoses are the most well known since they can be readily observed. They commonly occur on the hair, nails and skin of infected individuals. They have been recorded in various compilations of medical literature for well over a thousand years as ring worm, athlete's foot, jock itch and piedra. For each type of infection, there can also be a variety of species that may be causing the disease. Thus, we will only have a general discussion on this group of diseases. 
Ringworm and Related Dermatophytes
Ringworm usually occurs on the exposed parts of the body, forming circular growths that may appear darker or lighter than the normal skin color, with symptoms that include skin lesion, rash and itching of the infected area.  Ringworm infections are common where conditions are unsanitary and crowded with people and has been known since early historical time. There are indications that ringworm was more prevalent in the recent past than now because of improvements in sanitary conditions and health habits. The Greeks called it Herpes (=circular or ring form) and the Romans associated the disease with the larval stage of Tinea, the genus for clothes moth. The two names were eventually combined to "ringworm". Although the actual cause of ringworm was not known until the early 1800s, the practice of segregating infected individuals to prevent spread of the disease indicated that there was knowledge that this disease was contagious and prevalent, and could be passed from person to person was known prior to the cause of infection. 
It was Gruby that isolated and described one of the ringworm fungi, Trichophyton, meaning "thread plant", and through inoculation on healthy parts of the scalp, was able to reproduce the disease. He also carried out the same experiment with several other human pathogenic fungi and inoculated himself with the pathogen, as well as others. Although this was a great accomplishment, Gruby also had a great deal of luck since, at the time, isolation of specific fungi was not common practice, and this was also 30 years prior to the development of techniques to grow fungi and bacteria in pure culture.
According to Ainsworth, more than 350 species of dermatophytes have been proposed and given approximately 1,000 names, which has caused some confusion in medical mycology. The proliferation in names have come about because different researchers have worked with the same species of a pathogen, in a different place and time, and each were familiar with that particular isolate of that particular species of fungus and probably not too familiar with that isolate. They grew it in culture briefly and published on it. Thus, each newly isolated dermatophytic fungus was given a name, sometimes according to the symptoms with which it was associated or according to the part of the body affected, i.e. top of the head, neck, face, hand, arm, leg and foot, or even the geographical region, or sometimes just for the sake of publication (due to the competitiveness of medical schools) . This led to a great deal of confusion in the understanding of mycoses.
Although the first species were described in the 1840s, they were little studied until the 1940s, when the United States military personnel, while fighting in the South Pacific, during WWII, contracted ringworm and other fungi in the humid tropics (an example of advancement of knowledge due to driven research). This led to an intensive study, by the government of such fungi with many species being reduced to synonyms. For example, 172 species were reduced to Candida albicans.
Epidemiology of Ringworm
Fungi that cause ringworm are widespread, geographically, and usually not of major concern, other than as cosmetic problems. However, cases in which these diseases cause extreme disfigurements and infections are known to occur, but are rare outside of the tropics, and are believed to be due to poor diet and unsanitary condition (Christensen, 1965). At one time ringworm was a common disease, particularly of children of poorer classes. The inferences usually is that this was mainly a matter of such children being exposed to less soap and water than were children of the well-to-do. It is probable that deficiency in diet may also have made them more susceptible. There have been epidemics of ringworm that have developed in many cities in the United States. Several species of fungi that cause ringworm are common on adults, and it seems highly probable that some of them are regularly present without causing any obvious symptoms. Species that cause ringworm belong to the genera Trichophyton and Microsporum. These genera of fungi are somewhat unusual in that they produce asexual spores, but not sexual spores or at least produce them so infrequently that they have not been observed. Species of fungi causing ringworm can be ecologically divided into three groups:

1. Zoophilic or "animal loving." Species infect animals primarily, e.g. cats, dogs, horses, cows, poultry, but can readily be transmitted to people. This is probably the most common source of ringworm in people, and is usually caused by Microsporum canis, a species usually found on cats and dogs. Animals that are carriers of ringworm do not necessarily show outward signs of the disease. Symptomless animals and probably people as well are carriers of these diseases. The infections are spread mainly by spores, but mycelial fragment in skin and hair can presumably also occur. Spores are very long lived and can remain alive for years in blankets, in clothing, bedding, combs and other grooming tools.
2. Anthropophilic or "man loving." Species infect people and cannot be transferred to animals. 
3. Geophilic or "earth loving." Species occur naturally in soil, presumably as a saprobe, but is capable of infecting animals and people. Another words these are facultative parasites!

There must be great differences among individuals in susceptibility to infection of these ringworm fungi as well as great differences in susceptibility of an individuals at different times. There are many questions that remain unanswered concerning this species causing the various forms of ringworm.
Ringworm infections are conveniently divided into categories, based on the part of the body that was infected:

• Tinea capitis: Ringworm of the scalp, eyebrow and lashes.
• Tinea corporis: Ringworm of the body.
• Tinea cruris: Ringworm of the groin, perineum and perianal region. Infections are commonly referred to as "jock itch".
• Tinea unguium: Ringworm of the nail.
• Tinea barbae: Ringworm of the beard.
• Tinea pedis: Ringworm of the feet. Infections are commonly referred to as athlete's foot.
• Tinea manuum: Ringworm of the hand.

Left Image: Example of Tinea capitis. Middle Image: Example of Tinea corporis. Right Image: Example of Tinea pedis (Athlete's Foot). All images courtesy of Dr. Glenn Bulmer, from http://www.medicalmycology.net.

Note that the various "Tinea" names given to the various forms of ringworms do not constitute species names. A summary of the above ringworm diseases, based on anatomical locations can be found on the Medline Plus Health Information. There is also discussion on treatment for the various types of ringworms that have been omitted on this web page. Warning, this site has very explicit graphics of these diseases!
Presumably infection is spread mainly by air-borne spores which is why veterinarians do not want ring-worm infected animals to remain in their clinics or hospitals. If this is the case, all of us at one time must be exposed to infections by various ringworm fungi. Why is it then that few of us become infected? Why is infection usually localized, e.g. ringworm of the scalp only occurs in part while most areas are not affected? Surely, there are enough spores produced that the entire scalp will be infected. Sometimes one person in a family, or animal in a herd, will get ringworm and it will not spread to others, whereas other times it is highly contagious. There is a great deal to be learned about ringworm.
An interesting disease that is not one of the ringworms is piedra. This is a disease of the hair where mycelium grows along the shaft of the hair and often fuses clumps of hair together. Usually occurs in unsanitary conditions, in tropical countries. To treat piedra the infected hair is cut or shaved and a topical azole cream, salycylic acid or 2% formaldehyde is applied to the affected area.
Systemic or Deep-Seated Mycoses
There are a dozen or more species of fungi causing various systemic or deep-seated mycoses in man and animals. We will discuss several of the more prevalent species or because of some interesting aspect of the fungus or disease.
Coccidioides immitis, the cause of Coccidioidomycosis (Valley Fever)
This species is endemic to the southwest, in the United States (California, eastward through Arizona, New Mexico, and western half of Texas), Northern Mexico and some areas of Central and South America. In the United States, it is most commonly recorded from Kern County, in the San Joaquin Valley of California. Infection may occur following travel to one of the endemic areas. The first case of coccidioidomycosis was described in Argentina shortly before 1890; the patient suffered for seven years before finally dying and by 1915, there were 40 known cases of this disease, which was thought to be a rare and universally fatal. However, by this time it was already known that there was a disease called Valley Fever, which was not associated, at that time, with C. immitis. It would not be until Dickson (1937) that it was realized that Valley Fever was just a milder form of coccidioidomycosis. Dickson & Gifford (1938) carrying out coccidioidin skin test of long time residents of Kern County demonstrated that 50-70% have, at some time been infected by this fungus. The test is like a tuberculosis (TB) test where substances called antigens that are associated with the disease are injected just below the skin, of your forearm, and the results read 24 to 48 hours later. If an infection of C. immitis has occurred, antibodies will be produced by the body that will react with the antigen that has been injected, causing a large red swelling in the area of the injection.
Coccidioides immitis is contracted by inhalation of spores and primarily causes a respiratory disease in animals and people, but from the lungs it may spread throughout the body by way of the bloodstream and cause pathologic changes - skin lesions of one sort or another - in just about all tissues in all parts of the body. In the usual course of events, infection results in a more or less acute but benign and self-limiting respiratory disease, but once the patient recovers from this, they are likely to be permanently immune from further infection. Fiese (1958), an authority on this disease, says that about 60% of those infected have few or no symptoms, and 40% have symptoms of varying degrees of severity; chills, fever, chest pains, coughing, lassitude - symptoms typical of a dozen other infections as well. These symptoms develop ten to fourteen days after infection, and may persist for some time, but eventually, in most cases, the immunological processes of the body take over and rids it of infection, although lesions and scars in the lungs may remain. In a relatively few cases (1 in 500) the fungus is disseminated from the lungs to other parts of the body, and this secondary stage may result in severe lesions in the skin, bones, and internal organs and the victim will have massive external and internal lesions and abscesses. If this stage is reached, it is unlikely that the victim will recover, death will occur within weeks or after a long and lingering illness. Sometime the disease proceeds to a fairly advanced stage and then remains static for years, and it may regress and later reappear. Amphotericin B is the drug of choice to treat this disease.

Left Image: Positive reaction to coccidioidin skin test. Middle Image: Skin lesions from C. immitis infection, from http://drugster.info/img/ail/1899_1911_2.jpg. Right Image: Skin lesion from C. immitis infection on face, courtesy of Glenn Bulmer.

Histoplasma capsulatum and Histoplasmosis
Histoplasmosis occurs in people and dogs, rarely has it occurred in other domestic or wild animals. Infection occurs through inhalation of spores from this fungus. The history of this disease is similar to that of coccidiomycosis. The first three cases of histoplasmosis was described in the Panama Canal Zone in 1905 and 1906. The patients died of massive infections, and in postmortem examination of diseased tissues, the disease was thought to have been caused by a protozoan (Darling, 1906). Thus, the name H. capsulatum, which refers to what was believed to be an encapsulated plasmodium found during the autopsy. The first case occurring in the United States was recorded in 1926 and by 1934 only six cases had been described in Panama and the United States, all postmortem.
Until 1940, Histoplasmosis was thought to be a rare and almost invariably fatal disease, and little attention was paid to it. However, in 1940, many men who were given chest x-rays as part of their physical examination to determine their fitness for military service, were found to have calcified pulmonary lesions indicative of healed-over infections, which is normally a positive test for tuberculosis. The incidence of these lesions were especially high in men from the Mississippi and Ohio River valleys; few of these men tested positive for tuberculin test and so it was unlikely that these lesions were due to tuberculosis infections. In 1945, Histoplasmin skin test revealed that a large number of people in some areas of the United States tested positive for Histoplasmosis, but appeared to be perfectly healthy; at some time in the past they had been infected with Histoplasma capsulatum (Christie & Peterson, 1945). It was estimated that as many as 20% of the population of the United States are or have been infected by this fungus. The great majority of these either have no symptoms at all or suffer only miscellaneous aches and pains, with a light cough, perhaps some dysentery, very much like symptoms of coccidioidomycosis, flu, and various bacterial infections. The symptoms soon disappear and the individual is then highly resistant or immune from further infection by this fungus.
However, again, in a small percentage of cases the fungus spreads, by way of the blood stream, from the source of the original infection in the lungs throughout the body, and this may result in massive infection that is usually rapid and fatal. Thus, the disease is very widespread, but until 1940, it was thought to be a rare, but fatal disease which was usually not diagnosed until an autopsy was carried out and may not have been recognized even then. More cases probably occurred, but because few pathologists were trained to recognize fungal diseases. Medical mycology was still a little studied area at this time. As was the case in coccidioidomycosis, once the disease has been disseminated from the lungs to the rest of the body, it is likely to be fatal and nothing can be done.
Although there is a high incidence of this disease, it is not communicated from animal to animal or person to person or even animal to people. It seems likely that the infection source is from the soil where it has been demonstrated to exist as a saprobe. However, it apparently does not sporulate in soil, but rather only in droppings of birds and bats. The fungus grows there and presumably sporulates on the droppings. This is the reason that public parks throughout the country do not allow people using the park to feed the birds. Large number of birds feeding in a given area, where there are often a lot of people, would present an environment where there is greater probability that someone may catch this disease.
Although this disease is little known, several years ago, on May 25, 1997, Bob Dylan was hospitalized, with histoplasmosis, although his life was threatened, he apparently was never in danger of dying of this disease. However, the disease became far better known after he contracted it. I was still able to find a brief mention of this news story in the archives of the Los Angeles Times. If you wish to read this article, click here. 

Left Image: Histoplasmosis infection of gum, from http://www.doctoribolit.ru/images/Histoplasmosis/Histoplasmosis04.gif. Right Image: Skin lesion of upper lip due to histoplasmosis infection, from Centers for Disease Control and Prevention's Public Health Image Library #6840.

Blastomyces and Blastomycosis
There are two species of this genus, Blastomyces dermatitidis and B. brasiliensis that occur in North America and South America, respectively. These species occur naturally in soil, especially soil in animal habitats. It is apparently widespread in Kentucky and Arkansas where infection in dogs is common. Infection is rare in other animals, but have been recorded in cats, one horse and one sea lion.
Infection apparently comes from spores or mycelium in the soil and any part of the body may be invaded. Infections usually are first detected as skin lesions; the lesions may remain localized or may gradually enlarge. In some case the fungus can spread throughout the whole body, resulting in extensive ulceration. Males are infected more frequently than female - in some studies the ratio is 15:1. There is no effective treatment.

Intermediate Infections
These are diseases that are intermediate between the first two categories. These fungal infections may extend to a considerable depth within the tissue, but unlike the systemic diseases will not be distributed to the rest of the body. One of the most common intermediate infection is Candida albicans.

Candida albicans and Candidiasis
Candida albicans is a dimorphic fungus. That is, it grows as both mycelium and yeasts. This is one reason why there were so many names given to this fungus. This fungus normally occurs in the mouth, digestive tract, and vagina of perfectly healthy people, but under some circumstances, and for reasons unknown, it may cause severe and even fatal infections, with lesions and eruptions of the skin, nails, mouth, bronchial tubes and lungs. There are suggestions that there are special strains of this species that are pathogenic. This is suggested by the fact that this disease can be contagious and epidemics have occurred. Predisposition may also play a role in infection. Oral infections known as thrush is relatively common. Infections can occur on various parts of the body.

Candidiasis infections on various parts of body: Left Image: On tongue, commonly referred to as Thrush. Middle Image: On neck. Right Image: Is a case where it is fatal. Lack of T-Cells allowed infection to occur on many parts of body. Images courtesy of Glenn Bulmer, from http://www.medicalmycology.net.

Chromoblastomycosis
Disease is mostly tropical to subtropical, but was first reported from Boston in 1915 and may be caused by several species of fungi. Species causing this disease are mostly soil inhabiting or on decaying vegetation and typically enter the foot or lower part of the leg through wounds from walking bare-footed. Early treatment involves excision of infected area or cryosurgery. Chemical treatments vary in their success of controlling this disease. 

Left Image: Fonsecae pedrosoi infection of left leg. Right Image: Same leg after daily treatment with Itraconazole. Images courtesy of Glenn Bulmer, from http://www.medicalmycology.net.

Aspergillus fumigatus and Aspergillosis
Aspergillus fumigatus is a species complex rather than a single species. It is actually composed of ten species. These species are commonly found in decaying vegetation, especially when the latter is undergoing microbiological heating, because this complex is thermophilic, adapted to growing at high temperatures 50 - 55ºC (120 -130ºF).
Aspergillus fumigatus sometimes parasitizes animals, especially birds, infecting mainly lungs and causing heavy mortality - up to 50% in young turkeys and up to 90% in young chicks. Heavy losses have also been reported in herring gulls, ostriches and diving ducks in the wild and in penguins in zoos. The fungus can also invade the embryos of eggs in incubators, and probably does the same in eggs in nest in the wild. It also invade the uterus of pregnant cattle and grows through the placenta into the fetus, which then dies and is aborted. It has been estimated that 64% of bovine abortion investigated were due to infection of A. fumigatus.
In people, the disease can lead to a chronic lung infection which is apparently very contagious. The fungus is thought to cause death, but that is not certain. In patients that have died and A. fumigatus has been isolated, many have also had underlying disease that possibly lowered their resistance to the fungus. However, it is also possible that the fungus had lowered their resistance to the other infective agents. It is difficult to know what came first.

Concluding Comments
Human pathogenic then can indeed be very serious and almost any fungus can potentially cause an infection. Although these diseases are not common, there is now a higher incidence of fungal diseases. This is due to the increased number of transplants that are being carried out and to the rise in the number of people afflicted with AIDs. In those individuals requiring transplants in order to be able to continue with a normal life, they must take powerful drugs that suppress the immune system so that the transplanted organ will not be rejected by their body, and of course the immune system of individuals afflicted with AIDs have been comprised by the nature of the disease. With an immune system that has been compromised, there has been a rise in the number of people that have succumbed to fungal diseases.
Unlike bacterial diseases, fungal diseases are more difficult to treat. Often topical and oral treatments are long term and may only be partially successful in controlling the fungus, if they work at all. Many infections will be chronic and if you are fortunate enough to rid the infection from your body, there is always the possibility of recurrence of the disease. Why the difficulty in treating fungal diseases? Many serious bacterial diseases have been successfully treated and usually without side affects from the drugs used. This usually is not the case with treatment of fungal diseases. The reason for this is that fungi, like people, are eukaryotes, making the two types of cells similar, at least more similar than to bacterial cells. There is enough similarity that when attempts are made to rid your body of a fungal infection, with chemicals, it is difficult to find a treatment that can remove the fungus without doing significant damage to your own cells.

Literature Cited
Christie, A. & Peterson J. C. 1945. Pulmonary calcification in negative reactors to tuberculin. Am J Public Health. 35:1131.
Darling, S.T. 1906. A protozoan general infection producing pseudo tubercles in the lungs and focal necrosis in the liver, spleen and lymph nodes. JAMA 46,1283-1285
Dickson, E. C. 1937. "Valley fever" of the San Joaquin Vallen and fungus Coccidioides. California West. Med., 47: 151-155.
Dickson, E. C., & Gifford, M. A. 1938. Coccidioides infection (Coccidioidomycosis): the primary type of infection. Arch. Intern. Med., 62: 853-871.
Edwards, L. B., & Palmer, C. 1957. Prevalence of sensitivity to coccidioidin, with special reference to specific and non-specific reactions to coccidioidin and histoplasmin. Dis. Chest. 31: 35-60.
Fiese, M. J. 1958, Coccidioidomycosis. Charles C. Thomas, Springfield, IL, 253 p.
Hawksworth, D. L. 1992. Fungi: A neglected component of biodiversity crucial to ecosystem function and maintenance. Canadian Biodiversity 1: 4-10.
Hudler, G. W. 1998. Magical Mushrooms, Mischievous Molds. Princeton University Press. Princeton, New Jersey, 248 p.
Lacaz, C. da S., E.M. Heins-Vaccari, N. Takahashi de Melo, and G.L. Hernandez-Arriagada. 1996. Basidiomycosis: a review of the literature. Rev. Inst. Med. Trop. S. Paulo, 38(5): 379-390.

Speller, D.C.E. and A. G. MacIver. 1970. Endocarditis caused by a Coprinus species: A fungus of the toadstool group. J. Med. Microbiol. 4:370-374

Kern, M.E. and F.A. Uecker. 1986. Maxillary Sinus Infection Caused by the Homobasidiomycetous Fungus Schizophyllum commune. Journal of Clinical Microbiology. 23: 1001-1005.
Rippon, J. W. 1988. Medical Mycology: The Pathogenic Fungi and the Pathogenic Actinomycetes. W. B. Saunders Company Harcourt Brace Jovanovich, Inc. Philadelphia, PA, 797 p.
There are a number of web sites that have concise descriptions of diseases with pictures:
National Center for Mycology: An excellent page for superficial infections, i.e., dermatophytes.
Doctor Fungus: Web site has an excellent medical mycology section, but also has general information about fungi, an image bank, and "sick building syndrome" (a topic we will cover later in the semester).
Merck Manual of Diagnosis and Therapy (Chapter 158: Systemic Fungal Diseases)
Terms and Concepts
Anthropophilic: Literarily "man loving." Species infect people and cannot be transferred to animals.
Aspergillosis: Disease caused by Aspergillus fumigatus parasitizes animals, especially birds, infecting mainly lungs, through inhalation of spores, and causing heavy mortality
Blastomycosis: Infection apparently comes from spores or mycelium of Blastomyces dermatitidis and B. brasiliensis, in the soil and any part of the body may become infected through access of wound on body. Infection form lesion that may stay localized, but may spread throughout body forming extensive ulceration.
Candidiasis: Fungal disease caused by Candida albicans. This fungus is found among the normal flora of the mouth, digestive tract, and vagina of perfectly healthy people, but under some circumstances, and for reasons unknown, it may cause severe and even fatal infections, with lesions and eruptions of the skin, nails, mouth, bronchial tubes and lungs.
Chromoblastomycosis: Disease caused by several species of fungi. Species of fungi normally in soil or decaying plant material, and enters the body, usually foot or lower leg, through a break in the skin. Fungus causes a chronic infection in which there are raised crusted lesions affecting the skin and subcutaneous tissue.
Coccidioidomycosis: Systemic mycosis, also known as Valley Fever. Contracted through inhalation of spores of Coccidioides immitis,  from soil, causing respiratory problems in animals. However, may spread throughout the body by way of the bloodstream and cause pathologic changes - lesions of one sort or another - in just about all tissues in all parts of the body, and may be fatal in such cases.
Dermatophyte: Fungus that attacks the skin.
Histoplasmosis: Systemic mycosis, usually occurring in people and dogs. Contracted through inhalation of spores of Histoplasma capsulatum, that occur in droppings of birds, and bats as well as other rodents. May only cause respiratory if remaining localized, but if infection spreads through blood stream, it may be fatal.
Intermediate infections: Fungal infections occurring below the skin, but remaining localized.
Geophilic: Literarily "earth loving." Species that occur naturally in soil, presumably as a saprobe, but is capable of infecting animals and people.
Medical Mycology: The study of Fungi as animal and human pathogens.
Mycoses: Diseases of warm blooded animals caused by fungi.
Opportunistic Fungi: These are Fungi that normally do not cause diseases, but if opportunity arises, e.g. compromise immune system or open wound entry, they can cause an infection and often times are fatal. Also referred to as facultative parasites.
Pleomorphism: Ability of fungi to take on different forms.
Ringworm: Superficial disease of skin caused by various species of fungi.
Superficial infections: Fungal infections that attack the skin or appendages (nails and hair).
Systemic infections: Fungal infections that occur deep within the tissues, involving vital organs and/or the nervous system, and which may be fatal, but may also be chronic.
Tinea: Term referring to various roundworm diseases. Used as part of a binomial, but not a species name, to refer to infections to various parts of the body, e.g., Tinea barbae = ringworm of beard, Tinea pedis = ringworm of feet.
Veterinary Mycology: The study of fungi as animal pathogens, such as those of pets and farm animals.
Zoophilic: Literarily animal loving. Said of fungal dermatophytes that infect animals. Diseases can be transmitted from animals to people.
Questions to Think About

1. Although both Bassi, in 1835, and Gruby, in 1841, demonstrated that fungi could be the cause of diseases long before Pasteur's Germ Theory (1862), it appears that the knowledge of medical mycology was well ahead of knowledge in bacterial diseases at that time. Yet, today, medical mycological knowledge appears to be lagging well behind that of bacterial diseases. What reasons can you give for this disparity in knowledge?
2. Based on the severity of infections, how are fungal infections classified?
3. Why is a fungal infection by an opportunistic fungus more severe than that of an obligate fungal parasite that cause human disease?
4. We have various treatments for bacterial diseases, but for most fungal diseases, even those that are very superficial, successful treatment sometimes has been difficult, at best. Why is treatment of fungal diseases so much more difficult than for bacterial diseases?
5. What are the two main drugs used for treatment of mycoses?
6. As you have seen in lecture, fungal diseases are not a pretty sight to look at. Although you should be cautious, the average person probably does not have to worry too much about fungal diseases. Why not?
7. Why has the incidence of fungal disease been on the rise in recent years?