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Chapter 5 fungal zoonoses.

Objectives

After completing this chapter, the learner should be able to

* Describe properties unique to fungi

* Identify the appearance of fungi microscopically and by culture methods

* Identify the different types of fungal groups and describe the properties of these groups

* Identify the appearance of fungi microscopically and by growth patterns

* Briefly describe the history of specific fungi zoonoses

* Describe the causative agent of specific fungal zoonoses

* Identify the geographic distribution of specific fungal zoonoses

* Describe the transmission, clinical signs, and diagnostic procedures of specific fungal zoonoses

* Describe methods of controlling fungal zoonoses

* Describe protective measures professionals can take to prevent transmission of fungal zoonoses

Key Terms

anthropophilic

budding

dimorphic fungi

ectothrix

endothrix

fermentation

fungi

geophilic

heterotrophic

hyphae

macroconidia

microconidia

mold

mycelium

nonseptate

opportunistic mycoses

opportunistic pathogen

pseudohyphae

saprophytes

septate

superficial mycoses

systemic mycoses

true pathogen

yeast

zoophilic

OVERVIEW

The Kingdom Fungi includes some of the most important organisms, both in terms of their ecological and economic roles, found on earth. Fungi perform a variety of different functions, such as breaking down dead organic material, providing the roots of plants with essential nutrients, providing the medical communities with numerous drugs (such as penicillin and other antibiotics), providing foods such as mushrooms, truffles and morels, and supplying the bubbles in bread, champagne, and beer. Macroscopic fungi include mushrooms and puffballs, whereas microscopic fungi include molds and yeasts. About 70,000 species of fungi have been described; however, the medical community focuses on molds and yeast because they can produce a number of diseases including ringworm, yeast infections, and several systemic diseases. Fungi are eukaryotic; therefore, fungi are more chemically and genetically similar to animals than other organisms making them more challenging to treat. Fungi are nonmotile and heterotrophic (cannot make their own food).

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TYPES OF FUNGI

Fungi are classified into a variety of categories based on the way in which the fungus reproduces and the presence or absence of branching filaments called hyphae. Some fungi exist only in a yeast form; others exist primarily as hyphae; a few are dimorphic.

* Yeasts are unicellular fungi with round to oval cells that reproduce asexually by giving off small cells called buds (budding) (Figure 5-1). Some yeast may form pseudohyphae (a string of yeast cells that have not separated after each new bud is formed).

* Molds or filamentous fungi are multicellular and form long, tubular chains of cells called hyphae (Figure 5-2).

* Dimorphic fungi can exist as yeast or mold depending upon the growth conditions.

WHAT DO FUNGI LOOK LIKE TO THE NAKED EYE?

Fungi are routinely grown on Sabouraud Dextrose Agar (SDA), which contains starch and has an acidic pH favored by fungi, but there are other specialized agars for fungal growth as well. When growing fungi, their appearance on culture media varies depending upon whether they are a yeast or mold. Yeast grow in colonies on agar much like typical bacterial colonies (Figure 5-3). Depending upon the yeast the colonies may appear mucoid (especially yeast cells that have capsules). Some commercial agars allow particular yeast to grow particular colors, aiding in their identification.

Molds grow as fuzzy colonies. Some molds grow particular colors or may be one color growing on the surface of the plate and another color when viewing the agar from the underside (called the reverse growth) (Figure 5-4).

WHAT DO FUNGI LOOK LIKE UNDER THE MICROSCOPE?

Molds

Molds are eukaryotic and multicellular organisms. Another feature of mold is the presence of chitin in their cell walls (not cellulose as in plants). Chitin is a long carbohydrate polymer that also occurs in the exoskeletons of insects, spiders, and other arthropods. Chitin adds rigidity and structural support to the thin cells of the fungus.

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Molds are composed of filaments called hyphae; their cells are long and thread-like and connected end-to-end. Hyphae twist and tangle together to form a fuzzy mass called mycelium, a term which is applied to the mass of hyphae. Hyphae may be nonseptate (consists of one long, continuous cell not divided into individual compartments) or septate (consists of cross walls that divide the hyphae into individual compartments) (Figure 5-5). Nonseptate hyphae allow the cytoplasm and organelles to move freely from one region to the next and each hypha may contain many nuclei. Septate hyphae may have solid partitions with no communication between compartments or they may have small pores in the cross walls to allow some degree of communication between compartments.

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Hyphae can be categorized by their function. Vegetative hyphae are responsible for the fuzzy appearance of mold. Vegetative hyphae also penetrate into agar or substrate to digest and absorb nutrients. Vegetative hyphae give rise to aerial hyphae. Aerial hyphae, also known as reproductive hyphae, form the reproductive spores of the fungus.

Yeast

Microscopically, yeast cells are larger than bacteria and are round or oval in shape (Figure 5-6). Budding may be seen in yeast that are reproducing asexually; however, some yeast produce sexual spores. Nuclei may be seen in yeast cells because they are eukaryotic. Some yeast are encapsulated.

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HOW DO FUNGI REPRODUCE?

Molds

Molds have a complex reproductive cycle that may be either sexual or asexual. In either case, the important feature of mold reproduction is a single cell known as a spore. In contrast to bacterial endospores (commonly called spores) that are used as a resistance mechanism, fungal spores are used for reproduction. A single spore is capable of regenerating the entire mycelium of a fungal mold.

Asexual spores are produced by mitosis from a single parent cell. Asexual reproduction in mold occurs at the tip of aerial hyphae. Daughter cells develop into spores that move with wind currents and land at distant locations. The spore then germinates and new cells emerge to form filaments and reproduce the mold. Asexual reproduction occurs without a union of sexual cells, and asexually produced spores are generally very numerous. All the spores are genetically identical.

A mold can produce a variety of asexual spores. An arthrospore is a spore formed by fragmentation of the tip of the hyphae, whereas a blastospore is produced as an outgrowth along a septate hypha. Conidiospores are unprotected spores formed by mitosis at the tips of hyphae, and sporangiospores are spores produced within a sac called a sporangium.

Although mold spends much of its time in the asexual phase of its life cycle, some types of mold produce sexual spores. Sexual spores are formed through a process of fusion of parental nuclei, followed by meiosis. Most molds that cause disease in animals and humans do not reproduce sexually.

Yeast

Budding is a type of asexual reproduction that occurs in yeast cells. The yeast cell undergoes mitosis and one daughter nucleus is isolated to one part of the cell. This nucleus is in a small amount of cytoplasm and becomes divided from the parent cell by the formation of a new wall. This cell is called a bud and it increases in size and eventually separates from the parent cell. In some species such as Candida albicans, a series of buds remain attached to one another and to the parent cell to form long filaments called pseudohyphae.

HOW DO FUNGI OBTAIN NUTRIENTS?

Fungi are not able to ingest their food nor can they manufacture their own food. Instead, fungi feed by absorption of nutrients from the surrounding environment.

Molds accomplish this by growing their vegetative hyphae through and within the substrate on which they are feeding. Many yeast are facultative anaerobes (organisms that use oxygen to grow when it is available but can also grow without oxygen) that obtain energy from fermentation (energy obtained through anaerobic degradation of substrates into simpler metabolites). Fermentation in yeast typically involves their use of sugar as an energy source.

Some fungi are saprophytes (feeding on dead or decaying material) and some fungi are parasitic (feeding on living organisms without killing them). Ringworm is a disease caused by parasitic fungi.

HOW DO FUNGI CAUSE INFECTION?

Most fungi are free-living and do not require a host to complete their life cycles. Most human and animal infection occurs through accidental contact from an environmental source such as soil, water, or dust. Humans and animals are generally tolerant of fungi except for two main kinds of pathogens: true pathogens (those that can infect healthy people and animals) and opportunistic pathogens (those organisms present in low numbers in people or animals that cause disease when the host environment is altered).

Fungal diseases are described based on the location of the infection they cause. Categories of fungal diseases include superficial mycoses (those located on the outer surface of hair, nails, and skin known as dermatophytoses caused by such dermatophytes as Trichophyton and Microsporum, the fungi that cause ringworm and those located subcutaneously such as Fonsecaea, the fungi that causes chromblastomycosis), systemic mycoses (those that invade body tissues and tend to be dimorphic fungi such as Blastomyces), and opportunistic mycoses (those fungi such as Candida that are normally harmless, but can cause disease in a compromised/ altered host).

DERMATOPHYTOSES

Overview

Dermatophytoses are infections caused by dermatophytes (which literally mean plants that live on skin) but are actually fungi that only grow on skin, hair, and nails. Dermatophytoses are commonly referred to as ringworm as a result of its classic circular, scaly patches (ring) that resemble a worm lying below the skin surface (worm). The fungi feed on dead skin and hair cells causing a round, red lesion with a ring of scale around the edges and normal skin in the center. The characteristic ring is typically seen in humans; ringworm in animals frequently appears as a dry, grey, scaly patch that looks like many other skin lesions.

The Greeks referred to dermatophytoses as herpes (to creep around) and the Romans thought the disease resembled the larval stage of the worm Tinea (which is Latin for worm). The actual cause of ringworm was not discovered until the 1800s; however, people understood that it was transmitted from person-to-person because infected individuals were isolated from uninfected people. In 1841, a Hungarian Jew living in Paris named David Gruby demonstrated for the first time that an infection of the scalp called favus was caused by a fungus. Favus is Latin for honeycomb and this disease is characterized by thick yellow honeycomb-like crusts over the hair follicles. The following year Gruby described Trichophyton ectothrix, another fungi, found at the roots of a man's beard. Shortly afterward he discovered Oidium albicans (Monilia albicans, which is now known as Candida albicans), the cause of thrush in infants. In 1843, Gruby described another fungus, Microsporum audouini, which he named in honor of Jean Victor Audouin, a French entomologist. In humans, Microsporum causes a form of tinea (ringworm) that is also called microsporia or Gruby's disease. Gruby's research in these areas had mostly been ignored during his time, possibly a result of strong anti-Semitic feelings. It was only slowly realized that in the short period of his scientific activity Gruby had made very original and important contributions to science and is now known as the father of medical microbiology.
The spores of M. canis cannot penetrate
healthy, intact skin. A scratch or fleabite,
for example, is needed to start the
infection. The fungus invades the hair
shafts and top layer of the skin.


Table 5-1 summarizes tinea infections, which are named for the area they infect. Tinea capitis, ringworm of the scalp, was epidemic in North America during World War II. It was believed to be spread by children leaving dermatophytes on movie theater seats followed by another child picking up the fungus from these seats. Some doctors prescribed x-ray treatments to kill the fungus because they believed the rays made the infected hairs fall out (these people later died of radiation toxicity). During the 1940s, U.S. military personnel who were fighting in the South Pacific during World War II contracted ringworm and other fungi in the humid tropics. This led to intensive study of these organisms by the U.S. government. At one time ringworm was a common disease especially in poor children, where it was believed that poor children were not cleaned as often with soap and water as were affluent children. It is now believed that dietary deficiencies and unsanitary conditions both play a key role in the pathogenesis of this disease.

Causative Agent

Dermatophytes are a group of fungi that invade the dead keratin of skin, hair, and nails. Dermatophytes use keratin as a nutrient source; therefore, they only colonize dead layers of skin, hair, and nails. Dermatophytes have the ability to penetrate all layers of skin, but generally stay to the nonliving keratin layer. These fungi do not penetrate beyond the stratum corneum layer as a result of antifungal activity of serum and body fluids and perhaps the decreased tolerance for temperature over 35[degrees]C. Three genera of dermatophytes infect humans (Epidermophyton, Microsporum, and Trichophyton) and only two infect animals (Microsporum and Trichophyton). Some sources only consider fungi dermatophytes if they cause ringworm in both animals and humans; therefore, only certain species of Microsporum and Trichophyton would be considered dermatophytes (See Table 5-2).

Dermatophytes are classified based on their natural habitats. These categories are anthropophilic (those associated with humans only and are transmitted by close, direct human contact or through contaminated fomites), zoophilic (those associated with animals and are transmitted by close contact with animals or contaminated animal products), and geophilic (soil fungi transmitted to humans through direct exposure to soil or to dusty animals).

Dermatophytes are aerobic, nonfastidious organisms that require moisture for growth. Dermatophytes are so closely related and morphologically similar that they are difficult to differentiate; however, different species have unique macroconidia (large, multinuclear asexual spore), microconidia (small, single-celled asexual spore), and hyphae (filaments). Trichophyton spp. produce thin-walled, smooth macroconidia, and numerous microconidia (Figure 5-7); Microsporum spp. produce thick-walled, rough macroconidia, and fewer microconidia (Figure 5-8); and Epidermophyton spp. produce smooth, ovoid, clustered macroconidia, and no microconidia.

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Dermatophytes are keratinophilic and keratinolytic, meaning they digest keratin and utilize it as a nutrient source. These fungi produce keratinases and collageneases that provide nutrients to the fungi by digesting host tissues. Some dermatophytes produce extracellular products that induce inflammation at the infection site.
Epidermophyton infects skin and nails;
Microsporum infects skin and hair;
Trichophyton infects skin, hair, and nails.


Epizootiology and Public Health Significance

Microsporum infections occur worldwide with cats being an important transmission source of the most common species M. canis. Trichophyton infections occur worldwide with a variety of animal transmission sources.

Dermatophyte infections in humans occur worldwide with tinea pedis being the most common type (including in the United States). Tinea capitis is one of the most common infections in children, accounting for up to 92% of dermatophytoses in children younger than 10 years of age. Tinea capitis is rare in adults, but may be found in elderly people. Tinea capitis is widespread in some urban areas in North America, Central America, and South America and is common in parts of Africa and India. In Southeast Asia, the rate of infection has been reported to have decreased dramatically as a result of improved general sanitary conditions and personal hygiene. Onychomycosis (fungal infection of the nail) is a common problem, especially in adults. Onychomycosis accounts for approximately 30% of all cutaneous fungal infections and the prevalence of onychomycosis in the United States is approximately 3% in males and 1.4% in females.
Humid environments or moist skin
provides a favorable environment for
establishing a fungal infection.


Transmission

Dermatophytes can be transmitted in a variety of ways. One way is through direct contact with an infected person or animal. Other ways include indirect contact with contaminated fomites (such as soil, clothing, shower floors, riding equipment, straw, towels, and bedding), and through air-borne spores. Transmission by lice, fleas, flies, mites, or spiders has not been ruled out.

Pathogenesis

The pathogenicity of dermatophytes depends on its ability to produce enzymes, such as proteinases, collagenase, and keratinases. Dermatophytes invade keratinized tissue and are not able to penetrate the dead cornified layer of the epidermis. Dermatophyte infection may result in a hypersensitivity state with the nature of the lesion depending on the host immune response. Although no living tissue is infected, the fungi can provoke cell-mediated immunity that can damage living tissues. Blister-like lesions may appear on various body parts as a result of hematogenous spread of the fungus or its products.

Initially, the skin is infected with a fungal spore and the dermatophyte begins to grow in its filamentous form within the stratum corneum. The hyphae extend downward, but growth is restricted to the superficial layers because certain nutrients (mainly iron) are not available below the stratum corneum. Lateral expansion of the hyphae within the stratum corneum continues for 10 to 35 days during which time the infected skin appears normal or only very slightly inflamed. After 2 to 3 weeks, the advancing border of the infection may become inflamed producing the typical ringworm lesions.

During fungal colonization the host begins to mount an immune response by becoming sensitized to soluble fungal antigens. The first response is cell-mediated immunity, which is characterized by an intense inflammatory process and produces much of the pathology of these diseases. This inflammation produces clinical signs ranging from erythema (redness) and edema of the dermis and epidermis to the formulation of vesicles and pustules. As skin becomes damaged, oozing and weeping of tissue fluid occurs and hair follicles become inflamed and potentially infected with secondary microbes. The second part of the disease pathogenesis is the hostparasite interaction phase. Several host defense mechanisms such as antibodies or lymphocytes do not appear to minimize fungal growth. One host substance that affects dermatophyte growth and spread is transferin, a serum protein that binds and transports iron. Transferin will diffuse into the stratum corneum and bind iron making it unavailable for fungal utilization.

If the cell-mediated response to the dermatophyte antigen does not develop or is suppressed, the skin will not become sufficiently inflamed to reject the fungus. Therefore, dermatophyte infections can occur in two ways: an acute or inflammatory type of infection, which is associated with cell-mediated immunity to the fungus (which generally heals spontaneously or responds well to treatment) and a chronic or noninflammatory type of infection (which is associated with an inability to mount a cell-mediated response to the fungus at the site of infection resulting in relapses and poor response to treatment).

Hair infection with dermatophytes can occur in two ways. One way is endothrix in which fungal growth and spore formation are confined mainly within the hair shaft without formation of external spores. Endothrix infections begin by penetration of the hair, and the organism then grows up the interior main axis of the hair. Examples of fungi that cause endothrix infections are Trichophyton tonsurans and T. violaceum. The second way is ectothrix in which fungal growth occurs within the hair shaft but also produces spores on the outside of the hair. Ectothrix infections begin as in endothrix, but they then extend back out through the hair cuticle (the outer wall of the hair) and form a mass of spores both within and around the hair shaft. Examples of fungi that cause ectothrix infections include M. canis, M. audouinii, M. gypseum, T. verrucosum, and T. mentagrophytes.
Dermatophytes do not produce irritants
or toxins to cause disease.


Clinical Signs in Animals

Ringworm affects a wide variety of animals with a number of different fungal species causing skin lesions. In dogs, approximately 70% of cases are caused by M. canis, 20% by M. gypseum, and 10% by T. mentagrophytes. Lesions in dogs include alopecia, scaly patches, broken hairs, folliculitis, and pustules. Generalized ringworm in adult dogs is uncommon and usually results from immunodeficiency conditions such as hyperadrenocorticism.

In cats, 98% of ringworm cases are caused by M. canis. Lesions in cats are quite variable, with kittens being most frequently affected. Lesions in cats include focal alopecia, scaling, and crusting (mostly around the ears and face or on the extremities). Some cats have no clinical signs but can still serve as a source of infection to other cats or people. Ringworm in cats can also cause feline miliary dermatitis (lesions resemble millet seeds) and these cats are pruritic. Cats with generalized dermatophytosis may develop cutaneous ulcerated nodules, known as dermatophyte granulomas or pseudomycetomas. Ringworm in cats is more frequently seen in indoor-outdoor cats, those in poor health, older cats that may not be able to groom themselves as well, kittens who may not be able to groom their face and ears as well, or those with a compromised immune system.
Long-haired cats may suffer more from
ringworm because their hair protects
spores from mechanical removal
through grooming.


Dermatophytosis in cattle is usually caused by T. verrucosum, but T. mentagrophytes, T. equinum, M. gypseum, M. nanum, M. canis, and other fungi have occasionally been isolated from cattle. Dermatophytosis in cattle occurs most frequently in calves with the classic clinical sign of periocular lesions (that are not pruritic). Cows and heifers tend to develop lesions on the chest and limbs, while bulls develop lesions in the dewlap and intermaxillary skin regions. Lesions in cattle include scaling patches of hair loss with gray-white crusts or thick crusts with discharge. Ringworm as a herd health problem is more common in the winter and is more commonly seen in temperate climates (Figure 5-9).

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In horses, ringworm is most commonly caused by T. equinum and the disease signs can vary from subclinical or mild disease (crusty lesions and alopecia) to severe lesions such as folliculitis.

In Guinea pigs, ringworm is most often caused by Tricho. mentagrophytes and less frequently by Microsporum spp. Lesions are more often seen in younger or stressed Guinea pigs, with patchy alopecia (usually starting at the head), crusts, and flakey skin lesions with reddened margins. Facial lesions may occur around the eyes, nose, and ears, but the disease can spread over the back.

In pigs, ringworm is usually caused by M. nanum, which produces lesions that appear as rings of inflammation or brown discoloration. Lesions are not pruritic in adult pigs.
Sometimes one person in a family or one
animal in a herd will get ringworm and
it will not spread to others, even though
other ringworm infections are highly
contagious.


In sheep, ringworm is common in lambs (especially show lambs) but is otherwise uncommon in production flocks of sheep. Lesions in lambs are most often seen on the head, but widespread lesions under the wool may be apparent in sheared lambs. The fungi that cause ringworm in sheep include M. canis, M. gypseum, and T. verrucosum. Ringworm is uncommon in goats.

Clinical Signs in Humans

The incubation period of dermatophytoses is uncertain as a result of the insidious onset of infection, but is typically believed to vary from several days to several weeks. Ringworm infections in people are divided into categories based on the body part infected and includes:

* Tinea capitis, dermatophytosis of the scalp, appears as single or multiple round or ovoid lesions of varying size over the scalp. Hairs will break off 2 to 4 centimeters from the skin and the hair stumps lose their shiny appearance and appear gray. Inflammation is typically absent and if present redness and swelling may occur around lesion margins. The hair of head, eyebrows, and eyelashes may also be involved with tinea capitis. Tinea capitis commonly affects children, mostly in late childhood or adolescence (Figure 5-10).

* Tinea corporis, dermatophytosis of the body, can present on any area of the body (Figure 5-11).

Zoophilic dermatophytes commonly affect exposed areas like the face, neck, and arms, whereas anthropophilic dermatophytes typically affect occluded areas of the skin or areas of trauma.

The clinical appearance of tinea corporis is quite variable and can present as circular lesions with active, erythematous (red), spreading borders with central clearing, as an erythematous, scaly rash, or as nodular granulomas.

* Tinea barbae (or barber's itch), dermatophytosis of the bearded area of the face and neck, presents with swelling, crusting, often pruritus, and occasional hair breakage.

* Tinea cruris (or jock itch), dermatophytosis of the groin, tends to produce reddish-brown lesions that extend from the folds of the groin down onto one or both thighs. Tinea cruris may or may not be symmetrical.

* Tinea pedis (or athlete's foot), dermatophytosis of the feet, causes scaling and inflammation in the toe webs (especially the one between the fourth and fifth digits) or thickening or scaling of the skin on the heels and soles.

* Tinea unguium (or onychomycosis), dermatophytosis of the nails, causes the fingernails and, more often, the toenails to appear yellow, thick, and crumbly.

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[FIGURE 5-11 OMITTED]

Diagnosis in Animals

Dermatophytoses in animals are diagnosed with Wood's light examination, direct examination of hairs, and fungal culture. A Wood's light emits 253.7 nm of ultraviolet light, which causes the tryptophan metabolites produced by some dermatophytes to emit fluorescent light that appears bright apple green. Only 50% of M. canis fluoresce. The light must be used for several minutes before fluorescence will appear and absence of fluorescence does not mean the animal does not have a dermatophyte. Electric Wood's lights are preferred over battery-powered models. There are many false-positive and -negative results with Wood's light examination.

Direct examination of hairs involves examining hair under a microscope using a clearing agent such as potassium hydroxide (KOH). Superficial scraping from the spreading border of the lesion is recommended. The presence of fungal spores indicates an ectothrix fungal infection; however, interpretation is difficult as a result of confusion with melanin granules or saprophytic fungi.

Fungal culture is the definitive test for dermatophytes. Samples are collected by combing a toothbrush over the suspect area of the skin and then gently stabbing the bristles into a fungal culture plate (SDA). The culture plate is examined daily for up to 21 days. Pathogens produce pale or white growth. Cultures are then examined under a microscope to identify the fungus. Dermatophyte test media (DTM) is used to detect dermatophytes via a color change in the media if the fungus is present. Dermatophytes metabolize nutrients in the media to produce alkaline by-products causing the phenol red acid-base indicator in the media to turn red. Dermatophytes produce alkaline by-products as soon as colonies are visible on the media. Dermatophytes will produce the color change within 7 days and should be checked daily. Saprophytic fungi metabolize the nutrients in the media to alkaline byproducts after several weeks (2 to 3 weeks typically). Any growth is then examined under a microscope to diagnose the fungus. It may take up to 3 weeks for macroconidia to form to enable identification of fungal species.

Diagnosis in Humans

Diagnosis of dermatophytoses is the same for humans as in animals. Occasionally a biopsy is needed diagnosis. Biopsies are stained with periodic acid-Schiff (PAS), silver methenamine, or other fungal stains.

Treatment in Animals

Dermatophytoses in dogs and short-haired cats are usually self-limiting, but treatment usually speeds recovery. Some advocate total body hair clipping (especially in cats) as a treatment adjunct for ringworm. Whole-body topical therapy is controversial and is typically done with enilconazole (a rinse not currently available in North America), miconazole shampoo, or lime sulfur dip. Local lesions can be effectively treated with topical miconazole or clotrimazole. Systemic treatment is recommended for chronic or severe cases and for ringworm cases in long-haired breeds of cats. The microsized formulation of griseofulvin can be used in dogs and in cats. Alternative treatments include terbinafine or itraconazole, but neither of these drugs is approved for use in domestic animals. Systemic and topical treatments for dermatophytosis should be continued for 2 to 4 weeks past clinical cure or until a negative toothbrush culture is obtained. The efficacy of lufenuron in treating ringworm in dogs and cats was promising, but is now dropping out of favor with dermatologists. Thorough and repeated vacuuming and scrubbing of surfaces daily is necessary to prevent contamination of the home. Bedding and blankets should be washed daily in hot water and a 1:10 bleach solution. Cleaning heating ducts and vents, installing air filters, dusting with electrostatic dust clothes, and using HEPA filters have been recommended in households with ringworm-positive animals.
Dermatophytosis will spontaneously
resolve in most healthy cats within
60 to 100 days, but treatment is
recommended because the disease is
highly contagious.


Many topical treatments have been reported to be successful in cattle, but their claims of efficacy are difficult to substantiate. Valuable individual animals should still be treated to limit both progression of existing lesions and spread to others in the herd. Thick crusts should be manually removed gently with a brush and the infective material burned or disinfected with hypochlorite solution. Effective agents include washes or sprays of 4% lime sulfur, 0.5% sodium hypochlorite (1:10 household bleach), 0.5% chlorhexidine, 1% povidone-iodine, natamycin, and enilconazole. Individual lesions can be treated with miconazole or clotrimazole lotions. In sheep treatment is application of sodium hypochlorite solutions or enilconazole rinses (where available). Laboratory animals such as guinea pigs are treated for 5 to 6 weeks with oral griseofulvin. Isolated skin lesions may be treated effectively with topical griseofulvin, tolnaftate, or butenafine creams applied daily for 7 to 10 days.

Treatment in Humans

Treatment of dermatophytoses in humans includes terbinafine, ketoconazole, or griseofulvin. Animals should be treated at the same time as people to avoid reinfection.

Management and Control in Animals

A killed fungal cell wall vaccine is approved for treatment and prevention of M. canis in cats. The vaccine helps decrease the time needed for improvement of clinical signs, but does not affect cure time. The vaccine also reduces the severity, but not the frequency, of re-exposed kitten infections.

An attenuated fungal vaccine for cattle that prevents development of severe clinical lesions and has reduced the incidence of zoonotic disease in animal care workers is used in some European countries. Vaccinated animals shed fungal spores for a period after vaccination. No live vaccine is available in North America.

Some rugs used in animals are treated with chemicals such as tolnaftate can help prevent the fungus from persisting within the rug.

Management and Control in Humans

There are a variety of recommendations for limiting the potential for acquiring dermatophytoses including:

* Keep skin, hair, and nails clean and dry. Fungal colonization is favored by moisture, so keeping skin and hair clean and dry helps minimize infection.

* Do not walk barefoot outside or on unwashed floors.

* Never lend or exchange hair brushes, combs, or clips.

* Practice good hygiene.

* Reduce stress levels and seek treatment of immunocompromising diseases.

* Wear gloves and practice proper hygiene procedures when handling animals.

* Treat infective animals.

* People who have ringworm and are involved in contact sports should be restricted from practices and events until cleared by a physician.

Summary

Dermatophytes are a group of fungi that invade the dead keratin of skin, hair, and nails causing dermatophytoses (commonly known as ringworm). Three genera of dermatophytes infect humans (Epidermophyton, Microsporum, and Trichophyton) and only two infect animals (Microsporum and Trichophyton). Categories of dermatophytes include anthropophilic, zoophilic, and geophilic. Dermatophytes are aerobic, nonfastidious organisms that require moisture for growth. Microsporum infections occur worldwide with cats being an important transmission source of the most common species M. canis. Trichophyton infections occur worldwide with a variety of animal transmission sources. Ringworm affects a wide variety of animals with a number of different fungal species causing skin lesions. In dogs, approximately 70% of cases are caused by M. canis, 20% by M. gypseum, and 10% by T. mentagrophytes. In cats, 98% of ringworm cases are caused by M. canis. Lesions in cats are quite variable, with kittens being most frequently affected. Dermatophytosis in cattle is usually caused by T. verrucosum, but T. mentagrophytes, T. equinum, M. gypseum, M. nanum, M. canis, and other fungi. In horses, ringworm is most commonly caused by T. equinum. In guinea pigs, ringworm is most often caused by T. mentagrophytes and less frequently by Microsporum spp. In pigs, ringworm is usually caused by M. nanum. The fungi that cause ringworm in sheep include M. canis, M. gypseum, and T. verrucosum.

Ringworm infections in people are divided into categories based on the body part infected and include tinea capitis, tinea corporis, tinea barbae, tinea cruris, tinea pedis, and tinea unguium. Dermatophytoses are diagnosed with Wood's light examination, direct examination of hairs, and fungal culture. Treatment of dermatophytoses includes oral and topical antifungal treatment (although the disease may be self-limiting, it is treated to prevent spread). Cleaning of the area and any equipment is essential to controlling these fungi. A killed fungal cell wall vaccine is approved for treatment and prevention of M. canis in cats. There is no vaccine in people. The disease can be prevented with proper hygiene practices.

SPOROTRICHOSIS

Overview

Sporotrichosis, also called rose gardener's disease, is a subcutaneous fungal disease caused by Sporothrix schenckii, a dimorphic fungus that occurs in nature and is associated with soil, wood, and vegetation (such as rosebushes, barberry bushes, sphagnum moss, and other mulches). The first case of sporotrichosis was identified in 1898 by Benjamin Robinson Scheck at the Johns Hopkins Hospital in Baltimore. He described the fungus as related to Sporotricha, because it resembled a species of the plant Sporotrichum. The second report of the disease occurred in 1900 and involved a boy who had developed a lesion on a finger that had been hit with a hammer. Hektoen and Perkins isolated the fungus and named the organism Sporotrichum schenckii. The name Spo. schenckii was used in a few of the early reports; however, the name Spo. schenckii was used for about 50 years. During the early 1900s in France, sporotrichosis was a common disease and scientists such as Beurmann, Ramond, and Gougerot described the fungus and its clinical signs. The use of potassium iodide to treat sporotrichosis was suggested by Sabouraud to Beurmann and Gougerot in 1903 and this treatment is still used today. The incidence of the sporotrichosis in France declined after the 1920s. In 1908 in Brazil, Splendore described the asteroid bodies seen around Spo. schenckii that is used in the histologic diagnosis of sporotrichosis. In 1927, Pijper and Pullinger reported a sporotrichosis outbreak involving 14 gold mine workers in Witwatersrand, South Africa. Between 1941 and 1944 nearly 3,000 workers from these mines were infected (the origin of infection was traced to the mine timbers). The outbreak was brought under control by treating the timbers with fungicides and using potassium iodide as therapy for the affected miners. In 1988 an outbreak of sporotrichosis in the United States affected 84 people in 15 states who handled conifer seedlings that were packed in Pennsylvania with sphagnum moss harvested in Wisconsin. From 1998 to 2001, 178 culture-proven cases have been identified and treated, predominantly among women at a median age of 39 years and predominantly among those with infected cats.
Rose gardener's disease is a common
name of sporotrichosis because people
tend to become infected by thorn pricks
of rosebushes.


Causative Agent

Sporotrichosis is a cutaneous or extracutaneous infection caused by Spo. schenckii, a rapidly growing fungus. Spo. schenckii exists as a saprophytic mold on vegetative matter in humid climates worldwide. It is a dimorphic fungus that grows in the yeast form in the body and in culture at 37[degrees]C and grows as a filamentous mold exhibiting mycelial forms at 25[degrees]C (Figure 5-12). Microscopically, Spo. schenckii appears as small (2 to 5 micrometers), round to oval to cigar-shaped yeast cells or fine, branching septate hyphae with either ovoid microconidia borne in clusters from the ends of conidiophores (having a flowerette arrangement) or are brown, oval or triangular, thick-walled, and directly attached to the sides of the hyphae. If stained with periodic acid-Schiff (PAS) stain, an amorphous pink material may be seen around the yeast cells. Spo. schenckii grows readily on brain heart infusion agar, blood agar, and Sabouraud dextrose agar (SDA).

[FIGURE 5-12 OMITTED]

Epizootiology and Public Health Significance

Spo. schenckii is found worldwide and sporotrichosis occurs worldwide especially in areas in which the humidity is between 92% and 100% and there is temperature between 80[degrees]F and 85[degrees]F. Sporotrichosis occurs mainly in moist tropical and subtropical areas such as Brazil, Columbia, and Mexico; although outbreaks from infective sphagnum moss harvested in Wisconsin have been reported. In the United States, sporotrichosis is most commonly found in coastal regions and river valleys.
Spo. schenckii survives in the
environment and becomes pathogenic
in animals as a result of its dimorphic
qualities.


The incidence of sporotrichosis is unknown. The mold itself is endemic to the Missouri and the Mississippi River Valleys. Sporotrichosis is the most common subcutaneous mycosis in South America and it is rare in Europe. Sporotrichosis is associated with minimal morbidity, unless the fungus infects patients who are immunologically compromised.

Transmission

Any compromise of the skin barrier with fungal contact could potentially cause infection. Cutaneous infection often results from a puncture wound involving thorns or other plant matter (less common infection sources have been squirrel bites and trauma induced by liposuction). Sporotrichosis has been transmitted by cat bites and occasionally dog and squirrel bites. Direct skin contact with the ulcerated and draining lesions or exudates also transmits the fungus. Small wounds created by splinters, thorns, and insect bites serve as portals of fungal entry. Person-to-person transmission is rare. Pulmonary sporotrichosis is rare and is caused by inhalation of the fungus into the lungs. Sporotrichosis usually occurs sporadically.
Proteases are possible virulence factors
of Spo. schenckii.


Pathogenesis

Sporotrichosis infections are classified as cutaneous (more common) or extra-cutaneous. Cutaneous infections are subclassified into fixed cutaneous and lymphocutaneous forms. Fixed cutaneous sporotrichosis infections occur at the site of inoculation and remain confined entirely to the skin. Fixed cutaneous lesions are painless, nodular lesions that form around the site of inoculation and with time produce pus that eventually drains because of ulceration of the lesion. Lymphocutaneous disease results from the fungi entering the lymphatic system near the primary lesion site with satellite lesions developing along the path of the lymphatic vessels (sporotrichoid spread) resulting in lymphadenopathy. The lymphocutaneous form is restricted to the subcutaneous tissues and does not enter the blood. Extracutaneous, or disseminated sporotrichosis, can present as pyelonephritis, orchitis, osteomyelitis, septic arthritis (monoarthritis), mastitis, synovitis, or meningitis. Extracutaneous sporotrichosis usually occurs in immunocompromised animals and people. Pulmonary involvement is rare.

Infection in animals and humans is a result of the fungus' ability to change phases from an organism that survives on living or decaying plant material to a yeast phase upon entering the skin. The fungus is typically acquired by traumatic implantation into the skin and the fungus converts to its yeast phase causing local or systemic infection. Clinically a local pustule or an ulcer with nodules develops along the draining lymphatics. As the fungus grows, it is recognized by the immune system and an inflammatory response occurs. Clinical signs relate to the location and degree of inflammation. Primary organ systems involved in sporotrichosis include the skin and the lungs. Unless the fungus is inhaled or acquired by an immunocompromised person or animal, it remains cutaneous. In a host who is immunocompromised, disseminated infection can occur from skin involvement or from primary pulmonary infection.

Clinical Signs in Animals

Sporotrichosis is a sporadic chronic granulomatous disease of various domestic and laboratory animals. Sporotrichosis has been reported in dogs, cats, horses, cows, camels, dolphins, goats, mules, birds, pigs, rats, and armadillos. In animals, sporotrichosis occurs in three forms: cutaneous, lymphocutaneous, and disseminated, with the lymphocutaneous form being most common. Small nodules (1 to 3 centimeters in diameter) develop at the inoculation site. The cutaneous form remains localized to the inoculation site, although lesions may be multicentric. As infection ascends along the lymphatic vessels, new nodules develop producing the lymphocutaneous form of the disease. Lesions typically ulcerate and discharge a serohemorrhagic fluid. Chronic illness may result in fever and lethargy. Disseminated sporotrichosis is rare and may involve the bone, lungs, liver, spleen, testes, gastrointestinal tract, or central nervous system (CNS).

Sporotrichosis is more commonly seen in cats and tends to occur in sexually intact male cats with initial lesions occurring more frequently on the distal extremities, head, or base of the tail. Lesions appear as small, draining, puncture wounds that look like bacterial abscesses or cellulitis from cat bite wounds. Lesions will ulcerate and drain potentially exposing muscle and bone. Cats spread the disease by licking and grooming affected sites resulting in secondary infection sites and disseminated disease. Cats with disseminated disease are febrile and anorexic. Cats produce the greatest zoonotic potential, and transmission from cat to human has been reported without evidence of trauma. Cats shed a large number of organisms from wounds and in the feces. In contrast, transmission from other infected species requires inoculation of traumatized skin.

Clinical Signs in Humans

In people there are a few clinical manifestations of sporotrichosis including:

* Fixed cutaneous sporotrichosis in which primary lesions develop at the inoculation site and begin as a painless nodule that enlarges and ulcerates releasing a serous or purulent fluid (Figure 5-13). This form is the most common.

* Lymphocutaneous sporotrichosis in which primary lesions develop at the inoculation site, but secondary lesions also appear along the lymphatic channels. Lesions are most common on the nose, mouth, pharynx, larynx, and trachea.

* Pulmonary sporotrichosis in which conidia are inhaled or there is hematogenous spread of fungi produce clinical signs such as cough, sputum production, fever, and weight loss.

* Osteoarticular sporotrichosis in which people have cutaneous lesions that spread to joints and bones. People typically have one enlarged joint (usually the knee).

[FIGURE 5-13 OMITTED]

Diagnosis in Animals

Diagnosis can be made by culture or microscopic examination of the exudate or of biopsy specimens. In tissues and exudate, the tissue is stained using PAS, GMS (Grocott's methenamine silver), or Gram stain. Tissue biopsies will demonstrate few to many organisms that are cigar-shaped, single cells within macrophages. The fungal cells are pleomorphic and small and ping-pong paddle buds may be present. In species other than cats, Sporothrix fungi numbers are low so diagnosis usually requires culturing the organism on primary isolation media such as SDA and brain heart infusion agar. In cultures incubated at 25[degrees]C colonies are white and soft initially then become wrinkled and coarsely matted with the color becoming tan to dark brown or black and the colonies leathery. At 25[degrees]C, true mycelia are produced, with fine, branching, septate hyphae bearing pear-shaped conidia on slender conidiophores. Cultures incubated at 37[degrees]C grow rapidly (3 to 5 days) and produce small, moist, soft cream to white-colored yeast-like colonies. A fluorescent antibody technique has been used to identify the yeast-like cells in tissues.

Diagnosis in Humans

Diagnosis in people is similar to animals except there is a sporotrichin test available that is an intradermal skin test.

Treatment in Animals

Few treatments have been critically evaluated in animals; however, itraconazole is considered the treatment of choice. Treatment is continued 3 to 4 weeks beyond apparent clinical cure.

Treatment in Humans

Itraconazole is the treatment of choice in people. Oral potassium iodide, terbinafine, and local heat therapy have also been used. The systemic form of sporotrichosis is treated with amphotericin B.

Management and Control in Animals

Sporotrichosis in animals can be prevented by limiting their exposure to potentially infective animals (such as outdoor cats) and by proper cleaning and examination of wounds.

Management and Control in Humans

People can limit their exposure to Spo. schenckii by practicing strict hygiene when handling animals with suspected or diagnosed sporotrichosis. Wearing gloves and long sleeves when handling pine seedlings, rose bushes, hay bales, and other plants that can cause minor skin breaks is recommended. Prudent use of pine seedling packing materials especially sphagnum moss is also recommended.

Summary

Sporotrichosis is a cutaneous or extracutaneous infection caused by Spo.

schenckii, a rapidly growing fungus. It is a dimorphic fungus found worldwide most commonly seen in areas in which the humidity is between 92% and 100% and there is temperature between 80[degrees]F and 85[degrees]F. Sporotrichosis occurs mainly in moist tropical and subtropical areas such as Brazil, Columbia, and Mexico; although outbreaks from infective sphagnum moss harvested in Wisconsin have been reported. In the United States, sporotrichosis is most commonly found in coastal regions and river valleys. Sporotrichosis has been transmitted by animal bites (cats, dogs, and squirrels) and direct skin contact with the ulcerated lesions or exudates. Small wounds created by splinters, thorns, and insect bites serve as portals of fungal entry. Sporotrichosis is a sporadic chronic granulomatous disease of various domestic and laboratory animals with cats shedding a large number of organisms from wounds. In contrast, transmission from other infected species requires inoculation of traumatized skin. In animals, sporotrichosis occurs in three forms, cutaneous, lymphocutaneous, and disseminated, with the lymphocutaneous form being most common. Sporotrichosis in cats tends to occur in sexually intact male cats with initial lesions occurring more frequently on the distal extremities, head, or base of the tail. In people there are a few clinical manifestations of sporotrichosis including fixed cutaneous sporotrichosis, lymphocutaneous sporotrichosis, pulmonary sporotrichosis, and osteoarticular sporotrichosis. Diagnosis can be made by culture or microscopic examination of the exudate or of biopsy specimens. Itraconazole is considered the treatment of choice in animals and people. Sporotrichosis in animals can be prevented by limiting their exposure to potentially infective animals (such as outdoor cats) and by proper cleaning and examination of wounds. People can limit their exposure to Spo. schenckii by practicing strict hygiene when handling animals with suspected or diagnosed sporotrichosis.

[FIGURE 5-14 OMITTED]

[FIGURE 5-15 OMITTED]

[FIGURE 5-16 OMITTED]

[FIGURE 5-17 OMITTED]

[FIGURE 5-18 OMITTED]

Review Questions

Multiple Choice

1. Fungi of medical importance are

a. yeasts and molds.

b. yeasts and endospores.

c. molds and puffballs.

d. molds and sphirochetes.

2. Yeast cells look differently than bacteria under the microscope because

a. they are stained with different stains that allow visualization of the bacterium's nucleus.

b. yeast are larger than bacteria, are round or oval in shape, contain nuclei, and may be seen budding.

c. they contain filaments called hyphae that bacteria do not possess.

d. they form pseudohyphae, are filamentous in shape, and feed by growing into the surrounding environment.

3. Most fungal diseases are spread through

a. ingestion of the fungal spores.

b. absorption through the skin and mucous membranes.

c. accidental contact from an environmental source.

d. vertical transmission.

4. The function of 10% potassium hydroxide in the direct examination of a fungal specimen is

a. to permanently fix fungal elements.

b. to digest and dissolve cellular debris.

c. to eradicate bacterial contaminants.

d. to stain existing hyphae.

5. The toxicity of antifungal drug therapy is attributed to

a. the virulence of fungal organisms.

b. the similarities between mammalian and fungal cells.

c. the poor health of the patient.

d. the resistance of fungal organisms.

6. A dimorphic fungus is one that a. changes its form on different media types.

b. changes its form as a result of different temperatures.

c. starts to grow as a mold, but becomes more yeast-like.

d. exhibits yeast and mold forms at the same time.

7. Yeast reproduce by (and can be identified by) a process called

a. budding.

b. binary fission.

c. binary fusion.

d. meiosis.

8. The India ink stain is combined with cerebrospinal fluid (CSF) to identify

a. Coccidioides immitis.

b. Cryptococcus neoformans.

c. Candida albicans.

d. Histoplasma capsulatum.

9. A human patient with subcutaneous ulcerated lesions on the arm is seen by

a physician. The lesions appear to follow the distribution of the lymphatic drainage, and regional lymph nodes are enlarged. The patient states that she has several indoor-outdoor cats at home. Microscopic examination of the subcutaneous aspirate shows cigar-shaped yeast cells. What disease does this patient most likely have?

a. ringworm

b. histoplasmosis

c. coccidiodes

d. sporothrichosis

10. Bats serve as a source of infection for a. Coccidioides immitis.

b. Histoplasma capsulatum.

c. Paracoccidioides brasiliensis.

d. Blastomyces dermatitidis.
Matching

11. --dermatophyte        A. dimorphic fungi that produces
                             lymphocutaneous infection
12. --Microsporum canis   B. captain's wheel buds seen in South and
                             Central America
13. --Trichophyton        C. fungus that invades dead hair, skin,
                             or nails
14. --Microsporum         D. 50% of this dermatophyte fluoresces

15. --Cryptococcus        E. produce thick-walled, rough
      neoformans             macroconidia, and fewer microconidia

16. --Sporothrix          F. broad-based budding yeast seen
      schenckii              in southeastern and northcentral
                             United States

17. --Coccidioides        G. large, tuberculate macroconidia in
      immitis                fungal form seen in Ohio River Valley

18. --Blastomyces         H. spherule at 37[degrees]C seen in San
      dermatitis             Joaquin Valley

19. --Paracoccidioides    I. yeast with thick capsule seen in urban
                             brasiliensis areas with pigeons

20. --Histoplasma         J. produce thin-walled, smooth
      capsulatum             macroconidia, and numerous microconidia


Case Studies

21. A 3-year-old child is seen by her pediatrician for alopecia and inflammation of the scalp. Broken hair shafts fluoresced under a Wood's lamp, and skin and hair samples were collected for fungal culture. The colonies grew quickly on SDA and appeared fluffy and white with a yellow reverse side. Microscopic examination revealed numerous spindle-shaped, thick-walled, multicellular macroconidia.

a. What disease does this child most like have?

b. What is the most likely etiologic agent?

c. How may this child have acquired this infection?

d. What is the recommended treatment and guidelines for this child?

22. A 65-year-old male presents to his physician with complaints of prolonged fever, cough, and shortness of breath. His illness began as a mild flu-like episode 1 week ago, just after returning from a visit to his sister in Ohio. His dog has also developed a cough following their trip. The physician ordered a chest radiograph of the patient which showed nodular infiltrates and enlarged lymph nodes. A fungal culture of the patient's sputum produced slow-growing white mold colonies, with small microconidia and large tuberculate macroconidia.

a. Based on this person's history and laboratory results, what disease do you think he might have?

b. What organism causes this disease?

c. What tests can be done to confirm the diagnosis?

d. Describe the tissue phase of this organism.

e. Since this patient's dog is also sick, is the dog the source of the infection?

23. A 4-year-old intact male Labrador retriever was presented to his veterinarian with nystagmus, ataxia, and circling. During his examination the dog had a grand mal seizure. Diagnostic tests including complete blood count (CBC), chemistry panel, and urinalysis (UA) were normal. As the dog worsened he was sent to a referral center where a cerebrospinal fluid (CSF) tap was done. A Gram stain of the CSF was negative for bacteria, but revealed large purple ovals that were budding.

a. What type of infection might this dog have?

b. Based on the answer for a, what is the most likely genus and species?

c. What is a quick test that should be done next?

d. How could this dog have acquired this infection?

e. Is there anything else of concern in this dog?

References

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Merck Manual. 2006. Dermatophytoses. http://www.merckvetmanual.com/mvm/ index.jsp?cfile5htm/bc/71300.htm&word5dermatophytes (accessed February 13, 2006).

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Table 5-1 Dermatophytes and the Diseases They Cause

Fungus           Disease Name                     Target Tissue

Microsporum      * Tinea capitis                  * Scalp hair
                   (ringworm of scalp)
                 * Tinea corporis                 * Skin, not nails
                   (ringworm of body)

Trichophyton     * Tinea capitis                  * Scalp hair
                   (ringworm of scalp)
                 * Tinea corporis                 * Skin, not nails
                   (ringworm of body)
                 * Tinea barbae (ringworm of      * Beard
                   the beard)
                 * Tinea unguium (ringworm of     * Nails
                   the nail; also known as
                   onychomycosis)
                 * Tinea pedis (athlete's foot)   * Feet

Epidermophyton   * Tinea cruris (ringworm of      * Groin area
                   the groin or jock itch)
                 * Tinea unguium (ringworm of     * Nail
                   the nail)

Fungus           Transmission

Microsporum      Microsporum canis is spread through contact with
                 dogs, cats, horses, pigs, sheep, rabbits, hamsters,
                 rats, and zoo animals
                 Microsporum canis is the most common dermatophyte
                 seen in humans

Trichophyton     Trichophyton mentagrophytes, T. verrucosum,
                 T. equinum, T. quinckeanum, and T. erinacei are the
                 only zoonotic species of the 26 Trichophyton spp.
                 Trichophyton rubrum is the most common dermatophyte
                 in the United States, but is not found in animals

Epidermophyton   Epidermophyton is not zoonotic; it is only
                 transmitted by person-to-person contact

Table 5-2 Summary of Veterinary Dermatophytes

                 Principle
Organism         Hosts             Fluorescence       Spore Location

Microsporum      Dog, cat,         Positive (50%)     Ectothrix
canis            humans,
                 monkey, horse

Microsporum      Dog, cat,         Negative           Ectothrix
gypseum          horse

Microsporum      Swine             Negative           Ectothrix
nanum

Trichophyton     Many animal       Negative           Ectothrix
mentagrophytes   species

Trichophyton     Cattle, sheep     Negative           Ectothrix
verrucosum

Trichophyton     Fowl              Negative           Ectothrix
gallinae

Trichophyton     Horse             Negative           Ectothrix
equinum

                 Culture
Organism         Appearance        Macroconidia       Microconidia

Microsporum      White to buff;    Many; spindle      Few; attached
canis            reverse yellow    shaped             at the base
                 to orange

Microsporum      Buff; reverse     Many; elliptical   Few; attached
gypseum          is orange brown   shaped             at the base;
                 to yellow                            club-shaped

Microsporum      White to buff;    Many; oblong to    Club-shaped
nanum            reverse is red    elliptical
                                   shaped

Trichophyton     Granular, light   Spindle or club-   Abundant; ovoid
mentagrophytes   buff to tan;      shaped; 5-6        or club-shaped
                 reverse is        septa (divisions
                 variable from     within each
                 red to yellow     macroconidia)

Trichophyton     Deeply folded;    Rare; long and     Abundant; ovoid
verrucosum       white to          thin walled        or club-shaped
                 brilliant
                 yellow

Trichophyton     Radial folds,     Infrequent;        Single;
gallinae         white to pale     club-shaped        club-shaped
                 rose; reverse
                 red

Trichophyton     White, cottony,   Rare;              Many; spherical
equinum          yellow; reverse   club-shaped
                 yellow to
                 red-brown

Source: A Concise Review of Veterinary Virology
by G. R. Carter, D. L. Wise, and E. F. Flores

Table 5-3 Fungal Zoonoses Acquired Through Animal-Contaminated Soil

                                              Infectious
Fungus              Disease                   Form

Cryptococcus        Cryptococcosis            Yeast: spherical
neoformans          (older names              to ovoid in
(serotypes A,       include                   shape with small,
B, C, and D)        torulosis and             constricted buds
(See                European                  and a large
Figure 5-14)        blastomycosis)            capsule (that
                                              contributes to
                                              its virulence)

Blastomyces         North American            Dimorphic
dermatitidis        blastomycosis,            fungi; conidia
(See                Gilchrist's               are the likely
Figure 5-15)        disease,                  infectious
                    Chicago                   form with
                    disease                   the organism
                                              growing
                                              and causing
                                              disease as a
                                              yeast in the
                                              body; the cell
                                              wall structure
                                              is responsible
                                              for its
                                              virulence

Histoplasma         Histoplasmosis,           Dimorphic
capsulatum          Ohio Valley fever,        fungi; conidia
(See                Darling's                 are the
Figure 5-16)        disease,                  infectious
                    reticuloendo-             form;
                    theliosis                 virulence
                                              factors
                                              include its
                                              cell wall
                                              composition,
                                              intracellular
                                              growth, and
                                              thermotolerance

Coccidioides        Coccidioido-              Dimorphic
immitis             mycosis, Valley           fungi;
(See                Fever, San                arthroconidia
Figure 5-17)        Joaquin Fever,            are the
                    California                infectious form;
                    Disease                   virulence
                                              factors include
                                              extracellular
                                              proteinases

Paracoccidioides    Paracoccidio-             Dimorphic fungi
brasiliensis        idomycosis,               with conidia as

(See Figure 5-18)   paracoccidi-              infectious form;
                    oidal                     virulence factors
                    granulomas,               include estrogen-
                    South                     binding proteins
                    American                  and its cell wall
                    blasto-                   components
                    mycosis

Pneumocystis        Pneumo-                   Atypical fungus
carinii             cystosis,                 that is currently
                    parasitic                 classified as a
                    pneumonia,                fungi based on
                    interstitial              RNA analysis. Has
                    plasma cell               flexible-walled
                    pneumonia                 trophozoite form
                                              (predominant) and
                                              firm-walled cystic
                                              form (infectious
                                              form).
                                              Originally thought
                                              to be a trypano-some

                    Predominant
                    Signs in                  Clinical Signs
Fungus              People                    in Animals

Cryptococcus        Meningitis (in 2/3        * Dogs and cats are
neoformans          of people),                 most commonly
(serotypes A,       disseminated disease        infected: CNS signs,
B, C, and D)        in immunocom-               eyes and orbit, skin,
(See                promised people,            & nasal cavity;
Figure 5-14)        respiratory disease         some cases show
                    (cough, fever, and          dissemination to
                    lung nodules);              the lungs, kidney,
                    skin infection              and joints
                                              * Cattle: sporadic
                                                cases of mastitis
                                              * Horses: paranasal
                                                sinus infection,
                                                CNS, abortion

Blastomyces         Produces a chronic        * Dogs: produces
dermatitidis        suppurative and             granulomatous
(See                granulomatous               nodules in lungs
Figure 5-15)        infection; begins           on skin. Skin lesions
                    as an upper                 and disseminated
                    respiratory                 blastomycosis
                    infection and may           result from
                    spread to the               hematognous spread
                    lungs, bones, soft          from the original
                    tissue, and skin            respiratory lesions.
                                                Disseminated disease
                                                can spread to the
                                                bone, eyes, brain,
                                                and genitalia.
                                              * Has been described
                                                in horses, cats,
                                                dolphins, ferrets,
                                                and sea loins but
                                                is rare

Histoplasma         Can produce               * Dogs and cats:
capsulatum          pulmonary,                  ulceration of the
(See                systemic, or                intestinal tract,
Figure 5-16)        cutaneous                   hepatomegaly,
                    lesions                     splenomegaly,
                                                lymphadenopathy;
                                                necrosis and
                                                tubercle-like
                                                lesions in the
                                                lungs, liver,
                                                kidneys, and spleen
                                              * Other animals
                                                infected include
                                                cattle, nonhuman
                                                primates, horses,
                                                sheep, swine,
                                                and various wild
                                                animals

Coccidioides        Asymptomatic              * Cattle: resembles
immitis             in 60% of                   tuberculosis with
(See                infected                    nodular lesions
Figure 5-17)        people;                     in the bronchial
                    self-limiting               and mediastinal
                    respiratory                 lymph nodes
                    infection;                  (occasionally
                    disseminated                lungs)
                    disease can               * Dogs: formation
                    affect visceral             of nodules in
                    organs,                     lung, brain, liver,
                    meninges, bone,             spleen, bones,
                    skin, lymph                 and kidney
                    nodes, and                * Horses: disseminated
                    subcutaneous                infection
                    tissue                      and abortion

Paracoccidioides    Most infections are       Nine banded
brasiliensis        self-limiting; if         armadillo may
(See Figure 5-18)   systemic disease          have lung granulomas;
                    occurs the lungs,         typically
                    skin and mucous           asymptomatic
                    membranes, and
                    lymphatic organs
                    are most
                    frequently involved

Pneumocystis        Many infections are       Common in mice
carinii             asymptomatic and          and rats that are
                    rarely caused disease     asymptomatic.
                    until the advent of       May also be
                    HIV. Now seen mainly in   found in zoo
                    cancer patients with      animals, pigs,
                    T-cell deficiency         rabbits, sheep,
                    caused by chemotherapy    goats, and dogs.
                    and HIV-infected people   Some believe
                    producing moderate        the infection is
                    fever, intense dyspnea,   not zoonotic.
                    unproductive cough,
                    tachypnea, and
                    cyanosis.

                                              Animal
Fungus              Transmission              Source

Cryptococcus        Contact with              Feces of birds
neoformans          contaminated              (especially
(serotypes A,       soil (usually             pigeons), bird
B, C, and D)        respiratory               nests, and soil
(See                inhalation)               contaminated
Figure 5-14)                                  with bird
                                              excreta

Blastomyces         Inhalation;               Unknown;
dermatitidis        infection via             found in soil
(See                and wound                 and wood
Figure 5-15)        contamination
                    is rare

Histoplasma         Inhalation (and           Bat and
capsulatum          less commonly             bird feces;
(See                ingestion)                of soil
Figure 5-16)        soil contaminated
                    with bat and bird
                    feces (especially
                    starlings and
                    pigeons)

Coccidioides        Inhalation                Soil
immitis                                       (dispersal
(See                                          is aided
Figure 5-17)                                  by wind-storms,
                                              dust
                                              storms,
                                              drainoff
                                              water,
                                              and
                                              burrowing
                                              animals)

Paracoccidioides    Inhalation and            Soil and
brasiliensis        trauma                    plants
(See Figure 5-18)

Pneumocystis        Inhalation of             Dust
carinii             dust particles            contaminated
                    or aerosolized            with cysts or
                    respiratory               respiratory
                    secretions.               secretions

                    Geographic
Fungus              Distribution              Pathology

Cryptococcus        Worldwide                 Prevalent in urban
neoformans          with the                  areas where
(serotypes A,       primary                   pigeons congregate;
B, C, and D)        ecological                proliferated
(See                niche revolving           in the high
Figure 5-14)        around birds              nitrogen content of
                                              bird feces; as
                                              masses of yeast
                                              cells dry they are
                                              scattered in the
                                              air and dust

Blastomyces         Primarily the             After inhalation
dermatitidis        northcentral and          of only 10-100
(See                southeastern              conidia disease
Figure 5-15)        U.S. extending            can begin in the
                    from Canada to            respiratory system
                    the Mississippi,          when the conidia
                    Ohio, and                 convert to yeast
                    Missouri River            and multiply. As
                    Valleys, Mexico,          these organisms
                    and Central               multiply an
                    America; has              inflammatory
                    been reported             response begins
                    in Africa                 and alveolar
                                              granulomas are
                                              formed.

Histoplasma         All continents            A benign form occurs
capsulatum          except Australia;         after inhaling a small
(See                especially                amount of conidia into
Figure 5-16)        common in                 the deep recesses of
                    the eastern               the lung establishing
                    and central               a primary fungal
                    regions of the            infection with mild
                    U.S. (the Ohio            signs (cough, aches,
                    River Valley)             and pains) that may
                    and the mid-west          become severe in some
                                              people (fever, night
                                              sweats, and weight
                                              loss); chronic disease
                                              occurs in
                                              immunocompromised
                                              people in which the
                                              fungus disseminates
                                              within the macrophages
                                              leading to systemic
                                              disease

Coccidioides        Desert                    This fungus favors a
immitis             southwestern              habitat with high
(See                portion of the            carbon and salt
Figure 5-17)        U.S., semi-arid           content and a
                    regions                   semiarid, relatively
                    of Mexico and             hot climate. Infection
                    Central and               follows a cyclic
                    South America             pattern with a period
                                              of dormancy in winter
                                              and spring, followed
                                              by growth in summer
                                              and fall. Arthrospores
                                              are inhaled and
                                              converted to spherules
                                              in the lung where they
                                              swell, sporulate,
                                              burst, and release
                                              spores. Chronic
                                              pulmonary disease
                                              manifests itself with
                                              nodular growths called
                                              fungomas and cavity
                                              formation in the
                                              lungs. Spores will
                                              disseminate in
                                              immunocompromised
                                              people/animals in
                                              which multisystem
                                              organ involvement
                                              may occur.

Paracoccidioides    Cool, humid               Paracoccidiodomycosis
brasiliensis        soil of tropical          begins as a primary
(See Figure 5-18)   and semitropical          pulmonary infection
                    regions                   that is often
                    of South                  asymptomatic. It can
                    and Central               disseminate to produce
                    America                   ulcerative lesions of
                                              the mucous membranes
                                              with a serpiginous
                                              (snakelike) active
                                              border and a crusted
                                              surface. Cervical lymph
                                              node involvement is
                                              common.

Pneumocystis        Worldwide;                Following inhalation
carinii             most                      of the cyst, the fungus
                    common in                 attaches to type I
                    an immuno-                pneumocytes where
                    compromised               it exists and replicates
                    host                      extracellularly.
                                              Replication of the
                                              organism fills the
                                              alveolar spaces
                                              impairing oxygen
                                              diffusion and producing
                                              hypoxia.

Fungus              Diagnosis                 Treatment

Cryptococcus        Identification of yeast   Amphotericin B;
neoformans          with thick capsule in     amphotericin B
(serotypes A,       India ink wet mounts;     and flucytosine
B, C, and D)        yeast stain gram          combination
(See                positive; isolation on    therapy;
Figure 5-14)        Sabouraud dextrose agar   ammonia foot
                    yields wrinkled,          baths are
                    whitish granular          recommended
                    colonies in about 7       for people
                    days when incubated at    entering a
                    25[degrees]C; colonies    facility
                    will become mucoid and
                    cream to brown as they
                    age; commercial
                    identification systems
                    such as API-20C AUX
                    Yeast System are also
                    available; cryptococcal
                    latex agglutination
                    antigen assay

Blastomyces         Direct examination of     Amphotericin B;
dermatitidis        microscopic smears        ketaconazole
(See                showing large,
Figure 5-15)        spherical, thick-walled   Disseminated
                    yeast cells about 8-15    disease does not
                    [micro]m in diameter,     respond well to
                    typically with a single   treatment
                    bud connected to the
                    parent cell by a broad
                    base; culture at
                    37[degrees]C on
                    enriched media produces
                    waxy colonies that are
                    whitish and turn gray
                    to brown with age; mold
                    form has septate hyphae
                    with single, pyriform
                    conidia; identification
                    can also be done with
                    an exoantigen test or
                    nucleic acid probe

Histoplasma         Direct microscopic        Amphotericin B,
capsulatum          examination often         ketoconazole
(See                fails to reveal this      or miconazole;
Figure 5-16)        fungi but if found        surgery may
                    will appear               be needed to
                    intracellularly within    remove masses
                    mononuclear cells as
                    small, round to oval
                    yeast cells that are
                    2-5 [micro]m in
                    diameter; fungal
                    culture reveals a
                    slow-growing mold at
                    25[degrees]C taking
                    2-4 weeks to grow
                    appearing as white,
                    fluffy mold that turns
                    brown to buff with
                    age; yeast grows at
                    37[degrees]C as
                    wrinkled, moist,
                    yeastlike colonies
                    that are soft and
                    cream, tan, or pink;
                    microscopically hyphae
                    are small with
                    spherical or pyriform,
                    smooth-walled
                    macroconidia that
                    become roughened or
                    tuberculate with age;
                    exoantigen test
                    (complement fixation
                    and immunodiffusion)
                    and nucleic acid
                    probes are available

Coccidioides        Direct microscopic        Amphotericin B
immitis             examination
(See                demonstrates
Figure 5-17)        nonbudding,
                    thick-walled spherules
                    that are 20-200
                    [micro]m in diameter
                    and contain granular
                    material or numerous
                    small nonbudding
                    endospores; fungal
                    culture is a biohazard
                    to laboratory workers
                    and needs to occur
                    inside a biosafety
                    cabinet; culture shows
                    delicate, cobweb-like
                    growth at 25[degrees]C
                    with most isolates
                    appearing fluffy
                    white; small septate
                    hyphae with
                    barrel-shaped
                    arthroconidia that
                    stain darkly with
                    lactophenol cotton
                    blue; exoantigen test
                    and nucleic acid
                    probes are available

Paracoccidioides    Direct microscopic        Amphotericin B,
brasiliensis        examination shows         ketoconzaole,
(See Figure 5-18)   multiple buds, a          (sulfa drugs may
                    thin cell wall, and a     also be effective)
                    narrow base; fungal
                    culture on Sabouraud
                    dextrose agar at colony
                    has a dense, white
                    mycelium; culture at
                    37[degrees]C produces
                    slow growing white-tan,
                    thick colonies;
                    immunodiffusion tests
                    are also available

Pneumocystis        Direct examination of     Co-trimoxazole
carinii             bronchoalveolar lavage    or dapsone plus
                    fluid or sputum using     trimethoprim or
                    Giemsa stain,             clindamycin plus
                    calcofluor white stain,   primaquine
                    or methenamine silver
                    stain. Cysts are          Human-to-human
                    spherical to concave      transmission is
                    and 4-7 [micro]m in       possible making
                    diameter and may          patient isolation
                    contain intracystic       important.
                    bodies. Trophozoites
                    are difficult to see
                    and are pleomorphic.
                    Monoclonal antibody
                    tests and PCR tests
                    are also available.
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Author:Romich, Janet Amundson
Publication:Understanding Zoonotic Diseases
Article Type:Disease/Disorder overview
Geographic Code:1USA
Date:Jan 1, 2008
Words:11010
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