Department of Pathology,Faculty of Veterinary Medicine, Zagazig University, Egypt.

Diseases Caused by Fungi and MycotoxinBY

Prof. Dr. Mohamed Hamed Mohamedmohamedelariny@yahoo.com

+201224067373

2013

Diseases Caused by Fungi and MycotoxinFungi are group of eukaryotic microorganisms, Fungi can

occurs as yeast mold or as a combination of both forms. Some fungi are capable of causing superficial, cutaneous,

subcutaneous, systemic or allergic diseases. Pathogenic fungi elaborate mycotoxins and enzymes. New born and very old

animals are most often affected by these factors.

Fungus can produce diseases through three pathways: 1-Direct invasion of tissues by fungi (mycosis).

2-Development of hypersensitivity (allergic disease). 3-Through production of toxic substance which affect different tissue (mycotoxicosis) the ingestion of toxic fungal metabolites.

General concepts for fungal infection:1-Entry: Fungi infect the body through several portal of entry.

The first exposure to fungi occurs during birth. Fungi rarely cause disease in health, immuno-competent host, even though we are constantly exposed to infectious stages. The infection occurs

when fungi accidentally penetrate body barrier, such as intact skin and mucous membrane lining, or when the immunologic defect or other debilitating conditions exist in the host. These

condition favorable for fungal colonization and growth occur. 2-Adaptation: Many fungi have developed mechanisms that

facilitate their multiplication within host such as dermatophytes that colonize skin elaborate enzymes that digest keratin.

Candida albicans exist as unicellular yeast like, but when it invades tissue it becomes filamentous.

3-lesions induced by fungus: There are general basic lesions usually seen associate with fungal infection, but there are

difference in specific lesions associated with every one.

The basic lesions are :i-The organism can be detected in routine tissue section stained by H&E or with special stains as Gomori methamine silver, periodic

acid Schiff (PAS) or Gridley’s fungus stain.ii-Homogenous bright eosinophilic material (Splendore-Hoeppli

material) often with serrated edge or as a radially arranged clubs of baseball bates surrounding organism may be seen with some

diseases especially coccidioidomycosis and sporotrichosis or with high bacterial infection as actinomycosis.

iii-Classic granulomas are usually seen with deep invasive fungi which consisted of central core of necrotic debris (usually containing

pus) surrounded by zone of epithelioid cells, macrophages and multinucleated giant cells.

iv-Variable numerous numbers of lymphocytes, plasma cells, and eosinophils may be present.

v-The entire lesions surrounded by fibrovascular connective tissue.vi-The superficial mycosis does not induce the formation of

granulomas.

Fungal diseases are divided into three categories: 1-Superficial mycosis: invade the skin and its appendages eg. Dermatophytosis. 2-Subcutaneous mycosis: mostly saprophytic (not produce disease).3-Systemic (deep) mycosis: saprophytic fungi. Induced severe disease in immunosuppressed animals.

I-Diseases caused by superficial fungi1-Dermatophytosis

(Dermatomycosis, ringworm, Trichophytosis, tinea)It is a superficial infection of the keratinized layers of the skin and its appendages by a group of dermatophytes. Causes: Dermatophytes are 3 genera:1-Microsporum2-Trichophyton3-Epidermophyton (less common).NB:

Dermatophytes do not invade living tissue but remain confined to the keratinized layer, which they attack with proteolytic enzymes having keratinolytic activity.

Host susceptibility: The susceptibility to infection usually depend on several predisposing factors. Young animals are more susceptible than adult. Moreover, it is more common in hot and humid environment, overcrowded, dirty or damp areas and with inadequate nutrition.Macro:1-Circular areas of alopecia that may coalesce to cover large portion of the body.2-Scales, crusts and pustules or ulceration.3-The fungi tend to die in the area of inflammation in the center of lesion and more actives peripherally, which give rise the peripheral red ring and the name ringworm.4-The lesions are limited to hairs, nails, epidermis and dermis. The fungi grow within or upon stratum corneum or the hair. 5-In dog and cat, discolored, malformed, friable, broken nails are seen (onychomycosis = a fungal disease of the nails = ringworm of the nails).

Micro:1-Branched, septated hyphae on the surface or in the hair follicles.2-Round or oval arthospores either within the hair (endothrix) or on the external surface (ectothrix). (PAS-positive).Microsporum is ectothrixTichophyton is endo and ectothrix3-Ortho- and parakeratotic hyperkeratosis with congestion and lymphocytic infiltration in the dermis.4-Folliculitis and perifolliculitis are noticed

2-Candidiasis (Moniliasis, thrush)It is a superficial mycosis specially of mucous membrane caused by Candida albicans . Systemic candidiasis is less frequent but has been described in human, calves, swine and mice.Macro:1-The superficial candidiasis shows white pseudomembrane on the skin and mucous membrane particularly of the mouth, esophagus, crop and proventriculus of birds.2-Systemic candidiasis was observed in calves, mice and man which cause bronchopneumonia, valvovaginitis, mastitis and abortion.

Micro:1-Budding yeast like organism and pseudo hyphae are seen invading the epithelium but rarely beyond the basal layer.2-The dermis infiltrate with neutrophils and lymphocytes.3-Suppuration and necrosis are seen in the kidney4-The causative agent not seen easily in HE section, but is seen well in section stained with PAS

II- Diseases caused by systemic (deep) fungi1-Aspergillosis

Aspergillus spp are saprophytic molds that are extremely common in nature. Ordinarily they are not pathogens, but once established in a susceptible host, it leads to a serious disease.Cause: Aspergillosis is an infectious disease caused by genus Aspergillus, particularly Asp. fumigatus. The disease is most prevalent in birds but may occur in mammals.

Route of infection and Susceptible hosts:Most infection are established by inhalation of spores. Hematogenous

spread is common due to the ability of Aspergillus to invade blood vessels and established mycelial emboli. Debilitated or

immunocompromised animals and those on prolonged antibiotic therapy are at particular risk.

The young chicks and turkeys poults particularly in the brooder stage of growth are Highly susceptible to infection with Asp fumigatus

(brooder pneumonia). In mature chickens the pulmonary lesions are diffuse.

Macro:-Pale yellow nodules in lungs, air sac, syrinx, sinus, liver, brain, cloudy cornea, etc. -White plaques with fuzzy green or gray or blue material (conidiophores-fruity bodies) on air sacs (fructification). NB: Mycotic placentitis and abortion are recorded in cattle and swine.

Micro:1-Thin branched and septated hyphae are seen on the caseated nodules

2-Granulomatous reaction of macrophages, epithelioid and giant cells are predominant.

3-Vasculitis (aortic rupture), which explicate the pathogenesis of the disease (invasion the wall of blood vessels with the hyphae) lead to

thrombosis and infarction with necrosis.4-Occasionally, mycelia are surrounded by eosinophilic radiating clubs

(Splendore-Hoeppli material).

2-BlastomycosisBlastomycosis is an infectious disease of humans and animals caused by

the thermal dimorphic Fungus (yeast form in tissue and mycelia in culture). Blastomyces dermatities causes a cutaneous and pulmonary

infection in cat and man, pulmonary infection in dogs and mammary infection in mare. In dog and cat pulmonary infection is most common,

but dissemination of the organism may results in involvement of any system.

Macro:1-Ulceration and pustules are seen in the dermis and subcutis.2-The lungs show gray nodules with purulent exudate.3-Diffuse consolidation is seen in advanced infection.4-The healing of the ulcers is slowly by scar formation.Micro:

1-Blastomycosis is characterized by a mixed cellular reaction. The reaction is purulent in early stage which become granulomatous in long

standing lesions.2-Atypical lesions in dogs are consisted of central core of neutrophils

and caseous necrosis surrounded by epithelioid cells containing foci of neutrophils and diffusely distributed lymphocytes, besides giant cells.

3-The causative agent (spherical or yeast-like cells with double wall) is seen free or inside macrophages.

4-The organism is seen as a central granular mass surrounded by refractile, double contoured, unstained zone which is bounded by a thin

outer wall. Daughter cell (budding) is an important in differential diagnosis.

1-The pulmonary lesions show massive aggregations of epithelioid cells, neutrophils, lymphocytes and giant cells.

Caseation and calcification are seen.2-The lesion usually limited to the lungs and disseminated with abscess formation to the subcutis, spleen, kidneys, liver, brain,

bones and intestine.3-These lesions were rarely or not encapsulated by fibrous

connective tissue.

3-CoccidioidomycosisCoccidioidomycosis is occurs in wide variety of wild and

domesticated animals. It is a chronic progressive disease in animals characterized by pyogranulomatous reaction. It caused by dimorphic fungus called Coccidioides immitis. The infection

occurs through inhalation of spores (arthroconidia) produced by mycelia.

Macro:The lesions are similar to TB. 1-Multiple granulomatas (nodules) with or without suppuration and calcification2-In cattle: the lesions usually limited to small nodules in lungs and mediastinal lymph nodes. 3-In the disseminated form of the disease (as in dog) grayish nodules of various size may be found in the lungs, lymph nodes, liver, spleen, meninges, eye, bone marrow and other organs.Micro:1-Thick walled organism containing large spherules (filled with endospores) are usually surrounded by a wide zone of epithelioid cells, admixed with few neutrophils and lymphocytes. 2-In cattle, the spherules are surrounded with radiating clubs.3-When the spherules are ruptured the tissue reaction becomes rich in neutrophils and lymphocytes with few epithelioid cells (immature).4-As these endospores mature, lymphocytes and epithelioid cells tend to predominate the inflammatory exudate.

4-AdiaspiromycosisIt is self-limiting disease resulting from the inhalation of non-

replicating spores of the fungi Chrysosporium parvum var. parvum. The disease has been reported in wide variety of wild animals. The disease

may be affects the lungs of dog and goat.Pathognomic Lesions:

1-Double refractile thick wall spherical organism containing single spore which grow in size without reproduction of other.

2-They are seen in the pulmonary passage or tissue inducing granulomatous reaction consisting of epithelioid cells and

multinucleated giant cells surrounded by fibrous connective tissue .

5-CryptococcosisIt is a disease of many animal species and human. It is distributed worldwide and is caused by yeast like fungus called Cryptococcus

neoformans. It infects cattle, swine, horse, cats and dogs and affect the respiratory and nervous systems.

Macro:1-The gross lesions is not diagnostic.2-The lesions occurs as nodules of typical granulomatous diseases. 3-Multiple tumor–like masses of gelatinous or mucinous materials with ulcerated mucous membranes. 4-Edematous lymph nodes, thickened translucent meninges besides diffuse or patchy indurations of mammary glands are recorded.Micro:1-The organisms occurs in tissue as ovoid, or spherical thick walled yeast-like bodies with budding. They are surrounded with wide gelatinous capsule which stained with PAS ( not by HE).2-The brain, lungs,, adrenals, lymph nodes and mammary glands show cystic spaces filled with a huge number of these organisms surrounding with few number of macrophages engulfing the organisms. 3-In other sites, the organisms are less numerous and the tissue reaction consist of numerous epithelioid cells, lymphocytes surrounded with connective tissue.

6-HistoplasmosisThree species of histoplasmosis are of medical significance: 1-Histoplasma capsulatum: the cause of classic Histoplasmosis. 2-Histoplasma capsulatum var, duboisii, the cause of Africane His. 3-Histoplasma farciminosum, the cause of epizootic lymphangitis.

A-Classic HistoplasmosisCause: -Histoplasma capsulatumPathogenesis:

Infection is acquired through inhalation of spores from infected soil. The yeast form of the fungus proliferated in pulmonary macrophages.

After that the disease spread through mononuclear cells to different system.

Macro:The affected organs (lungs, spleen, liver, intestine, adrenals, skin, pancreas, heart, genitalia and kidneys) become enlarged and loss their functions.

Micro:1-The normal tissue replaced by proliferated reticuloendothelial cells which overdistends with yeast like causative agent ( appear as central

spherical basophilic bodies surrounded by unstained zone followed by a thin cell wall).

2-Primary disease in the lung may take the form of classic granuloma composed of epithelioid cells, multinucleated giant cells (contain

organisms) and lymphocytes with or without central caseous core.3-The lesions are replaced by fibrocalcareous nodules in benign form.

B-Epizootic lymphangitisIt is chronic disease of the skin and superficial lymphatics of horse and other equidae, but rarely humans and characterized by lymphangitis. It caused by Cryptococcus farciminosum. The microorganism exist as saprophyte and enter the body through skin. It is yeast shape in tissue and cannot be differentiated from Histoplasma capsulatum.Macro:1-The initial cutaneous lesion is a wound has tendency to ulcerate or undergo alternating periods of discharge and closure for several weeks before scaring.

2-The infection spread in the adjacent tissues and along the lymphatics.

3-The lesions appeared as small nodules (1 cm in diameter) in the subcutaneous tissue and along the course of lymph vessels. The

nodules ulcerated with pus discharge. The ulcerated nodules heal by scar formation.

4-The superficial lymphatics are thickened and cord-like and contain pus.

5-The skin between nodules firstly is normal but later is thickened due to granulation tissue and yellow purulent foci are present.

6-Enlarged regional lymph nodes and abscesses are seen.7-Granulomata are seen in the conjunctiva, nasolacrimal and

pulmonary tissue.Micro:

1-Granulomatous reaction, composed mainly from macrophages, is replacing the normal tissue.

2-The causative organism (oval organism with unstained capsule) are seen in the cytoplasm of macrophages. The capsule is stained with

PAS.

7-MucormycosisThe disease caused by several fungi in the order mucorales which grow in tissue as thick, non-septated, branching filaments organism.Macro:

1-The stomach (abomasum) show ulcer with raised edges.2-The lymph nodes are enlarged and replaced by yellowish

granuloma with caseous and calcified foci.Micro:

1-The normal tissue is ulcerated and replaced by granulation tissue infiltrated with macrophages and epithelioid besides varying degree

of necrosis and calcification2-The fungi appear as thick, non-septated, branching filaments

organism (hyphae) are seen in the necrotic area or in giant cells.3-Invasion of blood vessels by the fungus resulted in thrombus

formation, serofibrinous inflammation and ulceration of gastric mucosa.

8-Mycotic abortionCauses and hosts:- Aspergillus fumigatus and mucor species infect the placenta of cows, mares and ewe.Macro:1-The placenta show enlarged cotyledons which are thickened at the margins and necrotic at the center.2-The center of the caruncles show hyperemia, hemorrhage, necrosis and finally become leathery.Micro:1-The maternal and fetal layers of the placenta are separated by eosinophils, neutrophils and necrotic tissue containing the fungal hyphae.

III- MycotoxicosisThe majority of molds (filamentous fungus) are saprophytes. A large number of disorders attributed to ingestion of molds and their products (toxins) are called mycotoxicosis. They may be hepatotoxic, nephrotoxic or produce neoplasia or neurological dysfunction.

1-AflatoxicosisAflatoxins (highly toxic and carcinogenic metabolites) the best known mycotoxin, are a group of hepatotoxic metabolites produced by some strains of Aspergillus flavus. Most animals are susceptible, but male young animals consider more susceptible. Duckling, dogs and swine are among the most susceptible animals. Aflatoxin is direct to a DNA dependent RNA polymerase in the nucleolus which lead to prevent protein synthesis in the hepatocytes.Lesions:1-In Acute aflatoxicosis: i-Toxic hepatitis represented by coagulative necrosis, fatty changes, vacuolar and hydropic degenerations.ii-The lesions are periportal in duckling, cats, adult rats, Turkey, chicken and monkeys, midzonal in rabbits, and centrolobular in pigs, dogs, guinea pigs and cattle. Moreover, diffuse necrosis are seen in neonatal rats and trout. iii-Nodular regeneration of hepatic lobules are noticed.2-In chronic aflatoxicosis : (more usual form) i-Fibrosis and cirrhosis besides bile duct hyperplasia.ii-Hepatoma, hepatic cell carcinoma and cholangiocarcinoma.

2-ErgotThe fungus Claviceps purpurea parasitize the small grains and grasses forming hard black elongated bodies that replace the grain or seed of

the mature plant. The toxin is produced by Claviceps purpurea and contains a variety of toxic substances including several alkaloids.Chronic poisoning (ergotism) is characterized by dry gangrene of limbs, tail and ears due to continuous contraction of the vascular

musculature.

3-OchratoxicosisIt is a diseased caused by moldy grains spoiled by penicillium

viridicatum and characterized by nephropathy of swine and horse.Lesions:

1-The kidneys are enlarged, gray yellow and fir.2-The epithelial lining of proximal convoluted tubules lost their brush border, became more shorter with enlarged vesicular nuclei.3-Thick tubular membrane besides peritubular fibrosis are seen.4-Necrotizing gastroenteritis, lymphoid tissue necrosis, hepatic fatty change and necrosis are recorded.

4-Moldy corn poisning(Equine leukoencephalomalacia)

It is a disease of horse and donkey feed on moldy corn for over 4 months and characterized by drowsy, walk in circles, stagger, fall

on ground and stay till death.Survival animals show permanent cerebral damage, dysphagia,

laryngeal paralysis.Lesions

1-White matter of cerebrum is soft and liquefied.2-Edema and congestion with little inflammatory cells are seen.

Ringworm or Dermatophytosis