Infectious Diseases: Fungal, Parasitic, and Prion Diseases – BCSE Study Guide

Overview and Clinical Importance

Infectious diseases caused by fungi, parasites, and prions represent significant clinical challenges in veterinary medicine. Understanding these pathogens is essential for BCSE success, as Domain 4 (Medicine) comprises 50-55 questions - the largest domain on the examination. This guide covers systemic mycoses, key parasitic diseases, and transmissible spongiform encephalopathies (prion diseases) with emphasis on clinical diagnosis, treatment, and species-specific considerations.

SECTION 1: SYSTEMIC FUNGAL DISEASES

Systemic mycoses are invasive fungal infections that can affect multiple organ systems. The primary pathogenic fungi in veterinary medicine are dimorphic, meaning they exist as molds in the environment and convert to yeast forms in tissues at body temperature.

MEMORY TIP - Dimorphic Fungi: "Mold in the Cold, Yeast in the Beast" - Environmental mold form converts to tissue yeast form at body temperature (37 degrees C).

Geographic Distribution of Systemic Mycoses

MEMORY TIP - Geographic Rivers: "Blasto and Histo Live by the MISSISSIPPI" - Both blastomycosis and histoplasmosis are endemic to the Mississippi River valley and surrounding waterways.

[Include Image: Figure 1. Geographic distribution map of endemic mycoses in North America] Source: https://commons.wikimedia.org/wiki/File:Blastomycosis_Epidemiological_Map.svg

Blastomycosis

Etiology and Epidemiology

Causative agent: Blastomyces dermatitidis. Blastomycosis primarily affects dogs (more common than cats). Young male dogs, especially hunting breeds with outdoor exposure near water sources, are at highest risk. The organism exists as mycelium (mold) in soil and converts to broad-based budding yeast in tissues.

Clinical Signs

Dogs: Respiratory signs predominate (cough, dyspnea, exercise intolerance) in up to 85% of cases. Other manifestations include ocular disease (uveitis, chorioretinitis, retinal detachment), skin lesions (draining nodules), bone lesions causing lameness, and lymphadenopathy.

Cats: Less common; may present with respiratory, cutaneous, or CNS signs.

MEMORY TIP - Blastomycosis Broad-Based Budding: "B for Blasto = B for Broad-Based Budding" - The distinctive microscopic feature is large (8-25 micrometer) yeast with broad-based budding (daughter cell attached by wide connection).

[Include Image: Figure 2. Cytology showing Blastomyces dermatitidis broad-based budding yeast] Source: https://commons.wikimedia.org/wiki/File:Blastomyces_dermatitidis_yeast_form.jpg

Diagnosis

Treatment

First-line therapy: Itraconazole 5-10 mg/kg PO once daily for at least 60 days past clinical resolution (typically 4-6 months total). Monitor liver enzymes. Generic formulations may have reduced bioavailability compared to brand-name products.

Alternative: Fluconazole is preferred when CNS or ocular involvement exists due to better penetration. Standard dose is 5-10 mg/kg PO once to twice daily.

Severe cases: Amphotericin B (lipid formulations preferred) provides rapid fungicidal activity. Indicated when patient is critically ill or not responding to oral azoles. Monitor renal function.

MEMORY TIP - Azole Selection for CNS/Eye: "Flu Goes Through" - FLUconazole has better penetration through the blood-brain barrier and blood-ocular barrier than itraconazole.

Histoplasmosis

Etiology and Epidemiology

Causative agent: Histoplasma capsulatum. Histoplasmosis affects cats MORE commonly than dogs (one of the few fungal diseases where this is true). Infection occurs via inhalation of microconidia from contaminated soil, especially areas with bird or bat feces.

MEMORY TIP - Histo Hits Cats: "H for Histo = H for Higher in cats" - Histoplasmosis is the systemic mycosis that more commonly affects cats.

Clinical Signs

Cats: Respiratory signs (cough, dyspnea), weight loss, anorexia, fever, lymphadenopathy. Ocular, liver, spleen, and bone marrow involvement possible.

Dogs: GI signs more common than in cats (bloody diarrhea, tenesmus). Also respiratory signs, hepatosplenomegaly, and disseminated disease.

Diagnosis

Cytology: Look for small (2-4 micrometer) intracellular yeast surrounded by a clear halo, typically found inside macrophages. The organisms appear as tiny dots within cells.

Antigen testing: Same as blastomycosis (cross-reactive). Urine GM EIA has sensitivity of 92-95%.

[Include Image: Figure 3. Histoplasma capsulatum intracellular yeast in macrophages] Source: https://commons.wikimedia.org/wiki/File:Histoplasma_capsulatum.jpg

Treatment

Same azole protocols as blastomycosis. Itraconazole is first-line; treatment duration averages 6 months. For severe respiratory compromise, amphotericin B may be necessary initially, followed by itraconazole maintenance.

Coccidioidomycosis (Valley Fever)

Etiology and Epidemiology

Causative agent: Coccidioides immitis and C. posadasii. This is the ONLY major endemic mycosis of the SOUTHWESTERN United States. Infection occurs via inhalation of arthroconidia from desert soil, often after soil disturbance or dust storms.

MEMORY TIP - Cocci in the Desert: "Coccidioides = California, Arizona desert" - The only major systemic mycosis in arid southwestern regions.

Clinical Signs

Dogs: Chronic cough, fever, weight loss, lameness (bone involvement common), lymphadenopathy, skin lesions. Disseminated disease affects bones, eyes, CNS, heart, liver, spleen.

Diagnosis

Key difference: Unlike blastomycosis and histoplasmosis, ANTIBODY testing is the initial biomarker of choice for coccidioidomycosis. Antigen testing has much lower sensitivity (approximately 20%) for Coccidioides.

Cytology: Large spherules (20-200 micrometer) containing endospores.

Treatment

Azole therapy (fluconazole or itraconazole) for 6-12 months minimum. Bone and CNS infections may require lifelong therapy. Ketoconazole is less effective.

Cryptococcosis

Etiology and Epidemiology

Causative agent: Cryptococcus neoformans and C. gattii. Unlike other endemic mycoses, cryptococcosis occurs WORLDWIDE. C. neoformans is associated with pigeon droppings; C. gattii with eucalyptus trees. Cats are affected more commonly than dogs.

Clinical Signs

Cats: Nasal cavity and CNS involvement predominate. Signs include chronic nasal discharge (often unilateral), facial swelling over nasal bridge ("cryptococcal nose"), neurological signs.

Dogs: CNS, ocular, and respiratory involvement. May present with seizures, vestibular signs, or blindness.

MEMORY TIP - Crypto Capsule Cats: "Crypto = Capsule, Cats, and CNS" - Cryptococcus has a large polysaccharide capsule, commonly affects cats, and frequently involves the CNS.

Diagnosis

Latex Cryptococcal Agglutination Test (LCAT): Detects capsular antigen (glucuronoxylomannan). Sensitivity 91% in dogs and 98% in cats with near 100% specificity. Can test serum or CSF.

Cytology: Large (5-20 micrometer) encapsulated yeast with narrow-based budding. Capsule visible with India ink (negative staining).

[Include Image: Figure 4. Cryptococcus neoformans with India ink showing capsule] Source: https://commons.wikimedia.org/wiki/File:Cryptococcus_neoformans_using_a_light_India_ink_staining_preparation_PHIL_3771_lores.jpg

Treatment

Fluconazole is often preferred due to good CNS penetration. Treatment duration 2-6 months beyond clinical cure. Amphotericin B for severe CNS disease followed by fluconazole maintenance.

Systemic Mycoses Comparison Summary

MEMORY TIP - Antigen vs Antibody Testing: "COCCI is the ODD one out" - Coccidioidomycosis uses antibody testing first. All others use antigen testing (GM or LCAT).

SECTION 2: PARASITIC DISEASES

Heartworm Disease (Dirofilariasis)

Etiology

Causative agent: Dirofilaria immitis, a filarial nematode. Adult worms reside in the pulmonary arteries and right heart. Female adults reach 15-36 cm; males approximately half that size. Dogs are the definitive host; cats and ferrets are aberrant hosts with typically lower worm burdens.

Life Cycle

The heartworm life cycle requires a mosquito intermediate host (Aedes, Culex, Anopheles, Mansonia species) and takes 6-7 months to complete in dogs:

• Adult female worms produce microfilariae (L1) that circulate in blood
• Mosquito ingests microfilariae during blood meal
• L1 develops to L3 (infective stage) in mosquito over 10-14 days
• L3 deposited on skin when mosquito feeds; enters through bite wound
• L3 migrates in subcutaneous tissue, molts to L4 then L5 (immature adult)
• Immature adults reach pulmonary arteries approximately 70 days post-infection
• Adults mature and mate; microfilariae appear in blood approximately 6-7 months post-infection

MEMORY TIP - Heartworm Timeline: "6-7 months to maturity" - It takes approximately 6 months for heartworms to mature and produce microfilariae. This is why antigen tests may be negative early in infection.

[Include Image: Figure 5. Dirofilaria immitis life cycle diagram] Source: https://www.cdc.gov/dpdx/dirofilariasis/index.html (CDC DPDx)

Wolbachia Endosymbiont

Critical concept: Heartworms harbor Wolbachia pipientis, an obligate bacterial endosymbiont. Wolbachia is required for heartworm fertility and long-term viability. Elimination of Wolbachia with doxycycline reduces worm fitness and inflammatory response to dying worms. This is why doxycycline is a key component of heartworm treatment protocols.

Clinical Signs

Dogs: Early infection often subclinical. Progressive disease causes cough, exercise intolerance, dyspnea. Advanced disease leads to right-sided heart failure (ascites), caval syndrome (acute cardiovascular collapse with massive worm burden).

Cats: Often subclinical or sudden death. Heartworm-Associated Respiratory Disease (HARD) causes asthma-like signs. No approved adulticide treatment for cats.

Diagnosis

MEMORY TIP - Occult Heartworm: "Occult = Only females, no males" - Occult infections (antigen-positive, microfilaria-negative) occur with single-sex infections, immune destruction of microfilariae, or low worm burdens.

Treatment Protocol (AHS Guidelines)

American Heartworm Society recommended protocol for dogs:

• Day 0: Begin monthly macrocyclic lactone preventive, start doxycycline 10 mg/kg PO q12h for 28 days
• Day 60: First melarsomine injection (2.5 mg/kg IM in epaxial muscles L3-L5)
• Day 90: Second melarsomine injection
• Day 91: Third melarsomine injection (24 hours after second)
• Prednisone (tapering anti-inflammatory dose) with melarsomine injections
• STRICT exercise restriction throughout treatment

MEMORY TIP - Melarsomine Protocol: "30-30-1" - First injection at Day 60, second at Day 90 (30 days later), third at Day 91 (1 day later).

Exercise restriction is CRITICAL: Dead worms cause pulmonary thromboembolism (PTE). Activity increases blood flow and risk of PTE complications including respiratory distress and death.

Prevention

Monthly macrocyclic lactone preventives (ivermectin, milbemycin oxime, moxidectin, selamectin) kill L3 and L4 larvae. Year-round prevention recommended. Test annually even on prevention.

Giardiasis

Etiology

Causative agent: Giardia duodenalis (syn. G. intestinalis, G. lamblia). This protozoan parasite exists in two forms: motile trophozoite (pear-shaped with two nuclei, attaches to intestinal villi) and environmentally resistant cyst (infective stage).

Transmission and Clinical Signs

Transmission: Fecal-oral route via ingested cysts from contaminated water, food, or fomites. Trophozoites colonize small intestine and cause malabsorption.

Clinical signs: Many infections are subclinical. Symptomatic animals show small bowel diarrhea (soft, pale, fetid, fatty stools), weight loss, poor body condition. Blood typically absent.

MEMORY TIP - Giardia GI Signs: "Giardia = Gray, Greasy, Gardia" - Think pale, fatty, malodorous diarrhea from malabsorption.

Diagnosis

• Zinc sulfate fecal flotation (SG 1.18) with centrifugation - look for cysts
• Giardia antigen ELISA (SNAP test) - more sensitive than flotation
• Direct fecal smear (fresh sample) - may see motile trophozoites

Treatment

Fenbendazole: 50 mg/kg PO once daily for 5 days (often extended from 3-day label). Safe and effective against concurrent parasites.

Metronidazole: 15-25 mg/kg PO q12h for 5-7 days. May cause neurologic side effects at high doses.

Combination therapy (fenbendazole + metronidazole) may be more effective for resistant cases.

Bathing removes cysts from coat and reduces reinfection risk.

Coccidiosis

Etiology

Causative agent: Cystoisospora species (formerly Isospora) in dogs and cats. These are host-specific intestinal coccidia that undergo both asexual and sexual reproduction in the intestinal epithelium, producing oocysts that are shed in feces.

Transmission and Clinical Signs

Transmission: Ingestion of sporulated oocysts from contaminated environment or ingestion of paratenic hosts (rodents). Common in puppies and kittens from crowded, contaminated environments (shelters, kennels).

Clinical signs: Often subclinical in adult animals with immunity. Young or immunocompromised animals develop watery diarrhea, weight loss, dehydration. Severe infections can be hemorrhagic.

Diagnosis and Treatment

Diagnosis: Fecal flotation reveals oocysts. Note oocyst size and morphology to differentiate Cystoisospora from pseudoparasites (Eimeria from coprophagy).

Treatment: Sulfadimethoxine is the only FDA-approved treatment (55 mg/kg day 1, then 27.5 mg/kg daily for 10-20 days). Ponazuril is also commonly used off-label.

Toxoplasmosis

Etiology and Life Cycle

Causative agent: Toxoplasma gondii. Cats are the DEFINITIVE HOST (only host where sexual reproduction occurs). All other mammals and birds are intermediate hosts where only asexual reproduction (tachyzoites, bradyzoites in tissue cysts) occurs.

MEMORY TIP - Toxoplasma and Cats: "T. gondii's True love is the CAT" - Cats are the only definitive host. Sexual cycle occurs only in feline intestinal epithelium.

Life cycle: Cats become infected by ingesting tissue cysts in prey (mice, birds) or sporulated oocysts. They shed oocysts for only 1-3 weeks after PRIMARY infection. Oocysts require 2-3 days in environment to sporulate and become infective.

Clinical Signs

Most infections are subclinical. Clinical toxoplasmosis in cats may cause fever, anorexia, uveitis, pneumonia, hepatitis, myositis, and CNS signs. Most severe in neonates infected transplacentally or via milk.

Dogs: Not definitive hosts. Clinical disease rare; CNS and muscle involvement when it occurs.

Zoonotic Considerations

Critical public health message: T. gondii is zoonotic. Human infection occurs from ingesting undercooked meat containing tissue cysts OR ingesting sporulated oocysts from environment (contaminated soil, vegetables). Direct cat contact is NOT a major risk factor if litter boxes are cleaned daily (oocysts need 2-3 days to sporulate).

Diagnosis and Treatment

Diagnosis: Serology (IgM for acute, IgG for chronic exposure). Oocyst shedding is brief, so fecal flotation is rarely positive.

Treatment: Clindamycin (10-12.5 mg/kg PO q12h for 4 weeks) is the treatment of choice for clinical toxoplasmosis. Pyrimethamine/sulfonamide combinations also used.

Parasitic Disease Comparison Table

SECTION 3: PRION DISEASES (Transmissible Spongiform Encephalopathies)

Overview of Prion Diseases

Prions are infectious agents consisting solely of misfolded protein (PrPSc) that does not contain nucleic acid. The normal cellular prion protein (PrPC) is converted to the abnormal, disease-associated form (PrPSc) upon contact, creating a self-propagating chain reaction. PrPSc aggregates in neurons, causing vacuolation (spongy appearance) and neurodegeneration.

MEMORY TIP - Prion Protein: "PrP-Sc = Scrapie form" - The Sc stands for scrapie, the first recognized prion disease. PrPSc is the misfolded, disease-causing form.

Key Characteristics of Prions

• No nucleic acid (not detected by PCR)
• No immune response (no antibody production)
• Extremely resistant to heat, chemicals, radiation, proteases
• Long incubation periods (months to years)
• 100% fatal - no treatment
• Diagnosis confirmed only by detecting PrPSc in brain tissue (postmortem)

Major Veterinary Prion Diseases

Bovine Spongiform Encephalopathy (BSE - Mad Cow Disease)

Background

BSE was first recognized in the UK in 1986. The epidemic was caused by feeding cattle rendered ruminant protein (meat and bone meal from infected cattle and sheep). Over 180,000 cattle were diagnosed in the UK.

Zoonotic Significance

BSE is ZOONOTIC: Consumption of BSE-infected nervous tissue causes variant Creutzfeldt-Jakob disease (vCJD) in humans. This is why BSE is a critical food safety concern and subject to extensive surveillance.

MEMORY TIP - BSE and vCJD: "BSE = Bad for Steak Eaters" - BSE is the only major veterinary prion disease proven to cause human disease (vCJD) through food consumption.

Clinical Signs

BSE has long incubation (2-8 years). Signs include behavioral changes (apprehension, nervousness, aggression), hyperesthesia, ataxia, weight loss, decreased milk production. Progressive and fatal.

Control

Feed bans on ruminant-derived protein have essentially eliminated BSE in cattle. Surveillance programs continue. BSE is a reportable/foreign animal disease in most countries.

Scrapie

Overview

Scrapie is the prototypical prion disease, recognized in sheep for over 250 years. It affects sheep and goats. Despite extensive study, there is NO evidence that scrapie can infect humans.

MEMORY TIP - Scrapie Scratching: "Scrapie = Scraping against fences" - Name comes from the characteristic scratching/rubbing behavior due to intense pruritus.

Clinical Signs

Intense pruritus (scraping against objects causing wool loss), behavioral changes, tremors, ataxia, weight loss despite good appetite. Progressive over weeks to months.

Transmission

Horizontal transmission via placenta (most infectious tissue), birth fluids, and environmental contamination. Vertical transmission also occurs. Genetic susceptibility influenced by PRNP gene polymorphisms.

Chronic Wasting Disease (CWD)

Overview

CWD is the most contagious prion disease. It affects cervids: deer (white-tailed, mule), elk, moose, and reindeer. CWD has spread extensively in North America and has been detected in Scandinavia.

Transmission

Highly efficient horizontal transmission through saliva, urine, feces, and blood. Prions persist in environment (soil, plants) for years. Environmental contamination creates ongoing infection pressure in endemic areas.

Clinical Signs

Long incubation (16+ months). Signs include chronic weight loss ("wasting"), behavioral changes, ataxia, head tremor, drooping ears, excessive salivation, polydipsia/polyuria. Always fatal.

MEMORY TIP - CWD Signs: "Chronic Wasting = Chronic weight loss" - The name tells you the cardinal sign. Think thin, wasting deer/elk.

Diagnosis

Approved diagnostic tests: Immunohistochemistry (IHC) and ELISA on brainstem (obex) and retropharyngeal lymph nodes. IHC is considered the gold standard. Tests detect PrPSc (PrPCWD).

Research tests: Real-time quaking-induced conversion (RT-QuIC) shows promise for detection in urine, feces, and antemortem samples.

Zoonotic Potential

Currently NO confirmed human CWD cases. Research suggests a strong species barrier. However, given BSE precedent, public health agencies recommend caution. Hunters should avoid consuming meat from CWD-positive animals.

Prion Disease Summary

Systemic Mycoses

• Blastomycosis and Histoplasmosis: Mississippi/Ohio River valleys, diagnose with urine GM antigen (cross-reactive)
• Coccidioidomycosis: Southwest US, diagnose with ANTIBODY serology (antigen has low sensitivity)
• Cryptococcosis: Worldwide, diagnose with LCAT antigen test, cats more affected
• Treatment: Itraconazole first-line; fluconazole for CNS/ocular; amphotericin B for severe cases

Parasitic Diseases

• Heartworm: Mosquito-transmitted, melarsomine is ONLY adulticide (dogs), doxycycline kills Wolbachia, STRICT exercise restriction
• Giardia: Fecal-oral, ZnSO4 flotation or antigen test, treat with fenbendazole
• Coccidia: Young animals, sulfadimethoxine treatment, oocyst presence alone does not equal disease
• Toxoplasma: Cats are definitive host, shed oocysts briefly, clindamycin for clinical disease

Prion Diseases

• BSE: Cattle, feed-borne, ZOONOTIC (causes vCJD)
• Scrapie: Sheep/goats, pruritus ("scraping"), NOT zoonotic
• CWD: Cervids, MOST CONTAGIOUS prion disease, shed in saliva/urine/feces, zoonotic potential under study
• All prion diseases: No treatment, 100% fatal, IHC is gold standard diagnosis