Fungal Diseases

Medical Mycology

Diagnosis, management, and prevention of FUNGAL DISEASES (MYCOSES)

Mycoses are among the most difficult disease to diagnose and treat

i. signs of mycoses are often missed or misinterpreted

ii. Fungi are often resistant to antimicrobial agents

The Epidemiology of Mycoses

- Fungi and their spores are almost everywhere in the environment

- Most people will experience a mycosis at some time

i. typically acquired via inhalation, trauma, or ingestion

- Infrequently spread from person to person

- MOST mycoses are NOT CONTAGIOUS

i. Dermatophytes are the major exception

- Epidemics due to MASS EXPOSURE to environmental source of fungi

- Mycoses are generally not reportable

- Adequate information on their occurrence is often lacking

Categories of Fungal Agents

TRUE FUNGAL PATHOGENS and OPPORTUNISTIC FUNGI

- only four fungi usually are considered true pathogens

- other fungi are opportunistic

- certain factors increase risk for opportunistic mycoses

i. invasive medical procedure, medical therapies, certain disease conditions, and specific lifestyle factors

- True pathogens endemic primarily in the Americas

- Opportunists distributed throughout the world

Clinical Manifestations of Fungal Diseases

FUNGAL INFECTIONS

- most common mycoses

- caused by the presence of true pathogens or opportunists

FUNGAL TOXICOSES

- acquired through ingestion

- occur when poisonous mushrooms are eaten

ALLERGIES

- Most often result from the inhalation of fungal spores

Anti fungal therapies

Mycoses are among the most difficult diseases to heal

- Fungi often resist T cell-mediated immune responses• Fungi biochemically similar to human cells

- Anti fungal drugs can harm human tissues

- ERGOSTEROl is often a target of anti fungal drugs• Sterol in cell membrane (humans and animals have cholesterol)

Amphotericin B

gold standard of antifungals

-One of the more toxic antifungal agents

- Less toxic alternatives include Ketoconazole, Clotrimazole, and Fluconazole

IMIDAZOLES : treat cutaneous (skin) mycoses

- Clotrimazole (Lotrimin), Miconazole (Monistat)

- Ring worm infections (Athlete's foot, jock itch); vaginal yeast infections

- Ketoconazole (Nizoral) broader spectrum; anti-dandruff•

TRIAZOLES: treat systemic fungal infections

- Fluconazole

-Voriconazole and Posaconazole (newest) Aspergillus infections

Systemic mycoses

- Infections spread throughout the body

- Caused by FOUR pathogenic fungi of the division ASCOMYCOTA:

i. histoplasma, blastomyces, coccidioides, and paracoccidioides

- All four pathogenic fungi are DIMORPHIC

- Acquired through inhalation

i. begins as generalized pulmonary infection

- disseminates via the blood to the rest of the body

Dimorphic fungi

- Grow as MYCELIAL THALLI (MOLDS) in the ENVIRONMENT

- Grow as SPHERICAL YEASTS in the body

i. invasive form

- Individuals working with these fungi must take precautions to avoid exposure to spores

Histoplasmosis

- Most common fungal pathogen affecting humans

- Found in the eastern United States, Africa, and South America

i. Fungi found in moist soils containing high nitrogen levels

-Most infections occur through INHALATION OF SPORES

i. Cutaneous (through the skin) infections are extremely rare

- H. capsulatum is phagocytized by macrophages in the lungs

- DISPERSE the fungi beyond the lungs via the BLOOD AND LYMPH

-Diagnosis based on IDENTIFICATION OF YEAST in patient sample

- Infections in healthy individuals resolve on their own

-Treated with amphotericin B or ketoconazole when needed

Blastomycosis

- BLASTOMYCES DERMATIDIS is the causative agent

i. Endemic in southeastern United States north to Canada

ii. Fungi found in soils rich in organic matter

- PULMONARY BLASTOMYCOSIS

i. Most common manifestation

ii. Initial pulmonary lesions are mostly asymptomatic

iii. When symptoms occur they are nonspecific

iiii. The disease typically resolves but may become chronic

- CUTANEOUS BLASTOMYCOSIS

i. Painless lesions on the face and upper body

- Diagnosis based on identification of fungi in culture or samples

- Treat with oral itraconazole or amphotericin B

- Relapse is common in AIDS patients

Coccidiodomycosis

Coccidioides immitis is the causative agent

- Almost exclusively in the southwestern United States and northern Mexico

i. Valley fever or San Joaquin fever

- Infection rates have risen in endemic areas

i. Population expansion and increased recreational activities

- Inhaled ARTHROCONIDA germinate into SPHERULES in the lung

i. Spherules release large number of spores as they mature

- Coccidioidomycoses most often result in pulmonary conditions

i. Many patients show no or few symptoms

ii. Infections in healthy individuals resolve on their own

iii. Some individuals develop more serious infections

iiii. Dissemination to other sites occurs mostly in immunocompromise

- Diagnosis based on PRESENCE OF SPHERULES in patient samples or a positive COCCIDIOIDIN TESTt

- Amphotericin B is the drug of choice for treatment

i. Wearing protective masks in endemic areas can prevent exposure to spores

Paracoccidioidomycosis

PARACOCCIDIOIDES BRASILIENSIS is the causative agent

- Found in southern Mexico and regions of South America

- Disease found mostly in farm workers in endemic areas

- Similar to blastomycosis and coccidioidomycosis

i. Infection begins as a pulmonary condition

ii. The fungus can spread and create lesions

- Diagnosis based on the presence of yeast in a "steering wheel"formation in patient tissue samples

i. YEAST CELLS with multiple buds

- Treatment is with itraconazole, ketoconazole, or amphotericin B

Systemic mycoses caused by OPPORTUNISTIC fungi

- Opportunistic mycoses don't typically affect healthy humans

- Infections limited to people with poor immunity or patients whose normal microbiome has been disrupted

- More important as the number of AIDS patients rises

- Difficult to identify because their symptoms are often atypical

- PNEUMOCYSTIS PNEUMONIA, CANDIDIASIS, and ASPERGILLOSIS

- Cryptococcosis, Zygomycoses, and Microsporidiosis

Pneumocystis Pneumonia

- PNEUMOCYSTIS JIROVECI is the causative agent

i. Formerly referred to as P. carinii (originally thought to be a protozoan!)

ii. Obligate parasite

- Majority of individuals exposed to P. jiroveci by age five

i. Transmission most likely occurs through inhalation

ii. Infection in immunocompetent is usually asymptomatic

- Common opportunistic fungal infection of AIDS PATIENTS

i. PRESENCE OF DISEASE IS ALMOST DIAGNOSTIC FOR AIDS

- Can result in death if left untreated

- Diagnosed based on clinical and microscopic findings

- Treatment is with trimethoprim and sulfamethoxazole (nantiprotozoal drugs)

CandidiaSIS

- CANDIDA ALBICANS is the most common causative agent

i. Common microbiota of the skin and mucous membranes

- Candida is one of the few fungi TRANSMITTED BETWEEN INDIVIDUALS

- All cases of disease result from an opportunistic infection

- Can produce a wide range of diseases

i. Oropharyngeal = THRUSH

ii. Vulvovaginal

- CANDIDA AURIS - Multi-drug resistant• Spreading rapidly in hospitals

Aspergillosis

- Several diseases caused by fungi in the GENUS ASPERGILLUS

i. Can be found throughout the environment

ii. Disease occurs from the inhalation of the fungal spores

- Most commonly causes only allergies

- Three pulmonary diseases may develop:

HYPERSENSITIVITY ASPERGILLOSIS

- Manifests as asthma or other allergic symptoms

i. Treated with allergy medications

NONINVASIVE ASPERGILLOMAS - - Masses of fungal hyphae form in the cavities following pulmonary tuberculosis

ACUTE INVASIVE PULMONARY ASPERGILLOSIS

- May present as pneumonia•

- Treated by surgical removal of aspergillomas and intravenous voriconazole

Emergence of fungal opportunists in AIDS Patients

- AIDS patients vulnerable to opportunistic fungal infections

i. Permanent immune dysfunction makes cure of infections unlikely

ii. Mycoses account for most deaths associated with AIDS

iii. Infection with various fungi partly define end-stage AIDS

FUSARIUM species

- Cause respiratory distress, disseminated infections, and fungemia

- Toxin accumulation can occur when fungi ingested in food

TALAROMYCES MARNEFFEI

- Produces pulmonary disease if inhaled

TRICHOSPORON BEIGELII

- Can cause fatal systemic disease in AIDS patients

- Enters through the lungs, gastrointestinal tract, or catheters

Superficial, Cutaneous, and Subcutaneous Mycoses

- Are the most commonly reported fungal diseases

- All are opportunistic infections

- Localized at sites at or near the surface of the body

- Acquired by person-to-person contact or environmental exposure

- Diseases are usually not life threatening

- Can cause chronic or recurring infections

Superficial Mycoses

- Are the MOST COMMON FUNGAL INFECTIONS

- Confined to the outer, dead layers of the skin, nails, or hair

- All composed of dead cells that contain KERATIN

- Different genera of ASCOMYCETES cause most dermatophytoses

- Dermatophytoses show a variety of clinical manifestations

i. Tinea pedis ("athlete's foot") - Trichophyton rubrum

ii. Tinea cruris ("jock itch") - Trichopyton rubrum

iii. Tinea capitis - Microsporum gypseum

- Treat limited infections with TOPICAL antifungal agents

- Treat widespread infections with ORAL antifungal agents

i. Terbinafine is usually effective

ii. Griseofulvin is used for chronic or difficult cases

Dermatophytoses

- Infections of the skin, nails, or hair caused by DERMATOPHYTES

i. Previously called RINGWORMS

ii. Produce circular patches that resemble a worm lying below the skin!

iii. Diseases STILL involve the word "TINEA" - Latin for worm

- Fungi use keratin as nutrient source and colonize dead tissues

- May trigger cell-mediated immune response that damages living tissues

- Can be spread from person to person

Fungal Intoxications and Allergies

- Some fungi produce MYCOTOXINS or CAUSE ALLERGIES

- Fungal mycotoxins can cause toxicosis

- Two types of toxicosis:

MYCOTOXICOSIS: Caused by eating mycotoxins

MYCETISMUS: Mushroom poisoning from eating a fungus

- Deadliest mushroom toxins produced by the "DEATH CAP" MUSHROOM

i. Damage cell structure and inhibit mRNA synthesis

ii. Cause liver damage

- Fungal allergens can elicit hypersensitivity response in sensitive individuals

i. About 10% of the population is allergic to Penicillin - produced by Penicillium species (fungus - mold)

Mycotoxicoses

- Mycotoxins - Produced by fungi during normal metabolic activities• i. Often consumed in grains or vegetables

AFLATOXINS are the best-known mycotoxins

i. Produced mainly by Aspergillus flavus

ii. Fatal to many vertebrates• Carcinogenic at low levels when consumed continually

iii. Can cause liver damage and liver cancer

iiii. Prevalent in the tropics

- Some mycotoxins are used to make drugs

i. Include ergot alkaloids produced by Claviceps purpurea