Carey Z. August, M.D. UIC College of Medicine
Attending Pathologist, Advocate Illinois Masonic Medical M2 Pathology Course
Center Lecture #39
Clinical Assistant Professor of Pathology, UIC Wednesday, October 30, 2002
Phone: 773-296-7900 9:30 a.m.
e-mail: carey.august-MD@advocatehealth.com
FUNGAL INFECTIONS LEARNING OBJECTIVES
1. Explain which fungi are opportunists and which have the potential to be primary pathogens.
2. Explain the mechanisms of immunity operative in fungal infections. 3. Describe the spectrum of Candida infections
4. Distinguish between ABPA, Asperigilloma, and Invasive Aspergillosis. 5. Name the predisposing factors to mucomyocotic infections
6. Discuss the types of infections seen with Cryptococcus neoformans.
7. Explain the factors governing the outcome of infection with Histoplasma capsulatum. 8. Describe the morphology and clinical features of coccidiomycosis.
1. Basicprinciples
A. Are they all pathogenic for everyone?
1. Dermatophytes-primary pathogens 2. Others-opportunistic pathogens
B. Immune mechanisms-phagocytosis, cell-mediated immunity C. Morphology
1. Yeast vs. mold vs. dimorphic 2. GMS (silver) stain, PAS II. CANDIDA
A. Where does it come from? Many infections are from endogenous species of Candida
B. Morphology-yeast and pseudohyphae C. What determines the severity of infection?
1. Superficial vs. deep infection
2. Host defenses-breach of normal barriers, decreased cell mediated immunity, alteration in normal flora
D. Superficial infections and host defenses
1. Breach of normal barriers (mechanical defenses) such as disrupted skin and mucous membranes, e.g. diaper rash, intertrigo, paroncychia-all involve skin maceration
2. Decreased cell mediated immunity, e.g oral thrush, Candida esophagitis 3. Alteration in normal flora-normal flora compete for sites, nutrients, and
prevent conversion to tissue invasive form, e.g. vulvovaginitis E. Deep infections and host defenses, #1 predisposing factor=antibiotics
1. Deep infections include sepsis, endocarditis, urinary tract infections 2. Involve multiple insults to host defenses
Examples
a. Candida sepsis in a cancer patient made neutropenic by chemotherapy, with an indwelling catheter, on antibiotics suppressing normal flora.
b. Candida endocarditis in a patient with an abnormal cardiac valve who has an indwelling vascular catheter and/or is on antibiotics suppressing normal flora; also, IV drug abusers
c. Candida urinary tract infection in a patient with an indwelling Foley catheter
II. ASPERGILLUS
A. Where does it come from? – in the soil, inhalation of tiny spores
B. Morphology – in tissue, forms septate hyphae with acute angle branching C. What determines the severity of infection – 3 basic forms of infection:
2. Aspergilloma (Fungus Ball) 3. Invasive Aspergillosis
D. ABPA-primary in asthmatic patients. Allergic response. Spores germinate in airways leading to chronic exposure and sequelae of the inflammation, with eosinophilia and impaction of mucoid material.
E. Aspergilloma-usually occurs in the setting of an underlying lung disease with cavitation (e.g. TB) or bronchiectasis. Hyphae grow in the cavity. Hyphae DO NOT invade the surrounding lung. Mass lesion which is sometimes treated by surgery.
F. Invasive aspergillosis
1. Seen most commonly in neutropenic patients-e.g. acute leukemias, patients on chemotherapy
2. Hyphae grow, invade blood vessels, resulting in thrombosis with infarcts and wide dissemination
3. Can affect multiple major organs, with high mortality rate III. MUCORMYCOSIS (ZYGOMYCOSIS)-Rhizopus, Mucor, Absidia
A. Where do they come from?-ubiquitous, in the soil, in mold growing on food-inhalation of spores
B. Morphology-non-septated, right angle branching hyphae, big, “twisted ribbons” C. What determines the severity of infection? – 3 basic types of infection:
1. Rhinocerebral mucormycosos-bad 2. Pulmonary mucormycosis-bad
3. Subcutaneous zygomycosis-a little less bad (affects only subQ tissue, can be treated by oral meds), but only in the tropics
So in general, the mucormycoses you will see are bad infections.
Almost always have predisposing factors: neutropenia, uncontrolled diabetes D. Rhinocerebral mucormycosis
Proliferation in nasal sinuses, tissue and vascular invasion-septic infarction, encephalitis
E. Pulmonary mucormycosis
Vascular invasion and septic infarction IV. CRYPTOCOCCOSIS-Cryptococcus neoformans
A. Where do they come from?-pigeon droppings-inhaled tiny organisms
B. Morphology-small yeast with mucoid capsule-stain with mucin stain; India ink test
C. What determines the severity of the infection?-cell-mediated immunity 1. LUNGS and MENINGES are primary infection sites
Lungs-inhaled organisms-then, they disseminate
Meninges-CSF is good environment for growth of cryptococci D. Pulmonary cryptococcosis
1. If the patient is immunocompetent, may be contained by a granulomatous response
2. If the patient is not immunocompetent, pulmonary consolidation with little inflammatory response
E. Cryptococcal meningoencephalitis Fatal if not aggressively treated V. HISTOPLASMOSIS-Histoplasma capsulatum
A. Where do they come from?-in soil and in bird droppings-inhaled spores
(microconidia): world-wide but in US, remember Ohio-Mississippi River Valley region
B. Morphology-dimorphic; hyphae in soil; yeast in the body. Like to grow in
macrophages; small, round yeast with a clear zone and cell wall around the central body. Formation of caseating granulomata
C. What determines the severity of the infection?-acute, self-limited vs. disseminated 1. Size of inoculum
2. Immune status
D. Acute self-limited-end up with fibrocaseous nodules which may calcify
1. SMALL inoculum, good immunity-macrophages contain the yeast, form granulomata, limited to lungs and local lymph nodes
2. BIG inoculum, good immunity-extension to other parts of the reticuloendothelial system, but macrophages eventually contain the infection
E. Disseminated-bad immunity in the face of either new exposure or reactivation VI. COCCIDIOMYCOSIS (Coccidioides immitis)
A. Where do they come from?-soil-inhaled spores (arthroconidia); in US, in southwest (“San Joaquin Valley Fever”)
B. Morphology-dimorphic: hyphae in soil; yeast in body. Spores enlarge, eventually form sporangia, which are filled with little endospores, which are released when sporangia rupture. Inflammatory response with neutrophils and macrophages. Formation of caeasting granulomata
C. What determines the severity of infection?-acute, self-limited vs disseminated 1. Size of inooculom
2. Immune status-Host response by macrophages and neutrophils AND development of specific hypersensitivity and cell-mediated immunity D. Acute self-limited-in immunocompetent people-severity depends on size of the
innoculum-end up with fibrocaseous nodules which do NOT calcify
E. Disseminated-bad cell-mediated immunity in the face of either new exposure or reactivation
In addition to the usual patients at risk: African-Americans, Filipino patients, pregnant patients
VII. BLASTOMYCOSIS-Blastomyces dermatiditis
A. Where do they come from?-in decaying vegetable matter in the soil-inhaled spores; in North America, along Mississippi and Ohio Rivers, Great Lakes, and St. Lawrence River
B. Morphology-dimorphic: hyphae in the soil; Broad-Based Budding yeast in the body. Formation of suppurative granulomata (granulomata with neutrophils) C. What determines the severity of the infection?-self-limited pulmonary,
progressive pulmonary, disseminated
- Host response by macrophages and neutrophils AND development of specific hypersensitivity and cell-mediated immunity
D. Self-limited pulmonary disease-bronchopneumonic consolidation with
suppurative granulomatous response eventually contains the infection; may result in scarring. May resolve without treatment
E. Progressive pulmonary disease-uncontained infection resulting in cavities and miliary pulmonary disease: usually upper lobe disease. Can’t resolve without treatment
F. Disseminated disease-most common site of involvement = skin, where it may clinically mimic a skin cancer. Can’t resolve without treatment.
VIII. DERMATOPHYTES-Trichophyton, Microsporum, Epidermophyton
- Differ from II-VII in that they are not restricted to opportunistic infection.
A. Where do they come from?-in soil, on animals and on people. Infection of keratin by direct contact.
B. Morphology-hyphae and spores in the acellular keratin C. Athlete’s foot, etc.
