Fungi

Front 1

What is the definition of dimorphic fungi?

Back 1

live in the environment in one form and in the infected tissue in another form

Front 2

What is the geographic distribution of histoplasmosis?

Back 2

Mississippi / Ohio River Valleys

also St. Lawrence river valley

Central and souther America

anywhere with moist soils lacking montmorillonite clay and enriched with bird or bat droppings

Front 3

What are risks for getting histoplasmosis?

Back 3

working in contaminated soils, chicken coops, exploring caves, renovating old houses.

in endemic areas more than 80% of people may be sero positive

Front 4

What is the pathogenesis of histoplasmosis?

Back 4

Intracellular growth of tiny yeasts within macrophages.

Epithelioid granulomatous cellular reaction resembling tuberculosis with abundant fibrosis and rare caseation necrosis.

Cell mediated immune mechanisms: cytokines (interferon gamma) activate macrophages to kill yeasts. Chemokines stimulate cellular rxn to create mature granulomas with abundant fibrosis. This has traditionally been thought of as walling off infection but may cause damage to organs as well.

Front 5

What is the primary clinical syndrome histoplasma causes?

Back 5

freuqnetly asymptomatic or mild disease, but may be flu-like with cough, fever, malaise, hilar adenopathy. can lead to mediastinal fibrosis with fibrous encasement of major vessels.

Front 6

What does reinfection with histoplasma look like?

Back 6

Exposure to large numbers of aerosolized spores in previously infected individuals may result in febrile illness with acute pulmonary infiltrates.

Front 7

Whatissues can result from chronic histoplasma infection?

Back 7

progressive fibrous and nodular apical infiltrates, which cavitate.

Clinical findings of cough, fever, and wt loss mostly in men over 40.

DIFFICULT TO DISTINGUISH FROM TB ON CXR

Front 8

What does disseminated histoplasmosis disease look like?

Back 8

resembles miliary TB. It is a chronic progressive infection in AIDs w/ histoplasma disseminating to multiple organs

Front 9

How is histoplasmosis diagnosed?

Back 9

1) Culture: yeast can be grown from respiratory specimens. Yeast converts to mycelia (aerial mycelium looks spikey as the hyphae grow up) in room temp cultures. Characteristic fruiting bodies (wheel with knobs) seen in mature cultures.

2) Histopath: macs stuffed with small budding yeasts are seen in lymph nodes, spleen, liver, and bone marrow. Granulomas with marked fibrosis may be seen in lung and other tissues. Fibrosis may distort anatomy of major vessels.

3) serology: antibody tests are useful for epidemiology but the humoral immune resposne is not reliable for the acute dx of infection, espeically in the immuno suppressed.

4) URINE ANTIGEN: Detection of histo antigen in urine is a useful correlate of active disease. histo urine natigen has high sensitivity only in disseminated isease especially AIDs it may cross react with cocci and blasto but not aspergillus.

Front 10

What is the tx of histoplasma?

Back 10

Not all infections require chemotherapy especially mild.

Amphotericin B used in severe, progressive disease especially with CNs involvement.

Azoles- itraconazole may be used to suppress chronic infection when the host does not have normal immune response.

Front 11

What is the geographic distribution of blastomycosis?

Back 11

Overlaps with histoplasmosis but is much less frequent.
Major river valleys of Midwest, south central US, scattered worldwide.

Moist soils, river and pond edges with organic content.

Front 12

What is the pathology / pathogenesis of blastomycosis?

Back 12

extracellular yeast may be seen in macrophages but do not multiply there.

Thick walled yeast with broad-based buds

non-caseating loose granulomas with neutrophils pyogranuloma. epithelial hyperplasia prominent. Immunopathology little studied.

Front 13

What are the clinical syndromes of blastomycosis?

Back 13

pulmonary probably most frequent, sometimes asymptomatic

Cutaneous--first recognized, but still uncommon- the lesion can be verrucous or can ulcerate and resemble squamous carcinoma grossly and microscopically.

bone- one of the few fungal infections with a predilection for this site.

Disseminated- GU tract, CNS

Front 14

How do you diagnose blastomycosis?

Back 14

1) stains of pus / tissue, histopath show the yeast forms. Thick walled.

2) Culture: mycelial form appears in days to weeks. "lollipop" fruiting structures on hyphae. Look like lollipop trees.

3) serology not useful, antibodies are boradly cross-reactive with other fungal antigens

Front 15

How do you treat blastomycosis?

Back 15

Amphotericin B for serious or progressive disease

Itraconaole for non-meningeal disease of moderate severity

Front 16

What are risk factors for blastomycosis?

Back 16

Male predominance, outdoor occupations

(exposure to infected dogs? they can be infected and are symptomatic...)

Front 17

Geographic distribution of Coccidioidomycosis

Back 17

lower sonoran life zone of the southwest: where the creosote bush grows, alkaline soils, mouths of rodent burrows, mycelial growth following spring rain

San Joaquin Valley, Central Valley of California, dust from agricultural operations blows over coastal cities, hundreds of thousands of cases (30-80% seropositivity of population in highly endemic areas)

Also in Central and South America

Front 18

Pathology / pathogenesis of coccidioidomycosis

Back 18

Inhalation of arthrospores, pulmonary infection, possible hematogenous dissemination of it.

Granulomatous response, endospores in characteristic spherules or varying size (this can be confusing), no true yeast forms seen. In patients with bronchiectasis, mycelial forms can be seen where the organism is exposed to the air.

Front 19

Disease syndromes of coccidioidomycosis

Back 19

Primary pulmonary- Valley fever: fever, cough, fatigue, arthralgias

Sometimes associated with eosinophilia (25% of pts), erythema nodosum (also assoc with other infections)

Disseminated- bone, skin, meninges, higher risk in pregnancy, black and Filipino populations. This is an important disease in AIDS patients.

Front 20

Diagnosis of coccidioidomycosis

Back 20

Serology, complement fixation, immunoprecipitin and ELISA tests

Culture--sputum or tissue can be sampled, the white fluffy mycelia appear within one week. This is a very hazardous culture in the laboratory; the barrel-shaped arthrospores are easily aerosolized.

Histopath: ID endospores within granulomatous reaction.

There is a skin test that can confirm exposure (most often asymptomatically.)

Front 21

Coccidioidomycosis Therapy

Back 21

Most primary disease is not treated.

Amphotericin B for progressive primary disease and immunosuppressed patients.

Meningitis: intrathecal Ampho B

? Role of azoles, may be used for chronic tx in the immunosuppressed.

Front 22

Sporotrichosis geographic distribution

Back 22

worldwide

association with rotting wood, sphagnum moss, potting soil, rose plants

Front 23

sporotrichosis pathology / pathogenesis

Back 23

Local inoculation, frequently upper limb

pyogranulomatous response

lymphangitic spread

Front 24

Clinical syndromes of sporotrichosis

Back 24

Cutaneous lymphangitis with nodules (not in classic lymph nodes) more serious infections have osteoarticular involvement and tenosynovitis. Systemic symptoms rare.

Pulmonary uncommon can cavitate more frequent in men, 30-60 yo

Disseminated in immunosuppressed.

Front 25

Diagnosing sporotrichosis

Back 25

Culture, yeast-like colonies grow in one week, begin to convert to mycelia at room temperature.

Histopathology difficult, cigar-shaped yeast not common in tissue

Serology not useful.

Front 26

Treating Sporotrichosis

Back 26

Potassium iodide, may work by increasing macrophage intracellular killing mechanisms.

Local heat for cutaneous lesions.

Itraconazole may have fewer side effects than iodide.

Front 27

Dimorphic fungi in nature?

Back 27

mycelia, fruiting body, spores

Front 28

dimorphic fungi in tissue?

Back 28

yeast (unicellular and divides almost always by budding)

Front 29

What other organism is histoplasma capsulatum similar to?

Back 29

mycoplasma tuberculosis

Front 30

What other organism is histoplasma capsulatum similar to?

Back 30

mycoplasma tuberculosis

Front 31

What dose histoplasma look like on the plate when cultured?

Back 31

moist creamy colonies with fuzzy edges

Front 32

In what patients are you worried about coccidioides?

Back 32

HIV patients or any immunocompromised patients in endemic areas. So many people are exposed there but control it. Those who are HIV positive do not and can have disseminated disease (in lots of organs).

Front 33

Where have you seen penicillium?

Back 33

Covering bread and fruit... bluish gray colored. Same deal but only one of the penicilliosis (penicillium marneffei) is pathologic to humans

If you see this, get a travel hx. Southeast Asia

only in immunosuppressed patients... an AIDS defining disease.

Front 34

Moulds

Back 34

tubular “hyphae” that grow by branching and longitudinal extension


Examples: Aspergillus, Zygomycetes (Mucormycosis)

Front 35

Dimorphic fungi

Back 35

yeast-like form in the host, but grow as mould in vitro at room temperature


Examples: Histoplasmosis, Blastomycosis, Coccidiodomycosis, Sporotrichosis.

Front 36

Opportunistic Infections

Back 36

Take advantage of defect in host defense
Not usually pathogenic

Front 37

What host factors contribute to acquisition of opportunistic infections?

Back 37

Impaired barrier defense (lines, etc.)

Depressed cell-mediated immunity (AIDS, transplant, chemotherapy, steroids)

Neutrophil dysfunction (chemotherapy, Diabetes)

Front 38

How do you diagnose opportunistic infections?

Back 38

histology- actually seeing the fungi growing into the tissue.

culture

Others such as classic clinical presentation or serologic tests.

Front 39

Thrush

Back 39

Common. Creamy white, curd-like patches/plaques on the tongue and other oral mucosal surfaces. Removed by scraping leaving a raw, bleeding, painful surface. Plaques are a pseudomembrane of fungus, PMN’s and epithelial debris. Can also just present as erythema. Variations: acute atrophic candidiasis, chronic atrophic candidiasis (“denture sore mouth”), angular cheilitis.

Front 40

What are risk factors for thrush?

Back 40

inhaled steroids, dentures, cancer, antibiotics, HIV

Front 41

How do you diagnose thrush?

Back 41

clinical appearance, scraping with KOH or Gram’s smear. >90% C. albicans

Front 42

Esophagitis

Back 42

Painful swallowing, feeling of obstruction, substernal chest pain. Most have oral thrush also.

Front 43

Esophagitis risk factors

Back 43

: AIDS, chemotherapy for hematopoetic malignancies

Front 44

Esophagitis diagnosis

Back 44

characteristic appearance or biopsy during endoscopy, >90% C. albicans

Front 45

Vulvovaginitis

Back 45

Common. thick, creamy cottage cheese-like discharge, intense pruritis, vaginal and labial erythema

Front 46

vulvovaginitis risk

Back 46

Diabetes, HIV, antibiotic therapy, pregnancy

Front 47

vulvovaginitis diagnosis

Back 47

: exam and wet mount or KOH of secretions showing hyphae and pseudohyphae.

Front 48

What are some other syndromes caused by candidiasis?

Back 48

Intertrigo
Paronychia and onychomycosis
Diaper rash
Perianal Candidiasis
Balanitis
Cutaneous lesions of Disseminated Candidiasis
Chronic Mucocutaneous Candidiasis (CMC)

Front 49

Candidemia

Back 49

. The presence of Candida in the blood. Spectrum of disease from mild fever to sepsis. If persistent, may disseminate (see below). May only become evident after dissemination to skin or other organs.

Front 50

Candidemia risk factors

Back 50

Immunocompromised, intensive care units, central IV catheters

Front 51

Candidemia diagnosis

Back 51

blood culture

Front 52

Disseminated Candidiasis

Back 52

When Candida disseminates, multiple organs can also be involved: kidney brain, myocardium and eye being the most common. In cancer patients, may get hepatosplenic involvement. The hallmarks of the pathologic changes are diffuse microabscesses with a combined acute suppurative and granulomatous reaction. Establishing the diagnosis can be difficult.

Front 53

Candida in the urinary tract- epi, sx.

Back 53

It is common to find Candida in the urine of hospitalized persons (up to 50%). It does not usually represent infection and is typically asymptomatic. Rarely Candida in the urine is a manifestation of systemic disease

Front 54

Upper urinary tract infection caused by candidiasis

Back 54

Usually a complication of disseminated disease, hematogenous spread and microabscess formation. May occur via the “ascending route” (ureteral reflux) but is RARE this way.. Can cause papillary necrosis, caliceal invasion, fungus ball formation, and perinephric abscess.

Front 55

Upper urinary tract infection caused by candidiasis risk factors

Back 55

diabetes, candidemia, anatomic or functional abnormalities

Front 56

Candida Cystitis sx, dx.

Back 56

Pyuria, fever and visualization (Gram’s stain) and culture of Candida as the predominant organism in the urine. These are actually poor indicators of infection rather than colonization; however, there are no other good indicators. Usually a complication of an indwelling Foley catheter, especially with concurrent antibiotic use. Fever may be absent in immunocompromised, so treatment may be indicated in the absence of symptoms or signs.

Rarely disseminates

Front 57

What is not a risk factor for disseminated candidiasis?

Back 57

HIV infection.

Front 58

The major risk factor for disseminated candidiasis?

Back 58

Neutrophil dysfunction.

Others include: central line for TPN, transplant recipient (receive immunosuppressive tx that affect neutrophils), leukemia for the same reason.

Front 59

What non-pharmacological interventions should be considered in a pt with candidemia and disseminated candidiasis?

Back 59

a. Removal of infected foreign bodies required, endocarditis of a native valve should be removed. Surgery may be required for closed-space infections (e.g., pericarditis)

Front 60

Antimicrobials used for candidemia and disseminated candidiasis.

Back 60

Amphotericin B (i.v.), Caspofungin/Micafungin (i.v.) or Fluconazole

Guidelines:

(1) Depends on the clinical status of the patient, drug toxicities, previous antifungal exposure and if the identification of the isolate is known.
(2) When the species and/or susceptibility are known, may consider a switch. Some Candida can be intrinsically resistant to Fluconazole (C. glabrata) and require alternative therapy (e.g., an echinocandin, Amphotericin). Treatment should continue for at least 2 weeks past the last positive culture, depending if the immune status of the patient is improved.
(3) Persistently positive cultures. a nidus (e.g., prosthetic, abscess) should be sought. It is important to note that Caspofungin is a large molecule and does not get into the urine or CSF well.

Front 61

Risk factors for patients with candida cystitits.

Back 61

a. Indwelling catheter: usually resolves without antifungal therapy assuming that the catheter is removed or changed.

concurrent antibiotic use.

Front 62

candida cystitis tx?

Back 62

b. Antifungal therapy: Symptomatic disease that does not resolve with removal of catheter or in asymptomatic persistent candiduria in severely immunocompromised hosts (e.g., renal transplantation, neutropenia).

Consider (1) Amphotericin bladder wash via catheter has the least systemic toxicity. Fluconazole (p.o. or i.v.) can be used

Front 63

How is aspergillosis acquired?

Back 63

Aspergillosis is usually acquired by inhalation of airborne spores, which are small enough to reach the alveoli and paranasal sinuses. Trauma (e.g., cornea, skin) also a nidus.

Front 64

Pathologic features of aspergillus

Back 64

2. Pathology of invasive aspergillosis in immunosuppressed persons: vascular invasion, leading to infarction, necrosis, edema, and hemorrhage. Hyphae are abundant: 2-4 µm wide, frequently septate and 45°angle branching.

**be aware that some pts have an allergic reaction to aspergillus which may contribute to the pathology.

Front 65

Dx of aspergillus

Back 65

1. Culture. Because it is in the environment, Aspergillus can be detected by culture of respiratory tract specimen where it can simply reside without causing disease (colonization) and rarely is it a contaminant in the lab.
2. Histology. Direct visualization of the organism invading tissue.
3. Serology. Galactomannan (aka Aspergillus antigen) –serologic test which detects a component of Aspergillus cell wall in the blood. Indicates invasive disease. Used only as an adjunct to diagnosis, best validated in patients with hematologic malignancy. If positive, look for evidence of invasive disease and confirm. Additional diagnostics are presented with each entity below.

Front 66

Tx overview of aspergillus

Back 66

1. Surgery: Aggressive debridement is necessary for sinus disease, brain disease and extensive focal necrotic cutaneous lesions. Surgery can be curative for a fungal ball, but it is usually reserved for those with recurrent hemoptysis.
2. Reduction of immunosuppression. Should be done if possible, but not always feasible. Poor prognosis if unable to reduce immunosuppression.
3. Medical therapy.

Front 67

What are the medical therapies for aspergillosis?

Back 67

a. Voriconazole has shown improved outcomes compared to conventional Amphotericin B in invasive pulmonary aspergillosis and is now the standard of care
b. Amphotericin products are also effective, but limited by toxicity. Aspergillus terreus is resistant (low ergosterol content);
c. Caspofungin is FDA approved for refractory aspergillosis.
d. Combination therapy may work but is still being evaluated.

Front 68

Epidemiology of zygomycosis (mucormycosis)

Back 68

Ubiquitous fungi, common inhabitants of decaying matter (fruit, bread, soil). Inhalation of conidia must be a daily experience, the infrequency of disease due to these organisms attests to their low virulence potential in humans.

It is limited to people with various immune compromise but is even RARE in this population.

Front 69

Pathogenesis of mucormycosis

Back 69

Usually enters the body through the respiratory tract. In animal models, high blood sugar and steroid use predispose to invasive disease after exposure. Presumed due to some combination of defects in macrophages and neutrophils. Once the fungus begins to grow, the hyphae invade tissue with affinity to blood vessels. Results in thrombosis and necrosis, two major hallmarks of the histopathology.

Front 70

Risk factors for mucormycosis

Back 70

Diabetes (particularly in the setting of acidosis), leukemia with prolonged neutropenia, iron overload with deferoxamine use., High level of suspicion in persons who develop the following clinical entities while taking Voriconazole because the drug has no activity against Zygomycetes.

Front 71

Rhinocerebral mucormycosis

Back 71

Acute sinusitis, facial pain, headache, fever, proptosis, orbital cellulitis. May erode through face and hard palate causing black escars. Cerebral abscess, cavernous sinus thrombosis can occur.

Front 72

Dx of rhinocerebral mucormycosis

Back 72

Diagnosis: CT scan showing erosion through the bone in the sinus or orbit. Often fatal.

Front 73

Dx of mucormycosis

Back 73

: Tissue for histopathology and culture are necessary to differentiate from Aspergillus. Vascular invasion with tissue necrosis.

Front 74

Tx overview of mucormycosis

Back 74

1. Surgery is necessary
2. Reversal of underlying problem. e.g., hyperglycemia and acidosis.
3. Medical therapy

Prognosis is very poor. (Rhinocerebral: 25-50% mortality; Pulmonary 80% mortality)

Front 75

What medical therapies do you use to treat mucormycosis?

Back 75

a. Amphotericin B
b. Posaconazole, has good activity (available only p.o.).
c. Voriconazole, Echinocandins are not active

Front 76

Clinical manifestations of cryptococcus infection.

Back 76

Meningoencephalitis

Respiratory.

Other spots like skin, bone, kidneys, eyes, heart, joints, muscle, prostate.

Front 77

Clinical manifestations of Meningoencephalitis caused by cryptococcus

Back 77

Insidious and subacute onset (weeks to months). May wax and wane. Headache, malaise. Impaired memory or judgment and behavior changes. Cranial nerve involvement (e.g., facial weakness, numbness, diplopia). Fever is variable. Hydrocephalus is a late sequellae.

Front 78

How do you diagnose cryptococcus?

Back 78

1) antigen testing=mainstay of dx. can test the CSF or serum. Titer indicates burden of disease.

2) CNS- CSF reveals elevated opening pressure. India Ink prep may revela organisms as it stains the capsule.

3) direct exam- supports dx esp. in CSF. stain with KOH, india in ink, or other stains to see the organisms also in sputum, bronchoscopy washings, CSF, or other fluids.

4) culture

Front 79

Principles of cryptococcus treatment and prophylaxis.

Back 79

1. Improve immune status. If possible, improve immune status by decreasing/removing immunosuppressive factors/medications. In AIDS, should institute anti-cryptococcal therapy prior to antiretroviral therapy to prevent Immune Reconstitution Inflammatory Syndrome (IRIS), a potentially serious inflammatory reaction to indolent infection.
2. Treatment of increased intracranial pressure. Serial lumbar puncture may be performed to lower intracranial pressure (keep < 200mmH20) by removing CSF. For serious disease requiring frequent LP’s, lumbar drain placement may be used. More permanent shunt may be necessary for those with elevated pressure after 4 weeks
3. Medical therapy

Front 80

What is the medical tx used to treat cryptococcus?

Back 80

a. Mild-moderate Pulmonary Disease, HIV-negative: May use Fluconazole.
b. Others: “Gold standard” is Amphotericin B and flucytosine (5FC) for all patients initially for “induction.” Depending on severity, improvement, and reversibility of immunodeficiency, treatment may be changed after the initial 2 weeks to Fluconazole, which is usually continued at a high dose for at least an additional 6 weeks, possibly longer.