Dimorphic Fungi Flashcards
General principles of Dimorphic fungi
- Mold in the cold, yeast in the heat (except coccidiomycosis). Regulate morphology in response to environment.
- Virulence limited by temp, low redox potential (dead/decaying organic matter), and cell mediated immune defenses
- Infecivity determined by organism
- clinical manifestations determined by host (primarily cell mediated immunity. most common path = chronic granulomatous response but variation in granuloma).
- Thus have variation in sxs: asymptomatic w/ recovery, latent, local dz, disseminated with time slow or fulminant
- Natural habitat = soil/vegatation and infection = accidental. Main route = inhalation but direct inoculation can occur
- Specific host risk factors: higher incidence/more severe dz with compromised cellular immunity (AIDS, SOT, SCT, imunomodulator drugs, heme malignancy, etc.)
Generalized life cycle
- saprophytic mould (hyphae in soil at lo temp
- hyphae sporulate– infectious conidia/spores
- host inhales conidia/spores that develop into yeast at body temp
- tissue from host grows mold on artificial media at low tempes
Medically important dimorphic fungal dz
Sporotrichosis Coccidiomycosis Histoplasmosis Blastomycosis Paracoccidiomycosis Penicilliosis
“Some Can Have Both Phases”
Blastomycosis
GENERAL
Soil saprophyte, requires high humidity and low pH; may also affect dogs
Highest in Mississippi-Ohio River Valley region in US, Africa
Dimorphic fungus that exists as yeast phase (thick wall with broad based budding) in body and in culture at 37 deg; exists as mycelial phase in environment/room temp (white cottony)
INFECTION
Most acquired via pulmonary route; more in men than women
Primary pulmonary blastomycosis: may be asymp or alveolar pneumonitis (40-50 d incubation) typically resolves
Systemic: hematogenous spread from lungs; most commonly affects skin (50%) > bone (25-50%) >GU system, esp prostate (5-22%)
Primary cutaneous inoculation (i.e. from dog bite) rare
Diagnosis KOH of skin or sputum (find in 60%); gram stain, Calcofluor white, PAS Culture - Sabourauds Biopsy Serology DNA probe Urine antigen test- if prostate involvement - Antibody not useful for diagnosis
Treat:
- consider for every case to prevent extrapulm dz
- Pulm/extra pulm: Itraconazole 6-12 mo for mild-mod and Lipid Amphotericin B 1-2 wk then itraconazole f6-12 mo or mod-severe dz
- CNS: LAmB 4-6 wks then azole 12 mo
- Prego: LAmB
- IC: LaAmB 1-2 weeks then itraconazole 12 mo; lifelong maintenence if remains immunocompromised. Can discontinue of good HAART response in HIV
AmB > ITRA > VORI > FLU > KETO
Coccidiomycosis (coccidioides immitis)
GENERAL
Posada’s disease, San Joaquin Valley fever, desert fever
Soil saprophyte found in dry, sandy, and alkaline soils associated with hot summers and mild winters; only western hemisphere
150,000/yr with 70 deaths in US (usually in Sonoran life zone=desert i.e. Arizona)
Common in certain occupations: agricultural workers, military, construction;
May be worse (i.e. systemic infection) in AA, Filipinos, Asians
INFECTION
Usually pulmonary infection
Primary pulmonary: 60% asymp; 1-4 wks after inhalation can have flu-like illness or pneumonia that resolves; may have nonspecific skin manifestations (erythema nodosum and multiforme) or nonmigratory arthralgias (triad of E. nodosum + arthralgias + fever = “desert rheumatism”). 5% may develop cavity or nodule
Systemic: in 5% of pts with pneumonia may manifest lung nodules, chronic cavitary diseae and coccidiomas (granulomas with caseating necrosis); extrapulmonary most commonly disseminates to skin, bone > meninges. only in 0.5% nl hosts but up to 50% IC
Primary inoculation from accidental inoculation in labs, barbed wire or splinter injuries chancriform complex with ulceration, lymphangitis, regional LAD
DIAGNOSIS
Mycelial phase
Macro: glabrous but become white
Micro: alternating “barrel-shaped” arthrospores
Yeast phase: thick walled spherules with endospores; spherules resemble cocci
KOH, Calcofluor white of skin, sputum; NOT gram stain
- culture: white/cottony mould at 25 deg; septate hyaline hyphae with alternating arthroconidia (barrel-shaped arthroconidia in each cell then every other cell loses conida)
PCR
Serology: Ab
Complement fixation titer: posiive >/= 1 mo
Treat:
- Acute pneumonia: watch nl host; mod-severe or high risk host = fluconazole
- diffuse pneumonia - LAmB then fluconazole 12 mo-life
- No treatment for nodule unless enlarges
- Cavity: observation up to 1 yr in nl hosts. Fluconazole for high risk/symptomatic until closure/sxs resolve’ surgical resection for selected pts.
- Chronic progressive fibrocavitary dz: Fluconazole at least 1 year
- Extrapulmonary: LAmB + surgical debridement for nonmeningeal; fluconazole, itraconazole, LAmB followed by lifetime maintenence for meningeal; shunt for hydrocephalus
Paracoccidiomycosis (paracoccidioides brasileinsis)
GENERAL
- S. America blastomycosis, Lutz-Splndore-Almeida dz
- soil saprophyte in subtropical humid mtn forests of S. America; GI tract of bats
- Primarily affects men working outdoors
- incubation may be 10-20 yrs
INFECTION
- initial infection subclinical
- Childhood rom rapidly progressive
- chronic adult form 25% MORTALITY despite treatment
Primary pulmonary disease: cough dyspnea, fever, weight loss or asymp, cervical lyphadenopathy
Secondary disease: progresses to acute pulmonary disease (usually in immunocompromised), but more commonly chronic progressive; loves mucocutaneous surfaces; regional LAD
Diagnosis
- KOH of ulcers or sputum
- Mycelial phase: Undistinctive colony with brown discoloration from melanin. thin septate hyphae with few chlamydoconida
- Biopsy (“mickey mouse” or “pilot wheel” appearance)
- ulceration or pseudoepitheliomatous hyperplasia with intraepidermal abscesses/granulomatous response
- Serology: immunodiffusion test, complement fixation test (quantitative for following treatment)
Treat:
- supportive, nutrition, correct anemia
- Itraconazole 6-12 mo
- TMP-SMX 1-2 yrs
- Amphotericin B for severe/refractory dz
- ITRA = VORI > KETO»_space;> FLU
Histoplasmosis (histoplasma capsulatum/Ajello myces capsulatus)
General
Darling’s disease, Spelunker’s disease, Ohio Valley Disease
Soil saprophyte—grows best with high nitrite concentration
Frequently assoc with birds, esp starlings or bat excreta
Highest in Ohio-Mississippi Valley (lots of starlings)
Infection
Primary pulmonary infection: most asymptomatic; mild flu-like; may have erythema nodosum
Chronic pulmonary infection: chronic calcified nodules (looks like TB on CXR)
Disseminated: rare, usu in young/old/immunocompromised usually oropharyngeal ulcers (tongue); can also affect bone, liver, spleen and adrenals
- African Histoplasmosis: skin ulcers, nodules. progressive disseminated form reported
Diagnosis
Very small yeast, usually in macrophages with clear space simulating capsule
- epitheliod granulomas, tuberculoid, caseating, noncaseating
- Urine antigen test- Direct smeal low yield
- fungal culture
- Saprophytic Mould phase: slow growing folony; microscopic, thin branching septate with tuberculate round, thick-walled macroconida
TREAT
- acute primary pulm and histoplasma: no treatment
- mild dz (IC, nonmeninges)- Itraconazole
- chronic cavitary: Itraconazole
- mediastinal granuloma, pericarditis may require adding prednisone
- mediastinal fibrosis- IV stent
- Progressive Dissemnated Histoplasmosis: Ampho 1-2 wks then Iconazole 1 yr- life
- HIV pts in endemic regions: Itraconazole if CD Itra > Flu > Keto (too little data for VORI/POSA)
Sporotrichosis
- Sporothrix schenckii–zoonotic
- soil saprophyte in decaying vegatation
- ROSE GARDENER
Diagnosis
- yeast = cigar shaped, oval, budding
- Mycelia = thin, septate, hyphae with conidophores–“Daisies”
Clincal Dz
- Lymphocutaneous form (sporotrichoid) = 70-80% of infections; primary inoculation usually ulcer with localized lymphangitis/lymphadenitis. Tracks up lymphatics
- Fixed cutaneous- 20% infections; local ulcer becomes verrucous. Lymphangitis absent
- Disseminated: 1% of cases. Nl or IC host (alcoholic, DM, sarcoid, AIDS, malignancy); 80% joint involement
- Mucocutaneous
- Primary Pulmonary (inhalation)
Diagnosis
- Sporotrichoid!! (nodules ascending up lymphatics)
- Culture
- Biopsy: orgs rare but cigar shaped. Can do PAS stain
- Serologic tests not available
Treat:
- Local dz in nl host: Apply heat every day; oral potassium, iodide
- Oral itraconazole 3-6 mo in systemic infection
- Terbinafide- limited studies
- Amphotericin B for systemic/resistant local dz
- Surgical debridement in some periarticular and articular cases
Penicillosis
Penicillium marneffei aka Talaromyces marneffei
- SE Asia, assumed soil saprophyte; INHALATION, mostly MALES
Clinical
- Disseminated infection: fever, weight loss, anemic, hepatosplenomegaly, ,ymphadenopathy, fungemia, papular skin lesions, osteolytic lesions, pulm infiltrates
Diagnosis
- Hist: caseating granulomas/pyogranulomas in nl hosts vs IC hosts who have necrotizing infilatration of macrophages engorged with intracellular yeast
- Stain: Giemsa of bone marrow or peripheral smear, skin scrapings
- Culture: thin, branching septate hyphae with phiallides bearing conida “skeleton hands” in saprophytic vs slipticall nonbudding with central septum yeast
- No serology
Treat:
- LAmB 1-2 wks then itraconazole or fluconazole for 3 mo-life
LAmB > ITRA> FLU
