fungi respi1

8/4/2019 Fungi Respi1

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SYSTEMIC MYCOSES

involve any tissue/organ

most serious of the fungal infections

2 main groups

1. Endemic respiratory mycoses

2. Opportunistic mycoses

ENDEMIC RESPIRATORY MYCOSES

acquired from inhalation of conidia (infectious

particles) from the soil

o portal of entry: respiratory tract

o 1 focus of infection: lungs

no evidence of [direct] transmission among

humans, animals

agents:

o have restricted geographic distribution

o exhibit thermal dimorphism (mycelia in

natural environment at room

temperature; yeast or spherules in

tissues at 37C)

o infect otherwise healthy individuals

1. Histoplasmosis2. Blastomycosis

3. Coccidioidomycosis

4. Paracoccidioidomycosis

5. Penicilliosis marneffei

HISTOPLASMOSIS

a.k.a. Darling’s/ Caver’s/ Spelunker’s disease,

North American Histoplasmosis

Discovered by Samuel Darling (hence, the name,

not darling BF/GF)

has worldwide distribution but particularly

common in Central and Eastern USE, Central andSouth America, Africa and Far East. Highest

distribution in the USA

1 sources of infection: soil, bat/avian habitat

may be contracted by occupational exposure

(e.g. cave explorers, bat guano miners, etc.).

risk factors: exposure to bird (e.g. chicken,

turkey, crow, blackbird, starling, etc.) or bat

droppings

DISEASE

Asymptomatic infection (90-95% of cases)

Pulmonary infection (5-10%)

o acute

very mild (e.g. fever, cough,

flu-like symptoms)

o chronic

can mimic any pulmonary

tuberculosis

Disseminated infection

o Reticulo-endothelial system (RES)

involvement

o muco-cutaneous infection

1 cutaneous infection (rare)

figure shows calcification in the hilar and mediastinal

nodes, chest x-ray mimicking pulmonary tuberculosis

CAUSATIVE AGENT

Histoplasma capsulatum

o a misnomer.

o fungi is not capsulated, but was once

thought so. Even when it was proven to

have no capsule, the name was

retained.

o anamorphic form ascomycete (teleomorphic form [sexual state]:

Ajellomyces capsulatus)

thermally dimorphic

facultative intracellular (resides intracellularly in

the Reticulo-endothelial system [RES])

grows in soil contaminated with bat/bird excreta

infectious particle: microconidia

tissue form: intra- and extra- cellular yeast cells

*There are 2 types of conidia: macro and micro. The

former cannot be the infectious particle, simply because

it is too big. It takes the smallest particle to reach the

lung alveoli

LABORATORY DIAGNOSIS

Histopathology sections

o Giemsa

o Periodic Acid Schiff (PAS)

o GMS

small, round to oval intra- and

extra- cellular yeast cells

*No KOH examination, because intracellular yeast cells

are difficult to demonstrate using it.

Culture at room temperature (RT)

Subject: MicrobiologyTopic: Fungi associated with RTI 1Lecturer: Dr. PadlaDate of Lecture: 9/1/11Transcriptionist: pinkyred Pages: 6 S

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o fine, sepatate hyphae

o large tuberculate macroconidia (quite

diagnostic)

o small microconidia

Culture at 37C

o small, single-budding yeast cells

o one has to demonstrate the multi-yeast

conversion because it is thermally

dimorphic

*cultures are the gold standard for diagnosis of endemic

respiratory mycoses

Identification of culture

o exoantigen test

o nucleic acid probe

*in lieu of the multi-yeast conversion

Other diagnostic tests

o Skin test: no diagnostic significance

o Serology (CF test)

o antigen detection

TREATMENT AND PREVENTION

treatment not required for most cases

itraconazole, ketoconazole, fluoconazole

(pulmonary), ampho B (systemic)

surgical resection of pulmonary lesions

wearing protective clothing, masks

soil decontamination with 3-5% formalin (when

feasible. of course one cannot decontaminate a

whole cave)

BLASTOMYCOSIS

a.k.a. North American Blastomycosis/ Chicago’s/

Gilchrist’s Disease

found in North America, Africa, Asia

outbreaks associated with activities around

moist soil (usually around rivers and creeks)

enriched with organic debris, rotting wood

natural disease common in cats and dogs (a

common veterinary problem)

canine blastomycosis is an indicator of the

fungus in the area

DISEASE

Asymptomatic infection (~50% of cases)

Pulmonary infection (acute/chronic)

o acute: pneumonia-like

o chronic: PTB-like


o skin, bone, GUT, CNS, spleen, kidney

Chronic cutaneous infection

o verrucous/ulcerative lesions

1 cutaneous infection (rare)

Left: X-ray shows infiltrates similar to TB

Right: verrucous/ulcerative lesions

CAUSATIVE AGENT

Blastomycoses dermatitidis

ascomycete (teleomorphic form: Ajellomyces

dermatitidis)

thermally dimorphic inhabits decaying wood materials

probably a soil saphrophyte

very rarely cultured from soils [sic] in endemic

areas

infectious particle: conidia

tissue form: broad-based yeast cells


KOH/Histopath

o thick-walled yeast cells (8-15 m) with

single, broad-based bud (characteristic

of Blastomyces dermatitidis) (unlikeusual yeast cells which are attached by

narrow-based buds)

Culture at RT

o Pyriform conidia (very infectious) borne

singly on sepate hyphae

Culture at 37C

o reveal double-walled yeast cells with

single broad-based bud

o demonstrate multi-yeast conversion



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Identification of Cultures

o exoantigen test

o nucleic acid probe

*more rapid, more specific, more accurate

Other Diagnostic Tests

o skin test: not much utility

o serology

o antibody detection

o antigen detectiono immunofluorescence

TREATMENT

Ketoconazole, Itraconazole, Fluconazole, Ampho

B (disseminated)

Excision/ corrective surgery for verrucous

lesions

COCCIDIOIDOMYCOSIS

a.k.a. Posada’s Disease/ San Joaquin Valley

Fever/ California disease/ desert rheumatism

endemic in the western hemisphere highest endemicity [sic] in semi-arid regions

with alkaline soil (specifically the Somoran

Desert)

outbreaks occur following dust storms,

earthquakes, earth excavations

DISEASE

Asymptomatic infection (~60% of cases)

Pulmonary infection (~30-40% of cases)

o chronic: can mimic carcinoma

o acute

Disseminated infection (<2% of cases)

o Infection of CNS, bones, skin

o meningitis: commonest (I was

surprised to find out this word

actually exists.) cause of death

Figure shows hilar adenopathy,

common in the disease

CAUSATIVE AGENT

Coccidioides immitis

a deuteromycete

thermally dimorphic

infectious particle: arthroconidia

o rectangular

o very resilient; highly infectious

(infectious dose: 1)

o abundant in alkaline soil

o develop into spherules in the lungs

tissue form: spherule

*If a spherule ruptures, it releases thousands of

endospores, each with the ability to become a spherule

itself.


KOH/Histopath

o thick-walled spherules (10-80 m)

filled with non-budding endospores (2-5 m)

Culture at RT

o hyphae bearing barrel-shaped

arthroconidia (2-4 x 3-6 m) separated

by dysjunctor cells (characteristic of

arthrospores of the organism)

Culture at 37C

o not routinely performed

Identification of Cultures

o Exoantigen test

o Nucleic acid probe

o Demonstration of spherule production

in animals, not in-vitro



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Other Diagnostic Tests

o Skin test (Coccidioidin/spherulla)

o Coccidioidin test using spherullin as

antigen: quite useful to determine

previous infection

o serology (complement fixation [CF]

test, immunodiffusion)

o CF titer is directly proportional: the

higher the antibodies, the poorer the

prognosis (unlike the usual casewherein higher Ab’s mean better

prognosis)

o immunofluorescence


Acute respiratory disease: not necessary to treat

traconazole, Ketoconazole, Fluconazole (for

meningitis), ampho B

surgery for skin lesions

reduce exposure to dust (soil) in endemic areas

vaccine development in progress

PARACOCCIDIOIDOMYCOSIS

a.k.a. South American Blastomycosis/ Lutz-

Splendore-Almeida’s Disease

incidence higher in males (male to female ratio

9-15:1)

o mycelium to yeast conversion inhibited

by estrogen (specifically -estradiol)

people >30 y/o

endemic in Central and South America,

Southern Mexico

DISEASE

Asymptomatic infection

Pulmonary infection

o acute: pneumonia-like

o chronic: PTB like


o granulomatous lesions in oral/nasal

mucosa: very characteristic, a.k.a.

Mulberry lesions

o cell wall polysaccharide (alpha-glucan)

stimulates granuloma formation

CAUSATIVE AGENT

Paracoccidioides brazillensis

A deuteromycete

Thermally dimorphic

Natural habitat remains unknown

found to reside in humid soil rich in protein

rarely recovered from endemic areas

has been cultivated in fruit bats (can be

naturally infected), armadillos (9-banded ones

are known hosts, but naturally-occurring

infection has not been proven)


tissue form: yeast cells with multiple, narrow-

based buds


KOH/Histopath

o yeast cells (10-30 m) with multiple,

narrow-based buds (characteristic)

Culture at RT

o septate hyphae with atypical pattern of

separation

Culture at 37C

o yeast cells with mariner’s/ steering

wheel appearance

o could be “hidden Mickeys” if there are

only 2 buds

IDENTIFICATION OF CULTURE

o Exoantigen test

o DNA probe

OTHER DIAGNOSTIC TESTS

o Skin test (Paracoccidioidin): not so

much use

o Serology (immunodiffusion [preferred],

CF)


Ketoconazole, Itraconazole, sulfa drugs, ampho

B

surgical exision of localized lesions

PENICILLIOSIS MARNEFFEI

endemic in South East Asia (Thailand, China, HK,

Vietnam, Indonesia, Taiwan, India)



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naturally-occuring infections have been found in

bamboo rats

bamboo rats

o reservoir of infection

o epidemiologic markers

has become an early indicator of HIV in endemic

areas

DISEASE

Pulmonary infectiono acute

o chronic


o similar to disseminated histoplasmosis

(RES involvement)

Left: X-ray shows infiltrates

Right: cutaneous manifestation

CAUSATIVE AGENT

Penicillium marneffei

Thermally dimorphic (only thermally dimorphic

Penicillium)

Yeast cells reproduce by schizogony (transverse

fission)

habitat: unknown


tissue form: yeast cells with transverse septum


KOH/Histopath

o small yeast cells (3-5 m), with

transverse septum (characteristic)

Culture at RT

o Conidiophores branch into metullae

that support the phialides that bear

chains of conidia

o colonies produce diffusible red pigment

(very characteristic)

Left: colonies with diffusible red pigment

Right: brush-like, fingerlike: characteristic of Penicillium

spp.

Culture at 37C

o round to oval yeast cells with

crosswalls

IDENTIFICATION OF CULTURES

o exoantigen test, conversion to yeast

forms

TREATMENT

Itraconazole, Ketoconazole, ampho B (seriously

ill)

___________END OF TRANX_____________

Hi to reych, arabels, anabels, eloh, jez, and to

gempot! Happy birthday to Quen! And to Ramone,

hehehe…hi din to Cuz! And to my dear roommate

maan…to Hannah, and rr! ^_^

Happy studying!



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