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BIOL 4849: Medical Mycology. 3. ▻ Widespread. □ Specifically in Southeast Asia o Burma (Myanmar), Cambodia, Southern China, Indonesia, ...

Typology: Lecture notes

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8/7/2011
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Penicillium marneffei
By: Jenee Thurston, Adam Speerstra, and Kelly Bees
Alternative Name: Penicilliosis
Taxonomy
Kingdom: Fungi
Phylum: Ascomycota
Class: Euascomycetes
Order: Eurotiales
Family: Trichocomaceae
Genus: Penicillium
Species: P. marneffei
Geographic Distribution
August 7, 2011 BIOL 4849: Medical Mycology 3
Widespread
Specifically in Southeast Asia
oBurma (Myanmar), Cambodia, Southern China, Indonesia, Laos,
Malaysia, Thailand and Vietnam
Cases were reported in HIV-positive patients in Australia,
Europe, Japan, the UK and the U.S..
All, except one traveled to Southeast Asia.
Courtesy of:
http://www.crownrms.com/rms/
office.southeast.asia.html
Epidemiology
Affects HIV-infected &
immunosuppressed patients
Discovered in bamboo rats
(Rhizomys & Cannomys )
Epidemiological markers and
reservoirs for human infections
High mortality and morbidity
rates
10% of HIV patients in Hong
Kong affected
Soil exposure, especially during
the rainy season, is a critical
risk factor.
Third most common
opportunistic infection (after
extrapulmonary tuberculosis
and cryptococcosis) in HIV-
positive individuals
8/7/2011 BIOL 4849: Medical Mycology 4
Courtesy of:
http://animaldiversity.ummz.umich.edu/site/accounts/pictures/Rhizomyinae.html
Life Cycle
8/7/2011 BIOL 4849: Medical Mycology 5
Thermally dimorphic
Divided into three distinct phases:
1. A multicellular, filamentous
(mold) vegetative form
2. Asexual reproductive stage
(conidiogenesis)
3. A unicellular yeast-
like/arthroconidial phenotype
Temperature and nutrition are key
factors to determine which
specific phase is displayed
8/7/2011 BIOL 4849: Medical Mycology 6
Young colonies are grown
on Sabouraud glucose agar
Rapid growing, flat,
filamentous, and velvety,
woolly, or cottony in texture
Usually appear bluish gray-
green
Mature colony is reddish
yellow, producing a pink or
red-rose pigment that
diffuses into the surrounding
medium
Courtesy of :http://cmr.asm.org/cgi/content/full/19/1/95
Morphologies of P marneffei under a microscope
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Penicillium marneffei

By: Jenee Thurston, Adam Speerstra, and Kelly Bees Alternative Name: Penicilliosis

Taxonomy

 Kingdom: Fungi

 Phylum: Ascomycota

 Class: Euascomycetes

 Order: Eurotiales

 Family: Trichocomaceae

 Genus: Penicillium

 Species: P. marneffei

Geographic Distribution

3 BIOL 4849: Medical Mycology August 7, 2011  Widespread  Specifically in Southeast Asia o Burma (Myanmar), Cambodia, Southern China, Indonesia, Laos, Malaysia, Thailand and Vietnam  Cases were reported in HIV-positive patients in Australia, Europe, Japan, the UK and the U.S..  All, except one traveled to Southeast Asia. http://www.crownrms.com/rms/ office.southeast.asia.html^ Courtesy of:

Epidemiology

 Affects HIV-infected & immunosuppressed patients  Discovered in bamboo rats (Rhizomys & Cannomys )  Epidemiological markers and reservoirs for human infections  High mortality and morbidity rates  10% of HIV patients in Hong Kong affected  Soil exposure, especially during the rainy season, is a critical risk factor.  Third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV- positive individuals 4 BIOL 4849: Medical Mycology 8/7/ http://animaldiversity.ummz.umich.edu/site/accounts/pictures/Rhizomyinae.html^ Courtesy of:

Life Cycle

5 BIOL 4849: Medical Mycology 8/7/

 Thermally dimorphic

 Divided into three distinct phases:

  1. A multicellular, filamentous (mold) vegetative form
  2. Asexual reproductive stage (conidiogenesis)
  3. A unicellular yeast- like/arthroconidial phenotype

 Temperature and nutrition are key

factors to determine which

specific phase is displayed

6 BIOL 4849: Medical Mycology 8/7/

 Young colonies are grown

on Sabouraud glucose agar

 Rapid growing, flat, filamentous, and velvety, woolly, or cottony in texture  Usually appear bluish gray- green  Mature colony is reddish yellow, producing a pink or red-rose pigment that diffuses into the surrounding medium Courtesy of :http://cmr.asm.org/cgi/content/full/19/1/ Morphologies of P marneffei under a microscope

Pathogenesis

7 BIOL 4849: Medical Mycology 8/7/

 Pathogen found in bamboo rat

feces, liver, lungs and spleen

 Higher incidence during rainy

season

 Favorable for production of fungal spores (conidia)

 Airborne spores inhaled by

susceptible individuals

 Unclear whether people get

the disease by eating infected

rats, or by inhaling fungi from

their feces

Courtesy of: http://medicine.med.nyu.edu/pulmonary/node/

Diagnosis and Histopathology

 Biopsy of skin lesions, lymph nodes or bone marrow

 The organism can also be identified on peripheral blood

smear or bone marrow aspirate

 Fungi shown:

 Spherical or oval in shape  Basophilic intracellular or extracellular yeastlike appearance on Wright stain, often with clear central septation

 Histopathologic features include granulomatous,

suppurative, or necrotizing inflammation

 Polymerase chain reaction (PCR) assay is under

evaluation for rapid diagnosis of P marneffei infection

8 BIOL 4849: Medical Mycology 8/7/

Clinical Manifestations

9 BIOL 4849: Medical Mycology August 7, 2011  Fever 99%  Anemia 78%  Weight loss 76%  Skin lesions 71%  Lymphadenopathy 58%  Hepatomegaly 51%  Pulmonary disease/symptom 49%  Diarrhea 31%  Splenomegaly 16%  Oral lesions 4%

Clinical Manifestations

 Duration of symptoms before presentation is 4 weeks.  Other common manifestations:  Skin lesions, anemia, lymphadenopathy, and hepatomegaly with or without splenomegaly.  Skin lesions are present in two thirds of cases  Include papular eruptions, central umbilicated papules, acnelike lesions and folliculitis.  Found on the face, trunk, and extremities.  Pharyngeal and palatal lesions  Subcutaneous nodules  Pulmonary symptoms (cough and dyspnea) occur in about 50% of cases. 10 BIOL 4849: Medical Mycology 8/7/ http://cid.oxfordjournals.org/content/32/4/e78/F2.expansion.html^ Courtesy of:

Treatment & Prevention

11 BIOL 4849: Medical Mycology August 7, 2011  Mortality is at a 20% rate with treatment  Amphotericin B with or without flucytosine, or itraconazole  Ketoconazole & miconazole  Newer azoles (posaconazole, ravuconazole, and voriconazole)  Clinical failure rates:  Fluconazole (63.8%)  Amphotericin B (22.8%)  Itraconazole (25%)  Primary prophylaxis with itraconazole 200 mg daily can prevent the occurrence of penicilliosis among patients with AIDS

Case 1.

12 BIOL 4849: Medical Mycology August 7, 2011

 Patient:

 Located in India

 27 - year-old male

 Recently developed multiple nodules on his face

 Other Symptoms:

 Fever, weight loss, anorexia, and general weakness.

 General examination revealed multiple molluscum

contagiosum-like papules of various sizes with

central umbilications mainly on his face, trunk, and

upper and lower limbs