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Penicillium marneffei Infections Jenee Thurston, Kelly Bees, Adam Speerstra Courtesy of: www.doctorfungus.com Courtesy of: http://www.hindawi.com/journals/pri/2011/764 293/fig4/

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Page 1: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Penicillium marneffei Infections Jenee Thurston, Kelly

Bees, Adam Speerstra

Courtesy of: www.doctorfungus.com

Courtesy of: http://www.hindawi.com/journals/pri/2011/764

293/fig4/

Page 2: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Penicillium marneffei Discovered in 1959 by G. Segratain in Paris Discovered in 1959 by G. Segratain in Paris Only known thermally dimorphic species of Penicillium Can cause penicilliosis with fever and anemia Dimorphic saprophyte of soil and decomposing organic

matter. Taxonomy Includes:

Kingdom: Fungi Phlyum: Ascomycota Class: Euascomycetes Order: Eurotiales Family: Trichocomaceae Genus: Penicillium

Page 3: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Geographic DistributionGeographic Distribution

August 7, 2011BIOL 4849: Medical Mycology3

Widespread Widespread Specifically in Southeast AsiaSpecifically in Southeast Asia

o Burma (Myanmar), Cambodia, Southern China, Indonesia, Laos, Burma (Myanmar), Cambodia, Southern China, Indonesia, Laos, Malaysia, Thailand and VietnamMalaysia, Thailand and Vietnam

Cases were reported in HIV-positive patients in Australia, Cases were reported in HIV-positive patients in Australia, Europe, Japan, the UK and the U.S.. Europe, Japan, the UK and the U.S..

All, except one traveled to Southeast Asia.All, except one traveled to Southeast Asia.

Courtesy of: http://www.crownrms.com/rms/o

ffice.southeast.asia.html

Page 4: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

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

08/07/11BIOL 4849: Medical Mycology4

Courtesy of: http://animaldiversity.ummz.umich.edu/site/accounts/pictures/Rhizomyinae.html

Page 5: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Life Cycle

08/07/11BIOL 4849: Medical Mycology5

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

Page 6: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

08/07/11BIOL 4849: Medical Mycology6

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

Page 7: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Pathogenesis

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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/673

Page 8: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

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

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Page 9: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Clinical ManifestationsClinical Manifestations

August 7, 2011BIOL 4849: Medical Mycology9

Fever 99% Fever 99% Anemia 78% Anemia 78% Weight loss 76% Weight loss 76% Skin lesions 71% Skin lesions 71% Lymphadenopathy 58% Lymphadenopathy 58% Hepatomegaly 51% Hepatomegaly 51% Pulmonary disease/symptom 49% Pulmonary disease/symptom 49% Diarrhea 31% Diarrhea 31% Splenomegaly 16% Splenomegaly 16% Oral lesions 4% Oral lesions 4%

Page 10: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Clinical Manifestations cont.... 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.

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Courtesy of: http://www.med.cmu.ac.th/student/patho/Kamthorn/050.html

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Treatment & PreventionTreatment & Prevention

August 7, 2011BIOL 4849: Medical Mycology11

Mortality is at a 20% rate with treatment Mortality is at a 20% rate with treatment Amphotericin B with or without flucytosine, or Amphotericin B with or without flucytosine, or

itraconazoleitraconazole Ketoconazole & miconazoleKetoconazole & miconazole Newer azoles (posaconazole, ravuconazole, and Newer azoles (posaconazole, ravuconazole, and

voriconazole)voriconazole) Clinical failure rates: Clinical failure rates:

fluconazole (63.8%)fluconazole (63.8%) amphotericin B (22.8%) amphotericin B (22.8%) itraconazole (25%)itraconazole (25%)

Primary prophylaxis with itraconazole 200 mg daily can Primary prophylaxis with itraconazole 200 mg daily can prevent the occurrence of penicilliosis among patients prevent the occurrence of penicilliosis among patients with AIDS with AIDS

Page 12: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Case 1. Case 1.

August 7, 2011BIOL 4849: Medical Mycology12

Patient:Patient: Located in India Located in India 27-year-old male 27-year-old male Recently developed multiple nodules on his faceRecently developed multiple nodules on his face Other Symptoms:Other Symptoms:

fever, weight loss, anorexia, and general weakness. fever, weight loss, anorexia, and general weakness. General examination revealed multiple molluscum General examination revealed multiple molluscum

contagiosum-like papules of various sizes with contagiosum-like papules of various sizes with central umbilications mainly on his face, trunk, and central umbilications mainly on his face, trunk, and upper and lower limbsupper and lower limbs

Page 13: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Case 1. He was diagnosed seropositive

for HIV infection. Mild anemia, leukopenia, and a

raised erythrocyte sedimentation rate (ESR).

A chest X ray revealed bilateral patchy pneumonitis, and an ultrasonogram (USG) of the abdomen revealed mild hepatomegaly.

08/07/11BIOL 4849: Medical Mycology13

Courtesy of: http://jcm.asm.org/cgi/content/full/37/8/2699

Page 14: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Case 1. A portion of the fine needle aspirate (FNA) when

cultured yielded a Penicillium species red diffusible pigment was produced

Giemsa-stained smears of the aspirate numerous intracellular and extracellular oval, elongated or sausage-

shaped yeast-like cells, cells divided by fission rather than by a budding process.

Three days before initiation of treatment, the patient died.

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Page 15: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Case 2. 29 year old Male Tay Ninh province, Vietnam Presented weight loss and a

maculopapular rash on his genitalia. No previous testing for HIV

antibody or virus. On examination, the only

momentous findings were oropharyngeal candidiasis, cervical lymphadenopathy, and the maculopapular rash on his genitalia.

08/07/11BIOL 4849: Medical Mycology15

Courtesy of: http://cid.oxfordjournals.org/content/32/4/e78/F2.expansion.html

Page 16: Penicillium marneffei Infections - …crcooper01.people.ysu.edu/Penicillium marneffei-v2-X11.pdf · Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom

Case 2. Examination of chest and abdomen revealed no abnormalities. A chest radiograph appeared normal. Blood samples were collected for microbiological culture and

HIV testing. On the second day of hospitalization, he developed generalized

maculopapular rash with pustules and lesions with central necrotic umbilication

Results confirmed patient to be HIV positve Culture of his blood sample yielded a red pigment–producing

fungus that was subsequently identified as P. marneffei. Patient died ten hours after discharge

08/07/11BIOL 4849: Medical Mycology16

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ReferencesReferences

August 7, 2011BIOL 4849: Medical Mycology17

Lindan CP, Lieu TX, Giang LT, et alLindan CP, Lieu TX, Giang LT, et al Rising HIV infection rates in Ho Chi Rising HIV infection rates in Ho Chi Minh City herald emerging AIDS epidemic in Vietnam. AIDS 1997;11(Suppl Minh City herald emerging AIDS epidemic in Vietnam. AIDS 1997;11(Suppl 1):S5-13.1):S5-13.

Remadi S, Lotfi C, Finci V, Ismail A, Rogiano D, Vassilakos P, Seemayer Remadi S, Lotfi C, Finci V, Ismail A, Rogiano D, Vassilakos P, Seemayer TA. Penicillium marneffei infection in patients infected with the human TA. Penicillium marneffei infection in patients infected with the human immunodeficiency virus. A report of two cases. Acta Cytol 1995; 39:798-802.immunodeficiency virus. A report of two cases. Acta Cytol 1995; 39:798-802.

Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Vanittanakom N, Cooper R, Fisher M, Sirisanthana T, Penicillium marneffei Infection and Recent Advances in the Epidemiology and Molecular Biology Infection and Recent Advances in the Epidemiology and Molecular Biology Aspects. Clinical Microbiology Reviews.2006; 19:95-110Aspects. Clinical Microbiology Reviews.2006; 19:95-110

Stephenie Y. N. Wong and K. F. Wong, “Stephenie Y. N. Wong and K. F. Wong, “Penicillium marneffeiPenicillium marneffei Infection in Infection in AIDS,” AIDS,” Pathology Research InternationalPathology Research International, vol. 2011, Article ID 764293, 10 , vol. 2011, Article ID 764293, 10 pages, 2011. doi:10.4061/2011/764293pages, 2011. doi:10.4061/2011/764293

Zhoulin D, Bilbas JL, Gibson DW, Connor DHZhoulin D, Bilbas JL, Gibson DW, Connor DH Infections caused by Infections caused by Penicillium marneffei in China and Southeast Asia: review of eighteen Penicillium marneffei in China and Southeast Asia: review of eighteen published cases and report of four more Chinese cases. Rev Infect Dis published cases and report of four more Chinese cases. Rev Infect Dis 1988;10:640-7.1988;10:640-7.

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Questions . 1. P. marneffei grows best in:

Dry temperature

Rainy seasons**

The cold

Heat

2. P. marneffei usually affects:

The elderly

HIV infected patients**

Infants

Women

3. P. marneffei is located in:

Southeast Asia**

Africa

South America

The Caribbean

4. All except one are common symptoms of this disease:

Cough

Fever

Lesions

Depression**

5. Which is a life cycle stage in p. marneffei?

Multicellular

Unicessulur

Aesexual

All of the above**

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