penicillium marneffei

8/4/2019 PENICILLIUM MARNEFFEI

http://slidepdf.com/reader/full/penicillium-marneffei 1/33

`



Stephenie Y.N Wong & K.F.Wong ; Penicillium

marneffei infection in AIDS ; Pathology ResearchInternational ; Jan 2011



Penicillium marneffei : exhibits temperature dependent

dimorphic growth

Causes opportunistic infection in immunocomprised patients

Third most opportunistic pathogen after tuberculosis and

cryptococcosis in HIV endemic areas

Disease -Penicillosis marneffei



First described - Capponi et.al in 1956

Isolated from hepatic lesions of Bamboo rats

Identified as a new species in 1959 , G.Segretain

First Human infection was reported by G.Segretain



In 1973, first natural human infection was reported from a

patient with Hodgkin’s Lymphoma in South East Asia

During the period 1988-1989,disseminated Penicillosis began

to be observed in AIDS patients

However the importance of penincillosis as a human disease

was well recognized only when the global HIV pandemic

arrived in Asia



P.marneffei infection is mainly seen in HIV positive patients

Endemic in many areas of South East Asia (Thailand, Vietnam,

Hongkong, India, Southern China and Taiwan)

Natural habitat - soil

Humans and bamboo rats are the only known natural hosts



SOURCES OF INFECTION : Bamboo rat and soil

MODE OF TRANSMISSION : Inhalation of conidia or

cutaneous inoculation



Sequence of events

Inhalation of conidia

Engulfed by macrophages

Multiply and transforms into yeast

Disseminates through lymphatics andhematogenously



Immunity

Cell mediated immunity

Types of reactions

A. Granulomatous

B. Suppurative

C. Necrotizing

The failure of CD4+ T cell dependent immunity in AIDSpatients contributes to the development of disseminated

infection



Clinical features of P.marneffei infection is similar in patients

with or without HIV infection

Signs and symptoms : Chills, persistent cough, fever, anemia ,

leucocytosis, lymphadenopathy,

hepatosplenomegaly

Skin manifestation : Subcutaneous abscesses and papules like

ulcers, molluscum contagiosum like

lesions



Contd

Respiratory involvement - productive cough, dyspnea,

hemoptysis associated with

bronchopneumonia and

bronchopulmonary abscesses

Chest X-rays - diffuse reticular infiltration, localized

alveolar infiltrate or cavitary lesions

CNS involvement – uncommon

(Syndrome of acute altered mental status)



Facial lesions Mucocutaneous lesion



Molluscum contagiosum like lesions



Symptoms : Relatively non-specific

Differential diagnosis : Disseminated histoplasmosis,tuberculosis, pneumocystosis,

molluscum contagiosum

Rapid onset and more severe symptoms are observed in late HIVinfection with CD4+ count less than 100/µl



SpecimensSputum

Skin biopsy and skin scrapping

Bronchioalveolar lavage

pleural fluid

Bone marrow aspirates

Lymph node biopsies

Blood and

Urine



1. Modified giemsa stain

2. Gomori’s Methanamine Sliver (GMS)

3. Periodic acid schiff (PAS)

4. Papanicolaou stain(PAP)

5. Hematoxylin and Eosin6. Fluorescent staining



Gomori’s methanamine silver stain

The organism appears as a fission arthroconidia or unicellular

round to oval yeast cells with central septate fission



Giemsa stain



Specimens : Bone marrow, skin biopsies, blood

Culture media : SDA without cyclohexamide

Cotton seed agar

Sheep blood agar



Temperature Incubationperiod

Colony morphology

Microscopicstructure

P.marneffei

25°C 5-7days

Greenish yellow,characteristics

bright reddiffusiblepigment

Hyalineseptatehyphae with

erectconidiophore,Conidia -round to oval,arranged inshort chain

37°C 2-3days

Colonies : yeast like,glabrous, off- white

globose to oval with singleseptum orarthroconidia



Colony morphology at 25ºC LPCB mount



Colony morphology at 37ºC LPCB mount



The mold to yeast conversion or the phase transistion which is

thermally regulated is a diagnostic characteristic of P.marneffei

When the mold form is incubated at 37°C on 5% sheep blood

agar, the hyphae become shorter, develop more septa and

branches and cease to produce conidia

After 2 weeks, there is a gradual shift to spherical or ellipsoidal

yeast like cells which are 2-6µm in diameter

divides by transverse septation



Antibody detection tests

1. Micro immunodiffusion test : Mycelial culture filtrate

2. Indirect fluorescent Ab test : Germinating conidia & yeast cells

( Detection of IgG Abs )

Merits

Useful in monitoring the efficacy of treatment

Demerits

Not useful in immunocompromised patients

False positive results



Antigen detection tests

1. Immunodiffusion2. Latex agglutination test.

3. ELISA

Rabbit polyclonal antibodies against arthroconidia filtrates

are used

Molecular diagnosis PCR



Susceptible to 5-flucytosine and the azoles (miconazole,

ketoconazole, variconazole and itraconazole)

Fluconazole - Least active among the azoles.

Amphotericin B - Clinically effective but in vitro susceptibility

test shows variable results



Mortality rate in case of HIV infected patients is 100% in the

absence of treatment

Initial treatment in HIV positive patient : Intravenous

Amphotericin B (0.6mg/kg) for 2 weeks followed by oral

itraconazole (400mg) alone for 10 weeks



1. Drug interaction between antifungal and antiretroviral agents.

Itraconazole do not have significant interactions with most

nucleoside reverse transcriptase inhibitors (NRTIs) and raltegravir,

an integrase inhibitor

But it interacts well with protease inhibitors( indinavir, retonavir

and saquinavir) and increases the plasma concentrations of

itraconazole



2. The optimal timing of initiation of Highly Active Antiretroviral

Therapy (HAART) and the risk of development of immune

restoration inflammatory syndrome(IRIS) after HAART

IRIS usually occur a month after the start of HAART

Simultaneous initiation of HAART with antifungal or

delayed initiation until the end of the 2 weeks of induction

therapy of antifungal agent is recommended



Half of the patients develop relapse of penicillosis within 6

months after discontinuation of antifungal treatment.

Secondary prophylaxis with itraconazole (200 mg/day)

is recommended to all the patients who have completed thetreatment for penicillosis.



Penicillosis remains as a significant public health problem in

endemic areas of South East Asia

Early diagnosis and treatment can reduced the mortality rate

among the HIV patients

Considered as an AIDS defining illness in HIV endemic areasand its diagnosis warrants the initiation of HAART



Medical microbiobiology by Jawetz, Melnick and Adelberg ,25th edition.

Clinical and Pathogenic microbiology by Barbara

J.Howard,3rd edition.

Medical mycology by Rippon,3rd edition. Diagnostic microbiology by Bailey & Scott’s 12th edition.

Microbiobiology & microbial infections,Topley &

Wilson,volume 4 ,9th edition.

Fundamentals of Diagnostic Mycology by Fran Fischer. Online mycology,Adelaid university of Australia



Stephenie Y.N Wong & K.F.Wong ; Penicillium marneffeiinfection in AIDS ; Pathology Research International ; Jan

2011

Nongunch Vanittanakom & et all; Penicillium marneffei

infection & recent advances in the epidemiology & molecular

biology aspects ; Clinical Microbiology Reviews, Jan 2006,

volume 19; Page 95-110

penicillium marneffei

Documents