Pathogen : Pathogen : Penicillium marneffeiPenicillium marneffei dimorphic fungus dimorphic fungus yeast like with cross septum yeast like with cross septum

Mode of transmissionMode of transmission

: respiratory infection: respiratory infection

disseminateddisseminated

: Wright stain or Giemsa stain : Wright stain or Giemsa stain yeast like with cross septum 3 yeast like with cross septum 3 µm µm ( ( uusually in macrophage sually in macrophage ))

Penicillium other than P.marneffeiPenicillium other than P.marneffei

organorgan numbernumberLungLung

Prosthetic endocarditicProsthetic endocarditic

Infected CAPDInfected CAPD

EndophthalmitisEndophthalmitis

SepticemiaSepticemia

EsophagitisEsophagitis

Upper respiratory infectionUpper respiratory infection

Brain infectionBrain infection

1212

44

66

55

11

11

11

11

( Lyratzopaelos G , etal J infect 2002 ; 45 :184 – 207 )

Hypersensitivity pneumonitisHypersensitivity pneumonitis

Cheese – worker lungCheese – worker lung

Peat moss worker’ lungPeat moss worker’ lung

Salami worker’s lungSalami worker’s lung

Malt worker ‘s lungMalt worker ‘s lung

Farmer ‘s lungFarmer ‘s lung

Vienman 1956Vienman 1956 : bamboo rat : bamboo rat (( Rhizomys Rhizomys sinesis sinesis ))

KhwaseKhwase 19861986 : Li , et al study 16 : Li , et al study 16 Rhizomys pruinosusRhizomys pruinosus

93.1 % identified P. Marneffei93.1 % identified P. Marneffei87.5 % culture from lung87.5 % culture from lung56.3 % culture from liver56.3 % culture from liver56.3 % culture from spleen56.3 % culture from spleen50 % culture from abdominal 50 % culture from abdominal lymph nodelymph node

Mode of TransmissionMode of Transmission

- RespiratoryRespiratory- Skin ??Skin ??- GI??GI??

PathologyPathology

1. Granulomatous reaction : 1. Granulomatous reaction : lymph modelymph mode

2. Suppurative form : microbuses2. Suppurative form : microbuses

3. Anergic and necrotizing lesion 3. Anergic and necrotizing lesion : focal necrosis : focal necrosis

Clinical manifestation of HIV infected patient withClinical manifestation of HIV infected patient with P.marneffei, Chiang mai university hospitalP.marneffei, Chiang mai university hospital

Sign and symptomSign and symptom Number Number ((%%))

Sign feverSign fever

skin lesionskin lesion

coughcough

diarrheadiarrhea

74 74 925( . )925( . )

5 45 4 (67.5)(67.5)5 55 5 (48.7)(48.7)25 25 (31.2)(31.2)

Sign and SymptomSign and Symptom Number Number ((%%))

Symptum : fever ≥ 38Symptum : fever ≥ 38°C°C

weight lossweight loss

anemiaanemia

jaundicejaundice

oral candidiosisoral candidiosis

hairy lenkoplakiahairy lenkoplakia

Patatal papulesPatatal papules

generalized generalized lymphadenopathylymphadenopathy

hepatomegalyhepatomegaly

splenomegalysplenomegaly

genital ular genital ular

79 79 95(95())

6161(76.2)(76.2)

62 62 777755

6 6 75( . )75( . )

7979 73 737. )7. )

6 6 75( . )75( . )

3337( . )37( . )

46 46 57575. )5. )

4141 51 512. )2. )

13 13 16162. )2. )

5562( . )62( . )

Renew of 155 reported case Renew of 155 reported case ( ( Duong TA .Clin Infect DIS 1996;23:Duong TA .Clin Infect DIS 1996;23:((25-3025-30))

Clinical sign and symptomClinical sign and symptom Number Number ( ( % % ))

feverfever

anemia anemia

weight lossweight loss

Skin lesion Skin lesion

HemocultureHemoculture

lymphadenopathylymphadenopathy

CoughCough

HepatomegalyHepatomegaly

DiarrheaDiarrhea

SplenomegalySplenomegaly

PericarditisPericarditis

Osteolytic lesionsOsteolytic lesions

arthritisarthritis

152152 98( )98( )

116 116 (74.8)(74.8)111 111 716( . )716( . )

108 108 697( . )697( . )

84 84 (54.2)(54.2)81 81 523( . )523( . )

77 77 497( . )497( . )

68 68 439( . )439( . )

3636 232( . )232( . )

21 21 135( . )135( . )

7 7 45( . )45( . )

6 6 39( . )39( . )

6639( . )39( . )

Diagnostic smearDiagnostic smear

Skin scraping Skin scraping ( ( skin biopsy touch skin biopsy touch smear , bone marrow , lymph node smear , bone marrow , lymph node biopsy touch smear biopsy touch smear

Wright’s stainWright’s stain Oral yeast , 3-5 micronOral yeast , 3-5 micron With septum With septum ( ( binary fission binary fission ))

80 Patients from Chiang Mai university hospital80 Patients from Chiang Mai university hospital

specimenspecimen numbernumber positivepositive %positive%positive

Blood cultureBlood culture

Skin cultureSkin culture

Bone marrow cultureBone marrow culture

Sputum cultureSputum culture

Lymph node cultureLymph node culture

CSFCSF

Palatal papule Palatal papule scrapingscraping

Liver biopsy cultureLiver biopsy culture

Pleural fluid culturePleural fluid culture

Pharyngeal ular Pharyngeal ular scrapingscraping

7878

5252

2626

4141

99

2020

--------

5959

4747

2626

1414

99

33

33

11

11

11

75.675.6

90.490.4

100100

34.134.1

100100

1515

--------

30 Sample from CMU , 199330 Sample from CMU , 1993antifungalantifungal numbernumber MICMIC ( ( µg/mlµg/ml))

Geometric Geometric mean mean

rangerange

FluconazoleFluconazole

ItraconazoleItraconazole

KetoconazoleKetoconazole

MiconazoleMiconazole

Amphotericin BAmphotericin B

5-Flucytosine5-Flucytosine

3030

2828

2929

2929

2929

2929

7.9377.937

0.0090.009

0.0270.027

0.0010.001

0.9760.976

0.2480.248

0.313-20.00.313-20.0

<0.002-<0.002-0.190.19

<0.002-<0.002-0.0780.078

<0.002-<0.002-0.1560.156

0.25-4.00.25-4.0

<0.015-<0.015-0.460.46

TreatmentTreatment

Severe case : Amphotericin B 0.6 Severe case : Amphotericin B 0.6 mg /kg/day for 2 weeks Itraconazole mg /kg/day for 2 weeks Itraconazole 200 mg bid for 10 weeks. 200 mg bid for 10 weeks.

Mild case : Itraconazole 200 mg bid Mild case : Itraconazole 200 mg bid for 10 weekfor 10 week

Amphotericin BAmphotericin B

1.1. Amphotericin B DeoxycholateAmphotericin B Deoxycholate

- drip with 5 % dextrose in water- drip with 5 % dextrose in water

2.2. Lipid-complexed Amphotericin BLipid-complexed Amphotericin B

- Ampho B colloidal dispersion - Ampho B colloidal dispersion ( ( Amphotec Amphotec ))

- - Ampho B lipid complex Ampho B lipid complex ( ( Abelect Abelect ))

- - Liposomal Ampho B Liposomal Ampho B ( ( Ambisome Ambisome ))

Side effect of Amphotericin BSide effect of Amphotericin B

: Acute infusion – related : Acute infusion – related reactionreaction

- Fever , chill , tachypnea- Fever , chill , tachypnea

- not anaphylaxis- not anaphylaxis

Side effect of Amphotericin BSide effect of Amphotericin B

: Nephrotoxicity: Nephrotoxicity- dose dependent- dose dependent- loss K , Mg , bicarbonate- loss K , Mg , bicarbonate- risk : combine with other nephrotoxic - risk : combine with other nephrotoxic drug drug

hypotensionhypotensiondehydrationdehydrationkidney diseasekidney disease

Side effect of Amphotericin BSide effect of Amphotericin B

: : other side effectother side effectnausea , vomitingnausea , vomitingthrombophlebitisthrombophlebitisanemia ,thrombocytopenia , anemia ,thrombocytopenia , leucopenialeucopenia