Emerging Dimorphic Fungi: Blastomyces Emergomyces...Blastomyces parvus B. silverae Emmonsia crescens Ea. sola Emergomyces canadensis Es. orientalis Jiang et al, Fungal Diversity 2018:90(1)245-291

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Ilan S. Schwartz MD PhD FRCPC

Assistant Professor

Division of Infectious Diseases

Department of Medicine

University of Alberta

Emerging Dimorphic Fungi:

Blastomyces & Emergomyces

MSGERC 2018, Big Sky, Montana

I have nothing to disclose.

Disclosures

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Emmonsia pasteurianaEmmonsia sp.Emmonsia sp.

B. dermatitidis/gilchristiiEmmonsia sp.Emmonsia helica

HistoplasmaParacoccidioidesEmmonsiellopsis terrestrisEmms. coralliformis

Emmonsia parvaEmmonsia sp.

Emmonsia crescensEmmonsia sp.Emmonsia sp.Emmonsia sp.

Emmonsia

Jiang et al, Fungal Diversity 2018:90(1)245-291

Ajellomycetaceae (Onygenales)

Emmonsia

Adiaspores

Dot et al. J Clin Microbiol 2009. 47(4):1269-1273

Sigler, L. J Med Vet Mycol, 1996; 34:303–14.

Borman AM et al, Emerging and Epidemic Fungal Infections in Animals 2018

100µm

Adiaspiromycosis

α– (not), –δια– (by), –σπορα (seed, sowing)

50 µm

E. crescens E. parva

Hubalek et al, Med Mycol 2005:43:692-697

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Emmonsia pasteurianaEmmonsia sp.Emmonsia sp.

B. dermatitidis/gilchristiiEmmonsia sp.Emmonsia helica


Emmonsia parvaEmmonsia sp.

Emmonsia crescensEmmonsia sp.Emmonsia sp.Emmonsia sp.

Emmonsia



Emmonsia

Es. pasteurianusEs. europaeusEs. africanus

B. dermatitidis/gilchristiiB. percursusB. helicus


Blastomyces parvusB. silverae

Emmonsia crescensEa. solaEmergomyces canadensisEs. orientalis

Emmonsia



Blastomyces

Emergomyces

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Blastomyces

Blastomyces dermatitidisSingle terminal conidia (“lollipop” like)

Double refractile, broad-based budding yeasts (~8-15 µm)

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Blastomyces dermatitidis

Davies et al, Can Vet J 2013: 54Baumgardner et al, J Med Vet Mycol 1995: 33

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Meece et al. Appl. Environ. Microbiol. 2011; 77 (15): 5123-31 Brown et al. PLoS ONE 2013; 8(3): e59237

Cryptic Speciation within B. dermatitidis

Epidemiology of B. dermatitidis species complex

Brown et al, PLoS One. 2013; 8: e59237.

Kenora, ON: 117.2 /100,000

Vilas County, WI: 40.4/100,000(Eagle River: 101.3/100,000)

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Blastomycosis Country?

Blastomyces helicus

Schwartz et al, Clin Infect Dis 2018

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Blastomyces helicus


Helical appendages

No conidia

Broad-based, multiply budding,short chains

B. helicus – human casesYear Location Medical History Sample Treatment Outcome

1970 Edmonton, Alberta

Alcoholic, diabetes CSF, blood None Fatal

1992 Swift Current, Saskatchewan

Chronic leukemia BM, blood, liver, sputum

Fatal

1999 Texas Lupus Blood Fluc, AMB Survived

2004 Okotoks, Alberta

Blood, BAL

2010 N. California Liver transplant Blood, pleural fluid

Vori, AMB Fatal

2010 Pocatello,Idaho

2013 Southern Texas None CSF Fluc Survived

2014 Salt Lake City, Utah

HIV, Hodgkin’s lymphoma

Blood Vori, AMB Fatal

2016 Alameda, California

HIV BAL Fluc, Mica, AMB

Fatal

2017 Omaha, Nebraska

BAL, pleural fluid


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B. helicus - Radiographic Findings


Courtesy of Robert Odrobina & Kim Hanson, University of Utah

Yeasts in vivo


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B. helicus - Veterinary Cases

ID Location Animal Exposures Sample

v1 Colorado Dog Prairie dog burrows Lung

v2 California Dog Lung

v3 Montana Cat Lung

v4 Colorado Cat Potted soil Lung

v5 Colorado ? ?


B. helicus - Veterinary Cases


ID Location Animal Exposures Sample

v1 Colorado Dog Prairie dog burrows Lung

v2 California Dog Lung

v3 Montana Cat Lung

v4 Colorado Cat Potted soil Lung

v5 Colorado ? ?

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Hannah et al, Clin Infect Dis 2001;32 De Groot et al, Clin Infect Dis 2000;30

B. helicus - Antifungal susceptibilities

Minimum inhibitory concentration (µg/mL)

Fluc Itra Vori Posa AMB Mica Caspo Anidulo Ref

h2 32 <0.016 <0.016 <0.016 0.0031 0.063 1

h5 0.125 <0.03 0.1250.5(24h)/

2(48h) 2

h7 1 <0.03 0.25 2 3

h8 ≤0.06 0.06 ≤0.06 0.5 1 1 1 3

h9 8 0.125 <0.03 0.125 0.06 4

h10 <0.03 <0.03 <0.03 1 2 3

1Dukik et al, AAC 2018; 2Kappagoda et al, EID 2017; 3Schwartz et al, CID 2018; 4Rofoel et al, EID 2017

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Where blastomycosis has been reported

Carman et al, Mycopathologia 1989;107(1):25-32; Frean et al, S Afr Med J 1989; 76(1):13–16; Randhawa et al, Med Mycol 2013;51(2):185–192; Kumar et al, Am. J. Trop. Med. Hyg., 2014;90(4):735–739

Serological Differences

Kaufman et al. JCM 1983; 18:110-4.

88/88

1/12

A

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What others have found

B. gilchristii

B. dermatitidis

Brown et al, PLoS One. 2013; 8: e59237.

A antigen (-)

Case isolates tested

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Blastomyces percursus

A exo-Ag (-)

24°C

37°C

Dukik et al, Mycoses 2017:1-14

Case DetailsYear Origin Comorbidities Sample Other sites Rx Outcome Ref

IHEM 26951

1964 Uganda NoneSynovial

fluid

Skin, bone, lung, liver, spleen, LN, thyroid, kidney

None Fatal 1

IHEM 26955

1972 Zaire None Skin Bone (rib) AMB 2g Survived 2

IHEM 26956

1975South Africa

Skin Unknown

CBS 514.14

1974 Angola Lymphoma Skin Lung Miconazole Survived 3

IHEM26957

1983 Morocco Skin Unknown

UAMH7425

1993 Israel None Skin/mouth Fluc x >6m Survived 4

CBS 142605

South Africa

HIV Skin Unknown

BP 222 2008South Africa

None Brain Lung AMB, itra Survived 5

NCPF 4091

SouthAfrica

HIV Skin

QGQT00000000

2010South Africa

NoneEndo-

bronchial mass

SkinAMB, itra x

11mSurvived 5

1Murray, Sabouraudia 1964; 2Bregant, Bull Soc Path Exot 1973; 3Bleeker, Trop. Geogr. Med. 1979; 4Kemna, ASM 1994; 5Heys, N Engl J Med 2014; 5Schwartz, CID 2065.

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Case Examples

Schwartz et al, Clin Infect Dis, 2015 Sep 15;61(6)

Case DetailsYear Origin Comorbidities Sample Other sites Rx Outcome Ref

IHEM 26951

1964 Uganda NoneSynovial

fluid

Skin, bone, lung, liver, spleen, LN, thyroid, kidney

None Fatal 1

IHEM 26955

1972 Zaire None Skin Bone (rib) AMB 2g Survived 2

IHEM 26956

1975South Africa

Skin Unknown

CBS 514.14

1974 Angola Lymphoma Skin Lung Miconazole Survived 3

IHEM26957

1983 Morocco Skin Unknown

UAMH7425

1993 Israel None Skin/mouth Fluc x >6m Survived 4

CBS 142605

South Africa

HIV Skin Unknown

BP 222 2008South Africa

None Brain Lung AMB, itra Survived 5

NCPF 4091

SouthAfrica

HIV Skin

QGQT00000000

2010South Africa

NoneEndo-

bronchial mass

SkinAMB, itra x

11mSurvived 5

1Murray, Sabouraudia 1964; 2Bregant, Bull Soc Path Exot 1973; 3Bleeker, Trop. Geogr. Med. 1979; 4Kemna, ASM 1994; 5Heys, N Engl J Med 2014; 5Schwartz, CID 2065.

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Courtesy of Lynelle Mottay, UCT

Blastomyces dermatitidis Blastomyces parvus (Emmonsia parva)

Blastomyces percursus

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Blastomyces



Blastomyces silverae


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Blastomyces parvus


(Formerly Emmonsia parva)

Budding cells?

Onygenales



HistoplasmaParacoccidioidesEmms. terrestrisEmms. coralliformis

B. parvusB. silverae

Ea. crescensEa. solaEs. canadensisEs. orientalis

Blastomyces

Emergomyces


Emmonsia

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Emmonsia crescens

(True) Adiaspore


Onygenales



HistoplasmaParacoccidioidesEmms. terrestrisEmms. coralliformis

B. parvusB. silverae

Ea. crescensEa. solaEs. canadensisEs. orientalis

Emergomyces


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Es. pasteurianusEs. africanus Es. orientalis Es. europaeusEs. canadensis

Schwartz et al, PLoS Pathog 2015: 11(11): e1005198

?

Schwartz et al, Emerg Infect Dis 2018; 24(4):758-761.

Emergomyces canadensis

35°C30°C

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Schwartz et al, Emerg Infect Dis 2018; 24(4):758-761.

?

*misidentified as Blastomyces dermatitidis based on positive DNA probe

Emergomycosis in North America

Year Location Age/ sex

MedicalHistory

Syndrome Sample Outcome

1 1992 Regina, Saskatchewan

68/M HIV Sepsis, skin lesions

Skinbiopsy

Fatal

2 2003 Saskatoon, Saskatchewan

39/M Kidney transplant,

DM2

Pneumonia, lymphad.,

esophagitis, fungemia

Blood, BAL

Survived

3* 2010 Colorado Springs,

Colorado

75/F ? Fungemia, endocervical

lesion

Blood Fatal

4 2015 Santa Fe, New Mexico

40/M HIV Pneumonia, skin lesions,

sepsis

Skin biopsy

Survived

Schwartz et al, Emerg Infect Dis 2018

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Kenyon NEJM 2013; Schwartz CID 2015, OFID 2016.

96%

87%

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Treatment and Outcomes

In vitro susceptibilities of Es. africanus (n=50)

Antifungal Method MIC50 (mg/L)

Itraconazole BMD 0.008

Voriconazole BMD 0.008

Posaconazole BMD 0.008

Fluconazole BMD 0.12

Caspofungin BMD 1

Micafungin BMD 2

Anidulafungin BMD 1

Flucytosine BMD 256

Amphotericin B Etest 0.006

Maphanga et al, JCM 2017

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✓✓

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✓✓

✓

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• Es. africanus detected 34 days (10%)

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✓✓

✓✓

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✓✓

✓✓

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Emmonsia



Blastomyces

Emergomyces

Es. africanusSouth Africa ImmunocompromisedSkin, bloodSmall narrow budding yeasts

B. percursusPan-African?, IsraelImmunocompetent Skin, bone> lung, brainLarge BBB yeasts

B. helicusWestern US/CanadaImmunocompromisedBlood, lung, CSFSmall yeasts (+/-chains)Mould: helices, sterile

Africa American West

Es. canadensisSK, CO, NMImmunocompromisedBlood, skinSmall narrow budding yeasts

Emer

go

myc

esB

last

om

yces

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Acknowledgements

Alfred BothaBarbra LermNadine Cronjé

Nelesh GovenderTsidiso Maphanga

Claire HovingMarc MendelsonSipho DlaminiDilys Berman

Chris KenyonYanping JiangKarolina DukikSybren de Hoog

Christina CuomoJosé Muñoz

Lynne Sigler

Nathan WiederholdTom Patterson

Estelle LevetinJosh McLoud

Bob Colebunders Kim Hanson

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B. helicus

• Mould– Absence of conidia

– Formation of helices

• Yeasts– Broad-based budding, singly

or multiply to form chains

– 4-9 µm in greatest diameter

B. dermatitidis

• Mould– Abundance conidia

– No helices

• Yeasts– Broad-based budding, singly

– 8-15 µm

Mycological Differences

B. helicus

• Immunocompromised >>> Immunocompetent

• Western or central parts of Canada/US

B. dermatitidis

• Immunocompromised <<< Immunocompetent

• Midwestern or eastern parts of Canada/US near great lakes, riverways

Epidemiological Differences

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B. helicus

• Disseminated, pulmonary

• Fungemia common

B. dermatitidis

• Lung >> Skin > elsewhere

Clinical Differences

Management Differences?

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Case 1

• CA ex HI, NM, CO, WY• Blood, BAL/sputum, BM, lung,

liver, brain

• CA ex Philippines via Ontario• Blood, BM, liver, skin, lung,

sputum, BAL, stool

Case 2

Case isolates tested

B. percursus

Documents

Emerging Dimorphic Fungi: Blastomyces Emergomyces...Blastomyces parvus B. silverae Emmonsia crescens Ea. sola Emergomyces canadensis Es. orientalis Jiang et al, Fungal Diversity 2018:90(1)245-291