Emerging Dimorphic Fungi: Blastomyces Emergomyces...Blastomyces parvus B. silverae Emmonsia crescens...
Transcript of Emerging Dimorphic Fungi: Blastomyces Emergomyces...Blastomyces parvus B. silverae Emmonsia crescens...
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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
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
Es. pasteurianusEs. europaeusEs. africanus
B. dermatitidis/gilchristiiB. percursusB. helicus
HistoplasmaParacoccidioidesEmmonsiellopsis terrestrisEmms. coralliformis
Blastomyces parvusB. silverae
Emmonsia crescensEa. solaEmergomyces canadensisEs. orientalis
Emmonsia
Jiang et al, Fungal Diversity 2018:90(1)245-291
Ajellomycetaceae (Onygenales)
Blastomyces
Emergomyces
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Es. pasteurianusEs. europaeusEs. africanus
B. dermatitidis/gilchristiiB. percursusB. helicus
HistoplasmaParacoccidioidesEmmonsiellopsis terrestrisEmms. coralliformis
Blastomyces parvusB. silverae
Emmonsia crescensEa. solaEmergomyces canadensisEs. orientalis
Jiang et al, Fungal Diversity 2018:90(1)245-291
Ajellomycetaceae (Onygenales)
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
Schwartz et al, Clin Infect Dis 2018
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
Schwartz et al, Clin Infect Dis 2018
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B. helicus - Radiographic Findings
Schwartz et al, Clin Infect Dis 2018
Courtesy of Robert Odrobina & Kim Hanson, University of Utah
Yeasts in vivo
Schwartz et al, Clin Infect Dis 2018
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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 ? ?
Schwartz et al, Clin Infect Dis 2018
B. helicus - Veterinary Cases
Schwartz et al, Clin Infect Dis 2018
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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Es. pasteurianusEs. europaeusEs. africanus
B. dermatitidis/gilchristiiB. percursusB. helicus
HistoplasmaParacoccidioidesEmmonsiellopsis terrestrisEmms. coralliformis
Blastomyces parvusB. silverae
Emmonsia crescensEa. solaEmergomyces canadensisEs. orientalis
Blastomyces
Jiang et al, Fungal Diversity 2018:90(1)245-291
Ajellomycetaceae (Onygenales)
Blastomyces silverae
Jiang et al, Fungal Diversity 2018:90(1)245-291
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Blastomyces parvus
Jiang et al, Fungal Diversity 2018:90(1)245-291
(Formerly Emmonsia parva)
Budding cells?
Onygenales
Es. pasteurianusEs. europaeusEs. africanus
B. dermatitidis/gilchristiiB. percursusB. helicus
HistoplasmaParacoccidioidesEmms. terrestrisEmms. coralliformis
B. parvusB. silverae
Ea. crescensEa. solaEs. canadensisEs. orientalis
Blastomyces
Emergomyces
Jiang et al, Fungal Diversity 2018:90(1)245-291
Emmonsia
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Emmonsia crescens
(True) Adiaspore
Jiang et al, Fungal Diversity 2018:90(1)245-291
Onygenales
Es. pasteurianusEs. europaeusEs. africanus
B. dermatitidis/gilchristiiB. percursusB. helicus
HistoplasmaParacoccidioidesEmms. terrestrisEmms. coralliformis
B. parvusB. silverae
Ea. crescensEa. solaEs. canadensisEs. orientalis
Emergomyces
Jiang et al, Fungal Diversity 2018:90(1)245-291
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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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Schwartz et al, Clin Infect Dis 2015
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Schwartz et al, Clin Infect Dis 2015
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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Es. pasteurianusEs. europaeusEs. africanus
B. dermatitidis/gilchristiiB. percursusB. helicus
HistoplasmaParacoccidioidesEmmonsiellopsis terrestrisEmms. coralliformis
Blastomyces parvusB. silverae
Emmonsia crescensEa. solaEmergomyces canadensisEs. orientalis
Emmonsia
Jiang et al, Fungal Diversity 2018:90(1)245-291
Ajellomycetaceae (Onygenales)
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