bartonellosis: one health perspectives on an …
TRANSCRIPT
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BARTONELLOSIS: ONE HEALTH
PERSPECTIVES ON AN EMERGING
INFECTIOUS DISEASE
Edward B. Breitschwerdt, DVM
CENTER FOR COMPARATIVE MEDICINE AND
TRANSLATIONAL RESEARCH
North Carolina State University College of Veterinary
Medicine
&
Galaxy Diagnostics, Research Triangle Park, NC
• Gram negative, short pleomorphic rods • Family: BARTONELLACEAE
● Order: Rhizobiales ● Class: Alpha Proteobacteria
• Fastidious: Division time 22-24 hrs • Cellular targets:
•Erythrocytes •Endothelial Cells •Microglia Cells •Macrophages •CD34 Progenitor Cells
BARTONELLA SPECIES
Kordick DL, Breitschwerdt EB: J Clin
Microbiol. 33: 1655-56, 1999
Rhizobiales
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THE STATE OF BARTONELLOSIS!
“It is the mark of an educated mind to be able
to entertain a thought without accepting it”
Aristotle
Bubonic Plague 1411
My Thought: Is Bartonellosis
A Modern Day “Hidden”
Epidemic?
HOW CAN YOU HIDE AN
EPIDEMIC?
PERHAPS IT IS EASY:
1. Start with an unknown genus of bacteria.
2. Behave as a stealth pathogen that is difficult to detect or isolate.
3. Maintain a large and diverse pet and wildlife reservoir in nature.
4. Facilitate transmission through multiple vectors and by other means.
BARTONELLA, HIV, PCR AND
VASOPROLIFERATIVE DISEASE!
Bacillary
Angiomatosis
1990,s
Peliosis Hepatis
Relman D, et. al.NEJM: 1990
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BARTONELLA SPECIES AND
VASOPROLIFERATIVE DISEASES
• Bacillary Angiomatosis (Dogs & Humans)
• Spontaneous Splenic Rupture (Jaguar & Human)
• Hemangiopericytoma in a 12 year-old Female English Sheepdog*
• Epitheloid Hemangioendothelioma in a 13-year-old male (Hepatic)*
• EHE in patients from Australia and England**
• Hemangiopericytoma (Dog, Wolf, Horse)***
*Breitschwerdt EB, et. al. JCM, 2009 **Mascarelli PE, et. al. JCM, 2011
***Beerlage C, et al. Bartonella vinsonii subsp. berkhoffii and Bartonella
henselae as potential causes of proliferative vascular disease in animals.
Med Microbiol Immunol 201: 319-26, 2012.
BARTONELLA ENDOCARDITIS
HUMAN YEAR
B. quintana 93
B. elizabethae 93
B. henselae 93
B. washoensis 98
B. vinsonii arup. 99
B. vinsonii berk. 00
B. koehlerae 04
B. alsatica 05
B. mayotimonensis 10
CANINE YEAR
B. vinsonii 95
(berkhoffii)
B. clarridgeae 01
B. washoensis 03
B. quintana 05
B. henselae 09
B. koehlerae 09
B. rochalimae 09
Chomel B B, et al. Bartonella endocarditis: A pathology shared by animal
reservoirs and patients. Ann NY Acad Sc 1166: 120-126, 2009.
THE POSTULATE OF COMPARATIVE
INFECTIOUS DISEASE CAUSATION
Vergil is credited with stating: “Happy is he
who knows the causes of things”.
Bartonella spp. and disease causation:
Endocarditis
Granulomatous Inflammatory Disease
Chronic Intravascular Infection
Vasoproliferative Tumors
Breitschwerdt EB, et al: Koch’s Postulates and the Pathogenesis of Comparative
Infectious Disease Causation associated with Bartonella species. J Comparative
Pathology 3: 1-11, 2013
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COMPARATIVE DISEASE FEATURES
OF BARTONELLOSIS
Canine Human
Peliosis hepatis + +
Bacillary angioma + +
Endocarditis + +
Myocarditis + +
Granulomatous
Lymphadenitis + +
Hepatitis + +
Encephalitis + +
ITP/IMHA + +
KNOWN VECTOR TRANSMITTED
BARTONELLA SPP.
B. bacilliformis - sandfly, Lutzomia verrucarum
B. quintana - human body louse, Pediculus humanus humanus
B. henselae - cat flea, Ctenocephalides felis
B. grahamii - rodent flea, Ctenphthalmus nobilis
B. bovis – horn fly, Haematobia spp
Source: www.earlham.edu
Feces
Internalization
1
Regurgitation
2,3 5 6
blood meal
Adapted and modified from Dehio et al. Nature 2005
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BARTONELLA: RESERVOIR
HOSTS
Reservoirs:
• Rodents
• Cats
• Dogs
• Wildlife
• Ruminants
• Human beings
• Others
BARTONELLA MELOPHAGI: NEW
ZOONOTIC BARTONELLA SPP.
Bartonella melophagi DNA Sequencing
Sheep keds (Michael Kosoy)
Sheep Blood (David Bemis)
Isolation from Human Blood (BAPGM Platform)
Patient 1: Pericarditis- California
Patient 2: Chronic fatigue syndrome-
Ohio/NC Maggi R, Breitschwerdt EB. Emerg Infect Dis 2009
FLEAS, CATS AND
BARTONELLA SPECIES • B. henselae
• B. clarridgeiae
• B. koehlerae
• B. bovis?
• B. quintana?
FLEA CONTROL!
Pet/Flea Cycle
Wildlife/Pet/Flea Cycle
Photo: Stephen Jaffee DVM
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BARTONELLA KOEHLERAE AND
NEUROCOGNITIVE ABNORMALITIES
• 18 Year-old Woman
• Peripheral Visual Loss, Sensory Neuropathy,
Hallucinations (4 year history)
• Progression: Headaches, joint pain, back
pain, mood swings, dizziness
• Neurologist, Psychiatrist, Neuro-ophthalmol
• B. koehlerae seroreactive, BAPGM
enrichment blood culture positive Breitschwerdt EB, et al. J Clin Microbiol 49: 3415-17, 2011.
BARTONELLA KOEHLERAE Breitschwerdt EB. et al J Clin Microb, 2011
Sample
Day
Blood
PCR
BAPGM
PCR
Bk IFA Bh IFA Bvb IFA
0 Bspp
Neg 64* <16 <16
294 Neg Bk
256 <16
<16
507 Neg Bk
256 <16
<16
801 Neg Neg
<16
<16
<16
TICK TRANSMISSION OF
BARTONELLA SPECIES Billeter SA, Levy MG, Chomel BB, Breitschwerdt EB:
Vector Transmission of Bartonella species with emphasis on the potential for tick transmission. Med & Vet Entomol 22: 2008.
YES (1995-2005)
Case-based evidence. (Dogs and Humans)
Epidemiological Data (Dogs)
PCR Data (Ticks)
MAYBE (2008)
Vector transmission of Bartonella henselae by Ixodes ricinus. EID, 2008.
YES!- Reis C, et al. Plos Neglected Trop Dis. 2011
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BVB GENOTYPE I:
HISTORICAL PROGRESSION
• Polyarthritis
• Wt Loss, Seizures,
Vasculitis
• Epistaxis
• Endocarditis
BARTONELLA IFA
B. HENSELAE B. VINSONII SUBSP.
BERKHOFFII
WILL AN INSECT TISSUE CULTURE
MEDIUM ENHANCE THE GROWTH
OF FASTIDIOUS BACTERIA?
Christmas Holiday , 2003
Dr. Sushama Sontakke
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GALAXY DIAGNOSTICS
www.galaxydx.com Breitschwerdt EB, Sontakke S. US Patent #
7,115,385 Media and Methods for Cultivation of Microorganisms. Issued October, 2006
Chief Scientific Officer
A company devoted to diagnostic documentation of infections with Bartonella spp. and other fastidious bacteria.
Transfer of BAPGM isolation approach to CDC, Duke University & other researchers
Kosoy M, et al. Bartonella tamiae isolated from patients from Thailand J
Clin Microbiol, 46: 772-775, 2008
16S-23S PCR
Sequence
BAPGM culture
Sample DNA
DNA
Plate Isolates DNA
+ -
BARTONELLA SPP. DETECTION AND
ISOLATION USING BAPGM
Duncan AW, et al: A combined approach for the enhanced
detection and isolation of Bartonella species. J Microbiol
Methods 69:273-81, 2007
BARTONELLA VINSONII SUBSP.
BERKHOFFII & HUMAN INFECTION
Father 52 year-old male veterinarian
Progressive weight loss (HIV/cancer?)
Muscle weakness, Incoordination
Poorly defined vascular lesion MRI
Daughter 12 year-old, previously healthy
Headache, muscle pain, insomnia
Mother- BAPGM blood culture negative
Two Sons- BAPGM blood culture negative
Breitschwerdt EB, et al. Parasites and Vectors, Online, 2010
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CO-INFECTION: B. VINSONII & B.
HENSELAE
Neg
Neg
Bh (H1)
Bh (H1)
Neg
Neg
Bld ACD 1/18
Bld EDTA 1/18
NA
NA
NA
NA
Bvb II
B spp
Oral Swab 12/11*
Saliva
Neg Bvb II
Bvb II
Neg
Neg
Blood 11/5
CSF 11/5
Neg Neg Bvb II Blood 10/18
Isolate
Enrichment
Culture
Direct Sample Source
/Date: FATHER
Breitschwerdt EB, et al. Parasites and Vectors, Online, Open Access 2010
OCCULT INFECTION: B.
VINSONII SUBSP BERKHOFFII
Neg
Neg
Bvb II
Neg
Neg
Neg
Blood 03/20
Serum 03/20
Bvb II
Bvb II
Neg Blood 01/11
Neg
Neg
Bvb II
Bvb II
Neg
Neg
Blood 11/28*
Serum 11/28
Neg Bvb II
Neg Blood 11/07
Isolate
Enrichment
Culture
Direct Sample Source
/Date: Daughter
Breitschwerdt EB, et al. Parasites and Vectors Online, Open Access, 2010
BARTONELLA BACTEREMIA AND
NEUROLOGICAL DYSFUNCTTION
Patient Age Gender Neuro Abnor Barton sp.
1 23 F Seizures B. henselae
2 41 F H/I/ML B. henselae
3 44 F H/I/ML Bh/Bvb
4 54 F H/I/ML B. henselae
5 49 M Partial
Paralysis
B. henselae
6 14 M Migraines B. henselae
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SEIZURES WITH PERSISTENT
BARTONELLA HENSELAE Breitschwerdt EB. et al J Clin Microb 46:2856, 2008
Sample
Day
Blood
PCR
BAPGM
PCR
Bh IFA Bq IFA Bvb IFA
0 Bh
(H1)
Neg 256 128 256
31
*Isolate
Bh
(H1)
Bh
(H1)*
1024 256 256
256
(CSF)
Neg Bh
(H1)
NT NT NT
458
Neg Neg 64 64 64
HUMAN Perinatal TRANSMISSION
OF BARTONELLA SPP.
Father- B. vinsonii subsp. berkhoffii
Mother- B. vinsonii subsp. berkhoffii/B. henselae
Placental tissues (1998)- PCR negative
Cervical biopsy (1991)- B. henselae
Son (10 Yrs-old)- B. vinsonii subsp. berkhoffii/B. henselae
Daughter (Twin, died 8 days of age)- B. vinsonii subsp. berkhoffii/B. henselae
Entire family has been sick for 10-20 years. Breitschwerdt EB, et al J Clin Microbiol 48:2289, 2010.
NEEDLE STICK TRANSMISSION OF
BARTONELLA VINSONII (BERKHOFFII)
• 7 Year-old male Newfoundland Dog
• Referral- multiple cutaneous tumors
• Cytology- Histiocytic, lymphocytic or
undifferentiated epithelial neoplasia
• Fractious Dog- inadvertent needle stick
• Ehrlichiosis- Dx and Tx 5 months earlier
• ??? Needle Stick Transmission
• No seroconversion to Ehrlichia canis, PCR
negative
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NEEDLE STICK TRANSMISSION OF
BARTONELLA TO A VETERINARIAN
<16
Neg
Neg
234
32
(128)
Bvb I
Neg 81
<16 Neg
Bvb I* 33
<16 Neg
Neg 5
Bvb I
Seroconversion
Enrichment
Culture
Direct Day Post-
inoculation
*Headaches, Parathesias
BARTONELLOSIS: HIGH RISK AND
RHEUMATOLOGICAL PATIENTS
PARAMETER HIGH RISK RHEUMATOLOGIC
Patient # 192 296
Male/age 55/51 91/36
Female/age 137/40 205/46
Seroreactive (%) 49 63
PCR + (%) 24 41 Maggi RG, Mascarelli PE, Pultorak EL, Hegarty BC, Bradley JM, Mozayeni BR, Breitschwerdt
EB. Bartonella spp. bacteremia in high-risk immunocompetent patients. Diagn Microbiol
Infect Dis. 2011 Dec;71(4):430-7.
Maggi RG Pultorak EL, Mozayeni BR, Hegarty BC, Bradley JM, Correa, MT, Breitschwerdt
EB. Bartonella henselae, Bartonella koehlerae and Bartonella vinsonii subsp. berkhoffii
bacteremia in rheumatic patients from a Lyme disease endemic region. Emerging Infect Dis
18: 783-791, 2012
BARTONELLOSIS: A PROBLEM
IN ONE HEALTH
ENDOCARDITIS YEAR RESERVOIR VECTOR
B. quintana 93 Human/Cat Louse
B. elizabethae 93 Rat Flea
B. henselae 93 Cat Flea
B. washoensis 98 Gr. Squirrel Flea?
B. vinsonii arup. 99 Mice Tick?
B. vinsonii berk. 00 Dog/Coyote Tick?
B. koehlare 04 Cat Flea
B. alsatica 05 Rabbit Scratch
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ACKNOWLEDGEMENTS
• Colleagues
• VBDDL Staff
• Internal Medicine Residents
• Barbara Hegarty
• Ph.D. Graduate Students – Dr. Dorsey Kordick
– Dr. Brandee Pappalardo
– Dr. Jiraporn Suksawat
– Dr. Adam Birkenheuer
– Dr. Linda Kidd
– Dr. Ashlee Duncan
Center for Comparative Medicine
and Translational Research
OUR COMMUNITY: OUR WORLD: ONE HEALTH
Questions??