Abir Znazen, Adnene Hammami.

Laboratory of Microbiology, Habib Bourguiba University Hospital © by author Sfax, Tunisia. ESCMID Online Lecture Library  1875: outbreak of Oroya  1885: Daniel Carrion (Peruvian medical student) inoculated himself with infected material  Alberto Barton:© by discoveryauthor of the agent of Carrion’s Disease ESCMID Online Lecture Library ( bacilliformis)

Historical overview Chronic Phase: Peruvian wart Vector: phlebotomine sand (Verruga Peruana) flies

© by author ESCMID Online Lecture Library Historical overview

© by author : : ESCMIDCat scratch disease Online Lecture Library

New species…………  and genus description  Epidemiology and transmission  Clinical manifestations  Case presentation: ◦ Bacillary © by author ◦ ESCMID Online Lecture Library  Gram negative rods  Facultative intracellular  Slow growth on blood agar medium  Inert in most biochemical tests Limitation of Standard© by biochemical author methods for identification  ESCMIDMolecular methods: Online Lecture Library Position of Bartonella species

16S rRNA gene

α

© by author γ

ESCMID Online Lecture Libraryβ

© by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library Rapidly growing number of Bartonella species and genotypes

Multilocus typing and other molecular techniques

Full genome analyses of Bartonella strains appear to © by author be a more promising approach for developing a natural ESCMID Online Lecture Library typing system. Natural cycle => Hemotropic life form: persistent intra-erythrocyte infection Specific mammalian host Transmission via arthropod vector

© by author ESCMID Online Lecture Library

Harms A, CMR, 2012.  Ubiquity

 Various animals : reservoir of zoonotic infections (pets++) ◦ Cats: B. henselae, B. clarridgeiae and B. koehlerae

 Well adapted host: asymptomatic bactereamia

 Seroprevalence: 14 to 50%

 Cat : many species++, role in transmission ◦ Dogs: B.vinsonii. Subsp berkhoffi(endomyocarditis), B. henselae, B. clarridgeiae (endocarditis),© by B. washoensisauthor, B. elizabethae, B. quintana and B. bovis ESCMID◦ Cattles: B. bovis Online (Europe, North Lecture America and Asia)Library ◦ Rats: B. elizabethae

Table1: Bartonella species and their vectors and hosts Arthropod hosts Mammalian hosts Reservoir Incidental B. vinsonii subsp. berkhofii dog Human B. vinsonii subsp. vinsonii Vole ear Vole B. vinsonii subsp. arupensis Tick Mouse Human B. taylorii ? Mouse, vole B. quintana Body louse Human B. henselae Cat , tick Cat Human B. koehlerae ? Cat Human B. alsatica ? Rabbit Human B. grahamii Fleas Mouse, vole Human B. elizabethae ? Rat Human B. tribocorum ? Rat B. birtlesii ? Mouse B. doshiae ? Vole B. rochalimae © by? author Dog, fax B. clarridgeiae ? Cat B. bovis ? Cattle B.capreoli ESCMID Online? Lecture RoeLibrary deer B.chomelii ? cattle B.schoenbuchensis Deer ked Roe deer B. bacilliformis Sand flies Human © by author ESCMID Online Lecture Library B. bacilliformis B. quintana B. henselae

© by author

Homelessness ESCMID Online alcoholismLecture Library Poverty Poor conditions of hygiene Body louse Other Bartonella species

B. vinsonii subsp. berkhoffii B. grahamii B. doshiae B. vinsonii subsp. Berkhoffii B. alsatica B. elizabethae B. clarridgeiae B.myotimonensis B. koehlerae B. washoensis B. tamiae B. koehlerae

© by author ESCMID Online Lecture Library B. bacilliformis B. quintana B. henselae

•Carrion •Trench fever •Cat Scratch Disease •Bacillary disease ©angiomatosis by author •Bacillary •Infective angiomatosis ESCMID Onlineendocarditis Lecture Library•Infective endocarditis Table3: clinical presentation associated with Bartonella sp species Human disease B. elizabethae Endocarditis, neuroretinitis B. clarridgeiae CSD, sepsis, endocarditis B. koehlerae Endocarditis, CSD B. vinsonii subsp. berkhoffii Endocarditis, arthralgia / myalgia / © byheadache author /fatigue B. washoensis Fever and myocarditis B. tamiae Fever B.ESCMID grahamii Online NeuroretinitisLecture Library B. doshiae CSD B. alsatica Endocarditis, lymphadenitis B. henselae pathogenesis

Cat scratch disease

Intra-erythrocytic Infective bactereamia endocarditis

Peliosis Chronic © bybactereamia author Bacillary ESCMID Onlineangiomatosis Lecture Library Ctenocphalides felis B. quintana pathogenesis

 Trench© by authorfever  Chronic bactereamia ESCMID Online Bacillary Lecture angiomatosis Library  Infective endocarditis+++ © by author ESCMID Online Lecture Library

 50 year old women  Immunocompetent  Djbeniana (rural area)  Low socioeconomic level  Multiple angiomatosis lesions persisting more than 6 months.© by author

Figure: angiomatosis lesions ESCMID Online Lecturelocalized Libraryon the left hand © by author ESCMID Online Lecture Library Tunisia Sfax Diagnosis

Histological lesions:+++

© by author Hematoxylin eosin staining Warthin starry staining

ESCMIDMicrobiology: Online Lecture Library ITS-PCR: Bartonella quintana

Treatment

: 3g/day during 3 months  Outcome: favorable© by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library  61 year old men  Immunocompetent  Sfax (Awabed locality)  Continuous fever  Low socioeconomic  Dyspnea status (hygiene)  Abdominal pain  No history of any cardiac disease © by author ESCMID Online Lecture Library Patient’s characteristics Clinical features  Fever: 39°  BP: 100/40mmHg, HR: 84bpm, RR: 20C/mn  Systolic and diastolic murmur in the mitral and aortic areas  Chest X ray: infiltrates© by author  ESCMIDAbdominal echography:Online Lecture Library  CRP: 144mg/l  ESR: 70 mm  WCC: 17120/mm3, hb: 8.2g/dl, Pl: 65000/mm3  Liver enzymes: 33/19 IU/l  3 sets of blood cultures© by author : negative ESCMID Online Lecture Library © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library

ETT: performed march 14 2013: vegetations on mitral and aortic valves + calcifications  ETO (March 15 2013):

◦ Aortic valve: mobile vegetation (20mm)

◦ Mitral valve: many vegetations with

calcification+ perforation © by author ◦ Perivalvular ESCMID Online Lecture Library Diagnosis: infective endocarditis Geographic origin

Poorness Defective hygiene© by author DestructiveESCMID Online valve lesions Lecture Library © by author ESCMID Online Lecture Library

Znazen A et al, AJTMH, 2005  The clinical and pathological characteristics

of Bartonella endocarditis :

◦ Previous history a valvular disease :missing

◦ More often affecting the aortic valve © by author ◦ Highly vegetative lesions with calcification

ESCMID Online Lecture Library Raoult D, JAMA int Med,2003 Serology: burnetii Bartonella Brucella Secondly: , Legionella, …. PCR on whole blood: © by author Standard PCR/ RT-PCR+++ ESCMIDGenes: ITS, rnpb ,Online fur, pap, Groel Lecture….. Library Serology results Chlamydia Bartonella pneumoniae quintana/henselae Phase I /II IgT - 6400/3200 - IgG 2048 - Neg IgM Neg - Neg IgA Neg - Neg • What is your diagnosis? © by author Bartonella endocarditis ESCMIDCross reactions Online between Lecture Chlamydia Library and Bartonella +++  Previously : almost all cases of Chlamydia endocarditis were in fact Bartonella endocarditis. (Maurin M , JCM, 1997)  In our series of BCNE: 13 patients with Bartonella IE showed positive serology to three chlamydial species © by author(Znazen A , AJTMH, 2005) ESCMID Online Lecture Library  Micro immunofluorescence assay:

◦ Gold standard

◦ Cross reactions between species

 Western blott with cross adsorption: © by author ◦ To confirm species

ESCMID◦ Antigen consuming Online Lecture Library © by author

ESCMID Online LectureFournier Library PE, CDLI, 2002 IgG titer> 1:800: .PPV of 0.81in patients with chronic infection .PPV of 0.955 in patients with infective endocarditis Clinical case (continues):

Patient was operated on March 22 2013

Prosthetic Aortic and mitral valves © by author

ESCMID Online Lecture Library . Culture . PCR . Histology © by author . Immunohistochemistry ESCMID Online Lecture Library Antimicrobial drug susceptibility of Bartonella :

 Penicillin  Cephalosporin  Aminoglycosides Raoult D, JAMA int Med,2003  Chloramphenicol  ,  Macrolides © by author  Rifampin  Fluoroquinolones  ESCMIDcotrimoxazole Online Lecture Library

Rolain JM, AAC, 2004  Aminoglycosides: 14 days

 Recommended antibiotherapy:

◦ Doxycycline: 100mg*2/day for 6 weeks

◦ Gentamicin : 3m©g/kg/day by author for 2 weeks ESCMID Online Lecture Library  Bartonella species: several host reservoirs ◦ B.quintana: detected in fleas!

 Wide clinical spectrum

 Diagnosis: Serology / PCR++  MLST + complete genome© by sequences:author ◦ Natural history : reservoir-transmission-IE ESCMID Online Lecture Library  Bartonella Network : ◦ Better description of epidemiology and pathogenicity

 Cardiology department, Hedi Chaker university hospital  Infectious diseases department, Hedi Chaker university hospital  Laboratory of Micrbiology© by author , Habib Bourguiba university hospital ESCMID Online Lecture Library © by author ESCMID Online Lecture Library