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Bartonella

• Gram negative rod • Oxidase negative • aerobic (5% CO2) infections • GC content about 40% • Growth on blood agar Gilbert GREUB Institute of Microbiology University Hospital Center Lausanne, Switzerland

New permissive Angiogenesis cells Sanctuary site Multiplication VEGF Bartonella Bone marrow BadA = erythroblast ? VirB operon Alpha-2 Endothelial Related to: cells 4 to 8 days Invasion Endocytosis infection waves Potential for dissemination ICAM-1 Brucella Omp43 in many organs Invasome Agrobacterium tumefaciens Erythrocytes Bosea Afipia

Adhesion Invasion Multiplication Persistence

Spectrin Deformin Glycophorin Invasion-associated locus Bundle-forming pili Polar flagella

Blood-sucking arthropods B. quintana in homeless red blood cell, as seen by confocal microscopy © by authorGreub & Raoult J Med Microbiol 2002 Transmission

B. vinsonii subsp. vinsonii B. vinsonii subsp. arupensis ESCMIDBartonella Online LectureB. vinsonii subsp. berkhoffi Library Animal = reservoir of many Bartonella species B. washoensis B. quintana - in cats: retinitis, endocarditis, stomatitis B. henselae - in dogs: endocarditis, granulomatous hepatitis B. alsatica - in horses: osteoarthitis B. doshiae - in pigs, koalas, marsupials, sea mammals, … B. taylorii B. grahamii B. tribocorum 14 species may infect humans B. elizabethae B. bacilliformis B. clarridgeiae B. weissi B. birtlesii 0.1

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Bartonella Bartonella

B. bacilliformis Carrion disease B. bacilliformis Carrion disease

verruaga peruana verruaga peruana Oroya

Lutzomya Hemolytic anemia + fever

Bartonella Bartonella

B. bacilliformis Carrion disease B. bacilliformis Carrion disease B. quintana B. quintana Trench fever Chronic bacteremia

1914-1918 Quintan fieber - Trench fever © by author

ESCMIDBartonella Online LectureBartonella Library B. bacilliformis Carrion disease B. bacilliformis Carrion disease B. quintana Trench fever B. quintana Trench fever Chronic bacteremia Chronic bacteremia Bacillary Bacillary angiomatosis Hepatic peliosis Hepatic peliosis B. henselae Cat-scratch disease

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Bartonella B. bacilliformis B. quintana B. henselae B. bacilliformis Carrion disease B. quintana Trench fever Carrion disease Fièvre des Maladie des - verruaga peruana tranchées griffes de chat Chronic bacteremia - fièvre d’Oroya Bacillary angiomatosis Hepatic peliosis B. henselae Cat-scratch disease Endocarditis Angiomatose Endocardite bacillaire

Risk factors Risk factors B. henselae B. henselae Contact with a cat Cat-scratch disease Contact with a cat Cat-scratch disease + valvular disease Endocarditis + valvular disease Endocarditis + HIV infection Bacillary angiomatosis + HIV infection Bacillary angiomatosis

B. quintana Homeless, OH Chronic bacteremia Endocarditis + HIV infection Bacillary angiomatosis

Boillat & Greub. Rev Med Suisse 2008 © by authorBoillat & Greub. Rev Med Suisse 2008

ESCMIDRisk factorsOnline LectureCat-scratch diseaseLibrary B. henselae Contact with a cat Cat-scratch disease + valvular disease Endocarditis + HIV infection Bacillary angiomatosis

B. quintana Homeless, OH Chronic bacteremia Endocarditis + HIV infection Bacillary angiomatosis

B. bacilliformis Travellers (Peru, Bolivia, Ecuador) Oroya fever Autochtonous (Peru, Bolivia, Ecuador) Verruaga peruana

Boillat & Greub. Rev Med Suisse 2008 Dehio et al. Nat Microbiol Rev

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Inoculation lesions - present in 60% of cases - appear 3 to 10 days after inoculation Cat-scratch disease - 10 days before - persist during 1 to 3 weeks

- Isolated adenopathy - Persist during 2 to 6 months - Generally, spontaneous resolution

- Fever, myalgia, asthenia

Oculo-glandular sy. = Parinaud syndrome - following a conjounctival inoculation: - pre-auricular adenopathy What to do ? - conjonctivitis and/or retinitis

Complications of cat-scratch disease - suppuration (10-15%) - hepatosplenic lesions - neurological lesions - arthritis / osteomyelitis - endocarditis - … © by author

ESCMIDDiagnosis Online LectureDiagnosis (difficult Library to grow) Molecular diagnosis (PCR) Cell culture >> axenic culture - cat-scratch disease, endocarditis, … Endothelial cells + centrifugation Serology Sensitivity 10x better than blood agar - endocarditis (very high titres) p<0.001 from valves - microimmunofluorescence + W-blot p=0.045 from blood Fournier et al. J clin Microbiol 2002

(poor senitivity for bacillary angiomatosis) Better sensitivity when: - Subculture blood cultures bottles on agar after 7 days Histology + immunohistology - Congelation / saponin

Culture Attention: low CO2 production (undetected by automated systems)

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Diagnosis (difficult to grow) Shell vial Treatment Cat scratch disease Practically: Treatif major adenopathy or in case of immunosuppression - human endothelial cells (ECV304) - azithromycin 500 mg/day J1; then 250 mg/day for 2-5 days in RPMI 15% fetal calf serum 2% glutamine If retinitis or neurological involvment: - read-out: Gimenez staining, immunofluorescence - doxy 2x100 mg/day + rifampicine 2x 300 mg/day for 4-6 weeks on day 15 (30/45 if negative) Gouriet et al. J Clin Microbiol 2005 Bacteriemia / endocarditis - doxy 2x 100 mg/day for 4-6 weeks + gentamycin 3mg/kg for 2 weeks - Sensitivity: serology >> PCR >> culture 89.5% (39/48) 47.6% (10/21) 25.0% ( 9/36) on blood Bacillary angiomatosis 97.7% (44/45) 37.5% (18/48) on valve - 4 x 500 mg/day or doxy 2x100 mg/d for 3 months

Houpikian et al. Medicine 2002 Fournier et al. CDLI 2002

Boillat & Greub. Rev Med Suisse 2008; Rolain et al Ant Agents Chemother 2005

Conclusions Recommended readings: No need of antibiotic for uncomplicated Diagnosis and treatment Boillat & Greub cat-scratch disease Rev Med Suisse romande 2008;4:901-907

Include bartonella in the differential diagnosis Greub & Raoult of blood-culture negative endocarditis Chapter 2 in « Emerging Infectious Diseases » Kluwer 2003 Bacillary angiomatosis should be part of Rolain et al. differential diagnosis in HIV-infected patients Antimicrob Ag Chemother 2004 with low CD4 count and fever Pathogenesis Greub & Raoult Riess & al. J Med Microbiology 2002. J Exp Med 2004 Consider Carrion disease in a traveller returning from Andean with hemolytic anaemia Dehio et al Vayssier-Taussat et al. J Cell Sci 1997 PLOS pathogens 2010 © by author ESCMID Online Lecture Library

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