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Abir Znazen, Adnene Hammami. Laboratory of Microbiology, Habib Bourguiba University Hospital © by author Sfax, Tunisia. ESCMID Online Lecture Library 1875: outbreak of Oroya Fever 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 (Bartonella bacilliformis) Historical overview Chronic Phase: Peruvian wart Vector: phlebotomine sand (Verruga Peruana) flies © by author ESCMID Online Lecture Library Historical overview © by author Bartonella henselae: Bartonella quintana: Trench fever ESCMIDCat scratch disease Online Lecture Library New species………… Taxonomy and genus description Epidemiology and transmission Clinical manifestations Case presentation: ◦ Bacillary angiomatosis© by author ◦ Infective endocarditis 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 fleas: 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 Tick dog Human B. vinsonii subsp. vinsonii Vole ear mite Vole B. vinsonii subsp. arupensis Tick Mouse Human B. taylorii ? Mouse, vole B. quintana Body louse Human B. henselae Cat flea, 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 Hepatitis 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 Bacillary angiomatosis Treatment Erythromycin: 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 hepatomegaly 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 abscess 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: Coxiella burnetii Bartonella Brucella Secondly: Chlamydia, Legionella, Mycoplasma…. PCR on whole blood: © by author Standard PCR/ RT-PCR+++ ESCMIDGenes: ITS, rnpb ,Online fur, pap, Groel Lecture….. Library Serology results Chlamydia Bartonella Coxiella burnetii 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 Doxycycline, tetracycline 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 .
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  • Are Mycobacterium Drugs Effective for Treatment Resistant Lyme Disease, Tick-Borne Co-Infections, and Autoimmune Disease?

    Are Mycobacterium Drugs Effective for Treatment Resistant Lyme Disease, Tick-Borne Co-Infections, and Autoimmune Disease?

    Central JSM Arthritis Bringing Excellence in Open Access Case Report *Corresponding author Richard I. Horowitz, Hudson Valley Healing Arts Center, 4232 Albany Post Road, Hyde Park, New York 12538, Are Mycobacterium Drugs USA, Tel: 845-229-8977; Fax: 845-229-8930; Email: Submitted: 15 June 2016 Effective for Treatment Accepted: 14 July 2016 Published: 16 July 2016 Resistant Lyme Disease, Tick- Copyright © 2016 Horowitz et al. Borne Co-Infections, and OPEN ACCESS Keywords Autoimmune Disease? • Lyme disease • Bartonella Richard I. Horowitz* and Phyllis R. Freeman • Tularemia Hudson Valley Healing Arts Center, USA • Behçet’s Disease/Syndrome • Rheumatoid arthritis • Dapsone Abstract • Pyrazinamide Introduction: PTLDS/chronic Lyme disease may cause disabling symptoms with • Persister bacteria associated overlapping autoimmune manifestations, with few clinically effective published treatment options. We recently reported on the successful use of a mycobacterium drug, Dapsone, for those with PTLDS. We now report on the novel use of another mycobacterium drug, pyrazinamide, (PZA), in relieving resistant symptomatology secondary to Lyme disease and associated co-infections, while decreasing autoimmune manifestations with Behçet’s syndrome. Method: Disabling multi-systemic/arthritic symptoms persisted in a Lyme patient with co-infections (Bartonella, tularemia) and overlapping rheumatoid arthritis/ Behçet’s disease, despite several rotations of classic antibiotic and DMARD regimens. Dapsone, a published treatment protocol used for Behçet’s syndrome, recently has been demonstrated to be effective in the treatment of PTLDS/chronic Lyme disease and co-infections. It was superior to prior treatment regimens in relieving some resistant chronic tick-borne/autoimmune manifestations; however, it did not effectively treat the skin lesions and ulcers secondary to Behçet’s disease, nor significantly affect the granuloma formation, joint swelling, and pain associated with Lyme, Bartonella, and RA.