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Bartonella Infections

Description of Medical Condition

Bartonella infections cause manifestations in two broad categories:

  • Localized skin lesions and prominent regional lymphadenitis, i.e., typical cat scratch disease (CSD). Atypical CSD manifestations often represent disseminated infection.
  • Primary bacteremia, potential for persistent disseminated infection with localized inflammatory (and neovascular) lesions in a variety of organ systems and/or ongoing bacteremia.

System(s) affected: Nervous, Cardiovascular, Musculoskeletal, Pulmonary, Gastrointestinal, Skin/ Exocrine, Hemic/Lymphatic/lmmunologic

Genetics: No defined genetic predisposition

Incidence/Prevalence in USA:

Non-B. bacilliformis infections:

  • CSD: estimated 9.3/100,000 people (approximately 25,000 cases annually)

Others, no incidence estimates

Predominant age:

B. henselae infections:

  • CSD: 55% in persons < 18 years old
  • BA/BP, bacteremia, endocarditis, other syndromes: predominantly adults

Bartonella Infections

Predominant sex: Non-B. bacilliformis infections: Male > Female

Medical Symptoms and Signs of Disease

Carrion disease (the spectrum of B. bacilliformis infection)

  • Oroya fever (acute bacteremia): abrupt onset 3 weeks after inoculation, morbid course; severe anemia due to bacterial invasion of erythrocytes, many complications
  • Asymptomatic persistent bacteremia: <15% of Oroya fever survivors not treated with antibiotics
  • Verruga peruana: crops of nodular angiomatous skin lesions months after Oroya fever; mucosal and internal lesions also; involute in months to years

Typical CSD (89% of cases)

  • 4-6 days after inoculation: 50-75% develop 2-3 mm macule at the trauma site; progresses to a papule or pustule
  • Regional adenopathy 1-8 weeks post-inoculation; sole manifestation in up to 50%
  • Nodes involved: 80% upper extremities, neck, head
  • Suppuration of involved nodes: 15%.
  • Malaise and/or fever: 30% of patients
  • Spontaneous resolution: 2-4 months for majority

Atypical CSD (11% of cases)

  • Parinaud oculoglandular syndrome: granulomatous conjunctivitis and ipsilateral preauricular lymphadenitis Oneuroretinitis: usually unilateral; macular star exudate, papilledema, retinal nodules, angiomatous subretinai changes; self-limited, with return of visual acuity to near-baseline; concurrent B. henselae bacteremia found in some
  • Encephalopathy: mild-profound changes of higher cortical functions; seizures; neurologic sequelae rare
  • Other manifestations self-limited, sequelae rare: granulomatous hepatitis/splenitis, osteolysis, atypical pneumonitis, fever of undetermined origin (FUO). mononucleosis-type syndrome, others

Bacteremia due to non-B. bacilliformis species: short-term fatality uncommon

  • B. quintana: (Eponyms: Trench fever, Wolhynia fever, shin-bone fever, quintan fever) Incubation days-weeks; sudden onset of fever, non-specific symptoms/signs; self-limited illness may be brief (4-5 days), prolonged (2-6 weeks), most commonly paroxysmal (3-5 episodes of 5 days duration).
  • B. henselae: HIV-infected: insidious onset of fatigue, malaise, aches, weight loss, recurring fevers, headache; localizing findings uncommon. HI V-uninfected: abrupt onset of fever, may persist or become relapsing; myalgias, arthralgias, headache localizing findings unusual; asymptomatic persistence can evolve.

Endocarditis: fever, new or changed heart murmur

Bacillary angiomatosis/peliosis (BA/BP): neovascular proliferation disorders

  • BA: mostly immunocompromised hosts, e.g., HIV-infected; involves skin (crops of subcutaneous or dermal nodules, and/or skin-colored to purple papules; may ulcerate with serous or bloody drainage, and crusting), regional lymph nodes, internal organs; 6. henselae and B. quintana both inculpated
  • BP involves liver and spleen in HIV-infected and other immunosuppressed persons; can involve lymph nodes as well; nonspecific clinical manifestations

Neurologic in HIV-infected: cognitive dysfunction, behavioral disturbances; may be mistaken for HIV-related or other dementia, psychiatric disease

What Causes Disease?

  • B. bacilliformis: Carrion disease (limited to the Andes mountains)
  • B. quintana: Trench fever, BA/BP, endocarditis
  • B. henselae: Acute and persistent bacteremia, BA/BP complex, non-neovascular inflammation including endocarditis and CSD, neurologic manifestations
  • B. elizabethae: Bacteremia with endocarditis (1 reported case)
  • B. clarridgeiae: CSD (1 reported case)
  • B. vinsonii: bacteremia (1 reported case)

Risk Factors

Vector exposure with cutaneous inoculation

  • B. bacilliformis: Sandflies of the genus Lutzomyia (formerly Phlebotomus)
  • B. quintana: Human body louse, possibly others as yet unidentified
  • B. henselae: Domestic cat (especially scratch/bite from kitten < 1 year old), possibly cat fleas, possibly ticks
  • B. elizabethae, B. vinsonii: unknown

Cell-mediated immune dysfunction (a role in BA/BP. possibly endocarditis)

  • HIV infection, especially with CD4+ lymphocyte count <100/;UL
  • Chronic corticosteroid, azathioprine, cyclophosphamide, cyclosporine, ethanol

Diagnosis of Disease

Differential Diagnosis

  • Typical CSD: other causes of unilateral lymphade-nopathy: Sporothrix schenckii, Pasteurella species, Yersinia pestis, Francisella tularensis. Mycobacteria, Erysipelothrix rhusiopathiae, Staphylococci, Streptococci, other agents associated with injection drug use, lymphoma. metastatic malignancy
  • Atypical CSD: other agents causing similar syndromes
  • Non-bacilliformis Bartonella species bacteremia syndromes
    • In immunocompromised, especially HIV-infected Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, Mycobacterium avium-complex
    • After recent arthropod exposure: rickettsial infections, tularemia, plague, babesiosis, borreliosis (location-dependent).
    • After cat/dog scratch/bite: Pasteurella species infection
    • Viral illnesses: influenza, infectious mononucleosis. acute hepatitis, etc.
  • Endocarditis: other fastidious/slow-growing bacteria associated with endocarditis, e.g. species of Hae-mophilus, Actinobacillus, Cardiobacterium. Eikenella, Kingella, Coxiella
  • BA/BP: Kaposi sarcoma; pyogenic granuloma
  • Neurologic in HIV-infected: other causes of encephalopathy, e.g., primary HIV-related, tertiary syphilis, cryp-tococcal meningitis, toxoplasmosis of brain, progressive multifocal leukoencephalopathy, alcohol or drug abuse


Non-bacilliformis Bartonella spp

Blood cultures: lysis-centrifugation (Isolator) cultures plated on blood or chocolate agar, incubated at 35-37°C in 5% C02 > 2 weeks; enriched broth media, e.g. BACTER, incubated at 35-37°C in 5% C02 >2 weeks and subculture to agar if bacilli detected by periodic acridine orange staining.

Tissue cultures: recovery from tissue homogenate plated on blood or chocolate agar may require >4 weeks

01 st generation serologic tests available in reference labs

Drugs that may alter lab results: Antibiotics: cultures falsely negative

Disorders that may alter lab results: N/A

Pathological Findings

  • Verruga peruana: neovascular proliferation, bacteria uncommonly identified
  • CSD: stellate abscesses, mixed inflammatory infiltrates, granulomata, follicular hyperplasia of lymph nodes; bacilli in tissue demonstrable by silver impregnation stains (Warthin-Starry or Steiner) in about 1/3 cases
  • Endocarditis: Warthin-Starry stained bacilli may be seen in vegetations
  • BA/BP
    • BA lesions: tabular proliferations of small blood vessels containing cuboidal endothelial cells interspersed with inflammatory cells, mostly neutrophils. Fibrillar- or granular-appearing amphophilic material often seen in interstitium hematoxylin and eosin stain. Warthin-Starry stain or electron microscopy demonstrate these to be clusters of bacilli.
    • BP: involved organs contain blood-filled, partially endothelial cell-lined cystic structures and surrounding clumps of bacilli (identified by Warthin-Starry stain) in the midst of inflammatory cells.
  • Neurologic in HIV-infected: little information

Special Tests

  • Skin testing reagents: not commercially available or standardized; use is not recommended
  • Co-incubation of tissue homogenates with cell culture lines to enhance culture recovery; PCR and immunohis-tochemical labeling for non-culture detection in tissue currently remain research tools


Ultrasonography or CT as indicated

Diagnostic Procedures

  • Biopsies for histology/culture of cutaneous nodules, lymph nodes, or internal organs as necessary
  • Typical CSD; traditionally, diagnosis required 3 of 4 criteria fulfilled:
    • Animal contact (usually cat or dog) resulting in a scratch, abrasion or ocular lesion
    • Positive serologictest (replaces positive skin test)
    • Characteristic lymph node pathology
    • Absence of evidence of other causes of lymphadenopathy
  • Atypical CSD: compatible syndrome, absence of other evident cause; positive skin or serologic testing
  • Bacteremia: clinical suspicion; use of appropriate culture methods
  • Endocarditis: compatible clinical syndrome, evidence of valve lesion (ultrasonographic or tissue), positive culture of blood or valve (or non-culture demonstration, e.g., immunohistochemistry, polymerase chain reaction [PCR])
  • BA/BP: biopsy for definitive diagnosis; presumptive diagnosis by response to appropriate antibiotics
  • Neurologic in HIV-infected: (1) compatible clinical syndrome plus elevated antibodies in CSF or detection in CSF by culture or PCR, (2) no other cause

Treatment (Medical Therapy)

Appropriate Health Care

  • Outpatient for uncomplicated infection
  • Initial hospitalization may be necessary for complications

General Measures

  • CSD: symptom-specific supportive therapy, e.g., aspiration of suppurative lymph nodes to alleviate pain
  • Other syndromes (including CSD-associated neuroreti-nitis and encephalopathy): antibiotic therapy


Fully active if uncomplicated


No special diet

Patient Education


Medications (Drugs, Medicines)

Drug(s) of Choice

  • B. bacilliformis infection: chloramphenicol 500 mg po qid for 1 week
  • For typical CSD: no proven response to many agents including erythromycin, doxycycline, penicillin, cepha-losporins; anecdotal reports of efficacy of rifampin > ciprofloxacin > gentamicin > trimethoprim-sulfamethox-azole. One placebo-controlled trial of oral azithromycin found some efficacy for 5 day course.
    • Azithromycin dose:
    • Adults and children > 45 kg: 500 mg on day 1, 250 mg daily on days 2-5
    • Children < 45 kg: 10 mg/kg on day 1; 5 mg/kg daily on days 2-5
  • Non-bacilliformis Bartonella infections including bacteremia without endocarditis, cutaneous BA + local lymph node involvement, CSD-associated neuroretinitis and encephalopathy, 6. tense/ae-related neuro-psychiat-ric disorders in HIV-infected:
    • Erythromycin 500-1000 mg po bid or doxycycline 100 mg po bid for 4 weeks in immunocompetent; 8-12 weeks in immunocompromised (rifampin may play adjunctive role); azithromycin 250 mg qd for comparable duration should be effective as well
  • Endocarditis, visceral or bony involvement with BA/BP Erythromycin 500-1000 mg qid or doxycycline 100 mg bid x 2-4 weeks parenteral; complete 8-12 weeks po; azithromycin 250 mg qd for comparable duration should be effective as well

Contraindications: N/A

Precautions: N/A

Significant possible interactions: N/A

Alternative Drugs

  • B. bacilliformis infection: tetracyclines
  • Non-bacilliformis Bartonella infections: other tetracyclines, azithromycin, clarithromycin, chloramphenicol. ofloxacin, ciprofloxacin

Patient Monitoring

Relapse may occur in non-CSD syndromes if therapy is too brief, close follow-up after completion of antibiotics is warranted

Prevention / Avoidance

Avoid contact with potential vectors, especially young cats. If cat scratch or bite occurs, wash the wound promptly and thoroughly.

Possible Complications

especially in HIV infection

Expected Course / Prognosis

  • CSD — spontaneous resolution usually in 2-4 months without specific therapy
  • Other syndromes -with proper treatment, full resolution if relapse, consider long-term suppressive antibiotics after retreatment
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