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Bartonella infections
OVERVIEW: 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/Immunologic
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
Predominant sex: Non-B. bacilliformis infections: Male > Female
SIGNS AND SYMPTOMS: • Carrien's 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's oculoglandular syndrome: granulomatous conjunctivitis and ipsilateral preauricular lymphadenitis
• Neuroretinitis: usually unilateral; macular star exudate, papilledema, retinal nodules, angiomatous subretinal 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, 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. HIV-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; B. 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
CAUSES: • B. bacilliformis: Carrien's 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. clarridgiae: CSD (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: unknown
• B. vinsonii: Bacteremia (one reported case)
• Cell-mediated immune dysfunction (a role in BA/BP, possibly endocarditis)
• HIV infection, especially with CD4+ lymphocyte count < 100/µL
• Chronic corticosteroid, azathioprine, cyclophosphamide, cyclosporine, ethanol
DIAGNOSIS DIFFERENTIAL DIAGNOSIS: • Typical CSD: other causes of unilateral lymphadenopathy: Sporothrix schenckii, Pasteurella species, Yersinia pestis, Francisella tularensis, Mycobacteria, Erysipelothrix rhusiopathiae, Staphylococci, Streptococci, other agents associated 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 Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella, Coxiella
• BA/BP: Kaposi's sarcoma; pyogenic granuloma
• Neurologic in HIV-infected: other causes of encephalopathy, e.g., primary HIV-related, tertiary syphilis, cryptococcal meningitis, toxoplasmosis of brain, progressive multifocal leukoencephalopathy, alcohol or drug abuse
LABORATORY: • Non-bacilliformis Bartonella spp
• Blood cultures: lysis-centrifugation (Isolator) cultures plated on blood or chocolate agar, incubated at 35-37°C in 5% CO2 > 2 weeks; enriched broth media, e.g. BATEK, incubated at 35-37°C in 5% CO2 >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
• 1st 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: lobular 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
• Co-incubation of tissue homogenates with cell culture lines to enhance culture recovery; PCR and immunohistochemical labeling for non-culture detection in tissue: currently remain research tools
IMAGING: 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:
(1) Animal contact (usually cat or dog) resulting in a scratch, abrasion or ocular lesion
(2) Positive skin test with cat scratch antigen (not available commercially)
(3) Characteristic lymph node pathology
(4) Absence of evidence of other causes of lymphadenopathy
• Serologic testing preferable alternative to skin testing
• 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 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 (perhaps including CSD-associated neuroretinitis and encephalopathy): antibiotic therapy
SURGICAL MEASURES: N/A
ACTIVITY: Fully active if uncomplicated
DIET: No special diet
PATIENT EDUCATION: N/A
MEDICATIONS 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, cephalosporins; anecdotal reports of efficacy of rifampin > ciprofloxacin > gentamicin > trimethoprim-sulfamethoxazole. 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, B. henselae-related neuro-psychiatric disorders in HIV-infected:
• Erythromycin 500-1000 mg po qid or doxycycline 100 mg po qid for 4 weeks in immunocompetent; 8-12 weeks in immunocompromised (rifampin may play adjunctive role)
• 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
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
FOLLOW UP 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: Relapse, especially in HIV infection
EXPECTED COURSE AND 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
MISCELLANEOUS ASSOCIATED CONDITIONS: In advanced HIV infection, other opportunistic infections may be present
AGE-RELATED FACTORS:
Pediatric: N/A
Geriatric: N/A
Others: N/A
PREGNANCY: N/A
SYNONYMS: N/A
ICD-9-CM: 078.3 Cat scratch disease
083.1 Trench fever (B. quintana bacteremia)
083.8 Other Bartonella-related diagnoses, including BA/BP
088.0 B. bacilliformis infections (Oroya fever, verruga peruana)
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