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Cat scratch disease is the most common zoonotic infection caused by Bartonella bacteria. Among the many mammals infected with Bartonella spp., cats represent a large reservoir for human infection, as they are the main reservoir for Bartonella henselae, Bartonella clarridgeiae and Bartonella koehlerae. Bartonella spp. are vector-borne bacteria, and transmission of B. henselae by cat fleas occurs mainly through infected flea faeces, although new potential vectors (ticks and biting flies) have been identified. Dogs are also infected with various Bartonella species and share with humans many of the clinical signs induced by these infections. Although the role of dogs as source of human infection is not yet clearly established, they represent epidemiological sentinels for human exposure. Present knowledge on the aetiology, clinical features and epidemiological characteristics of bartonellosis is presented., (© 2010 The Authors. Journal compilation © 2010 The Society for Applied Microbiology.)

Cat-scratch disease (CSD) is largely due to infection with Bartonella henselae. Microbiologic detection is difficult, and molecular testing is not readily available. A monoclonal antibody (mAB) to B henselae has become commercially available. We evaluated the usefulness of immunohistochemical analysis (IHC) for diagnosing CSD on surgical specimens and compared these results with polymerase chain reaction (PCR) detection and serologic testing for B henselae. We studied 24 formalin-fixed, paraffin-embedded (FFPE) cases of lymphadenitis with histologic and/or clinical suspicion of CSD. Control cases included 14 cases of lymphadenopathy other than CSD. FFPE tissue sections were evaluated with an mAB to B henselae, Steiner silver stain (SSS), and PCR that targeted B henselae and Bartonella quintana. Positive cases were as follows: SSS, 11 (46%); PCR, 9 (38%); and IHC, 6 (25%). Only 2 cases (8%) were positive for all 3 studies. All control cases were negative for IHC and PCR. The diagnostic sensitivity of these 3 tests is low for CSD. SSS seems to be the most sensitive test but is the least specific. PCR is more sensitive than IHC and may, therefore, serve as a helpful second-line test on all IHC- cases.

Background: Musculoskeletal manifestations (MMs) are considered to be rare in cat scratch disease (CSD) and are not well characterized. We aimed to study MMs of CSD., Methods: A surveillance study performed over 11 years identified patients with CSD on the basis of compatible clinical presentation and confirmatory serological test or PCR results for Bartonella henselae. Patients with CSD who had MMs (i.e., myalgia, arthritis, arthralgia, tendinitis, osteomyelitis, and neuralgia) were compared with patients with CSD who did not have MMs (control subjects)., Results: Of 913 patients with CSD, 96 (10.5%) had MMs. Myalgia (in 53 patients [5.8%]) was often severe, with a median duration of 4 weeks (range, 1-26 weeks). Arthropathy (arthralgia and/or arthritis; in 50 patients [5.5%]) occurred mainly in the medium and large joints and was classified as moderate or severe in 26 patients, with a median duration of 5.5 weeks (range, 1-240 weeks). In 7 patients, symptoms persisted for >or=1 year; 5 developed chronic disease. Tendinitis, neuralgia, and osteomyelitis occurred in 7, 4, and 2 patients, respectively. Patients with MMs were significantly older than patients in the control group (median age, 31.5 years vs. 15.0 years). In multivariate analysis, age >20 years was associated with having any MM (relative risk [RR], 4.96; 95% confidence interval [CI], 2.79-8.8), myalgia (RR, 4.69; 95% CI, 2.22-9.88), and arthropathy (RR, 11.0; 95% CI, 4.3-28.2). Arthropathy was also associated with female sex (RR, 1.89; 95% CI, 1.01-3.52) and erythema nodosum (RR, 4.07; 95% CI, 1.38-12.02)., Conclusions: MMs of CSD are more common than previously thought and affect one-tenth of patients with CSD. MMs occur mostly in patients aged >20 years and may be severe and prolonged. Osteomyelitis, the most well known MM of CSD is, in fact, the rarest.

Objectives: Bartonella henselae is a fastidious slow growing pathogen which is seldom cultured in the laboratory. Previous descriptions of antimicrobial susceptibility have been largely limited to feline isolates and/or laboratory reference strains, with no accounting for genotypic or phenotypic diversity., Methods: An optimal method of antimicrobial susceptibility testing by Etest was established to compare the antimicrobial susceptibilities of 12 different isolates of B. henselae, 5 human and 7 feline, which have previously been well characterized by 16S rRNA sequencing, multi-locus sequence typing (MLST), phase variation and passage number., Results: No difference in susceptibility could be attributed to differences in genotype, source of the isolate or passage number. Where comparisons were drawn with previously published results, these were found to be concordant., Conclusions: We conclude that antibiotic susceptibility can be determined by a simple Etest method for B. henselae isolates. This method is reproducible among diverse strains, and is sufficiently predictable that generalizations can be confidently made about optimal antibiotic choices.

We report a case of isolated splenic cat scratch disease in an immunocompetent woman. The clinical presentation of prolonged fever, night sweats, weakness, and intrasplenic lesions was highly suggestive of lymphoma. This is the second reported case of isolated splenic cat scratch disease in an adult and the first in a healthy adult.

We describe 2 adult patients (1 of whom was infected with human immunodeficiency virus) with osteomyelitis due to Bartonella henselae. Diagnosis was established on the basis of direct identification of the microorganism in one case and seroconversion in the other. Both patients recovered completely within 3 months.

Bartonella henselae is the causative agent of cat-scratch disease (CSD), which usually manifests as acute regional lymphadenopathy. The causes of cervical lymphadenopathy, with special regard to CSD, were investigated in a study of 454 patients who presented with unclear masses in the head and neck from January 1997 through January 2001. Sixty-one patients (13.4%) experienced CSD; 54 (11.9%) had primary lymphadenopathy due to other infectious agents, and 41 (9.0%) had lymphadenopathy that occurred in association with primary infections of other organs. For 171 patients (37.7%), the cause of the cervical lymph node enlargement could not be found. B. henselae DNA was detected in extirpated lymph nodes only during the first 6 weeks of lymphadenopathy, which indicates that the results of polymerase chain reaction strongly depend on the duration of illness. CSD should be included in the differential diagnosis of adenopathy in the otorhinolaryngologic patient population, to avoid unnecessary treatment.

Diagnosis of cat-scratch disease (CSD) by polymerase chain reaction (PCR) of lymph node fineneedle aspiration (FNA) and primary lesion specimens can be difficult owing to the minute amount of available material. A PCR assay specifically suited to test these specimens was developed. First, small-quantity (10 microL) samples were prepared from 17 CSD-positive and 16 CSD-negative specimens, and DNA extraction and amplification from these samples were compared using 3 methods. Sensitivity and specificity of PCR were 100% using material collected on glass microscope slides and by using Qiagen (Hilden, Germany) columns for DNA extraction. Then, this method was used to test 11 archival glass microscope slides of FNA (7 malignant neoplasms, 4 undiagnosed lymphadenitis) and 2 primary lesion specimens. Two of the 4 lymphadenitis samples and the 2 primary lesion specimens were PCR positive. The technique presented could facilitate CSD diagnosis from a wider range of clinical samples.

We evaluated a pediatric patient for transverse myelitis associated with Bartonella henselae infection. There was no adenopathy in our patient, but the diagnosis was made serologically. It is necessary to keep cat-scratch disease in mind even in the absence of typical findings.

Bartonella henselae was recovered from the conjunctival scraping of a 38-year-old woman who presented with a 2-week history of tender preauricular lymphadenopathy and a 1-day history of a red left eye. Dry adherent colonies were observed on agar plates at 21 days of incubation, and the isolate was identified through conventional and molecular tests. Polymerase chain reaction (PCR) amplification of a specific region of the 16S rRNA gene and confirmation by a separate PCR reaction with hybridization of the product with a B. henselae-specific probe confirmed the isolate as B. henselae. This is the first reported isolation of the causative agent of cat scratch disease from ocular tissue in a patient with Parinaud's oculoglandular syndrome.

The case of a 9-year-old girl with cat-scratch disease (CSD) complicated by development of a paravertebral mass and osteomyelitis is presented. Following multiple scratches and inguinal lymphadenopathy, she developed back pain, and imaging demonstrated a paravertebral mass with evidence of osteomyelitis involving vertebra T9. The diagnosis was made on the basis of detection of Bartonella henselae by use of molecular techniques on an aspirate from the vertebral column and supportive serology for infection with B. henselae. Eleven other cases of this unusual manifestation associated with CSD have been reported in the literature and are reviewed. The patient was treated with gentamicin, followed by rifampicin and trimethoprim-sulfamethoxazole, orally and made a favorable recovery over 7 months. This is comparable with other case reports, regardless of the choice of antibiotic therapy. CSD in immunocompetent hosts is not always self-limiting, and tissues beyond the lymph nodes can be involved.

We assayed the ability of cat fleas to become infected with Bartonella henselae, using an artificial feeding device. Fleas fed a concentration of 1 x 10(5) cfu/ml in blood were examined using immunofluorescent antibody assay and polymerase chain reaction. Bacteria were present in the gut at 3 h, and persisted up to 9 d after infection. Qualitatively, the density of B. henselae was greater in the flea gut at 9 d, indicating that replication was occurring in the gut. B. henselae also was detected in the feces of infected fleas 9 d after infection, and produced viable colonies upon inoculation onto heart infusion agar/rabbit blood plates. Our results indicate that fleas can maintain infection with B. henselae, and may play a role in the transmission of this bacterium from infected cats to humans.

A prospective population-based surveillance system was established to characterize the epidemiology of cat-scratch disease (CSD) among residents of Connecticut who were reported to the state health department with a diagnosis of suspected CSD. During 1992 and 1993, 246 persons met the case definition, for an average statewide annual incidence of 3.7/100,000 persons. The median age of patients with CSD was 14 years (range, 1-64), and 52% were female. The age-specific attack rate was highest among persons < 10 years of age (9.3/100,000) and decreased with increasing age. Symptoms in addition to adenopathy were noted by 74% of case-patients. Eleven percent of all case-patients were hospitalized. There were no deaths. Most patients with clinically diagnosed CSD developed an immunologic response to Bartonella species. Our data suggest that although CSD is primarily a disease of younger persons, the age spectrum is wider than was commonly appreciated.

Bartonella (Rochalimaea) henselae causes a variety of diseases, including bacillary angiomatosis, peliosis hepatis, lymphadenitis, aseptic meningitis with bacteremia, and cat-scratch disease (CSD). Cases of B. henselae-related disease were collected from September 1991 through November 1993. Patients with suspected CSD, unexplained fever and lymphadenitis, or suspected B. henselae infection who were seen in the Infectious Diseases Clinic at Wilford Hall Medical Center (Lackland Air Force Base, TX) underwent physical and laboratory examinations. In addition to three previously described cases, 23 patients with R. henselae-related infection were identified. The patients included 19 immunocompetent individuals presenting with lymphadenitis (11), stellate neuroretinitis (5), Parinaud's oculoglandular syndrome with retinitis (1), chronic fatigue syndrome-like disease (1), and microbiologically proven adenitis without the presence of immunofluorescent antibodies to B. henselae (1) and four patients infected with human immunodeficiency virus type 1 presenting with isolated lymphadenitis (1), diffuse upper-extremity adenitis (1), neuroretinitis (1), and aseptic meningitis (1). A couple with neuroretinitis and their pet cat, a persistently fatigued patient, and a patient with Parinaud's oculoglandular syndrome were shown to have bacteremia. Tissue cultures were positive for B. henselae in three recent cases of adenitis. Twenty-two patients were exposed to cats. This series further demonstrates the similarities between B. henselae-related diseases and CSD and identifies several new syndromes due to B. henselae.

We describe an immunocompromised renal transplantation patient with opportunistic lung infection due to Bartonella henselae (formerly Rochalimaea henselae) and provide evidence suggesting transmission from a pet cat. Computed tomographic scans of the chest and lung biopsies provided material for diagnosis. The etiology was established by polymerase chain reaction and sequencing of a 16S ribosomal DNA segment from infected lung tissue. Histopathologic and serological evidence supported the molecular data. B. henselae was isolated from the blood of eight of the patient's many cats. The patient responded to prolonged therapy with doxycycline, and relapse did not occur during a 1-year follow-up. B. henselae joins a long list of pathogens that can cause lung infections in association with cell-mediated immunodeficiency states. Molecular methods are useful in diagnosis of this infection in light of the bacterium's fastidious growth characteristics. If an immunocompromised patient has lung nodules and a history of exposure to cats, B. henselae should be sought in biopsy specimens.

To determine the role of Bartonella (formerly Rochalimaea) species and Afipia felis in cat scratch disease (CSD), two polymerase chain reaction (PCR) hybridization assays were developed to detect DNA from these organisms. These assays were applied on 89 pus aspirates from skin test-positive CSD patients (group 1) and on 137 pus and lymph node specimens from CSD suspects (group 2). Bartonella DNA was detected in 96% of the samples from group 1 patients and in 60% of group 2 samples; however, A. felis DNA could not be detected in any clinical samples. These results suggest that CSD is caused by bartonellae and that A. felis does not play a significant role in this zoonosis. A strong correlation between Bartonella PCR positivity and Bartonella henselae antibody titer was found. Comparison of CSD skin test results with those obtained by Bartonella PCR suggests a low sensitivity of the skin test.

Twelve hybridoma clones producing monoclonal antibodies to Afipia felis, a putative causative agent of cat scratch disease, were derived from BALB/c mice immunized with A felis. All 12 monoclonal antibodies were species-specific for A felis and reacted with lipopolysaccharide antigens of A felis. These monoclonal antibodies belong to immunoglobulin (Ig) G1, IgG2a, IgG2b, IgG3, and IgM isotypes. All monoclonal antibodies reacted with both agar-grown A felis and tissue culture-propagated A felis. Formalin fixation did not alter the reactivity of the antigen with the monoclonal antibodies. These monoclonal antibodies could be a useful tool for investigation of the disputed role of A felis in cat scratch disease.

The identification of the causative organisms of cat scratch disease (CSD) has been elusive. The demonstration of Warthin-Starry stain-positive pleomorphic bacilli in lymph nodes of patients with CSD and recent serologic and epidemiologic data suggest an etiologic role of Rochalimaea henselae in CSD. The authors studied lymph node biopsy specimens of 46 patients with illnesses clinically consistent with CSD and found pleomorphic bacilli in 15 (33%). The organisms were labeled by polyclonal rabbit antibodies induced by outer surface proteins of R henselae. This finding further supports the possibility of an important role of R henselae in the pathogenesis of CSD.

One of the diagnostic criteria for cat-scratch disease is a positive delayed-type hypersensitivity skin test reaction to an antigen prepared from purulent material aspirated from a cat-scratch disease-involved lymph node. Polymerase chain reaction coupled with DNA sequence analysis was used to identify organisms found in these skin test antigen preparations that may be responsible for eliciting this response. Two independent sources of cat-scratch disease skin test antigens yielded DNA sequences characteristic of the newly described rickettsia, Rochalimaea henselae. These results coupled with previous serologic data strongly suggest that R. henselae plays a central role in the etiology of cat-scratch disease.

The primary structures of the small subunit rRNA of Bradyrhizobium japonicum and Blastobacter denitrificans were determined by direct sequencing of enzymatically amplified DNA. Comparative sequence analysis revealed that Bradyrhizobium japonicum and Blastobacter denitrificans are members of the alpha-2 subgroup of the Proteobacteria and show a very close phylogenetic relationship with the genus Afipia.

Because the causative bacterium of cat scratch disease has not been definitively cultured or fully characterized, the authors have studied its ultrastructure in lymph node biopsies from two patients using glutaraldehyde-fixed tissue. In both specimens, the organisms were invariably extracellular, forming small groups within bundles of collagen fibrils. Their appearance was similar in necrotic and viable regions of the nodes, although in the latter sites they could not be identified by light microscopic examination with the Warthin-Starry stain. The bacteria were pleomorphic rods, and, despite faint gram-negative staining, their walls were consistently thick and homogeneous.

Over a seven-year period, we identified 23 patients who had prolonged or recurrent, severe, systemic, cat-scratch disease (CSD). Compared with the usual, benign course in 1,038 patients with typical CSD, the course in these 23 patients included prolonged (two or more weeks) morbidity (fever, malaise, fatigue, myalgia, arthralgia, skin eruptions, weight loss, and splenomegaly). Five patients with systemic CSD had either neuroretinitis, pleurisy, arthralgia or arthritis, splenic abscesses, and mediastinal masses or enlarged nodes of the head of the pancreas. Recurrent CSD in two of three adults was confirmed by finding typical CSD bacilli in lymph nodes removed during separate episodes. The majority of patients were adult males, and all patients recovered completely without sequelae. Histopathologic studies of five skin and 18 lymph node biopsy specimens were diagnostic. CSD bacilli were detected in lymph nodes from 15 patients and in the primary skin lesions of four patients. CSD bacilli were found in both skin and lymph nodes of three patients.

A case of cat-scratch disease (CSD) in a patient with acquired immunodeficiency syndrome (AIDS) is reported. The lymph node pathologic characteristics were altered from those usually seen with CSD, showing clusters of vacuolated macrophages admixed with pycnotic nuclear debris instead of the usual suppurative granulomas. Evidence for the diagnosis was provided by Warthin-Starry stain and electron microscopic demonstration of the presumed CSD bacillus. Empiric treatment with antibiotics brought about clinical improvement. This case demonstrates the altered lymph node pathologic characteristics with CSD that may occur in a patient with AIDS.