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Isolated hepatic involvement of cat scratch disease in immunocompetent adults: Enhanced magnetic resonance imaging, pathological findings, and molecular analysis--two cases.

Visceral involvement in absence of lymphadenopathy is a rare manifestation in cat scratch disease; hepatic granulomas are rare, representing 0.3% of systemic manifestations of cat scratch disease, and gallbladder extension is a singular case. The present article refers to 2 rare cases of visceral cat scratch disease in immunocompetent adults with hepatic granulomatous inflammation, caused by Bartonella henselae infection, with gallbladder involvement in 1 case and no lymphadenopathy. Histological features demonstrated the presence of inflammatory necrotizing granulomatous nonneoplastic process. Molecular studies (polymerase chain reaction) were performed to confirm the infectious etiology.

Antigens, CD↗

Multifocal osteomyelitis in a child: a rare manifestation of cat scratch disease: a case report and systematic review of the literature.

We present a case of a 9-year-old immunocompetent girl who presented with pain in her left elbow and a painful swelling at her left clavicle. She had no lymphadenopathy or fever. Four hot spots were seen at her left clavicle, proximal and distal left humerus and lumbo-sacral spine on a bone scan. A magnetic resonance imaging showed an inflammatory process with bone destruction at her clavicle. Serological testing and polymerase chain reaction performed on a bone biopsy identified a Bartonella henselae infection. She was treated with rifampin and trimethoprim-sulphamethoxazole. After a relapse half a year later, the patient recovered fully. Multifocal osteomyelitis is a rare manifestation of cat scratch disease in children.

Anti-Bacterial Agents↗

Experimental infection of domestic cats with Bartonella henselae by inoculation of Ctenocephalides felis (Siphonaptera: Pulicidae) feces.

Caged cat fleas, Ctenocephalides felis (Bouché), were fed on 6 cats; 3 cats were injected with 5 x 10(7) colony forming units of Bartonella henselae intradermally and 3 cats were injected with an equal volume of saline. After the fleas fed for 4 d, 5 groups of 50 B. henselae-exposed fleas were caged and allowed to feed on 5 cats for 6 d. Five cats each were injected intradermally with 1 ml of saline containing 45 mg of feces from B. henselae-exposed fleas. Five cats were fed 50 B. henselae-exposed fleas and 45 mg of fresh feces from B. henselae-exposed fleas. Five cats received all 3 treatments by using fleas and feces collected from cats inoculated with saline (controls). Cats were bled weekly and tested by culture and serology. The cats that were injected with feces from infected fleas were positive by culture for B. henselae at 1 or 2 wk after exposure and were the only cats to become bacteremic or seropositive by week 20.

Animals↗

Bartonella quintana Bacteremia among Homeless People.

Bartonella quintana infections have recently reemerged, predominantly among the homeless populations in cities in both Europe and the United States. B. quintana can cause trench fever, endocarditis, and chronic bacteremia; the human body louse is the only known vector. Homeless people who presented to the emergency departments of University Hospital in Marseilles, France, were studied, as were those who had been admitted to other medical facilities in the city since 1 January 1997. Samples of blood and body lice were collected for culture for B. quintana and for serological testing. Bartonella bacteremia was associated with sweats, evidence of louse infestation, serological tests that were positive for B. quintana, and high titers of B. quintana antibody. Bacteremia was also associated with being homeless for <3 years. Asymptomatic, prolonged bacteremia (duration, up to 78 weeks) and intermittent bacteremia were found to occur. Data obtained regarding antibiotic regimens showed that treatment with gentamicin and doxycycline was effective in preventing relapses of bacteremia.

Bacteremia↗

Louse-borne bacterial pathogens in lice (Phthiraptera) of rodents and cattle from Egypt.

We collected 1,023 lice, representing 5 species, from rats and domestic cattle throughout 13 governorates in Egypt and tested these lice for Anaplasma marginale, Bartonella spp., Brucella spp., Borrelia recurrentis, Coxiella burnetii, Francisella tularensis, and Rickettsia spp. by PCR amplification and sequencing. Five different louse-borne bacterial agents were detected in lice from rodents or cattle, including "Bartonella rattimassiliensis", "B. phoceensis", and Bartonella sp. near Bartonella tribocorum, Coxiella burnetii, and Rickettsia typhi. More lice from governorates bordering the Mediterranean and Red Seas contained pathogens. Our data indicate that lice of urban and domestic animals harbor pathogenic or potentially pathogenic bacterial agents throughout Egypt.

Animals↗

Serologic response to Bartonella henselae in patients with cat scratch disease and in sick and healthy children.

Indirect fluorescent antibody assay (IFA) is the most reliable test for detecting antibody to Bartonella henselae in the diagnosis of cat scratch disease (CSD). Recently, an ELISA test has been proposed, but conflicting results are reported. We compared IgG-IFA and IgG-IgM ELISA methods in CSD patients and in healthy children. We also tested ELISA specificity in a large group of healthy controls and in children with lymphoma-associated lymphadenopathy and with pyogenic lymphadenitis. The ELISA procedure was positive in 69/78 patients with CSD (sensitivity 89.6%), in 5/100 healthy children (specificity 95%), in 2/51 patients with non-Hodgkin's lymphoma or pyogenic lymphadenitis (specificity 96%) and in 27/296 blood donors (specificity 91.6%). In 34 patients with CSD, ELISA IgM and IgG responses decreased significantly between time of diagnosis of the disease and recovery. We found significantly higher IgG-ELISA titres in cat-owners, whether blood donors or healthy children, than in non-cat-owners. The IgG-IFA test gave positive results in 69/78 patients with CSD (sensitivity 89.6%) and in 5/62 healthy controls (specificity 92.5%). The ELISA method is a cheap, sensitive method for determining antibody response to Bartonella henselae infection and is also important for evaluating the clinical course of the disease and the efficacy of antibiotic therapy. The high specificity of ELISA in patients with non-Hodgkin's lymphoma will help the clinician to exclude a potentially life-threatening disease associated with lymphadenopathy.

Adolescent↗

Culture-negative endocarditis due to Houston Complex Bartonella henselae acquired in Noumea, New Caledonia.

A 44-year-old man with a bioprosthetic aortic valve suffered destructive endocarditis with severe embolic disease due to Bartonella henselae infection. Multilocus sequence typing was successfully performed with crude preparations of operative tissue as templates, and the infecting organism was determined to be typical of the Houston clonal group, although it was never cultured from blood or tissue. This is the first report of B. henselae infection in the South Pacific, and it reminds one that B. henselae is a cause of potentially lethal culture-negative endocarditis which may respond poorly to conventional empirical therapy. Nothing is known of the epidemiology of the infection in this region, but it is likely to be common and to contain representatives of both major clonal complexes. This study emphasizes the ease with which multilocus sequence typing can be used directly with tissue, which is important because of suggestions of strain-dependent clinical outcomes.

Angiomatosis, Bacillary↗

Bartonella quintana and urban trench fever.

Contemporary Bartonella quintana infections have emerged in diverse regions of the world, predominantly involving socially disadvantaged persons. Available data suggest that the human body louse Pediculus humanus is the vector for transmission of B. quintana. Descriptions of the clinical manifestations associated with contemporary B. quintana infections have varied considerably and include asymptomatic infection, a relapsing febrile illness, headache, leg pain, "culture-negative" endocarditis, and, in human immunodeficiency virus-infected persons, bacillary angiomatosis. Laboratory diagnosis is most convincing when B. quintana is isolated in blood culture, but growth often takes 20-40 days; problems exist with both sensitivity and specificity of serological assays. On the basis of available information, use of doxycycline, erythromycin, or azithromycin to treat B. quintana infections is recommended. Treatment of uncomplicated B. quintana bacteremia for 4-6 weeks and treatment of B. quintana endocarditis (in a person who does not undergo valve surgery) for 4-6 months are recommended, with the addition of a bactericidal agent (such as a third-generation cephalosporin or an aminoglycoside) during the initial 2-3 weeks of therapy for endocarditis.

Animals↗

An unusual outcome in a child with hepatosplenic cat-scratch disease.

Typical cat-scratch disease (Bartonella henselae infection) in an immunocompetent child is usually associated with a history of scratch, bite or intimate contact with a cat. Most patients develop a non-tender papule in the scratch line after three to ten days. This may persist for only a few days or as long as two to three weeks. During the next two weeks or more, regional lymph nodes that drain the area gradually enlarge and then slowly resolve in more than 10% of patients. The nodes develop overlying erythema and may suppurate. Atypical forms of cat-scratch disease occur in a minority of cases and are characterized by ocular or neurological manifestations, hepatosplenic involvement, vertebral osteomyelitis, endocarditis etc. Immunocompromised individuals with B. henselae infection may develop bacillary angiomatosis, bacillary peliosis, and relapsing bacteremia. There have been several reports of hepatosplenic granulomas caused by B. henselae in immunocompetent children. We report a case of a 6-year-old boy with the hepatosplenic form of cat-scratch disease. Despite early diagnosis and long-term antimicrobial treatment, splenectomy could not be avoided.

Anti-Bacterial Agents↗

Systemic cat scratch disease.

Systemic cat scratch disease (CSD) is often associated with prolonged fever and microabscesses in the liver and/or spleen. We report a case of systemic CSD with hepatic, splenic and renal involvement in an aboriginal child in Taiwan. A previously healthy 9-year-old girl had an intermittent fever for about 17 days, and complained of abdominal pain, headache and weight loss. Abdominal computed tomography showed multiple tiny hypodense nodular lesions in the spleen and both kidneys. Laparotomy revealed multiple soft, whitish-tan lesions on the surface of the liver and spleen. Histopathologic examination of a biopsy specimen of the spleen showed necrotizing granulomatous inflammation with central necrosis surrounded by epithelioid cells and occasional Langhans' giant cells, strongly suggestive of Bartonella henselae infection. History revealed close contact with a cat. B. henselae DNA was detected by polymerase chain reaction in the tissue specimen, and the single antibody titer against B. henselae was greater than 1:2048. These results confirmed the diagnosis of visceral CSD caused by B. henselae. The patient's symptoms resolved after treatment with rifampin and tetracycline. This case illustrates the need for inclusion of systemic CSD in patients with fever of unknown origin and abdominal pain.

Animals↗

Erythrocyte macrocytosis in feline leukemia virus associated anemia.

Using erythrocyte volume distribution histograms (erythrograms), erythrocyte macrocytosis and anisocytosis were quantitated in 139 cats tested for feline leukemia virus group-specific antigen. Feline leukemia virus-negative cats with non-regenerative anemia or normal packed cell volumes had normal mean corpuscular volume values. Uninfected cats with regenerative anemia had prominent significantly increased macrocytosis and anisocytosis (p less than 0.01). Ninety percent of 62 feline leukemia virus-positive cats had altered erythrograms. Thirty-three feline leukemia virus-positive cats with non-regenerative anemia had marked macrocytosis. Their mean corpuscular volume values (mean 60 fl +/- 2 fl standard error, reference range of 37-49 fl) were significantly greater than those of feline leukemia virus-negative cats except for those with regenerative anemia. Feline leukemia virus-positive, non-anemic cats had significantly increased mean corpuscular volume values of intermediate magnitude. Nine adult cats experimentally infected with feline leukemia virus developed non-regenerative anemia with significant increases in mean corpuscular volume and anisocytosis. However, the macrocytosis observed in these cats was considerably less than in naturally occurring feline leukemia virus-positive cats with non-regenerative anemia. These observations indicate there are events in the pathogenesis of feline leukemia virus-associated anemia other than simple erythroid hypoplasia. We suggest that hemolysis and erythrocyte regeneration occur before erythroid hypoplasia and may partially account for macrocytosis observed in the face of non-regenerative anemia.

Anemia, Macrocytic↗

Activation of Rac, Cdc42 and other downstream signalling molecules by Bartonella bacilliformis during entry into human endothelial cells.

Bartonella bacilliformis is an intracellular bacterial pathogen of human endothelial cells. In vitro incubation of B. bacilliformis with human endothelial cells leads to the formation of filamentous actin extensions (filopodia) within 30 min, followed by formation of membrane rufflings or lamellipodia within 1 h of incubation. By immunofluorescence, F-actin phalloidin staining and anti-Rac antibodies were shown to co-localize in the membrane rufflings, indicating the recruitment of activated Rac at lamellipodia. Preincubation of endothelial cells with the Clostridial toxin, TcdB-10463, which inactivates the Rho-family GTPases, Rho, Rac and Cdc42, inhibited the entry of B. bacilliformis by 50-90%. Preincubation of endothelial cells with the Clostridial toxin, TcsL-1522, which specifically inactivates Rac and, to a lesser extent, Cdc42, but not Rho, inhibited entry by 30-40%. A 3.4-5.0-fold increase in activated (GTP-bound) -intracellular Rac and Cdc42 was observed in affinity precipitation assays. Increased kinase activity of p21-activated kinase (PAK), a specific downstream effector of activated Rac/Cdc42 was also observed during the time course of infection. Activation of SAPK/JNK-1 and 2, and p38 MAPKs in signalling pathways, was also detected during infection with Bartonella, as was increased binding activity of AP-1 transcription factor.

Actins↗

Bartonelosis (Carrion's Disease) in the pediatric population of Peru: an overview and update.

Bartonellosis, or Carrion's Disease, is an endemic and reemerging disease in Peru and Ecuador. Carrion's Disease constitutes a health problem in Peru because its epidemiology has been changing, and it is affecting new areas between the highland and the jungle. During the latest outbreaks, and previously in endemic areas, the pediatric population has been the most commonly affected. In the pediatric population, the acute phase symptoms are fever, anorexia, malaise, nausea and/or vomiting. The main signs are pallor, hepatomegaly, lymphadenopathies, cardiac murmur, and jaundice. Arthralgias and weight loss have also commonly been described. The morbidity and mortality of the acute phase is variable, and it is due mainly to superimposed infections or associated respiratory, cardiovascular, neurological or gastrointestinal complications. The eruptive phase, also known as Peruvian Wart, is characterized by eruptive nodes (which commonly bleed) and arthralgias. The mortality of the eruptive phase is currently extremely low. The diagnosis is still based on blood culture and direct observation of the bacilli in a blood smear. In the chronic phase, the diagnosis is based on biopsy or serologic assays. There are nationally standardized treatments for the acute phase, which consist of ciprofloxacin, and alternatively chloramphenicol plus penicillin G. However, most of the treatments are based on evidence from reported cases. During the eruptive phase the recommended treatment is rifampin, and alternatively, azithromycin or erythromycin.

Bartonella Infections↗

A family of variably expressed outer-membrane proteins (Vomp) mediates adhesion and autoaggregation in Bartonella quintana.

Bartonella species are fastidious, Gram-negative human pathogens that can persist in the host bloodstream for years and bind to and invade several types of host cells. For many pathogens, adhesion to host cells and extracellular matrix (ECM) components is a critical virulence determinant. Bacteria often vary expression of surface adhesins by phase or antigenic variation to subvert the host immune response and permit adaptive interaction with different host structures. We developed a macaque animal model for Bartonella quintana infection to detect changes in bacterial outer-membrane proteins (OMP) during prolonged bloodstream infection. We identified a gene family encoding four highly conserved, 100-kDa, variably expressed OMP (Vomp), two of which function as adhesins. The variable expression of Vomp family members appears to be mediated by deletion of one or more vomp genes during chronic bloodstream infection. vomp deletion was observed also in isolates from humans with chronic B. quintana infection. The Vomp are closely related to the afimbrial adhesin, YadA, a virulence factor of Yersinia enterocolitica. The surface-expressed Vomp contain conserved structural features of YadA, including collagen-binding motifs. We demonstrate that the B. quintana Vomp are multifunctional OMP involved in binding to collagen and autoaggregation: VompC confers the ability to bind collagen IV, and VompA is necessary and sufficient for autoaggregation. The B. quintana Vomp are members of the newly recognized family of YadA-like trimeric autotransporters; the Vomp constitute a multigene family, they are variably expressed, and different virulence properties are attributable to individual Vomp family members.

Adhesins, Bacterial↗

Shared vector-borne zoonoses of the Old World and New World: home grown or translocated?

Humans inhabiting the Old World and New World share a wide variety of pathogens. Processes that result in the disjunct biogeographic distribution of pathogens with common vertebrate reservoirs or vectors are more difficult to unravel than those influencing the distribution of infections spread only through human-to-human transmission. The origins of species and complexes of tick-borne bacteria are unclear. The agent of Lyme borreliosis may have speciated in the New World following geographical isolation of ticks harboring ancestral spirochetes; the subsequent spread to Europe of B. burgdorferi sensu stricto may have occurred within historical times. Other tick-borne agents, such as the ehrlichiae causing human granulocytic ehrlichiosis, are genetically very similar in the Old World and New World. As the taxonomic distinctions among these related agents of human and veterinary importance appear increasingly blurred, the processes leading to the current discontinuous geographic distributions will also become the source of continuing speculation. Accumulating data suggest an Old World origin for a group of bacteria that include B. elizabethae, a human pathogen first identified from the New World. The potential public health significance of these newly described organisms is undefined, but of international interest as their vertebrate reservoir has been introduced throughout the world.

Animals↗

Experimental model of human body louse infection using green fluorescent protein-expressing Bartonella quintana.

A laboratory colony of human body lice was experimentally infected by feeding on rabbits made artificially bacteremic with a green fluorescent protein-expressing Bartonella quintana. B. quintana was detected in the gut and feces until death but not in the eggs. The life span of the lice was not modified. The rabbit model should provide valuable clues to the role of lice in the transmission of B. quintana.

Animals↗

Detection by immunofluorescence assay of Bartonella henselae in lymph nodes from patients with cat scratch disease.

Laboratory diagnosis of Bartonella henselae infections can be accomplished by serology or PCR assay on biopsy samples. The purpose of our work was to assess immunofluorescence detection (IFD) in lymph node smears using a specific monoclonal antibody directed against B. henselae and a commercial serology assay (IFA) compared with PCR detection. Among 200 lymph nodes examined from immunocompetent patients, 54 were positive for B. henselae by PCR, of which 43 were also positive by IFD. Among the 146 PCR-negative lymph nodes, 11 were positive by IFD. Based on PCR results, the specificity of this new technique was 92.5%, the sensitivity was 79.6%, and the positive predictive value was 79.6%. At a cutoff titer of 64, the sensitivity of the IFA was 86.8% and the specificity was 74.1%. Diagnosis of cat scratch disease (CSD) may be improved, with a specificity of 100%, when the two tests (IFD and IFA) were negative; the sensitivity was 97.4% if one of the two tests was positive. Since PCR-based detection with biopsy samples is available only in reference laboratories, we suggest using IFD coupled with the commercial serology test for the diagnosis of CSD.

Adolescent↗

Rapid identification and differentiation of Bartonella species using a single-step PCR assay.

Five species of Bartonella have been reported to infect humans and cause a variety of diseases that can be difficult to diagnose. Four species of Bartonella have been reported to infect cats and dogs, and two of these species are considered to be zoonotic pathogens. Diagnosis of Bartonella infections is hampered by the slow, fastidious growth characteristics of Bartonella species. We report on the development of a single-step PCR-based assay for the detection and differentiation of medically relevant Bartonella species. PCR-mediated amplification of the 16S-23S rRNA intergenic region resulted in a product of a unique size for each Bartonella species, thereby allowing differentiation without the necessity of restriction fragment length polymorphism analysis or sequencing of the amplified product. The ability of the single-step PCR assay to differentiate between Bartonella species was determined with characterized isolates and blood samples from animals known to be infected with either Bartonella henselae, B. clarridgeiae, or B. vinsonii subsp. berkhoffii. The sensitivity of the single-step PCR assay relative to that of in vitro culture was determined with blood samples from B. henselae-infected cats. B. henselae target DNA was amplified from 100% of samples with greater than 50 CFU/ml and 80% of samples with 10 to 30 CFU/ml. The single-step assay described in the report expedites PCR-based detection and differentiation of medically relevant Bartonella species.

Animals↗