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Epidemiology of cat-scratch disease hospitalizations among children in the United States.

BACKGROUND: Cat-scratch disease (CSD), caused by infection with Bartonella henselae, affects both children and adults but is principally a pediatric disease. Typical CSD is generally benign and self-limited and is characterized by regional lymphadenopathy with fever. Infections can, however, be accompanied by focal or diffuse inflammatory responses (atypical CSD) involving neurologic, organ (liver/spleen), lymphatic or skeletal systems. METHODS: Pediatric hospitalizations with CSD listed as a diagnosis were examined using the Kids' Inpatient Database for the year 2000. National estimates of CSD-associated hospitalizations, hospitalization rates and various hospitalization statistics were examined for patients younger than 18 years of age. RESULTS: During 2000, an estimated 437 (SE 43) pediatric hospitalizations associated with CSD occurred among children younger than 18 years of age in the United States. The national CSD-associated hospitalization rate was 0.60/100,000 children younger than 18 years of age (95% confidence interval, 0.49-0.72) and 0.86/100,000 children younger than 5 years of age (95% CI 0.64-1.07). Accompanying diagnoses included neurologic complications (12%), organ (liver/spleen) involvement (7%) and "other" (5%). Atypical CSD accounted for approximately 24% of the CSD-associated hospitalizations. The median charge for a CSD-associated hospitalization was 6140 dollars with total annual hospital charges of approximately 3.5 million dollars among children in the United States. CONCLUSIONS: The CSD-associated hospitalization rate among children during 2000 appeared similar to those estimated for the 1980s in the United States, despite significant increases in cat ownership in the intervening time. Early serologic and molecular testing for CSD in children is suggested to minimize unnecessary interventions and promote optimally effective care when supportive measures are required.

Adolescent↗

[Tropical animal and human rickettsial infections].

Advances in molecular biology have provided tools that have greatly clarified our knowledge of rickettsial diseases. Most rickettsias have been reclassified in the alpha subgroup of proteobacteria. Four groups of rickettsias have been identified: the spotted fever group, the typhus group, Ehrlichia, and Bartonella. Although still considered as a rickettsia, Coxiella burnetti, the agent causing Q fever, has been reclassified separately in the gamma subdivision of proteobacteria. Recognition of rickettsial disease is still based mainly on clinical manifestations (rash, eschar, and scratching sores). Little progress has been made in serologic testing. Indirect immunofluorescence is the most common technique. Diagnostic techniques based on molecular biology are currently available in only a small number of laboratories. Treatment with tetracyclines is indicated but prophylaxis through proper hygiene is the most effective approach.

Animals↗

The role of molecular techniques in the understanding of emerging infections.

Emerging infections are defined as infections that are newly identified or recognized, or those whose incidence in humans has significantly increased over the past 20 years. The interaction of several factors contributes to the emergence of infectious disease, including changes in human behavior, technological advances, economic development, increased international travel, microbial adaptation and lapses in public health measures. Biomedical research has allowed us to identify and classify previously uncultured pathogens, characterize microbial virulence factors, create new diagnostic tests and develop vaccines. Here, we highlight a few emerging infections and illustrate the role that molecular medicine has played in furthering our understanding of these diseases.

Bartonella Infections↗

Bartonella quintana and Mycobacterium tuberculosis coinfection in an HIV-infected patient with lymphadenitis.

Cat scratch disease (CSD) is usually associated with Bartonella henselae infection in patients with a history of cat exposure, but Bartonella quintana may also be a cause of chronic lympadenopathy in patients with cat or flea contact. The lymph node histopathology of CSD and tuberculosis may be indistinguishable. We report herein the first description of lymph node coinfection with B. quintana and M. tuberculosis in a 32-year HIV-infected woman. Culture of lymph node biopsy material on Columbia agar with sheep blood and on human endothelial cells in shell vial allowed us to isolate not only B. quintana, but also M. tuberculosis hominis.

Adult↗

Survey of tickborne infections in Denmark.

We conducted a study of the distribution and prevalence of tickborne infections in Denmark by using roe deer as sentinels. Blood samples from 237 roe deer were collected during the 2002-2003 hunting season. Overall, 36.6% of deer were Borrelia seropositive, while 95.6% were Anaplasma phagocytophilum positive; all animals were negative for Bartonella quintana and B. henselae by indirect immunofluorescence assay. When a hemagglutination-inhibition test was used, 8.7% of deer were found positive for tickborne encephalitis (TBE)-complex virus. A total of 42.6% were found positive by polymerase chain reaction (PCR) for A. phagocytophilum with significant seasonal variation. All were PCR negative for Rickettsia helvetica. PCR and sequencing also showed a novel bacterium in roe deer previously only found in ticks. The study showed that the emerging pathogen A. phagocytophilum is widely distributed and that a marked shift has occurred in the distribution of TBE-complex virus in Denmark. This finding supports studies that predict alterations in distribution due to climatic changes.

Age Factors↗

[Bartonella and bartonellosis--emerging and re-emerging infections. Taxonomy, bacteriology, pathogenesis and genetics].

The review updates knowledge on the taxonomy, bacteriology and genetics of Bartonella as well as pathogenesis of bartonellosis. The role of Bartonella in human pathology, formerly considered to be rather modest, causes now growing anxiety. In this connection Bartonella are now believed to be the causative agents of so-called emerging and re-emerging diseases, i.e. diseases, formerly unknown to man, and diseases, believed to be eradicated and playing at present no important role in human pathology. These microorganisms are a bright example of successes of molecular biology in the detection of microorganisms, as well as in their phylogenetics and systematics.

Animals↗

High seroprevalence to Bartonella quintana in homeless patients with cutaneous parasitic infestations in downtown Paris.

Bartonella quintana infections have recently been reported in homeless patients. We prospectively studied the prevalence of and the factors associated with a positive serology to B quintana in the homeless population of downtown Paris. The following data were recorded: ongoing cutaneous parasitic infestation, years of homelessness, living status, previous episodes of body pediculosis and scabies, alcoholism, intravenous drug use, known immunodepression (including undernutrition and known HIV infection), and contacts with animals. B quintana serology was performed in 57 patients and in 53 age- and sex-frequency-matched downtown Paris volunteer blood donors. Thirty-one patients (54%; 95% confidence interval [CI], 41%-68%) had a positive B quintana serology as compared with 2% in the control group (P <.0001); 8 of 57 patients (14%; 95% CI: 6%-26%) had a serologic profile of an evolving infection. Age and years of homelessness were independently associated with a positive B quintana serology with adjusted relative risks (RRs) of 2.9 (95% CI, 1.4-5.9) for age 40 years and older and 1.7 (95% CI, 1.1-2.7) for years of homelessness 3 or more. Our results suggest a high prevalence of past and recent infections with B quintana in the downtown Paris homeless population with cutaneous parasitic infestations.

Adult↗

Bacillary (epithelioid) angiomatosis and concurrent Kaposi's sarcoma in acquired immunodeficiency syndrome.

Two patients with acquired immunodeficiency syndrome developed simultaneous Kaposi's sarcoma and bacillary (epithelioid) angiomatosis. The distinguishing clinical and histologic features of these two vascular proliferations associated with human immunodeficiency virus disease are described. The lesions of bacillary (epithelioid) angiomatosis contained bacteria, while the lesions of Kaposi's sarcoma did not. With erythromycin therapy, the lesions of bacillary (epithelioid) angiomatosis cleared, while those of Kaposi's persisted. Bacillary (epithelioid) angiomatosis, a treatable but potentially fatal opportunistic infection of human immunodeficiency virus disease, should be considered in the differential diagnosis of vascular lesions in immunosuppressed patients.

Acquired Immunodeficiency Syndrome↗

Immunologic response to Bartonella henselae as determined by enzyme immunoassay and Western blot analysis.

Bartonella henselae is now regarded as the etiologic agent of cat-scratch disease and a cause of bacillary angiomatosis. We examined the human immune response to Bartonella henselae infection using a newly developed enzyme immunoassay (EIA) and a Western blot procedure using outer-membrane proteins. The EIA showed 98.6% and 91.4% agreement with an indirect fluorescence method (IFA) for detection of IgM and IgG antibodies, respectively. By using Western blot analysis, reactivity to an 8-kd band showed significant correlation with positive results by the IgM IFA and EIA. In contrast, reactivity to 209-, 208.5-, 208-, 116-, and 80-kd bands was identified only in positive IgG IFA serum samples. The EIA and Western blot should be useful tests in determining the antibody response to B. henselae infection and may also be important in determining the critical epitopes in the host-parasite interaction of this organism.

Adolescent↗

Role of Bartonella henselae in the etiology of Henoch-Schönlein purpura.

BACKGROUND: The etiology of Henoch-Schönlein purpura (HSP) has been ascribed to a variety of infectious and noninfectious agents. Because we encountered a patient with HSP who had evidence of Bartonella henselae infection and a prior report of a patient with systemic cat-scratch disease presenting as leukoclastic vasculitis, we investigated the association of B. henselae infection with HSP. METHODS: We determined the antibody titers to B. henselae on the sera of 18 patients with HSP and on 57 controls. All patients presented with the characteristic leukoclastic rash of HSP. About one-half of the patients had joint or abdominal symptoms, and four had hematuria at presentation. An indirect immunofluorescent assay was used to determine serum antibody titers to B. henselae. Sera that were reactive at a dilution of 1/64 were considered positive. RESULTS: Eight of the 57 (14%) control sera and 12 of the 18 (67%) patient sera were positive for B. henselae antibody (P < 0.0001). CONCLUSION: The results of this study indicate a significant association of antecedent B. henselae infection with HSP. The frequency of this association (67%) exceeds that of previously ascribed etiologic agents for this disease, such as the group A Streptococcus.

Adolescent↗

Infective endocarditis due to unusual or fastidious microorganisms.

Infective endocarditis due to fastidious microorganisms is commonly encountered in clinical practice. Some organisms such as fungi account for up to 15% of cases of prosthetic valve infective endocarditis, whereas organisms of the HACEK group (Haemophilus parainfluenzae, H. aphrophilus, and H. paraphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) cause 3% of community-acquired cases of infective endocarditis. Special techniques are necessary to identify these microorganisms. A history of contact with mammals or birds may suggest infection caused by Coxiella burnetii (Q fever), Brucella species, or Chlamydia psittaci. A nosocomial cluster of postsurgical infective endocarditis may be caused by Legionella species or Mycobacterium species. If risk factors that are commonly associated with fungal infections (cardiac surgical treatment, prolonged hospitalization, indwelling central venous catheters, and long-term antibiotic use) are present, fungal endocarditis is possible. Patients with endocarditis and a history of periodontal disease or dental work in whom routine blood cultures are negative might have infection due to nutritionally variant streptococci or bacteria of the HACEK group. Communication between the microbiologist and the clinician is of crucial importance for identification of these microorganisms early during the course of the infection before complications such as embolization or valvular failure occur. In this article, we review the microbiologic and clinical features of these organisms and provide recommendations for diagnosis and treatment.

Anti-Bacterial Agents↗

Role of dendritic cell-derived CXCL13 in the pathogenesis of Bartonella henselae B-rich granuloma.

Dendritic cells (DCs) initiate adaptive immunity and regulate the inflammatory response by producing inflammatory chemokines. This study was aimed to elucidate their role in the pathogenesis of the suppurative granuloma induced by Bartonella henselae infection, which characterizes cat scratch disease (CSD). In vitro DC infection by B. henselae results in internalization of bacteria, phenotypic maturation with increased expression of HLA-DR and CD86, and induction of CD83, CD208, and CCR7. In comparison to LPS-activated DCs, B henselae-infected DCs produce higher amounts of IL-10, whereas the production of IL-12p70 is reduced. Infected DCs also produce high levels of CXCL8 and CXCL13, 2 chemokines active respectively on neutrophils and B lymphocytes. These results provide the molecular basis for the morphogenesis of CSD granuloma, which typically contains high numbers of neutrophils and B cells. Remarkably, CSD granulomas in vivo contain CXCL13-producing DCs. We further demonstrate that the B cells in CSD granulomas are represented by monocytoid B cells and, worth noting, they express T-bet, a transcription factor able to induce a T-independent immunoglobulin (Ig) class switch in B lymphocytes. These findings suggest that the humoral immune response to B henselae initiates in the extrafollicular areas of infected lymph nodes and is regulated by DCs.

Animals↗

Bacillary angiomatosis in patients with AIDS: multiorgan imaging findings.

PURPOSE: To describe the varied clinical manifestations and imaging findings encountered in bacillary angiomatosis, an infectious complication of the acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Clinical, imaging, and histopathologic findings in nine men (aged 26-50 years) with AIDS and bacillary angiomatosis were described. This condition often manifests as vascular skin lesions that resemble those of Kaposi sarcoma, fever, and anemia and is due to infection with Bartonella (Rochalimaea) henselae. RESULTS: Common imaging findings included lung nodules, mediastinal adenopathy, peripheral adenopathy, pleural effusions, ascites, abdominal adenopathy, soft-tissue masses, and low-attenuation lesions in the liver and/or spleen. Most notably, nodes and soft-tissue lesions were dramatically enhanced with injection of contrast material, which is presumably because the lesions are composed to a large extent of well-formed capillaries. CONCLUSION: Bacillary angiomatosis, a treatable infection, should be considered in patients with AIDS, particularly when Kaposi sarcoma is suspected clinically.

Acquired Immunodeficiency Syndrome↗

[Study on Bartonella species in rodents in western Yunnan, China].

OBJECTIVE: To study the infection status of Bartonella spp. in rodents in western part of Yunnan province. METHODS: Blood samples were collected from four species of rodents captured in four counties in western Yunnan in 2004. Bartomella was isolated through being cultured in brain and heart infusion agar media containing 5% rabbit blood. Suspective Bartomella strains isolates were confirmed by amplification of 379 bp of citrate synthase (gltA) gene with specific primer by polymerase chin reaction (PCR). RESULTS: Fifty-four strains of Bartomella isolates were obtained from 397 samples including four rodent species captured in the fields with an overall isolation-rate of 13.6% (54/397). The rates of isolation among different species were: 22.0% (22/100) in Rattus nitidus, 14.8% (31/210) in Rattus flavipectus and 1.2%(1/87) in Rattus norvegicus while in R. t. yunnanensis it was negative. CONCLUSION: These findings demonstrated that the local rodents in western Yunnan were widely infected by Bartomella spp. It is indispensable to study the vector and the route of transmission to discover the relations between Bartomella and human diseases.

Animals↗

[Reactive arthritis after cat bit: a rare manifestation of cat scratch disease--case report and overview].

Cat scratch disease (CSD) is a rarely recognized infectious disease in Germany. Only a few years ago the causative agent, Bartonella henselae, could be isolated. The typical clinical manifestations of CSD consist of skin changes at the inoculation site and a benign lymphadenopathy; other manifestations are rare. We report the case of a 47 year old woman, who developed a reactive spondylarthropathy with synovitis of finger joints, polyarthralgias of large- and medium-sized joints, and inflammatory spinal pain after a cat bite. The rheumatic manifestations resolved after 10 months by treatment with non-steroidal antirheumatic drugs. Only a few cases of rheumatic manifestations associated with CSD have been described in the literature. Because the prevalence of Bartonella henselae infection of cats is high in Europe, rheumatic manifestations might be more frequent. Diagnosis of CSD is now improved by the development of serological tests. We provide an overview of the clinical manifestations and the diagnostic criteria.

Animals↗

Experimental infection of white-tailed deer with Anaplasma phagocytophilum, etiologic agent of human granulocytic anaplasmosis.

Serologic and molecular evidence of Anaplasma phagocytophilum has been demonstrated in white-tailed deer (WTD; Odocoileus virginianus), and deer are an important host for the tick vector Ixodes scapularis. In this study, we describe experimental infection of WTD with A. phagocytophilum. We inoculated four WTD with a human isolate of A. phagocytophilum propagated in tick cells. Two additional deer served as negative controls. All inoculated deer developed antibodies (titers, > or =64) to A. phagocytophilum, as determined by an indirect fluorescent antibody test, between 14 and 24 days postinfection [p.i.]), and two deer maintained reciprocal titers of > or =64 through the end of the 66-day study. Although morulae were not observed in granulocytes and A. phagocytophilum was not reisolated via tick cell culture of blood, 16S reverse transcriptase nested PCR (RT-nPCR) results indicated that A. phagocytophilum circulated in peripheral blood of three deer through at least 17 days p.i. and was present in two deer at 38 days p.i. Femoral bone marrow from one deer was RT-nPCR positive for A. phagocytophilum at 66 days p.i. There was no indication of clinical disease. These data confirm that WTD are susceptible to infection with a human isolate of A. phagocytophilum and verify that WTD produce detectable antibodies upon exposure to the organism. Because adults are the predominant life stage of I. scapularis found on deer and because adult I. scapularis ticks do not transmit A. phagocytophilum transovarially, it is unlikely that WTD are a significant source of A. phagocytophilum for immature ticks even though deer have a high probability of natural infection. However, the susceptibility and immunologic response of WTD to A. phagocytophilum render them suitable candidates as natural sentinels for this zoonotic tick-borne organism.

Anaplasma phagocytophilum↗

Unsuspected extralymphocutaneous dissemination in febrile cat scratch disease.

Cat scratch disease (CSD) commonly manifests as regional self-limited lymphadenitis. However, dissemination of the infection to distant multiple sites may occur even in immunocompetent patients. We report a series of 11 children with fever and extralymphocutaneous manifestations of CSD, in order to highlight potential multiorgan involvement in patients with febrile CSD. To be eligible for enrollment, patients had to present with involvement of sites other than regional lymph nodes. The diagnosis was based on suggestive clinical criteria, histological findings and positive serology. The utilization of ultrasound imaging revealed hepatic lesions in 3 children and splenic lesions in 8 children, whereas osteolytic lesions were observed in 4 children by bone scan. Hepatic or splenic involvement was not suggested by clinical signs or biochemical investigation in 2/3 and 6/8 children, respectively. Bone involvement was supported either by relative symptoms or signs. Our findings indicate that, in the presence of fever, extralymphocutaneous manifestations have to be anticipated in patients with clinically suspected CSD. The systematic use of imaging modalities in patients with serologically documented Bartonella henselae infection could contribute to a better understanding of the clinical spectrum of CSD.

Adolescent↗