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Previously, we reported the isolation of Bartonella henselae from the blood of harbor porpoises (Phocoena phocoena) and loggerhead sea turtles (Caretta caretta) from the North Carolina coast. Hematologic, pathologic, and microbiologic findings surrounding the death of a juvenile captive beluga in Vancouver initiated an outbreak investigation designed to define the molecular prevalence of Bartonella infection in belugas. Using polymerase chain reaction analyses targeting the intergenic spacer region (ITS), two B. henselae ITS strains were identified in 78% of captive and free-ranging hunter-harvested belugas. These findings may have public health implications and may influence aquarium management procedures for captive marine mammals.

Bacillary angiomatosis is a recently recognized bacterial infectious disease that is seen mainly in patients with the acquired immunodeficiency syndrome. Including this publication, 45 patients have been described in the medical literature. In this report we describe examples of the clinical presentations of bacillary angiomatosis and review therapeutic strategies.

Bartonella henselae was discovered a quarter of a century ago as the causative agent of cat scratch disease, a clinical entity described in the literature for more than half a century. As diagnostic techniques improve, our knowledge of the spectrum of clinical disease resulting from infection with Bartonella is expanding. This review summarizes current knowledge regarding the microbiology, clinical manifestations, diagnostic techniques, and treatment of B henselae infection.

The antibody response to Bartonella henselae has been studied in a number of mammals; however, the human response needs to be further studied. After natural infection, humans have antibody reactivity to a large number of B. henselae proteins. We used a proteomic approach to identify antigenic proteins of B. henselae to determine their capacity to elicit a human antibody response. Comparing patient sera by Western blot analysis demonstrated significant amounts of reactivity to B. henselae. The immunofluorescence assay (IFA)-positive sera identified several protein spots of interest. However, a consistent reactivity to a single spot by all sera was not observed. Three of these spots demonstrated reactivity in 71%, 64%, and 64% of positive sera tested with negligible reactivity to the negative sera. These proteins were identified as GroES, BepA, and GroEL. Most IFA-positive sera demonstrated reactivity to GroES, GroEL, and BepA. The usefulness of these proteins for a clinical serologic assay is discussed.

Bacillary angiomatosis is a cutaneous or visceral infection with Bartonella henselae or Bartonella quintana. Cases usually occur in HIV infected individuals. We present a 60-year-old man with chronic lymphocytic leukemia and neutropenic fever caused by bacillary angiomatosis. The nine BA cases in oncology patients are reviewed.

Bartonella henselae lymphadenitis, or cat-scratch lymphadenitis (CSL), is classically associated with stellate microabscesses, occasional giant cells, and extension of the inflammatory infiltrate into perinodal soft tissue. Availability of B. henselae molecular testing on tissue specimens has broadened our understanding of the morphologic variation in this disease. Here we sought to describe the histopathologic features of the largest series to date of molecularly proven CSL. B. henselae polymerase chain reaction-positive tissue specimens from 2010 to 2012 were identified, and hematoxylin and eosin slides were reviewed. A single-step 16S-23S rRNA-based polymerase chain reaction testing was used to identify B. henselae on formalin-fixed, paraffin-embedded tissues. A total of 100 B. henselae-positive cases were identified. The median age of the patients was 26.5 years (range, 1 to 69 y). Ninety-two percent of cases presented in lymph nodes, with 66% of these occurring above the diaphragm, most commonly in the cervical chain. Of 100 cases, 57 had classical CSL features of necrotizing granulomas with microabscesses, with or without surrounding palisading histiocytes. In contrast, 43/100 cases lacked the prototypical microabscesses of CSL including: 23 cases (53.5%) with features of fungal/mycobacterial lymphadenitis, 6 (14%) cases with features of Kikuchi lymphadenitis, and 4 cases (9.3%) with the classic histologic triad of toxoplasma lymphadenitis. In summary, B. henselae lymphadenitis may lack the typical microabscesses in almost half of cases and may closely mimic other reactive, especially infectious, lymphadenopathies. Given the lack of specificity of many of these features, a low threshold for B. henselae molecular testing on tissue is warranted in the appropriate clinical context.

The gram-negative bacterium Bartonella henselae is capable of causing angiogenic lesions as a result of infection. Previously, it has been shown that B. henselae infection can result in production of the chemokine interleukin-8 (IL-8). In this study, we demonstrated that monocytes, endothelial cells, and hepatocytes produce IL-8 in response to B. henselae infection. We also investigated the role of IL-8 in B. henselae -induced endothelial cell proliferation and capillary tube formation. Both in vitro angiogenesis assays were IL-8 dependent. B. henselae -mediated inhibition of apoptosis, as indicated by gene expression of Bax and Bcl-2 , was also shown to be IL-8 dependent in endothelial cells. Furthermore, infection of endothelial cells with B. henselae stimulated upregulation of the IL-8 chemokine receptor CXCR2. Infection of human endothelial cells by B. henselae resulting in IL-8 production likely plays a central role in the ability of this organism to cause angiogenesis during infection.

Bartonella henselae has not only been identified as the causative agent of cat scratch disease, but it is also associated with other significant infectious syndromes in the immunocompromised population. We describe two cases of B. henselae associated diseases in liver transplant recipients who both had contact with cats. The first recipient developed localized skin manifestation of bacillary angiomatosis in association with granulomatous hepatitis. He tested positive for Immunoglobulin G (IgG) antibodies against B. henselae. The second patient developed axillary lymphadenopathy, with biopsy showing necrotizing granulomatous inflammation and polymerase chain reaction studies were positive for B. henselae DNA. Her serology for bartonellosis showed a fourfold rise in antibody titers during her hospitalization. Both patients responded to treatment with Azithromycin in combination with Doxycycline. These were the only cases within a series of 467 consecutive liver transplants performed in 402 patients performed during a 4-year period. Although bartonellosis is a rare infection in liver transplantation recipients, it should always be included in the differential diagnosis of patients presenting with fever, central nervous system (CNS) symptoms, skin lesions, lymphadenopathy, and hepatitis especially if prior contact with cats is reported.

Background. Bartonella quintana, the etiological agent of bacillary angiomatosis (BA), causes endothelial cell proliferation. Erythromycin has dramatic effects on BA, and the effects are largely unexplained by the compound's bacteriostatic properties. Our aim here was to evaluate the possibility that erythromycin alters angiogenesis. Methods. The effect of erythromycin on B. quintana-induced endothelial cell proliferation was studied using a wild-type strain and an erythromycin-resistant B. quintana mutant. The latter was generated by serial subcultures on blood agar plates. Results. We show that erythromycin significantly inhibits the proliferation of dermal microvascular endothelial cells induced either by wild-type B. quintana or by our erythromycin-resistant mutant. Doxycycline and gentamycin failed to exert such an effect. Finally, we found that the resistant strain harbored a 27-bp insertion in the highly conserved region of the gene encoding the ribosomal protein L4; this insertion may explain the existence of the resistance to erythromycin. Conclusion. The data presented here indicate that erythromycin profoundly down-modulates endothelial cell proliferation irrespective of its bacteriostatic effects and suggest that this may be a key component of the efficacy of the compound in the treatment of patients with BA.

Background Both endocarditis and Bartonella infections are neglected public health problems, especially in rural Asia. Bartonella endocarditis has been described from wealthier countries in Asia, Japan, Korea, Thailand and India but there are no reports from poorer countries, such as the Lao PDR (Laos), probably because people have neglected to look. Methodology/Principal Findings We conducted a retrospective (2006–2012), and subsequent prospective study (2012–2013), at Mahosot Hospital, Vientiane, Laos, through liaison between the microbiology laboratory and the wards. Patients aged >1 year admitted with definite or possible endocarditis according to modified Duke criteria were included. In view of the strong suspicion of infective endocarditis, acute and convalescent sera from 30 patients with culture negative endocarditis were tested for antibodies to Brucella melitensis, Mycoplasma pneumoniae, Bartonella quintana, B. henselae, Coxiella burnetii and Legionella pneumophila. Western blot analysis using Bartonella species antigens enabled us to describe the first two Lao patients with known Bartonella henselae endocarditis. Conclusions/Significance We argue that it is likely that Bartonella endocarditis is neglected and more widespread than appreciated, as there are few laboratories in Asia able to make the diagnosis. Considering the high prevalence of rheumatic heart disease in Asia, there is remarkably little evidence on the bacterial etiology of endocarditis. Most evidence is derived from wealthy countries and investigation of the aetiology and optimal management of endocarditis in low income countries has been neglected. Interest in Bartonella as neglected pathogens is emerging, and improved methods for the rapid diagnosis of Bartonella endocarditis are needed, as it is likely that proven Bartonella endocarditis can be treated with simpler and less expensive regimens than “conventional” endocarditis and multicenter trials to optimize treatment are required. More understanding is needed on the risk factors for Bartonella endocarditis and the importance of vectors and vector control., Author Summary Infection of heart valves (endocarditis) with bacteria is an important condition, especially afflicting those with rheumatic heart disease, and has a high mortality if untreated. Most of the evidence for optimal antibiotic and surgical management comes from wealthy countries. There are no published data from poorer countries in SE Asia despite a high burden of rheumatic heart disease. We investigated the bacterial infections of heart valves in the Lao PDR (Laos) through heart ultrasound scans and analysis of patients' blood. We provide evidence of infection with the poorly understood bacteria Bartonella henselae (the cause of cat scratch disease) in two patients from Laos. We argue that it is likely that Bartonella endocarditis is more widespread than appreciated, as there are few laboratories in Asia able to make the diagnosis. This is important as it is likely that proven Bartonella endocarditis can be treated with simpler and less expensive regimens than “conventional” endocarditis. There have been great advances in the wealthy world in the diagnosis and treatment of endocarditis but these have not been assessed or implemented in poorer countries. More evidence on the causes and optimal management of endocarditis in low income countries is needed.

Bacillary angiomatosis is a disorder of neovascular proliferation involving skin and lymph nodes of immunosuppressed patients. Bartonella henselae or Bartonella quintana have been inculpated as causative by direct culture or PCR amplification of DNA sequences. Here, we report the clinical evolution of a patient infected with human immunodeficiency virus (HIV) whose B. quintana infection was diagnosed by PCR.

Although there is evidence that endothelial cells are important targets for human pathogenic Bartonella species, the primary niche of infection is unknown. Here we elucidated whether human CD34+ hematopoietic progenitor cells (HPCs) internalize B henselae and may serve as a potential niche of the pathogen. We showed that B henselae does not adhere to or invade human erythrocytes. In contrast, B henselae invades and persists in HPCs as shown by gentamicin protection assays, confocal laser scanning microscopy (CLSM), and electron microscopy (EM). Fluorescence-activated cell sorting (FACS) analysis of glycophorin A expression revealed that erythroid differentiation of HPCs was unaffected following infection with B henselae. The number of intracellular B henselae continuously increased over a 13-day period. When HPCs were infected with B henselae immediately after isolation, intracellular bacteria were subsequently detectable in differentiated erythroid cells on day 9 and day 13 after infection, as shown by CLSM, EM, and FACS analysis. Our data provide, for the first time, evidence that a bacterial pathogen is able to infect and persist in differentiating HPCs, and suggest that HPCs might serve as a potential primary niche in Bartonella infections.

Bacteria of the genus Bartonella , a member of the Alphaproteobacteria , are fastidious, gram-negative, aerobic bacilli that comprise numerous species, subspecies, and subtypes. In human and veterinary medicine, species isolation remains a vital component of the diagnostic and therapeutic management of Bartonella infection. We describe a novel, chemically modified, insect-based liquid culture medium that supports the growth of at least seven Bartonella species. This medium will also support cocultures consisting of different Bartonella species, and it facilitated the primary isolation of Bartonella henselae from blood and aqueous fluid of naturally infected cats. This liquid growth medium may provide an advantage over conventional direct blood agar plating for the diagnostic confirmation of bartonellosis.

A 33-year-old man with a known bicuspid aortic valve presented with fever, chills, progressive fatigue, anorexia, and night sweats. Echocardiography confirmed aortic-valve endocarditis, but blood cultures remained negative. Bartonella henselae endocarditis was ultimately confirmed by serology as well as by immunohistochemistry and PCR testing of the excised valve. The patient recovered with appropriate antibiotic therapy. B henselae is a common cause of culture-negative endocarditis. It predominantly affects men with underlying valvular disease, and has a predilection for aortic valves. Diagnosis is usually made serologically and with either tissue culture, immunohistochemistry, or PCR. Treatment of this destructive endocarditis consists of a combination of long-term antibiotic therapy and surgical valve repair. This case is used to discuss the approach towards the treatment of patients with endocarditis that is blood-culture negative.

The prevalences of antibodies against Bartonella henselae and Ehrlichia canis were determined in sera from 228 dogs in 5 communal lands of Zimbabwe, areas where traditional subsistence agro-pastoralism is practised. The sera were collected from apparently healthy dogs during routine rabies vaccination programmes and tested with indirect fluorescent antibody assays using B. henselae (Houston-I) and E. canis (Oklahoma) as antigens. We found reactive antibodies (1:80) against B. henselae in 14 % of the dogs tested. Seropositive animals were found in Bikita (41 %; 17/42), Omay (13 %; 6/48), Chinamora (5 %; 2/38) and Matusadona (15 %; 7/48). No seropositive dogs were found in Chiredzi (0 %; 0/52). Antibodies reactive with E. canis (1:80) were found in 34%of the dogs tested, from Bikita (88 %; 37/42), Chiredzi (31 %; 16/52), Omay (17 %; 8/48), Chinamora (26 %; 10/38) and Matusadona (15 %; 7/48). Our survey shows dogs in the communal lands of Zimbabwe are frequently exposed to E. canis and B. henselae or closely related species. Further studies are indicated to determine the pathogenicity of the organisms infecting these dogs and their clinical significance.

The aim of this study is to understand host immune responses in immunocompetent and immunocompromised mice against Bartonella henselae infection. BALB/c and nude (BALB/c nu/nu) mice were inoculated intraperitoneally with 10(8) colony forming units of B. henselae (Houston-1 strain). Blood, brain, liver, spleen, kidney and bone marrow samples were collected 0, 3, 7, 14, 21 and 28 days after infection and submitted to bacteriological, serological and genetical examinations. B. henselae was isolated only from the liver 3 days after infection. DNA of the inoculums was detected by polymerase chain reaction from blood, liver, and spleen samples collected from BALB/c and blood from nude mice 3 and 7 days after infection. No bacterial DNA was detected from both BALB/c and nude mice thereafter during 4 weeks observation periods. These results indicate that the T-cell may not participate in the effective elimination of the organisms from mice. In addition, western blot analysis revealed that the antigens of 27.3- and 31.5-kDa reacted with IgM antibodies from the blood of BALB/c and nude mice after 3 days of infection, suggesting that these antigens were recognized by thymus-independent mechanism. Furthermore the antigens were detected from the culture-supernatants of B. henselae, indicating that these antigens were secreted from the organisms.

Bartonella henselae causes severe disease in immunocompromised individuals. B. henselae was isolated from 12 human immunodeficiency virus (HIV)‐infected individuals with bacillary angiomatosis and/or peliosis hepatis and from their 15 cat contacts. Specific associations between the 2 B. henselae genotypes, individual pulsed-field gel electrophoresis (PFGE) patterns, and different clinical syndromes and pathogenicity were investigated. The role of cat contacts as the source of human infection was also examined. Three of the 4 patients with B. henselae genotype I infection, but none of the 8 patients with genotype II infection, had hepatosplenic vascular proliferative lesions ( ). Four of 5 human-cat pairs had closelyP p .018 related PFGE patterns and concordant results by 16S rDNA typing, which strongly suggests that human infection was caused by the cat contact. These results corroborate the major role of cats in the transmission of B. henselae to humans and suggest that B. henselae genotypes may induce different pathological features in HIV-infected patients.

Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Knowledge of the conditions affecting muscle, bone, and joints in HIV-infected patients is essential for successful management. Myopathies may be caused by pyogenic infection (eg, pyomyositis), idiopathic inflammation (eg, polymyositis), or drug effect (eg, AZT myopathy). Characteristic skeletal infections, such as tuberculosis and bacillary angiomatosis, require a high index of suspicion for accurate diagnosis. Neoplastic processes, such as non-Hodgkin's lymphoma and Kaposi's sarcoma, occur more frequently as the immune system deteriorates. Inflammatory and reactive arthropathies are more prevalent in HIV-positive than HIV-negative individuals and include Reiter's syndrome, psoriatic arthritis, HIV-associated arthritis, painful articular syndrome, acute symmetric polyarthritis, and hypertrophic osteoarthropathy. Patients with atypical musculoskeletal complaints and a suspected history of exposure should be tested for HIV.

Bacillary angiomatosis is an opportunistic infection occurring predominantly in patients with HIV infection. The manifestations of this vasculoproliferative disorder vary markedly. Virtually any organ site may be involved, singly or multiply. However cutaneous involvement can be a valuable clue to its diagnosis. We report a case of bacillary angiomatosis in an HIV-infected patient presenting as isolated pyomyositis of the right leg. The rarity of such a presentation and paucity of cutaneous lesions, as in our case, may render timely diagnosis elusive and difficult. Its recognition however, is important since bacillary angiomatosis, if untreated, is potentially fatal.

Human bartonelloses are a group of illnesses of poorly understood pathogenesis. Bartonella henselae is one of the most studied bacterium of its genus. The objective of this study was to observe whether passages of these bacteria, in vivo, would determine ultrastructural changes in them. For this purpose, isogenic mice were inoculated with a standard strain of B. henselae (I). These were initially retrieved from genetically immunodeficient animals (II) and then inoculated in immunocompetent ones. The bacterial colonies obtained (III) were compared, by transmission electron microscopy, with colonies I and II. Loss of fimbriae and an abundant bleb formation were the most common morphological changes found in colony III. Also, on day 6 postinfection, the main histological abnormalities were the endothelial proliferation presented in immunodeficient animals and the incipient granulomata reaction found in one of the immunocompetent inoculated mice, which died spontaneously. These features agree with the Bartonella human disease clinical and histological observations. This study demonstrates that B. henselae in vivo passages induce significant morphological changes in the bacteria and that these abnormalities could explain their seemingly greater virulence. Most of these observations have not been previously described. Thus, further studies on the Bartonella species pathogenesis should consider these data.

In this study, we examine prevalences of three infectious pathogens with different transmission modes (Bartonella henselae, hemoplasma, and Toxoplasma gondii) in feral cats from urban and rural habitats. Infection status of the three pathogens in blood samples (n = 117) was determined through molecular or serological diagnostic methods. Overall prevalence of hemoplasma, Toxoplasma gondii, and Bartonella henselae was 47.9%, 50%, and 35.7%, respectively. Comparing the two habitats, only seroprevalence of Bartonella henselae was significantly higher in urban cats. Based on the results, we discuss how pathogens with distinct transmission modes may show different prevalence between urban and rural habitat types.

A patient with a prosthetic aortic valve, and culture negative endocarditis caused by Bartonella henselae presented with nonspecific constitutional symptoms, skin rash, and then later developed acute renal failure. The patient underwent redo sternotomy, aortic root, and ascending aorta replacement with a homograft, which resolved his symptoms and the renal failure.

Bacillary angiomatosis is an infectious disease caused by 2 gram-negative bacilli, Bartonella henselae and Bartonella quintana. This disease is characterized by vascular proliferations in the skin and/or visceral organs, and typically manifests in immunocompromised patients. However, we report a case of a 10-year-old immunocompetent female child with a questionable history of being scratched by a cat. Although initially diagnosed as a pyogenic granuloma, a diagnosis of bacillary angiomatosis was made based on histologic examination of the excised lesion demonstrating interstitial bacillary deposition on Warthin-Starry silver stain. The patient was successfully treated with 2 weeks of azithromycin after which all symptoms resolved.

Bacillary angiomatosis mainly affects the HIV-infected population. Information is limited on the evolution of bacillary angiomatosis during immune restoration following initiation of HAART. We report an unusual case of fatal Bartonella quintana bacillary angiomatosis occurring in an HIV-infected man during the immune restoration phase.

A 61-year-old male presented with fever. He had a history of aortic valve replacement, and infective endocarditis was suspected. The transthoracic and transesophageal echocardiography on admission could not detect vegetation, and all blood cultures obtained were negative. We concluded that infective endocarditis was not likely. However, repeated echocardiography revealed paravalvular regurgitation and paravalvular abscess. Serum antibody testing for Bartonella henselae was positive, leading to the diagnosis of blood culture-negative endocarditis. Even when blood cultures and echocardiography were negative on initial examination, careful history-taking, blood tests accounting for these pathogens, and repeated echocardiography are crucial for diagnosis.

Bartonella henselae (Bh) is an emerging zoonotic pathogen that has been associated with a variety of human diseases, including bacillary angiomatosis that is characterized by vasoproliferative tumor-like lesions on the skin of some immunosuppressed individuals. The study of Bh pathogenesis has been limited to in vitro cell culture systems due to the lack of an animal model. Therefore, we wanted to investigate whether the zebrafish embryo could be used to model human infection with Bh. Our data showed that Tg(fli1:egfp)y1 zebrafish embryos supported a sustained Bh infection for 7 days with >10-fold bacterial replication when inoculated in the yolk sac. We showed that Bh recruited phagocytes to the site of infection in the Tg(mpx:GFP)uwm1 embryos. Infected embryos showed evidence of a Bh-induced angiogenic phenotype and an increase in the expression of genes encoding pro-inflammatory factors and pro-angiogenic markers. However, infection of zebrafish embryos with a deletion mutant in the major adhesin (BadA) resulted in little or no bacterial replication and a diminished host response, providing the first evidence that BadA is critical for in vivo infection. Thus, the zebrafish embryo provides the first practical model of Bh infection that will facilitate efforts to identify virulence factors and define molecular mechanisms of Bh pathogenesis.

We report a case of blood culture-negative tricuspid infective endocarditis revealed after tick bite by repeated pulmonary infection during one year due to septic pulmonary emboli in a 67-year-old farmer woman. Tricuspid vegetation and pulmonary emboli are calcified. Lyme serology is negative. Serologic test and PCR analysis are positive to Bartonella henselae. The evolution is favorable after antibiotic and anticoagulant treatment. Infective endocarditis due to B. henselae is an exceptional complication of cat scratch disease. You have to think about in case of blood culture-negative endocarditis with calcified valvular lesions even without cat bite, tick seems to be vector of the bacteria.

Bartonella spp. are responsible for emerging and re-emerging diseases around the world. The majority of human infections are caused by Bartonella henselae, Bartonella quintana and Bartonella bacilliformis, although other Bartonella spp. have also been associated with clinical manifestations in humans. The severity of Bartonella infection correlates with the patient's immune status. Clinical manifestations can range from benign and self-limited to severe and life-threatening disease. Clinical conditions associated with Bartonella spp. include local lymphadenopathy, bacteraemia, endocarditis, and tissue colonisation resulting in bacillary angiomatosis and peliosis hepatis. Without treatment, Bartonella infection can cause high mortality. To date, no single treatment is effective for all Bartonella-associated diseases. In the absence of systematic reviews, treatment decisions for Bartonella infections are based on case reports that test a limited number of patients. Antibiotics do not significantly affect the cure rate in patients with Bartonella lymphadenopathy. Patients with Bartonella spp. bacteraemia should be treated with gentamicin and doxycycline, but chloramphenicol has been proposed for the treatment of B. bacilliformis bacteraemia. Gentamicin in combination with doxycycline is considered the best treatment regimen for endocarditis, and erythromycin is the first-line antibiotic therapy for the treatment of angioproliferative lesions. Rifampicin or streptomycin can be used to treat verruga peruana. In this review, we present recent data and recommendations related to the treatment of Bartonella infections based on the pathogenicity of Bartonella spp.

Angiolymphoid hyperplasia with eosinophilia is an uncommon, benign hyperproliferative disorder. Papules and nodules occur predominantly in the head and neck region. Involvement of other sites such as the trunk and mucosae has been rarely reported. We herein report a case of angiolymphoid hyperplasia with eosinophilia involving the right infra-axillary region.

A 29-year-old man presented with generalized, painless, erythematous lesions and fever. The patient had recently been diagnosed with human immunodeficiency virus (HIV) infection. His CD4 T-cell count at presentation was 14 cells/mm3, and he had been started on antiretroviral therapy 15 days before onset of disease. ..

International audience; We report the first documented case of Bartonella henselae infection in a dog from France and the first isolation of B. henselae from a dog with fever of unknown origin. This observation contributes to the "One Health" concept focusing on zoonotic pathogens emerging from companion animals. A 1-year-old female German shepherd dog was referred for evaluation of fever of unknown origin of 1 month duration. Diagnostic investigations confirmed diffuse pyogranulomatous lymphadenitis. The dog became afebrile, and lymph node size normalized in response to a 6-week course of doxycycline. Retrospectively, Bartonella DNA was amplified from an EDTA-anticoagulated blood sample obtained before antimicrobial therapy, with the gtlA fragment sharing 99 % identity with the 350-bp gtlA fragment of the B. henselae Houston-1 strain. The same strain was isolated in the blood of three healthy cats from the household. Two months after discontinuation of doxycycline, the dog experienced a febrile relapse. Bartonella DNA was again amplified from blood prior to and immediately after administration of a 6-week course azithromycin therapy. However, without administration of additional medications, PCR was negative 9 months after azithromycin therapy and the dog remains clinically healthy 12 months following the second course of antibiotics. The medical management of this case raises several clinically relevant comparative infectious disease issues, including the extent to which Bartonella spp. contribute to fever of unknown origin and pyogranulomatous inflammatory diseases in dogs and humans, and the potential of doxycycline and azithromycin treatment failures. The possibility that dogs could constitute an underestimated reservoir for B. henselae transmission to people is also discussed.

The aim of this study was to characterize a Bartonella strain (BA-1) isolated from a blood culture of an Italian, human immunodeficiency virus-positive patient with bacillary angiomatosis. We analyzed the isolate using molecular biology methods such as whole-cell fatty acid analysis, PCR-restriction fragment length polymorphism analysis, type-specific 16S rRNA PCRs, sequence analysis of the 16S rRNA, pulsed-field gel electrophoresis, and arbitrarily primed PCR. The BA-1 isolate turned out to be a Bartonella quintana strain, similar but not identical to B. quintana Oklahoma, which was used as a control strain.

Immune responses of the immunocompetent host toBartonella henselaeinfection were investigated in the murine infection model using C57BL/6 mice. Following intraperitoneal infection with human-derivedB. henselaestrain Berlin-1, viable bacteria could be recovered from livers and spleens during the first week postinfection, whileBartonellaDNA remained detectable by PCR in the liver for up to 12 weeks after infection. Granulomatous lesions developed in livers of infected mice, reached maximal density at 12 weeks after infection, and persisted for up to 20 weeks, indicating thatB. henselaeinduced a chronic granulomatous hepatitis in the immunocompetent murine host. T-cell-mediated immune responses were analyzed in vitro by means of spleen cell proliferation and cytokine release assays as well as analysis of immunoglobulin G (IgG) isotypes. Spleen cells from infected mice proliferated specifically upon stimulation with heat-killedBartonellaantigen. Proliferative responses were mainly mediated by CD4+T cells, increased during the course of infection, peaked at 8 weeks postinfection, and decreased thereafter. Gamma interferon, but not interleukin-4, was produced in vitro by spleen cells from infected animals upon stimulation withBartonellaantigens.Bartonella-specific IgG was detectable in serum of infected mice by 2 weeks, and the antibody concentration peaked at 12 weeks postinfection. IgG2b was the prominent isotype among theBartonella-specific serum IgG antibodies. These data indicate thatB. henselaeinduces cell-mediated immune responses with a Th1 phenotype in immunocompetent C57BL/6 mice.

The AIDS pandemic was identified almost 2 decades ago and it is still raging. The actual world-wide trend is 16,000 new cases of HIV infection per day. 21 The demographics of this disease are changing. According to the World Health Organization, in 1999 for the first time more women than men were found to be HIV-seropositive in sub-Saharan Africa, the epicenter of HIV infection. 45 Of the 22.3 million adults in that region infected with HIV, 55% are women. 21 Although an effective vaccine is still not available, the current drug therapies are effective at prolonging the life of patients with AIDS. According to figures released by the United Nations, there has been a steady rise (about 11% per year) in the number of Americans living with AIDS from 1993 through 1998. 21 Although musculoskeletal infections seem to be relatively uncommon in patients with AIDS, 35 the prevalence of such infections is likely to be rising with the increased longevity of these patients. Patients with AIDS are at risk of acquiring common and opportunistic infections that may involve the skin, subcutaneous tissues, muscles, bones, and joints. The axial and appendicular skeleton may be involved. Although opportunistic pathogens take advantage of the T-cell immunodeficiency of patients with AIDS, impairment of neutrophil maturation and function by various drug therapies that can be myelosuppressive predisposes patients with AIDS to the development of nonopportunistic bacterial and fungal infections. 36 Because of the immunodeficiency inherent to patients with AIDS, these infections tend to be more advanced at clinical presentation than those seen in immunocompetent patients. Musculoskeletal infections tend to occur in patients who are otherwise well, and may be the first manifestations of an unsuspected HIV infection. 7

The aim of this case series was to describe the clinical, laboratory and epidemiological characteristics and the presentation of bacillary angiomatosis cases (and/or parenchymal bacillary peliosis) that were identified in five public hospitals of Rio de Janeiro state between 1990 and 1997; these cases were compared with those previously described in the medical literature. Thirteen case-patients were enrolled in the study; the median age was 39 years and all patients were male. All patients were human immunodeficiency virus type 1 (HIV-1) infected and they had previous or concomitant HIV-associated opportunistic infections or malignancies diagnosed at the time bacillary angiomatosis was diagnosed. Median T4 helper lymphocyte counts of patients was 96 cells per mm³. Cutaneous involvement was the most common clinical manifestation of bacillary angiomatosis in this study. Clinical remission following appropriate treatment was more common in our case series than that reported in the medical literature, while the incidence of relapse was similar. The frequency of bacillary angiomatosis in HIV patients calculated from two of the hospitals included in our study was 1.42 cases per 1000 patients, similar to the frequencies reported in the medical literature. Bacillary angiomatosis is an unusual opportunistic pathogen in our setting. Esta série de casos foi conduzida com o objetivo de descrever a apresentação clínica, as características epidemiológicas, os exames laboratoriais e a evolução dos casos de angiomatose bacilar (e/ou peliose parenquimatosa bacilar) ocorridos em cinco hospitais públicos do Rio de Janeiro, no período de 1990 a 1997, comparando a casuística encontrada com a relatada na literatura médica. Foram incluídos 13 pacientes com mediana de idade de 39 anos, sendo todos pertencentes ao sexo masculino. Todos os pacientes apresentaram infecções oportunistas e/ou neoplasias associadas ao vírus da imunodeficiência humana (HIV-1) anteriores (ou concomitantes) ao diagnóstico de angiomatose bacilar. A mediana da contagem de linfócitos T Helper encontrada foi de 96 células por mm³. O acometimento cutâneo foi a apresentação clínica de angiomatose bacilar mais freqüente deste estudo. A freqüência de remissão após tratamento específico foi discretamente maior do que a relatada na literatura médica, enquanto a de recidiva foi semelhante. A freqüência de angiomatose bacilar entre indivíduos infectados pelo HIV de dois hospitais do Rio de Janeiro foi de 1,42 casos por 1.000 pacientes, semelhante ao relatado na literatura médica e sugestivo de que a angiomatose bacilar é relativamente incomum em nosso meio.

The ongoing human immunodeficiency virus (HIV) infection epidemic coupled with more efficacious and available treatments has led to a larger number of patients living with HIV or AIDS. As a result, skin manifestations related to HIV/AIDS or its therapy have become increasingly more common and are reported to occur in as many as 95% of patients. Herein, we review the most common HIV/AIDS related cutaneous pathologies and classify them into inflammatory, HAART-associated, neoplastic, and infectious manifestations. Cutaneous manifestations should be promptly recognized and treated by physicians and health care personnel in order to provide optimal care.

Bacterial htrA genes are typically activated as part of the periplasmic stress response and are dependent on the extracytoplasmic sigma factor rpoE . A putative promoter region, P1, of the ς E -type heat-inducible promoters has previously been identified upstream of the htrA gene of Bartonella henselae . Further analysis of the htrA mRNA by primer extension demonstrated that transcription initiates from P1 and a second region downstream of P1. This second promoter region, termed P2, had no sequence identity to ς E -type heat-inducible promoters. Promoter regions were cloned individually and in tandem into pANT3 upstream of a promoterless version of the green fluorescent protein (GFP) gene ( gfpmut3 ) and transformed into B. henselae by electroporation. The contiguous promoter region containing both P1 and P2 were necessary for the optimal transcriptional activation of the htrA gene. Promoter activity at 37°C was distinctively higher than at 27°C. However, thermal induction at 47°C did not increase expression of gfpmut3 . Invasion of human microvascular endothelial cells (HMEC-1) by B. henselae resulted in the formation of well-defined vacuoles containing clusters of bacteria exhibiting marked expression of gfpmut3 transcribed from the P1-P2 region. In addition, a moderate yet significant increase in the ratio of bacterial GFP to DNA was detected for intracellular bacteria compared to extracellular bacteria, indicating upregulation of htrA upon invasion of HMEC-1. The activation of specific genes in the intracellular environment may help us better understand the novel pathogenic mechanisms used by this bacterium.

The infection of and interaction of human endothelial cells with Bartonella henselae is one of the most interesting aspects of Bartonella -associated disease. The gene encoding the 43 kDa B. henselae outer membrane protein (Omp43) that binds endothelial cells was cloned and sequenced. Sequence analysis revealed an open reading frame of 1206 nucleotides coding for a protein of 402 amino acids. Analysis of the deduced amino acid sequence shows 38% identity over the entire sequence to the Brucella spp. In addition to this Omp2b porin also shows a signal sequence and peptidase cleavage site. Cleavage of the signal peptide results in a mature 380 amino acid polypeptide with a predicted molecular weight of 42 kDa. Omp43 was expressed in Escherichia coli as a fusion protein. Purified recombinant Omp43 at concentrations of 11 and 2.75 μg/ml bound to intact human umbilical vein endothelial cells. Membrane topology analysis predicts that Omp43 exists as a 16 stranded beta barrel protein, similar to that predicted for the Omp2b Brucella abortus porin. Characterization and expression of the gene encoding Omp43 should provide a tool for further investigation of the role of adherence to endothelial cells in the pathogenesis of B. henselae.

Background: No data were available on the epidemiological and clinical characteristics of bacillary angiomatosis (BA) in Germany. Objective: To determine epidemiological and clinical data on HIV-associated BA. Methods: A chart review of all BA cases between 1990 and 1998 was performed in 23 German AIDS treatment units. Results: A total of 21 cases of BA was diagnosed. During this period, the participating HIV centers treated about 17,000 HIV-infected patients. As a result, a BA prevalence of 1.2 cases/1,000 patients can be assumed. 19 BA were localized in the skin; in 5 cases bones and in 4 cases the liver were involved. Out of 20 patients who received antibiotic therapy, 13 had complete remission. The median time of duration up to complete remission was 32 days (9–82). During the follow-up of the 20 patients, 7 relapses were observed. Conclusion: BA is a rare HIV-associated disease with a prevalence of 1,2 cases/1,000 patients in the presented study.

We describe the development of an immunoglobulin M-specific enzyme-linked immunosorbent assay for the detection of an early antibody response to Bartonella henselae , the causative agent of cat scratch disease, bacillary angiomatosis, and endocarditis. This assay discriminates between B. henselae -positive and -negative patient samples with sensitivity and specificity values of 100% and 97.1%, respectively.

AIMS: Bacillary angiomatosis is a rare pseudoneoplastic angioproliferative lesion occurring in patients with AIDS. This condition has been associated with Bartonella henselae and Bartonella quintana infections. Human herpesvirus 8 (HHV-8) is thought to be the causative agent of Kaposi's sarcoma, a vasoproliferative neoplasm, also commonly found in patients with AIDS. The presence of HHV-8 in a cohort of patients with bacillary angiomatosis was investigated. METHODS: Eight cutaneous cases of biopsy confirmed bacillary angiomatosis were assessed for HHV-8 using standard solution phase polymerase chain reaction (PCR). RESULTS: No case of bacillary angiomatosis harboured HHV-8 DNA. CONCLUSIONS: HHV-8 was not demonstrated in the lesions of bacillary angiomatosis and therefore does not appear to play a role in the pathogenesis of this pseudoneoplastic angioproliferative disorder. This finding might be useful in the distinction of bacillary angiomatosis from Kaposi's sarcoma, because lesions from patients with Kaposi's sarcoma almost always contains HHV-8 DNA.

Bartonella quintana and Bartonella henselae are fastidious gram-negative bacteria responsible for bacillary angiomatosis, trench fever, cat scratch disease, and endocarditis. During a 5-year period, we received 2,043 samples for culture of Bartonella sp. We found Bartonella sp. to be the etiologic agent in 38 cases of endocarditis, 78 cases of cat scratch disease, 16 cases of bacteremia in homeless people, and 7 cases of bacillary angiomatosis. We correlated the results of positive cultures with the clinical form of the disease, type of sample, culture procedure, PCR-based genomic detection, and antibody determination. Seventy-two isolates of B. quintana and nine isolates of B. henselae from 43 patients were obtained. Sixty-three of the B. quintana isolates and two of the B. henselae isolates, obtained from patients with no prior antibiotic therapy, were stably subcultured. The sensitivity of culture was low when compared with that of PCR-based detection methods in valves of patients with endocarditis (44 and 81%, respectively), skin biopsy samples of patients with bacillary angiomatosis (43 and 100%, respectively), and lymph nodes of cat scratch disease (13 and 30%, respectively). Serological diagnosis was also more sensitive in cases of endocarditis (97%) and cat scratch disease (90%). Among endocarditis patients, the sensitivity of the shell vial culture assay was 28% when inoculated with blood samples and 44% when inoculated with valvular biopsy samples, and the sensitivity of both was significantly higher than that of culture on agar (5% for blood [ P = 0.045] and 4% for valve biopsy samples [ P < 0.0005]). The most efficient culture procedure was the subculture of blood culture broth into shell vials (sensitivity, 71%). For patients with endocarditis, previous antibiotic therapy significantly affected results of blood culture; no patient who had been administered antibiotics yielded a positive blood culture, whereas 80% of patients with no previous antibiotic therapy yielded positive blood cultures ( P = 0.0006). Previous antibiotic therapy did not, however, prevent isolation of Bartonella sp. from cardiac valves but did prevent the establishment of strains, as none of the 15 isolates from treated patients could be successfully subcultured. For the diagnosis of B. quintana bacteremia in homeless people, the efficiency of systematic subculture of blood culture broth onto agar was higher than that of direct blood plating (respective sensitivities, 98 and 10% [ P < 10 −7 ]). Nevertheless, both procedures are complementary, since when used together their sensitivity reached 100%. All homeless people with positive blood cultures had negative serology. The isolation rate of B. henselae from PCR-positive lymph nodes, in patients with cat scratch disease, was significantly lower than that from valves of endocarditis patients and skin biopsy samples from bacillary angiomatosis patients (13 and 33%, respectively [ P = 0.084]). In cases of bacillary angiomatosis for which an agent was identified to species level, the isolation rate of B. henselae was lower than the isolation rate of B. quintana (28 and 64%, respectively [ P = 0.003]). If culture is to be considered an efficient tool for the diagnosis of several Bartonella -related diseases, methodologies need to be improved, notably for the recovery of B. henselae from lymph nodes of patients with cat scratch disease.

Because of its high diagnostic sensitivity in detection of unknown primary tumors, F-18 FDG PET/CT was used in the exploration of a 51-year-old woman presenting with multiple lymphadenopathy of the hepatic hilum and several hepatic and splenic hypodensities on radiologic examinations for which malignancy was suspected. Despite the morphofunctional malignant appearance, both histologic examination and PCR analysis revealed Bartonella henselae infection. Moreover, repeat F-18 FDG PET showed disease regression during focused antibiotic therapy.

High seroprevalence rates for Anaplasma phagocytophilum (8.8%), Coxiella burnetii (6.4%), Bartonella henselae (9.6%), and Rickettsia typhi (4.1%) in 365 farm workers near Tianjin, People’s Republic of China, suggest that human infections with these zoonotic bacteria are frequent and largely unrecognized. Demographic features of seropositive persons suggest distinct epidemiology, ecology, and risks.

Bartonella henselae, the causative agent of cat scratch disease and bacillary angiomatosis, is associated with an expanding spectrum of diseases. Here, we report on a 40-year-old patient suffering from chronic recurrent painful ulcers of the toes, distal axonal sensomotor polyneuropathy and Raynaud's phenomenon. Biopsy of the sural nerve demonstrated an axonal neuropathy with a neurogenic muscular atrophy. Treatment with high dose corticosteroids had no beneficial effect. A biopsy taken from a recurring ulcer 7 years after the beginning of the disease revealed superficial ulcerated hyperkeratosis with subepithelial proliferation of small vessels compatible with a diagnosis of verruca peruana, however, without detection of microorganism. Serologic analysis revealed an elevated IFT titer of 1:1,024 against B. henselae. Treatment with erythromycin induced healing of the ulcer, remission of the vasculitis and the polyneuropathy, and a decline of the IFT titer. This case illustrates that B. henselae infection should be considered in patients with vasculitis and polyneuropathic syndromes.

✓ The authors report the first DNA-based diagnosis of Bartonella henselae cultured from a brain lesion in a patient with acquired immune deficiency syndrome. This human immunodeficiency virus—infected patient presented with altered mental status, fever, and diabetes insipidus. Magnetic resonance imaging revealed multifocal parenchymal and leptomeningeal involvement, which was confirmed on studies of tissue biopsy samples. Using the polymerase chain reaction and gene sequencing techniques, the authors definitively demonstrated the presence of B. henselae in the brain tissue biopsy specimen.

To report seven cases of bacillary angiomatosis; to evaluate the most useful diagnostic tools; to analyse the clinical and epidemiological features associated with Bartonella quintana or Bartonella henselae infections.Clinical, diagnostic and epidemiological evaluation of 37 speciated bacillary angiomatosis cases in the literature, including the seven patients in our study.Pathological examination of tissue samples, including Warthin-Starry staining and immunohistology; titre of antibodies to Bartonella sp.; detection of Bartonella sp. in blood and biopsy materials by culture or PCR; and statistical analysis of clinical and epidemiological features associated with B. quintana or B. henselae bacillary angiomatosis cases.Seven immunocompromised patients (six with AIDS and one patient with acute leukaemia) had bacillary angiomatosis confirmed by histology. B. quintana was cultured in three patients, whereas B. henselae DNA was amplified by PCR in the remaining four patients. Serum from only one patient reacted with Bartonella antigens. Amongst the 14 B. quintana and 23 B. henselae bacillary angiomatosis cases now reported in the literature, lymphadenopathies were significantly more frequent in B. henselae-infected patients, and neurological disorders of the central nervous system in B. quintana-infected patients. Risk factors were contact with cats, and homelessness or poor socioeconomic status in B. henselae and B. quintana bacillary angiomatosis cases, respectively.Although diagnosis of bacillary angiomatosis often remains solely based upon histology, culture or PCR-based methods are useful for the detection of Bartonella sp., and allow identification of the species involved, which is necessary to further characterize clinical and epidemiological features associated with B. quintana or B. henselae infections.

Fibrous long-spacing (FLS) collagen is a distinct ultrastructural form of collagen present in normal tissue, various tumors, and tissues degraded by bacterial collagenases in vivo and in vitro. An association between FLS collagen and bacillary angiomatosis has not been previously described. Six cases of bacillary angiomatosis, including one autopsy case with disseminated disease, were examined ultrastructurally. In addition, Kaposi sarcoma (3), pyogenic granuloma (3), capillary hemangioma (3), and cavernous hemangioma (2) were examined for comparison. A vascular proliferation in a lymph node from a patient with AIDS (1) and a case of pulmonary capillary hemangiomatosis (1), also in an AIDS patient, were studied. Abundant FLS collagen was identified in 4 of 6 cases of bacillary angiomatosis, in close association with the organisms. FLS collagen was not seen beyond the immediate vicinity of the organisms. The FLS collagen in bacillary angiomatosis was seen in skin biopsies and in lung and skeletal muscle in the autopsy case; in the latter case, as well as in the two AIDS-associated, nonbacillary angiomatosis, non-Kaposi sarcoma vascular proliferations, there was a striking distribution of FLS collagen around small blood vessels. Occasional FLS collagen was observed in all three pyogenic granuloma. When present in pyogenic granuloma, FLS collagen was intermixed with subendothelial collagen. Abundant FLS collagen was identified in close association with the organisms of bacillary angiomatosis in four cases; this morphologic alteration was seen in skin as well as lung and skeletal muscle. An association between FLS collagen and endothelial cells in normal tissue (Descemet's membrane) and in certain vascular proliferations appears to exist.