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Some bacterial pathogens can manipulate the angiogenic response, suppressing or inducing it for their own ends. In humans, Bartonella henselae is associated with cat-scratch disease and vasculoproliferative disorders such as bacillary angiomatosis and bacillary peliosis. Although endothelial cells (ECs) support the pathogenesis of B. henselae, the mechanisms by which B. henselae induces EC activation are not completely clear, as well as the possible contributions of other cells recruited at the site of infection. Mesenchymal stromal cells (MSCs) are endowed with angiogenic potential and play a dual role in infections, exerting antimicrobial properties but also acting as a shelter for pathogens. Here, we delved into the role of MSCs as a reservoir of B. henselae and modulator of EC functions. B. henselae readily infected MSCs and survived in perinuclearly bound vacuoles for up to 8 days. Infection enhanced MSC proliferation and the expression of epidermal growth factor receptor (EGFR), Toll-like receptor 2 (TLR2), and nucleotide-binding oligomerization domain-containing protein 1 (NOD1), proteins that are involved in bacterial internalization and cytokine production. Secretome analysis revealed that infected MSCs secreted higher levels of the proangiogenic factors vascular endothelial growth factor (VEGF), fibroblast growth factor 7 (FGF-7), matrix metallopeptidase 9 (MMP-9), placental growth factor (PIGF), serpin E1, thrombospondin 1 (TSP-1), urokinase-type plasminogen activator (uPA), interleukin 6 (IL-6), platelet-derived growth factor D (PDGF-D), chemokine ligand 5 (CCL5), and C-X-C motif chemokine ligand 8 (CXCL8). Supernatants from B. henselae-infected MSCs increased the susceptibility of ECs to B. henselae infection and enhanced EC proliferation, invasion, and reorganization in tube-like structures. Altogether, these results indicate MSCs as a still underestimated niche for persistent B. henselae infection and reveal MSC-EC cross talk that may contribute to exacerbate bacterium-induced angiogenesis and granuloma formation.

Bacillary peliosis hepatis is a well recognised manifestation of disseminated Bartonella henselae infection that can occur in immunocompromised individuals. Haemophagocytic lymphohistiocytosis is an immune-mediated condition with features that can overlap with a severe primary infection such as disseminated Bartonella spp infection. We report a case of bacillary peliosis hepatis and secondary haemophagocytic lymphohistiocytosis due to disseminated Bartonella spp infection in a kidney-transplant recipient with well controlled HIV. The patient reported 2 weeks of fever and abdominal pain and was found to have hepatomegaly. He recalled exposure to a sick dog but reported no cat exposures. Laboratory evaluation was notable for pancytopenia and cholestatic injury. The patient met more than five of eight clinical criteria for haemophagocytic lymphohistiocytosis. Pathology review of a bone marrow core biopsy identified haemophagocytosis. A transjugular liver biopsy was done, and histopathology review identified peliosis hepatis. Warthin-Starry staining of the bone marrow showed pleiomorphic coccobacillary organisms. The B henselae IgG titre was 1:512, and Bartonella-specific DNA targets were detected by peripheral blood PCR. Treatment with doxycycline, increased prednisone, and pausing the mycophenolate component of his transplant immunosuppression regimen resulted in an excellent clinical response. Secondary haemophagocytic lymphohistiocytosis can be difficult to distinguish from severe systemic infection. A high index of suspicion can support the diagnosis of systemic Bartonella spp infection in those who present with haemophagocytic lymphohistiocytosis, especially in patients with hepatomegaly, immunosuppression, and germane animal exposures.

Introduction Bacillary angiomatosis (BA) is a rare, opportunistic infectious disease caused by the aerobic Gram-negative bacilli Bartonella henselae or Bartonella quintana. The main reservoir for those microbes are cats. The disease mostly affects immunocompromised patients with human immunodeficiency virus infection, after organ transplantation, undergoing corticosteroid and methotrexate therapy or with oncological history. Case report We represent the case of a 65-year-old man who reported to the Department of Dermatology with a high fever and numerous nodular skin lesions on the 5th month of kidney transplantation. At that time, his immunosuppressive therapy consisted of tacrolimus 6 mg/day, mycophenolate mofetil 2 g/day, and prednisone 5 mg/day. Laboratory tests revealed an increased leukocyte count and elevated values of acute-phase proteins, but blood cultures were negative. Skin biopsy was performed and BA was diagnosed. The patient was given oral doxycycline 100 mg twice a day. During antibiotic therapy, his body temperature normalized and skin lesions began to resolve. The patient continued the above treatment for the next 3 months with good tolerance, and no relapse occurred in 1 year. Conclusion BA should be listed among possible opportunistic infections in organ transplant recipients.

We present the case of an HIV-positive patient who developed polymorphous lesions in which the evidence in the skin biopsy corresponds to the diagnosis of bacillary angiomatosis, and further tests proved the pathological agent involved in this case is not the usual Bartonella species, B. henselae and B. quintana, but B. elizabethae. As far as we know, this is the first case of bacillary angiomatosis secondary to this etiological agent.

The objective of this work was to determine the prevalence of Borrelia and Bartonella species in Ixodes spp. ticks collected from 16 USA states. Genus PCR amplification and sequence analysis of Bartonella and Borrelia 16SsRNA-23SsRNA intergenic regions were performed on DNA extracted from 929 questing adult ticks (671 Ixodes scapularis, 155 Ixodes affinis, and 103 Ixodes pacificus). Overall, 129/929 (13.9%) Ixodes ticks were PCR positive for Borrelia burgdorferi sensu stricto, 48/929 for B. bissettiae whereas 23/929 (2.5%) were PCR positive for a Bartonella henselae. Borrelia bissettiae or B. burgdorferi s.s. and B. henselae co-infections were found in I. affinis from North Carolina at a rate of 4.5%; in a single I. scapularis from Minnesota, but not in I. pacificus. For both bacterial genera, PCR positive rates were highly variable depending on geographic location and tick species, with Ixodes affinis (n = 155) collected from North Carolina, being the tick species with the highest prevalence’s for both Borrelia spp. (63.2%) and B. henselae (10.3%). Based on the results of this and other published studies, improved understanding of the enzootic cycle, transmission dynamics, and vector competence of Ixodes species (especially I. affinis) for transmission of Borrelia spp. and B. henselae should be a public health research priority.

A 37-year-old man with a history of renal transplantation in 2013 due to focal segmental glomerulosclerosis presented to the emergency room with a 2-week history of fever, chills, anorexia, weight loss, abdominal pain, diarrhea, and a new asymptomatic lesion on the right side of the neck. The patient worked as a truck driver and frequently traveled to Wisconsin; he had not traveled internationally in the past year. He lived with his brother who had a pet cat. He was compliant with his anti-rejection medication regimen, which included mycophenolate mofetil, tacrolimus, and prednisone. Physical examination of the neck revealed an 8-mm exophytic, friable, red papule with overlying blood crusts (Figure 1). The remainder of the mucocutaneous examination was unremarkable, and there was no palpable lymphadenopathy. The patient was started on empiric intravenous cefepime and metronidazole and admitted to the hospital for further management. A punch biopsy of the lesion was performed.

Background Tick-borne lymphadenopathy (TIBOLA) is an infectious disease, mainly caused by species from the spotted fever group rickettsiae and is characterized by enlarged lymph nodes following a tick bite. Among cases of TIBOLA, a case of scalp eschar and neck lymphadenopathy after tick bite (SENLAT) is diagnosed when an eschar is present on the scalp, accompanied by peripheral lymphadenopathy (LAP). Only a few cases of SENLAT caused by Bartonella henselae have been reported. Case presentation A 58-year-old male sought medical advice while suffering from high fever and diarrhea. Three weeks before the visit, he had been hunting a water deer, and upon bringing the deer home discovered a tick on his scalp area. Symptoms occurred one week after hunting, and a lump was palpated on the right neck area 6 days after the onset of symptoms. Physical examination upon presentation confirmed an eschar-like lesion on the right scalp area, and cervical palpation revealed that the lymph nodes on the right side were non-painful and enlarged at 2.5 × 1.5 cm. Fine needle aspiration of the enlarged lymph nodes was performed, and results of nested PCR for the Bartonella internal transcribed spacer (ITS) confirmed B. henselae as the causative agent. Conclusion With an isolated case of SENLAT and a confirmation of B. henselae in Korea, it is pertinent to raise awareness to physicians in other Asian countries that B. henselae could be a causative agent for SENLAT.

Patient: Female, 44 Final Diagnosis: Cat-scratch disease Symptoms: Lymfadenopathy Medication: — Clinical Procedure: Lymph node biopsy Specialty: Infectious Diseases Objective: Unusual clinical course Background: Bartonella infection is the causative organism of cat-scratch disease (CSD), which typically presents with self-limited localized lymphadenopathy. In HIV-infected patients, Bartonella infection can cause systemic illnesses with significant morbidity and mortality manifesting as bacillary angiomatosis (BA), hepatic peliosis, splenitis, bacteremic febrile illness, and other organ involvement. To the best of our knowledge, there have been no reports of HIV-infected patients presenting with generalized lymphadenopathy caused by Bartonella infection. We report an unusual case of CSD presenting with generalized lymphadenopathy in an AIDS patient with advanced immunosuppression. Case Report: A 44-year-old woman with AIDS, advanced immunosuppression, and intermittent adherence to antiretroviral therapy and medical care, presented with cough and increased generalized tender lymphadenopathy. A lymph node biopsy 1 year earlier was non-diagnostic for tuberculosis, fungal infection, and lymphoproliferative disorders. She remained with generalized lymphadenopathy. A repeat biopsy with the addition of Warthin-Starry silver staining suggested the diagnosis of cat-scratch lymphadenitis. She responded well to a long course of azithromycin antibiotic therapy, with the resolution of lymphadenopathy. Conclusions: Cat-scratch disease may present with prolonged generalized lymphadenopathy, an unusual presentation in HIV patients with advanced immunosuppression. Awareness of the possibility of CSD in a similar clinical scenario may prompt early recognition and management of this disease.

A new class of surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) biosensor has been developed for the simultaneous detection of dual DNA markers. The LFA strip in this sensor was composed of two test lines and one control line. SERS nano tags labeled with detection DNA probes were used for quantitative evaluation of dual DNA markers with high sensitivity. Target DNA, associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and bacillary angiomatosis (BA), were tested to validate the detection capability of this SERS-based LFA strip. Characteristic peak intensities of SERS nano tags on two test lines were used for quantitative evaluations of KSHV and BA. The limits of detection for KSHV and BA, determined from our SERS-based LFA sensing platform, were estimated to be 0.043 and 0.074 pM, respectively. These values indicate approximately 10 000 times higher sensitivity than previously reported values using the aggregation-based colorimetric method. We believe that this is the first report of simultaneous detection of two different DNA mixtures using a SERS-based LFA platform. This novel detection technique is also a promising multiplex DNA sensing platform for early disease diagnosis.

Bacillary angiomatosis is an infection determined by Bartonella henselae and B. quintana, rare and prevalent in patients with acquired immunodeficiency syndrome. We describe a case of a patient with AIDS and TCD4+ cells equal to 9/mm3, showing reddish-violet papular and nodular lesions, disseminated over the skin, most on the back of the right hand and third finger, with osteolysis of the distal phalanx observed by radiography. The findings of vascular proliferation with presence of bacilli, on the histopathological examination of the skin and bone lesions, led to the diagnosis of bacillary angiomatosis. Corroborating the literature, in the present case the infection affected a young man (29 years old) with advanced immunosuppression and clinical and histological lesions compatible with the diagnosis.

Infectious angiogenesis is the biological response of neoangiogenesis induced by infectious organisms. The authors present 3 exemplary entities which show paradigmatic clinico-pathological settings of infectious angiogenesis: Bacillary angiomatosis, Orf (ecthyma contagiosum), and Kaposi sarcoma. The authors review the literature and elucidate etiopathogenetic pathways leading to the phenomenon of neovascularization stimulated by infectious organisms. The authors describe the clinical and histological pictures, interactions between microorganisms and host cells, and changes that occur within cellular structures, as well as angiogenic factors that underpin infectious angiogenesis. The importance of chronic inflammation and tumor angiogenesis is emphasized.

Bacterial adherence determines the virulence of many human-pathogenic bacteria. Experimental approaches elucidating this early infection event in greater detail have been performed using mainly methods of cellular microbiology. However, in vitro infections of cell monolayers reflect the in vivo situation only partially, and animal infection models are not available for many human-pathogenic bacteria. Therefore, ex vivo infection of human organs might represent an attractive method to overcome these limitations. We infected whole human umbilical cords ex vivo with Bartonella henselae or Acinetobacter baumannii under dynamic flow conditions mimicking the in vivo infection situation of human endothelium. For this purpose, methods for quantifying endothelium-adherent wild-type and trimeric autotransporter adhesin (TAA)-deficient bacteria were set up. Data revealed that (i) A. baumannii binds in a TAA-dependent manner to endothelial cells, (ii) this organ infection model led to highly reproducible adherence rates, and furthermore, (iii) this model allowed to dissect the biological function of TAAs in the natural course of human infections. These findings indicate that infection models using ex vivo human tissue samples (“organ microbiology”) might be a valuable tool in analyzing bacterial pathogenicity with the capacity to replace animal infection models at least partially.

Bartonella species constitute emerging, vector-borne, intravascular pathogens that produce long-lasting bacteremia in reservoir-adapted (natural host or passive carrier of a microorganism) and opportunistic hosts. With the advent of more sensitive and specific diagnostic tests, there is evolving microbiological evidence supporting concurrent infection with one or more Bartonella spp. in more than one family member; however, the mode(s) of transmission to or among family members remains unclear. In this study, we provide molecular microbiological evidence of Bartonella henselae genotype San Antonio 2 (SA2) infection in four of six Danish family members, including a child who died of unknown causes at 14 months of age.

Bacillary angiomatosis (BA) is a disorder of neovascular proliferation involving skin and other organs of immunosuppressed patients caused by Bartonella species. BA has been recognized in both immunocompetent and immunodeficient patients, mostly in human immunodeficiency virus (HIV)-infected persons, much more rare in those with other immunodeficiencies, including organ transplantation. Diagnosis is based on serologic analysis, culture and molecular biology [detection of Bartonella species deoxyribonucleic acid (DNA) in tissue biopsy extracts by real-time polymerase chain reaction (PCR)]. All immunosuppressed patients with BA should be treated with antibiotics because of potentially life-threatening course of the disease. We report the first case of cutaneous bacillary angiomatosis due to Bartonella quintana in renal transplant recipient. This presentation demonstrates that BA should be considered a differential diagnosis in immunocompromised patients presenting with fever and cutaneous angioma-like lesions.

Bartonella henselae is the causative agent of cat scratch disease in humans, which is recognized as an emerging zoonotic disease. Ctenocephalides felis is the main vector, and transmission of B. henselae infection between cats and humans occurs mainly through infected flea feces. Control of feline infestation with this arthropod vector therefore provides an important strategy for the prevention of infection of both humans and cats. In the present study, a new challenge model is used to evaluate the efficacy of selamectin (Stronghold® spot on) in the prevention of B. henselae transmission by C. felis. In this new challenge model, domestic cats were infected by direct application of B. henselae-positive fleas. The fleas used for infestation were infected by feeding on blood that contained in vitro-cultured B. henselae. The direct application of the fleas to the animals and the use of different B. henselae strains ensured a high and consistent challenge. Two groups of six cats were randomly allocated on pre-treatment flea counts to either control (untreated cats) or the selamectin-treated group with one pipette per cat according to the label instruction. Stronghold (selamectin 6 % spot on solution) was administered on days 0 and 32. On days 3, 10, 19, 25, and 31, each cat was infested by direct application of 20 fleas that fed on blood inoculated with B. henselae. Polymerase chain reaction (PCR) on pooled fleas confirmed that the fleas were infected. Blood samples were collected from each cat on days −3 (prior to flea infestation and treatment), 9, 17, 24, 30, 37, and 44 and assayed for B. henselae antibodies using an indirect immunofluorescence (IFA), for the presence of bacteria by bacterial culture and for B. henselae DNA presence by PCR. Cats were also assessed on a daily basis for general health. There were no abnormal health observations during the study and none of the animals required concomitant treatment. None of the cats displayed any clinical signs of bartonellosis during the study. In the untreated group, all cats became bacteremic within 17 to 44 days. None of the selamectin-treated cats became positive during the study. It was concluded that Stronghold® spot on administered to cats was efficacious in the prevention of the transmission of B. henselae by fleas to cats in a high-challenge model.

Cat scratch disease is a relatively rare infection that is caused by the bacterium Bartonella henselae. This disease occurs after cat scratch or bite. The course of the disease depends on the patients immunity status. In immunocompetent patients, the disease typically runs as a lymph node syndrome. Sometimes, mild general symptoms may appear, or the course can be atypical with a more serious clinical manifestation involving various organs. In immunocompromised patients, Bartonella henselae can cause bacillary angiomatosis or peliosis with a severe course.

Background Previous reports suggest an association between Bartonella infection and effusions in dogs and human beings. Objectives The aims of this study were to determine the prevalence of Bartonella infection in canine effusions and to investigate historic and clinical parameters predictive of Bartonella in dogs with effusions. Methods Canine cavitary effusions submitted for analysis and, if available, paired EDTA blood, were screened for Bartonella infection using the Bartonella α-proteobacteria growth medium enrichment culture/PCR diagnostic platform (Bartonella enrichment PCR or ePCR) at Galaxy Diagnostics, Inc. Results Bartonella henselaeDNA was PCR-amplified and sequenced from 15% (12/80) of sampled dogs. Enrichment culture prior to PCR testing was required for Bartonella detection in 92% (11/12) of cases. Twenty percent (4/20), 13% (8/60), and 0% (0/4) of dogs with pleural, peritoneal, and pericardial effusions, respectively, tested positive. Bartonella henselae was detected most frequently in the fall, and young and middle-aged dogs appeared to be overrepresented. Golden Retrievers and Yorkshire/Silky Terriers each comprised 25% of infected dogs (odds ratio 3.4 for Golden Retrievers). There was a weak association with hemorrhagic effusions. Fifty percent of Bartonella-positive dogs had hemorrhage as a component of their effusion compared to 37% of PCR-negative dogs (odds ratio 1.7). Conclusions Viable B henselae organisms occur in pleural and peritoneal effusions of dogs; the clinical relevance of which remains unclear and may represent opportunistic infection. Associations found in this study included seasonal variation, age, breed, and site of effusion.

Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at the oriT gene, covalently attaches to it, and leads the single-stranded DNA (ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific integration of the transferred DNA into its target sequence present in the genome of the recipient bacterium. Here, we report the analysis of the efficiency and specificity of the integrase activity of TrwC in human cells, using the type IV secretion system of the human pathogen Bartonella henselae to introduce relaxase-DNA complexes. Compared to Mob relaxase from plasmid pBGR1, we found that TrwC mediated a 10-fold increase in the rate of plasmid DNA transfer to human cells and a 100-fold increase in the rate of chromosomal integration of the transferred DNA. We used linear amplification-mediated PCR and plasmid rescue to characterize the integration pattern in the human genome. DNA sequence analysis revealed mostly reconstituted oriT sequences, indicating that TrwC is active and recircularizes transferred DNA in human cells. One TrwC-mediated site-specific integration event was detected, proving that TrwC is capable of mediating site-specific integration in the human genome, albeit with very low efficiency compared to the rate of random integration. Our results suggest that TrwC may stabilize the plasmid DNA molecules in the nucleus of the human cell, probably by recircularization of the transferred DNA strand. This stabilization would increase the opportunities for integration of the DNA by the host machinery., This work was supported by grant BIO2013-46414-P from the Spanish Ministry of Economy and Competitiveness to M.L. and in part by grant 31003A_173119 from the Swiss National Science Foundation to C.D. C.G.-P. was a recipient of a predoctoral fellowship from the University of Cantabria, Spain.

Bartonella species cause several diseases in humans such as cat stratch disease, bacillary angiomatosis, peliosis hepatis, endocarditis, Carrion disease and trench fever. Cat scratch disease and bacillary angiomatosis cases have already been reported in Turkey. Studies from our region, namely Aydin (a province located at Western Anatolia, Turkey) indicated that mean Bartonella henselae IgG seropositivity rate is 11.5% in risk groups and may reach to 26.5% in pet owners. The aim of this study was to determine the seroprevalence of B.henselae and B.quintana in healthy blood donors in our university hospital in Aydin, for estimating the transmission risk via transfusion. The study was designed as a cross-sectional epidemiological study. A total of 333 samples taken from blood donors (49 female, 284 male) who were sequentially admitted to the blood center of the university hospital, in January 2011 were included in the study. All sera were screened in terms of B.henselae and Bartonella quintana IgG antibodies by using two different indirect immunofluorescent antibody (IFA) commercial kits (Vircell, Spain; Focus, USA). Slides were examined at a final magnification of x400 on fluorescent microscope by two different assigned researchers. Fluorescent intensity was graded between 1+ to 4+, and the samples with fluorescence value of ≥ 2+ were considered as positive. The seropositivity rate of IgG antibodies to B.henselae was found as 3.3% (11/333) in blood donors. This rate was 4.1% in female, and 3.2% in male donors, showing no statistically significant difference between the genders (p= 0.668). B.henselae antibody titers were detected as 1/64 in 6 (1.8%), 1/128 in 4 (1.2%) and 1/1024 in 1 (0.3%) patient. All of the B.henselae IgG positive samples also yielded relatively low positivity for B.quintana IgG, possibly indicating cross reactivity. The fluorescence intensity for different kits used was found to be the same in all but one titer. The results reported by two researchers were found to differ only in the samples graded 1+ or below. However, the evaluation differences between the kits and the researchers did not affect the results. It was concluded that B.henselae infection might be found in the blood donors in our region, thus, a detailed questionnaire prior to blood donation might be helpful to prevent transmission of B.henselae by blood transfusion.

We report a case of a 21-year-old young man with underlying congenital heart disease who developed Bartonella henselae endocarditis of the right ventricular outflow tract (RVOT) conduit of his Melody transcatheter (percutaneous) pulmonary valve (TPV), with an initial presentation of glomerulonephritis with a dominant C3 pattern, with renal failure and circulating cryoglobulins. There are few reports of a glomerulonephritis with a dominant C3 pattern presenting as a manifestation of B. henselae endocarditis. While most cases of B. henselae endocarditis affect the aortic valve, in this case the valve damage was to the RVOT of the Melody TPV, a percutaneous transcatheter valve delivery system that had previously replaced his pulmonary homograft, which had become dysfunctional as a result of prior Streptococcus viridans endocarditis. The pulmonary homograft had been in place since childhood as a result of a Ross procedure to repair his congenital aortic stenosis. The patient's renal failure significantly improved after surgical resection of the infected RVOT and institution of appropriate antibiotic therapy.

Background: Bacillary angiomatosis (BA) is a rare manifestation of infection caused by Bartonella species, which leads to vasoproliferative lesions of skin and other organs. Bacillary angiomatosis affects individuals with advanced HIV disease or other immunocompromised individuals. In sub-Saharan Africa, despite the high prevalence of HIV infection and documentation of the causative Bartonella species in humans, mammalian hosts, and arthropod vectors, BA has only rarely been described. Methods: Three adult patients from Uganda and Kenya with deep purple dome-shaped papules or nodules of the skin underwent punch biopsies for histopathologic diagnosis. The biopsies of all 3 patients were sent to a local pathologist as well as to a dermatopathologist at the University of California, San Francisco. Results: All 3 patients were clinically suspected to have Kaposi’s sarcoma (KS), and local pathologists had interpreted the lesions as KS in 2 of the cases and nonspecific inflammation in the third. Histologic examination by dermatopathologists in the United States revealed nodular dermal proliferations of irregular capillaries lined by spindled to epithelioid endothelial cells. The surrounding stroma contained a mixed inflammatory infiltrate with lymphocytes, eosinophils, and neutrophils. Extracellular deposits of pale amphophilic granular material were noted in the surrounding stroma. A Warthin-Starry stain highlighted clumps of bacilli, confirming the diagnosis of BA. Conclusions: These 3 cases, to our knowledge, are the first reports of BA in East Africa in the biomedical literature. Each had been originally incorrectly diagnosed as KS. We speculate BA is underdiagnosed and underreported in resource-poor regions, such as sub-Saharan Africa, that have high endemic rates of HIV infection.

Bacillary angiomatosis is an infection determined by Bartonella henselae and B. quintana, rare and prevalent in patients with acquired immunodeficiency syndrome. We describe a case of a patient with AIDS and TCD4+ cells equal to 9/mm3, showing reddish-violet papular and nodular lesions, disseminated over the skin, most on the back of the right hand and third finger, with osteolysis of the distal phalanx observed by radiography. The findings of vascular proliferation with presence of bacilli, on the histopathological examination of the skin and bone lesions, led to the diagnosis of bacillary angiomatosis. Corroborating the literature, in the present case the infection affected a young man (29 years old) with advanced immunosuppression and clinical and histological lesions compatible with the diagnosis.

Despite the publication of a number of case reports since the 1950s, physician awareness of the unique relationship between cat scratch disease (CSD) and acute encephalopathy remains limited. This report alerts emergency medicine physicians to include CSD encephalopathy (CSDE) in the differential diagnosis when a previously healthy child presents with status epilepticus. Prompt recognition of this relationship impacts the selection of initial diagnostic studies and antibiotic choices and permits reliable insight into prognosis. The 2 cases are from different eras and demonstrate the significant diagnostic advances in the past 3 decades for Bartonella henselae infection. Both children were treated with antibiotics, and both had resolution of all neurological symptoms. However, the role of antibiotics in the treatment and outcome of CSDE remains speculative. Lastly, the report suggests potential areas of investigation to address immune-mediated mechanisms in the pathogenesis of CSDE.

Bartonella henselae is a gram‐negative zoonotic bacterium that causes infections in humans including endocarditis and bacillary angiomatosis. B. henselae has been shown to grow as large aggregates and form biofilms in vitro. The aggregative growth and the angiogenic host response requires the trimeric autotransporter adhesin BadA. We examined the transcriptome of the Houston‐1 strain of B. henselae using RNA‐seq revealing nine novel, highly‐expressed intergenic transcripts (Bartonella regulatory transcript, Brt1‐9). The Brt family of RNAs is unique to the genus Bartonella and ranges from 194 to 203 nucleotides with high homology and stable predicted secondary structures. Immediately downstream of each of the nine RNA genes is a helix‐turn‐helix DNA‐binding protein (transcriptional regulatory protein, Trp1‐9) that is poorly transcribed under the growth conditions used for RNA‐seq. Using knockdown or overexpressing strains, we show a role of both the Brt1 and Trp1 in the regulation of badA and also in biofilm formation. Based on these data, we hypothesize that Brt1 is a trans‐acting sRNA that also serves as a cis‐acting riboswitch to control the expression of badA. This family of RNAs together with the downstream Trp DNA‐binding proteins represents a novel coordinated regulatory circuit controlling expression of virulence‐associated genes in the bartonellae.

A 69-year-old man was admitted to our institution because of a 1-week history of intermittent passage of tarry stools. His medical history was remarkable for uraemia, with regular dialysis for 5 years. He had not received non-steroidal anti-inflammatory drugs or anticoagulants. Four months previously, he had been admitted to our institution because of tarry stool passage. Prior endoscopic examination, including colonoscopy …

Bartonella henselae is responsible for the Cat Scratch Disease in humans, being it underdiagnosed. This study aims to detect and quantify the load of B. henselae DNA in oral and whole blood samples from stray and shelthered cats from Zaragoza (Spain), and analyze associations with epidemiological and clinical factors.47 cats entered in the estudy. Real time PCR was used to detect B. henselae DNA in blood and oral samples. The SPSS software was applied to the statistical analysis of positivity of paired samples and its relationship with variables as age, sex, origin, month of sampling and fleas/ticks observation in fur and clinical factors (health status and observation of oral lesions). To know the relationship between the presence in blood and oral cavity a logistic regression analysis was performed.A 23.40% of blood samples and the 27.65% of the oral swabs carried the B. henselae DNA. A fair agreement between paired samples was observed (kappa value = 0.33, p less than 0.05). Bacterial DNA detected in oral and blood samples were not significantly associated to any of the epidemiological and clinical factors. Positive cats having oral lesions carried higher loads (3,12/1x1,000,000 cells) of bacterial DNA in their oral cavity than those without lesions (2,58/1x1,000,000 cells) being p=0.032.Carriage of the B. henselae DNA in the blood samples appears not to be related with carriage of the DNA of the bacteria in mouth and vice versa. Positive cats having oral lesions carry a higher load of B. henselae DNA and may suppose a higher risk of transmission to people handling them.Bartonella henselae produce la enfermedad del arañazo del gato en las personas y se considera infradiagnosticada. El objetivo fue detectar y cuantificar la carga de ácido desoxiribonucleico (ADN) de B. henselae en muestras de sangre y orales de gatos callejeros y de albergue de Zaragoza, España y analizar su relación con factores epidemiológicos y clínicos.Se estudiaron 47 gatos. El ADN de B. henselae,se detectó mediante reacción en cadena de la polimerasa en tiempo real (qPCR) en sangre y muestras orales. Se usó el paquete estadístico SPSS para analizar la positividad de las muestras pareadas y su relación con factores epidemiológicos (edad, sexo, origen, mes de muestreo, presencia de pulgas/garrapatas) y clínicos (estado de salud y presencia de lesiones orales). Se realizó un análisis de regresión logística para conocer la asociación entre la presencia en sangre y cavidad oral y el resto de las variables.El 23,40% de las muestras de sangre y el 27,65% de las orales portaba el ADN de B. henselae. Se observó débil correlación de la positividad de las muestras pareadas (kappa=0,33; p inferior a 0,05). No se detectó asociación estadística entre la presencia de ADN de B. henselae en las muestras y los factores epidemiológicos y clínicos. Los gatos con lesiones orales portaban una carga más elevada de ADN (3,12/1x1.000.000 células) en la boca que los que no tenían lesiones (2,58/1por 1.000.000 células),(p=0,032).La detección de ADN de B. henselae en sangre no parece estar relacionada con su presencia en cavidad oral y viceversa. Los gatos positivos con lesiones orales pueden significar mayor riesgo de infección por B. henselae para las personas que los manejan.

We report the case of a Caucasian 73-year-old woman, without medical history, who is operated of two lesions of the forehead and the scalp measuring 0.4 and 1cm. There is no adenopathy. Histopathological examination revealed a diffuse vascular proliferation of the dermis and the hypodermis composed of small vessels bordered of plump "epthelioid" endothelial cells. There is no mitotic figure. The stroma is slightly fibrous accompanied by a polymorphic inflammatory infiltrate rich in lymphocytes, sometimes arranged in lymphoid follicles, plasma cells and eosinophils. The proposed diagnosis is angiolymphoid hyperplasia with eosinophilia. This is a rare vascular tumor, benign according with the OMS classification and preferentially observed in the skin. We report a cutaneous case, clinical and histopathological data of the reported cases and present the main differential diagnoses.

Angiogenesis is an important physiological and pathological process. Bartonella is the only genus of bacteria known to induce pathological angiogenesis in the mammalian host. Bartonella-induced angiogenesis leads to the formation of vascular tumors including verruga peruana and bacillary angiomatosis. The mechanism of Bartonella-induced angiogenesis is not completely understood. Pericytes, along with endothelial cells, play an important role in physiological angiogenesis, and their role in tumor angiogenesis has been extensively studied. Abnormal signaling between endothelial cells and pericytes contributes to tumor angiogenesis and metastasis; however, the role of pericytes in Bartonella-induced angiogenesis is not known. In this study, after infecting human brain vascular pericytes (HBVPs) with Bartonella henselae, we found that these bacteria were able to invade HBVPs and that bacterial infection resulted in decreased pericyte proliferation and increased pericyte production of vascular endothelial growth factor (VEGF) when compared to the uninfected control cells. In the context of pathological angiogenesis, reduced pericyte coverage, accompanied by increased VEGF production, may promote endothelial cell proliferation and the formation of new vessels.

Bacillary angiomatosis (BA) is an increasingly reported infection, mainly in patients with acquired immunodeficiency syndrome. Different epidemiological risk factors are associated with the transmission of the causative agents, Bartonella henselae and B. quintana. Vulval BA is described rarely. Two patients presented with a vulval mass (Patient 1) and a verrucous vulval growth (Patient 2), which were diagnosed clinically as tuberculosis and carcinoma, respectively. Patient 1 also had pulmonary tuberculosis and Kaposi sarcoma. Biopsy of the vulval lesions confirmed BA, characterized by a multilobular proliferation of blood vessels that were lined by epithelioid endothelial cells. There were prominent intervascular neutrophils, karyorrhectic debris, and clumps of paravascular argyrophilic organisms. The biopsy from Patient 1 was deep dermal/subcutaneous in location and displayed foci of confluent suppuration. There was florid pseudoepitheliomatous hyperplasia in the biopsy from Patient 2. Molecular investigations confirmed intralesional B. quintana, hitherto unreported in vulval BA, as the causative agent in both biopsies. On follow-up, Patient 2 had developed additional lesions in the vulva and thigh, but all her lesions and the vulval mass (Patient 1) responded to erythromycin treatment. Patient 1 succumbed to tuberculosis. Heightened recognition of BA underpins rapid and optimal clinicopathological diagnosis, even in uncommon locations. Identification of the causative Bartonella species is important for appropriate, interventive social management.

Bacillary angiomatosis (BA) is a rare vasculoproliferative disorder due to Bartonella henselae (BH) or Bartonella quintana. It can involve many organs, including the skin, and has been mainly reported in patients with acquired immunodeficiency syndrome. In organ transplant recipients (OTR), this disorder remains misdiagnosed and therapeutic guidelines are nonexistent. We report 3 cases of BA with skin involvement in OTR and review similar cases from the literature. BA manifests on the skin with violaceous lesions mimicking Kaposi sarcoma, and is associated with fever, lymphadenopathy, and liver, spleen, or lung nodules. Bartonellosis infections in OTR are due to BH, the agent causing cat-scratch disease (CSD), but BA comprises histologically a prominent vascular proliferation, which is usually lacking in CSD. Cultures and serologic tests are poorly reliable for the diagnosis, which relies on demonstration of BH within the lesions. A history of cat exposure exists in most cases and pediatric OTR are at higher risk. Prevention consists of regular use of a flea-control product in cats and prompt cleaning of scratches. Our cases highlight several original features of this rare condition, which could potentially improve the management of BA in OTR.

Between 2007 and 2010, a total of 268 Croatian patients with lymphadenopathy were tested for IgM/IgG antibodies to Bartonella (B.) henselae and B. quintana. Samples from 44.4% patients showed positive IgG antibodies: 35.8% to B. henselae, 6.7% to B. quintana and 1.9% to both Bartonella species. There was no difference in seropositivity between males and females (47.4% vs. 41.5%). Seroprevalence was high in all age groups (40.4-60.9%). Patients from urban and rural areas showed a similar seroprevalence rate (44.1% vs. 44.8%). Positive IgM antibodies were found in 28.3% patients varying from 17.5% and 37.5% among age groups. Most cases were reported from August to March.

Context.—Infection is a common cause of lymphadenopathy in children and has numerous microbial etiologies. Lymph node biopsy is considered a keystone in arriving at a definite diagnosis. An accurate differential diagnosis from a lymph node biopsy can expedite diagnosis and minimize ancillary testing. Objective.—To assess and compare the histopathologic and epidemiologic features of common and uncommon pediatric bacterial lymphadenitis. Design.—We searched our database for surgical specimens that had a positive identification of bacteria during an 8-year period. The chart was reviewed to assess the pathogen identified and epidemiologic data. The archival tissue sections were reviewed and the histopathologic findings described for each pathogen. Results.—The review of 368 pediatric lymph node biopsies identified 33 cases with a bacterial infection. These comprised 21 cases of Mycobacterium avium complex (60%), 1 of Mycobacterium fortuitum (3%), 7 of Bartonella henselae (20%), 2 of Yersinia enterocolitica (7%), 1 of Francisella tularensis (3%) and 1 of Streptococcus pyogenes (3%). Conclusions.—Each of these infectious lymphadenitides had distinct epidemiologic and histopathologic features that are discussed in this report.

Background Results of Bartonella henselae blood culture, polymerase chain reaction (PCR) assay on blood, or IgG antibody assays do not always correlate with the presence or absence of clinical disease in cats, and B. henselae IgG antibodies in serum do not always correlate with bacteremia. However, little is known concerning Bartonella spp. IgM antibodies in naturally exposed cats. Hypothesis Bartonella spp. IgM antibodies in serum are associated with fever, stomatitis, and bacteremia based on PCR assay results in experimentally infected or client-owned cats. Animals Stored sera from cats experimentally infected with B. henselae by exposure to Ctenocephalides felis, client-owned cats with and without fever, and client-owned cats with and without stomatitis were studied. Methods A Bartonella spp. IgM ELISA was titrated with samples from experimentally infected cats and then test sera from client-owned cats were assayed. Associations among IgM ELISA results, clinical findings, and bacteremia as defined by Bartonella spp. PCR assay were assessed. Results All experimentally infected cats developed Bartonella spp. IgM antibodies. Bartonella spp. IgM antibody assay results were not always in agreement with PCR assay results in client-owned cats (60%). Bartonella spp. DNA in blood, IgM antibodies, and IgG antibodies were not associated with the presence of fever or stomatitis. Conclusions and Clinical Importance Because Bartonella spp. IgM antibodies as measured by this assay were not associated with fever or stomatitis and were not always in agreement with PCR assay results, there appears to be little need for assessing individual client-owned cats for this antibody class alone.

Generalised pyogranulomatous disease and hyperviscosity syndrome associated with a presumed monoclonal gammopathy was diagnosed in a three-year-old intact female Pomeranian. The Bartonella henselae antibody titer was 1:64 and Bartonella species DNA was amplified from the splenic tissue. Monoclonal gammopathies in dogs are typically associated with plasma cell and lymphoid dyscrasias and other inflammatory or infectious diseases such as ehrlichiosis and leishmaniosis. Based on this case report, infection with Bartonella species should also be added to the differential diagnoses for gammopathy in dogs. To the authors' knowledge, this is the first report of molecular evidence of Bartonella species infection in a sick dog in Spain.

Bacterial type IV secretion systems (T4SSs) are involved in processes such as bacterial conjugation and protein translocation to animal cells. In this work, we have switched the substrates of T4SSs involved in pathogenicity for DNA transfer. Plasmids containing part of the conjugative machinery of plasmid R388 were transferred by the T4SS of human facultative intracellular pathogen Bartonella henselae to both recipient bacteria and human vascular endothelial cells. About 2% of the human cells expressed a green fluorescent protein (GFP) gene from the plasmid. Plasmids of different sizes were transferred with similar efficiencies. B. henselae codes for two T4SSs: VirB/VirD4 and Trw. A Δ virB mutant strain was transfer deficient, while a Δ trwE mutant was only slightly impaired in DNA transfer. DNA transfer was in all cases dependent on protein TrwC of R388, the conjugative relaxase, implying that it occurs by a conjugation-like mechanism. A DNA helicase-deficient mutant of TrwC could not promote DNA transfer. In the absence of TrwB, the coupling protein of R388, DNA transfer efficiency dropped 1 log. The same low efficiency was obtained with a TrwB point mutation in the region involved in interaction with the T4SS. TrwB interacted with VirB10 in a bacterial two-hybrid assay, suggesting that it may act as the recruiter of the R388 substrate for the VirB/VirD4 T4SS. A TrwB ATPase mutant behaved as dominant negative, dropping DNA transfer efficiency to almost null levels. B. henselae bacteria recovered from infected human cells could transfer the mobilizable plasmid into recipient Escherichia coli under certain conditions, underscoring the versatility of T4SSs.

The genus Bartonella is composed of a series of species and subspecies. Ten of them are responsible for human infections. The best-identified diseases are cat scratch disease (B henselae and possibly B clarridgeiae), trench fever (B quintana), bacillary angiomatosis (B quintana and B henselae), and the spectrum of verruga peruana, Carrion disease, and Oroya fever (B bacilliformis). Controversies exist about the implication of a few other microorganisms being involved in these diseases. Several other conditions have been associated with the presence of Bartonella spp, but these observations await confirmation.

Objective—To determine whether monthly topical administration of a combination of 10% imidacloprid and 1% moxidectin would lessen flea (Ctenocephalides felis) transmission of Bartonella henselae among cats. Design—Controlled trial. Animals—18 specific pathogen–free cats housed in 3 groups of 6. Procedures—3 enclosures were separated by mesh to allow fleas to pass among groups yet prevent cats from contacting one another. One group was inoculated IV with B henselae, and after infection was confirmed, the cats were housed in the middle enclosure. This infected group was flanked by a group that was treated topically with 10% imidacloprid–1% moxidectin monthly for 3 months and by an untreated group. On days 0, 15, 28, and 42, 100 fleas/cat were placed on each of the 6 cats in the B henselae–infected group. Blood samples were collected from all cats weekly for detection of Bartonella spp via PCR assay, bacterial culture, and serologic assay. Results—B henselae infection was confirmed in the cats infected IV and in all untreated cats after flea exposure; none of the cats treated with the imidacloprid-moxidectin combination became infected. Conclusions and Clinical Relevance—In this setting, monthly topical administration of 10% imidacloprid–1% moxidectin reduced flea infestation, compared with infestation in untreated cats, and thus prevented flea transmission of B henselae to treated cats. Regular monthly use of this flea control product in cats may lessen the likelihood of humans acquiring B henselae infection.

Peliosis hepatis is a vasculoproliferative disorder of the liver with infectious and noninfectious causes. In humans and dogs, Bartonella henselae has been linked to peliosis hepatis. Although domestic cats are the natural reservoir of B. henselae and although peliosis hepatis is common in this species, an association between this condition and infection with B. henselae has never been investigated in cats. In this study, 26 cases of peliosis hepatis in cats were tested for B. henselae infection by nested polymerase chain reaction and immunohistochemistry. The authors failed to detect B. henselae nucleic acid or antigen in any of the affected liver specimens. These findings suggest that, unlike in humans and dogs, peliosis hepatis in cats may not be significantly associated with a B. henselae infection.

Bartonella henselae is a slow growing, fastidious and facultative intracellular pathogen causing cat scratch disease and vasculoproliferative disorders. To date, knowledge about the pathogenicity of this human pathogenic bacterium is limited and, additionally, serodiagnosis still needs further improvement. Here, we investigated the proteome of B. henselae using 2-D SDS-PAGE and MALDI-TOF-MS. We provide a comprehensive 2-D proteome reference map of the whole cell lysate of B. henselae with 431 identified protein spots representing 191 different proteins of which 16 were formerly assigned as hypothetical proteins. To unravel immunoreactive antigens, we applied 2-D SDS-PAGE and subsequent immunoblotting using 33 sera of patients suffering from B. henselae infections. The analysis revealed 79 immunoreactive proteins of which 71 were identified. Setting a threshold of 20% seroreactivity, 11 proteins turned out to be immunodominant antigens potentially useful for an improved Bartonella-specific serodiagnosis. Therefore, we provide for the first time (i) a comprehensive 2-D proteome map of B. henselae for further proteome-based studies focussed on the pathogenicity of B. henselae and (ii) an integrated view into the humoral immune responses targeted against this newly emerged human pathogenic bacterium.

The cutaneous epithelioid angiomatous nodule is an uncommon benign vascular proliferation that has only recently been described. Clinically, it usually presents as a solitary, fast-growing, small reddish papulous or nodular lesion on the trunk or limbs of adults. Histopathologic study reveals a proliferation of epithelioid cells and predominantly solid, well delimited, unilobular growth in the superficial dermis. Well defined vessels are often found permeating the lesion, which also shows a certain degree of inflammatory infiltration. The cells contain abundant pink cytoplasm, often with vacuoles, and vesicular nuclei with prominent nucleoli. The morphology of these cells is relatively uniform, without atypia or pleomorphism, although mitoses are not uncommon. We report 2 new cases of cutaneous epithelioid angiomatous nodules, the first in a 28-year-old pregnant woman and the second in a 27-year-old man. In both cases, the usual characteristics of this entity were present, but with the peculiarity of a high mitotic index. We discuss the differential diagnosis of cutaneous epithelioid angiomatous nodules with other vascular proliferations that exhibit epithelioid cytology.