A comparison of Bartonella henselae infection in immunocompetent and immunocompromised mice.

Bartonellosis refers to disease caused by the Bartonella genus of bacteria. The breadth of disease manifestations associated with Bartonella is currently expanding and includes regional lymphadenopathy, rheumatic, ocular, and neurological disorders. The dearth of knowledge regarding diagnosis, treatment and pathogenesis of this disease can be partially attributed to the lack of a reliable small animal model for the disease. For this study, Bartonella henselae, the most common species associated with human disease, was injected into Swiss Webster (SW) mice. When the outcome indicated that productive infection did not occur, SCID/Beige (immune compromised) mice were inoculated. While SW mice may potentially harbor an acute infection, less than 10 days in length, the SCID/Beige model provided a sustained infection lasting up to 30-days. These data indicate that SCID/Beige mice can provide a model to study Bartonella infection, therapeutics, and vector dynamics in the future.

Pleural and pericardial effusions with fever and altered mental status: an atypical presentation of bartonellosis.

A male in his 60s presented to the emergency department (ED) with a 3-week history of fever and progressive confusion. Initial laboratory and radiographic workup was largely unremarkable except for moderate bilateral pleural effusions. The patient was admitted on broad-spectrum antibiotics and further workup for fever of unknown aetiology. The differential diagnosis was broadened to different zoonotic infections, and subsequent laboratory testing showed a markedly elevated Bartonella henselae IgG and Bartonella quintana IgG (1:4096 and 1:512, respectively) in addition to positive B. henselae IgM titre (>1:20). During hospitalisation, the patient became more hypoxic and was found to have enlarging pleural effusions as well as a new pericardial effusion. The patient was treated with intravenous then oral doxycycline 100 mg two times per day and oral rifampin 300 mg two times per day for 4 weeks with subsequent improvement in clinical status as well as both effusions. This case highlights a unique presentation of Bartonella and its rare manifestation of pleural and pericardial effusions.

Detection of Bartonella bovis DNA in blood samples from a veterinarian in Mexico.

The genus Bartonella encompasses 38 validated species of Gram-negative, facultative intracellular bacteria that colonize the endothelial cells and erythrocytes of a wide spectrum of mammals. To date, 12 Bartonella species have been recorded infecting humans, causing diseases of long historical characterization, such as cat scratch fever and trench fever, and emerging bartonellosis that mainly affect animal health professionals. For this reason, this study aimed to report a documented case of Bartonella bovis infecting a veterinarian from Mexico by the amplification, sequencing and phylogenetic reconstruction of the citrate synthase (gltA) and the RNA polymerase beta-subunit (rpoB) genes, and to report the natural course of this infection. To our knowledge, this work is the first to report the transmission of B. bovis via needlestick transmission to animal health workers in Latin America.

Bartonella henselae as a putative trigger for chronic type 2 leprosy reactions.

Leprosy reactions are an acute inflammatory phenomenon that can arise before diagnosis, during treatment, or after cure of leprosy. These reactions are considered one of the main diseases that cause physical disabilities. Immunosuppressive treatment for these immune responses makes these patients susceptible to coinfections, which can trigger new leprosy reactions. The main objective of this study was to evaluate the occurrence of infection by Bartonella sp. in blood samples from 47 patients who had untreatable episodes of type 2 leprosy reactions for more than six months, comparing them with a control group. Cultures and molecular methods (PCR) were used. Amplicons from species-specific reactions and sequencing showed a higher prevalence of Bartonella henselae infection in patients, 19/47 (40.4 %), compared to control, 9/50 (18.0 %), p = 0.0149. Five patients accepted treatment for coinfection, and all showed improvement in leprosy reactions with treatment for B. henselae infection. We conclude that these bacteria can trigger chronic reactions of type 2 leprosy and should be investigated in these patients. SUMMARY LINE: Patients who have chronic type 2 leprosy reactions are more susceptible to Bartonella henselae infection than controls: 19/47 (40.4 %) compared 9/50 (18.0 %), p = 0.0149.

Molecular evidence of Bartonella spp. in wild lowland tapirs (Tapirus terrestris), the largest land mammals in Brazil.

The genus Bartonella (Hyphomicrobiales: Bartonellaceae) encompasses facultative intracellular α-proteobacteria that parasite erythrocytes and endothelial cells from a wide range of vertebrate hosts and can cause disease in animals and humans. Considering the large diversity of vertebrate species that may act as reservoirs and arthropod species that may be associated with Bartonella transmission, the exposure of animals and humans to these microorganisms is likely underestimated. The present study aimed to investigate the occurrence of Bartonella sp. in wild tapirs (Tapirus terrestris; Perissodactyla: Tapiridae) from two biomes in Brazil: Pantanal and Cerrado. Ninety-nine GPS-monitored wild tapirs were sampled in Pantanal (n = 61/99) and Cerrado (n = 38/99). A qPCR (quantitative real-time polymerase chain reaction) assay targeting the nuoG gene was used for the screening for Bartonella spp. DNA. Positive samples were additionally subjected to conventional PCR assays targeting five molecular markers (ribC, gltA, rpoB, groEL, ITS). Eight (8/99; 08,08%) animals were positive in the qPCR assay for Bartonella spp.: 7 from Cerrado (7/8; 87.5%) and 1 from Pantanal (1/8; 12.5%). The 5 Bartonella ribC sequences obtained from tapirs' blood samples grouped together with Bartonella henselae obtained from cats, humans, wild felids and Ctenocephalides felis (Siphonaptera: Pulicidae) fleas. To the best of author's knowledge, this is the first report of Bartonella sp. in Tapirus terrestris. This finding contributes to the understanding of the occurrence of B henselae in wild mammals from Brazil as well as expands the knowledge regarding the potential vector-borne pathogens that may affect wild tapis from Cerrado and Pantanal biomes.

Molecular detection and characterization of Bartonella spp. in rodents from central and southern Chile, with emphasis on introduced rats (Rattus spp.).

Bartonella spp. was screened in 155 rodents from Chile, mainly the invasive rats Rattus norvegicus and Rattus rattus. A total of 155 spleen and 50 blood samples were analyzed through real-time PCR for Bartonella spp. (nuoG gene). Positive samples were subjected to amplification of fragment of loci gltA, rpoB and ITS by conventional PCR (cPCR). Overall, 43 spleen samples (27.7%) and 6 rodent blood samples (12%) were positive for nuoG-Bartonella spp. Positive samples were found in R. norvegicus, R. rattus, Abrothrix olivacea and Oligoryzomys longicaudatus. Bartonella spp. DNA was amplified by cPCR in 16 samples, resulting in 21 sequences (6 gltA, 5 ITS and 10 rpoB). Sequencing and phylogenic analyses identified genotypes from Rattus spp., potentially belonging to Bartonella coopersplainsensis, Bartonella henselae, Bartonella tribocorum, and an undescribed Bartonella sp. From native rodents, one sequence was identified, being related B. machadoae. In conclusion, this work describes diverse and potentially zoonotic Bartonella spp. genotypes in Rattus spp. Additionally, this is the first report of Bartonella in O. longicaudatus, including a potentially novel Bartonella genotype or species.

Blood Supplementation Enhances Bartonella henselae Growth and Molecular Detection of Bacterial DNA in Liquid Culture.

Bacteria of the genus Bartonella, a member of the Alphaproteobacteria, are fastidious, Gram-negative, aerobic bacilli that comprise numerous species, subspecies, and genotypes. Bartonella henselae, with a worldwide distribution, infects cats, dogs, horses, humans, and other mammals. Diagnostically, direct detection of Bartonella henselae in patient blood specimens by culture or molecular methods is required to confirm infection with this bacterium. Enrichment blood culture combined with quantitative PCR (qPCR) or ddPCR enhances the sensitivity of direct detection. The addition of sheep blood to liquid culture media increased the Bartonella henselae DNA concentration compared to controls, additionally improving PCR direct detection sensitivity. IMPORTANCE This study aims to improve diagnostic detection of Bartonella henselae. Patient samples are combined with enriched bacterial cultures aimed at growing Bartonella henselae for the best possible chance at detection. However, current Bartonella growth methods could be improved. The DNA extraction method used by most laboratories should also be optimized. Sheep blood was added to increase the growth of Bartonella henselae and multiple DNA extraction methods were to be compared to each other.

In-silico identification of linear B-cell epitopes in specific proteins of Bartonella bacilliformis for the serological diagnosis of Carrion's disease.

Carrion´s disease is caused by Bartonella bacilliformis, it is a Gram-negative pleomorphic bacterium. B. bacilliformis is transmitted by Lutzomyia verrucarum in endemic areas of the Peruvian Inter-Andean valleys. Additionally, the pathogenicity of B. bacilliformis involves an initial infection of erythrocytes and the further infection of endothelial cells, which mainly affects children and expectant women from extreme poverty rural areas. Therefore, the implementation of serological diagnostic methods and the development of candidate vaccines for the control of CD could be facilitated by the prediction of linear b-cell epitopes in specific proteins of B. bacilliformis by bioinformatics analysis. In this study, We used an in-silico analysis employing six web servers for the identification of epitopes in proteins of B. bacilliformis. The selection of B. bacilliformis-specific proteins and their analysis to identify epitopes allowed the selection of seven protein candidates that are expected to have high antigenic activity.

Infectious endocarditis caused by Bartonella henselae associated with infected pets: two case reports.

BACKGROUND: Blood culture-negative infective endocarditis is a potentially severe disease that can be associated with infectious agents such as Bartonella spp., Coxiella burnetti, Tropheryma whipplei, and some fungi. CASE PRESENTATION: Reported here are two cases of blood culture-negative infective endocarditis in patients with severe aortic and mitral regurgitation in Brazil; the first case is a 47-year-old white man and the second is a 62-year-old white woman. Bartonella henselae deoxyribonucleic acid was detectable in the blood samples and cardiac valve with vegetation paraffin-fixed tissue samples. Additionally, an investigation was carried out on patients' pets, within the context of One Health, and serum samples collected from cats and dogs were reactive by indirect immunofluorescence assay. CONCLUSIONS: Even though the frequency of bartonellosis in Brazil is unknown, physicians should be aware of the possibility of blood culture-negative infective endocarditis caused by Bartonella, particularly in patients with weight loss, kidney changes, and epidemiological history for domestic animals.

Angiomatosis bacilar y micobacteriosis atípica en paciente con diagnóstico reciente de infección por el virus de la inmunodeficiencia humana / Bacillary Angiomatosis and Atypical Mycobacteriosis in a patient recently diagnosed with Human Immunodeficiency Virus infection

Múltiples infecciones oportunistas pueden manifestarse simultáneamente cuando la inmunosupresión es grave en pacientes infectados por el virus de la inmunodeficiencia humana. Se presenta un caso de coinfección de VIH, Bartonella spp y Mycobacterium kansasii, siendo escasos los reportes a la fecha de dicha asociación y aun más en pacientes que desconocen su condición de VIH

Multiple opportunistic infections can manifest simultaneously when immunosuppression is severe in patients infected with the human immunodeficiency virus. A case of co-infection with HIV, Bartonella spp and Mycobacterium kansasii is presented, with few reports to date of this association and even more so in patients who are unaware of their HIV status.

Detection of Bartonella henselae DNA in the blood of patients with livedoid vasculopathy.

BACKGROUND: Livedoid vasculopathy (LV) manifests as ulcers and atrophic white scars on the lower extremities. The main known etiopathogenesis is hypercoagulability with thrombus formation, followed by inflammation. Thrombophilia, collagen and myeloproliferative diseases may induce LV, but the idiopathic (primary) form predominates. Bartonella spp. may cause intra-endothelial infection and skin manifestations caused by these bacteria may be diverse, including leukocytoclastic vasculitis and ulcers. OBJECTIVE: The aim of this study was to investigate the presence of bacteremia by Bartonella spp. in patients with difficult-to-control chronic ulcers diagnosed as primary LV. METHODS: Questionnaires and molecular tests (conventional PCR, nested PCR and real-time PCR) were applied and liquid and solid cultures were performed in the blood samples and blood clot of 16 LV patients and 32 healthy volunteers. RESULTS: Bartonella henselae DNA was detected in 25% of LV patients and in 12.5% of control subjects but failed to reach statistically significant differences (p = 0.413). STUDY LIMITATIONS: Due to the rarity of primary LV, the number of patients studied was small and there was greater exposure of the control group to risk factors for Bartonella spp. CONCLUSION: Although there was no statistically significant difference between the groups, the DNA of B. henselae was detected in one of every four patients, which reinforces the need to investigate Bartonella spp. in patients with primary LV.

Bartonellosis in Dogs and Cats, an Update.

The unique virulence factors of Bartonella spp make them stealth pathogens that evade the immune system and cause persistent infections that are often difficult to diagnose and treat. Understanding these pathogenic mechanisms allows clinicians to recognize when to pursue diagnostics, how to optimize diagnostic testing and treatment, and ultimately can lead to improved outcomes.

Molecular detection and identification of Bartonella species in cats from Hamedan and Kermanshah, Western Iran.

Bartonella species are emerging vector-borne zoonotic pathogens which infect a wide range of domestic and wild animals as well as humans. Cats are the primary reservoir hosts for several zoonotic Bartonella spp., the most common being B. henselae the causative agent of cat scratch disease. Despite the important role of cats in the epidemiology of bartonellosis, there is limited information about the prevalence and species infecting cats in Iran. The aim of present study was molecular detection and identification of Bartonella species in cats from two western provinces Hamedan and Kermanshah. From December 2018 to February 2021, 87 cats (n = 26 from Hamedan, n = 61 from Kermanshah) were examined clinically, their bodies were searched for collection of ectoparasites, and cephalic or saphenous blood specimens were collected. Genomic DNA was extracted from blood specimens and conventional PCRs targeting the rpoB, and ITS regions of Bartonella spp. were performed. Positive samples were sequenced and analysed phylogenetically. Bartonella DNA was detected in 11/87 cats (12.64 %). Sequencing results revealed the presence of B. henselae in cats from Hamedan, and B. clarridgeiae and B. henselae in cats from Kermanshah. A statistical association between cat origin and the prevalence of Bartonella spp. was observed in the studied population. This study confirms for the first time the circulation of Bartonella spp. in cats in two western Iranian provinces. Prevention strategies e.g. ectoparasites control, and regular examination of pet and urban cats are suggested for minimising Bartonella infection in cats and subsequently in humans.

Serological evidence of exposure to Bartonella sp. in dogs with suspected vector-borne diseases, toxoplasmosis and neosporosis.

Bartonellosis is a vector-borne zoonotic disease with worldwide distribution that infect a broad spectrum of mammalian species. Despite the recent studies carried out in Brazil, information regarding Bartonella in dogs are scarce. Therefore, we performed a retrospective study to investigate the exposure to Bartonella sp. in dogs by indirect immunofluorescence assay (IFA). Three hundred and thirty-five archived serum samples from dogs previously tested for vector-borne pathogens, Toxoplasma gondii, and Neospora caninum were screened for the presence of IgG antibodies to Bartonella sp. All dogs originated from the Metropolitan region of Ribeirão Preto, northeast of the State of São Paulo. Twenty-eight samples (8.3%) were positive for Bartonella sp. at the cut-off of 64. Among the 28 seropositive samples for Bartonella sp., 16 (57.1%) were also seropositive for Ehrlichia canis, 12 (42.8%) for Babesia vogeli, five (17.8%) for T. gondii and three (10.7%) for L. infantum and N. caninum. Our results demonstrated that dogs sampled were exposed to Bartonella sp. Since all the animals sampled in the present study were from private owners, our findings demonstrate that these people may also be exposed to Bartonella sp. Further studies designed to assess whether the infection by other arthropod-borne pathogens such as B. vogeli and E. canis are risk factors for Bartonella infection are needed.

Detection of Bartonella vinsonii subsp. berkhoffii in an HIV patient using metagenomic Next-Generation Sequencing.

Bartonella species are fastidious, aerobic bacteria that are transmitted by blood-sucking arthropods. Bartonella spp. are responsible for cat scratch disease, Carrion's disease, bacillary angiomatosis and trench fever. On the other hand, Bartonella vinsonii is rarely reported in the literature and there exist a few reports of systemic infection caused by Bartonella vinsonii in patients with acquired immunodeficiency syndrome. A 31-year-old male (diagnosed with AIDS six years ago) had persistent fever and ulceration in the right knee. The elevated levels of inflammatory markers suggested an infectious aetiology. Despite the negative findings of blood culture, metagenomic Next-Generation Sequencing of plasma detected Bartonella vinsonii. The polymerase chain reaction of whole blood and Sanger sequencing confirmed the mNGS findings. Immunohistochemical staining had later suggested bacillary angiomatosis, which was consistent with Bartonella infection. Following antibiotic treatment, the ulcers subsided significantly, but a high fever persisted. The patient died due to sudden respiratory failure.

Haemophagocytic lymphohistiocytosis associated with bartonella peliosis hepatis following kidney transplantation in a patient with HIV.

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.

Evaluation of ssrA-targeted real time PCR for the detection of Bartonella species in human clinical samples and reflex sequencing for species-level identification.

The genus Bartonella includes species capable of causing disease in animals and humans. Due to its fastidious nature, direct detection of Bartonella causing human infection relies largely on molecular microbiological methods. Thus, it is imperative that diagnostic assays in use have the ability to detect a range of Bartonella species associated with human disease. In this study, we compared the performance of a real time polymerase chain reaction (PCR) assay targeting the ssrA gene to conventional rpoB-targeted PCR and sequencing for detection and differentiation of Bartonella species in human clinical samples. The real time ssrA PCR performed better for non-Bartonella henselae species, detecting B. clarridgeiae and B. quintana DNA in heart valve specimens that were not detected by rpoB PCR, and improved the sensitivity of B. henselae detection in blood specimens. Our findings suggest the real time ssrA PCR assay is suitable for detection and identification of Bartonella species in human clinical specimens.

Two-year history of lymphadenopathy and fever caused by Bartonella henselae in a child.

We report the case of a 6-year-old boy that presented with enlarged lymph nodes on his neck. He complained of tiredness and discouragement, which worsened during feverish periods. There were no relevant laboratory test abnormalities and serological tests were not reactive. Bartonella henselae DNA was detected by species-specific nested polymerase chain reaction. After treatment, the patient progressed with no fever or lymphadenopathy. Bartonellosis is a group of infectious diseases caused by bacteria of the genus Bartonella. This case report is a useful reminder to clinicians that long-term fever of unknown origin can be related to B. henselae infection, even if the specific serology is not reactive.

Bartonella and Coxiella infections presenting as systemic vasculitis: case series and review of literature.

OBJECTIVES: Coxiella and Bartonella spp. display particular tropism for endothelial or endocardial tissues and an abnormal host response to infections with induced autoimmunity. We aimed, through a case series combined with a comprehensive literature review, to outline characteristics of Coxiella and Bartonella infections presenting as systemic vasculitis. METHODS: We retrospectively included cases of definite Coxiella and Bartonella infections presenting with vasculitis features and performed a comprehensive literature review. RESULTS: Six cases of Bartonella infections were added to 18 cases from literature review. Causative pathogens were mainly B. henselae. Bartonella infection mimicked ANCA-associated vasculitis in 83% with PR3-ANCA and presented as cryoglobulinaemic vasculitis in 8%. GN was present in 92%, and 88% had endocarditis. Complement fractions were low in 82% and rheumatoid factor positive in 85%. Kidney biopsies showed cell proliferation, mostly crescentic, with pauci-immune GN in 29%. Outcome was favourable, with the use of antibiotics alone in one-third. Five cases of Coxiella infections were added to 16 from literature review. Sixteen had small-vessel vasculitides, mainly cryoglobulinaemia vasculitis in 75%. One patient had polyarteritis nodosa-like vasculitis and four large-vessel vasculitis. Outcome was good except for one death. A highly sensitive next generation sequencing analysis on three Coxiella- and two Bartonella-related vasculitides biopsies did not find any bacterial DNA. CONCLUSION: Coxiella and Bartonella are both able to induce vasculitis but display distinct vasculitis features. Bartonella mimics PR3-ANCA-associated vasculitis in the setting of endocarditis, whereas Coxiella may induce vasculitis involving all vessel sizes.