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.

Treatment of a cat with presumed Bartonella henselae-associated immune-mediated hemolytic anemia, fever, and lymphadenitis.

A 2.5-year-old castrated male cat presented with fever and marked generalized lymphadenopathy of 4-months duration, despite treatment with amoxicillin-clavulanate/marbofloxacin. Abnormalities were not detected on complete blood count, serum chemistry, and FIV/FeLV test apart from a borderline, non-regenerative anemia. Peripheral lymph node fine needle aspirations revealed a marked increase in the percentage of intermediate- and lymphoblastic-lymphocytes in addition to reactive macrophages. Three weeks after presentation, the cat developed a severe, regenerative, immune-mediated hemolytic anemia (IMHA) which responded to immunosuppressive therapy. Fever and lymphadenopathy persisted. Peripheral lymph nodes tested positive for Bartonella henselae DNA in real-time PCR assay and sequencing. Treatment with pradofloxacin and doxycycline resulted in resolution of clinical signs, and negative PCR tests. Despite its reported low pathogenicity, B. henselae infection should also be considered in cats with protracted unexplained fever, lymphadenitis, and IMHA. Furthermore, a combination of pradofloxacin and doxycycline might be considered in cats with bartonellosis given its apparent clinical efficacy.

Identification of an Emergent Pathogen, Bartonella vinsonii, Using Next-Generation Sequencing in a Patient With Culture-Negative Endocarditis.

Diagnosis and treatment of culture negative endocarditis remains a challenge. This report describes a rare cause of endocarditis in humans, Bartonella vinsonii, identified through next generation sequencing of plasma microbial cell-free DNA with confirmation of cardiac valve tissue infection through immunohistochemical staining and polymerase chain reaction.

Atypical bartonellosis in children: What do we know?

AIM: To characterise Bartonella infections in a paediatric population requiring hospital admission and review its treatment. METHODS: Longitudinal observational retrospective data analysis of children and adolescents admitted with Bartonella infection at a paediatric tertiary hospital from 2010 to 2019. RESULTS: We identified 16 cases of bartonellosis, with a mean age of 8.0 ± 4.5 years old, no sex predominance and 14 had contact with cats. Most of the cases occurred in fall and winter. Clinical presentations included osteomyelitis/arthritis (n = 9), hepatosplenic disease (n = 2), lymphadenitis (n = 2), neuroretinitis (n = 2) and encephalitis (n = 1). Clinical diagnosis was confirmed by serology (n = 16) and Bartonella DNA detection in patient's lymph nodes/hepatic lesion (n = 3). Therapeutic approach varied according to the clinical presentation: azithromycin in lymphadenitis, rifampicin plus ciprofloxacin in hepatosplenic disease, rifampicin and doxycycline in neuroretinitis, ceftriaxone in encephalitis and azithromycin, cotrimoxazole or rifampicin plus azithromycin, cefuroxime, ciprofloxacin or doxycycline in osteomyelitis/arthritis. Immunodeficiency was excluded in seven patients. Seven patients' cats were screened by veterinarians and treated when infected (n = 5). CONCLUSIONS: In these clinical presentations, where other infections may be involved, a high index of suspicion is necessary, with emphasis on the epidemiological context. The association of systemic forms with immunodeficiency did not occur in our study. The lack of recommendations for treatment of atypical infection makes the approach of these cases a challenge. Randomised control studies are essential to define the best approach in each case.

Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach.

BACKGROUND Carrion's disease (CD) is a neglected biphasic illness caused by Bartonella bacilliformis, a Gram-negative bacteria found in the Andean valleys. The spread of resistant strains underlines the need for novel antimicrobials against B. bacilliformis and related bacterial pathogens. OBJECTIVE The main aim of this study was to integrate genomic-scale data to shortlist a set of proteins that could serve as attractive targets for new antimicrobial discovery to combat B. bacilliformis. METHODS We performed a multidimensional genomic scale analysis of potential and relevant targets which includes structural druggability, metabolic analysis and essentiality criteria to select proteins with attractive features for drug discovery. FINDINGS We shortlisted seventeen relevant proteins to develop new drugs against the causative agent of Carrion's disease. Particularly, the protein products of fabI, folA, aroA, trmFO, uppP and murE genes, meet an important number of desirable features that make them attractive targets for new drug development. This data compendium is freely available as a web server (http://target.sbg.qb.fcen.uba.ar/). MAIN CONCLUSION This work represents an effort to reduce the costs in the first phases of B. bacilliformis drug discovery.

Prioritisation of potential drug targets against Bartonella bacilliformis by an integrative in-silico approach

BACKGROUND Carrion's disease (CD) is a neglected biphasic illness caused by Bartonella bacilliformis, a Gram-negative bacteria found in the Andean valleys. The spread of resistant strains underlines the need for novel antimicrobials against B. bacilliformis and related bacterial pathogens. OBJECTIVE The main aim of this study was to integrate genomic-scale data to shortlist a set of proteins that could serve as attractive targets for new antimicrobial discovery to combat B. bacilliformis. METHODS We performed a multidimensional genomic scale analysis of potential and relevant targets which includes structural druggability, metabolic analysis and essentiality criteria to select proteins with attractive features for drug discovery. FINDINGS We shortlisted seventeen relevant proteins to develop new drugs against the causative agent of Carrion's disease. Particularly, the protein products of fabI, folA, aroA, trmFO, uppP and murE genes, meet an important number of desirable features that make them attractive targets for new drug development. This data compendium is freely available as a web server (http://target.sbg.qb.fcen.uba.ar/). MAIN CONCLUSION This work represents an effort to reduce the costs in the first phases of B. bacilliformis drug discovery.

B artonella endocarditis masquerading as systemic vasculitis with rapidly progressive glomerulonephritis (aka 'Löhlein nephritis').

Bartonella species are fastidious, Gram-negative aerobic rods and a well-recognised pathogen responsible for culture-negative endocarditis. The histopathological appearance of glomerulonephritis (GN) caused by Bartonella endocarditis may include a pauci-immune GN similar to that usually seen in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Herein, we present an unusual case report of Bartonella endocarditis masquerading as ANCA-positive vasculitis, with crescentic GN. A 66-year-old woman, who had undergone aortic valve replacement 2 years prior to admission, presented with confusion and loss of vision in her right nasal field. Following an extensive diagnostic evaluation, the main findings were right central retinal artery occlusion, ground-glass appearance on chest CT and ANCA-positive, anti PR-3 negative, rapidly progressive GN. The patient was scheduled to start treatment with rituximab for presumed ANCA-positive GN, when a positive serological test for Bartonella henselae was received. In view of this result, a diagnosis of endocarditis was made, based on fulfilment of five Duke minor criteria, namely fever, predisposition, arterial emboli, immunological phenomena and serological evidence of active infection with an organism consistent with infective endocarditis. Immunosuppressive treatment was withheld and antibiotic treatment initiated. This case report emphasises the need for maintaining a high index of suspicion regarding the diagnosis of Bartonella infection, which might mimic ANCA-associated GN.

Diagnosis and treatment of Bartonella endocarditis.

The Bartonella genus comprises more than 20 species of Gram-negative rods which are difficult to culture. These are facultative intracellular bacteria. Humans are reservoir hosts for B. quintana and B. bacilliformis or accidental hosts for other species. Bartonella is a cause of zoonosis. Bartonella infection can be completely asymptomatic or can be linked to various conditions. Our experience with Bartonella endocarditis from 2012-2017 is presented. The most effective diagnostic method for Bartonella endocarditis is PCR detection of DNA of the pathogen from excised valve tissue. The European Society of Cardiology (ESC) in the guidelines from 2015 recommends the combination doxycycline gentamycin for the treatment of Bartonella endocarditis.

Bartonella Quintana prosthetic aortitis successfully treated with doxycycline.

Bartonella quintana is a rare cause of culture-negative endovascular infection, characterised by intracellular persistence. We describe a case of ascending aortic prosthetic graft infection due to B. quintana, in a patient with past unrecognised necrotising aortitis, which was successfully treated with doxycycline monotherapy.

First isolation and genotyping of Bartonella henselae from a cat living with a patient with cat scratch disease in Southeast Europe.

BACKGROUND: The bacterial genus Bartonella is distributed worldwide and poses a public health risk. Cat-scratch disease caused by B. henselae in Croatia was first described in 1957. It is present throughout the country: a survey of serum samples from 268 Croatian patients with lymphadenopathy showed that 37.7% had IgG antibodies. Despite this prevalence, we are unaware of reports of Bartonella culturing from infected humans or cats in Croatia or elsewhere in southeast Europe. CASE PRESENTATION: Here we describe the diagnosis of a 12-year-old child with lymphadenopathy in Croatia with cat-scratch disease based on antibody detection and clinical signs, and the subsequent culturing and genotyping of B.henselae from the cat's blood. The B. henselae isolate was grown on different blood agar plates and its identity was confirmed based on polymerase chain reaction (PCR) amplification of 16S ribosomal deoxyribonucleic acid (16S rDNA) and sequencing. Multi-locus sequence typing (MLST) identified the strain genotype as sequence type 5, commonly found zoonotic B. henselae strain in cats. The child recovered after azithromycin therapy, and B. henselae in the cat was eliminated within three months after doxycycline treatment. CONCLUSIONS: This is, to our knowledge, the first report of B. henselae culturing and MLST-based genotyping from cat's blood in southeast Europe. Our ability to detect B. henselae in blood through culturing but not PCR suggests that the prevalence of infected cats with low bacteremia is very high, suggesting the need to develop faster, more sensitive detection assays.

False Negative Results in Bartonellosis Diagnosis.

We report a fatal case of Bartonella henselae bacteremic patient. He had negative serology and PCRs from whole blood and liquid culture; only ftsZ nested PCR was positive from the blood liquid culture. The isolate had positive PCRs. When considered, bartonellosis diagnosis can be still challenging because of technical limitations.

A miraculous recovery: Bartonella henselae infection following a red ant bite.

Infections caused by the Bartonella species are responsible for the human diseases collectively called 'bartonellosis'. The clinically important human infections are mostly caused by the three species (eg, B. bacilliformis, B. quintana and B. henselae) of Bartonella out of the many progressively increasing identified species. Bartonella henselae transmitted by the arthropod vector, fleas, after cat bite is responsible for the rare multisystem cat scratch disease in humans. We present an extremely rare case of B. henselae contracted presumably through a red ant bite. The patient had a prolonged hospital stay for persistent encephalopathy due to delay in diagnosis and initiation of antimicrobial therapy. His hospital course was complicated by two episodes of pulseless electrical activity cardiac arrest related to pulmonary embolism. However, he recovered to his baseline status in the hospital with timely administration of systemic anticoagulation and antimicrobials. He was discharged home with no neurological deficits.

Rheumatological presentation of Bartonella koehlerae and Bartonella henselae bacteremias: A case report.

INTRODUCTION: Systemic Bartonella spp. infections are being increasingly reported in association with complex medical presentations. Individuals with frequent arthropod exposures or animal contact appear to be at risk for acquiring long standing infections with Bartonella spp. CASE REPORT: This case report describes infections with Bartonella koehlerae and Bartonella henselae in a female veterinarian whose symptoms were predominantly rheumatologic in nature. Infection was confirmed by serology, polymerase chain reaction (PCR), enrichment blood culture, and DNA sequencing of amplified B koehlerae and B henselae DNA. Long-term medical management with antibiotics was required to achieve elimination of these infections and was accompanied by resolution of the patient's symptoms. Interestingly, the patient experienced substantial improvement in the acquired joint hypermobility mimicking Ehlers-Danlos Syndrome (EDS) type III. CONCLUSION: To facilitate early and directed medical interventions, systemic bartonellosis should potentially be considered as a differential diagnosis in patients with incalcitrant rheumatological symptoms and frequent arthropod exposures or extensive animal contact.

Carrion's Disease: the Sound of Silence.

Carrion's disease (CD) is a neglected biphasic vector-borne illness related to Bartonella bacilliformis. It is found in the Andean valleys and is transmitted mainly by members of the Lutzomyia genus but also by blood transfusions and from mother to child. The acute phase, Oroya fever, presents severe anemia and fever. The lethality is high in the absence of adequate treatment, despite the organism being susceptible to most antibiotics. Partial immunity is developed after infection by B. bacilliformis, resulting in high numbers of asymptomatic carriers. Following infection there is the chronic phase, Peruvian warts, involving abnormal proliferation of the endothelial cells. Despite potentially being eradicable, CD has been expanded due to human migration and geographical expansion of the vector. Moreover, in vitro studies have demonstrated the risk of the development of antimicrobial resistance. These findings, together with the description of new Bartonella species producing CD-like infections, the presence of undescribed potential vectors in new areas, the lack of adequate diagnostic tools and knowledge of the immunology and bacterial pathogenesis of CD, and poor international visibility, have led to the risk of increasing the potential expansion of resistant strains which will challenge current treatment schemes as well as the possible appearance of CD in areas where it is not endemic.

Ptosis, miosis and cats.

Horner's syndrome (HS) is caused by a disruption in the oculosympathetic pathway. Both congenital and acquired HS are unusual in children. Acquired HS can be caused by trauma, surgical intervention, tumours, vascular malformations or infection.We describe the case of a 6-year-old boy who was brought to our emergency department with ptosis, miosis, painful cervical lymphadenopathy and a cat scratch on a hand. The diagnosis of a cat scratch disease was confirmed by serology. A full recovery was observed on antibiotic treatment and cervical lymphadenomegaly reduction 3 weeks later.