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      Bartonella spp. Bacteremia in Blood Donors from Campinas, Brazil

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          Abstract

          Bartonella species are blood-borne, re-emerging organisms, capable of causing prolonged infection with diverse disease manifestations, from asymptomatic bacteremia to chronic debilitating disease and death. This pathogen can survive for over a month in stored blood. However, its prevalence among blood donors is unknown, and screening of blood supplies for this pathogen is not routinely performed. We investigated Bartonella spp. prevalence in 500 blood donors from Campinas, Brazil, based on a cross-sectional design. Blood samples were inoculated into an enrichment liquid growth medium and sub-inoculated onto blood agar. Liquid culture samples and Gram-negative isolates were tested using a genus specific ITS PCR with amplicons sequenced for species identification. Bartonella henselae and Bartonella quintana antibodies were assayed by indirect immunofluorescence. B. henselae was isolated from six donors (1.2%). Sixteen donors (3.2%) were Bartonella-PCR positive after culture in liquid or on solid media, with 15 donors infected with B. henselae and one donor infected with Bartonella clarridgeiae. Antibodies against B. henselae or B. quintana were found in 16% and 32% of 500 blood donors, respectively. Serology was not associated with infection, with only three of 16 Bartonella-infected subjects seropositive for B. henselae or B. quintana. Bartonella DNA was present in the bloodstream of approximately one out of 30 donors from a major blood bank in South America. Negative serology does not rule out Bartonella spp. infection in healthy subjects. Using a combination of liquid and solid cultures, PCR, and DNA sequencing, this study documents for the first time that Bartonella spp. bacteremia occurs in asymptomatic blood donors. Our findings support further evaluation of Bartonella spp. transmission which can occur through blood transfusions.

          Author Summary

          Bartonella is a genus of small bacteria with worldwide distribution, transmitted by blood-sucking insects, and is capable of causing disease in humans and animals. Some of the clinical presentations of Bartonella spp., such as cat scratch disease, trench fever, and bacillary angiomatosis are well documented; however, novel presentations have been described in the last two decades, ranging from cyclic flu-like syndrome to neurologic disease and life-threatening endocarditis. Asymptomatic human infection is possible and accidental blood transmission has been reported. Bacterium isolation is very difficult because they grow slowly and require special culture media and procedures. Serology testing poorly predicts active Bartonella infection, except in infection of cardiac valves. Therefore, diagnosis is generally challenging. However, when molecular detection techniques are coupled with special culture protocols, enhanced sensitivity and specificity can be achieved. We investigated Bartonella spp. infection prevalence in a large blood donor population and confirmed bacteremia in 1.2% of the subjects. Bloodstream infection was detected with at least three different molecular methods in 3.2% of donors. These results indicate that Bartonella is a genus of importance for transfusion medicine.

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          Most cited references43

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          Intruders below the radar: molecular pathogenesis of Bartonella spp.

          Bartonella spp. are facultative intracellular pathogens that employ a unique stealth infection strategy comprising immune evasion and modulation, intimate interaction with nucleated cells, and intraerythrocytic persistence. Infections with Bartonella are ubiquitous among mammals, and many species can infect humans either as their natural host or incidentally as zoonotic pathogens. Upon inoculation into a naive host, the bartonellae first colonize a primary niche that is widely accepted to involve the manipulation of nucleated host cells, e.g., in the microvasculature. Consistently, in vitro research showed that Bartonella harbors an ample arsenal of virulence factors to modulate the response of such cells, gain entrance, and establish an intracellular niche. Subsequently, the bacteria are seeded into the bloodstream where they invade erythrocytes and give rise to a typically asymptomatic intraerythrocytic bacteremia. While this course of infection is characteristic for natural hosts, zoonotic infections or the infection of immunocompromised patients may alter the path of Bartonella and result in considerable morbidity. In this review we compile current knowledge on the molecular processes underlying both the infection strategy and pathogenesis of Bartonella and discuss their connection to the clinical presentation of human patients, which ranges from minor complaints to life-threatening disease.
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            Bartonellosis: an emerging infectious disease of zoonotic importance to animals and human beings.

            To provide a review of clinically relevant observations related to Bartonella species as emerging pathogens in veterinary and human medicine. Literature as cited in PubMed and as generated by each of the authors who have contributed to various aspects of the clinical understanding of bartonellosis. Important historical and recent publications illustrating the evolving role of animal reservoirs as a source of human infection. Comprehensive review of the veterinary literature. In addition to inducing life-threatening illnesses, such as endocarditis, myocarditis, and meningoencephalitis and contributing to chronic debilitating disease, such as arthritis, osteomyelitis, and granulomatous inflammation in cats, dogs, and potentially other animal species; pets and wildlife species can serve as persistently infected reservoir hosts for the transmission of Bartonella spp. infection to veterinary professionals and others with direct animal contact.
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              Factors associated with the rapid emergence of zoonotic Bartonella infections.

              Within the last 15 years, several bacteria of the genus Bartonella were recognized as zoonotic agents in humans and isolated from various mammalian reservoirs. Based on either isolation of the bacterium or PCR testing, eight Bartonella species or subspecies have been recognized as zoonotic agents, including B. henselae, B. elizabethae, B. grahamii, B. vinsonii subsp. arupensis, B. vinsonii subsp. berkhoffii, B. grahamii, B. washoensis and more recently B. koehlerae. The present manuscript reviews the factors associated with the emergence of these zoonotic pathogens, including better diagnostic tools and methods to identify these fastidious bacteria, host immunosuppression (caused by infectious agents, cancer, aging or induced by immunosuppressive drugs), the interaction of co-infection by several infectious agents that may enhanced the pathogenecity of these bacteria, increased outdoor activity leading to exposure to wildlife reservoirs or vectors, poverty and low income associated with infestation by various ectoparasites, such as body lice and finally the dispersal of Bartonellae around the world. Furthermore, a description of the main epidemiological and clinical features of zoonotic Bartonellae is given. Finally, the main means for diagnosis, treatment and prevention of these diseases are presented.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                January 2015
                15 January 2015
                : 9
                : 1
                : e0003467
                Affiliations
                [1 ]Division of Dermatology, Department of Medicine, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
                [2 ]College of Veterinary Medicine, Western University of Health Sciences, Pomona California, United States of America
                [3 ]Department of Molecular & Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                [4 ]Centro de Hematologia e Hemoterapia (HEMOCENTRO), Department of Medicine, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
                [5 ]Laboratory of Animal Quality Control, Multidisciplinary Center of Biological Investigation (CEMIB), State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil
                [6 ]Department of Virology, Adolfo Lutz Institute (IAL), Secretaria de Estado de Saúde de São Paulo, São Paulo, Brazil
                [7 ]Intracellular Pathogens Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America
                [8 ]Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                University of Texas Medical Branch, UNITED STATES
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: EBB has a patent U.S.A. #7,115,385 for media and methods for cultivation of microorganisms issued to EBB, Dr. Sontakke and North Carolina State University. EBB is the chief scientific officer for Galaxy Diagnostics, a company that provides diagnostic testing for the detection of Bartonella species infection in animals and human patient samples. This does not alter our adherence to all PLOS policies on sharing data and materials. All other authors have no conflict of interest to declare.

                Conceived and designed the experiments: LHUP PPVdPD DGS PENFV. Performed the experiments: LHUP PPVdPD DGS MRD BGL MLBC SS. Analyzed the data: LHUP PPVdPD MRD PENFV. Contributed reagents/materials/analysis tools: RG SC EBB WLN. Wrote the paper: LHUP PPPVdPD DGS MRD SS EBB WLN PENFV.

                [¤]

                Current address: Department of Biomedical Sciences, Ross University School of Veterinary Medicine, Basseterre, St. Kitts, West Indies

                Article
                PNTD-D-14-01102
                10.1371/journal.pntd.0003467
                4295888
                25590435
                b87b88b8-1f8d-4ed3-9c2f-75d661bee812

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

                History
                : 1 July 2014
                : 10 December 2014
                Page count
                Figures: 1, Tables: 1, Pages: 12
                Funding
                This project was the basis for the PhD thesis of LHUP and was partially funded by the Faculty Grant in Global Health to DGS from the Johns Hopkins Center for Global Health; a grant from FAEPEX—UNICAMP (Fundo de Apoio ao Ensino, à Pesquisa e à Extensão—UNICAMP) under protocols number 234/10 and 292/10; and a summer research scholarship to SS from the Office of the Vice President for Research and Biotechnology, Western University, Western University of Health Sciences, Pomona, CA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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