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      Bartonella henselae Bloodstream Infection in a Boy With Pediatric Acute-Onset Neuropsychiatric Syndrome

      case-report

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          Abstract

          Background:

          With the advent of more sensitive culture and molecular diagnostic testing modalities, Bartonella spp. infections have been documented in blood and/or cerebrospinal fluid specimens from patients with diverse neurological symptoms. Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by an unusually abrupt onset of cognitive, behavioral, or neurological symptoms. Between October 2015 and January 2017, a 14-year-old boy underwent evaluation by multiple specialists for sudden-onset psychotic behavior (hallucinations, delusions, suicidal and homicidal ideation).

          Methods:

          In March 2017, Bartonella spp. serology (indirect fluorescent antibody assays) and polymerase chain reaction (PCR) amplification, DNA sequencing, and Bartonella enrichment blood culture were used on a research basis to assess Bartonella spp. exposure and bloodstream infection, respectively. PCR assays targeting other vector-borne infections were performed to assess potential co-infections.

          Results:

          For 18 months, the boy remained psychotic despite 4 hospitalizations, therapeutic trials involving multiple psychiatric medication combinations, and immunosuppressive treatment for autoimmune encephalitis. Neurobartonellosis was diagnosed after cutaneous lesions developed. Subsequently, despite nearly 2 consecutive months of doxycycline administration, Bartonella henselae DNA was PCR amplified and sequenced from the patient’s blood, and from Bartonella alphaproteobacteria growth medium enrichment blood cultures. B henselae serology was negative. During treatment with combination antimicrobial chemotherapy, he experienced a gradual progressive decrease in neuropsychiatric symptoms, cessation of psychiatric drugs, resolution of Bartonella-associated cutaneous lesions, and a return to all pre-illness activities.

          Conclusions:

          This case report suggests that B henselae bloodstream infection may contribute to progressive, recalcitrant neuropsychiatric symptoms consistent with PANS in a subset of patients.

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          Most cited references31

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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: one health perspectives for an emerging infectious disease.

            In recent years, an increasing number of Bartonella species have been identified as zoonotic pathogens, transmitted by animal bites, scratches, arthropods and even by needle sticks. Considering the diversity of newly discovered Bartonella species and subspecies and the large number and ecologically diverse animal reservoir hosts and the evolving spectrum of arthropod vectors that can transmit these bacteria among animals and humans, the clinical and diagnostic challenges posed by Bartonella transmission in nature are presumably much more complex than is currently appreciated by diagnosticians, vector biologists, ecologists, physicians, or veterinarians. Historically the term "bartonellosis" was attributed to infections with Bartonella bacilliformis, transmitted by sandflies in the Peruvian Andes. Currently, however, bartonellosis now includes infections caused by any Bartonella sp. anywhere in the world. Potentially, because Bartonella spp. can infect erythrocytes, endothelial cells, pericytes, CD34(+) progenitor cells, and various macrophage-type cells, including microglial cells, dendritic cells, and circulating monocytes in vitro, the clinical and pathological manifestations of bartonellosis appear to be very diverse in both sick animals and human patients. Because 75% of emerging infectious diseases are zoonoses, many of which are vector-transmitted by an arthropod, a One Health approach to bartonellosis and other zoonotic infections is needed to properly address animal health, public health, and environmental factors that influence the distribution and transmission of these bacteria. The One Health concept encourages a spirit of cooperation among animal, environmental, and human health professionals and promotes developing integrated solutions for complex problems that impact the health of animals, humans, and the planet. Importantly, substantial research is needed to define the medical importance of this genus as a cause of animal and human illnesses.
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              Persistence of Bartonella spp. stealth pathogens: from subclinical infections to vasoproliferative tumor formation.

              Bartonella spp. are facultative intracellular bacteria that typically cause a long-lasting intraerythrocytic bacteremia in their mammalian reservoir hosts, thereby favoring transmission by blood-sucking arthropods. In most cases, natural reservoir host infections are subclinical and the relapsing intraerythrocytic bacteremia may last weeks, months, or even years. In this review, we will follow the infection cycle of Bartonella spp. in a reservoir host, which typically starts with an intradermal inoculation of bacteria that are superficially scratched into the skin from arthropod feces and terminates with the pathogen exit by the blood-sucking arthropod. The current knowledge of bacterial countermeasures against mammalian immune response will be presented for each critical step of the pathogenesis. The prevailing models of the still-enigmatic primary niche and the anatomical location where bacteria reside, persist, and are periodically seeded into the bloodstream to cause the typical relapsing Bartonella spp. bacteremia will also be critically discussed. The review will end up with a discussion of the ability of Bartonella spp., namely Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis, to induce tumor-like vascular deformations in humans having compromised immune response such as in patients with AIDS. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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                Author and article information

                Journal
                J Cent Nerv Syst Dis
                J Cent Nerv Syst Dis
                CNS
                spcns
                Journal of Central Nervous System Disease
                SAGE Publications (Sage UK: London, England )
                1179-5735
                18 March 2019
                2019
                : 11
                : 1179573519832014
                Affiliations
                [1 ]Intracellular Pathogens Research Laboratory, Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
                [2 ]Medical Arts Psychotherapy Associates P.A., Summit, NJ, USA
                [3 ]Translational Medicine Group PC, North Bethesda, MD, USA
                [4 ]Sancta Familia Center for Integrative Medicine, Columbus, OH, USA
                Author notes
                [*]Edward B Breitschwerdt, Intracellular Pathogens Research Laboratory, Comparative Medicine Institute, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA. Email: ebbreits@ 123456ncsu.edu
                Author information
                https://orcid.org/0000-0002-3506-0279
                Article
                10.1177_1179573519832014 CNS-18-0038.R1
                10.1177/1179573519832014
                6423671
                30911227
                c690a77a-62bf-47d6-8fdf-ac5ba2df51e5
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 22 October 2018
                : 21 January 2019
                Funding
                Funded by: State of North Carolina Employer for Breitschwerdt, Maggi and Bradley, ;
                Funded by: donations to the Bartonella/Vector Borne Disease Research Fund, NCSU Veterinary Medical Foundation, ;
                Categories
                Case Report
                Custom metadata
                January-December 2019

                bacteria,psychosis,transmission,stretch marks,bartonella,schizophrenia

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