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      The Distribution and Diversity of Bartonella Species in Rodents and Their Ectoparasites across Thailand

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          Abstract

          Our study highlights the surveillance of Bartonella species among rodents and their associated ectoparasites (ticks, fleas, lice, and mites) in several regions across Thailand. A total of 619 rodents and 554 pooled ectoparasites (287 mite pools, 62 flea pools, 35 louse pools, and 170 tick pools) were collected from 8 provinces within 4 regions of Thailand. Bandicota indica (279), Rattus rattus (163), and R. exulans (96) were the most prevalent species of rats collected in this study. Real-time PCR assay targeting Bartonella-specific ssrA gene was used for screening and each positive sample was confirmed by PCR using nuoG gene. The prevalence of Bartonella DNA in rodent (around 17%) was recorded in all regions. The highest prevalence of Bartonella species was found in B. savilei and R. rattus with the rate of 35.7% (5/14) and 32.5% (53/163), respectively. High prevalence of Bartonella-positive rodent was also found in B. indica (15.1%, 42/279), and R. norvegicus (12.5%, 5/40). In contrast, the prevalence of Bartonella species in ectoparasites collected from the rats varied significantly according to types of ectoparasites. A high prevalence of Bartonella DNA was found in louse pools ( Polyplax spp. and Hoplopleura spp., 57.1%) and flea pools ( Xenopsylla cheopis, 25.8%), while a low prevalence was found in pools of mites ( Leptotrombidium spp. and Ascoschoengastia spp., 1.7%) and ticks ( Haemaphysalis spp., 3.5%). Prevalence of Bartonella DNA in ectoparasites collected from Bartonella-positive rodents (19.4%) was significantly higher comparing to ectoparasites from Bartonella-negative rodents (8.7%). The phylogenetic analysis of 41 gltA sequences of 16 Bartonella isolates from rodent blood and 25 Bartonella-positive ectoparasites revealed a wide range of diversity among Bartonella species with a majority of sequences (61.0%) belonging to Bartonella elizabethae complex (11 rodents, 1 mite pool, and 5 louse pools), while the remaining sequences were identical to B. phoceensis (17.1%, 1 mite pool, 5 louse pools, and 1 tick pool), B. coopersplainensis (19.5%, 5 rodents, 1 louse pool, and 2 tick pools), and one previously unidentified Bartonella species (2.4%, 1 louse pool).

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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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            Disparate rates of molecular evolution in cospeciating hosts and parasites.

            DNA sequences for the gene encoding mitochondrial cytochrome oxidase I in a group of rodents (pocket gophers) and their ectoparasites (chewing lice) provide evidence for cospeciation and reveal different rates of molecular evolution in the hosts and their parasites. The overall rate of nucleotide substitution (both silent and replacement changes) is approximately three times higher in lice, and the rate of synonymous substitution (based on analysis of fourfold degenerate sites) is approximately an order of magnitude greater in lice. The difference in synonymous substitution rate between lice and gophers correlates with a difference of similar magnitude in generation times.
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              Pathogenicity and treatment of Bartonella infections.

              Bartonella spp. are responsible for emerging and re-emerging diseases around the world. The majority of human infections are caused by Bartonella henselae, Bartonella quintana and Bartonella bacilliformis, although other Bartonella spp. have also been associated with clinical manifestations in humans. The severity of Bartonella infection correlates with the patient's immune status. Clinical manifestations can range from benign and self-limited to severe and life-threatening disease. Clinical conditions associated with Bartonella spp. include local lymphadenopathy, bacteraemia, endocarditis, and tissue colonisation resulting in bacillary angiomatosis and peliosis hepatis. Without treatment, Bartonella infection can cause high mortality. To date, no single treatment is effective for all Bartonella-associated diseases. In the absence of systematic reviews, treatment decisions for Bartonella infections are based on case reports that test a limited number of patients. Antibiotics do not significantly affect the cure rate in patients with Bartonella lymphadenopathy. Patients with Bartonella spp. bacteraemia should be treated with gentamicin and doxycycline, but chloramphenicol has been proposed for the treatment of B. bacilliformis bacteraemia. Gentamicin in combination with doxycycline is considered the best treatment regimen for endocarditis, and erythromycin is the first-line antibiotic therapy for the treatment of angioproliferative lesions. Rifampicin or streptomycin can be used to treat verruga peruana. In this review, we present recent data and recommendations related to the treatment of Bartonella infections based on the pathogenicity of Bartonella spp.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 October 2015
                2015
                : 10
                : 10
                : e0140856
                Affiliations
                [1 ]Department of Entomology, United States Army Medical Directorate—Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
                [2 ]Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, United States of America
                University of the Sunshine Coast, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: RT KK. Performed the experiments: KK SP SL. Analyzed the data: RT KK MK. Wrote the paper: RT KK ALS PWM.

                Article
                PONE-D-15-18152
                10.1371/journal.pone.0140856
                4617648
                26484537
                d09f8910-0d4a-48f9-88a6-5dbc3af95e5c

                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
                : 29 April 2015
                : 1 October 2015
                Page count
                Figures: 1, Tables: 7, Pages: 16
                Funding
                This work has been supported by the Department of Defense Global Emerging Infections Surveillance and Response System (GEIS, https://www.afhsc.mil/Home/Divisions/GEIS). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                All relevant data are within the paper and its Supporting Information files.

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