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      Emerging Infectious Disease Implications of Invasive Mammalian Species: The Greater White-Toothed Shrew ( Crocidura russula) Is Associated With a Novel Serovar of Pathogenic Leptospira in Ireland

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          Abstract

          The greater white-toothed shrew ( Crocidura russula) is an invasive mammalian species that was first recorded in Ireland in 2007. It currently occupies an area of approximately 7,600 km 2 on the island. C. russula is normally distributed in Northern Africa and Western Europe, and was previously absent from the British Isles. Whilst invasive species can have dramatic and rapid impacts on faunal and floral communities, they may also be carriers of pathogens facilitating disease transmission in potentially naive populations. Pathogenic leptospires are endemic in Ireland and a significant cause of human and animal disease. From 18 trapped C. russula, 3 isolates of Leptospira were cultured. However, typing of these isolates by standard serological reference methods was negative, and suggested an, as yet, unidentified serovar. Sequence analysis of 16S ribosomal RNA and secY indicated that these novel isolates belong to Leptospira alstonii, a unique pathogenic species of which only 7 isolates have been described to date. Earlier isolations were limited geographically to China, Japan and Malaysia, and this leptospiral species had not previously been cultured from mammals. Restriction enzyme analysis (REA) further confirms the novelty of these strains since no similar patterns were observed with a reference database of leptospires. As with other pathogenic Leptospira species, these isolates contain lipL32 and do not grow in the presence of 8-azagunaine; however no evidence of disease was apparent after experimental infection of hamsters. These isolates are genetically related to L. alstonii but have a novel REA pattern; they represent a new serovar which we designate as serovar Room22. This study demonstrates that invasive mammalian species act as bridge vectors of novel zoonotic pathogens such as Leptospira.

          Author Summary

          Leptospirosis is a global zoonotic disease. Pathogenic species of Leptospira are excreted in urine from asymptomatic carrier hosts which facilitates disease transmission to new hosts. To date, there are 10 species of pathogenic leptospires which comprise more than 200 serovars. Disease transmission of these strains is maintained by a wide range of domestic and wild animal species. In this work, we discovered that an invasive mammalian species, the greater white toothed shrew, which was first identified in Ireland in 2007, acts as a carrier for a species of leptospires never before identified in Ireland. Results demonstrate that invasive mammalian species act as bridge vectors of novel zoonotic pathogens such as Leptospira.

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          Leptospirosis: a zoonotic disease of global importance.

          In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.
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            Globalization, land use, and the invasion of West Nile virus.

            Many invasive species that have been spread through the globalization of trade and travel are pathogens. A paradigmatic case is the introduction of West Nile virus (WNV) into North America in 1999. A decade of research on the ecology and evolution of WNV includes three findings that provide insight into the outcome of future pathogen introductions. First, WNV transmission in North America is highest in urbanized and agricultural habitats, in part because the hosts and vectors of WNV are abundant in human-modified areas. Second, after its introduction, the virus quickly adapted to infect local mosquito vectors more efficiently than the originally introduced strain. Third, highly focused feeding patterns of the mosquito vectors of WNV result in unexpected host species being important for transmission. This research provides a framework for predicting and preventing the emergence of foreign vector-borne pathogens.
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              Global Burden of Leptospirosis: Estimated in Terms of Disability Adjusted Life Years

              Background Leptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis can cause life-threatening disease, there is no global burden of disease estimate in terms of Disability Adjusted Life Years (DALYs) available. Methodology/Principal Findings We utilised the results of a parallel publication that reported global estimates of morbidity and mortality due to leptospirosis. We estimated Years of Life Lost (YLLs) from age and gender stratified mortality rates. Years of Life with Disability (YLDs) were developed from a simple disease model indicating likely sequelae. DALYs were estimated from the sum of YLLs and YLDs. The study suggested that globally approximately 2·90 million DALYs are lost per annum (UIs 1·25–4·54 million) from the approximately annual 1·03 million cases reported previously. Males are predominantly affected with an estimated 2·33 million DALYs (UIs 0·98–3·69) or approximately 80% of the total burden. For comparison, this is over 70% of the global burden of cholera estimated by GBD 2010. Tropical regions of South and South-east Asia, Western Pacific, Central and South America, and Africa had the highest estimated leptospirosis disease burden. Conclusions/Significance Leptospirosis imparts a significant health burden worldwide, which approach or exceed those encountered for a number of other zoonotic and neglected tropical diseases. The study findings indicate that highest burden estimates occur in resource-poor tropical countries, which include regions of Africa where the burden of leptospirosis has been under-appreciated and possibly misallocated to other febrile illnesses such as malaria.
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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
                9 December 2016
                December 2016
                : 10
                : 12
                : e0005174
                Affiliations
                [1 ]Infectious Bacterial Diseases Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa, United States of America
                [2 ]University Centre of Veterinary Medicine JU-UAK, University of Agriculture, Krakow, Poland
                [3 ]OIE Leptospirosis Reference Laboratory, Veterinary Sciences Division, AFBI, Belfast, Northern Ireland, United Kingdom
                [4 ]UCD School of Agriculture & Food Science, University College Dublin, Belfield, Dublin, Ireland
                [5 ]UCD School of Biology & Environmental Science and UCD Earth Institute, University College Dublin, Belfield, Dublin, Ireland
                [6 ]UCD Centre for Food Safety, School of Public Health, Physiotherapy & Sports Science, University College Dublin, Belfield, Dublin, Ireland
                [7 ]Ecosystems and Environment Research Centre, School of Environment and Life Sciences, University of Salford, Salford, United Kingdom
                Instituto Butantan, BRAZIL
                Author notes

                The authors have declared that no competing interests exist.

                • Conceptualization: JEN BJM.

                • Data curation: DOB CG.

                • Formal analysis: JEN DOB ZA CG.

                • Funding acquisition: JEN BJM ZA ADM JY SF.

                • Investigation: JEN ZA DOB RLH CG SR ADM JY SF BJM.

                • Methodology: JEN ZA DOB RLH CG.

                • Project administration: JEN BJM.

                • Resources: JEN RLH ZA ADM JY SF BJM.

                • Software: DOB.

                • Supervision: JEN ZA JY BJM.

                • Validation: JEN ZA DOB RLH CG.

                • Visualization: JEN RLH DOB ZA CG.

                • Writing – original draft: JEN ZA DOB JY SF BJM.

                • Writing – review & editing: JEN ZA DOB RLH ADM JY SF BJM.

                Article
                PNTD-D-16-01622
                10.1371/journal.pntd.0005174
                5147805
                27935961
                7cf7375e-dd16-4ef7-a446-e2609f3420be

                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 September 2016
                : 8 November 2016
                Page count
                Figures: 4, Tables: 3, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100002081, Irish Research Council;
                Award ID: PD/2011/2093
                Award Recipient : Allan McDevitt
                Funded by: funder-id http://dx.doi.org/10.13039/501100001591, Heritage Council;
                Award ID: R02511
                Award Recipient : Allan McDevitt
                ADM acknowledges funding from the Irish Research Council (grant: PD/2011/2093), the Heritage Council, Ireland (grant: R02511), a Heredity fieldwork grant awarded by the Genetics Society, and the Vincent Wildlife Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Bacteria
                Leptospira
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Leptospira
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Leptospira
                Ecology and Environmental Sciences
                Species Colonization
                Invasive Species
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Bacterial Pathogens
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Serum
                Immune Serum
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Serum
                Immune Serum
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Blood Serum
                Immune Serum
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Blood
                Blood Serum
                Immune Serum
                Medicine and Health Sciences
                Hematology
                Blood
                Blood Serum
                Immune Serum
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Rodents
                Hamsters
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Shrews
                Biology and Life Sciences
                Veterinary Science
                Veterinary Diseases
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. The annotated assembly for L. alstonii serovar Room22 strain GWTS #1 is available in GenBank under the accession numbers CP015217 (Chromosome I) and CP015218 (Chromosome II).

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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