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      Geographic Distribution and Genetic Characterization of Lassa Virus in Sub-Saharan Mali

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          Abstract

          Background

          Lassa fever is an acute viral illness characterized by multi-organ failure and hemorrhagic manifestations. Lassa fever is most frequently diagnosed in Nigeria, Sierra Leone, Liberia, and Guinea, although sporadic cases have been recorded in other West African countries, including Mali. The etiological agent of Lassa fever is Lassa virus (LASV), an Arenavirus which is maintained in nature and frequently transmitted to humans by Mastomys natalensis. The purpose of this study was to better define the geographic distribution of LASV-infected rodents in sub-Saharan Mali.

          Methodologies/Principal Findings

          Small mammals were live-trapped at various locations across Mali for the purpose of identifying potential zoonotic pathogens. Serological and molecular assays were employed and determined LASV infected rodents were exclusively found in the southern Mali near the border of Côte d'Ivoire. Overall, 19.4% of Mastomys natalensis sampled in this region had evidence of LASV infection, with prevalence rates for individual villages ranging from 0 to 52%. Full-length genomic sequences were determined using high throughput sequencing methodologies for LASV isolates generated from tissue samples of rodents collected in four villages and confirmed the phylogenetic clustering of Malian LASV with strain AV.

          Conclusions/Significance

          The risk of human infections with LASV is greatest in villages in southern Mali. Lassa fever should be considered in the differential diagnosis for febrile individuals and appropriate diagnostic techniques need to be established to determine the incidence of infection and disease in these regions.

          Author Summary

          Lassa fever is an acute infection associated with hemorrhagic manifestations and multi-organ failure in West Africa. The etiological agent of Lassa fever is Lassa virus (LASV), a rodent-borne arenavirus, which is maintained in nature and transmitted to humans by the multimammate rat, Mastomys natalensis. Despite the ubiquitous nature of the rodent reservoir, LASV-infected animals are most commonly documented in Nigeria, Sierra Leone, Guinea and Liberia. These four countries represent the historic endemic region for Lassa fever, although there is increasing evidence of sporadic cases occurring in other West African nations including Mali. To better define the geographic distribution of LASV-infected rodents in Mali, we tested samples from small animals collected at 27 sites across the country. Although M. natalensis was the predominant rodent species in the majority of villages, evidence of LASV infection was exclusively found in southern Mali, where overall nearly 20% of rodents were positive. The full genomic sequence was determined for five isolates and confirmed LASV in Mali is closely related to strain AV. We conclude that there is a risk of human exposure to LASV in villages in southern Mali and Lassa fever should be considered in the differential diagnosis for acutely ill, febrile patients.

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          Most cited references18

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          Imported lassa fever in Germany: molecular characterization of a new lassa virus strain.

          We describe the isolation and characterization of a new Lassa virus strain imported into Germany by a traveler who had visited Ghana, Côte D'Ivoire, and Burkina Faso. This strain, designated "AV," originated from a region in West Africa where Lassa fever has not been reported. Viral S RNA isolated from the patient's serum was amplified and sequenced. A long-range reverse transcription polymerase chain reaction allowed amplification of the full-length (3.4 kb) S RNA. The coding sequences of strain AV differed from those of all known Lassa prototype strains (Josiah, Nigeria, and LP) by approximately 20%, mainly at third codon positions. Phylogenetically, strain AV appears to be most closely related to strain Josiah from Sierra Leone. Lassa viruses comprise a group of genetically highly diverse strains, which has implications for vaccine development. The new method for full-length S RNA amplification may facilitate identification and molecular analysis of new arenaviruses or arenavirus strains.
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            Lassa fever.

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              Experimental infection model for Sin Nombre hantavirus in the deer mouse (Peromyscus maniculatus).

              The relationship between hantaviruses and their reservoir hosts is not well understood. We successfully passaged a mouse-adapted strain of Sin Nombre virus from deer mice (Peromyscus maniculatus) by i.m. inoculation of 4- to 6-wk-old deer mouse pups. After inoculation with 5 ID(50), antibodies to the nucleocapsid (N) antigen first became detectable at 14 d whereas neutralizing antibodies were detectable by 7 d. Viral N antigen first began to appear in heart, lung, liver, spleen, and/or kidney by 7 d, whereas viral RNA was present in those tissues as well as in thymus, salivary gland, intestine, white fat, and brown fat. By 14 d nearly all tissues examined displayed both viral RNA and N antigen. We noted no consistent histopathologic changes associated with infection, even when RNA load was high. Viral RNA titers peaked on 21 d in most tissues, then began to decline by 28 d. Infection persisted for at least 90 d. The RNA titers were highest in heart, lung, and brown fat. Deer mice can be experimentally infected with Sin Nombre virus, which now allows provocative examination of the virus-host relationship. The prominent involvement of heart, lung, and brown fat suggests that these sites may be important tissues for early virus replication or for maintenance of the virus in nature.
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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, USA )
                1935-2727
                1935-2735
                December 2013
                5 December 2013
                : 7
                : 12
                : e2582
                Affiliations
                [1 ]Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
                [2 ]Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali
                [3 ]Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
                [4 ]Rocky Mountain Laboratory Research Technologies Section, Genomics Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
                [5 ]Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
                [6 ]Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
                [7 ]Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America
                [8 ]Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, Louisiana, United States of America
                [9 ]Autoimmune Technologies LLC, New Orleans, Louisiana, United States of America
                Centers for Disease Control and Prevention, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: DS NS TGS HF. Performed the experiments: DS NS JEL OM MZ FF EH RJF JMA VJM TGS HF. Analyzed the data: DS ED. Contributed reagents/materials/analysis tools: LB RG SFP. Wrote the paper: DS.

                [¤]

                Current address: Department of Biological Sciences, Mississippi State University, Starkville, Mississippi, United States of America.

                Article
                PNTD-D-13-01146
                10.1371/journal.pntd.0002582
                3855028
                24340119
                031ae470-2a8e-4540-9e75-612b81cfaabf
                Copyright @ 2013

                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 August 2013
                : 28 October 2013
                Page count
                Pages: 9
                Funding
                This work was funded by the International Centers for Excellence in Research program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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