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      Scrub Typhus, a Disease with Increasing Threat in Guangdong, China

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          Abstract

          There has been a rapid increase in the number of scrub typhus cases in Guangdong Province, China. For this reason, an epidemiologic study was conducted to understand the characteristics of scrub typhus epidemics in Guangdong. From 2006 to 2013, the incidence of human cases increased from 0.4321 to 3.5917 per 100,000 with a bimodal peak in human cases typically occurring between May and November. To detect the prevalence of Orientia tsutsugamushi among suspected human cases and rodents, we performed ELISA tests of IgM/IgG and nested PCR tests on 59 whole blood samples from the suspected cases and 112 spleen samples from the rodents. Suspected cases tested positive for anti- O. tsutsugamushi IgM and IgG 66.1% (39/59) and 50.8% (30/59) of the time, respectively. Additionally, 20.3% (12/59) of blood samples and 13.4% (15/112) of spleen samples were positive for PCR. Phylogenetic analysis revealed that there were four definable clusters among the 27 nucleotide sequences of the 56-kDa antigen genes: 44.4% Karp (12/27), 25.9% Kato (7/27), 22.2% Gilliam (6/27) and 7.4% TA763 (2/27). We concluded many suspected cases may result in diagnostic errors; therefore, it is necessary to perform laboratory tests on suspected cases in hospitals. The high infection rate of O. tsutsugamushi among the limited rodents tested suggested that further rodent sampling throughout the province is necessary to further define high-risk areas. Furthermore, the multiple co-circulating genotypes of O. tsutsugamushi play a key role in the pervasiveness of scrub typhus in the Guangdong area.

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          Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi.

          Orientia tsutsugamushi is the etiological agent of scrub typhus, an acute, mite-borne, febrile illness that occurs in the Asia-Pacific region. Historically, strain characterization used serological analysis and revealed dramatic antigenic diversity. Eyeing a recommendation of potential vaccine candidates for broad protection, we review geographic diversity and serological and DNA prevalences. DNA analysis together with immunological analysis suggest that the prototype Karp strain and closely related strains are the most common throughout the region of endemicity. According to serological analysis, approximately 50% of isolates are seroreactive to Karp antisera, and approximately one-quarter of isolates are seroreactive to antisera against the prototype Gilliam strain. Molecular methods reveal greater diversity. By molecular methods, strains phylogenetically similar to Karp make up approximately 40% of all genotyped isolates, followed by the JG genotype group (Japan strains serotypically similar to the Gilliam strain but genetically non-Gilliam; 18% of all genotyped isolates). Three other genotype groups (Kato-related, Kawasaki-like, and TA763-like) each represent approximately 10% of genotyped isolates. Strains genetically similar to the Gilliam strain make up only 5% of isolates. Strains from these groups should be included in any potential vaccine.
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            Diagnosis of Scrub Typhus

            Scrub typhus is transmitted by trombiculid mites and is endemic to East and Southeast Asia and Northern Australia. The clinical syndrome classically consists of a fever, rash, and eschar, but scrub typhus also commonly presents as an undifferentiated fever that requires laboratory confirmation of the diagnosis, usually by indirect fluorescent antibody (IFA) assay. We discuss the limitations of IFA, debate the value of other methods based on antigen detection and nucleic acid amplification, and outline recommendations for future study.
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              The past and present threat of rickettsial diseases to military medicine and international public health.

              Morbidity and mortality caused by rickettsioses have had a major influence on military activities and public health for >2000 years. The threat posed by the rickettsioses is reviewed, focusing on the impact and epidemiology of those that have adversely influenced wartime operations and the current challenges posed by these diseases. With their uneven worldwide distribution, the discovery of drug-refractory strains of Orientia tsutsugamushi, the increased threat of their use in acts of bioterrorism, frequent deployment of troops to regions of endemicity, and exposures due to increased humanitarian missions, these diseases continue to be a threat to military personnel in the field. Effective strategies to reduce the impact of these diseases include development of effective vaccines, enhanced surveillance, and development of new safe, effective, and odorless repellants. The continuation of a proven, highly productive military infectious disease research program is essential for providing solutions to these daunting tasks.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2015
                17 February 2015
                : 10
                : 2
                : e0113968
                Affiliations
                [1 ]Institute of Pathogenic Microbiology, Center for Disease Control and Prevention of Guangdong, Guangzhou, People’s Republic of China
                [2 ]Metabiota, Inc., San Francisco, California, United States of America
                [3 ]Department of Biological Sciences, Humboldt State University, Arcata, California 95521, United States of America
                University of Minnesota, UNITED STATES
                Author notes

                Competing Interests: Metabiota Inc., provided funding towards this study. Co-author Corina Monagin is employed by Metabiota, Inc. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: CWK JYL. Performed the experiments: DW JK HZ HQZ PH. Analyzed the data: DW CM JMZ. Contributed reagents/materials/analysis tools: DW JMZ. Wrote the paper: DW JMZ CM.

                Article
                PONE-D-14-23695
                10.1371/journal.pone.0113968
                4331496
                25689778
                d748b3da-6beb-41f6-8ed4-3ca41c37bb41
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 2 June 2014
                : 2 November 2014
                Page count
                Figures: 4, Tables: 1, Pages: 11
                Funding
                Blood sample collection of suspected cases and surveillance data analysis were supported by the Twelfth Five-Year Medical Research Key Project of PLA (AWS 11L 009), samples collection of rodents and sequencing were supported by Metabiota Inc. (formally known as Global Viral Forecasting). Co-author Corina Monagin is employed by Metabiota, Inc. Metabiota, Inc. provided support in the form of salary for author CM, and helped in the preparation of the manuscript, but did not have any additional role in the study design, data collection and analysis, or decision to publish.
                Categories
                Research Article
                Custom metadata
                The partial 56-kDa TSA gene sequences from this study are available in GenBank with the following accession numbers: KJ188179-KJ188198.KM492919-KM492925.

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