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      Scrub Typhus: Historic Perspective and Current Status of the Worldwide Presence of Orientia Species

      review-article
      1 , * , 2
      Tropical Medicine and Infectious Disease
      MDPI
      scrub typhus, Orientia species, Tsutsugamushi Triangle

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          Abstract

          Scrub typhus and its etiological agents, Orientia species, have been around for a very long time. Historical reference to the rickettsial disease scrub typhus was first described in China (313 AD) by Hong Ge in a clinical manual (Zhouhofang) and in Japan (1810 AD) when Hakuju Hashimoto described tsutsuga, a noxious harmful disease in the Niigata prefecture. Other clinicians and scientists in Indonesia, Philippines, Taiwan, Australia, Vietnam, Malaysia, and India reported on diseases most likely to have been scrub typhus in the early 1900s. All of these initial reports about scrub typhus were from an area later designated as the Tsutsugamushi Triangle—an area encompassing Pakistan to the northwest, Japan to the northeast and northern Australia to the south. It was not until the 21st century that endemic scrub typhus occurring outside of the Tsutsugamushi Triangle was considered acceptable. This report describes the early history of scrub typhus, its distribution in and outside the Tsutsugamushi Triangle, and current knowledge of the causative agents, Orientia species.

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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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            A review of the global epidemiology of scrub typhus

            Scrub typhus is a serious public health problem in the Asia-Pacific area. It threatens one billion people globally, and causes illness in one million people each year. Caused by Orientia tsutsugamushi, scrub typhus can result in severe multiorgan failure with a case fatality rate up to 70% without appropriate treatment. The antigenic heterogeneity of O. tsutsugamushi precludes generic immunity and allows reinfection. As a neglected disease, there is still a large gap in our knowledge of the disease, as evidenced by the sporadic epidemiologic data and other related public health information regarding scrub typhus in its endemic areas. Our objective is to provide a systematic analysis of current epidemiology, prevention and control of scrub typhus in its long-standing endemic areas and recently recognized foci of infection.
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              Estimating the burden of scrub typhus: A systematic review

              Background Scrub typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub typhus remains poorly known. Methods We systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub typhus since the year 2000. Findings In prospective fever studies from Asia, scrub typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%–27.9% (median 22.2% IQR 18.6–25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub typhus. Limited evidence suggests high mortality in complicated scrub typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes. Interpretation Scrub typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8–10 years from countries with an established surveillance system. A wider distribution of scrub typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches.
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                Author and article information

                Journal
                Trop Med Infect Dis
                Trop Med Infect Dis
                tropicalmed
                Tropical Medicine and Infectious Disease
                MDPI
                2414-6366
                01 April 2020
                June 2020
                : 5
                : 2
                : 49
                Affiliations
                [1 ]Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
                [2 ]Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA; jjiang@ 123456HJFresearch.org
                Author notes
                Author information
                https://orcid.org/0000-0002-1065-429X
                Article
                tropicalmed-05-00049
                10.3390/tropicalmed5020049
                7344502
                32244598
                e93790c2-69e7-44c0-a09d-9abf575e15a1
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 March 2020
                : 25 March 2020
                Categories
                Review

                scrub typhus,orientia species,tsutsugamushi triangle

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