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      Diagnosis of scrub typhus: recent advancements and challenges

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          Abstract

          Scrub typhus is a mite-borne, acute febrile illness caused by the bacterium Orientia tsutsugamushi. It is a re-emerging infectious disease of the tsutsugamushi triangle. Scrub typhus is transmitted through bites of contaminated chiggers (larval stage). Diagnosis of scrub typhus is challenging as its symptoms mimic with other acute febrile illnesses. Several methods are effectual for diagnosis of scrub typhus that includes enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA), immunochromatographic test (ICT), Weil–Felix, polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP). Weil–Felix test was initially used for the diagnosis of scrub typhus in underdeveloped countries but not preferred due to a lack of both specificity and sensitivity. Other immuno-based methods like IFA and ELISA are most outrank for detection of scrub typhus due to their higher sensitivity and specificity, but not vigorous to lay bare the infection at early stages and need the convalescent sampling for verification of positive samples. On another deed, PCR based methods becoming acceptable over era due to its dexterity of early-stage diagnosis with higher specificity and sensitivity but lack its applicability in circumstances of scrub typhus due to the variegated genetic makeup of Orientia tsutsugamushi among its serotypes. The present review focused on various detection methods along with their advantages and disadvantages used in the diagnosis of scrub typhus. A comparison between available methods of diagnosis with challenges in the detection of scrub typhus is also summarized.

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          Aptamers and Their Biological Applications

          Recently, aptamers have attracted the attention of many scientists, because they not only have all of the advantages of antibodies, but also have unique merits, such as thermal stability, low cost, and unlimited applications. In this review, we present the reasons why aptamers are known as alternatives to antibodies. Furthermore, several types of in vitro selection processes, including nitrocellulose membrane filtration, affinity chromatography, magnetic bead, and capillary electrophoresis-based selection methods, are explained in detail. We also introduce various applications of aptamers for the diagnosis of diseases and detection of small molecules. Numerous analytical techniques, such as electrochemical, colorimetric, optical, and mass-sensitive methods, can be utilized to detect targets, due to convenient modifications and the stability of aptamers. Finally, several medical and analytical applications of aptamers are presented. In summary, aptamers are promising materials for diverse areas, not just as alternatives to antibodies, but as the core components of medical and analytical equipment.
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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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                Author and article information

                Contributors
                deepakbiotech90cu@gmail.com
                shagungupta@shooliniuniversity.com
                rupaknagraik@shooliniuniversity.com
                vivek77verma@gmail.com
                athakur1@ggn.amity.edu
                ankur.biotech85@gmail.com , akaushal@ggn.amity.edu
                Journal
                3 Biotech
                3 Biotech
                3 Biotech
                Springer International Publishing (Cham )
                2190-572X
                2190-5738
                18 August 2020
                September 2020
                : 10
                : 9
                : 396
                Affiliations
                [1 ]GRID grid.444644.2, ISNI 0000 0004 1805 0217, Amity Center of Nanotechnology, , Amity University, ; Haryana, 122413 India
                [2 ]GRID grid.430140.2, ISNI 0000 0004 1799 5083, Shoolini University, ; Solan, 173229 India
                Author information
                https://orcid.org/0000-0003-2379-7422
                https://orcid.org/0000-0002-1981-8801
                https://orcid.org/0000-0003-2783-0007
                https://orcid.org/0000-0003-3167-2136
                https://orcid.org/0000-0002-2150-7826
                http://orcid.org/0000-0002-5922-4047
                Article
                2389
                10.1007/s13205-020-02389-w
                7431554
                8268737f-c72f-45f3-9678-d67b092ca7fa
                © King Abdulaziz City for Science and Technology 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 26 May 2020
                : 10 August 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001409, Department of Science and Technology, Ministry of Science and Technology;
                Award ID: SP/YO/079/2017
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © King Abdulaziz City for Science and Technology 2020

                biosensor,immunochromatographic test,immunoflourescence assay,polymerase chain reaction,scrub typhus,tsutsugamushi triangle

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