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      Scrub typhus, a salient threat: Needs attention

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      Journal: PLOS Neglected Tropical Diseases
      Publisher: Public Library of Science

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          Abstract

          Scrub typhus (ST) infection is one of the most significant causes of acute undifferentiated febrile illness, and its prevalence has been increasing across the globe. Clinical suspicion and growing clinical understanding among healthcare professionals have resulted in the rapid diagnosis and effective management. Since ST has the potential to cause multiorgan failure and a higher mortality rate, it is critical to enhance surveillance, make rapid diagnosis, and administer antibiotics appropriately.

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          Most cited references21

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          A review of the global epidemiology of scrub typhus

          Guang Zhou Xu, David Walker, Daniel Jupiter … (2017)
          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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            State of the art of diagnosis of rickettsial diseases: the use of blood specimens for diagnosis of scrub typhus, spotted fever group rickettsiosis, and murine typhus

            Daniel Paris, J. Dumler (2016)
            Purpose of review With improved malaria control, acute undifferentiated febrile illness studies in tropical regions reveal a startling proportion of rickettsial illnesses, especially scrub typhus, murine typhus, and spotted fever group rickettsioses. Laboratory diagnosis of these infections evolved little over the past 40 years, but combinations of technologies like PCR and loop-mediated isothermal amplification, with refined rapid diagnostic tests and/or ELISA, are promising for guidance for early antirickettsial treatment. Recent findings The long-term reliance on serological tests – useful only late in rickettsial infections – has led to underdiagnosis, inappropriate therapies, and undocumented morbidity and mortality. Recent approaches integrate nucleic acid amplification and recombinant protein-based serological tests for diagnosing scrub typhus. Optimized using Bayesian latent class analyses, this strategy increases diagnostic confidence and enables early accurate diagnosis and treatment – a model to follow for lagging progress in murine typhus and spotted fever. Summary A laboratory diagnostic paradigm shift in rickettsial infections is evolving, with replacement of indirect immunofluorescence assay by the more objective ELISA coupled with nucleic acid amplification assays to expand the diagnostic window toward early infection intervals. This approach supports targeted antirickettsial therapy, reduces morbidity and mortality, and provides a robust evidence base for further development of diagnostics and vaccines.
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              Scrub typhus point-of-care testing: A systematic review and meta-analysis

              Kartika Saraswati, Nicholas Day, Mavuto Mukaka … (2018)
              Background Diagnosing scrub typhus clinically is difficult, hence laboratory tests play a very important role in diagnosis. As performing sophisticated laboratory tests in resource-limited settings is not feasible, accurate point-of-care testing (POCT) for scrub typhus diagnosis would be invaluable for patient diagnosis and management. Here we summarise the existing evidence on the accuracy of scrub typhus POCTs to inform clinical practitioners in resource-limited settings of their diagnostic value. Methodology/principal findings Studies on POCTs which can be feasibly deployed in primary health care or outpatient settings were included. Thirty-one studies were identified through PubMed and manual searches of reference lists. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). About half (n = 14/31) of the included studies were of moderate quality. Meta-analysis showed the pooled sensitivity and specificity of commercially available immunochromatographic tests (ICTs) were 66.0% (95% CI 0.37–0.86) and 92.0% (95% CI 0.83–0.97), respectively. There was a significant and high degree of heterogeneity between the studies (I2 value = 97.48%, 95% CI 96.71–98.24 for sensitivity and I2 value = 98.17%, 95% CI 97.67–98.67 for specificity). Significant heterogeneity was observed for total number of samples between studies (p = 0.01), study design (whether using case-control design or not, p = 0.01), blinding during index test interpretation (p = 0.02), and QUADAS-2 score (p = 0.01). Conclusions/significance There was significant heterogeneity between the scrub typhus POCT diagnostic accuracy studies examined. Overall, the commercially available scrub typhus ICTs demonstrated better performance when ‘ruling in’ the diagnosis. There is a need for standardised methods and reporting of diagnostic accuracy to decrease between-study heterogeneity and increase comparability among study results, as well as development of an affordable and accurate antigen-based POCT to tackle the inherent weaknesses associated with serological testing.
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                Author and article information

                Contributors
                Kamran Zaman:
                ORCID: https://orcid.org/0000-0003-0172-7423
                Role: ConceptualizationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Sivanantham Krishnamoorthi: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS Negl Trop Dis
                Journal ID (iso-abbrev): PLoS Negl Trop Dis
                Journal ID (publisher-id): plos
                Title: PLOS Neglected Tropical Diseases
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Print): 1935-2727
                ISSN (Electronic): 1935-2735
                Publication date (Electronic): 29 June 2023
                Publication date Collection: June 2023
                Volume: 17
                Issue: 6
                Electronic Location Identifier: e0011427
                Affiliations
                [001] Scientist E, Department of Microbiology and Molecular Biology, Indian Council of Medical Research - National Institute of Traditional Medicine Belagavi (ICMR-NITM Belagavi), Karnataka, India
                All India Institute of Medical Sciences - Bathinda, INDIA
                Author notes

                The author has declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-0172-7423
                Article
                Publisher ID: PNTD-D-22-01547
                DOI: 10.1371/journal.pntd.0011427
                PMC ID: 10309619
                SO-VID: b5f20e73-fe37-4550-af18-c1c90e814064
                Copyright © © 2023 Kamran Zaman
                License:

                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
                Page count
                Figures: 0, Tables: 0, Pages: 4
                Funding
                The author received no specific funding for this work
                Categories
                Subject: Viewpoints
                Subject: Research and Analysis Methods
                Subject: Immunologic Techniques
                Subject: Immunoassays
                Subject: Enzyme-Linked Immunoassays
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Infectious Diseases
                Subject: Pediatric Infections
                Subject: Medicine and Health Sciences
                Subject: Pediatrics
                Subject: Pediatric Infections
                Subject: Medicine and Health Sciences
                Subject: Health Care
                Subject: Health Care Facilities
                Subject: People and Places
                Subject: Geographical Locations
                Subject: Asia
                Subject: India
                Subject: Medicine and Health Sciences
                Subject: Pharmacology
                Subject: Drugs
                Subject: Antimicrobials
                Subject: Antibiotics
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Microbial Control
                Subject: Antimicrobials
                Subject: Antibiotics
                Subject: Medicine and Health Sciences
                Subject: Medical Conditions
                Subject: Infectious Diseases
                Subject: Bacterial Diseases
                Subject: Typhus
                Subject: Scrub Typhus
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Eukaryota
                Subject: Animals
                Subject: Invertebrates
                Subject: Arthropoda
                Subject: Mites
                Subject: Biology and Life Sciences
                Subject: Zoology
                Subject: Animals
                Subject: Invertebrates
                Subject: Arthropoda
                Subject: Mites
                Subject: Medicine and Health Sciences
                Subject: Epidemiology
                Subject: Medical Risk Factors

                ScienceOpen disciplines: Infectious disease & Microbiology
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                ScienceOpen disciplines: Infectious disease & Microbiology

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