{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:17:26Z","timestamp":1783664246425,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Scrub typhus has nonspecific symptoms, making it easy to miss or underdiagnose. This retrospective study evaluated targeted next-generation sequencing (tNGS) for the early diagnosis of acute\n                      <jats:italic>Orientia tsutsugamushi<\/jats:italic>\n                      infection in terms of feasibility and application value.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included 49 patients with suspected scrub typhus as the case group. Among them, 28 patients with eschar or ulcers were assigned to the clinical diagnosis group. The remaining 21 patients without eschar or ulcers formed the clinically suspected group. Additionally, 48 patients with nonscrub typhus bloodstream infections during the same period were included in the negative control group. Clinical data and tNGS results were collected for all the patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No significant differences were found between the clinical diagnosis group and the clinically suspected group in sex, age, time from onset to sampling, season of onset, complications, or clinical prognosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;gt;\u202f0.05). The sensitivity of tNGS for diagnosing scrub typhus was 91.8% (45\/49), and the specificity was 100.0% (48\/48). No significant differences were observed between the clinically diagnosed group and the clinically suspected group regarding the positivity rate of\n                      <jats:italic>O. tsutsugamushi<\/jats:italic>\n                      detected by tNGS or the therapeutic response to doxycycline (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;gt;\u202f0.05). Significant changes were observed in the median eosinophil count (EOS), platelet count (PLT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) before and after doxycycline treatment in the case group (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      TNGS demonstrated high sensitivity and specificity for the detection of\n                      <jats:italic>O. tsutsugamushi<\/jats:italic>\n                      . It facilitates the early diagnosis of scrub typhus, particularly in suspected cases without eschars. However, prospective studies are needed for validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1875741","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:39:27Z","timestamp":1783661967000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Advancing the diagnosis of scrub typhus with targeted next-generation sequencing"],"prefix":"10.3389","volume":"17","author":[{"given":"Weijuan","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuni","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyi","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1007\/s11910-022-01215-5","article-title":"Neurological manifestations of scrub typhus","volume":"22","author":"Basu","year":"2022","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.rr6502a1","article-title":"Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever and other spotted fever group rickettsioses, ehrlichioses, and anaplasmosis - United States","volume":"65","author":"Biggs","year":"2016","journal-title":"MMWR Recomm Rep."},{"key":"ref2","volume-title":"Manual of Clinical Microbiology","author":"Carroll","year":"2024"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e018998","DOI":"10.1136\/bmjgh-2025-018998","article-title":"Spatiotemporal epidemiology and clinical manifestations of two decades of scrub typhus in India: a systematic review and meta-analysis","volume":"10","author":"Chaturvedi","year":"2025","journal-title":"BMJ Glob. Health"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"790","DOI":"10.4103\/ijmr.IJMR_1314_18","article-title":"Mortality due to scrub typhus - report of five cases","volume":"149","author":"Chaudhry","year":"2019","journal-title":"Indian J. Med. Res."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"810","DOI":"10.3390\/pathogens14080810","article-title":"Comprehensive laboratory analysis of a scrub typhus and H1N1 influenza co-infection: a case report from Hainan, China","volume":"14","author":"Chen","year":"2025","journal-title":"Pathogens"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"108291","DOI":"10.1016\/j.ijid.2025.108291","article-title":"Nonthyroidal illness syndrome and diagnostic utility of CSF mNGS: insights from a case series of neurological scrub typhus","volume":"163","author":"Chen","year":"2026","journal-title":"Int. J. Infect. Dis."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/s41598-024-61555-9","article-title":"Global seroprevalence of scrub typhus: a systematic review and meta-analysis","volume":"14","author":"Dasgupta","year":"2024","journal-title":"Sci. Rep."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1186\/s12879-025-11702-y","article-title":"Unveiling the unseen: generalized myoclonus status and MODS in scrub typhus, a case report and literature review","volume":"25","author":"Gan","year":"2025","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"97","DOI":"10.4103\/0974-777x.188584","article-title":"Determination of cutoff of ELISA and Immunofluorescence assay for scrub typhus","volume":"8","author":"Gupta","year":"2016","journal-title":"J. Glob. Infect. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"312","DOI":"10.53854\/liim-3203-5","article-title":"Frequency and distribution of eschar in patients with scrub typhus in India: systematic review of literature and meta-analysis","volume":"32","author":"Gupta","year":"2024","journal-title":"Infez. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.ijid.2023.12.013","article-title":"Changing epidemiologic patterns of typhus group rickettsiosis and scrub typhus in China, 1950-2022","volume":"140","author":"Han","year":"2024","journal-title":"Int. J. Infect. Dis."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e0011963","DOI":"10.1371\/journal.pntd.0011963","article-title":"Epidemiological and clinical characteristics of scrub typhus in Guizhou Province, China: an outbreak study of scrub typhus","volume":"18","author":"He","year":"2024","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1321123","DOI":"10.3389\/fpubh.2024.1321123","article-title":"mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases","volume":"12","author":"Jian","year":"2024","journal-title":"Front. Public Health"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1111\/j.1749-6632.2003.tb07380.x","article-title":"Real-time PCR duplex assay for Rickettsia prowazekii and Borrelia recurrentis","volume":"990","author":"Jiang","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e0008747","DOI":"10.1371\/journal.pntd.0008747","article-title":"Performance of molecular and serologic tests for the diagnosis of scrub typhus","volume":"14","author":"Kannan","year":"2020","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3201\/eid2301.161038","article-title":"Scrub typhus leading to acute encephalitis syndrome, Assam, India","volume":"23","author":"Khan","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e0294220","DOI":"10.1128\/jcm.02942-20","article-title":"Evaluation of the diagnostic accuracy of antibody assays for patients with scrub typhus","volume":"59","author":"Kim","year":"2021","journal-title":"J. Clin. Microbiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e2605","DOI":"10.1371\/journal.pntd.0002605","article-title":"Scrub typhus is an under-recognized cause of acute febrile illness with acute kidney injury in India","volume":"8","author":"Kumar","year":"2014","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"5832","DOI":"10.12998\/wjcc.v12.i25.5832","article-title":"Omadacycline in the treatment of scrub typhus: three case reports","volume":"12","author":"Lang","year":"2024","journal-title":"World J. Clin. Cases"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"484","DOI":"10.4269\/ajtmh.2009.81.484","article-title":"Risk factors leading to fatal outcome in scrub typhus patients","volume":"81","author":"Lee","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"3663","DOI":"10.1128\/jcm.01680-15","article-title":"Optimal cutoff Titers for indirect immunofluorescence assay for diagnosis of scrub typhus","volume":"53","author":"Lim","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e0006477","DOI":"10.1371\/journal.pntd.0006477","article-title":"Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand","volume":"12","author":"Marks","year":"2018","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1186\/s12879-017-2764-3","article-title":"Acute undifferentiated fever in India: a multicentre study of aetiology and diagnostic accuracy","volume":"17","author":"M\u00f8rch","year":"2017","journal-title":"BMC Infect. Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3760\/cma.j.issn.1674-2397.2024.06.001","article-title":"Expert consensus on the application of targeted next-generation sequencing in infectious diseases","volume":"17","year":"2024","journal-title":"Chin. J. Clin. Infect. Diseases"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1702","DOI":"10.4049\/jimmunol.1402244","article-title":"A nonhuman primate scrub typhus model: protective immune responses induced by pKarp47 DNA vaccination in cynomolgus macaques","volume":"194","author":"Paris","year":"2015","journal-title":"J. Immunol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1387208","DOI":"10.3389\/fmicb.2024.1387208","article-title":"A proof of concept for a targeted enrichment approach to the simultaneous detection and characterization of rickettsial pathogens from clinical specimens","volume":"15","author":"Paskey","year":"2024","journal-title":"Front. Microbiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"244","DOI":"10.5492\/wjccm.v4.i3.244","article-title":"Severe scrub typhus infection: clinical features, diagnostic challenges and management","volume":"4","author":"Peter","year":"2015","journal-title":"World J. Crit. Care Med."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1093\/cid\/civ116","article-title":"Risk factors for fatal outcome from rocky mountain spotted fever in a highly endemic area-Arizona, 2002-2011","volume":"60","author":"Regan","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"640","DOI":"10.4269\/ajtmh.2005.72.640","article-title":"Short report: detection of Orientia tsutsugamushi in clinical samples by quantitative real-time polymerase chain reaction","volume":"72","author":"Singhsilarak","year":"2005","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"4375","DOI":"10.3760\/cma.j.cn112137-20240927-02208","article-title":"Expert consensus on the application and practice of targeted next-generation sequencing in infectious diseases","volume":"104","year":"2024","journal-title":"Natl. Med. J. China"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"11","DOI":"10.2147\/rmhp.S55305","article-title":"Clinical risk-scoring algorithm to forecast scrub typhus severity","volume":"7","author":"Sriwongpan","year":"2013","journal-title":"Risk Manag. Healthc. Policy"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1093\/qjmed\/hcz308","article-title":"Scrub typhus in patients with acute febrile illness: a 5-year study from India","volume":"113","author":"Thakur","year":"2020","journal-title":"QJM"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3760\/cma.j.cn114452-20240817-00462","article-title":"Expert consensus on the standardized application of targeted next-generation sequencing in the infectious diseases","volume":"48","year":"2025","journal-title":"Chin. J. Lab. Med."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.ijid.2014.02.009","article-title":"Clinical profile and improving mortality trend of scrub typhus in South India","volume":"23","author":"Varghese","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1056\/NEJMp1608499","article-title":"Scrub typhus - scientific neglect, ever-widening impact","volume":"375","author":"Walker","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1753759","DOI":"10.3389\/fsurg.2026.1753759","article-title":"Scrub typhus complicated by cholecystitis: a case report","volume":"13","author":"Wang","year":"2026","journal-title":"Front. Surg."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"107151","DOI":"10.1016\/j.ijid.2024.107151","article-title":"Global and regional seroprevalence, incidence, mortality of, and risk factors for scrub typhus: a systematic review and meta-analysis","volume":"146","author":"Wang","year":"2024","journal-title":"Int. J. Infect. Dis."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"e11356","DOI":"10.1016\/j.heliyon.2022.e11356","article-title":"Successful diagnosis and treatment of scrub typhus associated with haemophagocytic lymphohistiocytosis and multiple organ dysfunction syndrome: a case report and literature review","volume":"8","author":"Wu","year":"2022","journal-title":"Heliyon"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1875741\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:39:31Z","timestamp":1783661971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1875741\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":39,"alternative-id":["10.3389\/fmicb.2026.1875741"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1875741","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"article-number":"1875741"}}