{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T02:45:24Z","timestamp":1775011524607,"version":"3.50.1"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Orientia tsutsugamushi<\/jats:italic>, the causative agent of scrub typhus, is increasingly recognised for its neurological complications. Among these, movement and gait disorders are poorly understood. We systematically examined their clinical spectrum and explored underlying mechanisms through in\u2010silico protein\u2013protein interaction modelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review was conducted following PRISMA guidelines, including studies published up to 5 November 2024. Principal component analysis was used to identify clinical patterns among neurological features. In\u2010silico protein\u2013protein interaction modelling was used to examine potential cross\u2010reactivity between <jats:italic>Orientia tsutsugamushi<\/jats:italic> proteins and human targets proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 76 cases, 50 presented with either isolated or combined movement disorders, most commonly opsoclonus (64.0%, 32\/50), with the opsoclonus\u2010myoclonus combination predominating (59.4%, 19\/32). Other hyperkinetic features included tremor (4.0%, 2\/50) and distinct forms of myoclonus\u00a0(without opsoclonus)\u00a0(8.0, 4\/50%). Parkinsonism was present in 26.0% (13\/50) of cases. Gait disorders, excluding parkinsonian gait and instability due to myoclonus, were well\u2010characterised in 27 patients, one of whom had concomitant opsoclonus and cerebellar ataxia. Ataxic gait was the predominant pattern, observed in 96.3% (26\/27), primarily cerebellar in origin. Principal component analysis revealed five principal components reflecting distinct clinical clusters: cerebellar dysfunction, tremor and parkinsonism, sensory ataxia and spinal involvement, myoclonus (diaphragmatic\/action\/segmental), and prolonged recovery and cranial nerve involvement. In\u2010silico analyses revealed high\u2010confidence interactions between bacterial epitopes and host proteins, including fibronectin\u20101 and Golgi\u2010associated molecules, suggesting mechanisms of immune\u2010mediated injury and neuroinflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Scrub typhus may lead to a range of movement and gait disorders through neuroimmune mechanisms and molecular mimicry. Principal component analysis offered a data\u2010driven framework to classify these manifestations, highlighting clinically relevant patterns. Early recognition and targeted treatment are critical to improving outcomes. Future studies should validate the molecular targets identified and evaluate immunomodulatory strategies for therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tmi.14114","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T05:30:17Z","timestamp":1745299817000},"page":"459-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Scrub typhus\u2010associated movement and gait disorders: A systematic review with principal component analysis and in silico mechanistic modelling"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-7661","authenticated-orcid":false,"given":"Ritwick","family":"Mondal","sequence":"first","affiliation":[{"name":"Department of Neurology Manipal Groups of Hospitals  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-4063","authenticated-orcid":false,"given":"Shramana","family":"Deb","sequence":"additional","affiliation":[{"name":"Department of Neurology Manipal Groups of Hospitals  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mrinmay","family":"Dhauria","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Regional Centre for Biotechnology  Faridabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purbita","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Neurology Manipal Groups of Hospitals  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vramanti","family":"Sarkar","sequence":"additional","affiliation":[{"name":"SN Pradhan Centre for Neuroscience University of Calcutta  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shramana","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IPGMER and SSKM Hospital  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dipanjan","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IPGMER and SSKM Hospital  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-9537","authenticated-orcid":false,"given":"Durjoy","family":"Lahiri","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine Queen's University  Kingston Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-2619","authenticated-orcid":false,"given":"Jayanta","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Neurology Manipal Groups of Hospitals  Kolkata India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-4809","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Benito\u2010Le\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Neurology 12 de Octubre University Hospital  Madrid Spain"},{"name":"Group of Neurodegenerative Diseases Hospital Universitario 12 de Octubre Research Institute (imas12)  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"},{"name":"Department of Medicine Complutense University  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prdoa.2024.100233"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13275"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000731"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13224"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10393-019-01409-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006062"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4103\/aian.aian_739_21"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2014.02.009"},{"key":"e_1_2_8_10_1","unstructured":"Team J. 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