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Neurological Manifestations of Scrub Typhus

  • Neurology of Systemic Diseases (J. Biller, Section Editor)
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Abstract

Purpose of Review

The occurrence of cases of scrub typhus is on the rise in South Asian and Southeast Asian countries. The present review discusses neurological complications following scrub typhus to appraise clinicians practicing in endemic regions about considering this treatable disease in the differential diagnosis of acute febrile illnesses, especially when accompanied with clinical neurological features.

Recent Findings

While the association of aseptic meningitis, encephalitis, and meningoencephalitis with scrub typhus is well known, more recently described neurological syndromes associated with scrub typhus include acute disseminated encephalomyelitis, various cranial nerve palsies, cerebellitis, cerebrovascular diseases including cerebral venous sinus thrombosis, transverse myelitis, longitudinally extensive transverse myelitis, Guillain-Barré syndrome, opsoclonus-myoclonus syndrome, parkinsonism, and many more. Early diagnosis is key to successful treatment. While diagnostic confirmation is generally made by the detection of IgM antibody by either ELISA or indirect fluorescent antibody tests, conventional PCR using 56 kDa gene (cPCR) and loop-mediated isothermal amplification assay (LAMP assay), as well as a newly introduced metagenomic next-generation sequencing (mNGS), are currently available for detection of Orientia tsutsugamushi infection in clinically suspected cases.

Summary

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The cutaneous hallmark of the disease is the “eschar.” Scrub typhus results in multisystem involvement. Neurological compromise is present in about 20% of scrub typhus patients and affects both the central nervous system and the peripheral nervous system. The postulated underlying mechanisms include direct invasion of the organism, a vasculitis-like process, or an immune-mediated injury. Diagnosis of scrub typhus is confirmed by detection of O. tsutsugamushi IgM antibody in serum. Awareness among clinicians regarding the varied presentations of this disease is very important in order to reduce morbidity and mortality. Co-infection with dengue and/or chickungunya viruses may occur in endemic regions. The history of an acute febrile illness preceding the neurological illness is crucial. A very careful search for the eschar is essential; however, the absence of the skin lesion cannot exclude the diagnosis of scrub typhus. Neurological manifestations mostly respond to doxycycline therapy.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. ••Bonell A, Lubell Y, Newton PN, Crump JA, Paris DH. Estimating the burden of scrub typhus: a systematic review.PLos Negl Trop Dis. 2017;11:e0005838. https://doi.org/10.1371/Journal.pntd.0005838. A highly informative epidemiological study of scrub typhus in South Asian and Southeast Asian countries.

  2. Red Mites and Typhus, by J. R. Audy. University of London Heath Clark Lectures 1965; pp 191. University of London—The Athlone Press, London

  3. Palm TA. Some account of the disease called ‘shima-mushi’ or ‘island insect disease’ by the natives of Japan; peculiar, it is believed and hitherto not described. Edinb Med J. 1878;24(1):128–32.

    PubMed  PubMed Central  Google Scholar 

  4. Shao P, You Xing W, Hashimoto H. Pioneers of epidemic doctrine in the history of diseases in China and Japan. Jpn J Soc Med His. 2001;47:604–5.

    Google Scholar 

  5. Chunchanur SK, Venugopal SJ, Ambica R, Dakshayani B. Phylogenetic diversity of Orientia tsutsugamushi isolates in patients with scrub typhus in Bengaluru, India. Indian J Med Microbiol. 2019;37(3):438–441. https://doi.org/10.4103/ijmm.IJMM_19_267

  6. Jamil M, Bhattacharyya P, Mishra J, Akhtar H, Roy A. Eschar in scrub typhus. A study from North-East India. J Assoc Physicians India. 2019;67:38–40.

    PubMed  Google Scholar 

  7. Sood AK, Chauhan L, Gupta H. CNS manifestations in Orientia tsutsugamushi disease (scrub typhus) in North India. Indian J Paediatr. 2016;83:634–9.

    Google Scholar 

  8. Verghese GM, Mathew A, Kumar S, Abraham OC, Trowbridge P, Mathai E. Differential diagnosis of scrub typhus meningitis from bacterial meningitis using clinical and laboratory features. Neurol India. 2013;61:17.

    Google Scholar 

  9. Dubot-Peres A, Mayxay M, Phetsouvanti R, Lees SJ, Rattanavong S, Vongsouvath M, et al. Management of central nervous infections, Vientiane, Laos 2003–2011. Emerg Infect Dis. 2019;25(5):898–910. https://doi.org/10.3201/eid2505.180914.

    Article  PubMed  PubMed Central  Google Scholar 

  10. • Jain P, Prakash S, Tripathi PK, Chauhan A, Gupta S, Sharma U et al. Emergence of O. tsutsugamushi as an important cause of acute encephalitic syndrome in India. PLosNegl Trop Dis. 2018;12(3):e 0006346. https://doi.org/10.1371/Journal.pntd0006346. Highlights the importance of recognizing scrub typhus as an important cause of acute encephalitic syndrome in tropical countries like India.

  11. •Boorugu H, Chrispol A, Gopinath KG, S. Chandy, Prakash JJ, Abraham AM et al. Central nervous involvement in scrub typhus. Trop Doct. 2014;44:36–7. In this prospective observational study, altered sensorium, headache, seizures and aseptic meningitis were found to be common central nervous system manifestations of scrub typhus. Prompt treatment with doxycycline reduces morbidity and mortality.

  12. •Rana A, Mahajan SK, Sharma A, Verma BS, Sharma A. Neurological manifestations scrub typhus in adults. Trop Doct. 2017;47:22–5. The authors studied 323 cases of Scrub typhus for neurological manifestations. These included: altered sensorium, cerebellitis, acute transverse myelitis and bilateral papilloedema without localizing signs. Patients presenting with altered sensorium included cases of meningoenencephalitis, cerebral hemorrhage, seizures and neuroleptic malignant syndrome. Cavernous sinus thrombosis was also noted. In most patients, CSF study revealed lymphocytic pleocytosis and raised protein. All patients recovered well with anti-rickettsial therapy.

    PubMed  Google Scholar 

  13. ••Mahajan SK, Mahajan SK. Neuropsychiatric manifestations of scrub typhus. J Neurosci Rural Pract. 2017;8(3):421–426. A major review detailing central and peripheral nervous system involvement in scrub typhus including pathology and pathogenesis.

  14. Drevets DA, Leenen PJ, Greenfield RA. Invasion of the central nervous system by intracellular bacteria. Clin Microbiol Rev. 2004;17:323–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. ••Kannan K, John R, Kundu D, Dayanand D, Abhilash KPP, Mathuram AJ et al. Performance of molecular and serologic tests for scrub typhus. PLoS Negl Trop Dis. 2020;14:e 0008747. An update on the laboratory aids in the diagnosis of scrub typhus.

  16. ••Coleman RE, Sangkasuwan V, Suwanabun N, Eamsila C, Mungviriya S, Devine P, et al. Comparative evaluation of selected diagnostic assays for the detection of IgG and IgM antibody to Orientia tsutsugamushi in Thailand. Am J Trop Med Hyg. 2002;67:497–503. Comparative evaluation of laboratory aids in the diagnosis of scrub typhus.

    CAS  PubMed  Google Scholar 

  17. Liu X, Zhang Y, Zhang J, Lou Z, Xia H, Lu Z. The early diagnosis of scrub typhus by metagenomic next-generation sequencing. Front Public Health. 2021;9:755228. https://doi.org/10.3389/fpubh.2021.755228.

    Article  PubMed  PubMed Central  Google Scholar 

  18. ••Misra UK, Kalita J, Mani VE. Neurological manifestations of scrub typhus. J Neurol Neurosurg Psychiatry. 2015;86(7):761–6. https://doi.org/10.1136/JnnP-2014-308722. Detailing of a large teaching institute’s experiences with neurological manifestations of scrub typhus from an endemic area.

    Article  CAS  PubMed  Google Scholar 

  19. Viswanathan S, Muthu V, Iqbal N, Ramalayam B, George T. Scrub typhus meningitis in South India. A retrospective study. PLoS ONE. 2013;8(6):e66595.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. •Kim DM, Kim SW, Choi SH, Yun NR. Clinical and laboratory findings associated with severe scrub typhus. BMC Infect Dis. 2010;10:108. The authors suggested that clinicians should be aware of the potential for complications, when scrub typhus patients are older (> or = 60 years), present without eschar, or with laboratory findings such as WBC counts > 10, 000/mm3, and serum albumin level < or = 3.0 g/dL. Close observation and intensive care management are needed for these patients to prevent fatality.

    PubMed  PubMed Central  Google Scholar 

  21. Kamath V, Ganguly S, Himabindu B. Neurological manifestations of scrub typhus from a case series in Southern India. APIK J Int Med. 2021;9:19–24.

    Google Scholar 

  22. •Sardana V, Shringi P. Neurological manifestations of scrub typhus: a case series from tertiary care hospital in southern-east Rajasthan. Ann Indian Acad Neurol. 2020;23:808–11. This case series highlights various neurological manifestations of scrub typhus as early diagnosis and treatment of neurological complications have good prognosis. Spectrum of neurological complications varied from common complications such as aseptic meningitis, meningoencephalitis and cerebellitis to rare complications such as myelitis, cerebral hemorrhage, acute disseminated encephalomyelitis (ADEM), and cerebral infarction.

    PubMed  Google Scholar 

  23. •Lee HS, Sunwoo J-S, Ahn S-J, Moon J, Lim J-A, Jun S-S, et al. Central nervous infection associated with Orientia tsutsugamushi in South Korea. Am J Trop Med Hyg. 2017;97:1094–8. The authors of this study retrospectively evaluated the clinical characteristics and laboratory findings of 16 patients with scrub typhus-related central nervous system (CNS) infections. Single titers ≥ 1:40 of total serum antibodies against O. tsutsugamushi detected by an indirect immunofluorescent assay were considered as positive results. Commonest CNS manifestation had been encephalitis manifesting with altered sensorium and /or seizures. CSF study revealed a lymphocytic pleocytosis and mildly raised protein content. The authors suggested empirical treatment with doxycycline in patients with CNS infections in scrub typhus endemic areas.

    PubMed  PubMed Central  Google Scholar 

  24. ••Kim H-C, Yoon K-W, Yoo D-S, Cho C-S. Hemorrhagic transformation of scrub typhus: a rare entity. Clin Neuroradiol. 2015;25:415–8. Report of an unusual manifestation due to vasculitis.

    CAS  PubMed  Google Scholar 

  25. •• Kakarlapudi SR, Chako A, Samuel P, Verghese VP, Rose W. Comparison of scrub typhus meningitis with acute bacterial meningitis and tuberculous meningitis. Indian Pediatr. 2018;55:35–7. Highlights a common diagnostic and therapeutic challenge faced by clinicians in an endemic tropical country with a high prevalence of different CNS infections in the population.

  26. Valappil AV, Thiruvoth S, Peedikayil JM, Roghunath P, Thkkdath M. Differential diagnosis of scrub typhus meningitis from tuberculous meningitis using clinical and laboratory features. Clin Neurol Neurosurg. 2017;163:76–80.

    PubMed  Google Scholar 

  27. •Basu S, Chattopadhyay S. A case of Rhombencephalitis. In: Chakravarty A, editor. Neurology and internal medicine: a case-based study. New Delhi London: Jaypee Brothers Medical Publishers; 2021. p. 68–73. First report of an unusual CNS complication of scrub typhus.

  28. Naoi T, Shimazaki H, Sawada M. The rapid effectiveness of Minocycline against scrub typhus meningo-encephalitis. Intern Med. 2016;55:805–9.

    CAS  PubMed  Google Scholar 

  29. Wangrangsimaku T, Phuklia W, Newton PN, et al. Scrub typhus and the misconception of doxycycline resistance. Clin Infect Dis. 2020;70(11):2444–9.

    Google Scholar 

  30. Chen PH, Hung KH, Cheng SJ, Hsu KN. Scrub typhus associated acute disseminated encephalomyelitis. Acta Neurol Taiwan. 2006;15:251–4.

    CAS  PubMed  Google Scholar 

  31. Kim DE, Lee SH, Park KI, Chang KH, Roh JK. Scrub typhus meningoencephalitis with prominent focal neurological signs. Arch Neurol. 2000;57:1770–2.

    CAS  PubMed  Google Scholar 

  32. Chung JH, Yun NR, Kim DM, Lee JW, Yoon SH, Kim SW. Scrub typhus and cerebrovascular injury: a phenomenon of delayed treatment? Am J Trop Med Hyg. 2013;89:119–22.

    PubMed  PubMed Central  Google Scholar 

  33. •Das S, Chattopadhyay S, Munsi K, Basu S. Scrub typhus with cerebral venous sinus thrombosis – a rare presentation. BMJ Case Rep. 2021;14:e 241401. https://doi.org/10.1136/bcr-2020-241401. Report of a rare but treatable complication.

  34. Jena SS, Mathew A, Sanjith A, et al. Cerebral venous sinus thrombosis in severe scrub typhus infection: a rare entity. Neurol India. 2014;62:308–10.

    PubMed  Google Scholar 

  35. Sardana V, Shringi P. Cerebral venous sinus thrombosis in scrub typhus infection: a rare presentation. Indian J of Case Rep. 2019;5:22–3.

    Google Scholar 

  36. •Lin WR, Chen TC, Lin CY, Lu PL, Chen YH. Bilateral simultaneous facial palsy following scrub typhus meningitis: a case report and literature review. Kaohsiung J Med Sci. 2011;27:573–6. Highlights an uncommon cause of bilateral facial nerve palsy – worth exclusion at the bedside.

    PubMed  Google Scholar 

  37. Gulati S, Maheshwari A. Neurological manifestations of scrub typhus. Ann Indian Acad Neurol. 2013;16:131.

    PubMed  PubMed Central  Google Scholar 

  38. Thakur JS, Mohindroo NK, Sharma DR, Soni K, Kaushal SS. Evoked response audiometry in scrub typhus: prospective randomized case-control study. J Layngol Otol. 2011;125:567–71.

    CAS  Google Scholar 

  39. Kalita J, Mani VE, Bhoi SK, Misra UK. Status epilepticus in scrub typhus. Epilepsia. 2016;57(7):e125–8. https://doi.org/10.1111/epi.13412.

    Article  PubMed  Google Scholar 

  40. •Kalita J, Jadhav MS, Singh VK, Misra UK. Prolonged coma in scrub typhus: consider non-convulsive status epilepticus. Trans R Soc Trop Med Hyg. 2021;115:1091–3. Report of a practical problem which may be encountered in an ICU setting.

    PubMed  Google Scholar 

  41. Mahajan SK, Sharma S, Kaushik M, Raina R, Thakur P, Taneja GP, et al. Scrub typhus presenting as acute cerebellitis. J Assoc Physicians India. 2016;64:69–70.

    PubMed  Google Scholar 

  42. ••Kaiser RS, Khemka A, Roy O, Das S, Datta K. An unusual etiology of cerebellar ataxia. Child Neurol Open. 2020;7:2329048X20907754. https://doi.org/10.1177/2329048X20907754. Report of a major CNS complication of scrub typhus – needs differentiating from other causes of treatable acute onset ataxias.

  43. Nam T-S, Choi S-M, Park K-H, Kim n-k, Cho M-K. Opsoclonus associated with scrub typhus. Neurology. 2010;74:1925.

    PubMed  Google Scholar 

  44. Sahu D, Varma M, Vidyasagar S. Opsoclonus in scrub typhus. J Clin Sci Res. 2017;6:113.

    Google Scholar 

  45. Choi YJ, Choi SY, Choi J-H, Choi K-D. Opsoclonus-myoclonus syndrome associated with scrub typhus. Res Vestib Sci. 2017;16:34–7.

    Google Scholar 

  46. ••Ralph R, Prabhakar AT, Satyendra S, Carey R, Jude J, Varghese GM. Scrub typhus associated opsoclonus: clinical course and longitudinal outcomes in an Indian cohort. Ann Indian Acad Neurol. 2019;22:153–8. An important CNS complication of scrub typhus which needs recognition and differentiation from paraneoplastic causes of myoclonus opsoclonus.

    PubMed  PubMed Central  Google Scholar 

  47. ••Saini L, Dhawan SR, Madaan P, Suthar R, Saini AG, Sahu JK, et al. Infection associated opsoclonus: a retrospective case record analysis and review of literature. J Child Neurol. 2020;35:4804. Same as reference no. 45

    Google Scholar 

  48. Ryu S, Moon BJ, Park J-Y, Kim S-D, Seo S-K, Lees J-K. Acute transverse myelitis following scrub typhus. A case report and review of literature. J Spinal cord Med. 2020;43:548–51.

    PubMed  Google Scholar 

  49. •Mahajan SK, Kumar S, George M, Kaushik M, Sharma S, Raina R. Scrub typhus with longitudinally extensive transverse myelitis. J Vector Borne Dis. 2016;53:84–6. An important differential to note in the evaluation of LETM.

    PubMed  Google Scholar 

  50. Soundarajan S, Viswanathan S, Jain D, Krishnamurthy V, Gayatri MS. Acute parkinsonism and cerebral salt wasting related hyponatremia in scrub typhus. Cureus. 2020;12:e6706.

    Google Scholar 

  51. Chiou YH, Yang CJ, Lai TH. Scrub typhus associated with transient parkinsonism and myoclonus. J Clin Neurosci. 2013;20:82–3.

    Google Scholar 

  52. Lee MS, Lee JH, Chang H, Kim YS, Choi KH, et al. Scrub typhus as a possible etiology of Guillain-Barre Syndrome: Two cases. Ir J Med Sci. 2009;178:347–50.

    PubMed  Google Scholar 

  53. •Ju IN, Lee JW, Cho SY, Ryu SJ, Kim YJ, Kim SI, et al. Two cases of scrub typhus presenting with Guillain-Barre syndrome with respiratory failure. Korean J Intern Med. 2011;26:474–6. Scrub typhus – a treatable cause to look for in all patients with GBS in endemic regions.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Kim KW, Kim YH, Kim BH, Lee CY, Cho KH, et al. Miller Fisher syndrome related to O. tsutsugamushi infection. J Clin Neurosci. 2014;21:2251–2.

    PubMed  Google Scholar 

  55. Ting KS, Lin JC, Chang MK. Brachial plexus neuropathy associated with scrub typhus: Report of a case. J Formos Med Assoc. 1992;91:110–2.

    CAS  PubMed  Google Scholar 

  56. Banda GR, Boddu SR, Ballal P, Belle J. An unusual presentation of scrub typhus. J Clin Diag Res. 2016;10:0007–8.

    Google Scholar 

  57. Hayakawa K, Oki M, Moriya M, Mizuna A, Ohnuki Y, Yanagi H, et al. A case of scrub typhus with acalculous cholecystitis, aseptic meningitis and mononeuritis multiplex. J Med Microbiol. 2012;61:291–4.

    PubMed  Google Scholar 

  58. Kim JH, Lee SA, Ahn TB, Yoon SS, Park KC, Chang DI, et al. Polyneuropathy and cerebral infarction complicating scrub typhus. J Clin Neurol. 2008;4:36–9.

    PubMed  PubMed Central  Google Scholar 

  59. •Das S, Islam R, Biswas PS, Munsi K, Basu S. Cranial neuropathy and triparesis due to mononeuritis multiplex in a case of scrub typhus. Int J Adv Med. 2021;8(2):297–9. Highlights multi-axial neurological involvement in scrub typhus.

    Google Scholar 

  60. ••Kalita J, Misra UK, Mani VE, Mahadevan A, Shankar SK. A study of muscle involvement in scrub typhus. J Neurol Sci. 2015;348:226–30. A major contribution revealing clinical and pathological aspects of muscle involvement in scrub typhus.

    PubMed  Google Scholar 

  61. Young PC, Hae CC, Lee KH, Hoon CJ. Tsutsugamushi infection associated rhabdomyolysis and acute renal failure. Korean J Int Med. 2003;18:248–50.

    Google Scholar 

  62. Himral P, Sharma KN, Kudial S, Himral S. Scrub meningitis complicated by multiple cranial nerve palsies and cerebellitis. J Assoc Physicians India. 2019;67:88–9.

    PubMed  Google Scholar 

  63. Tandon R, Kumar A, Kumar A. Long segment myelitis, meningoencephalitis, and axonal polyneuropathy in a case of scrub typhus. Ann Indian Acad Neurol. 2019;22:237–40.

    PubMed  PubMed Central  Google Scholar 

  64. Phillips A, Agarwal GR, Mittal V, Singh G. Central and peripheral nervous system involvement in a patient of scrub typhus infection. Ann Indian Acad Neurol. 2018;21:318–21.

    PubMed  PubMed Central  Google Scholar 

  65. •Park JH, Jang J-W, Lee S-H, Oh WS, Kim SS. A case of scrub typhus related encephalopathy presenting as rapidly progressive dementia. Dementia Neurocog Disord. 2017;16:83–6. The authors reported on an elderly woman presenting with a rapid decline in cognitive function resulting from a scrub typhus infection. Diffusion weighted images showed a high signal intensity at the splenium, and subcortical white matter of both hemispheres suggesting mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). On the neuropsychological test, the patient showed frontal executive dysfunction.

    Google Scholar 

  66. •Naveen V, Gaba S, Gupta M, Kaur D. Posterior reversible encephalopathy syndrome in scrub typhus fever. BMJ Case Rep. 2020;13:e237262. This article reports on the clinical course of a 40-year-old female patient, who presented with acute febrile illness due to scrub typhus fever which was complicated by seizures and posterior reversible encephalopathy syndrome (PRES), leading to a fatal outcome. This is extremely rare.

    PubMed  Google Scholar 

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  1. Department of Neurology, KPC Medical College, Kolkata, India

    Sagar Basu

  2. Department of Neurology, Vivekananda Institute of Medical Science, Kolkata, India

    Ambar Chakravarty

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Basu, S., Chakravarty, A. Neurological Manifestations of Scrub Typhus. Curr Neurol Neurosci Rep 22, 491–498 (2022). https://doi.org/10.1007/s11910-022-01215-5

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