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Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 1231-1233

Guillain-barre syndrome associated with scrub typhus infection: Uncommon or under-reported!

Department of Neurology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Date of Submission25-Jun-2022
Date of Decision01-Aug-2022
Date of Acceptance05-Aug-2022
Date of Web Publication3-Dec-2022

Correspondence Address:
Niraj Kumar
Department of Neurology, All India Institute of Medical Sciences, Rishikesh - 249203, Uttarakhand
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.aian_559_22

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How to cite this article:
Kumar M, Dhar N, Madhaw G, Tiwari A, Kumar N. Guillain-barre syndrome associated with scrub typhus infection: Uncommon or under-reported!. Ann Indian Acad Neurol 2022;25:1231-3

How to cite this URL:
Kumar M, Dhar N, Madhaw G, Tiwari A, Kumar N. Guillain-barre syndrome associated with scrub typhus infection: Uncommon or under-reported!. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Jan 29];25:1231-3. Available from:

Dear Sir,

Scrub typhus (ST) is a zoonotic disease, caused by Rickettsia, Orientia tsutsugamushi (OT), an obligate intracellular gram-negative bacterium, transmitted through the bite of the larval chiggers of the trombiculid mite. ST has varied presentation ranging from a nonspecific febrile illness to multi-systemic disorder. Neurological manifestations may appear either due to central nervous system (CNS) or peripheral nervous system (PNS) involvement. PNS involvement may result in mononeuritis multiplex, brachial plexus neuropathy, polyneuropathy, and rarely Guillain–Barre syndrome (GBS).[1] To date, only 16 cases of GBS following ST (ST-GBS) have been reported [Supplementary Table 1]. Herein, we describe clinical, neurophysiological characteristics and outcome in six ST-GBS patients. To the best of our knowledge, this is the largest series of ST-GBS reported to date.

This retrospective study includes six ST-GBS patients, admitted in neurology department of a University hospital in North India, from May 2018 to Jan 2021. The study was approved by Institute Ethics Committee (AIIMS/IEC/21/76/Date: 12/02/2021). GBS was diagnosed based on clinical, cerebrospinal fluid (CSF), and neurophysiological criteria. Collected data included demographic characteristics, symptom duration, preceding illness within 8 weeks of GBS onset, neurological examination including muscle tone, power, reflexes, sensory impairment, dysautonomia, and cranial nerve palsies along with details of nerve conduction studies (NCS) and CSF examination. Need for mechanical ventilation (MV) was noted. ST was suspected in patients of acute febrile illness having ≥1 of the following: (i) headache, cough with or without shortness of breath, abdominal pain, conjunctival infection, lymphadenopathy, or rash, (ii) eschar, and (iii) defervescence of fever within 48 h of tetracycline administration, after ruling out other causes of fever. Serological test for ST demonstrating IgM antibodies using IgM-ELISA method, and magnetic resonance imaging (MRI) of brain and/or spine findings in patients manifesting headache, altered sensorium, seizures, incontinence, sensory level or severe localized root pain, were recorded. Disability at admission was assessed using Hughes Disability Scale (HDS; grades 0-6).[2] Presence of leukocytosis (total leucocyte counts >11,000/mm3); thrombocytopenia (platelet count <10,000/mm3), anemia (hemoglobin <12 g/dL), raised serum creatine kinase (>192 U/L), hyperbilirubinemia (total bilirubin >2.5 mg/dL) and/or transaminitis (elevation > twice the upper limit of normal; after excluding prior history of liver diseases) were also recorded. Treatment given including intravenous immunoglobulin (IVIG) or Plasma exchange (PE) were noted.

Amongst 40 GBS patients admitted during the study period, six developed weakness following ST infection. Eschar was seen in two patients. The median age was 43.5 (20–60) years, with five being females. The median duration of illness was 7.5 (range = 2–15) days. All had fever at the onset of areflexic quadriparesis. One patient had multi-organ dysfunction including hemolysis, transaminitis, acute kidney injury and encephalopathy and four (66.7%) patients had elevated liver enzymes. Serum creatinine phosphokinase was significantly elevated in two (33.3%) patients. One of the patients recruited during SARS-CoV2 pandemic, tested negative for reverse transcriptase – polymerase chain reaction (RT-PCR).

Two (33.3%) patients reported CNS involvement. While one developed headache and seizures, the other had altered sensorium. Lymphocytic pleocytosis (≥10 cells/mm3) was present in three (50%) patients. The median CSF protein level was 169 mg/dL. While three patients showed demyelinating pattern on NCS, motor-sensory axonal, equivocal, and inexcitable motor nerves were seen in one patient each. IVIG was given to all except one patient whose weakness was improving at presentation. All six patients received doxycycline 100 mg PO BID for 14 days. While median HDS was 5 (range = 4–5) at admission, it was 4 (range = 3–4) and 3 (range = 2–3) at 1-month and 3-month follow-up, respectively. The clinical details of our ST-GBS patients are presented in [Table 1]. [Supplementary Table 2] compares the characteristics of ST-GBS with non-ST-GBS in our cohort.
Table 1: Demographic, clinical, investigational and therapeutic details of scrub typhus-related Guillain–Barre syndrome patients in the present study

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Present study shows that ST-GBS patients were febrile at onset of weakness, had CSF pleocytosis, and multi-system involvement. Although severely disabled at presentation, all patients recovered gradually following treatment with antibiotics and immunomodulation and improved to a median HDS of 3 at 3-month follow-up.

Presence of fever at GBS onset, observed in all our ST-GBS patients and those reported in the literature, [Supplementary Table 1] suggest parainfectious polyneuropathy, possibly due to a direct effect. This observation suggests that temporal profile of neurologic symptoms does not follow the classical post-infectious profile of GBS. On the contrary, onset of GBS in second–third week following ST as evidenced in few other patients suggest postinfectious pathology, likely immune mediated.[3],[4],[5],[6],[7],[8] Positive serum antiganglioside antibodies in ST-GBS patients has been reported previously,[9],[10] and was seen in one of our patients. Thus, both a direct effect along with an immunological damage might be responsible for nerve damage in ST. The temporal association in the present study supports the notion that GBS might have been triggered by humoral immune response against ST, similar to those reported following SARS-CoV-2 and Zika virus infections.[11],[12] A recent study reported neurologic symptoms in 98% (43/44) patients, during or immediately following SARS-CoV-2 infection-associated viral syndrome, with the median time from onset of antecedent illness to onset of neurologic symptoms being 11.2 days (range = 2–23).[13]

While only half of our patients had demyelinating pattern on NCS, 13 (81.2%) of the reported 16 literature cases had demyelinating GBS. All our ST-GBS patients were severely disabled at presentation. While five (83.3%) of our patients required MV, six (6/16 = 37.5%) of those in literature required MV. This possibly indicate a more aggressive nature of GBS following ST in our cohort, which might have resulted from the difference in the virulence and immunogenic characteristic of pathogenic strain of OT in our area, compared with those affecting reported cases in literature.

Our ST-GBS patients responded well to antibiotics along with immunomodulation. Ascertaining whether patients responded to immunotherapy or antibiotics is difficult. Even after receiving appropriate antibiotics for ST, one patient developed GBS[3] and GBS-related weakness in another patient failed to respond.[4] While the first patients improved with IVIG, second patient received both IVIG and oral prednisolone.[3],[4] However, absence of immediate recovery following antibiotics or recovery after IVIG and steroids do not rule out the direct effect of OT, as improvement following immunotherapy could be co-incidental and antibiotics could have halted further nerve damage, with recovery taking time.

ST may be associated with GBS. ST-GBS patients are usually febrile at onset of weakness and significantly disabled at presentation. Following treatment with appropriate antibiotics and immunomodulation, they gradually improve to ambulate with support at 3 months.

Authors' contributions

Dr. Kumar M: Writing the first manuscript; statistics; review and critique

Dr. Dhar N: Writing the first manuscript; data collection; statistics

Dr Madhaw G: Writing the first manuscript; data collection; statistics

Dr Tiwari A: Review and critique

Dr. Kumar N: Conception; design; review and critique.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Misra UK, Kalita J, Mani VE. Neurological manifestations of scrub typhus. J Neurol Neurosurg Psychiatry 2015;86:761-6.  Back to cited text no. 1
Hughes RAC, Newsom-Davis JM, Perkin GD, Pierce JM. Controlled trial of prednisolone in acute polyneuropathy. Lancet 1978;312:750-3.  Back to cited text no. 2
Lee SH, Jung SI, Park KH, Choi SM, Park MS, Kim BC, et al. Guillain-Barré syndrome associated with scrub typhus. Scand J Infect Dis 2007;39:826-8.  Back to cited text no. 3
Lee MS, Lee JH, Lee HS, Chang H, Kim Y-S, Cho K-H, et al. Scrub typhus as a possible aetiology of GuillainBarré syndrome: Two cases. Ir J Med Sci 2009;178:347-50.  Back to cited text no. 4
Kim K-W, Kim YH, Kim BH, Lee CY, Oh MS, Yu KH, et al. Miller Fisher syndrome related to Orientia tsutsugamushi infection. J Clin Neurosci 2014;21:2251-2.  Back to cited text no. 5
Gangula RS, Stanley W, Vandanapu A, Prabhu MM. Guillain-barre syndrome with falciparum malaria and scrub typhus mixed infection-an unusual combination. J Clin Diagn Res 2017;11:OD10-1.  Back to cited text no. 6
Phillips A, Aggarwal GR, Mittal V, Singh G. Central and peripheral nervous system involvement in a patient with scrub infection. Ann Indian Acad Neurol 2018;21:318-21.  Back to cited text no. 7
[PUBMED]  [Full text]  
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.  Back to cited text no. 8
[PUBMED]  [Full text]  
Ju IN, Lee JW, Cho SY, Ryu SJ, Kim YJ, Kim SI, et al. Two cases of scrub typhus presenting with guillain-barré syndrome with respiratory failure. Korean J Intern Med 2011;26:474-6.  Back to cited text no. 9
Sakai K, Ishii N, Ebihara Y, Mochizuki H, Shiomi K, Nakazato M. Guillan-Barré syndrome following scrub typus: Two case reports. Rinsho Shinkeigaku 2016;56:577-9.  Back to cited text no. 10
Parra B, Lizarazo J, Jiménez-Arango JA, Zea-Vera AF, González-Manrique G, Vargas J, et al. Guillain–Barré syndrome associated with zika virus infection in Colombia. N Engl J Med 2016;375:1513-23.  Back to cited text no. 11
Helbok R, Beer R, Löscher W, Boesch S, Reindl M, Hornung R, et al. Guillain-Barré syndrome in a patient with antibodies against SARS-COV-2. Eur J Neurol 2020;27:1754-6.  Back to cited text no. 12
Li X, Wang Y, Wang H, Wang Y. SARS-CoV-2-associated Guillain-Barré syndrome is a para-infectious disease. QJM An Int J Med 2021;114:625-35.  Back to cited text no. 13


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