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Year : 2018  |  Volume : 21  |  Issue : 4  |  Page : 318-321

Central and peripheral nervous system involvement in a patient with scrub infection

1 Department of Critical Care Medicine, SPS Hospitals, Ludhiana, Punjab, India
2 Department of Medicine, SPS Hospitals, Ludhiana, Punjab, India

Date of Web Publication2-Nov-2018

Correspondence Address:
Dr. Atul Phillips
Department of Critical Care Medicine, SPS Hospitals, Sherpur Chowk, Ludhiana - 141 001, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.AIAN_443_17

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Scrub infection is an important differential of undifferentiated febrile illness in the subtropical and tropical countries. Neurological complications of scrub infection have a varied spectrum of presentation involving both the central nervous system, among which meningitis and meningoencephalitis are the most common presentations. The peripheral nervous system manifestations include Guillain–Barre syndrome (GBS) is not commonly reported. The coexistence of both central and peripheral involvement is rare, and we would like to report a case of a patient who was diagnosed with scrub infection and presented with meningoencephalitis and later developed GBS in the course of the disease on treatment for scrub infection.

Keywords: Guillain–Barre syndrome, meningoencephalitis, neurological complications, scrub infection

How to cite this article:
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

How to cite this URL:
Phillips A, Aggarwal GR, Mittal V, Singh G. Central and peripheral nervous system involvement in a patient with scrub infection. Ann Indian Acad Neurol [serial online] 2018 [cited 2022 May 27];21:318-21. Available from:

   Introduction Top

Scrub typhus is a zoonotic disease present in subtropical and tropical countries in the postmonsoon season. Scrub infection commonly presenting as febrile illness can involve all the organ systems of the body.[1] Neurological complications of scrub infection are particularly debilitating and can affect both the central nervous system and the peripheral nervous system. Meningoencephalitis is the most common presentation of the central nervous system. Peripheral nervous system involvement albeit rare includes polyneuropathies and Guillain–Barre syndrome (GBS). Cranial nerve defects have been reported and commonly include the abducens nerve, and facial nerves have also been reported.[2] We would like to report a case of scrub typhus infection involving both central and peripheral nervous systems.

   Case Report Top

A 70-year-old male farmer by profession presented to the emergency department with a history of high-grade fever, generalized body ache and headache for 5 days, and altered sensorium for a day. He complained of joint pains and epigastric pain and had no other comorbidities. No history of drug addiction or intoxication was present. On examination, he had inguinal lymphadenopathy and mild generalized rash. No eschar was seen. He was hemodynamically stable and was disoriented but had no focal neurological deficit or neck rigidity. An initial provisional diagnosis of acute febrile illness with undifferentiated fever was kept. A workup to rule out tropical infections was done and was found to be negative for malaria, dengue, typhoid, and leptospira. Scrub typhus antigen card was positive. Scrub immunoglobulin M (IgM) (solid-phase immunochromatographic assay) was positive and confirmed the diagnosis of scrub typhus. Blood and other body fluid cultures were sterile. Complete blood count showed leukocytosis (15,800/cc). Liver function test showed mild hyperbilirubinemia with transaminitis (total bilirubin: 3.6 mg/dL, direct bilirubin: 2.6 mg/dL, serum glutamic oxaloacetic transaminase: 116 U/L, and serum glutamic pyruvic transaminase: 178 U/L) and slightly raised international normalized ratio (1.56). Viral markers were negative for hepatitis B antigen and hepatitis C antibody. Ultrasound of the abdomen showed mild fatty infiltration of the liver. Other investigations done were normal.

The patient was being managed conservatively and treated with tablet doxycycline 100 mg twice daily. Defervescence occurred in the next 2 days and patient's orientation improved. Four days later, the patient developed weakness of both lower limbs (Grade 2/5) which progressed to the upper limbs (Grade 2/5). Deep tendon reflexes were absent and plantar responses were flexor. There was bladder incontinence but no bowel incontinence. The patient was shifted to the Intensive Care Unit (ICU) because he developed breathing difficulty with signs of respiratory distress. Single breath count was 10 with respiratory acidosis, so the patient was intubated and put on mechanical ventilation. Magnetic resonance imaging (MRI) of the brain was done which was without any abnormality. MRI of the cervical spine was done to rule out cervical myelopathy which is commonly associated with scrub typhus and revealed no abnormality. Nerve conduction velocity (NCV) showed motor sensory demyelinating polyneuropathy which clinched the diagnosis of GBS [Table 1] and [Table 2]. However, cerebrospinal fluid (CSF) analysis did not reveal albuminocytologic dissociation (protein 146, cell count – 70 with lymphocytic predominance, sugar – 71 mg/dL with a corresponding blood sugar of 145 mg/dL), and the patient was started on intravenous immunoglobulin therapy 0.4 mg/kg/day for 5 days. Tablet rifampicin 600 mg twice daily for meningoencephalitis was added. He showed improvement in weakness of all four limbs and also in his respiratory parameters and was gradually weaned off and extubated from the ventilator with a total duration of mechanical ventilation of 10 days. Oral feeding was started, and aggressive limb and chest physiotherapy was continued. He was shifted out from ICU and later discharged from the hospital with full neurological recovery after a total duration of 4 weeks of hospital stay. The patient was followed up regularly in the outpatient department and presently has no functional disability.
Table 1: Motor nerve conduction velocity

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Table 2: Sensory nerve conduction velocity

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   Discussion Top

Rickettsial infections have been wreaking havoc in the Indian subcontinent for nearly a century now with the first case was documented in the 1930s from Kumaon region[3] and has been reported from almost all the states of India.[4] Scrub typhus infection is caused by Orientia tsutsugamushi and is transmitted by trombiculid mites. It remains an important differential diagnosis of acute undifferentiated febrile illness in the tropical and subtropical regions. The classical manifestations of rickettsial infections are nonspecific febrile illness accompanied by headache, myalgia, eschar, lymphadenopathy, multisystem involvement, and a rapid response to doxycycline.[1],[5] Although the exact prevalence of rickettsial infection is not known, a South Indian study estimated it to be 31.8% among all the patients admitted with acute febrile illness in the postmonsoon season and who tested positive for scrub infection.[2] Taylor et al. reported the case fatality rate of scrub typhus varies among different countries and regions and can be up to 30%–70% if no appropriate treatment is received.[6]

The differential diagnoses of a patient presenting with undifferentiated febrile illness in addition to scrub typhus include enteric fever, dengue, leptospirosis, and malaria which were negative in our patient. Although IgM detection by fourfold increase rise in titers by indirect immunofluorescence assay remains the gold standard, it is expensive, requires expertise, and is not widely available.[7] We diagnosed scrub typhus based on positive rapid antigen test and confirmed with positive scrub IgM antibodies (done by immunochromatographic assay) which has a good specificity (>90%) and low sensitivity (40%–70%).[8],[9]

Scrub typhus invades and activates the vascular endothelial cells, which results in widespread vasculitis due to the direct effect of the organism as well as an exaggerated immune response which leads to life-threatening multiorgan dysfunction.[10] O. tsutsugamushi is an obligatory intracellular organism which invades the CSF in a monocyte or grows through the endothelium and causes pleocytosis that occurs transiently in the early period of the infection and is followed by spontaneous clearing.[11]

Microscopic central nervous system findings in scrub infection include a diffuse or focal mononuclear cell exudate in the leptomeninges and the presence of typhus nodules in the brain.[12]

The spectrum of neurological presentations of patients with scrub infection involves both the central and peripheral nervous system. Meningitis and meningoencephalitis remain the most common neurological involvement in scrub infection and are present without any focal neurological deficits. The most common presenting symptom is altered sensorium along with fever and headache and myalgias followed by seizures. CSF reveals mild-to-moderate pleocytosis with mononuclear predominance.[9] The important differentials of scrub meningitis should include bacterial meningitis (higher pleocytosis, lower sugar levels, and neutrophilic predominant), tubercular meningitis (presence of focal neurological deficit and high adenosine deaminase levels and high TB [tuberculosis] PCRlevels), viral meningoencephalitis, and aseptic meningitis.[13]

Other central nervous involvements include infarction, cerebellitis, intracranial and subdural hematomas, cerebral venous thrombosis, transient  Parkinsonism More Details, and myoclonus-opsoclonus. Cranial nerve defects include involvement of the optic, abducens, facial, and cochlear nerves.[4],[11] Peripheral nervous system involvements reported are mononeuritis multiplex, brachial plexus neuropathy, polyneuropathy, myelitis, and GBS.[14] GBS in scrub typhus is rare and remains underreported as a neurological manifestation of scrub typhus,[15],[16] and to our knowledge, only one such case has been reported from India.[17]

Hearing loss[18] due to cochlear damage due to vasculitis or immune-mediated process and retinal vasculitis[19] leading to temporary loss of vision in children has also been reported.

Our patient too presented with a history of altered sensorium with a CSF cell count of 70 cells, and we treated for meningoencephalitis as it cannot be ruled out with a normal MRI brain. MRI cervical spine was done to rule out cervical myelopathy. NCV showed motor sensory demyelinating polyneuropathy and clinched the diagnosis of GBS, which was successfully treated with immunoglobulin therapy. Although doxycycline which is bacteriostatic to O. tsutsugamushi remains the drug of choice for treatment of scrub meningitis, resistance to doxycycline is known.[20],[21] Rifampicin was added to doxycycline for treatment in our patient as the patient deteriorated neurologically on treatment with doxycycline.

Serial liver function tests were monitored and were within normal range. The urinary bladder involvement was due to probably autonomic dysfunction and pelvic parasympathetic nerve dysfunction.[22]

In contrast to the previous cases reported, our patient had both central and peripheral nervous system involvement due to scrub infection which has not been reported to the best of our knowledge.

   Conclusion Top

We want to reiterate that scrub infection remains an important differential of acute febrile illness and it can have varied neurological presentation and complications. Moreover, as the neurological complications can involve both the central and peripheral nervous systems, the treating physician should be aware of these lethal and debilitating complications and should include scrub infection in the diffrential diagnosis of undiffrentited febrile illness presenting with altered sensorium.

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   References Top

Peter JV, Sudarsan TI, Prakash JA, Varghese GM. Severe scrub typhus infection: Clinical features, diagnostic challenges and management. World J Crit Care Med 2015;4:244-50.  Back to cited text no. 1
Trowbridge P, Premkumar D, Premkumar PS, Varghese GM. Prevalence and risk factors for scrub typhus in South India. Trop Med Int Health 2017;22:576-82.  Back to cited text no. 2
Blewitt B. Fevers of the typhus group in the Bhimtal area, Kumaun hills, UP, India. J R Army Med Corps 1938;70:241-5.  Back to cited text no. 3
Rahi M, Gupte MD, Bhargava A, Varghese GM, Arora R. DHR-ICMR guidelines for diagnosis and management of rickettsial diseases in India. Indian J Med Res 2015;141:417-22.  Back to cited text no. 4
[PUBMED]  [Full text]  
Sharma PK, Ramakrishnan R, Hutin YJ, Barui AK, Manickam P, Kakkar M, et al. Scrub typhus in darjeeling, India: Opportunities for simple, practical prevention measures. Trans R Soc Trop Med Hyg 2009;103:1153-8.  Back to cited text no. 5
Taylor AJ, Paris DH, Newton PN. A systematic review of mortality from untreated scrub typhus (Orientia tsutsugamushi). PLoS Negl Trop Dis 2015;9:e0003971.  Back to cited text no. 6
Kingston HW, Blacksell SD, Tanganuchitcharnchai A, Laongnualpanich A, Basnyat B, Day NP, et al. Comparative accuracy of the InBios scrub typhus detect IgM rapid test for the detection of IgM antibodies by using conventional serology. Clin Vaccine Immunol 2015;22:1130-2.  Back to cited text no. 7
Blacksell SD, Jenjaroen K, Phetsouvanh R, Tanganuchitcharnchai A, Phouminh P, Phongmany S, et al. Accuracy of rapid IgM-based immunochromatographic and immunoblot assays for diagnosis of acute scrub typhus and murine typhus infections in Laos. Am J Trop Med Hyg 2010;83:365-9.  Back to cited text no. 8
Blacksell SD, Bryant NJ, Paris DH, Doust JA, Sakoda Y, Day NP, et al. Scrub typhus serologic testing with the indirect immunofluorescence method as a diagnostic gold standard: A lack of consensus leads to a lot of confusion. Clin Infect Dis 2007;44:391-401.  Back to cited text no. 9
Brown GW. Scrub typhus; pathogenesis and clinical syndrome. In: Walker DH, editor. Biology of Rickettsial Diseases. Vol. 1. Boca Raton, Florida: CRC Press; 1988. p. 93-100.  Back to cited text no. 10
Pai H, Sohn S, Seong Y, Kee S, Chang WH, Choe KW, et al. Central nervous system involvement in patients with scrub typhus. Clin Infect Dis 1997;24:436-40.  Back to cited text no. 11
Settle EB, Pinkerton H, Corbett AJ. A pathologic study of tsutsugamushi disease (scrub typhus) with notes on clinicopathologic correlation. J Lab Clin Med 1945;30:639-61.  Back to cited text no. 12
Misra UK, Kalita J, Mani VE. Neurological manifestations of scrub typhus. J Neurol Neurosurg Psychiatry 2015;86:761-6.  Back to cited text no. 13
Viswanathan S, Muthu V, Iqbal N, Remalayam B, George T. Scrub typhus meningitis in South India – A retrospective study. PLoS One 2013;8:e66595.  Back to cited text no. 14
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. 15
Lee MS, Lee JH, Lee HS, Chang H, Kim YS, Cho KH, et al. Scrub typhus as a possible aetiology of Guillain-Barré syndrome: Two cases. Ir J Med Sci 2009;178:347-50.  Back to cited text no. 16
Sawale VM, Upreti S, Singh TS, Singh NB, Singh TB. A rare case of Guillain-Barre syndrome following scrub typhus. Neurol India 2014;62:82-3.  Back to cited text no. 17
[PUBMED]  [Full text]  
Premaratna R, Chandrasena TG, Dassayake AS, Loftis AD, Dasch GA, de Silva HJ, et al. Acute hearing loss due to scrub typhus: A forgotten complication of a reemerging disease. Clin Infect Dis 2006;42:e6-8.  Back to cited text no. 18
Thomas R, Puranik P, Kalal B, Britto C, Kamalesh S, Rego S, et al. Five-year analysis of rickettsial fevers in children in South India: Clinical manifestations and complications. J Infect Dev Ctries 2016;10:657-61.  Back to cited text no. 19
Watt G, Kantipong P, Jongsakul K, Watcharapichat P, Phulsuksombati D, Strickman D, et al. Doxycycline and rifampicin for mild scrub-typhus infections in Northern Thailand: A randomised trial. Lancet 2000;356:1057-61.  Back to cited text no. 20
Kim DM, Kim YS, Cho HY, Lee YB. Scrub typhus meningoencephalitis occurring during doxycycline therapy for Orientia tsutsugamushi. Diagn Microbiol Infect Dis 2011;69:271-4.  Back to cited text no. 21
Sakakibara R, Hattori T, Kuwabara S, Yamanishi T, Yasuda K. Micturitional disturbance in patients with Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 1997;63:649-53.  Back to cited text no. 22


  [Table 1], [Table 2]


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