Neurological Facets of Scrub Typhus: A Comprehensive Narrative Review

Abstract

Scrub typhus is one of the most frequent causes of acute febrile illness in South and South-east Asian countries. Neurological features accompany 20% of scrub typhus infections, and may affect the central or peripheral nervous system, and sometime, may even occur in combination. Of late, its recognition among clinicians has increased with widening detection of its cutaneous hallmark, called eschar. Multiple mechanisms underlie neurological involvement, including direct invasion (meningitis, encephalitis), vasculitis (myositis) or immune-mediated mechanisms (opsoclonus, myoclonus, optic neuritis, Guillain–Barre syndrome). Despite an immunological basis for several neurological manifestations, response to doxycycline is remarkable, although immune therapy may be necessary for severe involvement. Scientific literature on scrub typhus neurology chiefly emanates from case reports, case series and small studies, and a comprehensive review is warranted to aid clinicians in recognising neurological involvement. This review aims at enriching this gap, and summarises clinical features, laboratory findings, and treatment options for various neurological facets of scrub typhus.

Full text

© 2006 - 2021 Annals of Indian Academy of Neurology | Published by Wolters Kluwer - Medknow 849
Abstract
IntRoductIon
Scrub typhus is a rickettsial illness caused by Orientia
tsutsugamushi. It is due to the bite of the larval form of the
Leptotrombidium mite, termed ‘chigger’ which is both reservoir
and disease vector. The larval form survives by feeding on rats,
which are reservoir hosts. Humans are infected when they come
in contact with chiggers. Most descriptions of scrub typhus
have emanated from a distinct geographical region, termed
‘tsutsugamushi triangle.’ This triangles extend from northern
Japan and eastern Russia in the north, Pakistan and Afghanistan
in the west and northern Australia in the south.[1] However,
reports have also emerged from other regions such as South
America and Africa, lately.[2] Above one billion individuals
are at risk for scrub typhus in endemic areas.[3] Scrub typhus
typically leads to an acute febrile illness, associated with
thrombocytopenia, transaminitis and a sine qua non‑cutaneous
lesion at the site of the chigger bite, termed ‘eschar.’ This
has a ‘cigarette burn’ appearance with an ulcer with a scab at
the centre, and surrounding erythema or desquamation. The
eschar occurs at specic sites of predilection, including axilla,
submammary folds, gluteal cleft, inner thighs, abdomen, and
lower back [Figure 1]. Orientia tsutsugamushi is an obligatory
intracellular bacterium and replicates within endothelial cells
and phagocytes. Hence, it has a predilection for affecting highly
vascularised organs such as brain, lungs, and liver. Severity
of infection is determined by immune status of the host, and
the strain of O. tsutsugamushi, with Karp serotype being most
prevalent in endemic regions.
Nervous system involvement occurs in up to one‑fth of
the patients and is often prominent.[4] It may affect the
central or peripheral nervous system. A diverse range
of neurological features have been described, ranging
from the more frequent meningitis and encephalitis,
to rarer phenomenon such as opsoclonus, myoclonus,
parkinsonism and Guillain–Barre syndrome (GBS).[5] The
pathogenesis underlying neurological manifestations may
be a combination of vasculitis or other immune phenomena
triggered by the infection.
Despite the potentially serious consequences, scrub typhus
remains eminently amenable to therapy in the form of
doxycycline. The presentations are myriad and can easily
be mistaken for other tropical neurological syndromes.
Although there are individual case series and reports on
the neurological presentations in scrub typhus, an updated
review is lacking.
In this article, we aim to evaluate the clinical and epidemiological
profile, treatment outcomes and potential pathogenetic
mechanisms underlying neurological manifestations of scrub
typhus.
Scrub typhus is one of the most frequent causes of acute febrile illness in South and South‑east Asian countries. Neurological features
accompany 20% of scrub typhus infections, and may affect the central or peripheral nervous system, and sometime, may even occur in
combination. Of late, its recognition among clinicians has increased with widening detection of its cutaneous hallmark, called eschar. Multiple
mechanisms underlie neurological involvement, including direct invasion (meningitis, encephalitis), vasculitis (myositis) or immune‑mediated
mechanisms (opsoclonus, myoclonus, optic neuritis, Guillain–Barre syndrome). Despite an immunological basis for several neurological
manifestations, response to doxycycline is remarkable, although immune therapy may be necessary for severe involvement. Scientic literature
on scrub typhus neurology chiey emanates from case reports, case series and small studies, and a comprehensive review is warranted to
aid clinicians in recognising neurological involvement. This review aims at enriching this gap, and summarises clinical features, laboratory
ndings, and treatment options for various neurological facets of scrub typhus.
Keywords: Neurology, opsoclonus, orientia tsutsugamushi, scrub typhus, vasculitis
Address for correspondence: Dr. Divyani Garg,
Consultant Neurologist, Department of Neurology, Neo Hospital, Noida,
Uttar Pradesh, India.
E‑mail: divyanig@gmail.com
This is an open access journal, and arcles are distributed under the terms of the Creave Commons
Aribuon‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build
upon the work non‑commercially, as long as appropriate credit is given and the new creaons are
licensed under the idencal terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
DOI: 10.4103/aian.aian_739_21
Neurological Facets of Scrub Typhus: A Comprehensive
Narrative Review
Divyani Garg, Abi Manesh1
Department of Neurology, Neo Hospital, Noida, Uttar Pradesh, 1Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India
AIAN Review
Submitted: 15‑Aug‑2021 Revised: 18‑Oct‑2021 Accepted: 29‑Oct‑2021
Published: 17‑Dec‑2021
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
850
Methods
Search strategy
We searched three major electronic databases in an attempt to
locate all reports of neurological manifestations of scrub typhus
published until May 2021 in the electronic form.: MEDLINE
(PubMed), Google Scholar and ScienceDirect were searched.
Search terms were “neurology,” “encephalitis,” “meningitis,”
“meningoencephalitis,” “seizure,” “parkinsonism,”
“opsoclonus,” “myoclonus,” “ophthalmoplegia,” “ocular
utter,” “ataxia,” “neuropathy,” “Guillain–Barre syndrome,”
“myelopathy,” “myelitis,” “cranial neuropathy,” “facial palsy,”
“central nervous system.” These terms were combined with
“scrub typhus” and “Orientia tsutsugamushi.”
We included original articles, case series, case reports, letters to
the editor, posters and bulletins published up to May 2021 in this
review, which described neurological manifestations associated
with scrub typhus infection among adults (>18 years).
We restricted our search to articles in English. The two
authors (DG, AM) independently screened titles and abstracts
of all papers located in the initial search. From these articles, we
extracted author name, year of publication, journal name, age
and sex of the patients, type of neurological manifestation, day
of illness on which neurological feature appeared, diagnostic
method, neuroimaging and other evaluation details, treatment
details and outcome.
Results
Neurological features in scrub typhus can be classied as
those involving the central nervous system (CNS), peripheral
nervous system (PNS) and those with multi‑axial involvement.
Clinical, laboratory features and treatment modalities adopted
have been described below.
Pathogenesis of neurological features
Approximately 20%–25% of patients with scrub typhus suffer
from neurological complications, making this an important
part of the clinical constellation.[5‑88] Entry in to the CNS
is via invasion of endothelial cells by O. tsutsugamushi.
Endothelial cells are the primary cellular target. Subsequent
endothelial cell activation leads to leukocyte adhesion and
transmigration, platelet aggregation and cytokine release.
In the lung, this uncontrolled activation causes excessive
neutrophilic and monocytic infiltration, triggering acute
respiratory distress syndrome (ARDS).[6] In the CNS, resultant
vasculitis leads to a plethora of complications. Direct invasion
of the CSF has been reported in some studies, leading to
meningitis and meningo‑encephalitis.[7] A third mechanism
underlying neurological features is immune‑mediated, due to
type 2 hypersensitivity reaction targeting self‑antigens. This
explains certain late‑onset manifestations such as opsoclonus,
myoclonus, GBS and myelitis.
We have summarised these mechanisms in Figure 2 and the
timeline of development in Figure 3.
Central nervous system involvement in scrub typhus
The most frequently occurring CNS manifestations include
meningitis, meningo‑encephalitis, encephalitis, encephalopathy
and seizures. Less commonly, stroke, cerebellar involvement,
opsoclonus, myoclonus, cranial neuropathies, parkinsonism,
acute disseminated encephalomyelitis (ADEM), haemorrhagic
encephalitis and myelitis have been reported [Table 1]. The
word ‘typhus’ itself is derived from ‘typhos’ indicating stupor,
inspired from the diverse range of CNS involvement. CNS
involvement in scrub typhus is also a predictor of mortality.[8]
In the largest prospective series, 79/189 (41.8%) patients
diagnosed with scrub typhus had any form of CNS
manifestations; 42 (22.2%) had altered sensorium, 12 (6.3%)
had seizures, 39 patients were diagnosed to have aseptic
meningitis based on CSF ndings.[9]
Meningitis, encephalitis and encephalopathy
Meningitis and meningoencephalitis are the most frequent
neurological features of scrub typhus, with data emanating
from larger case series [Table 1]. Scrub typhus accounted
for 18% of all CNS bacterial infections in Laos.[10] In a
large series of patients from India, 37/323 (11.5%) patients
Figure 2: Pathogenesis of neurological features of scrub typhus
Figure 1: Sites of distribution of eschar of scrub typhus on the human
body
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021 851
with scrub typhus had CNS involvement.[11] In studies from
India, 20%–25% cases with acute encephalitis had IgM/PCR
positivity for scrub typhus although this effect is uncertain
as IgM response in scrub typhus may persist for more than
a year.[12,13]
Patients with scrub typhus meningitis present with classical
clinical features of meningeal involvement.[14] They report
fever, headache, vomiting, neck stiffness and altered
sensorium. Neck stiffness may be reported in up to 67% of
patients.[5] Presence of altered sensorium/seizures including
status epilepticus and focal decits is seen in encephalitis.[15]
The median duration from onset of fever may ranges from 3 to
22 days as per literature. In one rare case report, haemorrhagic
conversion of encephalitis was reported and was postulated
to be consequent to vessel wall fragility in vasculitic blood
vessels.[16]
Scrub typhus yields a cerebrospinal uid (CSF) picture akin
to aseptic meningitis, with lymphocytic pleocytosis, mild to
moderate protein elevation and normal or borderline low sugar
levels. In endemic regions, bacterial and tubercular meningitis
form close differentials. Some of the pointers towards scrub
typhus as the underlying aetiology of meningitis compared to
tuberculosis include a relatively shorter duration of illness, less
severe neurological decits at presentation, presence of hepatic
involvement, thrombocytopenia and CSF parameters including
lower degree of protein elevation and lymphocytosis.[17,18] In
comparison to acute bacterial meningitis, shorter duration
of symptoms, higher levels of obtundation, absence of
hepatic involvement, higher CSF pleocytosis, neutrophilic
predominance in CSF and higher degree of protein elevation
favour bacterial meningitis over scrub typhus meningitis.[4]
Although doxycycline is the treatment of choice for scrub
typhus, several authors have noted the development of
meningitis or meningoencephalitis during the course of
doxycycline therapy. This may be due to the bacteriostatic
action of doxycycline, relatively poor penetration through
the blood–brain barrier and drug resistance. For this reason,
some authors advocate the use of rifampicin alone or in
addition to doxycycline for CNS involvement in scrub typhus.
Minocycline has also been found to be effective in treatment
of CNS scrub typhus with good response.[19] Overall, response
to antimicrobial therapy is favourable with most patients
responding well. However, since CNS involvement may also
be mediated by immunological mechanisms apart from just
direct invasion, this issue may not be related to doxycycline
penetration alone.
Cranial nerve palsies
Individual as well as multiple simultaneous nerve involvement
has been reported with scrub typhus [Table 1]. Involvement
may be indirect, as a result of an immune‑mediated process,
such as optic nerve involvement in post‑infectious optic
neuritis, which is steroid‑responsive. Multiple extraocular
nerve involvement may occur as part of cavernous sinus
inammation or infection. The latter seem to respond well to
antibiotic therapy alone. In a series of patients with meningitis
due to scrub typhus, cranial nerve palsies were observed to
respond to doxycycline therapy.[15] However, development after
scrub typhus infection has been treated may raise concerns of
post‑infectious demyelination. Additional clues may be derived
from CSF analysis, with albumin‑cytological dissociation
favouring inammation over infection. Similarly, in patients
with scrub typhus with lateral rectus palsy, only one patient
presented with diplopia in concert with fever.[20] In the other
two cases, it was detected on examination. Moreover, CSF was
normal in two cases and showed mild elevation in protein in
one patient, suggesting that the mechanism of involvement may
be leptomeningeal inammation or raised intracranial pressure
or even microvasculitis‑mediated nerve injury.
Hearing loss is a unique and interesting phenomenon noted in
scrub typhus and is acute and reversible. It is believed to be
present in nearly one‑third of patients although only limited cases
have been reported [Table 1].[21] The mechanism could be due to
immune‑mediated or vasculitis‑related damage to the VIIIth nerve
or demyelinating neuropathy involving the cochleovestibular
nerve. In a histopathology study of louse‑borne typhus, cochlear
and retro‑cochlear injury was noted.[22]
Figure 3: Timelines of evolution of neurological manifestations in scrub typhus
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
852
Contd...
Table 1: Summary of studies describing central nervous system (CNS) involvement in association with scrub typhus
Author/Year Country Type of study No. of participants/case clinical details Age (yrs) Sex Interval (days) between onset of
fever and neurological symptom
Meningitis/Encephalitis
Lee et al.[15]/2017 Korea Retrospective case series 16 35.5 62.5% F 3‑22
Dhanapriya et al.[39]/2017 India Case report Fever, chills, headache, vomiting in a renal
transplant recipient
45 F 6
Sharma et al.[40]/2015 India Prospective case series 23 Range: 19‑68 years 56.5% F Not mentioned
Jamil et al.[41]/2015 India Prospective case series 13 Mean 34.8+16.2 M: F=2.25:1 Mean 5.6+3.08 days
Abhilash et al.[42]/2015 India Retrospective case series 189 41±16.3 56.8 9.4±3
Misra et al.[5]/2015 India Cross‑sectional 37 3‑71 49 Not reported
Boorugu et al.[9]/2014 India Prospective case series 189 Not reported Not reported Not reported
Kar et al.[43]/2014 India Prospective case series 6 35‑62 5/6 males 2‑4 (mean 3)
Viswanathan et al.[44]/2013 India Retrospective case series 17/65 had meningitis 41.8+17.7 33 M/32 F Not reported
Kim et al.[45]/2013 Korea Case‑control study 22 70 63.6% F Not reported
Khan et al.[12]/2017 India Retrospective case series 104/511 AES cases had scrub typhus Median age 25 55.7% males Not reported
Gaba et al.[46]/2020 India Case report Fever with chills followed by headache,
vomiting, stupor
19 F 4
Mahajan et al.[28]/2016 India Retrospective 44/253 (17.4%) 41.4+31.7 69.6% F Not mentioned
Encephalomyelitis
Chen et al.[30]/2006 Taiwan Case report Fever, altered sensorium, dysarthria and left
hemiparesis, seizure, left facial paresis
77 M 10
Kim et al.[31]/2000 Korea Case report Headache, fever, vomiting, drowsiness
followed by dysarthria and quadriparesis,
bilateral abducens palsies, facial paralysis
22 F 5
Status epilepticus
Kalita et al.[33]/2021 India Case report Fever, persistent altered sensorium 50 F Simultaneous
Kalita et al.[32]/2016 India Prospective 13/66 patients with scrub typhus had status
epilepticus. 10 included.
34 (range 18‑71) 7 females; 3
males
4 and 30 (median 11)
Rapidly progressive dementia
Park et al.[34]/2017 Korea Case report Acute cognitive impairment with reversible
splenial lesions
78 F Not specied
Posterior Reversible
Encephalopathy Syndrome
Naveen et al.[35]/2020 India Case report Fever followed by headache, hypotension,
seizure and obtundation
40 F 4
Cranial neuropathy
Optic neuritis
Jessani et al.[47]/2016 India Case report Fever, headache, right eye pain and visual
loss
8 F Not reported
Cho et al.[48]/2013 Korea Case report Bilateral loss of vision two weeks after
resolution of febrile illness
8 M 21
Bae et al.[49]/2018 Korea Case report Post‑infectious ON with NMO+ 82 F 21
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021 853
Table 1: Contd...
Author/Year Country Type of study No. of participants/case clinical details Age (yrs) Sex Interval (days) between onset of
fever and neurological symptom
Ophthalmoplegia
Kim et al.[50]/2015 Korea Case report Fever followed by ptosis and
ophthalmoplegia
69 M 5
Trigeminal neuralgia
Arai et al.[51]/2007 Japan Case report Fever and headache followed by electric
shock‑like pain in the left eye
64 M 1
Abducens palsy
Ozair et al.[20]/2020 India Case report Fever, altered sensorium followed by
diplopia
27 F 6
Ete et al.[52]/2016 India Case report Fever, altered sensorium 22 F 5
Bhardwaj et al.[53]/2013 India Case report Fever, headache, altered sensorium 23 F 7
Facial palsy
Lin et al.[54]/2013 Taiwan Case report Fever and bilateral sequential facial palsy 49 M 13, 23 (left, followed by right)
Hearing loss
Premaratna et al.[55]/2005 Sri
Lanka
Case series 6 patients 1. 47‑5. 57‑58
6.52
F
F
F
14
12‑15
9
Kang et al.[56]/2009 Korea Case series 4 (Patients 2,3 had otalgia without hearing
loss)
1. 60
2‑4. Not mentioned
F
Not mentioned
10
Not reported
Venketesan et al.[57]/2019 India Case report Loin pain, dysuria, fever, hearing loss in a
diabetic
52 F Not mentioned
Opsoclonus and/or myoclonus
Nam et al./2010[23] Case reports 2 64
40
F
M
Not mentioned
Not mentioned
D’sa et al.[58]/2012 India Case report Fever, headache, oscillopsia 54 M 5
Koti et al.[59]/2015 India Case report Fever, dyspnea, restlessness followed by
opsoclonus myoclonus
26 M 6
Sahu et al.[60]/2017 India Case report Fever, ataxia, tremulousness, pancerebellar
syndrome, opsoclonus
60 M 3
Choi et al.[61]/2017 Korea Case report Fever, rash, tremors, parkinsonism 59 M 8
Ralph et al.[24]/2019 India Case series 18 patients in a retrospective series
had opsoclonus, of which 9 (50%) had
myoclonus associated
‑ ‑ Mean 11 days (range 7‑18 days)
Saini et al.[62]/2020 India Retrospective case series 1 had scrub typhus in this series of children
with ‘infection‑associated opsoclonus’
7 F 5
Garg and Dhamija[63]./2021 India Case report Abnormal eye and limb movement, fever 23 F 7
Cerebellar dysfunction
Gupta et al.[25]/2020 India Case report Fever for 4 days followed by pan‑cerebellar
symptoms
26 F 5
Contd...
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
854
Table 1: Contd...
Author/Year Country Type of study No. of participants/case clinical details Age (yrs) Sex Interval (days) between onset of
fever and neurological symptom
Kaiser et al.[64]/2020 India Case report Fever, difculty in walking, visual
impairment
7 F 12
Bhat et al.[65]/2015 India Case report Fever followed by dysarthria and cerebellar
signs
6 F 3
Bhoil et al.[26]/2016 India Case report Fever, semiconscious state, pancerebellar
involvement
21 M 3
Didel et al.[66]/2017 India Case report Fever, headache, vomiting, swaying to the
left
9 M Not mentioned
Karanth et al.[27]/2013 India Case report Fever, drowsiness, cerebellar features 24 M 12
Mahajan et al.[28]/2016 India Case report Fever, headache, vomiting followed by
ataxia
22 F 9
Parkinsonism
Soundararajan et al./2020[67] India Case report Fever, cough, dyspnoea, slurred speech, ret
tremor, hypomimia, hypophonia
50 M 14
Ralph et al.[24]/2019 India Case series reporting on
opsoclonus in scrub typhus
6/18 (33%) had EPS ‑ ‑ ‑
Premaratna et al.[68]/2015 Sri
Lanka
Case report Fever, right sided rest tremors, stiffness
right leg
62 M 5
Chiou et al.[69]/2013 Taiwan Case report Fever, rash, rigidity, myoclonus, tremors 55 M 2
Transverse myelitis
Ryu et al.[70]/2020 Korea Case report Fever, headache; responded to doxycycline;
then developed sudden paraparesis with
bowel and bladder involvement
66 M 7
Yun et al.[29]/2017 Korea Case report Fever, chills followed by ascending
paraparesis (power grade 2/5)
67 M 14
Mahajan et al.[71]/2016 India Case report Fever, chills, headache, paraparesis 35 F 4
Lee et al.[72]/2008 Korea Case report Fever, headache followed by right lower
limb weakness, left lower limb paresthesias,
bladder involvement
54 M 7
Author/Year Diagnostic testing Neuro‑imaging/other investigations Treatment Outcome
Meningitis/Encephalitis
Lee et al.[15]/2017 Indirect IFA MRI: leptomeningeal enhancement in 4
patients; abnormal CSF in 13/16
Doxycycline with/without
clarithromycin/azithromycin
15/16=improved completely
1/16=persistent facial palsy
Dhanapriya et al.[39]/2017 IgM ELISA CT normal; CSF 607 cells; protein 203 mg/dL;
sugar 77 mg/dL
Oral doxycycline for 5 days followed
by IV azithromycin
Responded well to azithromycin
Sharma et al.[40]/2015 Weil‑Felix test/Positive IgM
ELISA
Median CSF cell count, CSF protein, CSF
glucose/blood glucose were 17 cells/µL,
86 mg/dL, 0.6605
Doxycycline No mortality
Jamil et al.[41]/2015 CT/MRI normal; Mean CSF
cells 152 + 67 cells/mm3, 55
+ 12.7 mg/dL,
Mean CSF protein, glucose 152.16±16.88
mg/dl, respectively. Mean total count of CSF
leukocytes 46.07±131 cell/mm3; 98.66±3.09% L
Tablet doxycycline with or without
injection azithromycin
2/13 (15%) died; both has multi organ
dysfunction.
Contd...
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021 855
Table 1: Contd...
Author/Year Diagnostic testing Neuro‑imaging/other investigations Treatment Outcome
Abhilash et al.[42]/2015 ELISA/PCR + eschar Mean CSF WBC count 80±120 cells/mm3
(range 5‑900); mean CSF protein 105.9±80.9
(range 13‑640 mg%), mean CSF sugar level
69.4±89.6 mg% (range 25‑350 mg%)
Doxycycline with or without
intravenous azithromycin
for 7 days
11 patients died (5.8%)
Mean duration of hospital stay was 6.9 days (SD
5.1 days)
Misra et al.[5]/2015 Solid phase
immunochromatographic
assay or Weil‑Felix test
MRI revealed meningeal enhancement in only
1/25 (4%) patient and EEG showed generalised
slowing in 6/28 (21.4%)
Doxycycline Patients with low GCS score had signicantly
more focal neurological decit (r=0.5; P=0.002),
longer hospital stay (r= ‑0.4; P=0.03) and more
disability on discharge (r= ‑0.4; P=0.01)
Boorugu et al.[9]/2014 IgM serology and/or
presence of eschar
Headache‑ 79 (41.8%)
Altered sensorium‑ 42 (22.2%)
Seizures‑ 12 (6.3%)
CSF (47 patients): 39 had aseptic meningitis
Not mentioned Not mentioned
Kar et al.[43]/2014 IgM ELISA CSF suggestive of meningitis in 2; All had renal
dysfunction
MRI: cerebral edema, hyperintense putamen
and thalamus on T2/FLAIR
Oral doxycycline All responded well
Viswanathan et al.[44]/2013 IgM ELISA, Weil‑Felix test,
eschar
Median CSF cells=54, protein 88, sugar 0.622
U/mL
Doxycycline, chloramphenicol Recovery in all patients
Kim et al.[45]/2013 Positive PCR or indirect IFA CSF TLC=median 24 cells/mm3, protein
median 78 mg/dL, glucose median 56.5 mg/dL
Doxycycline, rifampicin,
telithromycin
Recovery in all patients
Khan et al.[12]/2017 IgM ELISA ‑ ‑ 53/104 patients could be followed up; 26 died
after discharge
Gaba et al.[46]/2020 IgM ELISA
RT‑PCR
CSF cell count 16 cells µ/L; 80% lymphocytes;
total protein 51 g/dL, glucose
73 mg/dL
MRI: Hemorrhagic encephalitis
Ceftriaxone, doxycycline,
dexamethasone, mannitol
Complete recovery
Mahajan et al.[28]/2016 IgM ELISA 18/44 had abnormal CSF Doxycycline/azithromycin Altered sensorium risk factor for mortality
Encephalomyelitis
Chen et al.[30]/2006 Increase in IgG antibodies
on serial serum and CSF
testing during acute and
convalescent phase
Serial MRIs: progressive areas of signal
hyperintensity involving periventricular white
matter
CSF=230 cells/mm3, glucose 41 mg/dL, protein
219 mg/dL
No response to minocycline;
Intravenous high dose corticosteroids
Developed coma and quadriparesis despite
steroids.
Limited improvement; persistent quadriplegia,
transferred to a long‑term care facility
Kim et al.[31]/2000 Serum (IFA) and CSF IgM
and IgG antibodies positive
MRI: T2/FLAIR hyperintense lesions in lower
brainstem, cerebellar peduncles, spinal cord
(grey matter)
Doxycycline Complete motor recovery by day 24
Status epilepticus
Kalita et al.[33]/2021 IgM ELISA MRI brain normal;
EEG =>2.5 hertz generalised epileptiform
discharges; CSF abnormal
Lorazepam, valproate, levetiracetam
Doxycyline
Complete recovery
Kalita et al.[32]/2016 Solid phase immuno
chromatography assay
MRI normal
EEG normal
As for SE; all patients received
doxycycline
Complete recovery at 1 month
Contd...
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
856
Table 1: Contd...
Author/Year Diagnostic testing Neuro‑imaging/other investigations Treatment Outcome
Rapidly progressive dementia
Park et al.[34]/2017 Repeat scrub typhus
antibody titres
MRI=high signal intensity at splenium and
subcortical white matter of both hemispheres
which resolved on repeat MRI; CSF=normal
Doxycycline Residual cognitive dysfunction remained even
after two months of follow up
Posterior Reversible
Encephalopathy Syndrome
Naveen et al.[35]/2020 IgM ELISA MRI suggestive of PRES Doxycycline and other supportive
treatment
Developed seizures requiring levetiracetam and
valproate.
Patient did not regain consciousness after
seizures and died on fth day of admission due
to refractory shock
Cranial neuropathy
Optic neuritis
Jessani et al.[47]/2016 IgM ELISA CSF=TLC 60 cells/mm3, 70% lymphocyte,
glucose 54 mg/dL. MRI brain/orbit=normal
Doxycycline and IVMP for 5 days Complete recovery at one month of follow up
Cho et al.[48]/2013 Elevated antibody titre MRI=bilateral optic neuritis IV MP for 5 days followed by oral
steroid taper
Complete recovery at three months of follow up
Bae et al.[49]/2018 Not mentioned, eschar + MRI=enhancement of the right optic nerve,
AQP4‑AB +
IV MP 1000 mg for 5 days followed
by oral steroid taper
Complete recovery at 4 months; no further
treatment taken; no repeat attacks till 5 years
Ophthalmoplegia
Kim et al.[50]/2015 Eschar MRI=anterior cavernous lesion and meningeal
thickening; CSF=mildly elevated protein, CSF
IgG for scrub typhus elevated
Doxycycline Complete resolution
Trigeminal neuralgia
Arai et al.[51]/2007 Not mentioned CT brain, CSF normal Minocycline Complete resolution
Abducens palsy
Ozair et al.[20]/2020 IgM ELISA positive for
scrub, dengue, CKV
MRI brain: leptomeningeal enhancement Doxycycline Resolution of LR palsy over months
Ete et al.[52]/2016 IFA IgM MRI brain, CSF normal Doxycycline and azithromycin Improved
Bhardwaj et al.[53]/2013 CSF PCR MRI brain, CSF normal Doxycycline Resolution
Facial palsy
Lin et al.[54]/2013 Not mentioned CSF abnormal; CT brain normal Doxycycline and intravenous
dexamethasone
Partial improvement at 3 months
Hearing loss
Premaratna et al.[55]/2005 Rise in antibody titres on IFA
Rise in antibody titres on IFA
IgM antibodies
MRI normal IV chloramphenicol and
doxycycline
Oral tetracycline
Chloramphenicol, tetracycline
Complete recovery
Hearing improvement over 2 weeks to 3 months
Patient died 48 hours after admission
Kang et al.[56]/2009 IFA/PCR/Eschar
Not reported
Not mentioned Not reported Resolution
Venketesan et al.[57]/2019 IgM antibody Not mentioned Doxycycline Hearing improved
Contd...
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021 857
Table 1: Contd...
Author/Year Diagnostic testing Neuro‑imaging/other investigations Treatment Outcome
Opsoclonus and/or myoclonus
Nam et al./2010[23] Elevated serum antibody
titres
Elevated antibody titres
CSF cells=49 cells/mm3
CSF protein=102 mg/dL
CSF cells=28 cells/mm3
CSF protein=91 mg/dL
MRI brain normal in both
Not available
Not available
Not available
Not available
D’sa et al.[58]/2012 IgM ELISA in serum
positive for scrub typhus
MRI brain and CSF normal Doxycycline Complete recovery at 2 weeks
Koti et al.[59]/2015 IgM Scrub typhus ELISA
positive
MRI brain and CSF normal Doxycycline Opsoclonus subsided on day 3,4 of treatment and 9th
and 10th day of illness
Sahu et al.[60]/2017 IgM Scrub typhus ELISA
positive
MRI brain normal; CSF normal Doxycycline and azithromycin Opsoclonus decreased 2 days after initiation of therapy
and resolved by day 3
Choi et al.[61]/2017 IgM indirect IFA Imaging normal Doxycycline and steroid IV MP
pulse for 5 days
‘Good’ outcome
Ralph et al.[24]/2019 Scrub typhus ELISA 14/18 patients had abnormal CSF (2 were not
tested)
Normal MRI in 9/12 patients
Doxycycline + /‑ azithromycin 13/17 followed up at 6 weeks; myoclonus completely
resolved in all, opsoclonus persisted in nine.
At 3 months, 12 were followed up. Complete resolution
of myoclonus in all
Saini et al.[62]/2020 IgM ELISA MRI brain normal
CSF showed 30 cells/m3, 55 mg/dL protein
Doxycycline Resolved completely over 7 days
Garg and Dhamija[63]./2021 IgM ELISA MRI and CSF normal; multiorgan dysfunction Azithromycin Resolved completely over two weekd
Cerebellar dysfunction
Gupta et al.[25]/2020 ELISA IgM MRI and CSF normal Doxycycline Improved over 10 days; residual nystagmus at one
month
Kaiser et al.[64]/2020 IgM ELISA CSF: 102 cells/mm3, 92% mononuclear,
glucose ‑59 mg/dL, protein 119 mg/dL
Doxycycline Improvement reported
Bhat et al.[65]/2015 Weil‑Felix OXK titre=1:320 MRI: Diffuse increase in T2/FLAIR signal in
cerebellum with swelling
CSF: not done
Not mentioned Not mentioned
Bhoil et al.[26]/2016 Weil‑Felix OXK titre=1:320/
IgM ELISA
MRI: cerebellitis; CSF normal Doxycycline Improvement
Didel et al.[66]/2017 IgM ELISA and RT‑PCR MRI=left focal cerebellar tonsillar
hyperintensity
Doxycycline Resolved in one week
Karanth et al.[27]/2013 Weil‑Felix OXK titre=1:640
and IgM ELISA
MRI brain normal.
CSF cells 25/mm3, protein 60 mg/dL
Doxycycline Resolved
Mahajan et al.[28]/2016 IgM ELISA MRI=pachymeningeal enhancement, bilateral
cerebellar edema
CSF=15 lymphocytes, protein 90 mg/dL, sugar
52 mg/dL
Doxycycline, IV
dexamethasone
Complete resolution at four weeks
Parkinsonism
Soundararajan et al./2020[67] IgM serology CSF normal
Non contrast CT=parietal granuloma
Doxycycline for 14 days Complete recovery
Contd...
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
858
Table 1: Contd...
Author/Year Diagnostic testing Neuro‑imaging/other investigations Treatment Outcome
Ralph et al.[24]/2019 IgM ELISA Details not available Doxycycline + /‑ azithromycin Recovery in all except one patient who had persisting
EPS at 3 months
Premaratna et al.[68]/2015 IgM ELISA Normal CT brain and EEG Oral doxycycline and
azithromycin
Parkinsonism resolved over two weeks
Chiou et al.[69]/2013 IgM ELISA MRI normal Doxycycline, amantadine,
clonazepam
Improvement in parkinsonism and myoclonus
Transverse myelitis
Ryu et al.[70]/2020 Indirect IFA Dorso‑lumbar cord hyperintensity Steroid pulse for 5 days Improved at one‑year follow up
Yun et al.[29]/2017 Indirect IFA Swelling of cervicodorsal cord with grey matter
involvement
Doxycycline led to no response
in ATM. This was followed by
pulse steroids, oral steroids
Near normal power at three months
Mahajan et al.[71]/2016 IgM ELISA LETM on MRI‑ C4‑D11 Doxycycline
IV MP followed by oral steroids
Weakness improved but had residual bladder
complaints at one year
Lee et al.[72]/2008 Presence of typical eschar T1‑T3 increased signal intensity/enhancement
Normal CT brain, CSF
Doxycycline and steroids Not available
ATM=Acute transverse myelitis; CKV=Chikungunya virus; CSF=Cerebrospinal uid; CT=Computed tomography; EEG=Electroencephalography; EPS=Extrapyramidal syndrome; F=female; GCS=Glasgow
coma scale; IFA=Indirect immunouorescence assay; IV=intravenous; LETM=Longitudinally extensive transverse myelitis; M=male; MP=methyl prednisolone; MRI=magnetic resonance imaging;
NMO=Neuromyelitis optica; AQP4=Aquaporin 4; PCR=Polymerase chain reaction; SD=Standard deviation
Opsoclonus‑myoclonus syndrome
Scrub typhus has been recognised as a para‑infectious cause of
opsoclonus and/or myoclonus syndrome. First reported by Nam
et al. in 2010,[23] it was subsequently described in isolated case
reports [Table 1]. The largest data emanate from a retrospective
series of 18 cases.[24] In this series, opsoclonus with/without
myoclonus was a transient and self‑limited phenomenon
following onset of fever. All patients had complete resolution
at three months of follow‑up. The usual onset is in the
second week following fever and hence, it is likely to be an
immune‑mediated phenomenon, although immune modulation
seems not to be required for treatment. Neuroimaging is usually
normal or may show associated meningeal involvement. CSF
may reveal albumino‑cytologic dissociation. It is important
to recognise scrub typhus as a cause of this often dramatic
neurological condition, particularly considering its high
amenability to antibiotic therapy alone.
Cerebellar involvement
Scrub typhus can rarely cause acute cerebellitis. We identied
seven case reports in the literature describing cerebellitis
in association with scrub typhus [Table 1]. MRI revealed
cerebellar lesions in three of these cases. Most of these patients
showed resolution of symptoms with doxycycline alone.
Pure cerebellitis in the absence of meningitis may also occur,
as reported in four cases.[25–28] In this latter context, acute
cerebellar ataxia due to Plasmodium falciparum malaria forms
an important differential in tropical regions.
Parkinsonism
Parkinsonism is also uncommonly reported in scrub
typhus. Three individual case reports have described
parkinsonism occurring during the course of scrub typhus with
complete improvement following initiation of doxycycline.
Imaging (CT/MRI) was normal in all these patients. In two of
these cases, myoclonus was associated with parkinsonism. This
co‑occurrence of myoclonus and parkinsonism has also been
noted in a case series reported from southern India focussed on
delineating details of opsoclonus in scrub typhus, suggesting
a shared immunological mechanism. Of 18 patients with
opsoclonus in this retrospective series, 6 (33%) were noted
to have associated parkinsonism.[24] Although this completely
resolved in five, persistent asymmetrical extrapyramidal
features were noted in one patient at 12 weeks of follow‑up.
Whether Parkinson disease was uncovered by scrub typhus or
triggered by it in this patient remains conjectural.
Transverse myelitis
Four patients with acute transverse myelitis have been reported.
The onset of symptoms ranged from 4 to 14 days after onset
of fever. MRI variably showed cervical, dorsal and lumbar
cord enhancement and swelling. All patients were managed
with steroids in conjunction with doxycycline. In one patient,
initial doxycycline therapy alone was insufcient to stimulate
improvement, prompting the clinicians to initiate steroids,
triggering recovery. This favours an immunological basis
underlying this presentation in scrub typhus. The grey matter
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021 859
Author/Year Diagnostic test for scrub typhus Neuroimaging/other investigations Treatment Outcomes reported
Brachial plexopathy
Ting et al.[36]/1992 Weil‑Felix/IFA Electrophysiology suggestive of brachial plexus
neuropathy
Not known Substantial recovery
Contd...
Table 2: Peripheral nervous system involvement in scrub typhus other than meningitis/encephalitis
Author/Year Country Type of
study
Number of cases Age (years) Sex Onset of neurological
illness after fever (days)
Brachial plexopathy
Ting et al.[36]/1992 Taiwan Case report Fever, headache, pneumonitis 20 M Not reported
Banda et al.[37]/2016 India Case report Fever and right shoulder pain; difculty in raising right arm 45 F 5
Radiculopathy/Radiculoneuropathy
Dev et al.[73]/2019 India Case report Leptospirosis and scrub typhus co‑infection 20 M 8
Muranjan and Karande[74]/2017 India Case report Fever, vomiting, irritability, paraparesis 13 months M 3
Gangula et al.[75]/2017 India Case report Mixed infection with P. falciparum and scrub typhus 40 M 10
Sawale et al.[76]/2014 India Case report Fever, rash, eschar‑treated with doxycycline and defervesced.
Four days later, developed accid quadriparesis
41 M 15
Ju et al.[77]/2011 Korea Case series 1. Headache, fever‑ treated with doxycycline‑ developed lower
limb weakness on treatment
2. Fever, myalgia, presented in diabetic ketoacidosis.
Quadriparesis noted on examination.
60
46
M
F
10
7
Sakai et al.[78]/2016 Japan Case series 1
2
66
58
M
F
7
15
Lee SH et al.[79]/2007 Korea Case series 1. Fever which defervesced with doxycycline. Developed
quadriparesis after discharge.
42 F 14
Lee MS et al.[80]/2009 Korea Case
reports
1. Fever followed by quadriparesis and facial palsy
2. Chills, myalgia followed by quadriparesis and facial weakness
54
74
M
F
16
8
Miller Fisher syndrome
Kim et al.[38]/2014 Korea Case report Fever followed by facial palsy and bilateral ptosis 70 M 14
Mononeuritis multiplex
Hayakawa et al.[81]/2012 Japan Case report Fever, vomiting, abdominal pain due to acalculous cholecystitis.
Developed right hand hypesthesia and of both lower extremities.
Eschar present.
72 F 12
Muscle involvement
Ki et al.[82]/2018 Korea Case report 1 54 F Not reported
Kalita et al.[83]/2015 India Case series 33 patients=13 had muscle involvement Median age: 32 years
(range 15‑70 years)
61%
males
Median :15
Range: 4‑30 days
Young et al.[84]/2003 Korea Case report Fever, diffuse myalgia and muscle weakness 71 F Not reported
Multi‑axial involvement [Central
plus Peripheral Nervous System]
Kim et al.[85]/2008 Korea Case report Peripheral neuropathy plus stroke 64 M Not reported
Himral et al.[86]/2019 India Case report Multiple cranial nerve palsies and cerebellitis 24 F 4
Tandon et al.[87]/2019 India Case report Myelitis, meningoencephalitis, and axonal polyneuropathy 17 M 4
Phillips et al.[88]/2018 India Case report Meningoencephalitis and GBS 70 M 5
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
860
Table 2: Contd...
Author/Year Diagnostic test for scrub typhus Neuroimaging/other investigations Treatment Outcomes reported
Banda et al.[37]/2016 ELISA and PCR NCS suggestive of brachial neuritis Doxycycline for 10 days Pain and weakness resolved
Radiculopathy/
Radiculoneuropathy
Dev et al.[73]/2019 ELISA for scrub and
microagglutination for Leptospira
Both conrmed by PCR
NCS=demyelinating Doxycyline, cephalosporine, other
supportive measures
Rapid recovery over 10 days
Muranjan and
Karande[74]/2017
Weil‑Felix and ELISA MRI=hydrocephalus and meningeal enhancement;
CSF=5 neutrophils/mm3, 13 lymphocytes/mm3, protein
77 mg/dL, sugar 37 mg/dL.
NCS/EMG suggestive of lumbosacral radiculopathy
Chloramphenicol for 10 days Complete improvement at 2
months
Gangula et al.[75]/2017 ELISA IgM NCS=demyelinating
Blood smear: gametocyte of Plasmodium falciparum
Doxycycline, artesunate, antibiotics,
primaquine
Gradual improvement
Sawale et al.[76]/2014 Solid phase
immunochromatographic assay
antibody positive for scrub typhus
NCS=Demyelinating neuropathy with absent F waves,
CSF showed albuminocytological dissociation
Five cycles of plasmapharesis given
Previously treated with doxycycline
Gradual improvement
Ju et al.[77]/2011 Serum O. tsutsugamushi titre +
Serum O. tsutsugamushi titre +
NCS=demyelinating
NCS=Acute sensorimotor polyneuropathy
IVIg+doxycycline
Supportive
Improved
Improved
Sakai et al.[78]/2016 IgM ELISA
IgM ELISA
NCS=demyelinating
NCS=axonal
IVIg
IVIg
Improvement
Improvement
Lee SH et al.[79]/2007 IgM ELISA NCS=demyelinating IVIg Improved
Lee MS et al.[80]/2009 Indirect IFA
Indirect IFA
NCS=demyelinating
NCS=demyelinating
IVIg and prednisolone (5 days)
IVIg and prednisolone (5 days)
Improved gradually
Improved gradually
Miller Fisher syndrome
Kim et al.[38]/2014 ELISA
Anti‑GQ1b antibodies negative
NCS=Reduced SNAPs, absent H reexes IVIg for 5 days (had previously
received doxycycline)
Gradual recovery
Mononeuritis multiplex
Hayakawa et al.[81]/2012 Indirect IFA NCS=mononeuritis multiplex Minocycline 100 mg twice daily for
10 days
Improved
Muscle involvement
Ki et al.[82]/2018 Presence of eschar; Indirect IFA CPK=3337 U/L; Increased to 18,262 U/L; myocarditis Doxycycline Complete recovery
Kalita et al.[83]/2015 Immuno‑chromatographic assay of
scrub typhus antibodies and/or a
positive Weil‑Felix test
CPK levels ranged between 287‑3166 U/L
EMG=short duration polyphasic potentials
Muscle biopsy=evidence of vasculitis
Doxycycline Complete clinical recovery and
normalisation of CPK levels at
one month
Young et al.[84]/2003 Indirect IFA CPK=3250 U/L, deranged KFT; dark brown urine Doxycycline Complete recovery
Multi‑axial involvement
[Central plus Peripheral
Nervous System]
Kim et al.[85]/2008 Serum indirect IFA positive MRI=multiple infarcts; NCS=demyelinating
neuropathy; bilateral sensorineural deafness
Doxycycline Improvement in NCS and
audiometry ndings at 3 months
Himral et al.[86]/2019 IgM ELISA MRI=right frontoparietotemporal region, right thalamus,
left temporal lobe, bilateral cerebellar hemispheres
Doxycycline Improvement
Contd...
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021 861
of the spinal cord has been noted to have a specic predilection
to be affected, which may be attributable to the high metabolic
demands of spinal cord grey matter.[29]
Encephalomyelitis
Two cases of acute encephalomyelitis have been reported in
association with scrub typhus.[30,31] Both patients developed
obtundation and quadriparesis accompanied by sixth and/or
seventh cranial nerve involvement. One patient was treated
with steroids apart from doxycycline but did not respond well.
The second patient showed favourable response to doxycycline
therapy alone.
Status epilepticus
Although seizures have been reported in 6.3–21.6% of patients
with scrub typhus, status epilepticus (SE) is reported less
commonly. In one study, 13 out of 66 (19.7%) patients with
scrub typhus admitted at a tertiary centre in northern India had
SE.[32] All responded to antiseizure medications (ASMs) and
scrub typhus treatment. ASMs could be stopped within one
year in all patients as all had normal MRI and resolution of
EEG abnormalities. Non‑convulsive SE has been reported in
one patient with scrub meningo‑encephalitis.[33]
Other central nervous system manifestations
Scrub typhus has been implicated as a cause of rapidly
progressive cognitive impairment in one report.[34] However,
causality was uncertain in this case report as baseline
cognitive status of the patient prior to acute deterioration was
uncertain. Cognitive issues persisted despite improvement
in neuroimaging features after treatment for scrub typhus. In
another case report, the development of posterior reversible
encephalopathy syndrome (PRES) was also attributed to
scrub typhus.[35] However, the mechanism was unclear and
the authors attributed it to a precipitous decline in blood
pressure. Hence, strength of causation remains weak in both
these reports.
Peripheral nervous system involvement in scrub typhus
Plexus involvement
Plexus involvement in the setting of scrub typhus is rare.
We found three reports of plexus involvement with scrub
typhus. Two of these reported brachial plexopathy which
responded well to medical therapy.[36,37] One of these patients
had presented with fever along with unilateral shoulder pain
and shoulder weakness which resolved completely with
doxycycline therapy [Table 2].
Radiculoneuropathy
We found 11 reports of acute radiculoneuropathy in association
with scrub typhus.[38,73‑80] The age ranged from 13 months
to 74 years. The range of duration from onset to weakness
was 3‑16 days. Nerve conduction studies revealed both
demyelinating and axonal patterns. There was one report of
Miller Fisher syndrome.[38] Nearly all patients were managed
with intravenous immunoglobulins. All patients showed
improvement to complete resolution of weakness. The
pathogenesis appears to be immune‑mediated [Table 2].
Table 2: Contd...
Author/Year Diagnostic test for scrub typhus Neuroimaging/other investigations Treatment Outcomes reported
Tandon et al.[87]/2019 IgM ELISA C2‑D1 cord hyperintensity, NCS: sensory motor axonal
neuropathy
Doxycycline, albendazole,
azithromycin and methyl prednisolone
Incomplete recovery
Phillips et al.[88]/2018 IgM) (solid‑phase
immunochromatographic assay
MRI brain and cervical spine: normal
NCS=sensory motor demyelinating neuropathy; protein
146, cell count ‑ 70 with lymphocytic predominance,
sugar ‑ 71 mg/dL
IVIg, doxycycline, rifampicin Complete recovery
CPK=Creatine phosphokinase; CSF=cerebrospinal uid; F=female; EMG=Electromyography; GBS=Guillain‑Barre syndrome; IVIg=Intravenous immunoglobulins; IFA=Indirect immunouorescence assay;
M=male; MRI=magnetic resonance imaging; NCS=Nerve conduction studies; PCR=polymerase chain reaction
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
862
Peripheral neuropathy
One patient with mononeuritis multiplex developing in
association with scrub meningitis and acalculous cholecystitis
has been reported.[81] This patient was managed with
minocycline for 10 days with complete response.
Muscle involvement[82‑84]
In one case series, 13 of 33 (39%) patients were noted
to have muscle involvement, in the form of myalgia or
muscle weakness, in combination with elevated CPK
levels [Table 2].[83] All these patients reported severe and
generalised myalgia. They had moderately elevated creatine
phosphokinase (CPK) levels ranging from 287‑3166 U/L.
The electromyographic ndings demonstrated short‑duration
polyphasic potentials. Muscle biopsy exhibited features of
vasculitis. Treatment with doxycycline led to improvement
in clinical symptoms as well as CPK levels.
In one other case report, myalgias and high CPK levels were
associated with rhabdomyolysis and in another report, severe
myocarditis accompanied muscle involvement.[82,84] Both
patients showed complete resolution with doxycycline alone.
Despite the demonstration of vasculitis on muscle biopsy in the
series by Kalita et al., immunomodulation in terms of steroids
seems not to be necessary for the management of myositis.[83]
Multi‑axial involvement
Several case reports describe simultaneous or tandem
involvement of central and peripheral nervous system
including peripheral neuropathy/Guillain–Barre syndrome
with stroke/myelitis/meningoencephalitis, multiple cranial
nerve palsies and cerebellitis.[85‑88]
Diagnostic issues
The mainstay of diagnosis in scrub typhus is via serological
testing.[89] In primary scrub typhus, IgM antibodies usually
develop by the end of the rst week and IgG antibodies develop
by the second week. The diagnosis of scrub typhus among the
reports included in this review included mainly Weil‑Felix test,
enzyme‑linked immunosorbent assay (ELISA) and indirect
immunouorescent antibody (IFA) test. Since these tests are
associated with nuances and pitfalls, it is essential to discuss
their importance in the context of diagnosis of scrub typhus.
Since O. tsutsugamushi is an intracellular pathogen, it cannot
be isolated through standard bacterial culture but requires
cell culture. Hence, nucleic acid amplication tests form the
mainstay of diagnosis. Weil‑Felix test is the oldest diagnostic
test available, and it is based on cross‑reaction with proteus
OXK strain. It is, however, hindered by low sensitivity and
cross reacts with other rickettsial agents. IFA is considered to
be the diagnostic gold standard. This test detects the presence
of antibodies in the sera of infected individuals that bind to
immobilised antigen, using uorescein labelled anti‑human
immunoglobulin. IFA requires demonstration of four‑fold rise
in antibody titre in acute and convalescent phase sera, and no
absolute value can be used for diagnosis. ELISA is frequently
used, as it is widely available and requires less technical input
compared to IFA. The antigen used is a 56 kDa antigen which
combines with IgM antibodies against Karp, Kato, Gilliam and
TA716 strains in acute infection. Immunochromatographic
tests are rapid point‑of‑care tests, which also use the 56 kDa
antigen of Karp, Kato and Gilliam strains and have variable
sensitivity and specicity. Polymerase chain reaction (PCR)
directly detects the organism with high sensitivity and
specicity, even at low copy numbers. However, cost is a
prohibitive element, especially in low‑resource settings. In the
studies included in the review, the diagnosis was made on the
basis of ELISA in the majority of patients, followed by IFA.
ELISA has very high sensitivity of 92%–97% and specicity
of 94%–99%.[89] A false positive may arise with other acute
febrile illnesses, such as dengue, leptospirosis and spotted
fever. A purely clinical diagnosis, hinging on the presence of
an eschar was made in a handful. Eschar, if present, has high
specicity (98.9%), but its presence may be highly variable
among patients.
Treatment considerations
Doxycycline (100 mg twice daily, oral/intravenous) is the
treatment of choice. Azithromycin is an alternative agent. Most
of the neurological manifestations of scrub typhus, including
meningitis, encephalitis, myositis, cerebellar dysfunction
responded to these antibiotics. However, some of those
with an immune pathogenesis, such as transverse myelitis,
Guillain–Barre syndrome and optic neuritis, required treatment
with steroid therapy or intravenous immunoglobulins. It
is noteworthy that even neurological features with likely
immune mechanisms were reported to respond to antibiotic
therapy alone, without the need for steroids, as in several
cases of opsoclonus myoclonus, cerebellar dysfunction and
parkinsonism. Other antibiotic treatment options include
chloramphenicol, rifampicin and tetracycline.
conclusIons
Our review informs comprehensive detailing of neurological
facets related to scrub typhus described till date. Information
was gleaned from individual case reports, case series,
retrospective and prospective data. The pathogenesis of this
wide array of manifestations is also unclear, and probably
multifactorial. Among the most important observations is that
most of these neurological manifestations respond exceedingly
well to doxycycline or other appropriate antibiotics. Only few
immune‑mediated conditions such as post‑infectious optic
neuritis, cerebellitis, Guillain–Barre syndrome required
immune therapy in the form of steroids. Other dramatic
clinical conditions including opsoclonus‑myoclonus,
meningitis/encephalitis, and even ADEM responded promptly
to antibiotic therapy. Or review highlights that scrub typhus
must be enlisted high in the differential diagnosis list among
patients in endemic areas presenting with acute febrile
illness, especially in the setting of multi‑organ dysfunction
and presence of an eschar due to its eminently treatable yet
potentially lethal nature.
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021 863
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conicts of interest.
RefeRences
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. doi: 10.1371/journal.pntd.0005838.
2. Jiang J, Richards AL. Scrub typhus: No longer restricted to the
tsutsugamushi triangle. Trop Med Infect Dis 2018;3:11.
3. Fisher J, Card G, Soong L. Neuroinammation associated with scrub
typhus and spotted fever group rickettsioses. PLoS Negl Trop Dis
2020;14:e0008675.
4. Varghese 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.
5. Misra UK, Kalita J, Mani VE. Neurological manifestations of scrub
typhus. J Neurol Neurosurg Psychiatry 2015;86:761‑6.
6. Trent B, Fisher J, Soong L. Scrub typhus pathogenesis: Innate immune
response and lung injury during orientia tsutsugamushi infection. Front
Microbiol 2019;10:2065.
7. Pai H, Sohn S, Seong Y, Kee S, Chang WH, Choe KW. Central nervous
system involvement in patients with scrub typhus. Clin Infect Dis
1997;24:436‑40.
8. Varghese GM, Trowbridge P, Janardhanan J, Thomas K, Peter JV,
Mathews P, et al. Clinical prole and improving mortality trend of scrub
typhus in South India. Int J Infect Dis 2014;23:39‑43.
9. Boorugu H, Chrispal A, Gopinath KG, Chandy S, Prakash JJ,
Abraham AM, et al. Central nervous system involvement in scrub
typhus. Trop Doct 2014;44:36‑7.
10. Dubot‑Pérès A, Mayxay M, Phetsouvanh R, Lee SJ, Rattanavong S,
Vongsouvath M, et al. Management of central nervous system infections,
Vientiane, Laos, 2003‑2011. Emerg Infect Dis 2019;25:898‑910.
11. Rana A, Mahajan SK, Sharma A, Sharma S, Verma BS, Sharma A.
Neurological manifestations of scrub typhus in adults. Trop Doct
2017;47:22‑5.
12. Khan SA, Bora T, Laskar B, Khan AM, Dutta P. Scrub typhus leading
to acute encephalitis syndrome, Assam, India. Emerg Infect Dis
2017;23:148‑50.
13. Jain P, Prakash S, Tripathi PK, Chauhan A, Gupta S, Sharma U, et al.
Emergence of Orientia tsutsugamushi as an important cause of acute
encephalitis syndrome in India. PLoS Negl Trop Dis 2018;12:e0006346.
14. 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.
15. Lee HS, Sunwoo J‑S, Ahn S‑J, Moon J, Lim J‑A, Jun J‑S, et al. Central
nervous system infection associated with orientia tsutsugamushi in
South Korea. Am J Trop Med Hyg 2017;97:1094‑8.
16. Kim H‑C, Yoon K‑W, Yoo D‑S, Cho C‑S. Hemorrhagic transformation
of scrub typhus encephalitis: A rare entity. Clin Neuroradiol
2015;25:415‑8.
17. Valappil AV, Thiruvoth S, Peedikayil JM, Raghunath P, Thekkedath M.
Differential diagnosis of scrub typhus meningitis from tuberculous
meningitis using clinical and laboratory features. Clin Neurol Neurosurg
2017;163:76‑80.
18. Kakarlapudi SR, Chacko 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.
19. Naoi T, Shimazaki H, Sawada M. The rapid effectiveness of minocycline
against scrub typhus meningoencephalitis. Intern Med 2016;55:805‑9.
20. Ozair A, Kumar V, Himanshu D, Bhat V. A rare etiology behind
isolated lateral rectus palsy: Scrub typhus. J Family Med Prim Care
2020;9:2538‑40.
21. Thakur JS, Mohindroo NK, Sharma DR, Soni K, Kaushal SS. Evoked
response audiometry in scrub typhus: Prospective, randomised,
case‑control study. J Laryngol Otol 2011;125:567‑71.
22. Friedmann I, Frohlich A, Wright A. Epidemic typhus fever and hearing
loss: A histological study (Hallpike collection of temporal bone
sections). J Laryngol Otol 1993;107:275‑83.
23. Nam T‑S, Choi S‑M, Park K‑H, Kim M‑K, Cho K‑H. Opsoclonus
associated with scrub typhus. Neurology 2010;74:1925.
24. Ralph R, Prabhakar AT, Sathyendra 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.
25. Gupta S, Grover S, Gupta M, Kaur D. Cerebellitis as a rare manifestation
of scrub typhus fever. BMJ Case Rep 2020;13:e233993.
26. Bhoil R, Kumar S, Sood RG, Bhoil S, Verma R, Thakur R. Cerebellitis as
an atypical manifestation of scrub typhus. Neurology 2016;86:2113‑4.
27. Karanth SS, Gupta A, Prabhu M. Pure cerebellitis due to scrub typhus:
A unique case report. Trop Doct 2013;43:41‑2.
28. 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.
29. Yun JS, Song JS, Choi EJ, Hwang J‑H, Lee C‑S, Park EH. Successfully
managed acute transverse myelitis related to scrub typhus and serial
image ndings. Am J Trop Med Hyg 2017;96:557‑60.
30. Chen P‑H, Hung K‑H, Cheng S‑J, Hsu K‑N. Scrub typhus‑associated
acute disseminated encephalomyelitis. Acta Neurol Taiwan
2006;15:251‑4.
31. Kim DE, Lee SH, Park KI, Chang KH, Roh JK. Scrub typhus
encephalomyelitis with prominent focal neurologic signs. Arch Neurol
2000;57:1770‑2.
32. Kalita J, Mani VE, Bhoi SK, Misra UK. Status epilepticus in scrub
typhus. Epilepsia 2016;57:e125‑8.
33. 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.
34. Park JH, Jang J‑W, Lee S‑H, Oh WS, Kim SS. A case of scrub typhus
related encephalopathy presenting as rapidly progressive dementia.
Dement Neurocogn Disord 2017;16:83‑6.
35. Naveen V, Gaba S, Gupta M, Kaur D. Posterior reversible encephalopathy
syndrome in scrub typhus fever. BMJ Case Rep 2020;13:e237262.
36. 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.
37. Banda GR, Boddu SR, Ballal P, Belle J. An unusual presentation of
scrub typhus. J Clin Diagn Res 2016;10:OD07‑8.
38. 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.
39. Dhanapriya J, Dineshkumar T, Sakthirajan R, Murugan S, Jayaprakash V,
Balasubramaniyan T, et al. Scrub typhus meningitis in a renal transplant
recipient. Indian J Nephrol 2017;27:151‑3.
40. Sharma SR, Masaraf H, Lynrah KG, Lyngdoh M. Tsutsugamushi
disease (scrub typhus) meningoencephalitis in North Eastern India:
A prospective study. Ann Med Health Sci Res 2015;5:163‑7.
41. Jamil MD, Hussain M, Lyngdoh M, Sharma S, Barman B,
Bhattacharya PK. Scrub typhus meningoencephalitis, a diagnostic
challenge for clinicians: A hospital based study from North‑East India.
J Neurosci Rural Pract 2015;6:488‑93.
42. Abhilash KPP, Gunasekaran K, Mitra S, Patole S, Sathyendra S,
Jasmine S, et al. Scrub typhus meningitis: An under‑recognized cause
of aseptic meningitis in India. Neurol India 2015;63:209‑14.
43. Kar A, Dhanaraj M, Dedeepiya D, Harikrishna K. Acute encephalitis
syndrome following scrub typhus infection. Indian J Crit Care Med
2014;18:453‑5.
44. Viswanathan S, Muthu V, Iqbal N, Remalayam B, George T. Scrub
typhus meningitis in South India‑‑A retrospective study. PLoS One
2013;8:e66595.
45. Kim D‑M, Chung J‑H, Yun N‑R, Kim SW, Lee J‑Y, Han MA, et al.
Scrub typhus meningitis or meningoencephalitis. Am J Trop Med Hyg
2013;89:1206‑11.
46. Gaba S, Garg S, Gupta M, Gupta R. Haemorrhagic encephalitis in the
garb of scrub typhus. BMJ Case Rep 2020;13:e235790. doi: 10.1136/
bcr‑2020‑235790.
47. Jessani LG, Gopalakrishnan R, Kumaran M, Devaraj V, Vishwanathan L.
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]

Garg and Manesh: Neurology of scrub typhus
Annals of Indian Academy of Neurology ¦ Volume 24 ¦ Issue 6 ¦ November-December 2021
864
Scrub typhus causing unilateral optic neuritis. Indian J Pediatr
2016;83:1359‑60.
48. Cho H‑J, Choi J‑H, Sung S‑M, Jung D‑S, Choi K‑D. Bilateral optic
neuritis associated with scrub typhus. Eur J Neurol 2013;20:e129‑30.
49. Bae DW, An JY. Anti‑aquaporin‑4 antibody positive optic neuritis
following scrub typhus in an elderly female. Neurologist 2018;23:183‑4.
50. Kim J, Kim JS, Shin D‑I, Lee S‑H, Lee S‑S, Choi S‑Y. Ophthalmoplegia
due to scrub typhus. J Neuroophthalmol 2015;35:284‑6.
51. Arai M, Nakamura A, Shichi D. [Case of tsutsugamushi disease (scrub
typhus) presenting with fever and pain indistinguishable from trigeminal
neuralgia]. Rinsho Shinkeigaku 2007;47:362‑4.
52. Ete T, Mishra J, Barman B, Mondal S, Sivam RKN. Scrub typhus
presenting with bilateral lateral rectus palsy in a female. J Clin Diagn
Res 2016;10:OD16‑7.
53. Bhardwaj B, Panda P, Revannasiddaiah S, Bhardwaj H. Abducens
nerve palsy in a patient with scrub typhus: A case report. Trop Biomed
2013;30:706‑9.
54. Lin W‑R, Chen T‑C, Lin C‑Y, Lu P‑L, Chen Y‑H. Bilateral simultaneous
facial palsy following scrub typhus meningitis: A case report and
literature review. Kaohsiung J Med Sci 2011;27:573‑6.
55. Premaratna R, Chandrasena TGAN, Dassayake AS, Loftis AD,
Dasch GA, de Silva HJ. Acute hearing loss due to scrub typhus:
A forgotten complication of a reemerging disease. Clin Infect Dis
2006;42:e6‑8.
56. Kang J‑I, Kim D‑M, Lee J. Acute sensorineural hearing loss and severe
otalgia due to scrub typhus. BMC Infect Dis 2009;9:173.
57. Venketesan S, Jain D, Viswanathan S, Gayathri MS. Case report: Acute
pyelonephritis and hearing loss in scrub typhus. F1000Res 2019;8:312.
58. D’sa S, Singh S, Sowmya S. Opsoclonus in scrub typhus. J Postgrad
Med 2012;58:296‑7.
59. Koti N, Mareddy AS, Nagri SK, Kudru CU. Dancing eyes and dancing
feet in scrub typhus. Australas Med J 2015;8:371‑2.
60. Sahu D, Varma M, Vidyasagar S. Opsoclonus in scrub typhus. J Clin Sci
Res 2017;6:113.
61. Choi YJ, Choi SY, Choi J‑H, Choi K‑D. Opsoclonus‑myoclonus
syndrome associated with scrub typhus. Res Vestib Sci 2017;16:34‑7.
62. 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;35:480‑4.
63. Garg D, Dhamija RK. Opsoclonus‑myoclonus syndrome as a heralding
feature of scrub typhus: An illustrative case with a video vignette. J Mov
Disord 2021. doi: 10.14802/jmd.20148.
64. Kaiser RS, Khemka A, Roy O, Das S, Datta K. An unusual etiology of
cerebellar ataxia. Child Neurol Open 2020;7:2329048X20907754. doi:
10.1177/2329048X20907754.
65. Bhat MD, Vykuntaraju KN, Acharya UV, Ramaswamy P, Prasad C.
Isolated cerebellitis in scrub typhus. Indian J Pediatr 2015;82:1067‑8.
66. Didel S, Basha M A, Biswal M, Suthar R, Sankhyan N. Acute cerebellitis
in a child with scrub typhus. Pediatr Infect Dis J 2017;36:696‑7.
67. Soundararajan S, Viswanathan S, Jain D, Krishnamurthy V, Gayathri MS.
Acute Parkinsonism and cerebral salt‑wasting‑related hyponatremia in
scrub typhus. Cureus 2020;12:e6706.
68. Premaratna R, Wijayalath SHNC, Miththinda JKND,
Bandara NKBKRGW, de Silva HJ. Scrub typhus mimicking Parkinson’s
disease. BMC Res Notes 2015;8:438.
69. Chiou Y‑H, Yang C‑J, Lai T‑H. Scrub typhus associated with transient
parkinsonism and myoclonus. J Clin Neurosci 2013;20:182‑3.
70. Ryu H‑S, Moon BJ, Park J‑Y, Kim S‑D, Seo S‑K, Lee J‑K. Acute
transverse myelitis following scrub typhus: A case report and review of
the literature. J Spinal Cord Med 2020;43:548‑51.
71. Mahajan SK, Kumar S, Garg M, Kaushik M, Sharma S, Raina R. Scrub
typhus with longitudinally extensive transverse myelitis. J Vector Borne
Dis 2016;53:84‑6.
72. Lee KL, Lee JK, Yim YM, Lim OK, Bae KH. Acute transverse myelitis
associated with scrub typhus: Case report and a review of literatures.
Diagn Microbiol Infect Dis 2008;60:237‑9.
73. Dev N, Kumar R, Kumar D. Guillain‑Barre syndrome: A rare
complication of leptospirosis and scrub typhus co‑infection. Trop Doct
2019;49:248‑9.
74. Muranjan M, Karande S. Acute paraparesis due to lumbosacral
radiculopathy with concomitant meningitis: Unusual presentation of
scrub typhus. Pediatr Infect Dis J 2016;35:1279‑80.
75. 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.
76. 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.
77. 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.
78. 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.
79. Lee S‑H, Jung S‑I, Park K‑H, Choi SM, Park MS, Kim BC, et al.
Guillain‑Barré syndrome associated with scrub typhus. Scand J Infect
Dis 2007;39:826‑8.
80. Lee M‑S, Lee J‑H, Lee H‑S, 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.
81. Hayakawa K, Oki M, Moriya Y, Mizuma 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.
82. Ki Y‑J, Kim D‑M, Yoon N‑R, Kim S‑S, Kim C‑M. A case report of scrub
typhus complicated with myocarditis and rhabdomyolysis. BMC Infect
Dis 2018;18:551.
83. 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.
84. Young PC, Hae CC, Lee KH, Hoon CJ. Tsutsugamushi
infection‑associated acute rhabdomyolysis and acute renal failure.
Korean J Intern Med 2003;18:248‑50.
85. Kim JH, Lee SA, Ahn T‑B, Yoon SS, Park KC, Chang DI, et al.
Polyneuropathy and cerebral infarction complicating scrub typhus.
J Clin Neurol (Seoul, Korea) 2008;4:36.
86. 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.
87. 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.
88. 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.
89. Kannan K, John R, Kundu D, Dayanand D, Abhilash KPP, Mathuram AJ,
et al. Performance of molecular and serologic tests for the diagnosis of
scrub typhus. PLoS Negl Trop Dis 2020;14:e0008747.
[Downloaded free from http://www.annalsofian.org on Friday, December 17, 2021, IP: 51.175.129.108]