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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 6  |  Page : 283-287

Scrub typhus meningoencephalitis in children: A single centre, observational study from Eastern India


1 Department of Biochemistry, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Submission16-Aug-2021
Date of Decision29-Sep-2021
Date of Acceptance11-Oct-2021
Date of Web Publication19-Nov-2021

Correspondence Address:
Dr. Sibabratta Patnaik
Associate Professor, Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcc.jpcc_74_21

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  Abstract 


Background: Scrub typhus is being reported from different parts of India. Meningitis or meningoencephalitis among various neurological complication seen in scrub typhus is not uncommon. Delay in diagnosis may cause higher mortality without prompt treatment. The aim of the study was to describe the various manifestations of scrub typhus meningoencephalitis and their outcome from eastern part of India.
Subjects and Methods: A prospective observational study of scrub meningoencephalitis was carried out at Kalinga Institute of Medical Sciences, between October 2018 and August 2020.The diagnosis was made based on the compatible clinical features, positive Scrub Ig M by ELISA and cerebrospinal fluid lymphocytosis (>5 cell/cmm), after excluding other causes of meningoencephalitis.
Results: Twenty-seven (12.38%) cases of scrub meningoencephalitis were included in the study with male (66.6%) predominance. All had presented with fever of mean duration of 8.5 days of illness. Altered sensorium and seizure was observed in 70.5% and 62.9% of our patients along with two patients who had sixth cranial nerve palsy. Eschar was found in 25.9% of our children. The mean CSF cell count, protein and glucose were 25 cells/cmm,84.2 mg/dL and 62.9 mg/dL respectively with lymphocytosis in all cases. There was no mortality in this study.
Conclusion: Meningoencephalitis is an important complication of scrub typhus in children. Unlike most viral encephalitis cases, it has a definite treatment with good outcome, if treated early.

Keywords: Children, Eastern India, meningitis, scrub typhus


How to cite this article:
Parida P, Agrawal AK, Biswal S, Patnaik S, Behera CK. Scrub typhus meningoencephalitis in children: A single centre, observational study from Eastern India. J Pediatr Crit Care 2021;8:283-7

How to cite this URL:
Parida P, Agrawal AK, Biswal S, Patnaik S, Behera CK. Scrub typhus meningoencephalitis in children: A single centre, observational study from Eastern India. J Pediatr Crit Care [serial online] 2021 [cited 2021 Nov 27];8:283-7. Available from: http://www.jpcc.org.in/text.asp?2021/8/6/283/330731




  Introduction Top


Scrub typhus, tsutsugamushi disease, or chigger-borne rickettsiosis is an acute febrile illness among children that is caused by infection with the bacterium Orientia tsutsugamushi following the bite of infected mite.[1] The word “scrub” refers to the type of vegetation that harbors the vector and “typhus” has been derived from the Greek word “Typos” which means “fever with stupor.”[2]

It is characterized by fever, rash, eschar, hepatosplenomegaly, lymphadenopathy, edema (periorbital or pedal edema or anasarca), conjunctival injection, and other systemic presentations involving the respiratory, gastrointestinal, renal, central nervous system (CNS).[3]

Neurological manifestations are quite varied. Meningoencephalitis due to scrub typhus is usually seen without focal neurological signs. However, focal neurological signs such as bilateral sixth and seventh cranial nerve palsies, isolated sixth cranial nerve palsy have been reported.[4],[5] Scrub typhus has also been associated with opsoclonus, transient parkinsonism, and myoclonus.[6] Pathological findings of CNS involvement include diffuse or focal mononuclear cellular infiltration of the leptomeninges, typhus nodules which are clusters of microglial cells, and brain hemorrhage.[7] Even in suspected cases of scrub typhus, due to paucity of laboratory investigations in all places in developing countries, results in delay in diagnosis of scrub meningoencephalitis, causing higher mortality. Though it has been reported from various parts of India, there are only few case series from Eastern India.[8] Hence this prospective observational study was done on meningoencephalitis in scrub typhus and its outcome in pediatric patients admitted to a tertiary care teaching hospital in Eastern India.


  Materials and Methods Top


All cases of scrub typhus meningoencephalitis, below 18 years admitted to Pediatrics department in tertiary care hospital of Eastern India between October 2018 to August 2020 were prospectively evaluated. The study was cleared by the Institutional Review Board and Ethics Committee (No.KIMS/KIT/IEC/165/2018) date 19.8.2018. Scrub typhus was diagnosed by detecting scrub typhus IgM by ELISA method (Bio-Rad, Califonia, USA). Lumbar puncture was performed in Scrub typhus patients with signs of meninigitis and also for those presented with seizures, neurodeficits or altered mental states such as confusion, obtundation, stupor or coma without evident cause like shock or hypoglycemia. In addition to cell counts, cerebro spinal fluid (CSF) protein, and glucose estimation, the centrifuged deposit was subjected to the Grams, Ziehl-Neilsen and India ink staining techniques to identify bacteria, acid-fast bacilli, and Cryptococcus respectively. Patients who had a positive Scrub IgM in blood and CSF analysis suggesting lymphocytic pleocytosis (>5 cells/cmm), in whom other causative organisms were not found on stains or cultures, were defined as scrub meningoencephalitis cases. During admission, detailed clinical history, physical examination, and laboratory tests were carried out. Signed informed consent was obtained from parents prior to inclusion in the study. All patients were treated with doxycycline (oral/parenteral) depending upon the severity of illness along with other supportive management. The details about clinical examination, laboratory investigation, treatment and complications were recorded in a predesigned format. The data was processed using IBM SPSS statistics for Windows, Version 25.0. Armonk, NY: IBM Corp. Numerical data were analyzed by descriptive statistics. Categorical variables were expressed as percentage. Continuous variables were expressed as mean ± standard deviation. P < 0.05 was considered as significant.


  Results Top


A total of 27 cases (12.38%) were confirmed as scrub meningoencephalitis by scrub typhus IgM ELISA and CSF study. Mean age of patients was 6.6 years and there was a male preponderance (66.6%). Mean duration of fever before presentation was 8.5 days. Along with fever and neurologic manifestations, majority had a toxic look (84.2%) and facial suffusion (51%). Only one patient had papilledema with clinical features of raised intracranial pressure (ICP) and two had sixth cranial nerve palsy. Eschar was seen in only 7 patients (25.9%). Other common presenting complaints were altered sensorium (70.3%), seizures (62.9%), pain abdomen (22.2%) and vomiting (22.2%). Spleno-hepatomegaly was present in 48.1% and 44.4% of the patients respectively [Table 1].
Table 1: Demography and clinical presentations of scrub meningoencephalitis

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Mean hemoglobin was 10.1 g/dl, mean total leucocyte count (TLC) was 16951/cmm and mean platelet count was 1.98 lakh/cmm. All children had abnormal CSF findings which includes mean CSF protein, sugar, cell count as 84.2 mg/dl, 62.9 mg/dl and 25 cells/mm3 respectively and CSF lymphocytosis was seen in all cases. Hepatic involvement in the form of raised alanine aminotransferase (ALT) >35 U/L and aspartate aminotransferase (AST) >40 U/L was seen in 85% cases. Pulmonary involvement was predominantly in the form of cough (48%) and pneumonia (22.2%). None of our patients had renal dysfunction [Table 2].
Table 2: Laboratory parameters in scrub meningoencephalitis

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Neuroimaging in the form of computed tomography (CT scan) and magnetic resonance imaging (MRI) of brain was done in 6 and 2 cases respectively. CT scan of brain was normal in all 6 cases while MRI done on child with bilateral abducens palsy showed prominent perioptic CSF space suggestive of raised ICP. The child with unilateral abducens palsy showed features of cerebral edema and raised ICP. All patients were treated with doxycycline (Injectable or oral) for 7-10 days depending upon the severity. Out of total 27 cases of Scrub meningoencephalitis, 12 (44.4%) required pediatric intensive care unit (PICU) admission: 8 (6.66%) for altered sensorium, 4 (33.3%) for convulsion, 3 (25%) for meningoencephalitis with shock requiring inotropes and 3 (33.3%) for respiratory distress. One patient required mechanical ventilation due to acute respiratory distress syndrome (ARDS). Seizure was controlled with appropriate anti-epileptic drugs. Additional anti-edema measures were given in selected cases with raised ICP or cranial nerve palsy. None of our patients received any form of renal replacement therapy. No one died due to illness with gradual improvement of neurological deficits in affected cases. During the study period total 56 cases of encephalitis were admitted to PICU and six of them died (two in autoimmune encephalitis, one in Japanese encephalitis, one in subacute sclerosing panencephalitis and two from other viral encephalitis with multi organ dysfunctional syndrome), whereas all children with scrub meningoencephalitis recovered.


  Discussion Top


In a study from PGI, Chandigarh, 29% of scrub typhus cases had features of meningoencephalitis,[9] while we found meningoencephalitis in 12.4% cases only. Most commonly affected children in this study were between 5 years and 10 years (29.6%) followed by 1 month to 1 year and 10–18 years with 25.9% each, while children between 1 and 5 years (18.5%) were affected less frequently. A study from Uttarakhand, reported scrub meningoencephalitis more commonly in 11–18 years age group (92.3%)[10] though the sample size included in that study was relatively small. Male children outnumbered females with a ratio of 2:1 in present study. Similar observations were found from Kolkata[8] (4:1), however another one showed ratio of 0.4:1 with more female patients.[10]

Fever was a presenting symptom in 100% of cases with similar findings in most of the studies. Seizure was the most common CNS manifestation seen in 17 (62.9%) patients. In a study from North India, seizure was detected in 90.9% cases[11] while other studies had found seizures in 46.1% cases[12] and 23.08%[10] respectively. Though headache is a common complaint in meningoencephalitis, we found it only in 37.04% of children. Studies have found varied incidence of headache ranging from 16% to 100% cases.[10],[11]

Neurological deficits found in our study include altered sensorium (70.3%), seizure (62.9%) and sixth cranial nerve palsy (one had unilateral palsy and other had bilateral palsy). Both of them recovered over a period of 8–10 weeks. Other patients have no residual deficit after recovery. Involvement of both central and peripheral nervous system is not uncommon in scrub typhus.[13] Reported cranial nerves to be affected are optic, abducens, facial and cochlear nerves.[4],[5],[14] Two of our patients had abducens palsy along with feature of raised ICP. As neuro imaging studies were normal, raised ICP behaving as false localising sign could be possible. But microinfarction involving vasa narvorum has been postulated to be the cause of abducens palsy in few case reports. Some studies had reported facial palsies, hemiparesis, Guillain–Barre syndrome and cortical blindness[13],[15],[16] which were absent in our study. Nuchal rigidity was found in 40.7% of our cases, while two other pediatric studies had detected meningeal signs in 100% and 47% of their cases respectively.[10],[11]

CSF analysis was done in all patients and was found to be abnormal in all (100%) patients. CSF cell count was 25.2 cells/mm3, with lymphocyte predominance (mean 89.8%), and elevated protein (mean 84.2 mg/dl) with glucose value of 62.9 mg/dl. High protein levels were consistently found in most studies.[10],[13] Though CSF sugar was normal in index study, one study had documented hypoglycorrhachia.[11]

Other common examination findings in these children were splenomegaly (48.1%) and hepatomegaly (44.4%). There are evidence of varying degree of hepatomegaly and splenomegaly in different studies.[8],[10] Eschar, considered to be pathognomonic of scrub typhus was detected only in 25.9% of our patients. We found more cases with eschar as compared to other pediatric studies, where eschar was found in 7.6% and 15.38% of cases respectively.[10],[11] However our data was similar to two adult studies where eschar was found in 30.77% and 27.5% respectively.[10],[12]

Investigations showed mean value of TLC was 16951/cmm. Leucocytosis is a common finding in most studies. Though thrombocytopenia more commonly seen in scrub typhus, we did not find similar results.[10] The mean value of C-reactive protein was high (65.7 mg/L), similar to other studies. The level of both ALT (79.6 U/L) and AST (125.4 U/L) levels were elevated. Though mild hepatitis like features are common in scrub typhus meningitis,[10] elevated level of AST (>120 IU/L) has been associated with severity of scrub typhus.[17] Mean serum albumin level was 3.2Gm/dL. Hypoalbuminemia was reported in previous study and was significantly correlated with severity.[18] Renal function tests were normal in all of our patients. It seems that CNS involvement occurs early, leading to early hospitalisation and initiation of treatment, resulting in avoidance of complications like kidney injury and ARDS.[19]

Though CT brain was normal in 6 patients, MRI brain done in 2 patients revealed evidence of cerebral edema. Some studies have shown various neuroimaging features like infarcts, cerebral edema, raised ICP.[20] One study showed that with newer and advanced MRI sequences; features such as hemorrhages, meningoencephalitis, infarctions, cranial nerve involvement, thrombosis, and hypoperfusion can be detected more frequently compared to routine MRI sequences[20] Amongst all acute encephalitis syndromes, presence of fever of >8 days, cerebrospinal fluid protein >1000 mg/L, serum glutamic oxaloacetic transaminase >100 IU/L, pneumonia at admission, and absence of petechiae are significant independent predictors for scrub typhus meningoencephalitis diagnosis.[11]

Presence of meningoencephalitis in scrub typhus, is one of the independent predictors of severity and it requires intensive care management.[9] There are many treatments proposed for management of Scrub typhus. In a study from North East, cases were treated with injectable Azithromycin and oral Doxycycline.[12] Parenteral azithromycin was found to be effective in cases where doxycycline is contraindicated or not available.[21] Some studies showed the effectiveness of clarithromycin in management.[22] In this study, we used both oral and injectable doxycycline. Injectable drugs were used for children who are critically ill and later converted to oral form. Everyone responded well. Duration of treatment was 7-10 days in all patients. Safety of doxycycline in children has been discussed in many forums because of the concern about staining of teeth. However, a recent systematic review gives reassurance about the use of doxycycline.[23] In our study length of hospital stay of scrub typhus cases was 8.5 days. Another study conducted by Rakholia et al. also reported average hospital stay 9.4 ± 2.3 days. There is no mortality in our study population, similar to the study from Uttarakhand.[10] In a study from North India mortality was as high as 10.6%.[11]

Though we had done a prospective study, sample size and single centre study were the major limitations.


  Conclusions Top


Meningoencephalitis is an important complication of scrub typhus, among which 40% required admission to PICU. It should be differentiated from other acute encephalitis syndrome. Clinical suspicion and laboratory tests including CSF study are required to fetch the diagnosis. Unlike most viral encephalitis cases, it has a definitive therapy with good outcome, if started early. Our findings would help clinicians in early identification of severe cases who might get benefit from intensive care treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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