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Introduction

Encephalitis refers to acute inflammatory process

affecting the brain. AES may present as encephalitis,

meningoencephalitis or meningitis and may be caused

by viruses, bacteria, mycobacteria, rickettsia and rarely

by toxoplasma. Viral infections are most common and

important cause of encephalitis. JE and Dengue are

more prevalent in South East Asia1. As a part of efforts

to control JE the World Health Organization (WHO)

is providing a set of standards for JE surveillance, which

require the identification of patients with AES.2,3

According to clinical case definition by WHO,

AES is defined as acute onset of fever and a change in

mental status including symptoms such as confusion,

disorientation, or inability to talk and/ or new onset of

seizures excluding febrile convulsions in a person of

any age at any time of year.4 Cerebral malaria and non

infectious causes of encephalopathy are required to

be excluded while considering AES. Confirmation of

diagnosis of JE is usually done by JE specific titers of

IgM antibodies in serum and or in CSF during acute

illness of suspected AES case.2

JE is caused by a zoonotic flavivirus which is one

of the common causes of AES. It is difficult to eradicate

Study of acute encephalitis syndrome in children

Y. R.Khinchi1, A. Kumar2, S. Yadav3

1Associate professor, 2Second year MD resident, 3Third year MD resident; Department of   Pediatrics and Neonatology,

College of Medical Sciences, Bharatpur, Nepal

Abstract

Objective: To determine the profile and outcome of children admitted with Acute Encephalitis Syndrome

(AES) and to find out the prevalence of Japanese Encephalitis (JE) IgM antibodies positive cases among

these patients with their case fatality rate (CFR).

Materials and methods: Study consist of retrospective analysis of hospital records of children up to 15

years of age admitted with diagnosis of AES in pediatric wards of College of Medical Sciences- Teaching

Hospital, Bharatpur from January 2007 to December 2008.

Results: During two years, 61 patients of AES were admitted. Male and female patients were 33 and 28

respectively. Meningitis accounted for 29 and encephalitis for 32 patients. JE IgM seropositive cases

contributed for 18% of all AES cases. Case fatality for JE was 16.6%.

Conclusions: Japanese Encephalitis is endemic in catchment area of the hospital. JE has significant

morbidity and mortality which can be prevented by immunization and mortality can be reduced if supportive

interventions are provided in time.

Key words:  AES, JE, CFR.

Correspondence: Dr. Y. R.Khinchi

E-mail: dr_khinchi@yahoo.com

, 7-13 Original ArticleJournal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1

7



JE because it is transmitted from natural reservoirs like

pigs, waddling birds which are important amplifying

hosts and man is involved as an accidental host. JE

has been controlled effectively through vaccination

programs in several Asian countries like Japan, Korea,

China and Thailand.5 Culex tritaeniorhyncus is the

principle vector of JE in Nepal, as the species is

abundantly found in the rice field ecosystem of the

endemic areas during the transmission season. Increase

in JE cases is observed after the rainy season peaking

between August and September.6

JE was first observed in Nepal in 1978 as an

epidemic in Rupandehi district of the Western

Development Region and Morang of eastern region.6

Between 1978 and 2004 around 27000 cases

reported with approximately 5000 deaths. From 2004

to 2006, 1323 cases of JE were confirmed in lab. Total

24 Tarai districts are endemic with CFR ranging from

5-29% with 10% as an average.  Average case fatality

in all ages is about 20% in Nepal.6 CFR and morbidity

due to JE can be reduced significantly by early diagnosis

and appropriate supportive care.5

Present study is carried out with the objective to

evaluate the clinical profile of hospitalized pediatric AES

cases, to determine the prevalence and outcome of

meningitis or encephalitis presentation of AES and to

document what proportion of these cases are serology

proven JE with case fatality.

Materials and methods

This study is carried out in children with clinical

diagnosis of AES admitted in pediatric wards of College

of Medical Sciences Teaching Hospital, Bharatpur, Nepal

for 2 years from January 2007 to December 2008.

This is a retrospective descriptive study done on

61 patients up to 15 years of age diagnosed as AES

according to WHO case definition admitted during two

years. Case records of these patients were analyzed

in detail and data recorded for history, examination,

investigation and outcome. Patients were categorized

on the basis of predominant clinico-investigational

picture suggestive of meningitis or encephalitis.

Surveillance of JE is being done by WHO in

endemic areas through detection of JE IgM antibodies

in acute stage of AES patients either in serum or serum

and CSF samples. College of medical sciences-

teaching hospital is one of the JE surveillance center

recognized by WHO, Nepal. Blood and or CSF

samples of all clinical AES cases from our institution

are routinely being sent to WHO program for

immunization preventable diseases (WHO IPD) field

office, Hetauda as per requirement suggested by WHO

for confirmation by JE IgM (ELISA) which is

processed at Nepal public health laboratory Teku,

Kathmandu. Reports of these cases were correlated

later with respective patient when received through

WHO IPD field office, Hetauda.

All pediatric patients upto 15 years of age fulfilling

the standard WHO case definition of AES as

mentioned above were included in the study. Exclusion

criteria included patients presented like AES picture

but with clinico-investigational diagnosis confirmative

of cerebral malaria, Reye syndrome or other non

infectious encephalopathy. Statistical significance was

analyzed by deriving p value.

Results

There were 61 cases of AES pediatric patients up

to 15 years of age during two years of study period

fulfilling the WHO definition. Profile of these cases is

shown in table-1. Age distribution of these cases was

14, 16 and 31 in less than 1 year, 1 to 5 year and 5 to

Journal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1

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15 years respectively. Male and female patients were

33 and 28 and this was statistically insignificant

(p>0.05, Table-2). Meningitis and encephalitis cases

were 29 and 32 respectively. Encephalitis was

documented significantly more in male as compared

to female (p<0.015) whereas meningitis was more

commonly observed in female (Table-3). Out of total

61 cases of AES, 30 were discharged home, 13

expired, 9 were referred most often on request and

another 9 left against medical advice (LAMA).

Statistically significant patients of meningitis (p<0.0003)

and encephalitis (p<0.04) were discharged home as

compared to LAMA, referred or expired (Table-4).

Excluding LAMA and referred cases there was

statistically less mortality in meningitis (p<0.05) as

compared to high mortality in encephalitis patients

(Table-5).

Serology for JE IgM (ELISA) was positive in 11

cases as per documented reports received from WHO

field office out of 61 total cases of AES. Most of these

patients (72.7%) were from Nawalparasi (8 out of 11)

and one each from Chitwan, Tanahu and Makwanpur

districts. In year 2007, one, 3 and 4 cases were

documented in August, September and November

respectively, whereas in 2008, 2 cases occurred in July

and 1 in August. IgM seropositive cases consisted of

18% of all AES patients (Table-6). Among 11

seropositive cases male patients were 7 (63.6%) as

compared to 4 (36.3%) female cases. No JE

seropositive case was found in less than 1 year, only 2

(18.1%) cases belonged to 1 to 5 years age group

and maximum 9 (81.8%) patients were between 5 to

15 years of age. Table-6 shows that statistically highly

significant less number of patients had positive JE IgM

serology in year 2008 (p<0.00004) as compared to

year 2007 (p<0.0157). Among those 11 cases positive

for JE IgM, 6 (54.5%) were discharged home, 2

(18.1%) were taken LAMA, none was referred and

remaining 3 (27.2%) expired in the hospital.

Discussion

The JE is the single largest cause of viral encephalitis

in the world7. To monitor JE surveillance, WHO has

given clinical case definition of AES so that  these cases

are subjected for confirmative diagnosis by IgM

captured ELISA in blood and or CSF and preventive

and supportive interventions can be planned and

implemented in endemic or epidemic situations.

JE is a significant health problem throughout Asia.

Epidemics of JE are documented in Southeast Asia

and most of the Indian subcontinent. In 2005, there

was a severe epidemic of JE in the Eastern Uttar

Pradesh, as well as in the adjoining areas of the

neighboring state of Bihar and in Nepal.7 The clinical

disease presents with a prodromal stage, an acute

encephalitic stage with varying grades of coma,

convulsions and neurological deficits with high mortality

or convalescent stage of recovery often with sequelae.

Clinical profile of AES patients in this study (Table-

1) included vomiting, seizures, Glasgow coma scale

(GCS) <8, meningeal irritation signs,  neurological

deficit in 49.1%, 90.1%, 29.5%, 49.1% and 16.2%

respectively. Study done by Gupta N et al. observed

vomiting in 41.4%, seizures in 79.3%, altered

sensorium in 51.7%, signs of meningeal irritation in

17.2% and neurological deficit in 34.5% of their cases

in the study done in hospitalized patients suspected of

JE.8 Some of these findings are comparable with present

study. In another study done to determine the etiology

of febrile encephalopathy by Rayamajhi et al. seizures

was documented in 58% of cases which is less than

our data.9 Kumar et al. described vomiting in 6.5%,

Y. R.Khinchi et al. Study of acute encephalitis syndrome in children

9



meningeal signs in 35.1%, GCS <7 in 44.1%,

extrapyramidal features in 31.1% and convulsions in

98.7% in hospitalized patients during JE epidemic in

2005 which occurred in Eastern Uttar Pradesh and

adjoining areas of India. These all patients were IgM

positive for JE.7 Differences in clinical picture may be

variable depending on various factors like sample size,

demographic and epidemiological differences as well

as study objective including whether done entirely on

encephalitis, investigation of JE epidemic or as per

WHO case definition of AES surveillance.

Prevalence of meningitis and encephalitis (Table-3) was

47.5% and 52.4% respectively among 61 cases of

AES. Prevalence of JE patients presenting with

encephalitis form ranged between 60 to75% and

presenting with meningitis form consisted up to 5 to

10% cases.10 Though these data cannot be compared

with our observations which were covering all patients

of AES, whereas the data in the reference cited above

are for JE cases but still this suggest that patients may

present in either way.

Number of AES patients discharged home (58.6%)

was significantly more in meningitis (total 29) group

(Table-4, p<0.0003) as compared to LAMA (17.2%),

referred (17.2%) or expired (6.8%). Out of 32 cases

of AES diagnosed as encephalitis 40.6% were

discharged home, 12.5% taken LAMA, 12.5%

referred and 34.3% patients expired (Table-4,

p<0.41). High mortality in this group is consistent with

universal observations of more number of deaths in

encephalitis including JE.

Encephalitis in this study was statistically more

frequent in 2007 and meningitis was more common in

2008 (Table-3, p<0.015). There was significantly less

number  JE IgM positive cases documented in 2008

(Table-6, p<0.00004) as compared to 2007 (Table-

6, p<0.0157). Less number of JE IgM positive cases

(3, 9.3%) in the year 2008 as compared to 2007 (8,

27.5%, Table-6) may be because of the fact that

effective active immunization campaign involving our

institution also by WHO IPD with SA14-14-2 vaccine

to all children up to 15 years of age before rainy season

in 2008 was undertaken in JE endemic areas identified

based on surveillance done in 2007.

In this study most of the cases were confined to

Nawalparasi district and occurred after rainy season

in September and November in 2007 and July and

August in 2008. Other studies also documented

prevalence of disease during these months8,11. This is

because of increase mosquito density during post

monsoon period.

Among 11 seropositive cases 7 (63.6%) were

male as compared to 4 (36.3%) female patients. Similar

trend was also observed in other studies.9,11 This may

be attributed partly because male children are more

likely to go out doors or to agriculture area where

mosquito vector of the disease is abundant. Most often

affected (81.8%) children were between 5 to 15 years

of age in the present study which is more or less

comparable to other studies.8,9 This may be correlated

to more ambulation in this age group like playing

outdoors, going to school or agriculture rice fields

predisposing them to vector mosquito bite.

After excluding LAMA and referred cases there

were 9 patients seropositive for JE IgM who stayed in

hospital till final outcome. Out of these 6 were

discharged home whereas 3 died in the institution during

two years of study period. Out of those 6 patients who

survived 4 were asymptomatic, 1 developed motor

deficit with extrapyramidal features and another one

had dysphasia on discharge. CFR is the number of

deaths/ number of cases diagnosed per year.12 CFR in

Journal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1

10



this study was 16.6%. CFR due to JE in Nepal ranged

from 9.8% to 46.3% from 1978 to 2003. During recent

years CFR has declined and contained below 20%

which is comparable to this study.6 CFR according to

the study conducted over wide geographical area

covering South Asia, Southeast Asia, China, Pacific

Rim and North Australia was between 20-30%.10

Other studies reported CFR for JE as 8.3% by

Rayamajhi A et al. and 12.5% by Shrestha SR et al.,

which is less than our study.9,11 These differences may

be due to severity of disease at presentation, delay in

referral, different geographical and epidemiological

factors.

Conclusions

JE confirmed by JE IgM serology contributed to

significant cases of AES in children up to 15 years of

age. JE is endemic in catchment region of this institution.

Male were found to be at more risk for JE and

significant number of patients were between 5 to 15

years. CFR for JE in this institution is comparable to

global results. JE has significant morbidity and mortality

which can be prevented by highly effective live

attenuated single dose vaccination or other preventive

measures. Sequelae and mortality can be reduced if

patients are referred in time for supportive interventions

at proper place.

Acknowledgements

We are highly thankful to Dr Umesh K. Shukla,

Surveillance Medical Officer, WHO IPD field office,

Hetauda for his help in JE surveillance and providing

data of samples collected from our patients. We are

also thankful to Mr Naresh Manandhar, Assistant

Professor, department of community medicine of this

institution for his kind help in statistical analysis.

References

1. Mishra U K, Tan C T, Jayanti K. Seizures in encephalitis.

Neurology Asia; 2008:1-13.

2. Fidan J, Emsley H, Fischer M et al. The incidence of

acute encephalitic syndrome in western industrialized

countries. Virology journal 2008, 5: 134 (http://

www.virologyj.com/content/5/1/134; assessed on

12.2.2010)

3. WHO-recommended standards for surveillance of

selected vaccine preventable diseases (http://

www.who.int/vaccine-documents/DocsPDF/843.pdf;

assessed on 10.2.2010)

4. Solomon T, Thao TT, Lewthwaite P et al. A cohort study

to assess the new WHO Japanese Encephalitis

surveillance standards. Bulletin of the World Health

Organization 2008;86:178-86

5. Rao PN. Japanese Encephalitis. Indian Pediatrics

2001; 38:1252-64.

6. Bista M B, Shrestha J M. Epidemiological situation of

Japanese Encephalitis in Nepal. J Nep Med Assoc; 44:

51-6.

7. Kumar R, Tripathi P, Singh S et al. Clinical features in

children hospitalized during the 2005 epidemic of

Japanese Encephalitis in Uttar Pradesh, India. Clinical

infectious diseases, 2006; 43:123-31.

8. Gupta N, Chatterjee K, Karmakar S et al. Bellary, India

achieves negligible case fatality due to Japanese

Encephalitis despite no vaccination: An outbreak

investigation in 2004. Indian J Pediatr 2008;

75(1):31-7.

9. Rayamajhi A, Singh R, Prasad R et al. Clinico-

laboratory profile and outcome of Japanese

Encephalitis in Nepali children. Annals of tropical

pediatrics: International child health. 2006; 26, 4:293-

301.

Y. R.Khinchi et al. Study of acute encephalitis syndrome in children

11



10. Solomon T. Current concepts: Flavivirus Encephalitis.

N Eng J Med 2004; 351:370-8.

11. Shreshta SR, Awale P, Neupane S et al. Japanese

encephalitis in children admitted at Patan hospital. J

Nepal Paediatr. Soc. 29, 1:17-21.

12. Joshi AB, Banjara MR, Bhatta LR et al. Status and trend

of Japanese encephalitis epidemics in Nepal: A five-

year retrospective review. Journal of Nepal health

research council, 2004; 2, 1:59-64.

Table-2: Distribution of AES cases According to Age, Sex and Year:

Table-1: Profile of Acute Encephalitis Syndrome (AES) cases (61):

Journal of College of Medical Sciences-Nepal, 2010, Vol. 6, No. 1

12

Feature Number (%)

Fever 61(100%)

Altered Sensorium 61(100%)

Vomiting 30(49.1%)

Headache/ Excessive cry 27(44.2%)

Seizures 55(90.1%)

Glasgow Coma Scale (GCS) < 8 18(29.5%)

Extrapyramidal features 8(13.1%)

Signs of Meningeal Irritation 30(49.1%)

Neurological deficit 10(16.2%)

Fundoscopy

Normal 47(77%)

Suggestive of papilledema 2(3.2%)

Not required (anterior fontanel was open and flat) 12(19.6%)

 CSF

Suggestive of Bacterial meningitis

(Cell counts/ Biochemistry/Gram stain or C/S) 25(40.9%)

Suggestive of viral Meningitis/ Encephalitis

(Cell counts/Biochemistry/Neg. Gram stain/Sterile C/S) 22(36%)

Normal CSF/ Refused for Lumber puncture 14(22.9%)

Age 2007 (AES 29) 2008 (AES 32) 2007 & 2008 Total (61)
Male Female Male Female Male Female

<1 yr 4(13.7%) 2 (6.8%) 6 (18.7%) 2 (6.2%) 10 4 14(22.9%)
1 to 5 yr 2 (6.8%) 3 (10.3%) 7 (21.8%) 4 (12.5%) 9 7 16(26.2%)
5 to15 yr 8(27.5%) 10(34.4%) 6 (18.7%) 7 (21.8%) 14 17 31(50.8%)
Total 14(48%) 15(51.7%) 19(59.3%) 13(40.6%) 33 28 61
p value p >0.05 p >0.05



Table-3: Distribution of total cases of Meningitis / Encephalitis according to Sex in 2 yrs

Table-4: Outcome of Encephalitis/ Meningitis (AES) cases in 2 years

Table-5: Outcome of Encephalitis/ Meningitis (AES) excluding LAMA/ Referred cases

Table-6: AES cases according to Serology for JE IgM

Y. R.Khinchi et al. Study of acute encephalitis syndrome in children

13

Diagnosis 2007 and 2008 Total (AES)

Male (33, 54%) Female (28, 46%) 61

Meningitis 11 (33.3%) 18 (64.2%) 29 (47.5%)

Encephalitis 22 (66.6%) 10 (35.7%) 32 (52.4%)

p value                           p < 0.015

Diagnosis Encephalitis (32, 52.4%) Meningitis (29, 47.5%) AES (61)

Discharged 13 (40.6%) 17 (58.6%) 30 (49.1%)

LAMA 4 (12.5%) 5 (17.2%) 9 (14.7%)

Referred 4 (12.5%) 5 (17.2%) 9 (14.7%)

Expired 11 (34.3%) 2 (6.8%) 13 (21.3%)

p value  p <0.41  p <0.0003 p <0.0001

Diagnosis Encephalitis (24, 55.8%) Meningitis (19, 44.1%) Total  (43)

Discharged 13 (54.1%) 17 (89.4%) 30 (69.7%)

Expired 11 (45.8%) 2 (10.5%) 13 (30.2%)

p value  p>0.05  p<0.05  43

Year JE IgM Positive JE IgM Negative Total AES (61) p value

2007 8 (27.5%) 21 (72.4%) 29 (47.5%) P<0.0157

2008 3 (9.3%) 29 (90.6%) 32 (52.4%) P<0.00004

2007-08 11 (18%) 50 (81.9%) 61


