Background: AES is defined as an acute onset of fever and a change in mental status manifesting as confusion, disorientation, coma, inability to talk and or new onset seizures (except febrile seizure). It is a major public health problem in India, particularly in Assam, and is linked to significant morbidity and mortality. Viruses are the main causes of AES. Objectives: To study the clinical and etiological profile of AES in hospitalized children of urban tertiary care centre. Methods: This prospective hospital based observational study, conducted among children between 1m to 12 yrs of age as per inclusion criteria admitted as AES in Pediatric ward and PICU, Gauhati Medical Cllege and hospital, Assam from July 2023 to June 2024. Data were collected and all relevant investigations like serum and CSF were analysed in search of the etiologic agent. Radio imaging of brain MRI and CT scan was done after stabilization whenever is indicated. All the cases were managed as per institutional treatment protocol. The collected data was statistically analysed. Results: The most common age group was 6-10 years (43%), and maximum cases were males 68%. The mean age of presentation was 6.7 years. Majority of the cases were from rural area (81%). All the cases (100%) presented with fever and altered sensorium, 85% children presented with convulsion and 42% presented with vomiting. JE was the commonest cause of AES (22%), non-JE encephalitis (18%) and unknown etiology (60%). Out of 100 cases 49% cases recovered completely, 34 % recovered with neurological sequelae and 17% cases died. Conclusion: AES is a major public health problem of multiple and varying etiology with significant mortality and morbidity. Early diagnosis, appropriate investigation, prompt management and prevention by vaccination go a long way in reducing mortality and sequalae in AES.
Acute Encephalitis Syndrome (AES) is defined by the World Health Organization (WHO) as “a syndrome in a person of any age, at any time of year, with the acute onset of fever and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) AND/OR new onset of seizures (excluding simple febrile seizures)”. Other clinical symptoms include increased irritability, somnolence, or abnormal behaviour unexplained by a usual febrile illness[1]. The presence of this issue is a major public health problem in India, particularly in Assam, and it is linked to significant morbidity and mortality. The causes of acute encephalitis syndrome are numerous and divided into two groups- Infective etiology and non infective etiology. The most frequent cause of AES are viruses. Japanese Encephalitis Virus (JEV), Herpes Simplex Virus (HSV), Varicella Zoster virus (VZV), Influenza A virus, West Nile virus, Chandipura virus, Mumps, Measles, Dengue, Parvovirus B19, Enteroviruses, Epstein-Barr virus, Nipah virus, Zika virus and Rabies virus. Scrub typhus, Leptospirosis and Streptococcus pneumoniae are among the other causes of AES in India.[2] Japanese encephalitis (JE) virus has been reported as the single most important virus causing AES (5-35%) in India. The common bacterial agents are Orientia tsutsugamushi,which causes scrub typhus. In the majority of AES cases, the etiology remains unknown [2,4].
AES is a common emergency problem among children, the presentation is acute and often associated with poor outcomes contributing to significant morbidity and mortality. The mortality rate in children with AES in India has reduced considerably after the widespread use of JE vaccination, adequate vector control measures, and improvements in the field of health and sanitation . The case fatality rate in JE-related AES coming down gradually compared to 30-40% in the previous decades [5,6] . Several studies have shown that the long-term neurological sequelae in children with AES may be as high as 60-80% [6,7]. This study was undertaken for a better understanding and to determine the clinical and etiological profile of AES in children admitted in Gauhati Medical College and Hospital, Assam.
Objectives of the study:
(b)Patients with structural CNS malformation or congenital anomalies predisposing to CNS infections. (c) Patients with non-infectious CNS conditions like epilepsy, electrolyte imbalance, trauma, vascular, and demyelination disorders.
The history , clinical features and physical examination findings were noted. Relevant investigations like lumber puncture,CSF analysis – for IgM JE, DNA PCR herpes simplex virus and other viral panel, Serum IgM Eliza scrub typhus, leptospirosis, dengue serology, IgM , malaria (pv,pf), complete blood count, blood glucose, serum electrolytes, liver and kidney function tests, blood culture , EEG etc. were done as per the need of the patient. Radio imaging of brain Like MRI, C T scan done after stabilization of the child and whenever necessary. The outcome of the patients at the time of discharge was recorded. The findings of the cases were recorded in the proforma and the comparative analysis was done.
Table 1: Age and Sex wise distribution of the AES cases (n=100)
The most common age group was 6-10 years (43%), and maximum cases were males 68% out of which 39.7% males presented in 6-10 years age group. The mean age of presentation was 6.7 years [Table1]
Table 2: Distribution of the AES cases according to location (n=100)
RESIDENCY |
FREQUENCY |
PERCENTAGE (%) |
Urban |
19 |
19 |
Rural |
81 |
81 |
Total |
100 |
100 |
Majority of the cases (81%) were from rural area and the remaining 19% of cases were from urban area.[Table 2]
Table 3: Distribution of AES cases according to residence, coming from various district of Assam.
DISTRICT |
FREQUENCY |
PERCENTAGE (%) |
Baksa |
6 |
6 |
Barpeta |
6 |
6 |
Bongaigaon |
1 |
1 |
Cachar |
1 |
1 |
Darrang |
16 |
16 |
Dhubri |
2 |
2 |
Goalpara |
2 |
2 |
Gohpur |
1 |
1 |
Hojai |
1 |
1 |
Kamrup metro |
6 |
6 |
Kamrup rural |
15 |
15 |
Karbi angling |
1 |
1 |
Kokrajhar |
1 |
1 |
Morigaon |
14 |
14 |
Nagaon |
8 |
8 |
Nalbari |
9 |
9 |
Sonitpur |
1 |
1 |
South salmara |
1 |
1 |
Tamulpur |
6 |
6 |
Udalguri |
2 |
2 |
Total |
100 |
100 |
Maximum number of cases (16 %) came from Darrang district, followed by Kamrup rural (15%) and Morigaon (14%) . Most of the cases from rural districts of Assam [Table 3]
Table 4: Showing the clinical features of the AES cases (n=100)
PRESENTING SIGNS AND SYMPTOMS |
FREQUENCY |
PERCENTAGE (%) |
Fever |
100 |
100 |
Headache |
32 |
32 |
Convulsion |
85 |
85 |
Altered sensorium |
100 |
100 |
Diarrhoea |
7 |
7 |
Vomiting |
42 |
42 |
Rash |
3 |
3 |
Neck rigidity |
10 |
10 |
Papilledema |
22 |
22 |
Shock |
8 |
8 |
All the cases (100%) presented with fever and altered sensorium, 85 children presented with convulsion (85%) and 42 children presented with vomiting (42%) [Table 4]
AGE GROUP |
JE |
NON-JE |
UNKNOWN |
|
≤1 year |
N |
2 |
1 |
10 |
1-2 years |
N |
2 |
0 |
10 |
2-6 years |
N |
4 |
5 |
8 |
6-10 years |
N |
11 |
9 |
23 |
>10 years |
N |
3 |
3 |
9 |
Total |
N |
22 |
18 |
60 |
|
% |
22% |
18% |
60% |
Table 5: Showing distribution of the AES cases according to various etiology
In the present study, 22 patients were JE positive (22%), 18% cases were diagnosed as Non JE acute encephalitis syndrome and 60% cases were remained undiagnosed. Maximum JE positive cases were observed in 6-10 years age group [Table 5].
Table 6: Distribution of NonJE AES cases (n=18)
ETIOLOGIES OTHER THAN JE |
FREQUENCY |
PERCENTAGE (%) |
Dengue |
2 |
2 |
Scrub typhus |
8 |
8 |
HSV |
2 |
2 |
Mumps |
1 |
1 |
Leptospira |
5 |
5 |
This study showed Scrub typhus was leading causes among Non JE cases (8 cases ) followed by Leptospirosis (5 cases) and Dengue, HSV encephalitis 2cases each [Table 6].
Table 7: Showing outcome of the AES cases (n=100)
The present study showed out of 100 cases, 49% recovered completely, 34% recovered with neurological sequelae and 17% cases died [Table 7].
The present study was conducted in the department of Pediatrics at Gauhati Medical College and Hospital with a sample size of 100 cases of acute encephalitis syndrome from 1st July 2023 to June 2024.
Acute encephalitis syndrome predominantly affects children below 15 years; most vulnerable age group being 1-5 years followed by 5-10 years. In the present study, out of 100 enrolled patients, highest number of patients were in the age group of 6-10 years.They accounted for 43 cases which formed 43% of our entire study population. 17% patients were in the age group of 2-6 years and 15% patients were in the age group of >10 years. Cases were lowest in the age group 1-2 years and formed 12% of our entire study population. The Mean age was 6.70 ± 3.16 years. In this study majority (68%) were males out of which maximum (27 cases) belonged to 6-10 years age group. The remaining 32% were females. Studies from various region of India suggest that AES is more common among males than in females with a 2:1 male preponderance. The findings in this study are congruent with this gender variation in studies conducted elsewhere with a Male:Female ratio of 2.1:1. The findings in our study were concordant to those found in rest of the similar studies conducted by Sethi A et al [9], De S et al [8] and Adhikari A et al [12]. But, Kakoti G et al [13] conducted a study in Dibrugarh, Assam in 2012and found a higher percentage of females than males in their study at 52.24% against 47.76% males.
In this study we found that majority of the cases (81%) belong to rural area and 19% belong to urban area. This findings corroborate with other studies. Kakoti G et al [13] in their study in 223 cases found that 89.5% of the cases belong to rural area and 10.5% belong to urban area. Adhikari A et al [12] had similar finding in their study with 85% of the cases belonging to rural area and rest 15% to urban area.
In the present study it was observed that maximum number of cases (16%) came from district of Darrang followed by Kamrup rural (15%) and Morigaon district (14%). Medhi M et al [10] in their study in Upper Assam districts found that maximum cases were from Dibrugarh district followed by Sivasagar and Tinsukia district. Our finding of geographical distribution could not be compared well as not many studies have been done regarding distribution of AES cases across various districts of Assam.
Among 100 cases of AES in the present study, all children presented with fever and altered sensorium (100%), 85% children presented convulsion and 42% presented with vomiting and 32% with headache. This correlates with other studies. Rebecca et al [4] in their study among 250 children between the ages of 1 month to 15 years, also showed that most common presentation is fever (100%) followed by convulsion (74.7%) and altered sensorium (74.3%).
Kakoti G et al [13]in their study showed that the most common presenting symptoms were moderate to high grade fever (100%), altered sensorium (83.58%), seizure (82.08%), headache (41.79%), and vomiting (29.85%). In another study done by Chakrabarti S et al [11] in 100 children in Tripura found fever (100%) and altered sensorium (100%) to be the most common presentation followed by seizure (92%). It is a point worth mentioning that a patient of AES may have had one or all of these features at the time of admission. In our analysis, we have included only the chief complaints of the child as given by their parents during history taking.
In the present study we found JE virus to be the most common etiology (22%). In 60 % cases the etiology was unknown and in rest 18% cases other etiologies [Non JE] were identified. Among the other etiologies Scrub typhus was the most common (8 cases) followed by 5 cases of Leptospira, 2 cases of Dengue and herpes simplex encephalitis each . Chakrabarti S et al [11] in their study (100 cases) in Tripura found JE to be the most common etiology (19%), followed by 6% cases of scrub typhus, 2 % each HSV and Dengue and 1% each Measles and eneterovirus. However, in majority of cases (69%) the etiology remained unidentified. De S et al [8] in their study done in 24 patients in NRS Medical college, West Bengal also found JE to be the most common etiology (25%). Similar etiological agents were observed in a study done by Kakoti G et al [13] in 223 patients in Assam Medical College, Dibrugarh. Rebecca B et al [4] in their study done in 250 patients in South India found Scrub typhus (11.2%) to be the most common etiology, followed by Dengue (9%).
In the present study out of 100 cases, 17 patients died (17%). We assessed the neurological status of the rest 83 cases at discharge and found that 34 patients (34%) had neurological sequelae and 49 patients (49%) recovered completely without any sequelae. The most common neurological sequelae were movement disorder (13%) followed by seizure (8%) and paresis (6%) and speech impairment (5%). There were 2 cases had cranial nerve palsy (9th nerve). Both the patients had drooling of saliva and feeding difficulty at the time of discharge.
Sl no |
Author |
Year |
Recovered completely (%) |
Recovered with neurological sequelae (%) |
Death (%) |
1 |
De et al |
2015 |
25 |
45.83 |
29.16 |
2 |
Adhikari et al |
2021 |
40 |
33.33 |
26.66 |
3 |
Chakrabarti et al |
2022 |
57.4 |
14.8 |
27.7 |
4 |
Basu et al |
2018 |
57.74 |
23.23 |
19.01 |
5 |
Present study |
2023-2024 |
49 |
34 |
17 |
AES is a major public health problem of multiple and varying etiology with significant mortality and morbidity. Now, there is changing spectrum of etiological agents of acute encephalitis syndrome in India. Before 2000, JE was the leading cause of AES in India but there is paradigm shift of the causes and now, scrub typhus , enterovirus71 become the most common cause. Hence, we should be vigilant for emerging diseases like scrub typhus as the cause of AES and also about AES like presentation of other Non JE etiological agent beyond viruses. Advanced and newer diagnostic tests at referral hospitals will aid in making specific diagnosis and initiation of specific treatment. Periodic review of data of AES in regard to various etiological agent from sentinel centres will aid in possible paradigm shift in treatment and prevention including immunization and vector control measure. Early diagnosis, appropriate investigation, prompt management and prevention by vaccination go a long way in reducing mortality and sequalae in AES.
Funding: None
Competing interest: None declared.
Ethical Approval: The study was approved by Institutional ethics committee.