International Journal of Health Sciences and Research

www.ijhsr.org ISSN: 2249-9571

Original Research Article

Dengue Encephalitis: An Atypical Manifestation of Dengue Fever in

Children
Gitali Kakoti1*, Prafulla Dutta2*, Bishnu Ram Das3**
1
Former Women Scientist-A, DST & PhD Scholar, 2Scientist G & I/c Director, 3Prof & Head,
*
Regional Medical Research Centre, ICMR, Northeast Region, Post Box no. 105, Dibrugarh, Assam, India.
**
Department of Community Medicine, Jorhat Medical College, Jorhat-785001, Assam, India.
Corresponding Author: Bishnu Ram Das

Received: 21/02/2016 Revised: 11/03/2016 Accepted: 14/03/2016

ABSTRACT

Background: Recent studies have shown dengue viral infection causing encephalitis with high
morbidity and mortality. However, there is little clinical documented evidence of Dengue fever with
encephalitis in children in Assam. India
Aims: An attempt was made to determine the clinical spectrum and outcome in pediatric patients of
dengue fever with encephalitis.
Materials and Methods: The study was done in a multi-specialty teaching hospital on 513 Acute
Encephalitis Syndrome (AES) children with febrile illness.
Results: A total 513 AES patients were enrolled from 2011-2013. Of which 55.4% were male and age
group mostly affected were 5-12 years (51.1%). Among the AES cases, 15 were found to be positive
for Dengue IgM antibody. The age group mainly affected (73.3%) was 5-12 years. Majority of them
were Male (60%) and from rural area (93.3%).
Most common clinical features in DEN patients with encephalitis were fever (100%), seizure (86.7%),
altered sensorium (66.7%), vomiting (40%) and headache (33.3%). Around 20% of them had
Glasgow Comma Scale (GCS) within 3 to 8. Signs of meningeal irritation were present in 3.6% cases
and 20% cases were suffered from Diarrhea.
Outcome at discharge of DEN patients showed 66.7% were recovered completely, 13.3% had
neurological sequelae and 20% were died in hospital.
Conclusion: Dengue encephalitis an atypical manifestation of Dengue fever causing menace to the
children population which seeks attention for early diagnosis and prompt management through
disease surveillance .

Key words: Dengue Fever, Dengue Encephalitis, AES.

INTRODUCTION more than 100 different pathogens have

Encephalitis is an acute clinical been recognized as causative agents.
syndrome of the central nervous system India is endemic for important
(CNS), often associated with fatal outcome mosquito-borne viral diseases, viz. Dengue
and severe permanent damage including hemorrhagic fever (DHF), Japanese
cognitive and behavioural impairment, encephalitis (JE) and West Nile virus
affective disorders and epileptic seizures. To (WNV). [1]
date, the infection of the CNS is considered Dengue, which is the fastest re-
to be the major cause of encephalitis and emerging arboviral disease in the world,
imposes a heavy economic and health

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Vol.6; Issue: 4; April 2016
burden on countries, families and individual January, 2011 to December, 2013. All the
patients. [2,3] Over the past two decades there hospitalized AES cases up to 12 years of
has been dramatic global increase in Dengue age in pediatric ward of Assam Medical
fever (DF), Dengue haemorrhagic fever College hospital (AMCH) were included as
(DHF), and Dengue shock syndrome (DSS) study participants.
and their epidemics. [2,3] In India, there is For investigating AES cases, WHO
increased proportion of Dengue cases with case definition was adopted. Clinically a
severe disease. In recent years there have case of AES is defined as fever or recent
been an increasing number of reports of DF history of fever with change in mental status
or DHF with unusual manifestations. (including confusion, disorientation, coma,
Atypical central nervous system or inability to talk) and/or new onset of
manifestations, including convulsions, seizures (excluding simple febrile seizures).
spasticity, altered consciousness and Other early clinical findings could include
transient paresis, have been observed. an increase in irritability, somnolence or
Lately there have been report of abnormal behavior greater than that seen
neurological complications of dengue virus with usual febrile illness. Details of
infection and include encephalitis, myelitis, patients information, travel history,
Guillain-Barre (GB) syndrome and immunization history, clinical findings and
myositis. [4-6] There is insufficiency of data status at the time of discharge were recorded
looking at the atypical manifestation of on WHO standardized form.
Dengue fever in children. From a Children meeting the clinical
perspective of disease surveillance and diagnosis of AES and willing to give
control, it is important to differentiate consent for lumber puncture or for
Dengue encephalitis from other causes of collection of blood samples were included.
AES, in part because there is no antiviral Routinely, lumber puncture was performed
drug. Initial clinical manifestation of dengue and blood samples were taken by the
encephalitis and a complete medical attending pediatricians as a part of clinical
assessment are important for early diagnosis care. A part of CSF (1ml) and blood (2 ml)
and prompt supportive therapy. In view of samples were collected in sterile condition
the above an attempt was made to achieve a separately. The samples were then
better understanding of clinical transferred under cold chain to Regional
presentations and outcome of dengue fever Medical Research Centre Laboratory,
with encephalitis in AES children. ICMR, Dibrugarh. Blood samples were kept
at 4C overnight and sera were separated.
MATERIALS AND METHODS Both serum and CSF were then stored at -
Study Site 80C for further analysis. Reports of CSF
Assam Medical College & Hospital samples analyzed for physical, chemical,
is a tertiary level multi-specialty teaching and cytological examination and other
hospital providing health care services laboratory investigations done at the time of
mostly to the districts of upper Assam. admission were recorded from the bed head
People residing in neighbouring state like tickets of the patient. The study was
Arunachal Pradesh and Nagaland also approved by the Institutional Ethics
benefit health care services from this Committee (Human) of Regional Medical
medical college hospital. Most of the Research Centre (ICMR), NER, Dibrugarh.
patients referred to this apex level institute Serology
are from periphery for better supportive care Among the enrolled 513 AES
and treatment. participants we could collect at least one
Case Enrollment and Sample Collection CSF or Serum sample from 482(94%)
The case enrollment and sample patients at the time of admission. All the
collection was carried out for 3-years from serum samples obtained from AES patients

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Vol.6; Issue: 4; April 2016
were tested for the presence of Dengue viral Monthly admission pattern of AES patients
nonstructural 1 (NS1) antigen by using Admission pattern of AES patients
Platelia Dengue NS1 kits (Bio-Rad, USA) demonstrated that maximum numbers of
and DENV- specific IgM antibodies using patients were hospitalized in rainy season
MAC ELISA kits obtained from National starting from the month of May to October
Institute of Virology (NIV), Pune, India. with a clear peak in July in study years
DEN IgM positive samples were further (Figure 1).
tested for the presence of IgM antibody
against other flaviviruses viz. Japanese Figure 1: Monthly incidence of AES/DEN
encephalitis (MAC ELISA kit, NIV, Pune) 120 encephalitis cases
and West Nile (MAC ELISA kit, PanBio,
100
Australia) prevalent in this region. All tests
were performed according to manufacturers 80

Number of
instruction.

cases
60
Statistical analysis
A 2 or Fishers exact test was used 40

to analyze categorical variables. P values of 20 AES

less than 0.05 were considered to indicate as DEN
statistical significance. All statistical 0

Mar.11

Mar.12

Mar.13
May.11

May.12

May.13
Jan.11

Jan.12

Jan.13
Nov.11

Nov.12

Nov.13
Sep.11

Sep.12

Sep.13
Jul.12
Jul.11

Jul.13
analyses were performed with the use of
Statistical Package for Social Sciences
(SPSS) software, IBM SPSS - version 20. 2011-2013

Outcome of AES cases

RESULTS At the time of discharge of the total
Demographic profile of AES patients and 513 AES cases, 281(55%) were found to
distribution of study participants recover completely while 34(6.6%) patients
Over a period of three years from developed some short of neurological
2011 to 2013, a total of 513 AES patients disability and 139(27%) patients were died
admitted in pediatric ward of Assam in hospital.
Medical College & Hospital, Dibrugarh, Dengue Baseline characteristics
Assam were enrolled as study participants. Out of 482 AES cases 191children
Of these total participants, 186(36.2%) were found to be infected with flavivirus. Among
admitted in 2011, 224(43.6%) in 2012 and the flavivirus infections 15 were detected as
103(20%) in 2013. Among them, 494 were Dengue IgM positive during the study
from Assam, 16 were from Arunalchal period (Table 1). However, none were
Pradesh and 3 were from Nagaland. positive by NS1 Ag-ELISA kit. The age
Maximum no of AES patients of Assam groups mainly affected (73.3%) were 5-12
were from Dibrugarh district 217(43.9%) years. Majority of the patients were Male
followed by Tinsukia 107(21.7%), 9(60%) and from rural area 14(93.3%). The
Sivasagar 100(20.2%), Dhemaji 39(7.9%), district wise distribution of all the DEN
Golaghat 17 (3.4%) and from Jorhat 14 patients showed that maximum patients
(2.8%).Children from rural area were were from Sivasagar district 6(40%) while 4
predominantly affected 487(94.9%) and (26.7 %) each from Dibrugarh and Tinsukia
majority of them belonged to low district. Only one case was from Mon
socioeconomic group. district of neighboring state Nagaland.
Of the total AES patients, Clinical profile of DEN cases
284(55.4%) were male and age group Most common presenting symptoms
mostly affected were 5-12 years (51.1%). (Table 2) were fever 100%, Seizure 86.7%,
altered sensorium (66.7%), vomiting (40%)
and headache (33.3%). Around 20% of

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Vol.6; Issue: 4; April 2016
DEN patients had Glasgow Comma Scale irritation were present in 3.6% cases and
(GCS) within 3 to 8. Signs of meningeal 20% cases were suffered from Diarrhea.
Table 1: Demographic characteristics of Dengue cases
Characteristics Year wise DEN IgM positive cases Total
Age in years, no 2011 2012 2013 n = 15
(%) n =3 n = 11 n=1
<1 0(0) 0(0) 0(0) 0(0)
1 to 5 1(33.3) 3(27.3) 0(0) 4 (26.7)
5 to 12 2(66.7) 8(72.7) 1(100) 11(73.3)
Sex, no (%)
Male 1(33.3) 7(63.6) 1(100) 9(60)
Female 2(66.7) 4(36.5) 0(0) 6(40)
Settings, no (%)
Urban 1(33.3) 0(0) 0(0) 1(6.7)
Rural 2(66.7) 11(100) 1(100) 14(93.3 )

Table 2: Clinical Profile of children with Dengue (n=15) patients of flavivirus infection 7.9% were
Features Number %
Fever 15 100 laboratory confirmed Dengue. Earlier
Altered Sensorium 10 66.7 studies also confirmed that other agents that
Headache 5 33.3
Irritable 2 13.3 have been caused to AES in India include
Vomiting 6 40 dengue virus besides other etiologies. [8-10]
Abnormal behavior 0 0
Diarrhoea 3 20
In our study, majority of the AES
Seizure 13 86.7 children were male and age group mainly
Glasgow Coma Scale (GCS) 8 3 20 affected was 5 to 12 years. Study conducted
Signs of meningeal irritation 8 3.6
by Kumar et al., 2006; Bandyopadhyay et
Outcome of DEN Patients al., 2013, Avabratha et al., 2012 also
Outcome at discharge of DEN observed similar findings. [11-13] This may be
patients showed that 66.7% were recovered explained that among the AES patients,
completely while 13.3% cases had flavivirus infections like DEN, JE are more
neurological sequelae. 20% patients were common. Children in 5-12 years age group
died in the hospital (Figure 2). The mortality are actively mobile and they love to play
rate was more in patients with GCS between outside which make them more prone to get
3 to 8 (25.6 %). However, it was statistically mosquito bite. Moreover, in low
insignificant. socioeconomic status, male children are
Figure 2: Out come of DEN patients at the time of discharge
helping hands for their parents in cultivating
seasons. As such male children are more
DEN patients (n= 15)
exposed to the exophilic mosquito bites
Recovered
which are highly abundant outside the
with Death houses. [7]
neurological 20%
sequelae Monthly admission rate of AES
13% children were recorded more from May to
October with a peak in July. These findings
Recovered
completely are comparable with the findings of
67% previous studies that suggest a climate
dependent transmission cycle. [14-17] The hot
and humid time of the year is characterized
by water-logging, filling up of the perennial
DISCUSSION rivers, paddy fields, increased agricultural
The present study demonstrates that activity in the rural areas and more water
AES is a significant public health problem collection in artificial containers in nearby
in this part of country. We confirmed DEN houses. These conditions are attributable to
encephalitis as one of the important cause of enhance vector densities (e.g. via increased
AES in reference to flavivirus infection next mosquito breeding) and increased man
to Japanese encephalitis. [7] Of the total AES mosquito contact leading proportionately

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Vol.6; Issue: 4; April 2016
increased hospitalization of AES cases was severe with significant involvement of
(Borah et al., 2012). [18] CNS. Similarly, in earlier studies it was
Outcome of AES cases at the time of recorded that Dengue infection can cause
discharge showed that 6.6% patient neurological manifestation ranging from
developed neurological disability while 27% nonspecific symptoms to encephalitis. [24,25]
died in hospital. Mortality among children Predominant clinical features noted in the
with viral encephalitis is extraordinarily current study in order of frequency were
high in South and South-east Asia ranging fever 100%, Seizure 86.7%, altered
from 17 to 50%. [19-21] This high mortality sensorium (66.7%), vomiting (40 %) and
may be due to late reporting of cases or due headache (33.3%). Around 20% of DEN
to lack of availability standard neuro- patients had GCS within 3 to 8 and 20%
intensive care facilities. Moreover, in rural cases were found to suffer from Diarrhoea.
area initially people prefer to visit a Our findings were consistent with other
traditional faith healer than attending studies. [26-28]
recognized health care facility. This may be Among the other clinical findings
due to poor road communication, lack of rash was present in one patient. In another
transport facilities and more specifically patient who had thrombocytopania
prevailing ignorance among the rural under developed neurological sequelae at the time
privileged masses. of discharge. Kishore et al., 2006 also
The total numbers of dengue cases observed similar findings. Fatal disease
were 15 and all were positive for Dengue occurred in 20 % cases and 13.3% children
virus specific IgM antibody with MAC developed neurological sequelae. This may
ELISA. The mean age of all dengue cases be explained that enhanced mortality and
was 6.83 years. We did not find any neurological disability in our study may be
significant difference between male and due to dengue encephalopathy in contrast to
female ratio. However, disease was more low mortality in dengue fever. [29]
severe in male. The sex ratio of the patients
was rather equal in most studies CONCLUSION
(Witayathawornwong, 2006). [22] All the The present study reveals that
Dengue cases were found in rainy season Dengue virus infection in children is a
from May to September except one case in significant public health problem in this part
November, 2012. Similar findings were also of the country with climate dependent
observed by Witayathawornwong in transmission cycle. Our findings confirm
Thailand. This may be due to increase of that Dengue encephalitis is prevalent in
Aedes mosquito density in container pediatric age group and responsible for
habitats after rain posing risk of DENV creating the pool of differently able children
transmission. with increased fatal outcome. This public
Our study demonstrated that Dengue health menace is a growing challenge to
encephalitis were prevalent in the rural area. health officials and policymakers.
This may be due to the rapid growth of
industries and building activities, ACKNOWLEDGEMENT
improvement of transport facilities such as G. Kakoti acknowledges Department of
railway and roads, increased movement of Science and Technology, Government of India
people from urban to rural areas, and for providing Women Scientist-A fellowship to
environmental changes that all may have carry out the study and Director, National
Institute of Virology (NIV), Pune, India for
favoured the spread of dengue in rural as supplying the JE/Dengue IgM ELISA kits at no
well as urban areas. Other studies also cost. G. Kakoti also acknowledges Regional
observed the same. [23] Medical Research Centre (ICMR), Dibrugarh
Clinical characteristics of dengue for giving the infrastructure facility to carry out
positive patients indicated that dengue fever the lab work. Authors would like to thank the

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Vol.6; Issue: 4; April 2016
entire staff of pediatric department, AMCH, 8. Koley TK, Jain S, Sharma H et al.
Dibrugarh for their assistance during data and Dengue encephalitis. J Assoc Physicians
sample collection from study subjects. It is India. Apr 2003; 51:422-423.
gracefully acknowledged the pediatric 9. Muzaffar J, Venkata Krishnan P, Gupta
participants and their guardians for giving N et al. Dengue encephalitis: why we
unconditional consent to participate in this need to identify this entity in a dengue-
scientific research venture in spite of their prone region. Singapore Med J. Nov
adverse torment event of life. Thanks are due to 2006; 47(11):975-977.
Lab members of Entomology & Filariasis 10. Kumar R, Tripathi S, Tambe JJ et al.
section for their help during sample processing Dengue encephalopathy in children in
and Dr. Hiranya Saikia, Senior Lecturer of Northern India: clinical features and
Statistics at Department of Community comparison with non dengue. J Neurol
Medicine, AMC, Dibrugarh for his support in Sci. Jun 15 2008; 269(1-2):41-48.
analysis of data. 11. Kumar R., Tripathi P, Singh S et al.
Clinical features in children hospitalized
Conflict of Interests: The authors declare that during the 2005 epidemic of Japanese
they have no conflict of interests. encephalitis in Uttar Pradesh, India.
Clin Inf Dis. 2006; 43:123-131.
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How to cite this article: Kakoti G, Dutta P, Das BR. Dengue encephalitis: an atypical manifestation
of dengue fever in children. Int J Health Sci Res. 2016; 6(4):1-7.

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