Kathuria, Choudhary, Kashyap, Ansari, and Kamal: Dengue virus and Japanese encephalitis virus co-infection: A case report


Introduction

Dengue and Japanese encephalitis are major causes of morbidity and mortality in tropical and subtropical parts of world including India. It is estimated that there are 390 million dengue infections annually, and recently the number of dengue cases has increased exponentially worldwide.1 Dengue is endemic in almost all over India (31 states/UTs). All 4 serotypes of Dengue virus have been isolated while JE is endemic in 18 states of India of which include Assam, Bihar, Haryana, Uttar Pradesh, Karnataka, West Bengal & Tamil Nadu report out-breaks almost every year and contribute to 80% cases and deaths. Both being Arboviral diseases (Group B-Flaviviruses) are spread by bite of infected mosquitoes. They cross react with other in serological tests. Dengue virus usually causes classical dengue fever, DHF and DSS, JE virus typically causes encephalitis. In rare instances, Dengue virus may also cause encephalitis mimicking JE. Lab investigations therefore becomes essential for confirmation and discrimination between these two viral infections.

Case Report

A 4 year old girl child resident of Faridabad, Haryana presented to us with chief complaints of high grade fever (102°F), not associated with chills and rigors for last 4 days, abnormal body movements with up rolling of eyeballs for last 3 days followed by altered mental status, not recognising parents, not responding, not vocalizing or indicating bowel bladder. This was associated with loose stools and vomiting for last 1 day. There was no history of rash, bleeding from any site, cough or coryza. No history of any limb weakness or any cranial nerve deficit. She had not received any medication in recent past and no history of any Koch’s contact. Developmentally normal child with immunization complete for age.

At presentation, GCS was E1V3M4 and respiratory functions and hemodynamic parameters were stable. Neurological examination revealed altered state of consciousness, there was no neck rigidity and bilateral pupils were normally reacting to light. No evidence of any weakness and deep tendon reflexes were elicited normally. The Plantar reflex was extensor bilaterally. Rest of the systemic examination was within normal limits. Patient presented with active seizures in casualty which were aborted by Inj. Midazolam and loaded with Inj. Phenytoin subsequent to which she was admitted in PICU. NCCT head done which was unremarkable. The hemogram, Liver & Kidney function tests, CXR and ECG were normal. WIDAL and serology for Hep.B, Hep.C & HIV 1+2 were non reactive. Also peripheral smear was negative for Malarial parasites. Serial hemogram reports are listed in Table 1.

Examination of CSF revealed no cells and normal sugar and proteins. Gram stain and CSF culture showed no organisms. Although NS1 Ag was negative, Dengue serology in serum came out to be positive. Serum and CSF samples sent to NCDC, Delhi also confirmed the IgM antibodies against JE virus. MRI Brain reported T2/FLAIR hyper intensities involving the left thalamus, bilateral cerebral peduncle, temporal lobe, peri-aqueductal gray matter and midbrain and showing restriction on diffusion- likely viral encephalitis as represented in Figure 1.

Patient was given supportive treatment, improved gradually, discharged on oral phenytoin and followed up in OPD. Follow up at 4 weeks showed no extra-pyramidal features.

Table 1

Serialhemogram reports are listed.

Day

1

2

3

4

5

Hb

7.4

8.1

11.5

13.1

13.3

TLC

21700

18800

10400

8200

8200

Platelet count

38000

52000

66000

80000

92000

Figure 1

RI brain of the patient. . MRI Brain reported T2/FLAIR hyper intensities involving the left thalamus, bilateral cerebral peduncle, temporal lobe,peri-aqueductal gray matter and midbrain and showing restriction on diffusion- likely viral encephalitis.

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Table 2

Differences in clinical presentations and laboratory investigations between Japanese encephalitis and Dengue encephalitis2-

Points

Japanese encephalitis

Dengue encephalitis

Age

Children

All ages

Season

Rainy monsoon season

During or after rains

Geography

Rural

Semi-urban

Duration of illness

Fever of 2 to 3 days

Fever of 2 to 7 days

Prodromal illness

Sudden onset of fever, chills, headache, myalgia

High fever, severe headache, myalgia, arthralgia, nausea, vomiting, and rash

Clinical features

Rapidly progresses to deep coma focal deficit and seizures

Altered sensorium, focal deficit, and seizures

Blood changes

Leucopenia

Thrombocytopenia

Metabolic / circulatory changes

uncommon

Common (impaired liver and renal functions and shock)

CSF changes

Moderate pleocytosis (predominant lymphocytes), mildly raised protein, and a normal CSF glucose

Usually normal CSF, rarely pleocytosis

Neuroimaging

Signal changes in thalamus and substantia nigra

Variable, but usually Normal

Diagnosis

IgM antibody in serum or CSF

Dengue RNA PCR, IgM positive, NS1 antigen in CSF

Outcome

20-30% patients die

Variable, high mortality without supportive treatment

Sequelae

30% of survivors, many have cognitive or extrapyramidal syndromes

Rarely described

Discussion

In our patient the peripheral blood examination revealed features of severe dengue infection where as cerebrospinal fluid and magnetic resonance imaging data suggest diagnosis of Japanese encephalitis. The diagnosis of Japanese encephalitis is confirmed by presence of virus specific IgM antibodies in serum and/ or cerebrospinal fluid or four fold rise of IgG titre in paired sera. Virus can also be identified by polymerase chain reaction. Differences in clinical presentations and laboratory investigations between Japanese encephalitis and Dengue encephalitis have been presented in Table 2.2

A serological cross-reaction between DENV and JEV has been shown in studies to occur in up to 38.5 % patients; however, studies showing co-detection of disease specific IgM in the CSF are few and reveal a variable incidence from 8 to 50 %.3, 4, 5

The clinical significance of the serological cross reactivity between dengue virus and Japanese encephalitis virus is not exactly known and conflicting reports are available.

Cross-reactivity has been found to be associated with both immune-protection and an aggravated form of a viral disease (dengue or Japanese encephalitis).2

Conclusion

A possibility of dual infection or a cross reactivity between dengue and Japanese encephalitis needs to be considered if serological evidence of both the infections are present in same patient. But being in the endemic area and clinical features with which patient presents and serological and radiological features a diagnosis of co infection can be easily established.

Source of Funding

No financial support was received for the work within this manuscript.

Conflict of Interest

The authors declare they have no conflict of interest.

References

1 

S Bhatt P W Gething O J Brady The global distribution and burden of dengueNat20134965047

2 

RK Garg HS Malhotra A Jain Dual infection with Japanese encephalitis and dengue fever: Issues with diagnosisNeurol India2017651108910.4103/0028-3886.198210

3 

A A-Nuegoonpipat N Panthuyosri S Anantapreecha S Chanama A Sa-Ngasang P Sawanpanyalert Cross-reactive IgM responses in patients with dengue or Japanese encephalitisJ Clin Virol200842175710.1016/j.jcv.2007.10.030

4 

S Touch S Hills B Sokhal C Samnang L Sovann V Khieu Epidemiology and burden of disease from Japanese encephalitis in Cambodia: results from two years of sentinel surveillanceTrop Med Int Health2009141113657310.1111/j.1365-3156.2009.02380.x

5 

B V Cam E D Heegaard A Poulsen N B Hue L Fonsmark N T Phuong Prospective case-control study of encephalopathy in children with dengue hemorrhagic fever.Am J Trop Med Hyg20016568485110.4269/ajtmh.2001.65.848



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https://doi.org/10.18231/j.ijmpo.2020.039


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