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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 1  |  Page : 108-109

Dual infection with Japanese encephalitis and dengue fever: Issues with diagnosis

1 Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
2 Department of Microbiology, King George Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication12-Jan-2017

Correspondence Address:
Dr. Ravindra K Garg
Department of Neurology, King George Medical University, Lucknow - 226 003, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.198210

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How to cite this article:
Garg RK, Malhotra HS, Jain A. Dual infection with Japanese encephalitis and dengue fever: Issues with diagnosis. Neurol India 2017;65:108-9

How to cite this URL:
Garg RK, Malhotra HS, Jain A. Dual infection with Japanese encephalitis and dengue fever: Issues with diagnosis. Neurol India [serial online] 2017 [cited 2021 Jun 12];65:108-9. Available from:

Sivamani and co-workers have described an interesting case of acute encephalitic syndrome. In this patient, the peripheral blood examination revealed features suggestive of severe dengue infection whereas cerebrospinal fluid and magnetic resonance imaging data suggested the diagnosis of Japanese encephalitis.[1] Was it a case of dual infection? Was positive dengue serology an example of cross-reactivity? Were Japanese encephalitis and dengue infections interacting with each other?

The dengue virus infection and Japanese encephalitis virus are members of the Flaviviridae virus family. Japanese encephalitis is the predominant cause of acute encephalitic syndrome in India. The diagnosis of Japanese encephalitis is considered confirmed if IgM antibody against Japanese encephalitis virus is detected in serum and/or cerebrospinal fluid. Other confirmatory tests include a four-fold difference in IgG antibody titre in paired sera, virus isolation from brain tissue, antigen detection by immunofluorescence method, and nucleic acid detection by polymerase chain reaction.[2]

The mortality rate of Japanese encephalitis is as high as 30%. Disabling neurologic or psychiatric sequelae are common among survivors. Many effective vaccines are currently available to prevent Japanese encephalitis.[3] There are increasing reports regarding neurological complications of dengue virus infection. Dengue-associated acute brain involvement is frequently classified into either dengue encephalopathy or dengue encephalitis. Dengue encephalopathy is a condition that is characterized by altered sensorium and caused by certain metabolic/circulatory factors, but not by the dengue virus itself. These factors include hypovolemic shock, anoxia, cerebral edema, electrolyte and fluid imbalances, coagulation abnormalities, and liver and/or renal dysfunctions. In dengue encephalopathy, cerebrospinal fluid parameters are often normal. Dengue encephalitis is clinically indistinguishable from dengue encephalopathy. In dengue encephalitis, cerebrospinal fluid may show inflammatory changes, and dengue virus serology in cerebrospinal fluid is often positive. The outcome of dengue encephalitis is generally good and most of the patients recover completely [Table 1].[4]
Table 1: Differences in clinical presentations and laboratory investigations between Japanese encephalitis and Dengue encephalitis

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In India and in other parts of Southeast Asia, dengue virus infection and Japanese encephalitis very frequently co-exist in the same population. Dengue outbreaks in India often coincide with that of Japanese encephalitis epidemic. Both dengue and Japanese encephalitis transmission intensifies during the rainy season, during which the vector population increases. Both the diseases are important causes of mortality in human.

Antibodies produced against various flavivirus infections are known to cross-react with each other. Cross-reactivity is defined as immune reaction of one antigen with antibodies that have been produced against a different antigen. Cross-reactivity often complicates the issue of correct diagnosis by serological methods in endemic areas where dengue and Japanese encephalitis viruses co-circulate and frequent sequential infections are also likely to occur. For example, a group of authors assessed the serum samples of patients with central nervous system infection and thrombocytopenia, with anti-Japanese encephalitis virus and anti-dengue virus IgM antibodies. Among 1410 patients, both antibodies were present in 129 (9.14%) patients. Among these 129 co-positive cases, 76 were tested by conventional reverse transcriptase polymerase chain reaction for both flaviviruses, of which 8 cases were co-positive for dengue virus and Japanese encephalitis virus.[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 immuno-protection and an aggravated form of a viral disease (dengue or Japanese encephalitis). A study evaluated the significance of pre-existing Japanese encephalitis virus antibodies and the clinical severity of subsequent dengue infection. The authors noted that Japanese encephalitis virus antibodies were associated with an increased occurrence of symptomatic dengue infection.[6] Another recent study noted that the patients, who were hospitalized due to dengue, were significantly more likely to be seropositive for Japanese encephalitis.[7]

On the contrary, a prior infection with other flavivirus has been found to be protective in Japanese encephalitis. It was noted that absence of a prior flavivirus infection (presumably dengue) remained an independent risk factor for death or a severe neurological deficit in Japanese encephalitis. An anamnestic, anti-flavivirus immune response, induced by a prior dengue virus infection, was considered responsible for this phenomenon.[8]

In 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 the same patient.

  References Top

Sivamani K, Dhir V, Singh S, Sharma A. Diagnostic dilemma–dengue or Japanese encephalitis? Neurol India 2017; 65:105-7.  Back to cited text no. 1
  Medknow Journal  
World Health Organization. Manual for the Laboratory Diagnosis of Japanese Encephalitis Virus Infection. Downloaded from [Last accessed on 2016 Apr 20].  Back to cited text no. 2
World Health Organization. Japanese encephalitis. Fact sheet No 386, December 2015. Downloaded from [Last accessed on 2016 Apr 20].  Back to cited text no. 3
Carod-Artal FJ, Wichmann O, Farrar J, Gascón J. Neurological complications of dengue virus infection. Lancet Neurol 2013;12:906-19.  Back to cited text no. 4
Singh KP, Mishra G, Jain P, Pandey N, Nagar R, Gupta S, et al. Co-positivity of anti-dengue virus and anti-Japanese encephalitis virus IgM in endemic area: Co-infection or cross reactivity? Asian Pac J Trop Med 2014;7:124-9.  Back to cited text no. 5
Anderson KB, Gibbons RV, Thomas SJ, Rothman AL, Nisalak A, Berkelman RL, et al. Preexisting Japanese encephalitis virus neutralizing antibodies and increased symptomatic dengue illness in a school-based cohort in Thailand. PLoS Negl Trop Dis 2011;5:e1311.  Back to cited text no. 6
Jeewandara C, Gomes L, Paranavitane SA, Tantirimudalige M, Panapitiya SS, Jayewardene A, et al. Change in dengue and Japanese encephalitis seroprevalence rates in Sri Lanka. PLoS One 2015;10:e0144799.  Back to cited text no. 7
Libraty DH, Nisalak A, Endy TP, Suntayakorn S, Vaughn DW, Innis BL. Clinical and immunological risk factors for severe disease in Japanese encephalitis. Trans R Soc Trop Med Hyg 2002;96:173-8.  Back to cited text no. 8


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