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Clinical and immunological risk factors for severe disease in Japanese encephalitis
Daniel H Libraty1, Ananda Nisalak, Timothy P Endy
1Center for Infectious Diseases and Vaccine Research, University of Massachusetts School of Medicine, Worcester, MA, USA. dlibraty@mozart.inet.co.th
Insights
Low Japanese encephalitis virus (JEV) IgM antibody levels and no prior flavivirus infection predict severe outcomes in children. Prior dengue virus infection may offer protection against severe Japanese encephalitis (JE).
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Japanese encephalitis (JE) is a significant cause of neurological disease in children in endemic areas.
- Identifying risk factors for severe JE is crucial for timely intervention and improved patient outcomes.
Purpose of the Study:
- To determine risk factors associated with severe disease in paediatric patients with acute Japanese encephalitis (JE).
- To investigate the role of antibody response and prior flavivirus infections in JE severity.
Main Methods:
- Retrospective analysis of 85 paediatric patients admitted with acute JE in Thailand between 1987-1999.
- Univariate and multivariate analyses were performed to identify significant risk factors for death or severe neurological deficit.
- Serological markers including cerebrospinal fluid (CSF) protein, serum and CSF IgG, and serum IgM against Japanese encephalitis virus (JEV) were assessed.
Main Results:
- Depressed consciousness, elevated CSF protein, low JEV IgG, low JEV IgM, and primary flavivirus infection serology were associated with severe JE on univariate analysis.
- Low initial serum anti-JEV IgM (< 150 U) and the absence of prior flavivirus infection (likely dengue) were independent risk factors for severe outcomes on multivariate analysis.
- A robust early JEV-reactive antibody response correlated with better outcomes.
Conclusions:
- Early detection of low JEV IgM and lack of prior flavivirus exposure are critical indicators of severe JE risk.
- Prior dengue virus infection may confer protective immunity against severe JE through an anamnestic anti-flavivirus response.
Abstract:
Eighty-five paediatric patients in Thailand with acute Japanese encephalitis (JE) were studied in 1987-99 to determine risk factors present at hospital admission which were associated with severe disease. On univariate analysis, the following factors on admission were significantly associated with the combined end-point of death or a severe neurological deficit: depressed level of consciousness, elevated concentration of cerebrospinal fluid (CSF) protein, low levels of serum and CSF IgG antibody against Japanese encephalitis virus (JEV), low level of serum IgM antibody against JEV, and a serological response consistent with primary flavivirus infection. On multivariate analysis, an initial serum anti-JEV IgM < 150 U and the absence of a prior flavivirus infection, presumably dengue, remained independent risk factors for death or a severe neurological deficit. The ability to mount an early and vigorous JEV-reactive antibody response is associated with a better outcome from acute JE. An anamnestic, anti-flavivirus, immune response induced by a prior dengue virus infection can be an important means of providing this protection.