Human T cell responses to Japanese encephalitis virus in health and disease.

Japanese encephalitis (JE) virus (JEV) is an important cause of encephalitis in children of South and Southeast Asia. However, the majority of individuals exposed to JEV only develop mild symptoms associated with long-lasting adaptive immunity. The related flavivirus dengue virus (DENV) cocirculates in many JEV-endemic areas, and clinical data suggest cross-protection between DENV and JEV. To address the role of T cell responses in protection against JEV, we conducted the first full-breadth analysis of the human memory T cell response using a synthetic peptide library. Ex vivo interferon-γ (IFN-γ) responses to JEV in healthy JEV-exposed donors were mostly CD8(+) and targeted nonstructural (NS) proteins, whereas IFN-γ responses in recovered JE patients were mostly CD4(+) and targeted structural proteins and the secreted protein NS1. Among patients, a high quality, polyfunctional CD4(+) T cell response was associated with complete recovery from JE. T cell responses from healthy donors showed a high degree of cross-reactivity to DENV that was less apparent in recovered JE patients despite equal exposure. These data reveal divergent functional CD4(+) and CD8(+) T cell responses linked to different clinical outcomes of JEV infection, associated with distinct targeting and broad flavivirus cross-reactivity including epitopes from DENV, West Nile, and Zika virus.

Raine syndrome.

Raine syndrome is a rare genetic disorder with characteristic features of exophthalmos, choanal atresia or stenosis, osteosclerosis and cerebral calcifications. Most of babies with this disorder die immediately after birth. We report a baby who was 7 weeks old at the time of presentation.

Enterovirus 75 encephalitis in children, southern India.

Recent outbreaks of enterovirus in Southeast Asia emphasize difficulties in diagnosis of this infection. To address this issue, we report 5 (4.7%) children infected with enterovirus 75 among 106 children with acute encephalitis syndrome during 2005-2007 in southern India. Throat swab specimens may be useful for diagnosis of enterovirus 75 infection.

Disability after encephalitis: development and validation of a new outcome score.

OBJECTIVE: To develop a simple tool for assessing the severity of disability resulting from Japanese encephalitis and whether, as a result, a child is likely to be dependent. METHODS: A new outcome score based on a 15-item questionnaire was developed after a literature review, examination of current assessment tools, discussion with experts and a pilot study. The score was used to evaluate 100 children in Malaysia (56 Japanese encephalitis patients, 2 patients with encephalitis of unknown etiology and 42 controls) and 95 in India (36 Japanese encephalitis patients, 41 patients with encephalitis of unknown etiology and 18 controls). Inter- and intra-observer variability in the outcome score was determined and the score was compared with full clinical assessment. FINDINGS: There was good inter-observer agreement on using the new score to identify likely dependency (Kappa = 0.942 for Malaysian children; Kappa = 0.786 for Indian children) and good intra-observer agreement (Kappa = 1.000 and 0.902, respectively). In addition, agreement between the new score and clinical assessment was also good (Kappa = 0.906 and 0.762, respectively). The sensitivity and specificity of the new score for identifying children likely to be dependent were 100% and 98.4% in Malaysia and 100% and 93.8% in India. Positive and negative predictive values were 84.2% and 100% in Malaysia and 65.6% and 100% in India. CONCLUSION: The new tool for assessing disability in children after Japanese encephalitis was simple to use and scores correlated well with clinical assessment.

Evaluation of two commercially available ELISAs for the diagnosis of Japanese encephalitis applied to field samples.

OBJECTIVE: To compare two commercially available kits, Japanese Encephalitis-Dengue IgM Combo ELISA (Panbio Diagnostics) and JEV-CheX IgM capture ELISA (XCyton Diagnostics Limited), to a reference standard (Universiti Malaysia Sarawak - Venture Technologies VT ELISA). METHODS: Samples were obtained from 172/192 children presenting to a site in rural India with acute encephalitis syndrome. RESULTS: Using the reference VT ELISA, infection with Japanese encephalitis virus (JEV) was confirmed in 44 (26%) patients, with central nervous system infection confirmed in 27 of these; seven patients were dengue seropositive. Of the 121 remaining patients, 37 (31%) were JEV negative and 84 (69%) were JEV unknown because timing of the last sample tested was <10 day of illness or unknown. For patient classification with XCyton, using cerebrospinal fluid alone (the recommended sample), sensitivity was 77.8% (59.2-89.4) with specificity of 97.3% (90.6-99.2). For Panbio ELISA, using serum alone (the recommended sample), sensitivity was 72.5% (57.2-83.9) with specificity of 97.5% (92.8-99.1). Using all available samples for patient classification, sensitivity and specificity were 63.6% (95% CI: 48.9-76.2) and 98.4% (94.5-99.6), respectively, for XCyton ELISA and 75.0% (59.3-85.4) and 97.7% (93.3-99.2) for Panbio ELISA. CONCLUSION: The two commercially available ELISAs had reasonable sensitivities and excellent specificities for diagnosing JEV.

Chikungunya virus and central nervous system infections in children, India.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus best known for causing fever, rash, arthralgia, and occasional neurologic disease. By using real-time reverse transcription-PCR, we detected CHIKV in plasma samples of 8 (14%) of 58 children with suspected central nervous system infection in Bellary, India. CHIKV was also detected in the cerebrospinal fluid of 3 children.