To investigate the prognostic role of tumour necrosis factor (TNF) in Japanese encephalitis virus (JEV) infection, we measured the immunoreactive forms of TNF concentrations in the serum and cerebrospinal fluid (CSF) of 47 laboratory-confirmed cases of JE. It was observed that TNF levels were elevated (> 15 pgm/ml) in all the 47 serum samples (range 19.4-923.8 pg/ml), while in 46/47 CSF samples TNF was elevated (range 10.8-376 pg/ml). The mean (SD) TNF levels in the serum of fatal cases was 234.34 pg/ml (304.40) as compared to the mean of 85.31 pg/ml (SD 153.92) in nonfatal cases. Similar observations were also made with respect to the TNF levels in the CSF; the mean of fatal cases was 69.39 pg/ ml (SD 39.00) in contrast to the mean of 62.41 pg/ml (SD 75.25) of nonfatal cases. The increase in TNF levels did not show any correlation to the duration of illness. It was further observed that the mortality rate increased with increasing concentrations of TNF in the serum and CSF. Correlation of laboratory parameters to final outcome revealed that TNF concentrations above 50 pg/ ml in serum correlated significantly (P = .05) with a fatal outcome, whilst high levels of JEV-IgM antibodies (> 500 units) in the CSF correlated with a nonfatal outcome (P = .03). These results suggest that TNF can be used as a possible prognosticator of a fatal outcome in JEV infection.
Immunological and virological evidence for persistence of Japanese encephalitis virus (JEV) in the human nervous system is described in 16/323 (5%) laboratory-confirmed cases of Japanese encephalitis. In 9/16 patients, JEV specific IgM antibodies were detected in the CSF even at 50-180 days after the onset of symptoms. Similarly, in 7/16 patients, apart from IgM antibodies, viral antigen was also present in the CSF beyond the third week of illness and in one patient it could be detected even at 117 days. Infectious virus could be isolated from the CSF beyond the third week of illness in 3/16 patients. In one patient, JEV was isolated from the CSF on three consecutive occasions at 90, 110, and 117 days after onset of clinical symptoms. These findings suggest that JEV persists in the nervous system of a small proportion of patients.
This study reports the pathological findings and the distribution of viral antigen in the brains of 13 confirmed and autopsied cases of Japanese encephalitis (JE) in correlation with other virus-specific immunological parameters measured in the cerebrospinal fluid (CSF) antemortem. Japanese encephalitis virus (JEV)-specific antibodies were detected in the CSF of 10 of 13 patients, JEV antigen was detected in the CSF of 7 of 13 and JEV-specific immune complexes were detected in the CSF of 3 of 11 patients. Viral antigen was localised immunocytochemically in the brain tissue of 11 of 13 cases, indicating, that viral antigen could not be cleared from the tissues by the antibody. The topographic distribution of the tissue-associated antigen in the thalamus, hippocampus, substantia nigra and medulla oblongata explain the evolution of post JE sequelae.
Streptococcus pneumoniae remains the major aetiological agent of CAABM both in adults and children in our set-up. No penicillin resistance was detected among the isolates. Further research should focus on preventable aspects of CAABM, especially pneumococcal vaccines, to help reduce the disease burden.
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