Investigation of an epidemic of Reye's syndrome in northern region of India.

Objective: To determine the extent, epidemiological and clinical features of an epidemic of non-inflammatory encephalopathy in northern region of India.
Design: Surveillance of referred cases having unconsciousness after a short bout of fever during October and November 1997. Case control study in 7 most affected villages.
Methods: Active case finding was done to assess the extent and severity of the epidemic by interviewing health professionals and by reviewing mortality records in 10 districts of Haryana, Punjab and Chandigarh. A house to house survey was conducted in seven most affected villages. A case was defined as any child of less than 15 years of age, who had prodromal fever followed by vomiting and unconsciousness with subsequent recovery or death. Two age and sex matched controls who had fever without unconsciousness were taken for each case, one from nearby house and another staying furthest from the affected house. These groups were compared for various epidemiologic factors, clinical features and treatment pattern. Residual medicines used by affected patients were tested for presence of salicylate. Local village practitioners were interviewed for their knowledge and attitude towards use of aspirin in a febrile child.
Results: Information regarding 129 affected children (M: F=1 : 1) could be obtained. Age ranged between 1 to 12 years (mean 5.8 years). Most were from rural or semi-suburban areas. Attack rate was 5.4/1000 and case fatality rate was 72%. Multiple sibs were affected in 9.3%. History of fever was reported by 83%, vomiting preceding unconsciousness by 83% and abnormal behavior by 65%. Abnormal posturing was reported in 55%. Seventeen (61%) of 28 samples had IgM antibodies in serum/CSF against measles. Twelve (36%) of 33 serum samples tested positive for Varicella zoster virus. None gave history of aspirin intake and 10 samples of residual drugs did not contain salicylate. However, 6 out of 19 blood samples taken from affected patients contained salicylate. Environmental factors were in favor of Japanese encephalitis (JE) but brain biopsy and serology disproved it. Based on earlier report of JE from this area, the cases in present epidemic were being reported as JE before this study was undertaken. Intensive fogging with malathion was being undertaken as antimosquito measure, specially around the affected houses. Local village practitioners (n = 37) were unaware of contraindications of aspirin in a febrile child.
Conclusion: Measles and varicella zoster emerged as the probable etiologies for the viral prodrome precipitating these cases of Reye's syndrome. Aspirin might have a contributory role. Malathion is another putative cofactor.