Pathophysiological analysis of five severe cases with rotavirus infection

Introduction: Rotavirus infection is usually localized to the intestine. Severe cases with extraintestinal symptoms are rare, and its pathogenesis remains unclear. Case presentation: We report severe rotavirus infections in five previously healthy, unvaccinated children that occurred in the 2011 season in Aichi Prefecture, Japan. All cases had short histories of recurrent diarrhoea and vomiting that preceded extraintestinal symptoms. Two cases with prolonged seizures and unconsciousness were diagnosed with encephalitis/encephalopathy; one case died and the other survived with severe neurological sequelae in spite of intensive treatment including anticytokine therapy. Another two cases had rapidly worsening cardiopulmonary dysfunction and seizures, and they died a few hours after admission despite cardiopulmonary support. The last case was transferred to hospital in cardiopulmonary arrest and resuscitation was unsuccessful. All cases had positive stool samples for rotavirus RNA, and the rotavirus antigen was also detected in the serum of four cases, but not in the cerebrospinal fluid (CSF). Serum IL-6 and IL-10 levels were significantly higher in the severe cases than in children with rotavirus gastroenteritis without extraintestinal symptoms, and serum IL-10 levels were significantly higher than CSF levels in the severe cases. Conclusion: Cytokines appear to mediate the pathogenesis of severe rotavirus infection with extraintestinal involvement. In conclusion, these cases highlight the need for a routine rotavirus immunization programme.