Influenza-associated encephalopathy, a severe neurologic complication of influenza, is being reported more frequently in Japan. We investigated the transcription of cytokine genes in peripheral blood leukocytes and compared patients with influenza and with encephalopathy or febrile convulsions and patients with influenza but without neurologic complications. A quantitative polymerase chain reaction (PCR) revealed that transcription of the interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha genes was up-regulated to a greater extent in patients with encephalopathy than in those without neurologic complications. Plasma IL-6 levels also were higher in patients with encephalopathy, although the difference was marginal. Viral RNA in throat swabs was quantified using a real-time quantitative PCR. The virus load was similar among patients with encephalopathy or febrile convulsions or without neurologic complications. Furthermore, virus load was not correlated with either the transcription of cytokine genes or plasma cytokine concentrations. These results suggest that influenza-associated encephalopathy might be a consequence of systemic immune responses.
TT virus (TTV) is a newly discovered virus from a patient with post-transfusion hepatitis. We investigated the frequency and pathogenesis of TTV infection in children. A semi-nested PCR assay was used to amplify TTV-DNA in serum samples from 254 ambulatory children without liver disease, 20 with hepatitis of unknown etiology, and 18 transfusion recipients or hemophiliacs. In positive samples, TTV-DNA was quantified by real-time quantitative PCR using a fluorescent probe. We detected TTV-DNA in 20% of children with hepatitis of unknown etiology, which was not statistically different from the 23% prevalence in ambulatory children. In transfusion recipients or hemophiliacs, the frequency was higher (50%) than that in ambulatory children (P = 0.01). Among ambulatory children, TTV-DNA was frequently detected in children with acute gastroenteritis (36%). TTV-DNA was detected in 10% of the infants under 6 months old, and 20% of the children from 7 to 12 months old. The prevalence was constant after the age of 1 year; however, the copy number of TTV-DNA was significantly higher in children under 1 year of age (mean: 10(5.4) versus 10(3.8) copies/ml, P= 0.008). Finally, TTV-DNA was quantified serially in three children with chronic hepatitis who were positive for TTV-DNA. The presence or amount of TTV-DNA was unrelated to the serum alanine aminotransferase level. These results indicate that TTV infection is common in children. The larger quantity of TTV-DNA in infants and the high prevalence of TTV in children of all ages suggest that TTV may be transmitted in early childhood. Its relationship to hepatitis is doubtful in children.
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