Abstract

Human herpesvirus type 6 (HHV-6), a T-lymphotropic DNA virus commonly associated with exanthema subitum in 1-2 years-old children, has also been associated with sudden death and short-term mortality. Its authentic contribution to death is still debated and anecdotal evidence only has been provided. We evaluated the contributing role of HHV-6 in death of four children (4-months-, 3-years-, 6-years-, and 11-years-old). In all patients, death was initially associated with HHV-6. We used serum immunoassay, nested polymerase-chain-reaction (PCR) amplification of the viral genome, immunohistochemistry, transcriptosome analysis, and transmission electron microscopy (TEM) for detection of HHV-6 infection. HHV-6 DNA sequences were amplified in all four index cases and HHV-6 viral proteins were also detected by immunohistochemistry, but transcriptosome analysis and TEM failed to demonstrate either viral RNA replication or virus particles, respectively. On the basis of our data, we suggest more prudence in diagnosing HHV-6 infection as cause of death. Although electron microscopy may be a practicable detection technique for virus identification in specimens from living patients, its use with specimens coming from postmortem examination has not been completely validated and is very dependent from the time interval between death and autopsy. However, to the best of our knowledge the presence of HHV-6 DNA viral copies in serum may be considered necessary, but is not sufficient to identifying it as cause of death. Conventional PCR results have to be confirmed by transcriptosome analysis. A detailed review of the methods for diagnosing HHV-6, their advantages and disadvantages or limitations is provided.