A new cluster of hepatitis A infection in hemophiliacs traced to a contaminated plasma pool

Recently, several clusters of hepatitis A have been observed among hemophil iacs linked to factor VIII concentrates treated for virus inactivation sole ly with the solvent/detergent (S/D) method, a procedure that does not affec t nonenveloped viruses such as the hepatitis A virus (HAV). A new outbreak of hepatitis A in six hemophiliacs treated with the same lot of a factor VI II preparation occurred recently in Germany. The objective of the study was to clarify whether these diseases were caused by the administration of the S/D-treated plasma product, rather than a community-acquired infection. Po lymerase chain reactions designed to detect HAV nucleic acid have been carr ied out in the implicated factor VIII lots, in the corresponding plasma poo ls, and in serum samples of four out of six infected individuals. The nucle ic acid sequences were determined in samples that resulted in positive ampl ification products. HAV sequences were found in one of the two plasma pools used for manufacture of the incriminated product, in the incriminated lot itself, and in all recipient sera tested so far, although the latter were c ollected up to 7 weeks after the onset of jaundice. The sequences obtained were completely identical, revealing a unique HAV strain of genotype IA. Th is study provides conclusive evidence that hepatitis A can be transmitted b y factor VIII concentrates treated solely by the SID procedure for virus in activation. This inactivation method is not effective against nonenveloped viruses. Since a number of hepatitis A transmission episodes have been desc ribed with such preparations during the past 10 years, their continued use seems to be questionable unless additional virus removal or inactivation st eps are introduced to prevent the transmission of nonenveloped viruses. Mol ecular approaches again proved to be reliable tools for elucidating the cha in of virus transmission. (C) 1999 Wiley-Liss, Inc.