A study of the natural history and risk factors for hepatitis A can shed light on the potential for contamination of plasma concentrate with hepatitis A virus(HAV). According to the long-term Sentinel Counties Study conducted by Alter and colleagues at the Centers for Disease Control and Prevention in Atlanta, the most frequently reported risk factors for HAV infection are living with a patient who has hepatitis, homosexual activity, and close contact with young children. International travel to hepatitis A endemic areas and illicit parenteral drug use were less frequently documented risk factors, although illicit injectable drug use has been considered more significant in other hepatitis A studies. Approximately 40% of patients with hepatitis A reported no apparent risk factors. Hepatitis A occurs most often today in the 5- to 30-year-old age group. Young adults, who are also eligible donors, are thus at risk of infection. The natural history of hepatitis A was studied in New World owl monkeys. Fecal shedding of infectious virus was detected by 4 days after intravenous injection of infectious material and peaked at almost 10 million infectious particles per gram of feces just prior to onset of chemical evidence of liver disease. Viremia of substantial magnitude occurred throughout most of the 4-week incubation period and was maximal during the prodromal stage,prior to the development of clinical, chemical, or serologic manifestations of infection. Although the magnitude of hepatitis A viremia has not been well documented in humans, it is likely to reach levels of 104— 106 infectious particles per milliliter of blood. Thus, although almost all HAV infections are acquired by the fecal-oral route, blood-borne transmission of hepatitis A from asymptomatic individuals who are incubating the disease and who are also plasma donors is a possibility. A review of the solvent-detergent anionexchange chromatography method of producing factor VIII concentrates suggested that this process may not be adequate for the elimination of all infectious HAV from plasma pools.

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