Recent advances in hepatitis A vaccine development

Abstract

Type A viral hepatitis is usually a self-limiting, benign inflammation of the liver resulting from infection with hepatitis A virus (HAV). Its clinical course is characterized by a short phase of prodromal illness comprised of mostly general manifestations such as fatigue, malaise, fever, chills, and headache, followed by more specific symptoms of nausea, vomiting, and abdominal discomfort. In about two thirds of clinically overt cases, these symptoms are accompanied by the appearance of jaundice. The disease usually lasts 2 to 3 weeks but may be followed by a prolonged period of convalescence. Until recently, it was thought that only occasional patients experience a more protracted course with bimodal or even polyphasic elevation of liver enzymes. During the past few years, however, evidence has accumulated which suggests that a considerable number of affected individuals in one report up to 20% of pediatric cases may relapse and that relapses might be associated with reactivation of virus shedding (Chiriaco et al., 1986; SjGgren et al., 1987; Fagan et al., 1990). Nonetheless, persistent infections and chronic hepatitis A have not been documented. Severe, fulminant hepatitis A with a fatal outcome is rare. The overall mortality following infection is as low as O.l-0.5% (for references see Gust and Feinstone, 1988). HAV is shed in the feces early in the incubation period (which is usually 3-4 weeks in duration) and reaches a maximum just as symptoms begin to develop. Hence, the virus is efficiently transmitted under conditions of low hygienic standards. Contaminated drinking water and food, and shellfish harvested from estuaries or coastal regions polluted with human feces and unprocessed wastewater, serve as efficient vehicles for the virus. In addition, person to person spread among house-