New hepatitis A vaccines and their role in prevention

The hepatitis A virus (HAV) accounts for 20 to 25% of clinically apparent hepatitis cases worldwide. It generally causes mild to moderately severe acute illness. The serological prevalence of this virus is high in underdeveloped countries where poor sanitary conditions facilitate the spread of the virus. The Sentinel Counties studies of the Centers for Disease Control in the US have identified a number of factors associated with the acquisition of HAV, including household members, homosexual men, children and caretakers in day-care facilities who come into contact with individuals who are incubating or in the early phases of HAV infection. Poor sanitary conditions, international travel and intravenous drug use promote the transmission of the virus. However, in 40% of cases, no risk factor can be identified. Immune globulin (IG), once used exclusively for the prevention of HAV infection, acts by provoking passive-active immunity. It prevents clinical disease but permits subclinical disease to develop. Unfortunately, IG provides protection for only 3 to 6 months, necessitating repeat inoculation for exposure extending over 180 days. More recently, a number of live-attenuated and formalin-inactivated HAV vaccines have been developed and studied. The vaccines are well tolerated and highly immunogenic, with only mild local adverse reactions. The suggested dose and schedule is 720 ELISA units of inactivated vaccine injected intramuscularly at 0, 1 and 6 months. A single intramuscular dose of 1440 ELISA units followed 6 to 12 months later by a further injection has also been approved by the FDA and is available in several European countries. 90% of vaccines achieve protective levels of anti-HAV after the first injection. Routine use of the HAV vaccine for pre-exposure prophylaxis is expected to replace IG in healthy adults travelling to endemic areas, children in day-care centres, military personnel, homosexual men, healthcare workers and residents in institutions for the mentally disabled.