Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial

Summary

Background

Hepatitis A vaccination stops outbreaks of hepatitis A infection, but its efficacy against infection after exposure has not been proven. We investigated the use of hepatitis A vaccine to prevent secondary infections with hepatitis A virus (HAV).

Methods

We did a randomised controlled trial of hepatitis A vaccine in household contacts of people with sporadic HAV infection (index cases). Households (index cases and contacts) were randomly assigned to the vaccine group or unvaccinated group, according to the study week in which they were enrolled. All household contacts in the vaccine group received vaccination at the time of entry to the study.

Findings

During 45 days of follow-up, secondary infection had occurred in ten (13·3%) of 75 households (two families had two cases each) in the untreated group and in two (2·8%) of 71 households in the vaccine group. The protective efficacy of the vaccine was 79% (95% CI 7–95). The number of secondary infections among household contacts was 12 (5·8%) of 207 in the unvaccinated group and two (1·0%) of 197 in the vaccinated group. Therefore, 18 individuals needed to be vaccinated to prevent one secondary infection.

Interpretation

Hepatitis A vaccine is effective in the prevention of secondary infection of HAV and should be recommended for household contacts of primary cases of HAV infection.

Introduction

The importance of infection with hepatitis A virus (HAV) is increasing in western countries. Improved sanitation and living conditions have led to a decline in the rate of infection among children, but consequently incidence has increased among people aged 15–24 years because of the larger proportion of non-immune susceptible adults.1, 2, 3 This change has led to a shift of infection in older agegroups, in which clinical illness is more frequent and severe,⁴ with large outbreaks involving young adults.5, 6 Spread of infection is mainly by common sources of exposure and person-to-person transmission. Secondary infection may play an important part in the maintenance of outbreaks. This epidemiological pattern highlights the need for prevention of secondary infection of hepatitis A.

Immunoglobulin containing high titres of antibody to HAV given before exposure effectively prevents HAV infection or clinically apparent disease.7, 8 When given after exposure, HAV infection may occur, but clinical expression is lessened (eg, prevention of jaundice and clinical illness). Because of the passive nature of the conferred immunity, however, the protection provided by immunoglobulin is limited to about 3 months. Moreover, declining concentrations of antibodies to HAV have been reported for some globulin preparations.⁹

An attenuated live vaccine is available10, 11 and prevention of infection after exposure to HAV has been seen in chimpanzees.¹² In addition, the vaccine has stopped continuing outbreaks.13, 14 The efficacy of this vaccine in prevention of infection after exposure in human beings has not been assessed in a controlled trial. The secondary attack rate of HAV in household contacts of primary acute HAV cases is about 20%.¹⁵ We therefore did a randomised controlled trial to study the efficacy of a hepatitis A vaccine to prevent secondary infection among HAV-susceptible family contacts of people with acute primary HAV infection.