2012 Antigen Review for the New Zealand National Immunisation Schedule: Hepatitis A

Abstract

This report summarises new research on hepatitis A virus (HAV) vaccines and vaccination published during the past four years. HAV is an enterovirus of the family Piconoviridae. There is only one HAV serotype throughout the world; within this serotype there are seven recognised genotypes, of which four affect humans. The disease is spread from person to person by close contact, mostly within families and between sexual partners. A small number of outbreaks are associated with contaminated food, including raw or undercooked shellfish, raw fruit and vegetables. People at highest risk for infection are those who engage in personal contact with an infected person and travellers to countries with high rates of HAV infection. Most young children in endemic countries have asymptomatic or mild infections that confer long-term immunity. As living standards improve, such as sanitation, fewer younger children get infected and a greater proportion of the population become susceptible to infection. NZ Epidemiology The incidence of notified HAV infection in New Zealand has steadily declined in recent decades, from a rate of 145.7 per 100,000 in the population in 1971, to 0.6 in 2011. In this year there were a total of 26 cases, and there have been no deaths since 2002. Overseas travel is the most common risk factor, followed by consumption of contaminated food or water. Over two-thirds of cases had travelled overseas during the incubation period of the disease with the most common reported country being India. Most cases are from the Auckland region, primarily in Asian ethnic groups, and are distributed mostly across children and younger adults. Vaccines All currently available international inactivated HAV strain vaccines are grown in cell-culture. They are adjuvanted with aluminium or liposomes, and most monovalent vaccines do not use preservatives. Combination inactivated HAV vaccines are available combined with a hepatitis B or typhoid vaccine; these vaccines use aluminium adjuvant and the preservative phenoxyethanol. One live attenuated vaccine is produced in China. Safety There are no safety concerns with widespread use of the inactivated HAV vaccines. They appear safe when used in immunosuppressed recipients, including HIV-infected children. There is insufficient data to draw conclusions on the safety profile for live attenuated vaccines. Immunogenicity, efficacy, effectiveness A clear correlate of protection has not been established, and measures vary with different assays used. Despite this, all the inactivated HAV vaccines appear highly immunogenic after a single dose in all recipients over 12 months of age. A booster dose is likely to be important for long-term protection, in the absence of wild boosting. Immunogenicity rates are lower in HIV-infected patients but still likely to be effective. Duration of immunity after a single dose is likely to be up to 10 years in children and at least 15 years in adults. A second dose is likely to give protection for 25 years or longer. Universal vaccination programmes show strong herd immunity effects with herd immunity accounting for around one third of the cases prevented. HAV vaccines are highly effective in preventing clinical disease with efficacy measures of 94-100% from 6 weeks post-vaccination. Age and High Risk Specific Issues NZ currently has low rates of HAV notification with a concentration in children and young adults, particularly travellers. Low endemicity countries comparable to NZ show the second-highest risk group, after returning travellers, to be illicit drug users. Other high-risk groups to consider are men who have sex with men, poor food preparation environments and waterborne contamination from sewage. Individuals with chronic liver disease are not at higher risk of exposure, but at higher risk of severe outcomes. Options for scheduling For countries with low endemicity of HAV disease there are two options; a universal schedule, usually a single dose from one year or age, or a targeted schedule focused on those at higher risk of contracting the disease and/or higher risk of poor outcomes. The WHO recommends a single dose HAV schedule, if used as a national schedule vaccine. The evidence for the additional need for a booster is currently unclear. Combination vaccines are available with hepatitis B. Outbreak control can be effectively managed with vaccinations in healthy persons 40 years and younger both with pre- and post-exposure prophylaxis. For those over 40 years immunoglobulin is recommended. Eradication is theoretically possible but current international focus is on improving living conditions and the strategic application of vaccination. Implementation Issues Prevaccination serological testing is not recommended in children, but can be undertaken in others, particularly in populations with a high prevalence of infection. The most recent list of recommendations for administering the HAV vaccine to those considered at highest risk, as reported by the US ACIP, is reported on page 23 Table 3. Recent data on concomitant use shows co-administration with MMR-V, PCV7, and DTaP and Hib in the second year of live has no safety or immunogenicity concerns. Mixed schedules can be used with all commonly used monovalent inactivated vaccines. Vaccine safety in pregnancy is unknown, but is theoretically unlikely to be a concern with an inactivated vaccine. International Practice The majority of developed countries do not have HAV vaccination as part of their childhood immunisation schedule. In most developed countries the incidence of HAV is low, and only at-risk groups are recommended for vaccination. There are some countries with medium to low endemicity that offer a universal HAV programme, usually given at 12 months of age. The first country to offer this was Israel. The US offers a two dose regime at 12 months and a booster 6-18 months later. The UK and European countries offer vaccination to high risk groups only. Australia offers universal vaccination to all Aboriginal and Torres Strait Islander children at 12 – 24 months of age, and to other high risk groups only.