Editorials

Protecting travellers from hepatitis A

Vaccine should be used for almost every occasion when prevention is required

Infection with hepatitis A virus, an RNA virus of the picornoviridae family, remains an important public health problem in many regions of the world and is probably the commonest vaccine-preventable disease in travellers to developing countries. Although the incidence of acute hepatitis A virus infection is falling in developed countries, outbreaks continue to be reported¹ and it remains the cause of half the cases of acute viral hepatitis notified in England and Wales. Recent changes in official advice on protective prophylaxis need to be incorporated into the advice clinicians give to travellers who may be at risk of infection.

Hepatitis A infection usually follows oral ingestion of virus, spread by faecal shedding from an infected individual. The high seroprevalence of anti-hepatitis A virus antibodies in developing countries (more than 70% of adults), is largely due to a high rate of asymptomatic infection in childhood. As improved sanitation has led to less childhood infection in developed countries (less than 2% of 5-14 year olds are now seropositive in the United Kingdom²), fewer adults are now naturally immune, so a higher proportion of travellers are at risk of infection while abroad. Although the total number of cases of hepatitis A reported to the Public Health Laboratory Service in the UK has declined, the percentage of cases associated with a history of travel has risen from 7.6% in 1990 to 13.7% in 1998 (www.phls.co.uk/facts/hepat7.htm). Infection in adulthood results in acute icteric hepatitis in over 70% of cases. The case fatality rate is 0.3%-1.8%, and the risk of serious complications increases significantly with age.

The advent of hepatitis A virus vaccines means that protection may be provided by active immunisation. Universal childhood vaccination against hepatitis A has been debated³ but not been widely adopted, and wide geographical differences in the incidence of hepatitis A infection necessitate different vaccine strategies. Most vaccination is targeted at those populations at high risk of infection or of developing serious sequelae after infection. These groups include travellers to areas of high or intermediate endemicity; injecting drug users; patients with disorders requiring coagulation factor therapy; men who have sex with men; and patients with chronic liver disease, including chronic hepatitis C, who may have an increased risk of fulminant hepatic failure after hepatitis A virus infection.

Travellers were formerly offered either passive immunoprophylaxis with human normal immune globulin or active immunisation, and a recent survey of general practices in Scotland showed that 20% of travellers still receive passive immunisation as their sole prophylaxis, in part on grounds of cost.⁴ Every batch of immunoglobulin is manufactured from the pooled plasma of many blood donors, so attention has focused on its potential infective risks. Because of the theoretical risk of transmission of variant Creutzfeld-Jacob disease the British government decided, in 1998, that only plasma derived from outside the UK should be used for producing immunoglobulin. In the past few months, however, a change in immunisation policy means that human normal immunoglobulin will no longer be available to travellers in England and Wales for pre-exposure hepatitis A prophylaxis.⁵

Formerly, the addition of human normal immunoglobulin was recommended for those travelling within four weeks of receipt of vaccine, because of concern about the time taken to develop neutralising antibodies. However, data in chimpanzees suggest that vaccine protects against infection even if it is administered shortly after exposure.⁶ Although the effect of vaccination on virus shedding in exposed individuals remains to be more widely tested,⁷ the curtailment of Alaskan and Italian outbreaks through vaccination with a single dose, without concurrent administration of immunoglobulin, provides supportive evidence for the efficacy of one dose, post exposure prophylaxis. ^{8 9} Ideally, travellers should receive vaccine at least four weeks before travel, but, on the basis of available evidence, they should be vaccinated even up to the day of travel, particularly as the unavailability of human normal immunoglobulin now leaves vaccination as the only option for prophylaxis.

An economic appraisal of prophylactic measures against malaria, hepatitis A, and typhoid in travellers showed an unfavourable cost benefit ratio for hepatitis A prophylaxis.¹⁰ The analysis is, however, sensitive to the incidence of disease and suggests that hepatitis A vaccination can be made more cost effective by targeting travellers at particular risk. The communicable disease centres in both Britain and the US advise that travellers are at risk if they travel to regions of intermediate to high endemicity (which include Mexico, parts of the Caribbean, South America, Central America, Africa, Asia (except Japan), the Mediterranean basin, Eastern Europe, and the Middle East; www.cdc.gov/travel/diseases/hav.htm). The risk of infection increases with duration of travel and is highest for those living in unsanitary conditions,¹¹ although hepatitis A may also occur in those staying in luxury hotels.

Although the cost data provide an argument for targeting specific groups, they also show the difference between public policy and individual preference. General practitioners and nurse practitioners will have to evaluate the hierarchy of clinical and economic evidence for the efficacy and safety of hepatitis A vaccination. Practitioners may choose to target high risk travellers for vaccination but will need to discuss and record the rationale for their advice: they may want to confirm by serological screening that the individual is not naturally immune to infection. Advice should always be given about primary prevention in places with poor sanitation, although many cases of hepatitis A occur in travellers who have observed such measures. Though the cost effectiveness of vaccinating travellers against hepatitis A remains uncertain, clinicians may nevertheless want to advise prophylaxis, after discussing the risks of infection, side effects, and the costs. Then, if travellers are to receive protective prophylaxis, this should be as active vaccine, not human normal immunoglobulin.

George Webster, clinical research fellow. 

(g.webster{at}rfc.ucl.ac.uk)

Eleanor Barnes, clinical research fellow. 
Geoffrey Dusheiko, professor of medicine. 

Centre for Hepatology, Royal Free Campus, Royal Free and University College Medical School, London NW3 2 PF

Ian Franklin, national medical and scientific director. 

Scottish National Blood Transfusion Service, Edinburgh EH17 7QT

Acknowledgments

IF is the medical director of the Scottish National Blood Transfusion Service, which has produced an immunoglobulin preparation licensed for the prevention of hepatitis A. GD has 400 shares in GlaxoSmithKlineBeecham. His Universities Superannuation Scheme has large equity holdings in GlaxoSmithKlineBeecham (http://www.usshq.co.uk). He has received honoraria from GlaxoSmithKlineBeecham for consulting and research support.