Is travel prophylaxis worth while? Economic appraisal of prophylactic measures against malaria, hepatitis A, and typhoid in travellers

Incidence of disease in travellers

As country specific information on infectious disease was largely unknown, we estimated the incidences of hepatitis A, typhoid fever, and malaria in United Kingdom residents returned from disease endemic regions. The incidence of travel associated infections in journeys to endemic countries defined by the World Health Organisation2 was expressed as a proportion of the number of visits by non-immune and non- immunised United Kingdom residents. The incidence of travel associated hepatitis A and typhoid in United Kingdom residents was calculated from surveillance data3 by adjusting for underreporting.4, 5 Malaria cases were further adjusted for by excluding foreign visitors, immigrants, and cases in refugees (Malaria Reference Laboratory, Public Health Laboratory Service, London). Visits to countries outside eastern Europe, the European Union including its Mediterranean members, North America, Australia, and New Zealand were used as the denominator for hepatitis A and typhoid. Numbers of visits were provided by the International Passenger Survey,1 a longitudinal survey of passengers resident in the United Kingdom. The survey provides country specific departures from the United Kingdom. Numbers of overseas visits were used as the denominator and may represent repeated journeys by the same person. Ninety five per cent confidence intervals were used for the sensitivity analysis.

Provision of immunisation

Currently in the United Kingdom travel advice and vaccines are predominantly given by general practitioners as part of their service contract. The statistics unit of the Department of Health provided numbers of doses of whole cell killed monovalent typhoid vaccine and human normal immunoglobulin refunded through the NHS prescription pricing authority. These were used to estimate the numbers of travellers immunised during 1991. Prescriptions of multidose phials of typhoid vaccine suggested that around 32% of all travellers had received either a booster or a primary course of typhoid vaccine, consistent with the seroprevalence of antibodies to typhoid in departing travellers reported by Cossar et al.6 The proportion of travellers seropositive to hepatitis from published figures was 54%.6 In our analysis this was made up of 30% who were naturally immune and 24% who had received passive immunisation based on prescription data. We assumed that most of those immunised were not immune.

Several of the vaccines were not in widespread use in 1991 but it was important to include the likely costs of these newer vaccines in our estimates. In order to do this we used the 1991 prescription numbers for human normal immunoglobulin and whole cell killed monovalent typhoid vaccine and estimated the cost had oral typhoid Ty 21a, typhoid polysaccharide Vi, and hepatitis A vaccines been used instead. Private prescriptions and vaccines given in the private sector were unknown. A figure of 20% of total vaccines used was assumed with a range of 0-40% for the sensitivity analysis.

Malaria prophylaxis - The proportion of United Kingdom residents who visit malaria endemic countries and use chemoprophylaxis has been reported at about 50%.7, 8 We based the incidence of malaria on the proportion not using chemoprophylaxis. The cost of three months of chloroquine and proguanil chemoprophylaxis at 1991 retail recommended prices was used in estimating costs to the traveller.8 An estimated 30% of all prophylaxis used was prescribed,9 the cost being met by the health sector. As mefloquine was introduced in late 1991 and little used, an estimate of cost for its sole use had it been prescribed was used in the calculations.

Effectiveness of prophylaxis - All the typhoid vaccine preparations were assumed to provide similar protective efficacy of 70%.10 The duration of protection against hepatitis A of a single 5 ml does of human normal immunoglobulin was six months. A three dose course of hepatitis A vaccine protects for at least one year11 and probably for five years or more. Both regimens were assumed to protect 90% of those immunised against clinical disease. The antimalarial regimens were attributed a protective efficacy of 72% for chloroquine and proguanil and 92% for mefloquine.12

Estimating costs

For a cost-benefit analysis it is necessary to assess the costs of the prophylaxis and compare these with the gains that are attributable to its use. To do this it is necessary to trace the costs and benefits to all those concerned - namely, the public sector, including the public health service, community services, hospital services - and costs to individuals and society in terms of loss of productive capacity and, occasionally, life. We used the cost of avoided diseases estimated from prophylaxis use in 1991 and costed prophylaxis provision to derive a cost-benefit ratio.

Health sector costs

Hospital costs - The cost of imported disease to the health sector was calculated from the mean inpatient length of stay and the costs of laboratory confirmed typhoid (8.0 days; n=58), severe hepatitis A (5.0 days; n=43), and malaria (3.5 days; n=658) at the Hospital for Tropical Diseases, London. The severity of malaria and typhoid was assumed to be the same for each bed day, as no information about the marginal cost per bed day during the illness was available. Ninety per cent of cases of hepatitis A were categorised as mild and not requiring hospital treatment and 10% as moderate or severe diseases needing hospital treatment.

General practitioner costs - The costs of giving vaccine, including the cost of an eight minute (on average) consultation with a general practitioner, were obtained from a British Medical Association survey13 and included the vaccine cost and disposable and reimbursement fees, less the patient's prescription charge when appropriate. (Neither age nor health of travellers was known. It was assumed that all travellers pay prescription charges (pounds sterling 3.75 in 1991) as they are predominantly fit and employed. This assumption effects the distribution of costs but not total costs.) Though there is a range of disease severity, we assumed that all malaria and typhoid patients saw a general practitioner twice and that patients with hepatitis A (assumed to be mainly housebound14) saw a general practitioner four times.

Costs to travellers and society

Costs to the traveller and society include lost productivity time during illness - 21 days in mild hepatitis; 95 days in severe hepatitis; 29 days for typhoid; 17.5 days in malaria. Lost income was based on average earnings plus costs of employment in 1991 for non-manual employees.15 Costs of travel to the general practitioner's surgery and to hospital for diagnosis and treatment and prescription charges and expenses of obtaining prophylaxis were also included. Children with infection require the same care as adults of working age, and we assumed a productivity loss in all cases. Some argue against using lost productivity during periods of high unemployment but, as recruitment is expensive, this is irrelevant for short term illness.

Loss of life

As some people might have avoided death by being vaccinated, our study incorporated a value of life estimate of pounds sterling 1.4m,16 a midpoint estimate from other studies. This subject is contentious but if not confronted would severely misrepresent the benefits of the programme. In addition to including a value of life in the cost-benefit analysis, we calculated the implied value of life. We used reported case fatality rates for typhoid,17 hepatitis A,18 and malaria19 in table II to provide the number of lost lives and calculated the value of these lives by the incurred costs of avoidance.

Willingness to pay

In the model we estimated benefits as avoided costs of illness. This approach does not address the fundamental question of how much people would have been willing to pay to avoid the infection. It does provide estimates of the pool of potential resources, if any, that may be available for other uses as a result of the disease prevention. Alternatively it indicates resources that could more appropriately be used elsewhere had the intervention not take place. We did not measure the value that might be placed by individuals on reduced morbidity or its impact on the quality of life. Estimates of these values are difficult but in subsequent studies we hope to explore the amount people would be willing to pay to avoid risk of death and reduction in quality of life when they are properly informed.

Comparison of vaccine protection by discounting costs

Because different vaccines afford differing durations of protection, costs of prophylactics that are administered repeatedly were discounted annually at the treasury rate of 6% to calculate the present value of prophylaxis at future administrations. To compare vaccine protection against hepatitis A for repeated journeys an arbitrary four journeys in five years was postulated.

Implications for society and the individual

For society the estimated costs to the NHS of giving typhoid and hepatitis prophylaxis to a third of travellers was pounds sterling 25.8m compared with the estimated costs of treating (in a specialist London hospital) cases prevented by the use of vaccine of pounds sterling 1.03m. This, along with implied value of life, which is well in excess of most other lifesaving strategies, indicates that immunisation against hepatitis A and typhoid is not an efficient use of NHS resources. The cost and benefits of screening were excluded in this study because the high cost of screening and low seroprevalance of antibodies are likely only to increase the cost-benefit ratio.

For the individual, however, the perceived risk of infection and morbidity may be higher than the estimated incidence in this study. The analysis shows the proportion of illness costs borne by the travellers balanced against the cost to themselves of prescription charges and loss of earnings for a consultation. This makes the cost-benefit of immunisation with human normal immunoglobulin (cost-benefit ratio 3.4) more evenly balanced. But for whole cell killed monovalent typhoid vaccine or hepatitis A vaccine, even for the individual, costs outweigh the benefits (cost- benefit ratios 23.8 and 9.2). We recognise that there is a difference between public policy and individual preference. The value and benefits individuals would attribute to the various methods of immunisation would be linked to their perceived threat of disease and its likely impact on themselves. Some people are at greater risk or have lower thresholds about taking any health risk. Their needs could be accommodated either by a payment system or by designing a suitable protocol which would target high risk non-immune groups. These might be military personnel, overseas volunteer workers, expatriates, or elderly people, who, although they have a significantly higher morbidity and mortality from hepatitis A, have a higher seroprevalence of hepatitis A antibodies.23

With increasing numbers of travellers and marketing of more expensive vaccines, the disparity between costs and benefits will undoubtedly have risen since 1991. Data on the contribution of increasing herd immunity to disease incidence, the destination specific disease incidence, and the impact of repeated travel - especially stratified by reason and type of travel - would add to the value and sensitivity of our estimates. Immunisation has only a minor role in reducing travel illnesses, which are generally most effectively avoided by travellers adopting appropriate behaviour.24, 25 To provide substantive protection against malaria, for example, compliant and careful insect avoidance measures and drug use are necessary. Advice and information which influence and improve behaviour make the biggest impact on travel related illness and should be the priority health strategy in protecting travellers. A national policy of immunising all travellers against typhoid and hepatitis A does not seem be cost beneficial to the community, and public funding for such a policy should be critically reviewed.

We are grateful for the help and data provided by the statistics office of the Department of Health, the International Passenger Survey of the Office of Population Censuses and Surveys, and Marie Blaze of the Malaria Reference Laboratory. We thank our many colleagues for their helpful comments and discussion in preparing the manuscript.