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# Screening for human T cell leukaemia/lymphoma virus among blood donors in Sweden: cost effectiveness analysis

BMJ 1998; 316 (Published 09 May 1998) Cite this as: BMJ 1998;316:1417
1. Elsa Tynell, specialist, infectious diseases (elsa.tynell{at}inf.ds.sll.se)a,
3. Eva Lithander, senior officerc,
4. Malin Arneborn, nurse epidemiologistb,
5. Jonas Blomberg, associate professord,
6. Hans Bertil Hansson, county medical officere,
7. Aud Krook, associate professorf,
8. Mats Nomberg, head of computer departmentg,
9. Kristina Ramstedt, epidemiologistb,
10. Agneta Shanwell, associate professorg,
11. Anders Bjorkman, associate professora
1. a Division of Infectious Diseases, Karolinska Institutet, Danderyd University Hospital, Danderyd, Sweden
2. b Swedish Institute for Infectious Disease Control and Karolinska Institutet, Stockholm, Sweden
3. c National Board for Health and Welfare, Stockholm, Sweden
4. d Section of Virology, Department of Medical Microbiology, University of Lund, Lund, Sweden
5. e Regional Centre for Communicable Disease Control, University Hospital MAS, Malmo, Sweden
6. f Division of Infectious Diseases, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden
7. g Division of Transfusion Medicine, South Hospital, Stockholm
1. Correspondence to: Dr Tynell
• Accepted 4 February 1998

## Abstract

Objective: To analyse the cost effectiveness of a national programme to screen blood donors for infection with the human T cell leukaemia/lymphoma virus.

Design: Three models for calculating the costs and benefits of screening were developed. The first model analysed the cost of continuously testing all donations; the second analysed the cost of initially testing new blood donors and then retesting them after five years; the third analysed the cost of testing donors only at the time of their first donation. Patients who had received blood components from donors confirmed to be infected with the virus were offered testing.

Setting: Sweden.

Main outcome measures: Prevalence of infection with the virus among blood donors, the risk of transmission of the virus, screening costs, and the outcome of infection.

Results: 648 497 donations were tested for the virus; 1625 samples tested positive by enzyme linked immunosorbent assay. 6 were confirmed positive by western blotting. The prevalence of infection with the virus was 2/100 000 donors. 35 patients who had received blood infected with the virus were tested; 3 were positive. The cost of testing every donation was calculated to be $3.02m (£1.88m); this is 18 times higher than the cost of testing new donors only, and only 1 additional positive donor would be discovered in 7 years. Regardless of the model used, screening was estimated to prevent only 1 death every 200 years at a minimum cost of$36m (£22.5m).

Conclusion: Based on these estimates the Swedish National Board of Health and Welfare decided that only new blood donors would be screened for infection with the virus.

#### Key messages

• The human T cell leukaemia/lymphoma virus is primarily sexually transmitted; it may also be transmitted through blood transfusions

• Infection with the virus may cause adult T cell leukaemia/lymphoma or tropical spastic paraparesis

• Many countries including Sweden have begun screening blood donors for the virus; however a low prevalence of infection in non-endemic areas a low risk of developing adult T cell leukaemia/lymphoma in people infected with the virus a long incubation period and the older age of most transfusion recipients make screening costly

• Three models of screening were compared: testing every donation, testing new donors and then retesting them after five years, and testing new donors only

## Discussion

### Prevalence of infection

The prevalence found among blood donors in Sweden (2/100 000) was similar to that found in Denmark17 and the Netherlands.18 The slightly higher prevalence found in the United Kingdom (5/100 00019) and France (7/100 000 20 21) may reflect a higher proportion of donors who originally came from an endemic area, such as the Caribbean, or a greater likelihood of having a sexual partner from an endemic area. The prevalence rates among Europeans without obvious risk factors appear to be uniform at about 1 to 2/100 000. No donor of Swedish origin tested positive for infection with type II virus. In Europe, few donors have tested positive for infection with type II virus despite the relatively high prevalence of infection with type II among injecting drug users.13 This is in contrast to a study in the United States where almost half of the donors who tested positive for human T cell leukaemia/lymphoma virus were infected with type II.22

### Laboratory testing

We assumed that no donor infected with the virus escaped detection since enzyme linked immunosorbent assays have high sensitivity.23 In our study, samples that were positive when tested by enzyme linked immunosorbent assay were tested by western blotting for confirmation. Samples that were positive by western blotting also tested positive by polymerase chain reaction. However, no samples that were classed as indeterminate by western blotting were positive when tested by polymerase chain reaction. This is consistent with previous studies that found that samples classed as indeterminate only occasionally tested positive by polymerase chain reaction. 18 24 25 False positive results with the enzyme linked immunosorbent assay were found in 1 out of 400 donors, giving an overall specificity of 99.8%. This is similar to findings in Holland.18

We believe that the chance that our study failed to detect a donor positive for type II virus is low; the screening assays mainly were based on type I whole viral lysates and thus relied on cross reactivity for detection of type II virus. Our own evaluation of the type I derived assays has shown 85% to 100% sensitivity for type II virus (S Andersson, unpublished data).

Half of the samples that were positive on initial screening were classed as indeterminate by western blotting. We believe that these findings represent technical artefacts, although they could represent reactivities to other infectious agents that are as yet unrecognised or seroconversion of samples from people who had recently become infected. The large number of samples that tested positive at the initial screening and were classed as indeterminate by western blotting was a result of the large total number of donors screened. All donors who repeatedly tested positive by enzyme linked immunosorbent assay were excluded from making donations. Every year about 80 newly recruited blood donors are expected to be banned from further blood donation. The costs of screening include the psychological stress caused to donors because of learning potentially worrying information and the costs to the laboratories and blood banks in additional work. Improvements in screening tests may minimise these problems.

### Transmission

Thirty five patients who received blood components from donors who tested positive for the virus were tested. Three were positive; none of the three had any risk factors for infection other than the blood transfusion. This indicates that they became infected at the time of transfusion. Almost half of the patients who had received blood components from donors who tested positive for the virus had already died, since most of them had been transfused several years before the study. We have no reason to believe that infection would result in an increase in early mortality and an underestimation of transmission.

We found an overall risk of transmission of 9%. Recent studies have found risks of transmission from whole blood to be 13%15 and 27%,16 and older studies have found up to a 63% risk of transmission.10 The lower current risk probably reflects improved separation methods and increasingly efficient removal of white blood cells, where the virus is normally found.26

Infectiousness also depends on the length of time the blood is stored; there is little transmission of the virus after 10 days in storage.16 The amount of time blood components are stored varies between blood banks and at different times of the year. Platelets must be transfused within five days of collection and are likely to pose a relatively high risk of transmission. Theoretically the risk of transmission should decrease if blood components are transfused only after being stored for 10 days. However, waiting 10 days before using blood components could lead to problems such as an increased risk of haemolysis, increased storage costs, shortened half life of transfused red blood cells, and reduced access to donated blood.

One transfused patient who received plasma tested positive for the virus. This was unexpected since plasma normally contains only a few white blood cells and is often stored for a longer time than other blood components.

### Cost effectiveness

An analysis of the cost effectiveness of screening should take several variables into account, such as the prevalence and incidence of infection in the population, the risks of transmission, the mortality and morbidity of those infected with the virus, and the expected survival rate of patients receiving blood components from donors infected with the virus.

The calculation of the expected seroprevalence of human T cell leukaemia/lymphoma virus types I and II in new blood donors was based on the prevalence in donors who did not come from endemic countries.16 A more strict assessment of donors has been introduced in Sweden and potential donors from areas endemic for infection with HIV, human T cell leukaemia/lymphoma virus, or hepatitis B are excluded from donating blood. However, an increasing number of Swedish citizens are born to immigrants from endemic areas.

The incidence of infection among already established blood donors was estimated from the prevalence in Swedes and was based on the assumption that the risk of acquiring infection mainly occurs after age 15. With an assumed mean age of blood donors of 35 years, the cumulative incidence of 1/100 000 reflects 20 years of exposure to sexual transmission for each donor. This provides a risk of seroconversion among regular donors of about one in 4 million donations; this is similar to the risk found in France.21

In the cost effectiveness analysis the risk of transmission from a positive donor to a recipient was assumed to be 15% for each transfusion. This was based on findings both in the retrospective study and in other published data as discussed above. 10 15 16 A risk of 30% would obviously reduce the costs by half.

We assumed that adult T cell leukaemia/lymphoma is always fatal. The incubation time from infection to the development of clinical disease and death is normally more than 30 years. Only 10% of those patients who received transfusions in our pilot study in 1992 were likely to have lived for more than 30 years after transfusion. In our analysis, the risk of developing adult T cell leukaemia/lymphoma as a result of transfusion was therefore low and even this low risk may represent an overestimate, since it is possible that the development of adult T cell leukaemia/lymphoma may be associated only with infection in childhood or infancy.10

Complications occurring secondary to tropical spastic paraparesis may cause premature death but no data are available to quantify this risk and we have therefore not included mortality from tropical spastic paraparesis in our analysis.

It is not feasible to selectively screen only blood donations intended for specific groups of patients, such as pregnant women and children, although this might eliminate most of the deaths caused by transmission by transfusion. It might be more practical to improve filtration so that more leucocytes were removed from all blood components intended for use in pregnant women or children; this might further decrease the risk of transmission.

In our analysis the costs of preventing one transmission when only new donors were screened was $440 000 (£275 000). According to the findings of another study the costs in the United Kingdom would be about one tenth the costs in the United States ($47 000; £29 375),27 while in France the costs were estimated to vary from 1.3m French francs ($200 000; £125 000) in the first year of screening to 5.7m French francs ($900 000; £563 000) in the third year of screening.20 The differences in costs between our study and the others 19 27 reflect several differences in calculations. The two studies did not account for the benefits of excluding donors who test positive from donating in the future. The findings from the United Kingdom are based on only the first year of screening and the French study is based on screening all donations. The studies also do not report on the survival rates of patients who received transfusions from donors who tested positive so they do not include comparable information on the prevention of morbidity and mortality.

### Healthcare policy

Decisions on healthcare policy, as with many other decisions in society, are often taken in part as a result of an analysis of the cost effectiveness of different activities. In most healthcare systems there has been a reluctance to consider life and health in purely economic terms. Generally, however, insurance companies and traffic planning authorities are already dependent on such evaluations. In Sweden, the mean cost to society for a person killed in a traffic accident has been estimated to be about $1.4m (£875 000)28 The mean cost in seven other countries in western Europe was found to be similar at about$1.5m (£937 500).28 These estimates may form the basis for decisions on allocations of resources, for example the costs of the prevention of fatal car accidents. In Sweden the cost of saving one life if only new blood donors are screened for the human T cell leukaemia/lymphoma virus is 35 times higher than the value of the life of a person killed in a traffic accident.

Another way to estimate the value of a life is to determine how much the public is willing to pay to avoid a certain risk. In Britain the cost to society of a person killed in a car accident was found to be less than the cost to society of a person killed in a train accident.29 This discrepancy occurred because people were assumed to have less personal control when travelling by train as opposed to travelling by car. In the case of a transfusion then the recipient may be assumed to have an almost total lack of control. Thus, a relatively high cost for saving each life may therefore be reasonable.

The HIV epidemic has increased society's awareness of bloodborne infections and raised concern over their prevention. Swedish society seems prepared to allocate considerable resources to decrease risks and increase benefits. However there are limits to a society's resources and ultimately a political decision will be made; this decision should be based on sound calculations. In our analysis the older age of most transfusion recipients, the long incubation time of adult T cell leukaemia/lymphoma, and the low risk of developing clinical disease from infection with the virus strongly affected the benefits of screening. Thus, although the incremental costs for testing all blood donations were considered to be too high, not testing at all was considered unethical.

Most countries have not started screening blood donors for the human T cell leukaemia/lymphoma virus. Those countries that do screen generally test every unit. In May 1995, as a result of the cost effectiveness analysis presented here, the Swedish National Board for Health and Welfare decided that only new blood donors and donors who had not been tested earlier would be screened for the human T cell leukaemia/lymphoma virus.

## Acknowledgments

We thank Patrik Olin, Swedish Institute for Infectious Disease Control, for his contributions. We also thank those colleagues who participated in the screening programme, the general policy discussions, and specific investigations related to this publication: Jan Albert, Gunnel Biberfeldt, Ove Berglund, Bo Bresky, Hans Fredlund, Johan Giesecke, Lena Grillner, Åke Gustavsson, Mona Hild, Olle Järnmark, Björn Lager, Ami Lexmark, Anders Lindberg, Annika Lindholm, Lisbeth Messeter, Rut Norda, Olof Ramgren, Gunnar Sundström, Madeleine von Sydow, Jan Säfwenberg, Tommy Söderström, Carl Olof Welin, Bengt Wadman, Barbro Wiechel, Olof Åkerblom, and the Swedish Society for Transfusion Medicine.

Contributors: ET coordinated and performed most of the study, especially the final compilation and analysis of data. AB acted as a consultant to the national screening programme, assisted in the analysis of data, initiated the development of the cost effectiveness models, and is guarantor for the paper. SA was responsible for the polymerase chain reaction analysis and developing the guidelines, evaluation and analysis of the laboratory screening. MA coordinated the compilation of all data on blood screening. KR coordinated the tracing of transfusion recipients who had received infected blood. EL was instrumental in developing the structure of the national screening programme. JB conducted the pilot study. HBH directed the pilot study and was responsible for tracing the recipients of infected blood. AK assisted in compiling clinical data on donors infected with the virus. MN assisted with the pilot study. AS contributed to the discussion on the principles of blood transfusion. The paper was written by ET, SA, and AB.

Funding: None.

Conflict of interest: None.

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