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Is screening of Australian blood donors for HTLV-I necessary?

Gordon S Whyte

MJA 1997; 166: 478
For editorial comment see Kaldor

Subsequently cited in Wong et al. Should we be screening blood donors for hepatitis G virus? The case against screening. MJA 1998; 169: 375-377

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Abstract - Introduction - The decision to screen blood for HTLV-I - Blood donor data collection - Extrapolation of State data to national data - New and repeat Australian donors - Screening of donors - Prevalence and incidence of HTLV-I - Risk of HTLV-I transmission - Discussion - Acknowledgement - References - Authors' details

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Abstract

 Objective: To re-examine the 1992 decision by Australian Red Cross for its blood banks to screen blood donors for antibody to human T-cell lymphotropic virus type I (HTLV-I) by determining the risk of its transmission by blood transfusion.
Methods: Data on patterns of return behaviour by repeat blood donors in Victoria were modelled to deduce the number of donors giving repeat donations in Australia from March 1993 to December 1995. Data on annual donor and issued cellular blood products from 1992 to 1995 were obtained from national Red Cross statistics. From the numbers of donations given by repeat donors, together with the number of new donors, the number tested for HTLV-I was deduced. The number and characteristics of donors screened positive for HTLV-I antibody were collated. The crude prevalence of HTLV-I was calculated by dividing the number of donors with HTLV-I by the total number of donors (repeat donors and new donors). The incidence of HTLV-I was calculated by dividing the number of seroconversions in repeat donors by the cumulative period of donor exposure.
Results: Sixteen homologous and five autologous donors were found to be positive for HTLV-I; none seroconverted and no clear risk factors for HTLV-I were identified. The prevalence of HTLV-I in Australian donors is 1 in 100 000 and the incidence less than 1 in 1 million person-years. In the absence of HTLV-I screening, the calculated risk of a transfused patient developing HTLV-I infection is 1 in 370 000, with a risk of developing HTLV-I disease of 1 in 9 to 15 million.
Conclusion: Three possible future courses of action for screening for HTLV-I are to screen every donation, to screen only new donors or to discontinue screening altogether. Using the information in this study, public discussion should be encouraged to assist stakeholders to agree on an acceptable level of risk and an appropriate level of screening for HTLV-I in Australia.

MJA 1997; 166: 478-481  

Introduction

 Human T-cell lymphotropic virus type I (HTLV-I) is endemic in all continents including Australia,1,2 where in some Aboriginal communities it is present in up to 14% of individuals.3-6 HTLV-I was first described in cases of aggressive T-cell leukaemia in southern Japan7 and in a T-cell lymphoma in a Jamaican patient.8 In areas endemic for the virus, 2% to 4% of those infected rapidly develop fatal leukaemia, with a peak incidence in the sixth decade of life.9 Progressive spastic myelopathy (or tropical spastic paraparesis), first reported in association with HTLV-I infection in Caribbean patients,9 occurs infrequently (0.25%).9

Transmission of HTLV-I is primarily by sexual contact and by infected cellular blood products (packed red cells, platelet-rich plasma and whole blood); breast milk is a major route of HTLV-I transmission in communities where the virus is endemic.10 In predominantly white communities, occasional cases of HTLV-I infection, in the absence of any risk factors, may represent transmission across several generations in a family.11 In a survey of 11 121 Northern Territory blood donors in 1991-1992, only one donor (with no evident risk factors) was confirmed as HTLV-I seropositive.6

Since March 1993, all Australian blood donors have been screened for antibody to HTLV-I. The decision to implement screening was made by the National Executive of the Australian Red Cross in February 1992, despite a lack of agreement among some government advisory bodies. The decision to screen for a rare transfusion-transmitted disease can be re-examined in the light of the results of HTLV-I screening of Australian blood donors from 1993 to 1995.  

The decision to screen blood for HTLV-I in Australia

 In October 1986, the American Red Cross proposed that, when a test became available, blood donors should be screened for HTLV-I as this retrovirus could be spread by blood transfusion and had been detected in blood donors.12 In November 1988, the United States Food and Drug Administration recommended testing of whole blood and cellular blood products for antibodies to HTLV-I,13 which was followed by a public review of the issues involved.14 Universal screening was also introduced in Canada, France, the Netherlands and Sweden.

In Australia, after recommendations by the Red Cross National Blood Transfusion Committee (in September 1989 and later in March 1991) for HTLV-I screening to be funded, the then Federal Minister for Health sought advice from the National Health and Medical Research Council (NHMRC) in January 1992. In July 1991, the Communicable Diseases Standing Committee of the NHMRC had decided that the costs of screening Australian blood supplies (for HTLV-I) outweighed any public health benefits. This position was endorsed in 1992 by the Public Health Committee of the NHMRC15 and published by the Executive of the NHMRC in December 1992.16 However, the NHMRC also stated ". . . decisions on screening may have to be made on other than public health grounds".16

In February 1992, in the absence of a decision from NHMRC and acting on legal advice, the National Blood Transfusion Committee of the Australian Red Cross recommended that cellular blood products be screened from May 1992.17 By March 1993, although some State governments refused to fund HTLV-I screening, all Red Cross Blood Banks had commenced routine testing for HTLV-I under instruction from the Red Cross National Executive.

A report by the Australian Health Ethics Committee, which was endorsed by the NHMRC in November 1993, stated that the cost of screening for HTLV-I was considerable and the risk to the community was low, and that "the spectre of large damages (litigation) . . . probably had a significant influence on the reasoning leading to implementation".17 It considered that the risk of transfusing HTLV-I-infected blood, although real, was rare. The report concluded that a decision not to screen all blood in Australia for HTLV-I would not be unethical.17  

Blood donor data collection

 Data on the number of individuals who donated whole blood in Victoria between March 1994 and December 1995 and the interval from the date of the previous donation were extracted from Victorian Red Cross Blood Bank records. Patients attending for autologous, directed or therapeutic donations were excluded, as were donors returning for repeat testing or counselling only. Plasma donors were excluded because HTLV-I is not transmitted by plasma. The 1994-1995 attendance pattern was comparable with attendance patterns of repeat donors attending in June and July between 1993 and 1996 and was therefore applicable.

Data on the number of whole blood collections in Australia and the number of new donors each year were obtained from the annual statistics of the Australian Red Cross Society. Data on the number of blood donations and the number of issues of cellular blood products in Australia for the financial years 1992-95 were obtained from national Red Cross statistics.  

Extrapolation of State (Victorian) data to national data

  

Donor attendance patterns

 Repeat donors give many donations, so it is necessary to deduce the number of donors tested for HTLV-I from the total number of donations. The total number of repeat donations is used to calculate the number of repeat donors giving the donations by using a hypothetical model, together with the number of donations given by new donors. Using this information, the prevalence of HTLV-I in donors can then be estimated.

Iterative model: The pattern of return after previous donations by Victorian repeat donors was applied to a hypothetical model in which 1000 donations were given each month over 34 months. Using an iterative spreadsheet model, the number of donors giving 1000 repeat donations each month from March 1993 to December 1995 was calculated (Figure, below).


It was assumed that all repeat donors in Australia had a similar pattern of repeat donation. By analogy, the proportion of repeat donors contributing the 34 000 donations from repeat donors in the model was applied to the total number of donations from repeat donors in Australia over the 34-month period. To apply the model, it was assumed that the same number of repeat donations was given each month and that the discounting effect of donor rejection was constant over time.

The number of Victorian donors and the intervals between donations were extrapolated to all repeat donations in Australia between March 1993 and December 1995 to derive a figure for donor exposure in person-years. "Donor exposure" is the sum of the time between one donation and the next for all donation intervals during the period. The sex and age distribution of Victorian donors was extrapolated to all Australian donors.  

Prevalence, incidence and risks of HTLV-I

 The number and characteristics of donors confirmed positive for HTLV-I were provided by Red Cross blood banks in each State and Territory. Donors were confirmed positive if their plasma reacted in triplicate with one of seven HTLV-1 enzyme-linked immunosorbent assay screening tests (Genetic Systems; Abbott; Cambridge recombinant/Ortho; Serodia particle-agglutination; Murex; Sanofi Platelia new; Organon Teknica), as approved by the National Reference Laboratory, and showed a diagnostic pattern on a western blot.

The crude prevalence of HTLV-I was calculated by dividing the number of donors with HTLV-I by the total number of donors tested (repeat donors and new donors). The incidence of HTLV-I was calculated by dividing the number of seroconversions in repeat donors by the cumulative period of donor exposure.

The risk of disease transmission was calculated from the infectivity rate for HTLV-I and the long-term risk of HTLV-I disease in patients.  

New and repeat Australian donors

 The return patterns for repeat donors over the period remained much the same. No donors returned within 12 weeks of donating blood. Of the donors who returned after making a previous donation, 0.29, 0.74, 0.84, 0.89, 0.92 and 0.94 had returned after successive quarters and 0.06 had returned after 18 months.

Across Australia, first-time donors gave 335 183 whole blood donations and repeat donors gave 2 038 927 whole blood donations between March 1993 and December 1995. The proportion of first-time donations over the four fiscal years from July 1992 was 0.14, 0.14, 0.14, and 0.13, respectively.  

Screening of donors for HTLV-I

 By applying the pattern of return for repeat donors in Victoria to a hypothetical figure of 1000 donations a month over 34 months from repeat donors, it was concluded that the 34 000 donations would have been given by 19 197 donors in Victoria who had returned within 18 months. Furthermore, 6% (2040) would have been given by repeat donors whose previous donation was more than 18 months previously.

By applying the Victorian model to the national statistics, it was concluded that over the 34 months 2 038 927 donations were given by 1 273 550 repeat donors. In addition, there were 335 183 new donors and donations. Therefore, a total of 1 608 733 individuals had been screened for HTLV-I.

Some States had begun testing for HTLV-I before March 1993, but the high proportion of repeat donors in Australia, the small number of infected donors and the absence of serconversion permit the assumption that they would have been identified if screening had been delayed to March 1993.  

Prevalence and incidence of HTLV-I in blood donors

 To December 1995, 21 donors had been confirmed positive for HTLV-I in Australia, each on the first occasion the donor was tested. Five of the blood collections were for autologous transfusion. There were no seroconversions (a change in serological status from negative to positive) during the study period. Two donors were identified before June 1992, with 5, 8 and 6 in each subsequent 12 months. More men and more first-time donors were positive than expected, but the age distribution matched that of the general donor population (Box, below). There were no clear patterns of disease acquisition, although four of the five donors born in endemic areas were aged less than 40. Therefore, the crude prevalence of HTLV-I in Australian blood donors was 16 in 1 608 733, or 1 in 100 546.


In Victoria, repeat whole blood donors gave 358 332 donations between March 1994 and December 1995, with intervals from the previous donation of up to 23.5 years. The repeat donors represent 11 851 014 person-weeks of exposure, or 227 904 person-years. By extrapolation, 2 038 927 repeat donations in Australia represent 1 296 785 person-years of exposure. There were no seroconversions. Therefore, the crude incidence of HTLV-I in Australian blood donors was less than 1 in 1 000 000 person-years.  

Risk of HTLV-I transmission via blood transfusion

 The risk of transmitting HTLV-I in Australia by blood transfusion over the study period was calculated from the number of donations given by 16 donors in 2 374 110 donations. The spreadsheet calculations showed that 1.6 million donors gave 2.4 million donations, so 16 donors would have given 24.6 donations. Therefore, the risk of receiving blood infected with HTLV-I before testing was about 1 in 100 000. The infectivity rate has been recently reported as 0.27,18 so only 1 in 370 000 transfusion recipients would become infected.

Relatively few (2.5%-4%) people with HTLV-I infection not acquired by blood transfusion risk developing disease after 10 to 30 years.19 Therefore, the risk of developing HTLV-I disease from blood transfusion in Australia without testing would have been 1 in 9 to 15 million. Transfusion recipients, particularly those who are immunocompromised, may have a shorter incubation period,20 and infants of infected mothers have a 25% chance of becoming infected.21

If universal screening were discontinued, then the risk of transfusing infected blood would progressively return to the pretesting situation because of the recruitment of new donors from a population with the same characteristics as at present, as well as the retirement of repeat donors who have already been screened.

In the absence of seroconversion, if only previously untested donors are screened for HTLV-I then there will be a zero risk of transmitting HTLV-I by blood transfusion. However, seroconversion has been reported in Dutch, French and American studies.22-24

If only the 14% of donations by new donors are screened, then the costs to Red Cross and the community would be significantly reduced.  

Discussion

Our results have shown that the prevalence of HTLV-I in Australian donors is 1 in 100 000. By comparison, the prevalence of hepatitis C virus in new Victorian donors is 1 in 560; of hepatitis B virus, 1 in 650; and of HIV, 1 in 27 000. However, the introduction of universal blood screening for these diseases has reduced the risk to the transfused population for hepatitis C virus to 1 in 150 000, for hepatitis B virus to 1 in 150 000 and for HIV to 1 in 1.3 million.25 The risk of transfusing HTLV-I-infected blood would have been 1 in 100 000 without screening. In the United Kingdom, HTLV-I has been found in 1 in 20 000 donors; in the United States, in 1 in 6000; and in Sweden and the Netherlands, in 1 in 50 000.19

The decision by the Australian Red Cross to commence testing of all blood donations for HTLV-1 was contentious. Red Cross had shown that HTLV-I was present in the Australian blood supply,9 and believed that testing should be undertaken to ensure the safety of the blood supply as well as its own credibility.26 Our findings have shown that in the three years since screening began 16 Australian blood donors were found with HTLV-I. Without screening, the risk of viral transmission by blood transfusion would have been 1 in 100 000. On the other hand, the NHMRC and some State governments believed that universal screening was not justified on public health grounds. The findings in this study show that the risk of a blood transfusion recipient developing HTLV-I-related disease as a result of transfusion is about 1 in 10 million; these data were not available when Red Cross made their decision for universal screening.

From the perspective of Red Cross and transfusion recipients, screening affords the certain benefit27 of the removal of the threat of HTLV-I infection from transfusion whatever the future risk of developing leukaemia. From a public health perspective, the certain benefit is the prevention of the very low risk of leukaemia or spastic paraparesis.

Stakeholders (Australian Red Cross Blood Service, State and Federal governments and the community) would be assisted by public discussion of an acceptable level of risk and appropriate level of screening for rare transfusion-transmitted diseases; HTLV-I provides a suitable test case. It may be appropriate to screen only new donors for HTLV-I (at a lower cost) now that the donor base has been repeatedly screened. However, it is likely that Red Cross would need a form of statutory defence, such as that provided in Victoria for HIV and hepatitis C virus,28 if it were to apply less-than-universal screening for HTLV-I and other conditions of low risk to public health.  

Acknowledgement

 I thank the Directors of each State Blood Transfusion Service for providing the figures for HTLV-I and for constructive and critical comment.  

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(Received 5 Aug 1996, accepted 18 Feb 1997)

 

Authors' details

Australian Red Cross, Blood Bank of Victoria, Southbank, VIC.
Gordon S Whyte, FRACP, FRCPA, Director.
Reprints will not be available. Correspondence: Dr G S Whyte, PO Box 354, Southbank, VIC 3205.
E-mail: rcbb AT peg.apc.org

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