Acquired immune deficiency syndrome and blood transfusion

Journal of Hospital infection (1985) 6 (Supplement C), 27-34

Acquired i m m u n e deficiency s y n d r o m e and blood transfusion M a r c e l a Contreras a n d J o h n Barbara North London Blood Transfusion Centre, Deansbrook Road, Edgware, Middlesex Introduction T h e awareness that some sexually transmissible diseases can also be transmitted by blood transfusion is not new to the T r a n s f u s i o n Service. Over the years, we have gained considerable experience in dealing with the problems caused by the hepatitis B virus and, to a lesser extent, syphilis and cytomegalovirus; therefore, the alarmist publicity from the lay press has come as no surprise. T h e Transfusion Service has attempted to minimize the risk of transfusion-transmitted infection long before acquired i m m u n e deficiency s y n d r o m e ( A I D S ) came on the scene. All blood donations are screened routinely for H B s A g and syphilis by sensitive techniques. At the N o r t h L o n d o n Blood T r a n s f u s i o n Centre, collecting an average of 185,000 units of blood per year, until recently we used to find one HBsAg positive in 500 of our first-time donors and 1 per 40,000 of our established donors (Barbara et al., 1979). All donors found to be H B s A g and/or T P H A positive are exhaustively followed-up and counselled. We are, therefore, used to dealing with the problems associated with transfusion-transmitted infection. T h e likely infectious aetiology of A I D S was supported by the reports of transfusion-transmitted A I D S . T h e detailed study of C u r r a n et al. (1984) showed that only one 'at risk' donation of blood or components is necessary for A I D S transmission. At that time the overall risk of this transmission was of the order of 1 per 1,000,000 transfusions in the USA, although the incidence varies dramatically in different states. Not all the recipients of products from donors who have been implicated in a case of transmission of A I D S go on to develop A I D S ; m a n y have not even seroconverted, and of those who have, a high proportion has not developed chronic symptoms. It has been reported that some recipients of infected blood who have been followed-up carefully develop an acute glandular fever-like illness 2-4 weeks after transfusion. Recipients of certain unheated blood products made from pooled plasma (such as untreated Factor V I I I and Factor IX) and multi-transfused patients are at higher risk. Continuing analysis of transfusion-associated A I D S in the U S A (Feorino et al., 1985) has O195-6701/85/06C027 + 08 $03.00/0

9 1985 The Hospital Infection Society

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M. Contreras a n d J. Barbara

confirmed that in such cases a high-risk donor can usually be identified. T h e implicated donors are mainly male homosexuals and often a n t i - H T L V I I I positive. T h i s lends further support to the value of p r o g r a m m e s aimed at encouraging self-deferral of donors in the specified high-risk groups (especially male homosexuals). I m m u n o g l o b u l i n s and albumin preparations have not been implicated in the transmission of A I D S . W h e n a batch of blood product made from pooled plasma is implicated in A I D S transmission, all other recipients of material from the same batch should be rigorously followed-up. T h e same applies to blood or blood products obtained from donors who subsequently develop A I D S or progressive generalized lymphadenopathy. Acquired i m m u n e deficiency s y n d r o m e has had a p r o f o u n d impact on transfusion services. Apart from the obvious risk of infecting recipients, the problems it has caused include the following. 1. Loss of donors due to exclusion of subjects in high risk groups, especially male homosexuals. It is unfortunate that some donors have misinterpreted the A I D S publicity and have refrained from donating due to fear of contracting it by giving blood! 2. U p to 1983-84 an important source of a n t i - H B s and a n t i - C M V i m m u n e plasma was plasma obtained by apheresis from the male homosexual population. T h e s e donors have had to be replaced from alternative sources at considerable extra expense. 3. M o s t blood banks and transfusion centres have been approached to provide 'directed' donations. We have had to educate colleagues and the public with respect to the disadvantages of this procedure. Apart from the technical, logistical and economical drawbacks of supplying blood from specific donors for designated recipients, the practice is a dangerous one as potential donors approached directly by friends or relatives might find it difficult to admit to being in 'high-risk' groups. On the other hand, it grieves us to admit that the A I D S publicity has not been all to the detriment of the Transfusion Service; never before have funding and regulating bodies shown such interest in transfusion as a whole and in its associated hazards. F u r t h e r m o r e , this publicity has enabled us to m o u n t an intensive self-deferral campaign aimed at those groups of donors likely to transmit a range of infectious disease by blood transfusion. T h e higher the incidence of A I D S in a specific population, the greater the p r o b l e m of blood transfusion-transmitted A I D S . Consequently, the magnitude of this p r o b l e m in certain cities in the U S A , like San Francisco and N e w York, is considerable. T h e figures for transfusion-related A I D S cases in the U S A overall, as of F e b r u a r y 1985, are shown in T a b l e I. Numerically, the p r o b l e m in the U K is m u c h smaller. U p to April 1985, of 159 cases of A I D S , five were haemophiliacs (three have died) and no

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T a b l e I. Acquired immune deficiency syndrome and blood transfusion in the U S A as of February

1985 Adults

Children

Total

Haemophiliacs B l o o d or c o m p o n e n t s

61

5

66

100

15

115

T o t a l A I D S cases: > 8 0 0 0

161

20

181"

* 2% of total.

cases of A I D S have occurred in recipients of blood or fresh blood components collected in this country. T w o cases of A I D S have been reported in British hospitals following transfusion of blood received in foreign countries. W h a t a p p r o a c h e s c a n the T r a n s f u s i o n S e r v i c e t a k e to m i n i m i z e the risk o f t r a n s m i s s i o n o f HTLV-III by b l o o d transfusion?

Donor education and verbal screening If a defined section of the population is at risk of transmitting A I D S , the most obvious preventative measure is to encourage their self-deferral from blood donation. Similar measures would have proved fruitful in reducing hepatitis B transmission by transfusion, but the social climate and publicity were not favourable at the time. General public concern over A I D S has allowed, and even encouraged, us to be more explicit in our verbal screening and education of prospective blood donors. Up to now, this has been the mainstay of our approach at the N o r t h L o n d o n Blood T r a n s f u s i o n Centre. In the a u t u m n of 1983, the D H S S produced an informational leaflet on A I D S for distribution to all blood donors. T h i s leaflet implied that in the homosexual c o m m u n i t y it was only those with multiple partners who were likely to transmit A I D S . Subsequently, a revised leaflet was produced early in 1985 expanding the high risk groups to include, among others, all male homosexuals and bisexuals. Although a good proportion of the male homosexual population seemed to have excluded themselves from donating their blood after reading the leaflets, we suspected that there were still a n u m b e r of male homosexuals who were continuing to donate. This suspicion was p r o m p t e d by the persistence of detection of acute hepatitis B infections in our young male donors (Contreras et al., 1985). After contacting these subjects, we realized that they did not consider themselves to be in a high-risk group in the context of their interpretation of the first D H S S leaflet. F u r t h e r m o r e , our c o m m u n i c a t i o n with homosexual associations like the Terrence Higgins T r u s t made us realize that a proportion of male homosexuals would not admit openly to their homosexuality, either because

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they were bisexual or for fear of discrimination. We, therefore, provided a 'let out' p a m p h l e t informing prospective donors of the whole range of conditions which would preclude t h e m from donating. T h e conditions were purposely not centred around A I D S , to allow self-deferral w i t h o u t donor embarrassment. Despite all the above measures, we realized that some undisclosed male homosexual donors m i g h t still fear the risk of revealing their homosexuality if they withdrew from the donor panel (bisexual men attending with their wives and homosexual m e n regularly attending with their workmates). Inspired by our colleagues at the New York Blood Center, we designed a questionnaire to be completed confidentially by donors attending our static clinics. Donors were asked if they had read the D H S S A I D S leaflet and to request that their blood be used 'for research purposes only', if they considered themselves to be in a high-risk group. T h e main object of this questionnaire was to protect our blood recipient population by eliminating the residual high-risk donors. Obviously, blood donations from high-risk donors are discarded. In addition, we were also aiming to assess the impact of the D H S S leaflet, to estimate w h e t h e r gay donors were continuing to attend and, if so, in what numbers. T h e questionnaire was introduced experimentally in July 1984 at our donor clinic in the West E n d of L o n d o n ; the preliminary results (Contreras et al., 1985) are shown in Table II. Table II. Results of questionnaire administered to blood donors in central London Blood donor category

Total no.

No. (%) at high risk of AID S

Male established first time total

2105 228 2333

35 (1 '7) 3 (1.3) 38 (1-6)

Female Grand total

2053 4386

0 (0) 38 (0-9)

T h e results of serological tests on male donors who have admitted homosexuality at private interview (following up their response to the questionnaire) are shown in Table I II (serology, courtesy of the Department of Virology of the joint Middlesex Hospital and University College Medical Schools). By comparison, in a previous study ( T e d d e r et al., 1980) we f o u n d that 50% of homosexual men attending special clinics and 2-3% of blood donors in N o r t h L o n d o n were a n t i - H B c positive. We have extended the distribution of the questionnaire to our other static clinic in Edgware and we have also introduced it at our mobile donor clinics. It came as no surprise that the incidence of high-risk donors in the Edgware clinic was significantly lower than the 1"6% incidence which we found

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Table III. Serological results for donors attending the West End donor clinic who admitted being homosexual

July 1984 study Total tested to date

No. high-risk donors

No. (%) anti-HBc positive

No. anti-HTLVIII positive

38 46

7 (18.4) 10 (21"7)

0 0

initially at our West End clinic. Of 2000 male donors at Edgware who have completed the questionnaire to date, two (0-1%) have indicated being in a 'high-risk' group but so far, despite great efforts, we have been unable to contact t h e m to confirm that they have completed the questionnaire correctly. On follow-up, no female donors completing the questionnaire have proved to be in a high-risk group. T h e reduced incidence of high-risk donors attending the Edgware clinic also reflects the continuing vigorous A I D S publicity. As well as deferral of high-risk donors, the first generation of laboratory screening tests has been developed. However, we firmly believe that even if the tests prove reliable, we m u s t continue encouraging self-deferral of those donors likely to transmit A I D S by blood transfusion. We shall, therefore, continue to administer our questionnaire regardless of the introduction of testing. Non-specific tests

Before the isolation of H T L V I I I (or ARV) considerable interest centred around non-specific tests to identify donors likely to be infected with this agent. T h e high prevalence (89%) of anti-HBc positivity in homosexual m e n in San Francisco p r o m p t e d the Irwin Memorial Blood Bank to test all their donors for this marker. Even after the introduction of specific tests, they are continuing to test for anti-HBc as a further safety measure. A n o t h e r marker for 'high-risk' is the evidence of past syphilis infection. It is m a n d a t o r y that blood centres test for syphilis infection and at our centre, we have been using a sensitive Treponema p a l l i d u m haemagglutination assay which has proved useful in the detection of donors in high-risk groups. T h i s screening test is particularly appropriate in the context of the Blood Transfusion Service, as most new cases of syphilis in the U K now occur in y o u n g males. T h e value of these non-specific tests will depend on the prevalence of the markers in a given population. Specific tests

Since the beginning of 1985, specific tests for a n t i - H T L V I I I have become commercially available. Unfortunately, we are still far from the ideal test, which would be one that detects the agent itself as in the case of HBsAg for the hepatitis B virus. In the case of A I D S , we can only screen for evidence

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of past infection. T h e magnitude of the problem of false negatives for antiH T L V I I I is u n k n o w n ; there have been reports of virus isolation from lymphocytes of some a n t i - H T L V I I I negative subjects (Salahuddin et al., 1984). Before we consider introducing mass-screening in the donor population, several problems need to be solved. (a) T h e screening tests available need to be fully evaluated. (b) Provision for adequate follow-up of donors found to be a n t i - H T L V I I I positive must be available before the introduction of mass-screening-especially in the early stages definition of positives and confirmation by reference laboratories is essential. T h e follow-up includes counselling. We feel that counselling of confirmed positives will be an enormous task which will need financial support, organization and provision of fullytrained staff. We are already aware that a high proportion of general practitioners do not have the time or the facilities to undertake this task which involves follow-up not only of the index case, but also of all his or her sexual contacts. (c) Before a n t i - H T L V I I I screening is introduced in the Blood Transfusion Service, the tests should be widely available at alternative sites such as special clinics and public health laboratories to minimize the known risk of transfusion centres being used as a diagnostic facility (Miller & Simon, 1985; Perkins, Miceli & Janda, 1985). Even then we fear that some subjects in high-risk groups will come to donate their blood merely to check their a n t i - H T L V - I I I status. We, therefore, feel that it is imperative to continue encouraging self-deferral by means of education and questionnaires. Using a test in a diagnostic context is very different from using it for mass-screening. In the latter situation, several extra constraints apply: as well as being sensitive the test must be very specific. T o be feasible for the Transfusion Service, the test must also be rapid (for same day release of platelets), simple (staff on rotation m u s t be able to cope with it) and, naturally, it must be economical. It is envisaged that over 2,000,000 screening tests will be needed annually in the National Blood Transfusion Service. T h e repercussions for a person wrongly classified as a n t i - H T L V - I I I positive are staggering. Before a donor is informed, there m u s t be stringent validation and confirmation (the donor unit must be sampled and checked) and if proved positive, confirmatory samples should be obtained. T h e value of the screen test will lie in the protection of recipients by elimination of a n y suspect unit; this may mean discarding some units which later prove to have been falsely positive for the H T L V I I I antibody. In contrast, the confirmatory tests m u s t aim at providing an a c c u r a t e indication of the donor's antiH T L V I I I status so that only those who are u n a m b i g u o u s l y positive need be informed of the results. As with all transfusion-transmitted agents, the risk of infectivity is

A I D S a n d b l o o d transfusion

33

amplified b y p o o l i n g large n u m b e r s o f b l o o d d o n a t i o n s . Since H T L V I I I is p r e s e n t in plasma, as well as in cellular e l e m e n t s , p r o d u c t s like F a c t o r V I I I a n d F a c t o r I X have b e e n i m p l i c a t e d on n u m e r o u s o c c a s i o n s in the t r a n s m i s s i o n of A I D S . F o r t u n a t e l y , unlike hepatitis B virus, the A I D S a g e n t is i n a c t i v a t e d b y relatively m i l d heat t r e a t m e n t . H e a t t r e a t e d F a c t o r V I I I is n o w available f r o m c o m m e r c i a l c o m p a n i e s a n d f r o m the B l o o d P r o d u c t s L a b o r a t o r y . T h e o u t c o m e o f the use of s u c h m a t e r i a l s is b e i n g closely monitored. A t the N o r t h L o n d o n B l o o d T r a n s f u s i o n C e n t r e , o n e o b v i o u s c o n s e q u e n c e of e d u c a t i n g the d o n o r p o p u l a t i o n as to the h i g h - r i s k g r o u p s for A I D S has b e e n a d e c r e a s e in the n u m b e r o f d o n o r s f o u n d to be H B s A g positive ( i n c l u d i n g t h o s e u n d e r g o i n g acute H B V infection) as s h o w n in T a b l e IV. Table IV. H B V markers in donors after publicity about acquired immune deficiency syndrome

HBsAg positive Acute HBV infection

Expected number (from previous experience) for a half year

Observed number for first half of 1985

25 4*

13 1 (female)

*Usually, young male homosexuals. T h e B l o o d T r a n s f u s i o n Service is n o w at the stage of e v a l u a t i n g t h e available s c r e e n i n g tests f o l l o w i n g p r e l i m i n a r y a s s e s s m e n t b y the P u b l i c H e a l t h L a b o r a t o r i e s in C o l i n d a l e . It r e m a i n s to be seen w h e t h e r the p a t t e r n o f t r a n s f u s i o n - t r a n s m i t t e d A I D S seen in the U S A will follow the s a m e c o u r s e (allowing for the lag in the s p r e a d of the disease in E u r o p e c o m p a r e d w i t h the U S A ) in this c o u n t r y or w h e t h e r the p u b l i c i t y a b o u t A I D S a n d p r e v e n t a t i v e m e a s u r e s to date will m o d i f y the c o u r s e o f events. References

Barbara, J. A. J., Harrison, P. J., Howell, D. R., Cleghorn, T. E., Dane, D. S, Briggs, M. & Cameron, C. H. (1979). A sensitive single reverse passive haemagglutination test for detecting both HBsAg and anti-HBs. Journal of Clinical Pathology 32, 1180-1183. Contreras, M., Hewitt, P. E., Barbara, J. A. J. & Mochnaty, P. Z. (1985). Blood donors at high risk of transmitting the acquired immune deficiency syndrome. British Medical Journal 290, 749-750. Curran, J. W., Lawrence, D. N., Jaffe, H. et al. (1984). Acquired immunodeficiency syndrome (AIDS) associated with transfusions. New England Journal of Medicine 310, 69-75. Feorino, P. M., Jaffe, H. W., Palmer, E. et al. (1985). Transfusion-associated acquired immunodeficiency syndrome: evidence for persistent infection in blood donors. New England Journal of Medicine 312, 1293-1320. Miller, V. & Simon, E. R. (1985). AIDS Ethics, and the Blood Supply. A report of a conference of the American Blood Commission and the Hastings Centre, Institute of Society, Ethics and the Life Sciences, January 29 and 30, 1985 Transfusion 25, 174-175.

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Perkins, J. T., Miceli, C. & Janda, W. M. (1985). Does antibody screening of donors increase the risk of transfusion-associated AIDS? New England Journal of Medicine 313, 115-116. Salahuddin, S. Z., Groopman, J. E., Markham, P. D. et al. (1984). H T L V - I I I in symptomfree seronegative persons. Lancet i, 1418-14.20. Tedder, R. S., Cameron, C. H., Wilson-Croome, R., Howell, D. R., Colgrove, A. & Barbara, J. A. J. (1980). Contrasting patterns and frequency of antibodies to the surface, core and e antigens of hepatitis B virus in blood donors and in homosexual patients. Journal of Medical Virology 6, 323-332.