Prevalence of Transfusion-transmissible Infections, Not “Infection Pressure,” Should Dictate Suitability to Donate Blood

((See the Major Article by van Bilsen et al on pages 1001–8.).)

In controlling the risk of transfusion-transmitted infections (TTIs), blood services have long faced the challenge of balancing safety with adequacy of supply, through judicious use of screening tests and donor selection [1]. More recently, there has also been recognition that excluding certain populations from donation may constitute real or perceived discrimination, unless the policies are firmly grounded in sound scientific evidence. This issue has been most discussed in relation to men who report male sexual partners (henceforth referred to as “MSM”), who have been restricted from donating blood in most countries [2]. The restriction was based on the high rates of human immunodeficiency virus (HIV) in this population. It initially took the form of permanent bans but has been modified to deferrals based on the time since their most recent sexual contact, as screening tests for HIV have become increasingly sensitive with greatly reduced “window periods” during which infection could be present but undetected [3].

The issue of donor selection remains highly contested, with multiple reviews undertaken in recent years [4, 5] and little consensus among countries as to the ideal approach to take regarding deferral. One of the key issues has been whether nuanced behavioral risk assessments could be introduced to differentiate between members of the MSM population whose sexual practices do not place them at increased risk of TTIs as distinct from those who do present a higher risk to the blood system [2]. Behavioral criteria that do not differentiate between MSM sex partners and others have been adopted in some countries [6, 7], but this approach has been rejected by most countries due to the higher prevalence of TTIs in MSM populations generally [8].

The study reported by van Bilsen et al in this issue of Clinical Infectious Diseases presents a new approach, based on the joint analysis of data on behavior and infectious diseases. The study provides support for the potential suitability of some MSM to donate blood without deferrals based on last sex, but it also raises further questions [9].

The study found that MSM who self-reported “low risk” sexual practices and met Dutch donor selection criteria other than the MSM exclusion did not have TTIs (called “class A” infections in the article), apart from core antibody to hepatitis B (anti-HBc) in a few. While anti-HBc was more common in the qualified low-risk MSM than in matched repeat donors, two-thirds had anti-HBs titers at levels that made them acceptable blood donors according to current Dutch guidelines. Similarly, age-matched male repeat blood donors did not acquire any TTIs [9].

In contrast, TTIs did occur in MSM who reported medium- to high-risk sexual practices, whether or not they otherwise met Dutch donor selection criteria. Further, TTIs also occurred in MSM who reported current low-risk practices but did not meet Dutch donor selection criteria. These data demonstrate that without the MSM deferral, the Dutch donor selection criteria alone would not be sufficient to safeguard the blood supply. They also imply that the criteria could be sufficient to protect the blood supply if applied to MSM with additional specific sexual risk criteria—defined as either (i) no anal intercourse, (ii) a monogamous relationship with 1 male partner (including condomless sex with that partner), or (iii) consistent condom use during anal intercourse with casual partners. This conclusion must be drawn cautiously because the authors noted that the sample size was insufficient for accurate comparisons between groups regarding low-prevalence class A infections. Of note, new male blood donors had a higher prevalence of TTIs than both age-matched repeat male donors and qualified low-risk MSM, with high-risk and/or unqualified MSM having higher prevalence [9].

In addition to comparing rates of TTIs, van Bilsen et al also screened both MSM and the age-matched male repeat blood donors for antibodies against a range of infections for which blood donors are not routinely screened—cytomegalovirus, herpes simplex virus types 1 and 2, human herpesvirus type 8, hepatitis E virus, and parvovirus B19. These infections, referred to by the authors as “class B infections,” were proposed as additional biological markers of risk and, in combination with the class A (transfusion-transmissible) infection, used to create a measure they called “infection pressure.” The median infection pressure was then compared between the male repeat blood donors, low-risk MSM (stratified by those otherwise “qualified” according the Dutch blood donor criterion apart from the MSM exception and those not), and high-risk MSM (again stratified as “qualified” or not [9]).

When analyzed by this measure of infection pressure, male repeat blood donors had the lowest score while all the groups of MSM had significantly higher levels of infection pressure, with the unqualified, high-risk MSM having the highest score. The key point was that the low-risk, otherwise qualified MSM had higher infection pressure scores than the male repeat donors. New male blood donors were not included in this analysis, so it is not possible to assess how MSM might compare with this group regarding infection pressure [9].

The inclusion of the class B infections within the formula for infection pressure is not because of the risk the infections themselves pose to the Dutch blood supply, and which are largely mitigated by the procedures such as universal leukoreduction that are in place in the Netherlands. Rather, they are included as markers of sexual risk behavior, and therefore surrogates for exposure to sexually transmissible agents that might pose a risk to the blood supply. The premise of the infection pressure analysis appears to be that if a population has serological evidence of a higher rate of exposure to these common infections, it might also be at higher risk of other serious infectious agents, thus far unknown, that could emerge in the future.

It is reasonable to take a conservative approach to risk to protect the blood supply from known risks, but the concept of infection pressure—conflating the prevalence of known TTIs together with a group of other infections that are transmitted by close personal contact—is problematic. It implies that sexual practices other than those which transmit blood-borne viruses pose an inherent risk for the transmission of some putative new infectious agent.

Many serious new infectious diseases have emerged in the last 50 years: Ebola, prion diseases, HIV, hepatitis C virus, severe acute respiratory syndrome, Middle East respiratory syndrome, and Zika, to name but a few. These diseases have a wide range of transmission routes—some shared, some very different. New pathogens and their preferred transmission pathways are unpredictable, and new infectious disease outbreaks can occur in a variety of different circumstances and require different forms of containment and control.

The finding that qualified, low-risk MSM in this sample had similar prevalence of TTIs to age-matched repeat male donors, and lower rates than new male donors, sends a positive signal for the potential for some MSM to donate blood safely. Furthermore, the fact that where MSM were “unqualified” or “high risk” aligned with increased prevalence suggests that the behavioral risk criteria against which the men self-reported were well defined and that the Dutch donor criteria are appropriate.

Van Bilsen et al’s study provides evidence that some MSM are indeed at low risk for TTIs, and should these findings be borne out in a larger study, that they could be suitable blood donors with appropriate screening in place. The infection pressure analysis should not detract from this important message.

Notes

Financial support. J. M. K. and B. G. H. report grants from the National Health and Medical Research Council, including a partnership grant with the Australian Red Cross Service. J. M. K. is a member of an expert reference group on blood safety.

Potential conflicts of interest. Both authors: No reported conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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