1 Introduction : Transfusion - Transmitted Infections , Then and Now

In 1983, a small textbook was published entitled Microbiology in Blood Transfusion (Barbara, 1983). At the beginning of this book the characteristics of microbial agents that might predispose them to the potential for transmission by transfusion were explored. Some of the characteristics identified included: Presence of the agent in one or more of the constituent components of blood Propensity for causing asymptomatic (sub-acute) infections Protracted incubation period to the development of symptoms A long-term carrier state of expressed microbial components (e.g. HBsAg in the case of hepatitis B virus) A long-term latency of the agent via incorporation of the microbial nucleic acid into the white cells of the infected host. The microbial nucleic acid could reactivate to initiate infection in the recipient of a transfusion from an infected donor. In any table of transfusion-transmissible infections (TTIs) summarizing the situation at that time, the predominant microbial agents featured would typically be persistent rather than acute. More recently, the risk (actual or potential) from acute infections, especially in situations of high incidence and attack rates in a population, has also become a significant issue. The epidemic of West Nile fever virus (WNV, see Chapters 6 and 15) is a very good example of this. A summary of the currently clinically significant TTIs is shown in Table 1. These agents will all be covered in detail throughout the ensuing chapters. Chapter 6 also considers the potential risks from ‘new’ or newly recognized agents. In the 1983 book, the newly recognized acquired immune deficiency syndrome featured in a small paragraph, with the observation that the associated level of risk to transfusion recipients remained to be determined. Subsequently, as the tragic outcome of transfusion-transmitted HIV infections gradually became all too clear, the scope of transfusion microbiology changed irrevocably. Risk analysis (see Chapter 26), quality aspects (see Chapter 17) and regulatory control (see Chapter 27) became increasingly prominent. The transfusion risks from WNV in North America and vCJD in the UK clearly demonstrate that the potential risks of transfusion infection demand careful and continuing monitoring and surveillance. As a result of the above, increasingly sophisticated analyses and assessments of potential microbial threats to the safety of transfused blood have been developed. The following is an approach used by the UK Standing Advisory Committee on Transfusion Transmitted Infection (SACTTI) to assess the risk of potentially transfusion-transmissible agents (see Table 2). It was developed by Dr Roger Eglin, together with Professor Peter Simmonds, based on an original analysis by Dr Brian McClelland. It is summarized with the permission of Dr P Hewitt, chair UK SACTTI. The analysis is considered in several sections. In many instances, several questions may not have clear answers, or estimates (for example the duration of viraemia following certain infections) may have to be used. Gathering of data and extensive review of the literature is a crucial requirement. Even then, the analysis is more qualitative than quantitative: but even if it only generates a comprehensive checklist of the available data relevant to transfusion risk for a given agent, the often difficult decisions for managing possible risk will at least be better informed. The development of risk analysis methodology (Chapter 26) together with improvements in standardization, enhanced quality measures (see Chapter 17) and increasing regulatory control (see Chapter 27) has led to the consistency of both current microbiology testing and assessment of new and emerging agents within a standardized framework. Evidence of the latter is seen in the Blood Services’ reaction to the transfusion risks presented by the emergence of WNV in North America and vCJD in the UK. In addition, the continuing requirement for careful and continuing monitoring and surveillance of the potential risks of infection by transfusion is clearly demonstrated. The information is collated in individual templates and then used to complete Table 3 ‘Characteristics of New/Emerging Infectious Agents’. This Appendix also includes estimates of risk and cost effectiveness. Key entries into Table 3 automatically transfer into Table 4, which comprises levels 0 to 4, with level 0 equating to ‘no action required for donors but continue surveillance’ to level 4 equating to ‘priority action required’, for example HIV. The level is determined by the extent to which the entry ‘yes’ extends towards the bottom of this table. This sort of analysis can be applied to any newly recognized potential risk to the blood supply. Risk levels and a detailed checklist of possible interventions will then be readily available as a basis for informed decision making by blood services. Typical recent examples of agents that are being monitored by blood services as potential TTIs are simian foamy virus (SFV) and Chikungunya fever virus (CHIKV). Because cases of SFV transmission from infected chimpanzees to humans in contact with them have been reported (see Khan and Kumar, 2006, for detailed references), blood transfusion experiments from infected to uninfected macaques have shown that SFV can be transmitted by transfusion of blood (see Khan and Kumar, 2006). With CHIKV, the concern is that because infections have reached epidemic levels in parts of India and islands in the Indian Ocean since 2005, and viraemia can be demonstrated in symptomatic cases, there may be a potential transfusion risk from pre-symptomatic