Risks and side effects of therapy with plasma and plasma fractions.

Transfusion of plasma can lead to adverse reactions or events. Immune-mediated reactions are most common--these include allergic and anaphylactic reactions, transfusion-related acute lung injury (TRALI) and haemolysis. They can range in severity from mild to fatal. Fluid overload and citrate toxicity can occur after rapid or massive transfusion. In developed countries, microbial transmission rates are low because of donor selection and testing. Pathogen reduction processes can be applied to either single-unit components (methylene blue) or plasma pools (solvent-detergent). They have the unwanted effect of reducing some coagulation factors but reduce viral transmission risk even further. Reactions associated with plasma products or fractions also include allergic reactions, although TRALI is rare. Viral transmission risk is very low because of the use of two independent viral inactivation steps. Different products have particular specific unwanted effects: intravenous immunoglobulin has been associated with thrombotic events, renal toxicity and aseptic meningitis; coagulation factors are associated with development of inhibitors and thrombotic events. The risk of transmission of variant Creutzfeldt-Jakob disease in both plasma components and pooled plasma products is as yet unknown. If anything, the low titre of prion infectivity in the blood of an infected individual (approximately 10 infectious units/ml) will be massively diluted by the thousands of units of plasma in the pool. Subsequent manufacturing processes also remove prions from the final product.

The rationale for pathogen-inactivation treatment of blood components.

Blood transfusion provides an ideal portal of entry for microorganisms. Although current residual risks of microbial infection by transfusion are extremely low in the developed world, the requirements for even safer blood are paradoxically increasing. Such requirements are partly a legacy of the tragic transmissions of human immunodeficiency virus (HIV) by blood early in the acquired immunodeficiency syndrome pandemic and are legally expressed in consumer protection laws imposing strict product liability. Enhanced safety is called for, not only for recognized agents (especially bacteria, which cause most current transfusion-transmissible infections [TTIs]and have only recently been addressed) but also for potential future "emerging" TTIs. These possibilities are not merely theoretical. TTIs of HIV-1, HIV-2, hepatitis B virus vaccine escape mutants, human herpesvirus 8, West Nile fever virus, and variant Creutzfeld-Jakob disease amply demonstrate the continual emergence of such threats. For recognized agents, the possibilities of test errors, misreporting, process-control failures, and false-negative results (although rare with modern automation) remain. In principle, an all-embracing, pan-effective microbe-inactivation procedure offers a potential solution to blood safety concerns. Such procedures may also allow the removal of several existing antimicrobial interventions. However, blood services remain to be convinced that the various prerequisites for safe and effective pathogen inactivation have been met. Not the least of these prerequisites is that all blood components can be inactivated to provide a single streamlined alternative blood safety strategy. Furthermore, the huge potential value of effective pathogen-inactivation systems for developing countries should not be forgotten once such systems are perfected.

Evidence for a dynamic host-parasite relationship in e-negative hepatitis B carriers.

Anti-hepatitis Be (HBe) carriers are perceived as having low infectivity, with hepatitis B virus (HBV) DNA levels far below those seen in the HBeAg carrier. However, the temporal stability of HBV DNA in anti-HBe carriers remains poorly characterised. UK Department of Health guidelines use HBV DNA levels to define whether HBV-infected health care workers may perform exposure-prone procedures. Two samples separated by 1-23 years available from 147 carriers were analysed for precore variants and HBV DNA levels. Among 15 HBeAg carriers, HBV DNA was maintained at high levels. There was a 5 log(10) fold reduction in DNA in 11 individuals who developed anti-HBe during follow-up evaluation. Proportional changes in HBV DNA levels in anti-HBe carriers were similar to those in HBeAg carriers, although there was a trend for changes in viral DNA to be more marked in anti-HBe carriers followed up for longer periods. Closer sampling in 20 anti-HBe carriers demonstrated large fluctuations of DNA levels over short periods. Serum transaminases and precore mutant status at the outset failed to predict those in whom HBV DNA levels fluctuated. HBV DNA was below the detection threshold (<400 copies/ml) in 36 anti-HBe carriers at first sampling and remained so in all but 5 of these carriers. Twelve individuals who were previously viraemic lost detectable HBV DNA during follow-up evaluation. While HBV DNA levels are found to fluctuate in carriers, our results indicate that once below the threshold of detectability, levels are unlikely to rise. This is an important factor when assessing health care workers for exposure-prone procedures.

Evaluation of a transcription-mediated amplification-based HCV and HIV-1 RNA duplex assay for screening individual blood donations: a comparison with a minipool testing system.

BACKGROUND: NAT was introduced for HCV RNA in 1999 to screen blood donations and improve the safety of the blood supply. STUDY DESIGN AND METHODS: The performance of a NAT multiplex for HCV and HIV-1 RNA based on transcription-mediated amplification (TMA) was assessed with various sensitivity panels and by screening 50,000 serologically unscreened, first-time donor plasma samples. Results were compared with a routine NAT screening for HCV RNA by RT-PCR in pools of 96 plasma samples. RESULTS: The TMA multiplex 95 percent sensitivity ranged between 22 and 54 IU per mL for HIV-1 and 15 and 20 IU per mL for HCV RNA. The rate of test failure was 8.6 percent but decreased to 4.7 percent when results of two critical periods of equipment malfunction were excluded. Test failure was related to human error, minute control contamination, and insufficient mixing of reagents at the extraction stage. All 31 repeatedly reactive samples (0.06%) were seropositive for HCV (29) or HIV-1 (2) and contained RNA detectable by discriminatory TMA and confirmatory RT-PCR, indicating 100 percent specificity. A direct comparison of TMA in individual samples and RT-PCR in plasma pools was possible on 27 HCV RNA-containing samples. Twenty-six samples were detected in plasma pools; the lack of detection of 1 sample was due to an identification error at the pooling stage. CONCLUSION: The HCV and HIV-1 multiplex NAT had high specificity and sensitivity.