Prevention of infections transmissible by blood derivatives

Agents that are transmissible by blood or its derivatives typically have long incubation periods, may often be asymptomatic for several years and can set up carrier or latent persistent infections. Examples are hepatitis B virus (HBV), hepatitis C virus (HCV), the human immunodeficiency viruses (HIV 1 and 2) and cytomegalovirus. The prevention of transfusion-transmitted infection (TTI) is based on the exclusion of potential blood donors who are not fit and well, the education of donors to exclude themselves if they are at risk of contracting TTIs, the laboratory screening of all blood donations for evidence of infection with a range of potential TTIs, physical removal of white cells in those cases where the agent is cell associated, viral inactivation procedures for pooled plasma derivatives, detection of viral genomes in plasma pools and the avoidance of unnecessary transfusions.     

Risks of blood transfusion and their prevention

As a result of significant progress in reducing the risks of transfusion-transmitted viral infections, bacterial contamination of platelet components (1:2,000) and sepsis (1:50,000) are now the most frequent infectious complications of blood transfusions. Sepsis from bacterial contamination of red cell components is less frequent (1:500,000), because red blood cells, unlike platelet components, can be stored at refrigerated temperatures (1 degrees C-4 degrees C). Current risks for transfusion-transmitted viral diseases (per blood component transfused) are: human immunodeficiency virus, 1:2,135,000; hepatitis C virus, 1:1,935,000; hepatitis B virus, 1:205,000; and human T-lymphotropic viruses, 1:2,993,000. Transfusion-transmitted babesiosis has increased morbidity and mortality for splenectomized patients. Immunocompromised recipients are at increased risk of developing Chagas disease from blood contaminated by Trypanosoma cruzi. Reports of transfusion-related acute lunge injury and transfusion-associated graft-versus-host disease increase each year as physicians become increasingly aware of their varied clinical presentations. While strategies for preventing infections complications focus primarily on blood donor services, individual physicians can reduce risks to their patients by maintaining conservative "triggers" for transfusions, prescribing pharmacologic agents to reduce bleeding (antifibrinolytic drugs, serine protease inhibitors, fibrin sealants), and using epoetin alpha to reduce transfusion of red cells in selected patients.     

Exposure to blood or body fluids: management for health care

Health care workers are at risk of exposure to blood and body fluids from their patients through needlestick injuries or contamination of mucous membranes - a slash of blood in the eye, for example. Exposure to blood /body fluids is now the second biggest cause of occupational injury among NHS workers (UNISON, 2003). The first example of a case of occupational exposure of a health care worker to human immunodeficiency virus (HIV) and subsequent seroconversion following a needlestick injury was reported in the 1980s. This incident raised awareness of the risk that health care workers face when they are exposed to blood-borne viruses, in particular hepatitis B, hepatitis C and HIV.     

Nucleic acid testing for emerging viral infections

The development of new technologies leads to the discovery of new viruses. For each of these new infectious agents, relevance to transfusion, including transmissibility by transfusion, pathogenicity, prevalence in blood donors, persistence and the availability of screening assays needs to be assessed. Since 1995, one virus and a new family of viruses have been identified. GB virus-C/hepatitis G virus (GBV-C/HGV), a flavi virus with some homology with and epidemiological features of HCV, is not related to post-transfusion hepatitis but seems to positively interfere with human immunodeficiency virus replication. Human circoviruses include TT virus (TTV) and SEN-V. Both are highly variable, constituting a large family of distantly related viruses. They appear ubiquitous, infecting humans very early in life and are largely persistent. No clinical symptoms or pathogenicity is associated with TTV, but SEN-V might be associated with some non-A-E post-transfusion hepatitis. Parvovirus B19 has been known for many years, but its transmission to recipients of plasma derivatives despite viral inactivation raised the issue of screening plasma pools by nucleic acid testing. Most fractionators quantify B19 DNA in plasma pools to ensure a viral load of <10(4) IU mL-1.     

Viral hepatitis markers in Soviet and American blood donors

A cooperative study was undertaken to compare the frequency of hepatitis viral antigens and antibodies among blood donors in the Soviet Union and the United States. Age- and sex-stratified blood donors were identified and their sera tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), and antibody to the hepatitis A virus (anti-HAV). A total of 994 Soviet blood donor sera from five different regions and 1,178 American donor sera from six different regions were tested in the USA. Among the Soviet donors, 450 (45%) had some marker of exposure to the hepatitis B virus; while among the American donors, 94 (8%) did. Of the Soviet donors 848 (85%) were positive for anti-HAV, compared with 403 (34%) of the American donors. For 1,977 serum samples that were evaluated in both countries for HBsAg, techniques in the USSR identified 36 HBsAg-positive samples, while the technique in the USA found 38 HBsAg-positive samples; however, only 24 were judged to be HBsAg-positive by assays in both countries. Testing of these same 1,977 sera for anti-HBs revealed that the radioimmunoassay used in the USA identified many more antibody-positive donors than the immuno-autoradiography technique used in the Soviet Union. When a portion of the sera were tested by similar radioimmunoassay techniques in each country, there was comparability of results for anti-HBs, as well as for anti-HAV, and anti-HBc. The results permit calculation of age and sex prevalence of hepatitis B and hepatitis A serologic markers for blood donors within and between each country. They also allow comparison, on the same sera, of test methodologies in use in the Soviet Union and in the United States.     

闽南地区无偿献血者隐匿性乙型肝炎病毒感染研究

目的研究闽南地区无偿献血者中隐匿性乙型肝炎病毒感染(OBI)情况,探讨现有输血传播乙肝病毒(HBV)的检测方法的有效性。方法依据多种与HBV相关血清学指标的检测情况对献血者标本进行HBV携带风险评价分级,对较高携带风险的标本做单份多区段巢式-PCR检测其HBV DNA,对低携带风险的标本做10份混合的巢式-PCR检测。采用这一方案,对闽南地区19 360例HBsAg阴性的无偿献血者标本做检测分析。结果闽南地区HBsAg阴性献血者中的HBV DNA阳性检出率为0.21%(40/19 360,95%CI:0.15%—0.28%),属于OBI;其中抗-HBc阳性检出率85%(34/40),但阳性预测值仅为3.4%(34/995,95%CI:2.4%—4.7%);HBV NRAg阳性预测值30%(6/20),但灵敏度为15%(6/40)。结论现有筛查体系下无偿献血者中仍存在一定比例的OBI,需要寻求更为有效的检测方法。     

Viral safety of solvent/detergent-treated plasma

BACKGROUND: Pooling of plasma donations increases the risk for blood-borne infections. In solvent/detergent (SD)-treated plasma, lipid-enveloped viruses are efficiently inactivated. This method, however, does not affect non-lipid-enveloped viruses. The current study investigated the viral safety of SD-treated plasma (Octaplas) and paid particular attention to the transmission of non-lipid-enveloped viruses. STUDY DESIGN AND METHODS: The study comprised 343 adults undergoing cardiac surgery. Follow-up was performed 6 to 12 months and 2 years after operation. The sera were tested for hepatitis B surface antigen and specific antibodies against hepatitis A, B, and C; cyto-megalovirus; HIV, human T-lymphotropic virus types I and II; and human parvovirus B19 (B19). A total of 25 batches of SD-treated plasma prepared from Norwegian plasma were used. All batches were tested for hepatitis A virus and B19 by nucleic acid amplification testing and investigated for neutralizing antibodies directed against these viruses. RESULTS: In patients who received SD-treated plasma, B19 seroconversion occurred at a rate similar to that in nontransfused patients. No other seroconversions could be ascribed to the transfusion of SD-treated plasma. All 25 SD-treated plasma batches contained neutralizing antibodies against hepatitis A virus and B19. In nucleic amplification testing, all SD-treated plasma batches tested positive for B19, while five demonstrated borderline reactions for hepatitis A virus. CONCLUSION: Transfusion of SD-treated plasma was found to be safe with regard to lipid-enveloped viruses. Immune antibodies neutralize viral particles in plasma and are of importance in avoiding clinical disease with the non-lipid-enveloped hepatitis A virus and B19.     

Effects of multiple virus coinfections on disease progression in HIV-positive patients

OBJECTIVE: Since virus infections in AIDS patients are mostly inevitable and as they frequently cause disease deterioration and therapeutic failures, a comprehensive investigation was made of the influence of the coinfections of 9 well-known viruses on disease progression in patients infected with human immunodeficiency virus type 1 (HIV). METHODS: A cross-sectional study of 62 HIV-positive patients was conducted to correlate the prevalence rates for the 9 viruses with the alanine aminotransferase (ALT) levels and CD4 cell counts of the patients. RESULTS: The rates of HIV-positive patients infected with the 9 viruses are significantly higher than those of the control groups. Furthermore, almost one third of the patients in the studied group was coinfected with transfusion-transmitted virus (TTV) and manifested significantly higher ALT levels (p = 0.020), and these were raised further if coinfection with TTV and human hepatitis C virus had occurred (p = 0.010). By analyzing CD4 cell counts, the only significant effect on AIDS progression which could be detected was coinfection with human herpesvirus 8. CONCLUSION: This result confirmed that immune-suppressed persons are more vulnerable to common virus infections. Unlike hepatitis B or C virus, TTV seems to accelerate the progression of chronic hepatitis in HIV-infected patients.     

Predonation screening of blood donors with rapid tests: implementation and efficacy of a novel approach to blood safety in resource-poor settings

BACKGROUND: In sub-Saharan Africa, the percentage of screened blood is limited to approximately 75 percent for human immunodeficiency virus antibodies (anti-HIV), 50 percent for hepatitis B surface antigen, and 19 percent for hepatitis C virus antibodies (anti-HCV), mainly because of costs. STUDY DESIGN AND METHODS: In 2002 to 2003, candidate blood donors were screened before donation for HIV, HCV, and hepatitis B virus (HBV) serologic markers with rapid tests. The efficacy of this screening was assessed by nucleic acid testing (NAT) applied to pools of 10 plasma samples from donated units with a virus specific triplex assay. NAT-reactive pools were resolved by viral genome identification in individual plasma sample. Deferred candidate donors were referred to a donor-care program. RESULTS: A total of 9372 people were screened and 1534 (16.4%) were deferred. No HIV or HCV RNA-containing samples remained undetected by rapid tests unless a human testing error was involved. In contrast, 1.3 and 3.0 percent of HBV DNA-containing blood units were negative with rapid tests but were detected in individual donations with enzyme immunoassay and genomic amplification, respectively. Only half of these units were detectable in pools of 10 samples. One-third of deferred candidate donors attended the donor-care program and were informed and counseled. CONCLUSIONS: Predonation viral screening of blood donors is effective in high endemic areas, and the savings it generates may improve the safety and limit the cost of blood. Communication with deferred donors may contribute to public health. A new screening strategy associating serologic rapid test before donation and NAT on pools of 10 plasma samples after donation is proposed.     

Simultaneous amplification of DNA and RNA virus using multiplex PCR system.

A large number of disease-causing bacteria and viruses are being sequenced and PCR is increasingly used for the diagnosis of the diseases. We have designed a multiplex PCR system for hepatitis B virus (HBV), a DNA virus, and hepatitis E virus (HEV), an RNA virus. A modified technique has been standardized for simultaneous extraction of DNA and RNA, followed by a one-step RT-PCR/PCR.     

Cost-effectiveness of additional blood screening tests in the Netherlands

BACKGROUND: During the past decade, blood screening tests such as triplex nucleic acid amplification testing (NAT) and human T‐cell lymphotropic virus type I or I (HTLV‐I/II) antibody testing were added to existing serologic testing for hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV). In some low‐prevalence regions these additional tests yielded disputable benefits that can be valuated by cost‐effectiveness analyses (CEAs). CEAs are used to support decision making on implementation of medical technology. We present CEAs of selected additional screening tests that are not uniformly implemented in the EU. STUDY DESIGN AND METHODS: Cost‐effectiveness was analyzed of: 1) HBV, HCV, and HIV triplex NAT in addition to serologic testing; 2) HTLV‐I/II antibody test for all donors, for first‐time donors only, and for pediatric recipients only; and 3) hepatitis A virus (HAV) for all donations. Disease progression of the studied viral infections was described in five Markov models. RESULTS: In the Netherlands, the incremental cost‐effectiveness ratio (ICER) of triplex NAT is €5.20 million per quality‐adjusted life‐year (QALY) for testing minipools of six donation samples and €4.65 million/QALY for individual donation testing. The ICER for anti‐HTLV‐I/II is €45.2 million/QALY if testing all donations, €2.23 million/QALY if testing new donors only, and €27.0 million/QALY if testing blood products for pediatric patients only. The ICER of HAV NAT is €18.6 million/QALY. CONCLUSION: The resulting ICERs are very high, especially when compared to other health care interventions. Nevertheless, these screening tests are implemented in the Netherlands and elsewhere. Policy makers should reflect more explicit on the acceptability of costs and effects whenever additional blood screening tests are implemented.     

The hepatitis alphabet--hepatitis A-G and TTV.

During the past three decades the number of viruses known to be capable to inducing liver inflammation has been considerably expanded. This short review gives a quick overview of the virologic characteristics, clinical manifestations, diagnosis, and treatment options. Newer hepatitis viruses such as hepatitis E virus (HEV), hepatitis GB-virus C/hepatitis G virus (GBV-C/HGV), and transfusion-transmitted virus (TTV) are discussed and data concerning their disease-inducing capacity reviewed.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T- lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window- period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window- period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window- period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.     

Hepatitis A to G

Since the discovery that the “Australia antigen” was the surface antigen of the hepatitis B virus in the late 1960s, great advances have been made in the study of hepatitis B and other types of viral hepatitis. Different techniques have been used to characterise the non-B agents, resulting in the identification of hepatitis A, C, D and E. The agents causing hepatitis F and G remain to be characterised. Some of these viruses are transmitted enterically (A and E), the rest are transmitted parenterally. Workers in emergency medicine need to be aware of these entities and to ensure their own protection by immunisation against hepatitis B, and hepatitis A when a vaccine becomes available.     

Impact of screening blood donors for hepatitis C antibody on posttransfusion hepatitis: a prospective study with a second-generation anti-hepatitis C virus assay

BACKGROUND: Hepatitis C is the major cause of posttransfusion hepatitis. Blood components that are positive for antibody to hepatitis C virus (anti-HCV) can transmit posttransfusion hepatitis. STUDY DESIGN AND METHODS: To investigate the effect on posttransfusion hepatitis of screening blood donors with a second-generation test for anti-HCV, 249 transfusion recipients who underwent cardiovascular surgery were prospectively followed. Six recipients who were positive for anti-HCV before transfusion and 51 subjects with incomplete follow-up were excluded from this study. RESULTS: Eleven (13.8%) of 80 subjects who received unscreened blood had two successive serum alanine aminotransferase levels > 90 U per L. Seven (8.8% of total) developed anti-HCV and HCV RNA and two (2.5% of total) developed IgM antibody to cytomegalovirus (IgM anti-CMV). By contrast, 3 (2.7%) of the 112 subjects who received anti-HCV-screened blood had two successive serum alanine aminotransferase levels > 90 U per L. None of these three developed anti-HCV and HCV RNA, but two (1.8% of total) showed the development of IgM anti-CMV. The study shows that screening for anti- HCV in blood donors with a second-generation test almost abrogated posttransfusion viral hepatitis C. CONCLUSION: After anti-HCV screening, other body fluid-transmitted viruses such as CMV may become important in posttransfusion hepatitis.     

Infection with hepatitis delta and human immunodeficiency viruses among hemophiliacs in Japan

Two hundred two patients with hemophilia, dependent solely on imported coagulation factor concentrates, were tested for markers of hepatitis B virus infection, antibody to hepatitis delta virus (anti-HD), and antibody to human immunodeficiency virus (anti-HIV). Nine carriers of hepatitis B surface antigen (HBsAg) were identified. Six (66.7%) of them were positive for anti-HD, a prevalence much higher than that in HBsAg carriers without hemophilia in Japan (1/113 or 0.9%, p less than 0.001). Anti-HIV was found in 96 (47.5%), in sharp contrast to the low prevalence (0/1205) in apparently healthy blood donors (p less than 0.001). These results implicated imported plasma products in the transmission of both delta and human immunodeficiency viruses to hemophiliacs. An efficient method for the sterilization of plasma products is warranted to prevent exposure of hemophiliacs to the accompanying pathogenic viruses.     

Bloodborne pathogens and procedure safety in interventional radiology

Concern about possible transmission of bloodborne pathogens during medical procedures is growing among patients and healthcare workers alike. This fear has primarily been focused on nosocomial transmission of human immunodeficiency virus (HIV), but other bloodborne infectious agents may also be transmitted during procedures. Chief among these are the hepatitis viruses, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV), both of which are significantly more widespread than HIV. Although radiology is not traditionally thought of as a field with significant risk for exposure to or transmission of pathogens, the expanding role of interventional procedures in recent years belies that perception. The potential for exposure to blood or other possibly infectious material exists in virtually any invasive radiological procedure, from arteriography to image-guided biopsy. Fortunately, the risk of such exposure is low, and the risk of actual transmission of a bloodborne pathogen, whether from patient to healthcare worker or vice versa, is even lower. Nevertheless, it is important for all radiologists who perform invasive procedures to be aware of these risks and to observe pertinent safety and infection control recommendations. This article will review these topics.     

Transfusion-transmitted infections among multitransfused patients in Iran: a review

Transfusion-transmitted infections (TTI) continue to be a major challenge for Blood transfusion organizations across the world. The problem is more serious in the developing countries with lower economic means. Multitransfused patients (MTPs) in these countries are at higher risk of infection, and studies of infection in these patients can be a useful index for examining the blood safety filters in place. The present article reviews the situation in Iran, where prevalence of the major viruses of concern, namely, hepatitis B virus, hepatitis C virus (HCV) and human immunodeficiency virus, studied in these patients is reported over a 9-year period. It is demonstrated that HCV is the most prevalent TTI and remains a major health problem for these patients.