Estimation of the Infectious Risks of Blood Transfusion

Despite the success of efforts made to prevent the transmission of infections by blood transfusion, the risk of infectious donations entering the blood supply and transmitting infection to the recipients of blood components and blood products remains a concern. Following the implementation of donor selection and donation testing strategies to exclude HBV, HIV, and HCV infectious donations from the blood supply, direct observation of transmission of these viruses by blood transfusion has become rare and indirect estimation of the probable frequency of infectious donations entering the blood supply has become more common. Published estimates for different blood services and different periods of time have varied in their methods and scope. The limitations of the estimation process should be considered when using estimates of the risk of infectious donations entering the blood supply to address questions about blood safety.     

Current incidence and residual risk of HIV, HBV and HCV at Canadian Blood Services

Estimates of the viral residual risk should be updated to reflect current incidence of infection in blood donors. Incidence rates were estimated for allogeneic whole‐blood donations made to Canadian Blood Services from 2006 to 2009 based on transmissible disease conversions of repeat donations within a 3‐year period. Residual risk was estimated as the incidence multiplied by the window period. The residual risk of HIV was 1 per 8 million donations, HCV 1 per 6·7 million donations and HBV 1 per 1·7 million donations. The residual risk remains low and has decreased for HCV since our previous estimates due to reduced incidence.     

Estimation of the risk of hepatitis B virus,hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993-2001

BACKGROUND AND OBJECTIVES: The frequency of hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infectious donations entering the blood supply in England is too low to monitor using observational studies. The expected frequency of infectious donations can be estimated and these estimates may be used to contribute to monitoring of blood safety and used in the design of strategies to decrease the risk of transfusion-transmitted infections. MATERIALS AND METHODS: The prevalence and incidence of hepatitis B surface antigen (HBsAg), and antibodies to HCV and HIV (anti-HCV and anti-HIV, respectively) in donors in England, between 1993 and 2001, were used together with data about the length of negative 'window-periods' of current assays for each of these markers and data about test performance, to estimate the number of infectious donations that enter the blood supply. The risks were calculated separately for donations from new donors and from repeat donors, and for the three time periods 1993-95, 1996-98 and 1999-01. RESULTS: The estimated frequency of infectious donations entering the blood supply in England, between 1993 and 2001 was 1 in 260,000 for HBV and 1 in 8 million for HIV. For HCV, the frequency of infectious donations was 1 in 520,000 during 1993-98 and fell to 1 in 30 million during 1999-2001 when all donations were tested for HCV RNA. The frequency of HBV- and HCV-infectious donations entering the blood supply fell over these 9 years: the frequency of HIV-infectious donations remained essentially unchanged. The risk from donations from new donors was found to be approximately sevenfold higher than the risk from donations from repeat donors. CONCLUSIONS: The risks of HBV-, HCV- or HIV-infectious donations entering the blood supply in England are very low, and have decreased since 1993. Although the accuracy of these estimates is imperfect, mainly owing to uncertainty in some assumptions and to small numbers of infections, they provide some quantification of the risk of HBV, HCV or HIV transmission by transfusion, and allow comparison of the magnitude of these risks for each infection and over time. The methods we have used have been developed and improved from previously published methods.     

HIV,HTLV, and Hepatitis B and C Infection in Blood Donors in Bahia,Brazil from 2008 to 2017

Although blood transfusion is an important therapeutic resource, transfusion-transmitted infections (TTIs) are still a cause for concern. Measures to mitigate this risk involve improvement of donor screening criteria and improvements in laboratory tests, especially the use of nucleic acid test (NAT). In this retrospective study we evaluated HIV, HTLV, HCV and HBV infection rates in blood donors of the Hematology and Hemotherapy Foundation of Bahia (Hemoba), Brazil, through serological and NAT results and the characteristics of donors. From February/2008 to December/2017, 777,446 blood donations were made. Most donors were male, aged 25–44 years, black and mixed race, and single or divorced. The density-type incidence (DTI; per 100,000) for each virus was 91.1 for HBV; 66.5 for HCV; 54.3 for HIV; and 33.9 for HTLV, with a decreasing trend observed over the period studied, except in the last biennium. NAT detected only 1 donor in immunological window for HIV (0.46/100,000 donations) and 3 donors in immunological window for HBV (1.8/100,000 donations). Serological positivity for all viruses studied was higher in the metropolitan region of Salvador, the state capital. Conclusion: DTI rates show a decreasing trend over the years studied, with a predominance of HBV infection. NAT allowed the detection of donors in immunological window periods, having an important role in improving transfusion safety.     

An estimate of the current risk of transmitting blood-borne infections through blood transfusion in Italy

We conducted a retrospective cohort study to estimate the incidence of major blood-borne agents among Italian blood donors and calculated the risk of infection among blood recipients using the 'incidence/window period model'. The study was conducted among 46 180 blood donors enrolled in six blood centres between 1994 and 1999. During follow-up, seven new infections were confirmed: three donors seroconverted for anti-human immunodeficiency virus (HIV); two for anti-hepatitis C virus (HCV); and two showed hepatitis B surface antigen (HBsAg) reactivity; no cases of syphilis were observed. The incidence rates per 100 000 person/years were: 4.06 (95% CI: 0.82-11.85) for HIV; 2.41 (95% CI: 0.29-8.70) for HCV; and 2.70 (95% CI: 0.32-9.77) for HBsAg; the incidence for total hepatitis B virus (HBV) infection was 9.77 per 100 000 person/years (95% CI: 1.16-35.36). The estimated risk of an infectious blood unit not being detected was: 2.45 (95% CI: 0.13-12.33) per 1 million units for HIV; 4.35 (95% CI: 0.30-22.39) for HCV; and 15.78 (95% CI: 1.16-84.23) for HBV. Overall, an estimated 22.58 per 1 million units are infected. In Italy, the risk of transfusion-transmitted infections is low and is similar to that in other western countries. The introduction of new more sensitive screening tests could reduce the residual risk of transfusion-transmitted infection by 40-80%.     

The risks of transfusion-transmitted infection: direct estimation and mathematical modelling

Direct measurement of the risk of transfusion-transmitted infection (TTI) is practical and accurate only if the level of risk is high. Historically, studies that established frozen repositories of transfusion recipient and/or blood donor samples were important in establishing the risk of many TTI agents, including the human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). However, given the current very low risk of TTI, mathematical modelling is necessary to estimate the magnitude of such a risk. For agents for which routine blood donor screening is performed, most of this risk comes from transfusion of units collected in the window period between donor infection and a positive blood screening assay. The incidence/window period model has been used to estimate the magnitude of such risks (of the order of 1:100 000 to 1:1 000 000) and for predicting the extent of risk reduction that can be expected with implementation of new tests. Direct estimation and mathematical modelling approaches are both important tools for future assessment of potential, new or emerging TTI agents.     

有偿献血员中艾滋病病毒、乙型肝炎和丙型肝炎病毒感染状况的研究

目的 探讨有偿献血员艾滋病病毒(HIV)、丙型肝炎(丙肝)病毒(HCV)、乙型肝炎(乙肝)病毒(HBV)感染的特点。方法61份HIV阳性献血员及89份HIV阴性献血员的血清,经酶联免疫吸附试验(ELISA)检测HCV抗体(抗-HCV)及HBV血清学标志物,比较两组人群的HCV、HBV及HCV/HBV感染情况。结果HIV阳性献血员的抗-HCV阳性率为70.49％。乙肝病毒表面抗原(HBsAg)与抗体(抗-HBs)、乙肝病毒e抗原(HBeAg)与抗体(抗-HBe)、乙肝病毒核心抗体(抗-HBc)和HBV的阳性率分别为8.20％、29.51％、3.28％、44.26％、11.4896、47.54％;而HIV阴性献血员的抗-HCV阳性率为19.10％,HBsAg、抗-HBs、HBeAg、抗-HBe、抗-HBc、HBV的阳性率分别为2.25％、38.20％、1.12％、47.19％、6.74％、47.19％。经统计学分析,两组人群的HCV、HCV/HBV感染率的差异有显著的统计学意义,而HBV血清学标志物则无显著性差异。结论 与HIV阴性献血员相比。HIV阳性献血员的HCV感染率很高,而HBV血清学标志物则无显著性差异。对献血员进行HBV检测而未检测HIV、HCV造成的选择偏倚,可能是中国中部一些省份HIV感染者HCV感染率高而HBV感染并不相应增高这一现象的原因之一。     

Residual risk of transfusion transmitted human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T lymphotrophic virus

BACKGROUND: The risk of transfusion transmitted viral infection is now so low that mathematical modelling is required to estimate the residual risk. The first national viral risk estimates for hepatitis B virus (HBV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were recently published by the Australian Red Cross Blood Service. Using several refinements to the original methodology, as well as an additional 2 years of data, new risk estimates have been derived. METHODS: Viral screening data for Australian donors for 2000/2003 were retrospectively analysed. The data were applied to three published models to estimate the residual risk of transmitting HIV, HBV, HCV or human T lymphotrophic virus (HTLV) by blood transfusion in Australia. RESULTS: Applying the three models to HBV, HIV and HCV, three point estimates of the residual risk per unit were calculated for each virus. The median point estimates were 1 in 1,339,000 for HBV, 1 in 1 in 7,299,000 for HIV, and 1 in 3,636,000 for HCV. Although the HTLV risk could not be equivalently calculated because of the lack of incident infection it was estimated to be considerably less than 1 in 1,000,000 using a separate method. CONCLUSIONS: The most current and accurate estimate of residual risk of viral transmission in Australia has been provided in the present study. The residual risk in Australia is exceptionally small, continuing to decrease and is generally less than European or US risk estimates. These new estimates demonstrate that for viral transmission the Australian blood supply is amongst the safest in the world, and provide a basis for evaluating the cost benefit of future viral testing methodologies.     

A comparative review of HLA associations with hepatitis B and C viral infections across global populations

Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class Ⅰmolecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific therapeutic strategies for clearance of HBV and HCV infections or co-infections across global populations and aid in identification of HBV-HCV combined vaccine. HLA associations of chronic HBV or HCV development with confounding host factors including alcohol, drug abuse, insulin resistance, age and gender are lacking and warrant detailed investigation across global populations.     

Rate of Seroconversion in Repeat Blood Donors at The National Blood Centre,Kuala Lumpur

The World Health Organization (WHO) recommend that all donated blood are to be screened for at least three viral infections [human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV)]. The National Blood Centre, Kuala Lumpur (NBCKL) aims to reduce transfusion transmitted infections (TTI) as it still remains as one of the major risk for blood transfusion. A cross sectional study was conducted at the National Blood Centre, Kuala Lumpur from 1st January 2009 to 31st June 2010. Data from 581,020 donors were analyzed from year 2004 to 2008. All data were retrieved from NBCKL Blood Bank Information System (BBIS). A total of 201 repeat donors were included in the study based on the inclusion criteria but only 132 repeat donors agreed to participate. Information on sociodemographic, risk factors, knowledge of donors and high risk behavior were extracted from standardize questionnaire. Data were analyzed using SPSS version 14.0. The aim of this study was to determine the predictors of the seropositive infectivity among repeat blood donors at the NBCKL. The results showed Syphilis accounts for the highest and increasing seroconversion rate among other infections from 20.83 % in year 2004 to 44.6 % in year in year 2008. HIV and HCV infection also showed increasing seroconversion rate in 5 years’ time from 6.41 % in year 2004 to 17.54 % in year 2008 and 4.8 % in year 2004 to 5.94 % in year 2008 respectively. However, HBV infection alone showed a decreasing seroconversion rate from 20.83 % in year 2004 to 10.4 % in year 2008. Level of donors’ awareness regarding high risk factors (activities or behaviour) can lead to higher risk of TTI with significant p value in this predictors model(p < 0.05). Repeat blood donors with high risk activities are more likely to have seropositive results for HBV, HIV and Syphilis. This study found that the frequency of HCV seropositivity is higher among lapsed donor. Socio demographic factors such as male and working in the private sector predominates in all TTI markers. Majority of the respondents were aware about relation of high risk activities and risk of TTI.     

有偿供血员HCV、HIV和HBV感染的调查分析

目的 了解有偿供血员感染丙型肝炎病毒（HCV）、艾滋病病毒（HIV）和乙型肝炎病毒（HBV）的情况,分析HCV和HIV感染对HBsAg的影响。方法 检测296名供血员血清抗－HCV、抗－HIV和HBV的5项标志物（HBsAg、抗－HBs、HBeAg抗－HBe及抗－HBc）。结果 296例有偿供血员中,抗－HCV阳性194例,占65.5%。抗－HCV阳性者中,抗－HIV阳性为145例,占HCV总阳性的75％。本组AIDS患者均死于肝外感染或肿瘤而非肝病。HCV合并HIV感染组的HBsAg阳性率为2.8%,明显低于单纯HCV和单纯HIV感染者（10％）,两组比较差异有显著性（P＜0.05）。结论 在HIV高发区,抗－HCV阳性有偿献血员常合并HIV感染,是AIDS高危人群。HCV合并HIV感染,可能干扰HBsAg的合成。     

Assessment of hepatitis B virus and hepatitis C virus infections and associated risk factors in HIV infected patients at Debretabor hospital,South Gondar,Northwest Ethiopia

ObjectiveTo assess hepatitis B and hepatitis C virus infections and associated risk factors among HIV infected patients at Debretabor hospital.MethodsA cross-sectional study was conducted among HIV/AIDS patients attending Debretabor hospital from February to April, 2012. Venous blood samples were collected from study participants for HBsAg and anti HCV antibody tests. Bivariate and multivariate analyses were used to identify associated variables with HBsAg and anti HCV positivity. Variables having P<0.05 was taken as statistically significant association.ResultsFrom a total of 395 HIV infected patients included in this study, 234 (59.2%) were females and 161 (40.8%) males with mean (±SD) age of 36.31 (±9.91) years. The prevalence of HBsAg and anti HCV antibody was 6.1% and 1.3%, respectively. In multivariate analysis, multiple sexual partner (AOR=8.1, 95% CI=1.8–33.97) and history of opportunistic infections (AOR=3.17, 95% CI=1.3–7.7) were statistically associated with HBsAg positivity. History of blood transfusion (AOR=5.61, 95% CI= 1.03-36.59) was associated with presence of anti–HCV antibody.ConclusionsThe prevalence of HBsAg and anti HCV antibodies in HIV coinfected patients was intermediate. However, it is relevant for HIV infected patients since viral hepatitis co-infections in HIV patients can cause multiple complications. Therefore, routine HBV and HCV screening with reliable diagnostic markers need to be carried out for close monitoring and better management in HIV patients.     

Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century

In the past, transfusion-transmitted virus (TTV) infections were not uncommon. In recent years with advanced technologies and improved donor screening, the risk of viral transfusion transmission has been markedly reduced. Hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have all shown marked reduction in transmission rates. However, the newer technologies, including nucleic acid technology (NAT) testing, have affected the residual rates differently for these virally transmitted diseases. Zero risk, which has been the goal, has yet to be achieved. False negatives still persist, and transmissions of these viruses still occur, although rarely. It is known that HBV serological testing misses some infected units; likewise, HBV NAT-negative units have also been known to transmit the virus. Similarly, HIV minipool NAT-negative units have transmitted HIV, as recently as 2007; likely, these transmissions would have been prevented with single-unit NAT testing. Newer technologies, such as pathogen inactivation (PI), will (ideally) eliminate these falsely test negative components, regardless of the original testing method used for detecting the viruses.     

The burden of HBV infection in HCV patients in Italy and the risk of reactivation under DAA therapy

Background

There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs).

Prevalence of HIV and other infections and injection behaviours among people who inject drugs in Addis Ababa,Ethiopia

Background: Ethiopia is one of the sub-Saharan African countries most affected by HIV/AIDS. However, the country lacks data describing the extent of the epidemic among people who inject drugs (PWID). Thus, a bio-behavioural study was conducted in 2015 to generate strategic information on the magnitude of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis and related risk behaviours among PWID in Addis Ababa.

Methods: A cross-sectional study using respondent-driven sampling was conducted among people reported to have injected illicit drugs within 6 months before the study. Males and females aged 15 years or above and who were resident in Addis Ababa were included in the study between 26 March and 22 May 2015. Data was analysed using respondent-driven (RDS) Analyst software.

Results: A total of 237 participants, including 6 seeds, enrolled in the study; most of the PWID were males (96%) with a mean age of 26 years. Most (79%) of the PWID reported injecting heroin but also reported using non-injecting drugs, including marijuana or ganja (47%) and/or khat (31%). Forty per cent of PWID reported ever sharing needles and 56% reported sharing other injecting equipment. However, only 14% reported injecting daily, and 49% reported injecting only 1 to 3 times a month. HIV prevalence was 6%, HBV was 5.1%, HCV was 2.9% and syphilis 5.1% among PWID. Among HIV-positive PWID, 60% reported sharing a needle the last time they injected.

Conclusion: Even though the prevalence of HIV among drug users is not much higher than in the general population in Addis Ababa, the needle sharing prevalence was high. Thus, this baseline study shows the need to establish harm reduction programmes and prevention strategies for the PWID in Addis Ababa.     

HIV感染者中HCV及HBV感染状况的研究

目的 了解HIV感染者中HCV、HBV的感染状况。方法 对197例HIV感染者中的HCV、HBV感染情况进行了血清流行病学调查研究。结果 HIV感染者中HCV的感染率为90.35％,HBV的总感染率为51.94％,HIV、HCV、HBV三重感染率为49.35％。结论 HIV感染者中有极高的HCV感染率,有较高的HBV感染率。     

The use of molecular assays in the management of viral hepatitis

Molecular assays are instrumental in the clinical management of viral hepatitis. During the past years, a wide variety of molecular assays have been developed and implemented. This considerably improved the understanding of the natural history and pathogenesis of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Hepatitis delta virus (HDV) hepatitis, but also caused uncertainties in the selection of the most appropriate assays for clinical requirements. Indeed, a rational choice and application of these assays requires adequate knowledge of the performance of the single test. Moreover, the choice of the most accurate assay for patients’ needs and physicians’ objectives, needs to be oriented to specific contexts, such as diagnosis, management or treatment. In the past, a hurdle in the routine use of assays for hepatitis viruses nucleic acid quantification was represented by the availability of only “home brew” methods which lacked standardization. Major improvement in addressing the use of molecular assays for viral hepatitis has been derived from recent standardization procedures that allowed a comparison between different tests after results were given as International Units. In addition, it should be reminded that, before getting into the market, molecular assays should be approved by European regulation authorities and validated using internationally recognized standards. A subsequent clinical validation should address the diagnostic accuracy of the assay. These proceedings have the aim of identifying which molecular tests, among those currently available, meet clinical requirements for each specific application.