Safe supplies: few infections in UK blood and tissue donors.

AIMS/OBJECTIVES: Here, we describe the annual review of the UK blood services' infection surveillance schemes for 2017 (www.gov.uk/government/publications/safe-supplies-annual-review). BACKGROUND: The joint NHS Blood and Transplant/Public Health England Epidemiology Unit was set up in 1995 to ensure that blood and tissue safety is maintained, inform donor selection and testing policy and add to public health knowledge. METHODS: Several surveillance schemes for blood, tissues and bacterial screening collect the numbers of donations tested, reactive and confirmed positive in order to monitor trends in infection rates in donors and calculate residual risk of infection. Investigations of potential transfusion transmissions in recipients are also monitored. RESULTS: In the UK in 2017, the risk of testing not detecting a potentially infectious hepatitis B virus or hepatitis C virus or HIV donation was estimated as less than one in two million donations. One hepatitis A virus and one hepatitis E virus transmission incidents were proven to be transfusion-transmitted by unscreened donations. CONCLUSIONS: The Safe Supplies annual review provides a clear picture of the very low risk associated with blood and tissues in the UK nowadays. In November 2017, the blood services for England, Wales and Scotland implemented recommendations to reduce the deferrals for higher risk sexual behaviour from 12 to 3 months. The surveillance schemes are adapted to remain fit for purpose as testing and donor selection change.

Dissecting the decline of hepatitis C in first-time donors in England and Wales.

BACKGROUND AND OBJECTIVES: The rate of confirmed hepatitis C virus (HCV) cases, in first-time donors, is much lower in 2015 than 20 years ago. We investigate reasons for the decline. MATERIALS AND METHODS: HCV rates were analysed by gender and birth cohort for 1996 to 2015 and ethnic group for 2006 to 2015. Variables for confirmed positive cases were compared for two ten-year periods (1996 to 2005 and 2006 to 2015) including genotyping data for 2006 to 2015. RESULTS: There were 2007 confirmed HCV cases identified between 1996 and 2015. The rate per 100 000 donations fell from 78·6 in 1996 to 26·9 by 2015. By birth cohort, HCV rates were highest in donors born in the 1950s and 1960s who contributed a decreasing proportion of first-time donors. Between 2006 and 2015, there was no significant decline in HCV rate. The HCV-positive donor profile has changed in the last 10 years with increased proportions of younger donors, donors born abroad and decreased reported injecting drug use. Genotype 1a remains predominate, but genotype 1b has increased associated with this change in birth cohort and ethnicity. CONCLUSION: The decline in number and rate of confirmed HCV-positive first-time donors is mainly due to a decrease in first-time donors born before 1970, with the highest rate of HCV. However, the decline has slowed and the profile of HCV-positive first-time donors is changing. A better understanding of behaviour and sources of HCV in younger and ethnic minority donors are needed.

Getting personal with blood donors - the rationale for, methodology of and an overview of participants in the UK blood donor survey.

OBJECTIVE: To design and pilot a survey of UK blood donors to assess, on a large scale, their understanding of and compliance with the donor selection guidelines (DSG). BACKGROUND: Compliance with the DSG is important for maintaining blood safety, however, little is currently known about the extent of this among UK donors. MATERIALS AND METHODS: The online, unlinked survey was based on the donor health check form with a focus on behaviours associated with blood borne infections, sexual contact, drug use and travel. The survey materials were reviewed by a donor focus group and the survey was piloted among 2982 UK donors. Percentage responses were calculated, complaints monitored and answers to questions reviewed. The survey went live in 2013; 225 091 donors were invited via email to participate followed by two reminders. RESULTS: The survey was well received by the focus group, with little concern about the sensitive and personal questions. Their feedback led to important refinement in the survey materials. In the pilots, 21·0% (627/2982) responded, a reminder was necessary to achieve this. Among responders, there was evidence of non-compliance and test seeking behaviour, and no evidence that intention to donate again was affected. In the live survey, 29% (65 439) responded; responders were generally representative of donors overall. CONCLUSION: A large scale survey of donor compliances is feasible, acceptable and effective in ascertaining appropriate information; involving donors and the blood services in the development stages through a focus group and pilots was important to achieve this.

The risk of transfusion-transmitted HIV from blood donations of men who have sex with men, 12 months after last sex with a man: 2005-2007 estimates from England and Wales.

The risk of transfusion-transmitted HIV infection under (i) permanent exclusion and (ii) 12-month deferral of MSM in England and Wales during 2005-2007 was estimated. Assuming equal compliance with both scenarios, estimated risk under a 12-month deferral (0.228/million donations [range 0·168-0·306/million donations]) was only marginally greater (0·5%) than that under lifetime exclusion (0·227/million donations [range 0·157-0.318/million donations]), with one extra-HIV infectious donation every 455 years. Poorer compliance of MSM with a 12-month deferral would be expected to increase the estimated risk, whereas improved compliance could decrease risk by up to 29·1%.

Recruiting individuals into the HTLV cohort study in the United Kingdom: clinical findings and challenges in the first six years, 2003 to 2009.

Human T-lymphotropic virus (HTLV) infection is rare in the United Kingdom (UK) and few studies are available worldwide. Following introduction of blood donation testing in 2002, a cohort of individuals could be identified and prospectively recruited to describe progression and onset of disease. Here we describe baseline characteristics of participants, and evaluate recruitment into the UK HTLV National Register over the first six years, from July 2003 to June 2009. A multicentre cohort study recruited participants from the UK blood services (recipients and donors) and specialist HTLV clinics. Almost half of the 148 participants recruited were blood donors, nine were blood transfusion recipients, 40 contacts and 29 clinic attendees (nine asymptomatic and 20 symptomatic). Most participants were HTLV-1 positive (n=115); 11 had HTLV-2 and 22 were HTLV-negative. Baseline self-completion questionnaires were received for 83%. The most commonly reported condition was a past operation/serious illness (69%). Twenty-six participants reported four or more possible signs/symptoms of HTLV-1-associated myelopathy/tropical spastic paraparesis. Recruitment into a study of a rare, long-term infection is challenging. This cohort will enable descriptions of HTLV-associated disease progression amongst people recruited from varying sources; it is the first prospective study of its kind in Europe.

A re-evaluation of the risk of transfusion-transmitted HIV prevented by the exclusion of men who have sex with men from blood donation in England and Wales, 2005-2007.

BACKGROUND AND OBJECTIVES One component of the rationale for lifetime exclusion of men who have sex with men (MSM) from blood donation in the UK is the probable reduction in the risk of transfusion-transmitted HIV; this exclusion has recently been questioned. MATERIALS AND METHODS Data about HIV in blood donors and MSM were analysed to estimate the risk of infectious donations entering the blood supply under different scenarios of donor selection criteria (and donor compliance) for MSM and a heterosexual group with increased risk of HIV. RESULTS In 2005-2007, a change from lifetime exclusion of MSM to 5-year deferral or no deferral increased the point estimate of HIV risk by between 0·4% and 7·4% depending on compliance with the deferral (range -4% to 15%) and 26·5% (range 18% to 43%) respectively. A change from a 12-month deferral of the high-risk heterosexual group to lifetime exclusion reduced the estimated risk by about 7·2% (range 6% to 9%). Each point estimate was within the probable range of risk under the current criteria. CONCLUSION If prevalence is the only factor affected by a reduced deferral, then the increased risk of HIV is probably negligible. However, the impact of a change depends on compliance; if this stays the same or worsens, the risk is expected to increase because of more incident infections in MSM who donate blood. The risk of transfusion-transmitted HIV could probably be reduced further by improving compliance with any exclusion, particularly after recent risk behaviours.

The introduction of anti-HTLV testing of blood donations and the risk of transfusion-transmitted HTLV, UK: 2002-2006.

The objectives of the study were to describe the introduction of testing blood donations for antibodies to human T-cell lymphotropic virus (anti-HTLV) and to determine the risk of HTLV potentially infectious donations entering the UK blood supply. The rationale for testing was based on (i) evidence of transmission through transfusion in the UK, (ii) the serious nature of HTLV I-associated morbidity and (iii) evidence of infection in UK blood donors. From mid-2002, all blood donations made at UK blood centres were tested in pooled samples using Abbott-Murex HTLV I/II GE 80/81 enzyme immunoassay (EIA). Surveillance data were used to calculate the incidence and prevalence of anti-HTLV and derive estimates of risk. Between August 2002 and December 2006, 106 donations were confirmed positive for anti-HTLV (95 anti-HTLV I and 11 anti-HTLV II). Prevalence was 10-fold higher among donations from new donors than repeat (4.0 and 0.42 per 100 000 donations), and only one repeat donor had evidence of seroconversion. The risk of an HTLV I potentially infectious donation entering the UK blood supply was estimated at 0.11 per million donations (95% confidence interval 0.06 to 0.18). The current very low observed incidence and prevalence among blood donors reflect the very low estimated risk of an HTLV I-positive donation entering the UK blood supply. A change in either the epidemiology of HTLV in UK blood donors or the length of the window period of the test should prompt further review of the risk and a reassessment of anti-HTLV testing in the UK.

Infections detected in English surgical bone and deceased donors (2001-2006) and estimated risk of undetected hepatitis B and hepatitis C virus.

BACKGROUND AND OBJECTIVES: Infections can be transmitted through donated tissue products, such as femoral heads. Here we describe infections detected through microbiological testing of English surgical bone and deceased donors (2001-2006) and estimate the residual risk of infection. MATERIALS AND METHODS: Data on infected tissue donors identified by NHS Blood and Transplant (NHSBT) were collected through the NBS/Health Protection Agency Infection Surveillance programme. The blood donor model for estimating risk was adapted for tissue donors. Incidence among surgical bone donors was derived from new blood donor data and estimates of residual risk presented for surgical bone donors only. RESULTS: Fifty-seven surgical bone and four deceased donors were identified with 60 and five infections, respectively, during the 6 years. Syphilis was the most common infection detected, with no human T-lymphotropic virus infections and one HIV infection in a deceased donor. Hepatitis B virus, hepatitis C virus and syphilis prevalence was higher among surgical bone and deceased donors than new blood donors for the same period. The overall estimated risk of undetected hepatitis B and hepatitis C virus among surgical bone donors (2001-2006) on initial screening was 0.426 and 0.048 per 100 000 donors, respectively. Testing a follow-up sample made these risks almost negligible. CONCLUSION: The prevalence of infections was low among English tissue donors. Risk estimates were higher for surgical bone donors on first screening than among new blood donors. However, the probability of an infectious donation entering the tissue supply became negligible after obtaining a follow-up sample 6 months post-donation and were well below that of new blood donors.

Increase in recently acquired syphilis infections in English, Welsh and Northern Irish blood donors.

BACKGROUND AND OBJECTIVES: Syphilis can be transmitted by blood. We describe syphilis infections detected in blood donors and investigate the epidemiology of syphilis in English, Welsh and Northern Irish blood donors. MATERIALS AND METHODS: This article analyses routine surveillance data regarding syphilis infections in blood donors from England, Wales and Northern Ireland between 1998 and 2004. Infections are classified as recently acquired or past syphilis and donor characteristics and trends examined. RESULTS: A total of 518 syphilis-infected donors were identified; 40 had recently acquired infection and 407 had past syphilis (71 were unclassified). Thirteen times more recently acquired syphilis infections were identified among people who donated between 2002 and 2004 compared to 1998 to 2001. Young, white and regular donors were most likely to have recently acquired syphilis infections. Heterosexual sex was the main risk exposure identified overall; in contrast, the greatest proportion of recently acquired infections were in men who have sex with men. CONCLUSION: The increase in recently acquired syphilis, although low, indicates that risky sexual behaviours are increasing in the blood donor population, with implications for the microbiological safety of blood. Continued vigilance is required by blood services as the risk of syphilis increases in the general population.

Investigating the aetiology of and evaluating the impact of the Men C vaccination programme on probable meningococcal disease in England and Wales.

The aims were to (1) investigate the aetiology of probable meningococcal disease, where a clinical diagnosis is made in the absence of laboratory data, and (2) evaluate the impact of the Men C vaccination programme in England and Wales. Multiple linear regression analyses were carried out using data reported to Enhanced Surveillance of Meningococcal Disease (ESMD) and laboratory reports of isolates of organisms causing symptoms that mimic meningococcal disease. Confirmed meningococcal disease appeared to be a significant predictor of probable disease. Thus, an additional reduction in meningococcal disease attributable to the serogroup C vaccination campaign was evident in probable disease over and above that observed in confirmed cases alone. Enteroviruses were a significant contributor to cases of probable meningitis and influenza appeared to be a significant contributor to probable cases of septicaemia. This analysis confirms the success seen following the Men C vaccination campaign and gives an indication of the aetiologies of other causes of probable meningitis and septicaemia reported to ESMD.

Clusters of meningococcal disease in school and preschool settings in England and Wales: what is the risk?

AIMS: To assess the risk of further cases in educational settings in order to inform policy on managing cases and clusters of meningococcal disease. METHODS: Between 1 April 1995 and 31 March 2001, surveillance in preschool and school settings in England and Wales identified 114 clusters of meningococcal disease. Twenty clusters were reported in preschool settings, 43 in primary, 46 in secondary, and five in independent schools. Seventy three clusters (64%) consisted of two or more confirmed cases, of which 30 had two or more serogroup C cases. Following the introduction of the national meningococcal serogroup C vaccination programme in 1999, no serogroup C clusters were observed between April 2000 and March 2001. RESULTS: The relative risk of further cases in the four weeks after a single case compared with the background rate was raised in all settings, ranging from RR 27.6 (95% CI 15.2 to 39.9) in preschool settings to RR 3.6 (95% CI 2.5 to 4.6) in secondary schools. Absolute risk estimates ranged from 70/100 000 in preschool settings to 3.0/100 000 in secondary schools. The relative risk of clustering was similar for serogroup B and C strains. Most (68%) second cases occurred within seven days of the first case. CONCLUSIONS: Although there was a higher risk of further cases of meningococcal disease in schools and especially in preschool settings, it is not known whether widespread antibiotic use after single cases reduces risk of further cases and if there is a real risk of harm. Evidence of risk reduction is needed to inform public health policy.

Enhanced surveillance scheme for suspected meningococcal disease in five regional health authorities in England: 1998.

Enhanced surveillance of meningococcal disease (ESMD) began in five English regions on 1st January 1998. The aims of the scheme were to obtain accurate incidence data and develop a robust surveillance system with which to monitor the impact of a new meningococcal serogroup C conjugate vaccine. During 1998, 2,314 suspected cases of meningococcal disease were identified. The majority (84%) was classified as invasive meningococcal disease, with infection of N. meningitidis confirmed in 66%. Sixteen per cent of suspected cases were subsequently given an alternative diagnosis. Age differences between those classified as meningococcal disease and those not, implied a higher index of suspicion of meningococcal disease in younger children. Regions with high rates of meningococcal disease were due to a higher rate of serogroup C. ESMD increased ascertainment of meningococcal disease and deaths. Cases were 34% greater than identified through statutory notifications, an additional 6.8% confirmed infections were identified than were reported to the PHLS Meningococcal Reference Unit (MRU) and deaths were 24% greater than death registrations. These data were used to inform the national meningococcal serogroup C conjugate vaccination programme in England and Wales. In 1999 ESMD was extended to all regions of England, Wales and Northern Ireland.

Estimating the burden of serogroup C meningococcal disease in England and Wales.

In 1999 a new conjugate vaccine for serogroup C meningococcal disease was licensed for use in the UK. In order for an appropriate vaccination strategy to be developed the burden of serogroup C disease in England and Wales needed to be established. This was done using data from an enhanced surveillance scheme alongside routine laboratory reports and a total of 5,052 cases of serogroup C disease in England and Wales between 1993 and 1998 were estimated. Among these, an estimated 398 died and 1,767 were admitted to intensive care units (ITUs). The greatest burden of disease was in young children and teenagers. The current literature identified four studies reporting sequelae following serogroup C meningococcal disease. These provided estimates of sequelae in the range of 6.5% and 45% and presented some evidence of higher levels than occur following serogroup B meningococcal disease. This information was provided to the Joint Committee on Vaccination and Immunisation to inform policy to implement a serogroup C conjugate vaccination programme in the UK. The vaccination programme has since been justified by the dramatic reduction in serogroup C meningococcal cases.

National enhanced surveillance of meningococcal disease in England, Wales and Northern Ireland, January 1999-June 2001.

Enhanced surveillance of meningococcal disease (ESMD) was implemented nationally across ten regions of England, Wales and Northern Ireland from 1 January 1999. It aims to deliver more sensitive surveillance than laboratory reporting by including clinically diagnosed but laboratory unconfirmed cases. Consultants in Communicable Disease Control (CsCDC) report all clinically diagnosed cases of meningococcal disease (MD) to the Regional Epidemiologist in the relevant regional unit of the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC). These reports are reconciled with laboratory data from the PHLS Meningococcal Reference Unit and then forwarded to the national CDSC where further reconciliation with laboratory data takes place. In addition, CsCDC are asked to report any clusters of MD that occur. Between 1 January 1999 and 30 June 2001, 12,074 cases of MD were ascertained through ESMD. The majority (57%) were laboratory confirmed. The estimated incidence of MD fell between 1999 and 2001 from 9.2 to 8.0 per 100,000 population. Of laboratory confirmed cases, the number of cases of serogroups B and W135 increased and of serogroup C and of ungrouped meningococcal infection decreased. Variation between regions was considerable and deserves further investigation. Of 11,522 cases with a reported clinical diagnosis, 53.6% were diagnosed as septicaemia, 32.6% as meningitis, 12.5% as both septicaemia and meningitis, and 13% had other invasive MD. Between 1 January 1999 and 30 June 2001 698 deaths were reported, an overall case fatality rate (CFR) of 5.8%; 567 deaths were in confirmed cases and 131 probable (CFR 8.2% and 2.5%, respectively). CFR was higher in serogroup C (13.5%) than B (5.8%). No peak in serogroup C meningococcal infection occurred in the winter of 2000/1 and no clusters of serogroup C meningococcal infection were reported in the first half of 2001. ESMD provides information about the epidemiology of MD that is more complete than statutory notification and laboratory surveillance and is useful for evaluating the impact of the meningococcal serogroup C vaccination programme and of the other non-vaccine preventable serogroups.

An outbreak of hepatitis A among young men associated with having sex in public venues.

An increase in hepatitis A virus (HAV) infection was noted among young men in the former Thames regions during 1997. A retrospective case-control study, using a standardised questionnaire at interview, was conducted in the area most affected (London and East Sussex) to investigate the hypothesis that this increase was mainly among homosexual men and to establish the risk factors associated with transmission. Forty-eight cases and 161 controls completed questionnaires. Forty-one cases (85%) described their sexuality as homosexual (p < 0.0001). Cases were more likely than controls to have eaten shellfish (Odds Ratio (OR) 2.4; 95% Confidence Interval (CI) 1.16, 5.04) during the two months before onset of illness. Cases had more sexual partners (p = 0.015), and more casual sexual partners (p = 0.007) than controls. Cases were more likely to have had sex in a gay sauna (OR 3.5; 95% CI 1.53, 8.30), or in a gay club, pub or disco (OR 2.9; 95 CI 1.29, 6.63) than controls. After adjusting for confounding factors, cases were more likely to have eaten shellfish (adjusted [adj] OR 3.0; 95% CI 1.33, 6.59) and to have had sex in a gay sauna (adj OR 3.9; 95% CI 1.42, 10.59). Public health messages need to inform homosexual men about recognised risk factors such as eating shellfish and travel abroad to endemic areas, as well as sexual risks. Homosexual men can benefit from hepatitis A vaccine. We would suggest that in an outbreak situation men who have multiple anonymous partners and have sex in public venues should be targeted as a priority for health education and immunisation.

Guidelines for the control of hepatitis A virus infection.

The PHLS Advisory Committee on Vaccination and Immunisation, following a review of the evidence on control measures for preventing hepatitis A virus (HAV) infection and widespread consultation, has prepared the following guidelines. They include a description of the current epidemiology of HAV infection in England and Wales, where most individuals are now susceptible to HAV. HAV infection is uncommon, with around 1000 infections notified per year in England and Wales. Clusters occur in families and in settings where potential for faecal/oral spread is high, e.g. day care centres, nurseries, primary schools. Larger outbreaks have been recorded in men who have sex with men and injecting drug users. Personal hygiene remains the cornerstone of measures for preventing HAV infection and its spread. Those with haemophilia, hepatitis B or C virus infection or liver cirrhosis, intravenous drug users and men who have sex with men should be offered HAV vaccination as a preventive measure. HAV vaccine should be used for preventing secondary cases and outbreaks provided that patients are informed that the latest date the vaccine is most likely to be effective in preventing disease in contacts is probably 7 days from onset of illness in the primary case. Human normal immunoglobulin (HNIG) should be offered in addition or in preference to vaccine for contacts who are more than 7 days from onset of illness in the primary case, and for those at risk of adverse outcome of HAV infection. Individuals at particular risk of an adverse outcome to infection include those more than 50 years old, with liver cirrhosis of any cause, or with pre-existing hepatitis B or C virus infection. HAV vaccine should be used to prevent infection for travellers to countries where HAV infection is a risk. HNIG is no longer indicated for travellers. Children travelling to such countries should be offered vaccine from 5 years and consideration should be given to vaccinating those aged 1-4 years.

Failure to vaccinate current injecting drug users against hepatitis B in England and Wales.

In most industrialised countries the elimination of hepatitis B infection is highly reliant on effective vaccine delivery to injecting drug users. This paper highlights the very poor vaccine coverage achieved in England and Wales in the ten years since this problem was officially recognised and targeted. This is despite the existence of a comprehensive and well-utilised network of specialist services for injecting drug users.

Chlorinated dibenzo-p-dioxin and dibenzofuran concentrations in beef animals from a feeding study.

Four calves were fed polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans for 120 days at levels somewhat higher than what may be found in forage near some waste incinerators and manufacturing plants. Four calves were fed identical diets but without the chemicals. Using bioelectrical impedance measurements of total body fat, 30-50% of the dosed 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, and 2,3,4,7,8-PeCDF was estimated to be retained by the animals. Although these same congeners were bioconcentrated in adipose tissue (BCF approximately 10), consumer products such as ribeye showed concentrations less than what were found in the animal feed (BCF approximately 0.1). Distribution of the dioxins and furans into various lipid compartments appeared to be rather uniform in back fat, perirenal fat, and ribeye for tetra to hexa congeners. Ribeye, serum, and liver lipids had higher concentrations of the higher chlorinated congeners, due in part to not reaching a steady state. An unexpected source of dioxin and furan contamination was discovered during the experiment, resulting in the control animals having concentrations of some congeners that were equal to or in some cases greater than those of the dosed animals. Pentachlorophenol-treated wood components in the pole barn where the feeding experiment was conducted were found to have contributed to the animals' exposure.