Determining the strength of evidence for an association between sexual indicators and risk of acquiring HIV and sexulaly transmitted infections: Providing evidence for blood donation policy change.

In 2019 the For The Assessment Of Individualised Risk (FAIR) project began a review of UK blood donor selection policy to determine if a more individualised approach to donor selection could be safely implemented. An evidence base was required to inform selection policy to move from a population to a more individual based policy, specifically what sexual behaviours/indicators should be considered as screening questions to maintain the safety of the blood supply. Eight sexual behaviours/indicators were reviewed: history of bacterial sexually transmitted infections (STIs), chemsex, number of recent partners, condom use, type of sex, sexual health service (SHS) attendance, new sexual partner and exclusivity. We conducted searches in multiple databases to identify literature looking at the association between these behaviours/indicators and HIV/STI acquisition risk. A scoring system to determine strength of evidence was devised and applied to papers that passed screening. Key studies were identified which achieved the maximum score and more in-depth reviews were conducted for these. We identified 58 studies, including 17 key studies. Strong evidence was found linking a previous bacterial STI, chemsex and increasing numbers of sexual partners to acquisition risk. Condom use, type of sex and new partners were found to have some strength of evidence for this link. SHS attendance and exclusivity had minimal evidence. We recommended that the behaviours/indicators viewed as having strong or some strength of evidence should be considered as screening questions in a more individualised approach to donor selection criteria.

HIV residual risk in Canada for apheresis source plasma donation without deferral for men who have sex with men.

BACKGROUND AND OBJECTIVES: In Canada, men having sex with men (MSM) are deferred for 3 months from last sexual contact to reduce human immunodeficiency virus (HIV) risk to recipients. The aim of this paper was to model the Canadian residual risk of HIV-positive source plasma incorporating pathogen inactivation (PI) under no MSM deferral scenarios for apheresis plasma donations. MATERIALS AND METHODS: A combined Bayesian network (BN) and Monte Carlo approach were implemented to estimate the HIV residual risk under 3-month deferral compared with no deferral without quarantine scenarios for MSM donors. Models involve the stochastic generation of donation and its infection status based on its corresponding simulated donor profile. Viral load reduction conferred by PI used by source plasma fractionators was simulated. Model parameters were derived from Héma-Québec and Canadian Blood Services data, viral loads in a large sample of HIV-positive US blood donors, CSL Behring documentation and from published data. RESULTS: In the most likely scenario for the 3-month deferral model, there were 2.71 positive donations per 1,000,000 donations (95% confidence interval [CI] 2.63-2.78). For the no-deferral model, there were 3.01 positive donations per 1,000,000 donations (95% CI 2.94-3.09). For both scenarios, the risk of having an infectious pool was 0 in 300,000 pools (95% CI 0-0.0000123) after consideration of PI. CONCLUSION: Based on simulation results, there would be a negligible HIV residual risk associated with the removal of a time-based MSM deferral without quarantine for source plasma incorporating PI.

Hepatitis B infections among blood donors in England between 2009 and 2018: Is an occult hepatitis B infection a risk for blood safety?

INTRODUCTION: Hepatitis B virus (HBV) is one of the most frequent infections identified in blood donors in England and represents an ongoing blood safety risk. We have analyzed markers of HBV infections in blood donors in England between 2009 and 2018 and used these to estimate the likelihood of non-detection of occult HBV infection (OBI). METHODS: We collected epidemiological, virological, and genotyping information on HBV cases identified in England, 2009-2018. The estimated risk of non-detection and likely transmission of OBI were compared to lookback and transfusion-transmitted infections surveillance data. RESULTS: Six-hundered and fifty-five HBV-infected blood donors were identified in England during the 10-year period; 598 chronic, 32 acute, and 25 occult HBV infections. However, most donors with chronic and occult infections were born in Eastern Europe, Africa, or Asia (451/544, 83% and 14/24, 58%); acute infections were largely seen in UK-born donors (19/28, 68%). Genotyping of 266 HBV-positive samples revealed five genotypes (A-E), reflecting ethnicity and country of birth. Most OBIs were identified in repeat donors (19/25); lookback data identified a transmission rate of 8.3%. It is estimated that at least 13 potentially infectious donations from donors with OBI remain undetected annually, equating to an overall residual transmission risk of 3.1 per million donations using our current screening strategy of HBsAg screening with HBV nucleic acid testing (NAT) in pools of 24. CONCLUSIONS: OBI accounted for the majority of the HBV residual risk in England. Further cost-benefit analysis is required to estimate if our current HBV screening strategy should be changed.

Blood donation by men who have sex with men: using evidence to change policy.

BACKGROUND: In 2011 in the United Kingdom (UK), excluding Northern Ireland, the deferral of men who have sex with men (MSM) changed from lifetime to 12 months. We describe MSM who donated before and after this to inform further policy reviews. MATERIALS AND METHODS: Characteristics and sexual behaviours of donors identifying as male from routine surveillance are described. Rates of infections are compared pre- and post-implementation of a 12-month deferral. Donors are compared with screen negative male donors responding to a large-scale survey during 2013/2014. RESULTS: Comparing the five years pre- and post-change, the rate of confirmed positives for markers of HBV, HCV, HIV and syphilis decreased by 6·9% from 14·1 to 13·1/100 000 donations. The rate of recent infections was unchanged (1·72/100 000). Of 22 776 survey responses identifying as male, MSM disclosed sex between men over 12 months ago giving 99·35% compliance among male donors. Two-thirds of the 72 non-compliant MSM reported one to two partners and one-third had no new partners within 12 months. The most commonly reported reason for non-compliance from MSM both positive and negative for infection was 'not important to declare' (37·2% and 40·7%). Test seeking was rare (9·3% and 2·1%). CONCLUSION: Compliance with the 12-month MSM deferral policy was very high. The very low rates of infections post-change demonstrated the effectiveness of the policy. These data were an important part of the 2017 review of all sexual behaviour deferrals.

Re-assessing the risk of undetected HBV, HCV and HIV in deceased tissue and living surgical bone donors in England.

Testing of living surgical bone and deceased tissue donors by NHS Blood and Transplant (NHSBT) has included individual donation (ID) nucleic acid testing (NAT) for HBV, HCV and HIV since 2008. Here, the well-established window period methodology was used to estimate residual risk (RR). Prevalence of viral markers was calculated among both tissue donor populations. Incidence was derived by adjusting incidence among new blood donors by the prevalence ratio for tissue and new blood donors. Residual risk (RR) was calculated as the product of incidence and duration of WP for single donor HBV NAT at 0.058 years (21 days), HCV NAT at 0.008 years (3 days) and HIV NAT at 0.014 (5 days). Between 2013 and 2017, 7886 living surgical bone donors were tested, 16 were positive for markers of HBV, HCV and HIV. HCV had the highest prevalence at 114/100,000 donors. Incidence and RR was highest for HBV at 3.55/100,000-person years and 0.32/100,000 donors (95% CI 0.11/100,000-1.42/100,000). Among 9751 deceased tissue donors tested, 22 were positive for viral markers. HBV had highest prevalence at 174/100,000 donors, and the highest incidence and RR at 8.12/100,000 person years and 0.74/100,000 donors (95% CI 0.08/100,000-2.99/100,000). Using ID NAT, RR of not detecting a HBV, HCV and HIV WP donation among tissue donors is less than 1/100,000 donors. These estimates provide a good starting point for discussing potential risks of viral transmission through tissue transplant with patients.

What are blood donors telling us about injecting drug use?

BACKGROUND AND OBJECTIVES: Injecting drug use (IDU), a permanent deferral for blood donors, was included in a review of donor selection criteria completed in 2017. Here, we describe what is known about IDU in blood donors in the United Kingdom (UK). MATERIALS AND METHODS: Data were obtained from routine surveillance of donation testing and confirmed positive donors and a 2013/2014 UK survey of behaviour and compliance in screen-negative donors. RESULTS: Between 2009 and 2018, of 22 UK million donations screened, IDU was self-reported at the post-test discussion in 5% (86/1777) of donors with confirmed positive donations. Recent injecting within 12 months was reported in 8 HCV-positive donors, but only in 1/14 donors where it was clear HCV infection had been acquired in the previous 12 months. Of 65 439 survey responders, 25 reported IDU, which when weighted to the donor population gave 99·95% compliance. Most of the 111 donors reporting IDU felt it was not important to their donation, mainly because their injecting was in the past, while three HCV-positive recent injectors reported not sharing needles so presumably felt safe to donate. CONCLUSION: Compliance with the permanent deferral appeared extremely high with low levels of injecting reported by donors, mainly in the past. This agreed with the low-incident HCV infection observed in UK donors. These data contributed to a recommendation to reduce the deferral to 1 year. Ways of improving compliance in those few donors at current increased risk of infection need to be investigated.

HIV residual risk in Canada under a three-month deferral for men who have sex with men.

BACKGROUND AND OBJECTIVES: In Canada, the deferral for men who have sex with men (MSM) was decreased from a permanent deferral to a 5-year then a 12-month deferral. Current HIV testing can detect an HIV infection in donated blood within 2 weeks of exposure; thus, a 12-month deferral may be unnecessarily restrictive. We aimed to estimate the residual risk of HIV if the deferral were further decreased to 3 months. MATERIALS AND METHODS: Using a deterministic model with stochastic Monte Carlo simulation, residual risk of HIV was the sum of testing error, assay sensitivity and window-period risks. Data inputs were estimated from donor surveillance, donor surveys and published data. Residual risk was modelled at baseline and using three scenarios: (1) most likely - non-compliance, HIV prevalence and incidence rates of MSM are unchanged; (2) optimistic - non-compliance improves by 50%; and (3) pessimistic - non-compliance, HIV prevalence and incidence rates of MSM all double. RESULTS: HIV residual risk at baseline was 1 in 36·0 million donations (95% CI 1 in 1 504 907 million, 10·5 million); in the most likely scenario 1 in 34·2 million (1 in 225 534 million, 8·7 million); in the optimistic scenario 1 in 36·0 million (1 in 282 618 million, 9·5 million); in the pessimistic scenario 1 in 16·7 million (1 in 39 469 million, 6·0 million). All confidence intervals overlapped. CONCLUSION: With very low modelled risk under a 12-month deferral, the additional risk with a 3-month deferral is very low. This is true even with a pessimistic scenario.

Changing the deferral for men who have sex with men - an improved model to estimate HIV residual risk.

BACKGROUND AND OBJECTIVES: Eight published studies modelled the impact of changing from a lifetime to time-limited deferral for men who have sex with men (MSM); each predicted greater risk impact than has been observed. This study uses these previous efforts to develop an 'optimized' model to inform future changes to MSM deferrals. MATERIALS AND METHODS: HIV residual risk was calculated using observed HIV incidence/prevalence prior to the change in MSM deferral, then with the additional MSM expected under a 12-month deferral for five compliance scenarios, and finally using data observed after implementation of the deferral. Monte Carlo simulation calculated 95% confidence intervals (CI). RESULTS: The architecture of reviewed models was sound, and two were selected for combination into the optimized model. HIV risk estimated by this in the UK under MSM lifetime deferral was 0·102 (95% CI: 0·050-0·172) per million. The model predicted from a 27·8% decrease to a 47·6% increase depending upon compliance pre-implementation of the 12-month deferral. A decrease of 0·9% was observed post-implementation. For Canada, HIV risk under a 5-year deferral was 0·050 (95% CI: 0·00003-0·122) per million. Pre-implementation of the 12-month deferral, the model predicted from 30·2% decrease to 10-fold increase. A decrease of 47·0% was observed after implementation. CONCLUSION: The optimized model predicted HIV risk under 12-month MSM deferral in UK and Canada would remain low, and this was confirmed post-implementation. While the model is adaptable to other deferral scenarios, improved data quality would improve precision, particularly estimates of incidence in individuals likely to donate.

Infections and associated behaviors among deceased organ donors: Informing the assessment of risk.

BACKGROUND: For infectious disease risk assessment among deceased organ donors, pre-donation clinical, microbiological, and behavioral information are reviewed; however, uncertainty may arise due to false negative screening results of recently acquired infections. METHOD: The burden of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and residual risks (RR) of undetected virus was estimated, with the impact of more sensitive screening. RESULTS: For United Kingdom potential deceased organ donors between 2010 and 2014, prevalence of HBsAg was 0.1%, HIV 0.06% and HCV 0.9%, increasing to 25.7% in people who injected drugs (PWID). Incidence, derived from new blood donors, was multiplied by duration of screening assay window periods to give RR per 100 000 donors as 0.43 (95% confidence interval [CI] 0.03-3.99) for HBV, 0.08 (95% CI 0.02-0.21) for HIV, and 5.96 (95% CI 0.82-37.89) for HCV. For PWID, HCV RR was 163.3 (95% CI 22.8-1107.8) compared to 2.76 (95% CI 0.35-17.36) for non-PWID. RR decreased significantly with nucleic acid testing (NAT), and, for HCV, antigen testing had a similar impact. CONCLUSION: While the burden of HCV risk lies within PWID, these are in small numbers therefore few HCV antigen or NAT tests would be needed to more accurately assess risk.

Hepatitis B and residual risk of infection in English and Welsh blood donors, 1996 through 2008.

BACKGROUND: Globally, of all infections that donations are tested for, hepatitis B has the highest residual risk of transfusion transmission, despite donor selection criteria and advances in testing. Every blood donation in England and Wales is tested for hepatitis B surface antigen. Knowledge of infections being detected can inform donor selection and testing strategies. STUDY DESIGN AND METHODS: Data on donation testing and infections detected are collated by the NHS Blood and Transplant and Health Protection Agency Epidemiology Unit. Infected donors are classified as having acute or chronic hepatitis B virus (HBV) by a clinician; their demographic characteristics were described. The prevalence (by acute or chronic HBV status, ethnicity, and geography) and incidence of infection were calculated between 1996 and 2008. The residual risk was calculated for four periods using a modification of the incidence and window period model; the effects of modifying variables were investigated. RESULTS: Most infections (1047/1155) detected were chronic and seen in new donors. People with acute infections were more likely to be white and/or born in Western Europe. Prevalence was highest in donors from minority ethnic communities and in London. Incidence in repeat donors has halved in recent years. The estimated frequency of an infectious donation being missed was 1.37 per million donations (2006-2008), the lowest since surveillance began or three per year. CONCLUSION: Many HBV infections in England and Wales were detected among new donors, who had chronic infection and were born overseas. The residual risk of infection declined over the 13 study years, but is still higher for HBV than other viral infections for which testing is undertaken.

Viral encephalitis in England, 1989-1998: what did we miss?

We analyzed hospitalizations in England from April 1, 1989, to March 31, 1998, and identified approximately 700 cases, 46 fatal, from viral encephalitis that occurred during each year; most (60%) were of unknown etiology. Of cases with a diagnosis, the largest proportion was herpes simplex encephalitis. Using normal and Poisson regression, we identified six possible clusters of unknown etiology. Over 75% of hospitalizations are not reported through the routine laboratory and clinical notification systems, resulting in underdiagnosis of viral encephalitis in England. Current surveillance greatly underascertains incidence of the disease and existence of clusters; in general, outbreaks are undetected. Surveillance systems must be adapted to detect major changes in epidemiology so that timely control measures can be implemented.