Facing difficult but unavoidable choices: Donor blood safety and the deferral of men who have sex with men

Blood service organizations employ various ways to ensure transfusion blood safety, including the testing of all donations for transfusion-transmissible infections (TTI) and the exclusion of donors who are at increased risk of a recent infection. As some TTIs are more common among men who have sex with men (MSM), many jurisdictions (temporarily) defer the donation of blood by sexually active MSM. This boils down to a categorical exclusion of a large group solely on the basis of their sexual orientation, which is seen as unduly discriminatory and stigmatizing. Blood service organizations in the U.K. and the Netherlands have recently changed their deferral policies for MSM. The problem of the MSM deferral involves a conflict between fundamental rights: the right of MSM to equal treatment and the right to health of the recipients of blood and blood products. We distinguish and discuss three broad alternative options to the current categorical deferral of MSM donations: (1) completely abandoning donor selection on the basis of sexual behavior, (2) individual risk assessment of the sexual activities of each potential donor, and (3) individual risk assessment of the sexual activities of MSM only. The new U.K. policy falls within the second category, and the new Dutch policy is in the third category. We argue that each approach comes with moral costs but that the most reasonable option is different from the policies of both the U.K. and the Netherlands

Risk factors for hepatitis E virus seropositivity in Dutch blood donors

Background: A marked increase of hepatitis E cases has recently been observed in the Netherlands. Causes of the (re-)emergence of hepatitis E virus (HEV) and exact sources and routes of transmission of HEV infection are currently unknown. We aimed to identify risk factors for HEV seropositivity. Methods: Using the Wantai EIA, 2100 plasma samples of blood donors from all over the Netherlands aged 18-70 years were tested for anti-HEV IgG antibodies. A questionnaire on socio-demographic characteristics, health, and potential risk factors for HEV exposure was sent to these participants. Results: The overall IgG-seroprevalence was 31% (648/2100) and increased with age. Several food products were independently associated with IgG-seropositivity in a multivariate analysis adjusting for age and gender among 1562 participants who completed the questionnaire: traditional Dutch dry raw sausages called "cervelaat", "fijnkost", "salami" and "salametti" which are generally made from raw pork and beef (aOR 1.5; 95%CI 1.2-1.9), frequent consumption of bovine steak (aOR 1.3; 95%CI 1.0-1.7), and frequent consumption of smoked beef (aOR 1.3 95%CI 1.0-1.7). Although not frequently reported, contact with contaminated water was also a risk factor for seropositivity (aOR 2.5; 95%CI 1.5-4.4). Lower seroprevalence was associated with eating raspberries, going out for dinner, and contact with wild animals and dogs. Conclusion: Several pork food products, mainly dry raw sausages, and contact with contaminated water were associated with past HEV infection in the Netherlands. Further investigation is needed into the prevalence and infectivity of HEV in these risk factor food products, as well as investigation of the production methods and possible origin of HEV-contamination within these sausages, e.g. very small amounts of pork liver, pig-derived blood products as food additive, or the pork muscle tissue

Fluorescence Lifetime Imaging Microcopy of Extravasating Cancer Cells in the Mouse Microenvironment

Objective. To determine (i) whether early viral kinetics or other markers during a modified treatment regimen are predictors of treatment outcome and (ii) whether fast responders can be treated for 24 weeks, without compromising the sustained virologic response (SVR) rate. Material and methods. One hundred "difficult-to-treat'' chronic hepatitis C patients (46 previous non-responders/relapsers (any genotype), 54 treatment-naive patients genotypes 1 and 4) were treated with triple antiviral induction therapy: amantadine hydrochloride and ribavirin, combined with 6 weeks interferon alfa-2b induction (weeks 1-2: 18 MU/day, weeks 3-4: 9 MU/day, weeks 5-6: 6 MU/day), thereafter combined with weekly peginterferon alfa-2b. Fast responders (>= 3 log(10) HCV RNA decline at week 4) were randomized to 24 or 48 weeks. Slow responders (= or = 5 IU/mL at week 16 became non-SVR. In previous non-responders/relapsers, the predictive value for SVR was 83% if HCV RNA was = 5 IU/mL at week 8 became non-SVR. Conclusions. With high-dose interferon induction, SVR and non-SVR can be predicted reliably within 16 weeks. Fast responders can be treated for 24 weeks, and SVR is independent of baseline viral load in fast responders

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

Background:It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis.Methods:We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC.Results:BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HR mult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HR mult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HR mult 1.15; 95% CI 0.84-1.57) and OCSS (HR mult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HR mult 1.99; 95% CI 1.21-3.31).Conclusions:Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy

Hepatitis C virus infection among transmission-prone medical personnel

Hepatitis C virus (HCV)-infected physicians have been reported to infect some of their patients during exposure-prone procedures (EPPs). There is no European consensus on the policy for the prevention of this transmission. To help define an appropriate preventive policy, we determined the prevalence of HCV infection among EPP-performing medical personnel in the Academic Medical Center in Amsterdam, the Netherlands. The prevalence of HCV infection was studied among 729 EPP-performing health care workers. Serum samples, stored after post-hepatitis B virus (HBV) vaccination testing in the years 2000–2009, were tested for HCV antibodies. Repeat reactive samples were confirmed by immunoblot assay and the detection of HCV RNA. The average age of the 729 health care workers was 39 years (range 18–66), suggesting a considerable cumulative occupational exposure to the blood. Nevertheless, only one of the 729 workers (0.14%; 95% confidence interval [CI]: <0.01% to 0.85%) was tested and confirmed to be positive for anti-HCV and positive for HCV RNA, which is comparable to the prevalence of HCV among Amsterdam citizens. Against this background, for the protection of personnel and patients, careful follow-up after needlestick injuries may be sufficient. If a zero-risk approach is desirable and costs are less relevant, the recurrent screening of EPP-performing personnel for HCV is superior to the follow-up of reported occupational exposures

Variability and pathogenicity of hepatitis E virus genotype 3 variants

Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (P>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype

Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; A case series 2004 – 2006

<p>Abstract</p> <p>Background</p> <p>Human hepatitis E virus (HEV) infections are considered an emerging disease in industrialized countries. In the Netherlands, Hepatitis E virus (HEV) infections have been associated with travel to high-endemic countries. Non-travel related HEV of genotype 3 has been diagnosed occasionally since 2000. A high homology of HEV from humans and pigs suggests zoonotic transmission but direct molecular and epidemiological links have yet to be established. We conducted a descriptive case series to generate hypotheses about possible risk factors for non-travel related HEV infections and to map the genetic diversity of HEV.</p> <p>Methods</p> <p>A case was defined as a person with HEV infection laboratory confirmed (positive HEV RT-PCR and/or HEV IgM) after 1 January 2004, without travel to a high-endemic country three months prior to onset of illness. For virus identification 148 bp of ORF2 was sequenced and compared with HEV from humans and pigs. We interviewed cases face to face using a structured questionnaire and collected information on clinical and medical history, food preferences, animal and water contact.</p> <p>Results</p> <p>We interviewed 19 cases; 17 were male, median age 50 years (25–84 y), 12 lived in the North-East of the Netherlands and 11 had preexisting disease. Most common symptoms were dark urine (n = 16) and icterus (n = 15). Sixteen ate pork ≥ once/week and six owned dogs. Two cases had received blood transfusions in the incubation period. Seventeen cases were viremic (genotype 3 HEV), two had identical HEV sequences but no identified relation. For one case, HEV with identical sequence was identified from serum and surface water nearby his home.</p> <p>Conclusion</p> <p>The results show that the modes of transmission of genotype-3 HEV infections in the Netherlands remains to be resolved and that host susceptibility may play an important role in development of disease.</p