Current hepatitis E virus seroprevalence in Swiss blood donors and apparent decline from 1997 to 2016.

Background and aimHepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine. Studies from several European countries, including Switzerland, have reported high seroprevalence of hepatitis E as a consequence of endemic infections. Published HEV seroprevalence estimates within developed countries vary considerably; primarily due to improved diagnostic assays. The purpose of this study was to investigate the seroprevalence of anti-HEV IgG in Swiss blood donations. Methods: We used the highly sensitive Wantai HEV IgG EIA and assessed regional distribution patterns. We analysed age- and sex-matched archive plasma dating back 20 years from canton Bern to investigate recent changes in HEV seroprevalence levels. Results: On average, 20.4% (95% confidence intervals: 19.1-21.8) of the 3,609 blood samples collected in 2014-16 were anti-HEV IgG positive; however, distinct differences between geographical regions were observed (range: 12.8-33.6%). Seroprevalence increased with age with 30.7% of males and 34.3% of women being positive donors over > 60 years old. Differences between sexes may be attributed to dissimilarities in the average age of this group. Within the specified region of the Bern canton, overall prevalence has declined over two decades from 30.3% in 1997/98 to 27.0% in 2006 and 22.3% in 2015/6. Conclusions: HEV seroprevalence in Switzerland is high, but has declined over the last decades. The result shows that primarily endemic HEV infections occur and that current blood products may pose a risk to vulnerable transfusion recipients. Nucleic acid screening of all blood products for HEV will begin in November 2018.

Low-Frequency Blood Group Antigens in Switzerland.

BACKGROUND: High-frequency blood group antigens (HFA) are present in >90% of the human population, according to some reports even in >99% of individuals. Therefore, patients lacking HFA may become challenging for transfusion support because compatible blood is hardly found, and if the patient carries alloantibodies, the cross-match will be positive with virtual every red cell unit tested. METHODS: In this study, we applied high-throughput blood group SNP genotyping on >37,000 Swiss blood donors, intending to identify homozygous carriers of low-frequency blood group antigens (LFA). RESULTS: 326 such individuals were identified and made available to transfusion specialists for future support of patients in need of rare blood products. CONCLUSION: Thorough comparison of minor allele frequencies using population genetics revealed heterogeneity of allele distributions among Swiss blood donors which may be explained by the topographical and cultural peculiarities of Switzerland. Moreover, geographically localized donor subpopulations are described which contain above-average numbers of individuals carrying rare blood group genotypes.

MNSs genotyping by MALDI-TOF MS shows high concordance with serology, allows gene copy number testing and reveals new St(a) alleles.

Results of genotyping with true high-throughput capability for MNSs antigens are underrepresented, probably because of technical issues, due to the high level of nucleotide sequence homology of the paralogous genes GYPA, GYPB and GYPE. Eight MNSs-specific single nucleotide polymorphisms (SNP) were detected using matrix-assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS) in 5800 serologically M/N and S/s pre-typed Swiss blood donors and 50 individuals of known or presumptive black African ethnicity. Comparison of serotype with genotype delivered concordance rates of 99·70% and 99·90% and accuracy of genotyping alone of 99·88% and 99·95%, for M/N and S/s, respectively. The area under the curve of peak signals was measured in intron 1 of the two highly homologous genes GYPB and GYPE and allowed for gene copy number variation estimates in all individuals investigated. Elevated GYPB:GYPE ratios accumulated in several carriers of two newly observed GYP*401 variants, termed type G and H, both encoding for the low incidence antigen St(a). In black Africans, reduced GYPB gene contents were proven in pre-typed S-s-U- phenotypes and could be reproduced in unknown specimens. Quantitative gene copy number estimates represented a highly attractive supplement to conventional genotyping, solely based on MNSs SNPs.

Too Many Blood Donors - Response Bias in the Swiss Health Survey 2012.

BACKGROUND: Data on blood donor status obtained from general surveys and health interview surveys have been widely used. However, the integrity of data on self-reported blood donor status from surveys may be threatened by sampling and non-sampling error. Our study aimed to compare self-reported blood donors (including one-time as well as regular donors) from the Swiss Health Survey 2012 (SHS) with register-based blood donors recorded by blood establishments and evaluate the direction and magnitude of bias in the SHS. METHODS: We compared population-weighted SHS point estimates of the number of blood donors with their corresponding 95% confidence intervals to the respective figures from blood donor registries (birth cohorts 1978-1993) and estimates of donors based on period donor tables derived from blood donor registries (birth cohorts 1920-1993). RESULTS: In the birth cohorts 1978-1993, the SHS-predicted number of donors was 1.8 times higher than the respective number of donors based on registry data. Adjusting for foreign and naturalized Swiss nationals that immigrated after their 18th birthday, the SHS overall predicted number of donors was 1.6 times higher. Similarly, SHS estimates for the 1920-1993 birth cohorts were 2.4 and 2.1 times higher as compared to register-based estimates. Generally, the differences between SHS and register-based donors were more pronounced in men than in women. CONCLUSION: Self-reported blood donor status in the SHS is biased. Estimates of blood donors are substantially higher than respective estimates based on blood donor registries.

Molecular RHD screening of RhD negative donors can replace standard serological testing for RhD negative donors.

This work aims to assess the value of a generalized molecular RHD screening strategy which could replace routine serological screening of weak D by indirect antiglobulin test. Three independent studies were performed at the two Blood Transfusion Services Berne and Zurich. Donors investigated were 652 RhD negative, but RhC and/or RhE positive, 17,391 mainly Rhccee, and 8200 with normal RhCcEe phenotype distribution. In study I single samples, in studies II and III minipools of 24 and 20 donor samples were tested, respectively. Among 26,243 phenotypically RhD negative blood donors, 65 carriers of RHD alleles were identified. Thirty-one of them were redefined as RhD positive.

Prevalence of anti-tick-borne encephalitis virus (TBEV) antibodies in Swiss blood donors in 2014-2015.

BACKGROUND: Disease morbidity of tick-borne encephalitis (TBE) has been increasing over the last decades. Since the 1990s, however, no extensive seroprevalence studies on TBE in humans have been performed in Switzerland. Here we assessed the prevalence of anti-TBE virus (TBEV) antibodies among different groups of the Swiss blood donor population. MATERIALS AND METHODS: The study was carried out from July 2014 to January 2015. Blood donors participating in the study (n=9,328) were asked to fill in a questionnaire relating to vaccination against or infection with different flaviviruses, and blood samples were collected. All samples were screened for the presence of anti-TBEV IgG antibodies using ELISA testing. Seropositivity rates in different groups of blood donors were compared using Chi square tests with Bonferroni correction. RESULTS: In 2014 and 2015, 24.6% of healthy Swiss blood donors indicated vaccination against TBE. Among vaccinated blood donors, antibody prevalence was significantly higher in younger (<40y: 85.3%) than older individuals (≥40 to <55y: 80.0%, ≥55y: 76.7%; p=0.005). In non-vaccinated individuals, antibody prevalence was significantly higher in younger (<40y: 10.0%) than older (≥40 to <55y: 4.0%, ≥55y: 3.9%; p<0.005), male (6.8%) than female (3.7%, p<0.0001), and blood donors from endemic (7.0%) than border (6.2%) or non-endemic regions (4.2%, p<0.001). Possible asymptomatic infection, as defined by positive IgG ELISA results in blood donors indicating no vaccination against TBEV, was found in 5.6%. DISCUSSION: Our data importantly complement the knowledge on TBEV vaccination rates and estimate the frequency of subclinical TBE in Switzerland.

Risk factors for anastomotic leakage after rectal cancer resection and reconstruction with colorectostomy. A retrospective study with bootstrap analysis.

BACKGROUND: This study was designed to apply modern statistical methods to evaluate risk factors for anastomotic leakage after rectal cancer resection in a retrospective cohort of patients who received a colorectostomy. Whereas a diverting stoma and tumor height are considered proven risk factors for anastomotic leakage, a lack of evidence about additional risk factors persists. METHODS: In a single-center study, 527 consecutive patients who received a colorectostomy after rectal cancer resection between 1991 and 2008 were retrospectively assessed. In addition to traditional uni- and multivariate regression, locally weighted scatterplot smoothing (LOWESS) regression and bootstrap analysis were applied to increase internal validity. RESULTS: Anastomotic leakage occurred in 70 patients (13.3%; 95% confidence interval (CI), 10.5-16.5%) and mortality was 2.5% (95% CI, 1.4-4.2%). Diverting stoma (odds ratio (OR), 0.4; 95% CI, 0.17-0.61) and tumor height (OR, 0.88; 95% CI, 0.8-0.94) were proven to be protective. Neoadjuvant radiotherapy (OR, 2.15; 95% CI, 1.58-4.24) and intraoperative blood loss (OR, 1.05; 95% CI, 1.02-1.09) had a derogatory effect. Bootstrap analysis identified pre-existing vascular disease (95.5%), more advanced UICC stage III or IV tumors (95.7% or 91.5%, respectively), and intraoperative (96.1%) and postoperative (99.4%) blood substitution as harmful. Both intraoperative and postoperative blood substitution caused a dose-dependent increase in risk. CONCLUSIONS: Applying statistical resampling methods identified intraoperative blood loss, blood substitution, vascular disease, and advanced UICC stage as risk factors for anastomotic leakage. Greater distances between the tumor and the anal verge and performance of a diverting stoma were associated with a decreased risk of anastomotic leakage.

Red blood cell use in Switzerland: trends and demographic challenges.

BACKGROUND: Several studies have raised concerns that future demand for blood products may not be met. The ageing of the general population and the fact that a large proportion of blood products is transfused to elderly patients has been identified as an important driver of blood shortages. The aim of this study was to collect, for the first time, nationally representative data regarding blood donors and transfusion recipients in order to predict the future evolution of blood donations and red blood cell (RBC) use in Switzerland between 2014 and 2035. MATERIALS AND METHODS: Blood donor and transfusion recipient data, subdivided by the subjects' age and gender were obtained from Regional Blood Services and nine large, acute-care hospitals in various regions of Switzerland. Generalised additive regression models and time-series models with exponential smoothing were employed to estimate trends of whole blood donations and RBC transfusions. RESULTS: The trend models employed suggested that RBC demand could equal supply by 2018 and could eventually cause an increasing shortfall of up to 77,000 RBC units by 2035. DISCUSSION: Our study highlights the need for continuous monitoring of trends of blood donations and blood transfusions in order to take proactive measures aimed at preventing blood shortages in Switzerland. Measures should be taken to improve donor retention in order to prevent a further erosion of the blood donor base.