Neuropathies related to hepatitis E virus infection: A prospective, matched case-control study.

BACKGROUND: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking. AIMS: To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population. METHODS: Swiss multicenter, prospective, observational, matched case-control study over 3 years (September 2019-October 2022). Neurological cases with NA, GBS, or Bell's palsy were recruited within 1 month of disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti-HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by real-time polymerase chain reaction (RT-PCR). RT-PCR was performed on sera to confirm IgM positivity. RESULTS: We included 180 patients (59 GBS, 51 NA, 70 Bell's palsy cases) and corresponding matched controls (blood donors) with median age 51 years for both groups and equal gender distribution. Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti-HEV IgM-positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p = 0.027, Fisher's exact test; Cramér's V = -0.25) was observed only between acute HEV infection and NA. CONCLUSION: This prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy.

Epidemiology of HEV Infection in Blood Donors in Southern Switzerland.

From 2014 to 2016, the number of hepatitis E virus (HEV) infections in southern Switzerland increased dramatically and suggested food as a potential infection reservoir. We evaluated the effects of food control measures introduced to limit HEV infections, assessing anti-HEV IgG and IgM rates in blood donors before and after the implementation of food control measures in 2017. From 2012 to 2013, we screened 1283, and from 2017 to 2019, we screened 1447 donors for IgG and IgM antibodies. No statistically significant differences were detected for IgG (32.8% from 2012 to 2013 vs. 31.1% from 2017 to 2019, p = 0.337) or IgM rates (2.0% from 2012 to 2013 vs. 2.8% from 2017 to 2019, p = 0.21). Rural provenience and age > 66 are predictors for positive IgG serology. A total of 5.9% of 303 donors included in both groups lost IgG positivity. We also determined nucleic acid testing (NAT) rates after the introduction of this test in 2018, comparing 49,345 donation results from southern Switzerland with those of 625,559 Swiss donor controls, and only 9 NAT-positive donors were found from 2018 to 2023. The high HEV seroprevalence in southern Switzerland may depend on different food supply chains in rural and urban areas. Local preventive measures probably have a limited impact on blood HEV risk; thus, continuous NAT testing is recommended.

Do quantitative levels of antispike-IgG antibodies aid in predicting protection from SARS-CoV-2 infection? Results from a longitudinal study in a police cohort.

In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of antispike (anti-S1) IgG antibody levels, (ii) to evaluate whether the levels were associated with protection from SARS-CoV-2 infection, and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis before the Omicron surge included 3219, 2310, and 895 reactive serum samples from 949, 919, and 895 individuals, respectively. Mixed-effect linear, mixed-effect time-to-event, and logistic regression models were used to achieve the objectives. Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Higher antibody levels were significantly associated with protection from SARS-CoV-2 infection (0.89, 95% confidence interval [CI] 0.82-0.97), and the association was higher during the time period when Omicron was predominantly circulating compared with the ones when Alpha and Delta variants were predominant (adjusted hazard ratio for interaction 0.66, 95% CI 0.53-0.84). In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by approximately 20%-30% for 90 days. Though, such high levels were only found in 1.9% of the samples before the Omicron surge, and they were not durable for 3 months. Anti-S1 IgG antibody levels are statistically associated with protection from SARS-CoV-2 infection. However, the prediction impact of the antibody level findings on infection protection is limited.

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.

Evolution of Blood Safety in Switzerland over the Last 25 Years for HIV, HCV, HBV and Treponema pallidum.

During the last few decades, efforts to increase the safety of blood and blood products have mainly focused on preventing the viral infections HCV, HIV, HBV and Treponema pallidum. The evolution of these approaches and the achieved increase in safety is shown for the last 25 years in Switzerland. In detail, the prevalences and incidences of the infection disease and the theoretical estimated residual risks (RR) of these blood-borne infections are presented. Prevalences, incidences and, in particular, the RR have decreased considerably over the last 25 years. This was achieved primarily by the adoption of strict criteria for the selection of blood donors, refined questionnaires, the introduction of increasingly sensitive serological screening tests and the implementation of nucleic acid testing (NAT) for these blood-borne pathogens. These NAT assays have significantly shortened the window period between infection and the first detection of the infectious agent in the blood of an infected individual. A form of "real life" comparison or confirmation is provided by the reported lookback procedures (LBP) and the haemovigilance data of the Swiss competent authority, Swissmedic. These data are in agreement, and thus support the very low prevalences, incidences and RR.

Serosurveillance after a COVID-19 vaccine campaign in a Swiss police cohort.

INTRODUCTION: To assess the risk for COVID-19 of police officers, we are studying the seroprevalence in a cohort. The baseline cross-sectional investigation was performed before a vaccination campaign in January/February 2021, and demonstrated a seroprevalence of 12.9%. Here, we demonstrate serosurveillance results after a vaccination campaign. METHODS: The cohort consists of 1022 study participants. The 3- and 6-month follow-up visits were performed in April/May and September 2021. Data on infection and vaccination rates were obtained via measuring antibodies to the nucleocapsid protein and spike protein and online questionnaires. RESULTS: The mean age of the population was 41 (SD 8.8) years, 72% were male and 76% had no comorbidity. Seroconversion was identified in 1.05% of the study population at the 3-month visit and in 0.73% at the 6-month visit, resulting in an infection rate of 1.8% over a time period of 6 months. In comparison, the infection rate in the general population over the same time period was higher (3.18%, p = .018). At the 6-month visit, 77.8% of participants reported being vaccinated once and 70.5% twice; 81% had an anti-S antibody titer of >250 U/ml and 87.1% of ≥2 U/ml. No significant association between infection and job role within the department, working region, or years of experience in the job was found. Anti-spike antibody titers of vaccinated study participants showed a calculated decreasing trend 150-200 days after the second vaccine dose. CONCLUSION: These data confirm the value of the vaccination campaign in an exposed group other than healthcare professionals.

A Multidimensional Cross-Sectional Analysis of Coronavirus Disease 2019 Seroprevalence Among a Police Officer Cohort: The PoliCOV-19 Study.

BACKGROUND: Protests and police fieldwork provide a high-exposure environment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. In this cross-sectional analysis, we investigated the seroprevalence among a police cohort, and sociodemographic, work, and health-related factors associated with seropositivity. METHODS: Study participants were invited for serological testing of SARS-CoV-2 and to complete online questionnaires. Serum neutralization titers toward the wild-type SARS-CoV-2 spike protein (expressing D614G) and the Alpha and Beta variants were measured in seropositive study participants. RESULTS: A total of 978 police personnel representing 35% of the entire staff participated from February to March 2021. The seroprevalence was 12.9%. It varied by geographic region, ranged from 9% to 13.5% in 3 regions, including the city; and was 22% in Bernese Seeland/Jura with higher odds for seropositivity (odds ratio [OR], 2.38 [95% confidence interval {CI}, 1.28-4.44], P=.006). Job roles with mainly office activity were associated with a lower risk of seropositivity (OR, 0.33 [95% CI, .14-.77], P=.010). Self-reported compliance with mask wearing during working hours was 100%; 45% of seropositive vs 5% of seronegative participants (P<.001) reported having had contact with a proven coronavirus disease 2019 (COVID-19) case living in the same household prior to serological testing. The level of serum antibody titers correlated with neutralization capacity. Antibodies derived from natural SARS-CoV-2 infection effectively neutralized the SARS-CoV-2 spike protein, but were less effective against the Alpha and Beta variants. CONCLUSIONS: The seroprevalence of anti-SARS-CoV-2 antibodies of police officers was comparable to that reported in the general population, suggesting that the personal protective equipment of the police is effective, and that household contacts are the leading transmission venues. The level of serum antibody titers, in particular that of anti-spike antibodies, correlated well with neutralization capacity. Low antibody titers acquired from natural infection were not effective against variants. CLINICAL TRIALS REGISTRATION: NCT04643444.

Comparison of a New IgG-EIA for the Detection of Anti-Plasmodium Antibodies with Two Currently Used Assays.

BACKGROUND: Malaria is a mosquito-borne infectious disease caused by protozoan parasites of the genus Plasmodium. As migration of populations from endemic areas to Europe and overseas recreational travel to endemic regions increase, there is also a growing risk of transfusion-transmitted tropical diseases by blood components. MATERIAL AND METHODS: In the present study two routine Plasmodium spp. ELISA (CAPTIA™ Malaria EIA, Trinity Biotech, and Malaria EIA, BioRad) were compared with a new commercial ELISA (ELISA IgG, EUROIMMUN). From December 1, 2015 until November 30, 2016, 1,096 plasma samples from blood donors with a potential risk of malaria infection were collected at two blood transfusion centres in Germany and Switzerland. RESULTS: The samples were tested comparatively with the ELISA from EUROIMMUN and the routine test used at the respective centre. Thirty-four of 595 (5.7%) tested blood samples from centre 1 and 49 of 501 (9.8%) tested blood samples from centre 2 showed reactivity on either or both ELISAs. All 83 reactive samples were sent for confirmation to the Diagnostic Centre of the Swiss Tropical and Public Health Institute (Swiss TPH) in Basel, Switzerland. Sixteen samples, which previously were reactive in the routine Plasmodium spp. EIA assays, were proven positive after confirmation testing (i.e., 4 positive and 12 inconclusive results), indicating an anti-Plasmodium antibody prevalence in blood donations of 1.5%. From these 16 reactive samples, 13 were also detected by the index test, resulting in an assay sensitivity of 81.2%. A specificity of 98.6% was calculated (1,065/1,080 confirmed negative samples). The overall agreement with the reference centre was 95.8% in centre 1 and 94% in centre 2. CONCLUSION: The comparison of the new EUROIMMUN ELISA and the established CAPTIA™ Malaria EIA (Trinity Biotech) and Malaria EIA (BioRad) used for routine blood donor screening in two laboratory blood donation centres revealed that all tested ELISAs show comparable sensitivities and are equally suitable for anti-Plasmodium antibody screening in blood banks.

Transfusion-transmitted cytomegalovirus: behaviour of cell-free virus during blood component processing. A study on the safety of labile blood components in Switzerland.

BACKGROUND: Nowadays, most blood products are leukocyte-reduced. After this procedure, the residual risk for transfusion transmitted cytomegalovirus (TT-CMV) is mostly attributed to cell-free viruses in the plasma of blood donors following primary infection or viral reactivation. Here, objectives are: 1) to study the behaviour of cell-free CMV through the blood component processing; 2) to determine the anti-CMV seroprevalence, the level of viremia, the window-period in blood donor population; and 3) to identify cases of TT-CMV in bone marrow transplant (BMT) recipients. MATERIALS AND METHODS: Cell-free CMV was injected into blood bags originating from regular donors. Blood components were processed according to either the CompoSelect® or the CompoFlow® (Fresenius Kabi AG) techniques. Samples were analysed at each step for presence of virus DNA using quantitative polymerase chain reaction (PCR). The anti-CMV seroprevalence in our donor population was taken from our donor data system. The viremia was assessed in pooled plasmas samples from routine donations by quantitative PCR. Medical charts of 165 BMT anti-CMV seronegative recipients/anti-CMV seronegative donors who received CMV-unscreened blood products were reviewed. RESULTS: Cell-free CMV passes without any decrease in viral load through all stages of blood processing. The anti-CMV seroprevalence was 46.13%. Four DNA positive samples out of 42,240 individual blood donations were identified (0.009%); all had low levels of viremia (range 11-255 IU/mL). No window-period donation was identified. No TT-CMV was found. DISCUSSION: Cell-free CMV remains a concern with current blood component processing as it passes through all the processes. However, since low levels of CMV DNA were identified in the donations tested, and no BMT recipients had TT-CMV, the residual threat of TT-CMV after leukocyte reduction appears to be very low.

Safe-Testing Algorithm for Individual-Donation Nucleic Acid Testing: 10 Years of Experience in a Low-Prevalence Country.

INTRODUCTION: A highly sensitive and specific nucleic acid test (NAT) for the blood-borne viruses human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) is essential for the safety of blood components. Since more than 2 decades, NAT screening of blood donations has become standard in developed countries that have implemented the individual-donation (ID-NAT) and mini-pool NAT (MP-NAT) approaches. With this powerful technique, confirmation of initial reactive (IR) NAT samples becomes a challenge. Different algorithms are currently in use to eliminate false reactive results. To show that the algorithm implemented in 2007, that uses repeat testing of IR samples in duplicate runs, is a safe strategy, especially in low endemic countries, data from a 10-year experience of ID-NAT were extensively analyzed when follow-up data were available. METHODS: From July 2007 to December 2014, the Procleix Ultrio assay on a Procleix Tigris system, and from January 2015 to December 2017, the cobas MPX on a cobas 8800 platform, were used for ID-NAT screening. All IR samples were subjected to repeat testing in duplicate independent runs. Only when both tests remained negative were the products released. Donor data from the last 10 years were investigated retrospectively, looking for the reoccurrence of a reactive result in a follow-up sample. Only those donors with at least an x + 1 donation result were included for the confirmation of a false reactive result. RESULTS: From the 1,830,657 donations tested, 2,450 samples were IR (0.13%); only 228 were repeat reactive ([RR], 18 HIV, 61 HCV, and 149 HBV samples), and 2,222 were non-RR (0.12%). Follow-up data were available from 1,267 donors (57%) for further analysis. All except one of these donors were ID-NAT-negative in all follow-up samples. The one exception was from a donor who acquired a fresh HBV infection 10 years after the IR donation (in the x + 28 donation) and subsequently seroconverted. Subsequent serological tests from all succeeding donations (x + 1, x + 2, etc.) were negative in all the other cases, proving that no seroconversion took place after the IR ID-NAT result. CONCLUSIONS: The algorithm to deal with IR ID-NAT donations using duplicate repeat testing is very safe and cost-effective in low-prevalence countries. There is no unnecessary destruction of blood products, no counseling of false reactive donors, and also no need to add further complexity to the screening algorithm.

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.

Parvovirus B19 Passive Transmission by Transfusion of Intercept® Blood System-Treated Platelet Concentrate.

BACKGROUND: Pathogen reduction methods for blood components are effective for a large number of viruses though less against small, non-enveloped viruses such as Parvovirus B19 (B19V). This article describes the passive transmission by transfusion of two B19V-contaminated pooled platelet concentrates (PCs) which were treated with the Intercept® blood pathogen reduction system. CASE REPORTS: Two transfusion cases of B19V-contaminated Intercept-treated pooled PCs were described. Due to the analysis delay, the PCs were already transfused. The viral content of each donation was 4.87 × 10(10) IU/ml in case 1and 1.46 × 10(8) IU/ml in case 2. B19V (52 IU/ml) was detected in the recipient of the case 1 PC, whereas no virus could be detected in the case 2 PC recipient. A B19V IgM response and a transient boost of the underlying B19V IgG immune status and was observed in recipient 1. Recipient of the case 2 PC remained B19V IgG- and IgM-negative. B19V DNA sequence and phylogenetic analysis revealed a 100% homology between donor and recipient. CONCLUSION: This report describes passive B19V transmission by a PC with very high B19 viral load which elicited a transient boost of the B19V immunity, but not by a PC with a lower B19V content, suggesting that there is a B19 viral load threshold value at which B19V inactivation is exceeded.

Comparison of a conventional HIV 1/2 line immunoassay with a rapid confirmatory HIV 1/2 assay.

The performance of the rapid confirmatory HIV 1/2 assay Geenius was compared with the conventional HIV 1/2 line immunoblot (INNO-LIA HIV I/II Score). One hundred HIV 1/2 confirmed positive samples from donors and patients and 136 negative screening samples from blood donors were evaluated with both assays. A 20 member performance panel consisting of different HIV 1 and 2 subtypes was also analysed. Ninety-nine of the confirmed HIV positive samples were positive with both assays. One sample was positive with the INNO-LIA HIV I/II Score but indeterminate with the Geenius HIV 1/2. From 136 negative blood donor samples (negative with a combo HIV assay and a highly sensitive ID-NAT), 125 were concordant negative. Six and five samples were incorrectly indeterminate with the INNO-LIA HIV I/II Score and the Geenius HIV 1/2, respectively. One sample was weak positive with the INNO-LIA HIV I/II Score but negative with the Geenius HIV 1/2. The 20 member performance showed equivalent results with both assays. The rapid assay showed a comparable sensitivity and specificity for confirmation for positive and negative HIV donor and patient samples as well for a 20 member performance panel.

Implementation of a mandatory donor RHD screening in Switzerland.

Starting in 2013, blood donors must be tested at least using: (1) one monoclonal anti-D and one anti-CDE (alternatively full RhCcEe phenotyping), and (2) all RhD negative donors must be tested for RHD exons 5 and 10 plus one further exonic, or intronic RHD specificity, according to the guidelines of the Blood Transfusion Service of the Swiss Red Cross (BTS SRC). In 2012 an adequate stock of RHD screened donors was built. Of all 25,370 RhD negative Swiss donors tested in 2012, 20,015 tested at BTS Berne and 5355 at BTS Zürich, showed 120 (0.47%) RHD positivity. Thirty-seven (0.15%) had to be redefined as RhD positive. Routine molecular RHD screening is reliable, rapid and cost-effective and provides safer RBC units in Switzerland.

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.

Serologic and molecular investigations of DAR1 (weak D Type 4.2), DAR1.2, DAR1.3, DAR2 (DARE), and DARA.

BACKGROUND: The partial D variant DAR1 (weak D Type 4.2) is caused by three single-point mutations, 602C>G, 667T>G, and 1025T>C. Here we report a molecular study on different D variants belonging to the DAR category (DAR1, DAR1.2, DAR1.3, and DAR2) and their serologic data. STUDY DESIGN AND METHODS: A total of 42 samples belonging to the DAR category were screened for the presence of the silent mutations 744C>T and 957G>A. The samples were phenotyped for RhD and RhCE, characterized for RhD epitope expression, and sequenced for RHD exons. Flow cytometry was performed to determine RhD antigen density. RESULTS: The silent mutation 744C>T was found in all six samples previously typed as RHD*DAR2 (602C>G, 667T>G, 957G>A, 1025T>C). In addition to the three nucleotide changes originally reported for the RHD*DAR1 allele, the silent mutations 744C>T and 957G>A were found in 14 of 16 samples previously typed as RHD*DAR1. In the remaining two samples one additional silent mutation, 744C>T, was found. Serologically the DAR1.2 and DAR1.3 samples analyzed in this study showed no distinct difference in their anti-D reaction pattern compared to each other. The anti-D reaction pattern of DARA/DAR2 showed some distinct differences compared to those of DAR1.2 and DAR1.3. CONCLUSION: RHD*DARA and RHD*DAR2 are the same allele. Furthermore, the alleles RHD*DAR1.2 and RHD*DAR1.3 both exist; however, the silent mutation 957G>A (V319) showed no influence on the RhD phenotype.

Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion-transmitted hepatitis B virus infection in Switzerland, a low-endemic region.

BACKGROUND: The risk of transfusion-transmitted hepatitis B virus (HBV) in Switzerland by testing blood donors for hepatitis B surface antigen (HBsAg) alone has been historically estimated at 1:160,000 transfusions. The Swiss health authorities decided not to introduce mandatory antibody to hepatitis B core antigen (anti-HBc) testing but to evaluate the investigation of HBV nucleic acid testing (NAT). STUDY DESIGN AND METHODS: Between June 2007 and February 2009, a total of 306,000 donations were screened routinely for HBsAg and HBV DNA by triplex individual-donation (ID)-NAT (Ultrio assay on Tigris system, Gen-Probe/Novartis Diagnostics). ID-NAT repeatedly reactive donors were further characterized for HBV serologic markers and viral load by quantitative polymerase chain reaction. The relative sensitivity of screening for HBsAg, anti-HBc, and HBV DNA was assessed. The residual HBV transmission risk of NAT with or without anti-HBc and HBsAg was retrospectively estimated in a mathematical model. RESULTS: From the 306,000 blood donations, 31 were repeatedly Ultrio test reactive and confirmed HBV infected, of which 24 (77%) and 27 (87%) were HBsAg and anti-HBc positive, respectively. Seven HBV-NAT yields were identified (1:44,000), two pre-HBsAg window period (WP) donations (1:153,000) and five occult HBV infections (1:61,000). Introduction of ID-NAT reduced the risk of HBV WP transmission in repeat donors from 1:95,000 to 1:296,000. CONCLUSIONS: Triplex NAT screening reduced the HBV WP transmission risk approximately threefold. NAT alone was more efficacious than the combined use of HBsAg and anti-HBc. The data from this study led to the decision to introduce sensitive HBV-NAT screening in Switzerland. Our findings may be useful in designing more efficient and cost-effective HBV screening strategies in low-prevalence countries.

Molecular epidemiology of Campylobacter jejuni populations in dairy cattle, wildlife, and the environment in a farmland area.

We describe a cross-sectional study of the molecular epidemiology of Campylobacter jejuni in a dairy farmland environment, with the aim of elucidating the dynamics of horizontal transmission of C. jejuni genotypes among sources in the area. A collection of 327 C. jejuni isolates from cattle, wildlife, and environmental sources in a 100-km(2) area of farmland in northwest England was characterized by multilocus sequence typing. A total of 91 sequence types and 18 clonal complexes were identified. Clonal complexes ST-21, ST-45, and ST-61, which have been frequently associated with human disease, were the most commonly recovered genotypes in this study. In addition, widely distributed genotypes as well as potentially host-associated genotypes have been identified, which suggests that both restricted and interconnecting pathways of transmission may be operating in the dairy farmland environment. In particular, the ST-61 complex and the ST-21 complex were significantly associated with cattle. In contrast, complex strains ST-45, ST-952, and ST-677 were isolated predominantly from wild birds, wild rabbits, and environmental water. A considerable number of novel sequence types have also been identified, which were unassigned to existing clonal complexes and were frequently isolated from wildlife and environmental sources. The segregated distribution of genotypes among samples from different sources suggests that their transmission to humans is perhaps via independent routes. Insight into the dynamics and interactions of C. jejuni populations between important animal reservoirs and their surrounding environment would improve the identification of sources of Campylobacter infection and the design of control strategies.