Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study.

BACKGROUND: Viruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults. METHODS: We collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls. RESULTS: We enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (P = .016, R2 = .01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC] .83), viruses (AUC .95) or mixed origin (AUC .81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC .93) separation between cases and controls. CONCLUSIONS: Relative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices.

Balancing non-discriminatory donor selection and blood safety in the Netherlands: Evaluation of an individual risk assessment of sexual behavior.

BACKGROUND: To better balance the safety of the blood supply and the inclusion of men who have sex with men (MSM), further improvements are needed to the risk management strategy employed in the Netherlands to reduce transfusion-transmissible infections (TTIs). A gender-neutral individual risk assessment could provide a solution by determining donor eligibility based on sexual behaviors known to increase the risk of TTIs. Our objective is to estimate the proportion of blood donors that would be deferred by such an assessment, as well as their discomfort answering such questions. STUDY DESIGN AND METHODS: Two surveys were distributed in May 2020 to assess sexual behavior in blood donors in the last 4, 6, and 12 months, as well as their discomfort reporting such information. A combination of both surveys measured the extent to which discomfort was associated with reporting sexual behavior. A high-risk sexual behavior pattern was defined as having had multiple sexual partners and having engaged in anal sex, without consistent condom use. RESULTS: Of all 2177 participating whole blood donors, 0.8% report engaging in high-risk sexual behaviors over the last 4 months and would therefore be ineligible to donate. When accounting for the additional proportion of donors that reported such questions would stop them from donating, 2.0% and 3.2% of female and male donors, respectively, would be lost. DISCUSSION: Gender-neutral eligibility criteria based on high-risk sexual behaviors may reduce the overall number of eligible donors in the Netherlands, but could make blood donation more accessible to a broader group of donors.

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.

Diagnostic Performance of the Novel BioPlex Lyme Serological Assays in European Patients with Lyme Disease.

Serodiagnosis of Lyme borreliosis (LB) comes with several drawbacks, among which is limited sensitivity in early disease. This study assesses the sensitivity and specificity of the novel BioPlex 2200 Lyme IgG and Lyme IgM assays. It also assesses potential improvements to the assays through receiver-operating characteristic (ROC) analysis. The BioPlex assays were performed on sera of 158 Dutch patients with physician-confirmed LB (both early localized and disseminated), 800 healthy blood donors from the Netherlands, and 90 cross-reactive controls. The BioPlex (Biopl) assays were compared with two commercial enzyme immunoassays (Euroimmun [Eur]/C6-ELISA) and one immunoblot (recomLine). The highest sensitivity in early LB was achieved with the BioPlex assays, which outperformed the Euroimmun and C6-ELISA (Biopl: 81/88, 92.1%; Eur: 64/88, 72.7%; C6: 72/88, 81.8%). Sensitivity of all assays was comparable in patients with disseminated LB. The BioPlex assays were outperformed in terms of specificity (all healthy blood donors, Biopl: 571/800, 71.4%; Eur: 711/800, 88.9%; C6: 727/800, 90.9%), but further analyses showed promising avenues following cutoff optimization. ROC analysis showed that 2/6 antigens of the combined BioPlex IgG and IgM assays had significantly higher areas under the curve (AUCs) than those of the other analyses. Potential modified versions of the assays based on these antigens largely outperformed the Euroimmun and C6-ELISA in EM patients (Biopl: 81/80, 92.1%) while maintaining a comparable or even higher specificity (Biopl: 714/800, 89.3%). The BioPlex 2200 Lyme IgG and Lyme IgM assays are promising tools for the serodiagnosis of early LB, with the potential to be used as a standalone test. Further research is necessary to validate the findings of this discovery cohort.

Increasing the Efficiency of a National Laboratory Response to COVID-19: a Nationwide Multicenter Evaluation of 47 Commercial SARS-CoV-2 Immunoassays by 41 Laboratories.

In response to the worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent antibody tests that flooded the market, a nationwide collaborative approach in the Netherlands was employed. Forty-one Dutch laboratories joined forces and shared their evaluation data to allow for the evaluation of a quantity of serological assays for SARS-CoV-2 that exceeds the capacity of each individual laboratory. As of April 2020, these performance data had been aggregated and shared in regularly updated reports with other laboratories, Dutch government, public health organizations, and the public. This frequently updated overview of assay performance increased the efficiency of our national laboratory response, supporting laboratories in their choice and implementation of assays. Aggregated performance data for 47 immunoassays for SARS-CoV-2 showed that none of the evaluated immunoassays that detect only IgM or IgA met the diagnostic criteria, indicating that they are not suitable for diagnosing acute infections. For the detection of IgG, only the Biozek Corona virus COVID rapid test, Euroimmun SARS-CoV-2 IgG, and Wantai SARS-CoV-2 antibody (Ab) ELISA met predefined performance criteria in hospitalized patients where samples were collected 14 days post-onset of symptoms (DPO), while for patients with mild or asymptomatic infections, only the Wantai SARS-CoV-2 Ab ELISA met the predefined performance criteria if samples were collected 14 days postonset. Here, we describe this unique nationwide collaboration during the onset of the COVID-19 pandemic; the collected data and their results are an example of what can be accomplished when forces are joined during a public health crisis.

Blood donor screening in the Netherlands: Universal anti-HBc screening in combination with HBV nucleic acid amplification testing may allow discontinuation of hepatitis B virus antigen testing.

BACKGROUND: In the Netherlands, blood donor screening for hepatitis B virus (HBV) consists of HBsAg screening since the 1970s, HBV DNA minipool testing (MP-NAT) since 2008, and anti-HBc screening since 2011. Anti-HBc reactivity causes deferral only if anti-HBs titers are <200 IU/mL, or when anti-HBc was acquired during follow-up. STUDY DESIGN AND METHODS: Over 5.5 million donations from 582,459 Dutch donors were screened for HBV DNA, HBsAg, anti-HBc, and, if anti-HBc positive, also for anti-HBs. The added value, expressed as the yield of (potentially) infectious and/or recent HBV infections versus unnecessary donor loss, was evaluated for each of the three HBV screening tests. RESULTS: HBV donor screening identified 89 HBV-infected donors with at least two reactive HBV markers (MP-NAT, HBsAg and/or anti-HBc). Single HBV-marker yield was: 5 MP-NAT-only, 0 HBsAg-only, and 20 anti-HBc-only donors. In addition, anti-HBc screening yielded 1,067 potentially infectious donors at risk for occult HBV infection (OBI). In total, 4,126 (0.71%) donors were anti-HBc-reactive at first-time screening, and 1,098 (0.19%) seroconverted during follow-up. Anti-HBc-related donor loss was limited to 2,627 (0.45%) donors using anti-HBs titers and two-strike programs. Donor loss due to MP-NAT and HBsAg screening was extremely low: 0 and 128 donors, respectively. CONCLUSION: HBV donor screening could be limited to MP-NAT and anti-HBc screening. MP-NAT and anti-HBc improved blood safety by intercepting infectious donations from donors with recent infection or OBI, while HBsAg did not. Unnecessary donor loss related to anti-HBc screening is substantial but does not endanger the continuity of the blood supply.

Borrelia burgdorferi sensu lato seroconversion after intravenous immunoglobulin treatment: A cohort study.

OBJECTIVE: Intravenous immunoglobulin (IVIg) consists of pooled donor immunoglobulins (IgG), possibly including anti-Borrelia burgdorferi (Bbsl) antibodies. Apparent IVIg-related Bbsl seroconversion could lead to incorrect diagnosis of Lyme borreliosis. This cohort study was designed to determine how often IVIg treatment leads to apparent Bbsl seroconversion and whether antibodies disappear post-treatment. METHODS: Sera from chronic inflammatory demyelinating polyneuropathy (CIDP) and myositis patients were analyzed, drawn pre-treatment and 6-12 weeks after the start of IVIg. In patients with apparent seroconversion, follow-up samples after treatment withdrawal were analyzed, if available. Patients treated with corticosteroids were included as controls. A two-tier protocol was used for serological testing consisting of the C6 Lyme ELISA (Oxford Immunotec) and confirmation by immunoglobulin M (IgM) and immunoglobulin G (IgG) immunoblot (Mikrogen® ). RESULTS: We included 61 patients: 51 patients were treated with IVIg and 10 with dexamethasone. Of the patients treated with IVIg, 42 had CIDP (82%) and were treated with Nanogam® (Sanquin Plasma Products). Nine patients had myositis (18%) and were treated with Privigen® (CSL Behring). Anti-Bbsl IgG seroprevalence pre-treatment was 3% (2/61). Apparent seroconversion during IVIg treatment occurred in 39% (20/51) of patients, all treated with Nanogam. Post-treatment seroreversion occurred in 92% (12/13) of patients with available follow-up samples; in 78% (7/9) seroreversion was observed within 3 months. CONCLUSIONS: Transient presence of anti-Bbsl IgG antibodies after IVIg is regularly observed. This effect appears to be dependent on the IVIg brand, probably reflecting variation in Bbsl exposure of plasma donors. Lyme borreliosis serological testing during, and weeks to months after, IVIg is therefore of limited utility.

Hepatitis B core related antigen in relation to intrahepatic and circulating viral markers, before and after combination therapy.

INTRODUCTION AND OBJECTIVES: Covalently closed circular (ccc)DNA acts as a viral reservoir in the liver of patients with a chronic hepatitis B (CHB) infection and can only be quantified in liver biopsies. Hepatitis B core-related antigen (HBcrAg) levels in plasma/serum have been proposed to reflect intrahepatic cccDNA-levels and may therefore monitor treatment efficacy. This study aimed to validate the relationship between HBcrAg and other intrahepatic and circulating viral markers in CHB patients with high viral load, before and after combination treatment. MATERIALS AND METHODS: Plasma/serum levels of HBcrAg, HBsAg, HBV-DNA, and HBV pregenomic RNA (HBV-pgRNA), and intrahepatic cccDNA and HBV-DNA levels and fibrosis scores were measured in 89 CHB patients with HBV-DNA levels of >100,000 copies/mL (17,182 IU/mL). Measurements were done before and after a 48-week treatment with pegylated interferon alfa-2a and adefovir in a prospective study (ISRCTN77073364). RESULTS: Baseline HBcrAg-values correlated strongly with intrahepatic cccDNA (ρ 0.77, p < 0.001), intrahepatic HBV-DNA (ρ 0.73, p < 0.001) and plasma/serum HBV-DNA (ρ 0.80, p < 0.001), HBV-pgRNA (ρ 0.80, p < 0.001), and to lesser extend HBsAg (ρ 0.56, p < 0.001). Baseline HBcrAg-levels could not predict functional cure (FC) but HBcrAg-levels declined more strongly in patients who developed FC or HBeAg-loss. Furthermore, most correlations persisted at the end of treatment and follow-up. CONCLUSIONS: HBcrAg reflects cccDNA transcription activity more accurately than HBsAg and may replace HBV-DNA as a marker during future treatment regimens, especially when cccDNA transcription is targeted or nucleot(s)ide analogues are included in the treatment regime.

First autochthonous human West Nile virus infections in the Netherlands, July to August 2020.

In October 2020, the first case of autochthonous West Nile virus neuroinvasive disease was diagnosed in the Netherlands with a presumed infection in the last week of August. Investigations revealed five more cases of local West Nile virus (WNV) infection. The cases resided in a region where WNV was detected in a bird and mosquitoes in August 2020. Molecular analysis was successful for two cases and identified the presence of WNV lineage 2.

Infection Pressure in Men Who Have Sex With Men and Their Suitability to Donate Blood.

BACKGROUND: Deferral of men who have sex with men (MSM) from blood donation is highly debated. We therefore investigated their suitability to donate blood. METHODS: We compared the antibody prevalence of 10 sexually and transfusion-transmissible infections (TTIs) among 583 MSM and 583 age-matched repeat male blood donors. MSM were classified as low risk (lr) or medium-to-high risk (hr) based on self-reported sexual behavior and as qualified or unqualified using Dutch donor deferral criteria. Infection pressure (IP) was defined as the number of antibody-reactive infections, with class A infections (human immunodeficiency virus-1/2, hepatitis B virus, hepatitis C virus, human T-cell lymphotropic virus-1/2, syphilis) given double weight compared to class B infections (cytomegalovirus, herpes simplex virus-1/2, human herpesvirus 8, hepatitis E virus, parvovirus B19). RESULTS: Donors had a lower median IP than qualified lr-MSM and qualified hr-MSM (2 [interquartile range {IQR}, 1-2] vs 3 [IQR, 2-4]; P < .001). Low IP was found in 76% of donors, 39% of qualified lr-MSM, and 27% of qualified hr-MSM. The prevalence of class A infections did not differ between donors and qualified lr-MSM but was significantly higher in qualified hr-MSM and unqualified MSM. Recently acquired class A infections were detected in hr-MSM only. Compared to blood donors, human herpesviruses were more prevalent in all MSM groups (P < .001). CONCLUSIONS: IP correlates with self-reported risk behavior among MSM. Although lr-MSM might form a low threat for blood safety with regard to class A infections, the high seroprevalence of human herpesviruses in lr-MSM warrants further investigation.

Prevalence of DNA of fourteen human polyomaviruses determined in blood donors.

BACKGROUND: Human polyomaviruses (HPyVs), like herpesviruses, cause persistent infection in a large part of the population. In immunocompromised and elderly patients, PyVs cause severe diseases such as nephropathy (BK polyomavirus [BKPyV]), progressive multifocal leukoencephalopathy (JC polyomavirus [JCPyV]), and skin cancer (Merkel cell polyomavirus [MCPyV]). Like cytomegalovirus, donor-derived PyV can cause disease in kidney transplant recipients. Possibly blood components transmit PyVs as well. To study this possibility, as a first step we determined the presence of PyV DNA in Dutch blood donations. STUDY DESIGN AND METHODS: Blood donor serum samples (n = 1016) were analyzed for the presence of DNA of 14 HPyVs using HPyV species-specific quantitative polymerase chain reaction (PCR) procedures. PCR-positive samples were subjected to confirmation by sequencing. Individual PCR findings were compared with the previously reported PyV serostatus. RESULTS: MC polyomavirus DNA was detected in 39 donors (3.8%), JCPyV and TS polyomavirus (TSPyV) DNA in five donors (both 0.5%), and HPyV9 DNA in four donors (0.4%). BKPyV, WU polyomavirus (WUPyV), HPyV6, MW polyomavirus (MWPyV), and LI polyomavirus (LIPyV) DNA was detected in one or two donors. Amplicon sequencing confirmed the expected product for BKPyV, JCPyV, WUPyV, MCPyV, HPyV6, TSPyV, MWPyV, HPyV9, and LIPyV. For JCPyV a significant association was observed between detection of viral DNA and the level of specific IgG antibodies. CONCLUSION: In 5.4% of Dutch blood donors PyV DNA was detected, including DNA from pathogenic PyVs such as JCPyV. As a next step, the infectivity of PyV in donor blood and transmission via blood components to immunocompromised recipients should be investigated.

Usutu virus infection in Dutch blood donors.

BACKGROUND: The screening of Dutch blood donations for West Nile virus (WNV) may be imminent, as WNV emerges in nearby countries and more donors travel to WNV-affected regions. Since 2016 the related, mosquito-borne Usutu virus (USUV) causes seasonal mortality in Dutch birds. To what extent will human USUV infections affect Dutch WNV donor screening? STUDY DESIGN AND METHODS: From April through September 2018, plasma samples from blood donations in blackbird-rich regions were stored. When increased bird mortality was reported in August, samples from July, August, and September were tested for USUV-RNA in pools of eight, using a home-brew combined WNV/USUV-PCR assay. Reactive pools were deconstructed. Original plasma units and samples of previous and follow-up donations of reactive donors were tested for USUV- and WNV-RNA, and for antibody responses. RESULTS: The number of USUV RNA-positive, WNV RNA-negative donations was 0 of 2688 donations in July, 6 of 4416 in August (1:736), and 1 of 4936 in September. The seven infected donors tested negative for USUV-RNA in preceding and follow-up donations. For 6 donors, seroconversion for USUV-antibodies was demonstrated. All index donations tested positive in a commonly used PCR-assay for WNV donor screening. Three exposed recipients did not show signs of infection. Screening a random subset of 1092 donations from September for USUV-IgG antibodies showed that 22 donors tested reactive; for three donors retrospective testing identified an USUV PCR-positive pre-seroconversion donation. CONCLUSION: Seasonal USUV infection in Dutch blood donors is common. Cross-reactivity in molecular assays for WNV-screening occurs, but can be resolved using USUV- and WNV-specific PCR-primers and sequencing of viral RNA.

No increased risk of transfusion-transmissible infections after tattooing, body piercing, or acupuncture among blood donors in the Netherlands.

BACKGROUND: In the Netherlands, needle-related events (NREs) including tattoos, piercings, and acupuncture are a reason for temporary blood donor deferral. This study aims to evaluate whether donors with recent NREs had a higher risk of transfusion-transmissible infections (TTIs) compared to donors without recent NREs. STUDY DESIGN AND METHODS: Data from 2006 through 2015 on all blood donation attempts in the Netherlands were collected. Multivariate regression models (for repeated measurements) were used to assess the associations between recent NREs and the acquisition of TTIs. Posttest counseling data were used to determine the most likely risk factor in TTI-positive new and repeat donors. RESULTS: Recent NREs were documented in 97,518 out of 9,266,036 (1.1%) donation attempts; 14,097 (14.5%) NREs resulted in NRE-based donor deferral. Recent NREs reported pre-donation were not associated with an increased risk for TTIs. A total of 29 out of 287 TTI-positive donors (11 repeat donors, 18 new donors) reported a recent NRE pre- and/or post-donation. Recent NREs, all needle-stick injuries, were the likely route of transmission in 12 out of 287 (4.2%) of TTI-positive donors. The donor health questionnaire (DHQ) identified only 1 out of 12 TTI-linked NREs. Non-return after NRE deferral, any deferral, or no deferral was 24, 15, and 5%, respectively. DISCUSSION: Recent tattoos, body piercings, or acupuncture were not associated with an increased risk for TTIs in Dutch donors. Given the lower return rates of donors following a temporary NRE-based deferral, we advocate ending blood donor deferral policies for acupuncture, tattooing, and body piercings, but not needle-stick injuries, in countries where these practices can be considered safe.

When are infection risks of blood transfusion tolerable? Towards understanding the ethical views of stakeholders in the blood supply.

BACKGROUND AND OBJECTIVES: The perception of transfusion-transmitted infections (TTIs) is sensitive to various concerns besides the probability and impact of infection, and some of these concerns may be ethically relevant. This paper aims to advance thinking about blood safety policies by exploring and explaining stakeholders' reasons to consider TTI risks tolerable or intolerable. MATERIALS AND METHODS: Inspired by critical empirical ethics and phenomenological hermeneutics, we held interviews and focus group discussions to explore the moral experience of policymakers, hematologists, blood donors and recipients. Respondents were invited to discuss general concerns about the blood supply, to address the tolerability of TTI risks compared with other hazards and to comment on the costs of blood safety. Arguments for tolerance or intolerance towards TTI risks were analysed qualitatively. RESULTS: Stakeholders' views could be clustered into seven categories: (1) clinical impact; (2) probability of infection; (3) avoidability of infection; (4) cost and health benefits; (5) other consequences of safety measures; (6) non-consequentialist ethical arguments; and (7) stakeholders' interests. Various arguments were offered that resonate with current ethical thinking about blood safety. Assuming that resources spent on inefficient blood safety measures could be applied more beneficially elsewhere, for example, responders typically expressed tolerance towards TTI risks. Some other arguments seem novel, for instance arguments for risk intolerance based on the low probability of infection and arguments for risk tolerance if patients have a poor prognosis. CONCLUSION: Understanding the moral experience of stakeholders enriches ethical debate about blood safety and prepares developing more widely acceptable policies.

Development and Evaluation of a Broad Bead-Based Multiplex Immunoassay To Measure IgG Seroreactivity against Human Polyomaviruses.

The family of polyomaviruses, which cause severe disease in immunocompromised hosts, has expanded substantially in recent years. To accommodate measurement of IgG seroresponses against all currently known human polyomaviruses (HPyVs), including the Lyon IARC polyomavirus (LIPyV), we extended our custom multiplex bead-based HPyV immunoassay and evaluated the performance of this pan-HPyV immunoassay. The VP1 proteins of 15 HPyVs belonging to 13 Polyomavirus species were expressed as recombinant glutathione S-transferase (GST) fusion proteins and coupled to fluorescent Luminex beads. Sera from healthy blood donors and immunocompromised kidney transplant recipients were used to analyze seroreactivity against the different HPyVs. For BK polyomavirus (BKPyV), the GST-VP1 fusion protein-directed seroresponses were compared to those obtained against BKPyV VP1 virus-like particles (VLP). Seroreactivity against most HPyVs was common and generally high in both test populations. Low seroreactivity against HPyV9, HPyV12, New Jersey PyV, and LIPyV was observed. The assay was reproducible (Pearson's r2 > 0.84, P < 0.001) and specific. Weak but consistent cross-reactivity between the related viruses HPyV6 and HPyV7 was observed. The seroresponses measured by the GST-VP1-based immunoassay and a VP1 VLP-based enzyme-linked immunosorbent assay were highly correlated (Spearman's ρ = 0.823, P < 0.001). The bead-based pan-HPyV multiplex immunoassay is a reliable tool to determine HPyV-specific seroresponses with high reproducibility and specificity and is suitable for use in seroepidemiological studies.

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.

Cost-effectiveness of the screening of blood donations for hepatitis E virus in the Netherlands.

BACKGROUND: The incidence of hepatitis E virus (HEV) has increased substantially in Europe recently, thereby threatening blood safety. A cost-effectiveness analysis for HEV screening of blood donations in the Netherlands was performed. STUDY DESIGN AND METHODS: A simulation model was developed to mimic the process of donation, infections in the donor population, donation testing, and transmission to transfusion recipients. The variability of viral loads among donors was modeled using observed loads. The number of (incurable) chronic HEV infections among organ and stem cell transplant patients and the costs avoided by implementing blood screening were estimated. RESULTS: HEV screening of whole blood donations in pools of 24 would prevent 4.52 of the 4.94 transfusion-associated chronic HEV infections expected annually, at approximately €310,000 per prevented chronic case. Per case not curable by ribavirin prevention, costs are approximately 10 times higher. Selective screening, if logistically feasible, could reduce screening costs by 85%. Sensitivity analyses show that uncertainty in the HEV transmissibility and the frequency of HEV clearing greatly impact the estimated cost-effectiveness. Of all HEV infections nationwide one in 700 is estimated to be due to blood transfusion, while for chronic infections this is one in 3.5. CONCLUSION: Despite uncertainties in our estimates, preventing HEV transmission by screening of blood donations appears not excessively expensive compared to other blood-screening measures in the Netherlands. However, the impact on HEV disease burden may be relatively small as only a minority of all HEV cases is transmitted by blood transfusion.

Phylogenetic evidence for underreporting of male-to-male sex among human immunodeficiency virus-infected donors in the Netherlands and Flanders.

BACKGROUND: Separate transmission networks for human immunodeficiency virus (HIV) coexist. Molecular typing of viral genomes can provide insight in HIV transmission routes in donors for whom risk behavior-based donor selection failed. STUDY DESIGN AND METHODS: This study includes all HIV-infected Dutch and Flemish donors in the period 2005 to 2014 (n = 55). Part of the HIV polymerase (pol) gene was amplified, sequenced, and compared with more than 10,000 HIV strains obtained from HIV-infected Dutch and Flemish patients. The most likely transmission route was determined based on HIV phylogeny and the donor's self-reported risk behavior during the exit interview. RESULTS: HIV-infected donors were predominantly male (69%), were repeat donors (73%), were born in the Netherlands or Belgium (95%), and harbored HIV Subtype B (68%). Seventy-five percent of HIV-infected male donors were part of robust phylogenetic clusters linked to male-to-male sex, while only 24% of HIV-infected male donors reported male-to-male sex during posttest counseling. Sex between men and women accounted for 13% of HIV infections in male donors and 93% of HIV infections in female donors based on phylogenetic analysis. Only 40% of HIV-infected female donors had HIV Subtype B; 65% of female donors reported a foreign partner and indeed HIV sequences interspersed with sequences from HIV-endemic areas abroad, in particular sub-Saharan Africa. CONCLUSION: HIV typing helps to understand HIV transmission routes in donor populations. We found substantial underreporting of male-to-male sex among HIV-infected male donors. Donor education on HIV risk factors and the danger of window-period donations and a donor environment that encourages frank disclosure of sexual behavior will contribute to a decrease of HIV-infected donors.

The Precautionary Principle and the Tolerability of Blood Transfusion Risks.

Tolerance for blood transfusion risks is very low, as evidenced by the implementation of expensive blood tests and the rejection of gay men as blood donors. Is this low risk tolerance supported by the precautionary principle, as defenders of such policies claim? We discuss three constraints on applying (any version of) the precautionary principle and show that respecting these implies tolerating certain risks. Consistency means that the precautionary principle cannot prescribe precautions that it must simultaneously forbid taking, considering the harms they might cause. Avoiding counterproductivity requires rejecting precautions that cause more harm than they prevent. Proportionality forbids taking precautions that are more harmful than adequate alternatives. When applying these constraints, we argue, attention should not be restricted to harms that are human caused or that affect human health or the environment. Tolerating transfusion risks can be justified if available precautions have serious side effects, such as high social or economic costs.

Hepatitis E and blood donation safety in selected European countries: a shift to screening?

The public health implications of hepatitis E virus (HEV) in Europe have changed due to increasing numbers of hepatitis E cases and recent reports of chronic, persistent HEV infections associated with progression to cirrhosis in immunosuppressed patients. The main infectious risk for such immunosuppressed patients is exposure to undercooked infected pork products and blood transfusion. We summarised the epidemiology of HEV infections among blood donors and also outlined any strategies to prevent transfusion-transmitted HEV, in 11 European countries. In response to the threat posed by HEV and related public and political concerns, most of the observed countries determined seroprevalence of HEV in donors and presence of HEV RNA in blood donations. France, Germany, Spain and the United Kingdom (UK) reported cases of transfusion-transmitted HEV. Ireland and the UK have already implemented HEV RNA screening of blood donations; the Netherlands will start in 2017. Germany and France perform screening for HEV RNA in several blood establishments or plasma donations intended for use in high-risk patients respectively and, with Switzerland, are considering implementing selective or universal screening nationwide. In Greece, Portugal, Italy and Spain, the blood authorities are evaluating the situation. Denmark decided not to implement the HEV screening of blood donations.