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The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous boosters after Ad26.COV2.S-priming. We found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies, and T cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed., Competing Interests: Potential conflicts of interest. L. G. V. reports research grants from U Needle, MyLife Technologies, and Bavarian Nordic, all outside of the submitted work; consulting fees from Emergent for expert meeting travel vaccines; participation on a scientific advisory board for Geosentinel; and serving as committee member for the National Board Guideline Development Travel Medicine. A. G. reports participation on a data and safety monitoring board (DSMB) IDSCOVA (Establishing the tolerability, safety and immunogenicity of intradermal delivery of mRNA SARS-CoV-2 vaccine in healthy adults) study on intradermal COVID vaccinations and serving as member of national advisory board on coronavirus disease vaccinations for immunocompromised patients. A. L. W. H. reports support for the present research from the Dutch Research Council (ZonMw) to their organization. D. F. P. reports participation on the DSMB of the COBRA-KAI trial (COVID-19 vaccination in patients with reduced B-cell and T-cell immunity: response after vaccination in a kaleidoscopic group of hematologic patients: what's the impact?). V. A. S. H. D. reports research funding outside of the submitted work from ZonMw and EU Horizon 2020, consulting fees for an advisory board meeting from GSK, and honoraria for lectures from Pharming, Takeda. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The immune response to COVID-19 vaccination is inferior in kidney transplant recipients (KTRs) and to a lesser extent in patients on dialysis or with chronic kidney disease (CKD). We assessed the immune response 6 months after mRNA-1273 vaccination in kidney patients and compared this to controls., Methods: A total of 152 participants with CKD stages G4/5 (eGFR <30 mL/min/1.73 m2), 145 participants on dialysis, 267 KTRs, and 181 controls were included. SARS-CoV-2 Spike S1 specific IgG antibodies were measured using fluorescent bead-based multiplex-immunoassay, neutralizing antibodies to ancestral, Delta, and Omicron (BA.1) variants by plaque reduction, and T-cell responses by interferon-γ release assay., Results: At 6 months after vaccination, S1-specific antibodies were detected in 100% of controls, 98.7% of CKD G4/5 patients, 95.1% of dialysis patients, and 56.6% of KTRs. These figures were comparable to the response rates at 28 days, but antibody levels waned significantly. Neutralization of the ancestral and Delta variants was detected in most participants, whereas neutralization of Omicron was mostly absent. S-specific T-cell responses were detected at 6 months in 75.0% of controls, 69.4% of CKD G4/5 patients, 52.6% of dialysis patients, and 12.9% of KTRs. T-cell responses at 6 months were significantly lower than responses at 28 days., Conclusions: Although seropositivity rates at 6 months were comparable to rates at 28 days after vaccination, significantly decreased antibody levels and T-cell responses were observed. The combination of low antibody levels, reduced T-cell responses, and absent neutralization of the newly emerging variants indicates the need for additional boosts or alternative vaccination strategies in KTRs., Clinical Trials Registration: NCT04741386., Competing Interests: Potential conflicts of interest. C. C. B. reports a Dutch Kidney Foundation grant and support from the Procare II study unrelated to this work and a role as Executive Editor/Social Media Editor for Transplantation Journal. M. M. L. K. reports participation on an advisory board on maribavir for Takeda. All other authors report no potential conflicts.All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

There is an ongoing debate on airborne transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as a risk factor for infection. In this study, the level of SARS-CoV-2 in air and on surfaces of SARS-CoV-2 infected nursing home residents was assessed to gain insight in potential transmission routes. During outbreaks, air samples were collected using three different active and one passive air sampling technique in rooms of infected patients. Oropharyngeal swabs (OPS) of the residents and dry surface swabs were collected. Additionally, longitudinal passive air samples were collected during a period of 4 months in common areas of the wards. Presence of SARS-CoV-2 RNA was determined using RT-qPCR, targeting the RdRp- and E-genes. OPS, samples of two active air samplers and surface swabs with Ct-value ≤35 were tested for the presence of infectious virus by cell culture. In total, 360 air and 319 surface samples from patient rooms and common areas were collected. In rooms of 10 residents with detected SARS-CoV-2 RNA in OPS, SARS-CoV-2 RNA was detected in 93 of 184 collected environmental samples (50.5%) (lowest Ct 29.5), substantially more than in the rooms of residents with negative OPS on the day of environmental sampling (n = 2) (3.6%). SARS-CoV-2 RNA was most frequently present in the larger particle size fractions [>4 μm 60% (6/10); 1-4 μm 50% (5/10); <1 μm 20% (2/10)] (Fischer exact test P = 0.076). The highest proportion of RNA-positive air samples on room level was found with a filtration-based sampler 80% (8/10) and the cyclone-based sampler 70% (7/10), and impingement-based sampler 50% (5/10). SARS-CoV-2 RNA was detected in 10 out of 12 (83%) passive air samples in patient rooms. Both high-touch and low-touch surfaces contained SARS-CoV-2 genome in rooms of residents with positive OPS [high 38% (21/55); low 50% (22/44)]. In one active air sample, infectious virus in vitro was detected. In conclusion, SARS-CoV-2 is frequently detected in air and on surfaces in the immediate surroundings of room-isolated COVID-19 patients, providing evidence of environmental contamination. The environmental contamination of SARS-CoV-2 and infectious aerosols confirm the potential for transmission via air up to several meters., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Immunocompromised individuals can become chronically infected with norovirus, but effective antiviral therapies are not yet available., Methods: Treatments with nitazoxanide, ribavirin, interferon alpha-2a, and nasoduodenally administered immunoglobulins were evaluated sequentially in an immunocompromised patient chronically infected with norovirus. In support, these components were also applied to measure norovirus inhibition in intestinal enteroid cultures in vitro. Viral RNA levels were determined in fecal and plasma samples during each treatment and viral genomes were sequenced., Results: None of the antivirals resulted in a reduction of viral RNA levels in feces or plasma. However, during ribavirin treatment, there was an increased accumulation of virus genome mutations. In vitro, an effect of interferon alpha-2a on virus replication was observed and a genetically related strain was neutralized effectively in vitro using immunoglobulins and post-norovirus-infection antiserum. In agreement, after administration of immunoglobulins, the patient cleared the infection., Conclusions: Intestinal enteroid cultures provide a relevant system to evaluate antivirals and the neutralizing potential of immunoglobulins. We successfully treated a chronically infected patient with immunoglobulins, despite varying results reported by others. This case study provides in-depth, multifaceted exploration of norovirus treatment that can be used as a guidance for further research towards norovirus treatments., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Sars-CoV-2 outbreaks resulted in a high case fatality rate in nursing homes (NH) worldwide. It is unknown to which extent presymptomatic residents and staff contribute to the spread of the virus., Aims: To assess the contribution of asymptomatic and presymptomatic residents and staff in SARS-CoV-2 transmission during a large outbreak in a Dutch NH., Methods: Observational study in a 185-bed NH with two consecutive testing strategies: testing of symptomatic cases only, followed by weekly facility-wide testing of staff and residents regardless of symptoms. Nasopharyngeal and oropharyngeal testing with RT-PCR for SARs-CoV-2, including sequencing of positive samples, was conducted with a standardised symptom assessment., Results: 185 residents and 244 staff participated. Sequencing identified one cluster. In the symptom-based test strategy period, 3/39 residents were presymptomatic versus 38/74 residents in the period of weekly facility-wide testing (P-value < 0.001). In total, 51/59 (91.1%) of SARS-CoV-2 positive staff was symptomatic, with no difference between both testing strategies (P-value 0.763). Loss of smell and taste, sore throat, headache or myalga was hardly reported in residents compared to staff (P-value <0.001). Median Ct-value of presymptomatic residents was 21.3, which did not differ from symptomatic (20.8) or asymptomatic (20.5) residents (P-value 0.624)., Conclusions: Symptoms in residents and staff are insufficiently recognised, reported or attributed to a possible SARS-CoV-2 infection. However, residents without (recognised) symptoms showed the same potential for viral shedding as residents with symptoms. Weekly testing was an effective strategy for early identification of SARS-Cov-2 cases, resulting in fast mitigation of the outbreak., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: An outbreak of coronavirus disease 2019 (COVID-19) in a nursing home in the Netherlands, following an on-site church service held on 8 March 2020, triggered an investigation to unravel sources and chain(s) of transmission., Methods: Epidemiological data were collected from registries and through a questionnaire among church attendees. Symptomatic residents and healthcare workers (HCWs) were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction and subjected to whole genome sequencing (WGS). Sequences from a selection of people from the same area were included as community reference., Results: After the church service, 30 of 39 attendees (77%) developed symptoms; 14 (11 residents and 3 nonresidents) were tested and were positive for COVID-19. In the following 5 weeks, 62 of 300 residents (21%) and 30 of 640 HCWs (5%) tested positive for COVID-19; 21 of 62 residents (34%) died. The outbreak was controlled through a cascade of measures. WGS of samples from residents and HCWs identified a diversity of sequence types, grouped into 8 clusters. Seven resident church attendees all were infected with distinct viruses, 4 of which belonged to 2 larger clusters in the nursing home., Conclusions: Although initial investigation suggested the church service as the source of the outbreak, detailed analysis showed a more complex picture, most consistent with widespread regional circulation of the virus in the weeks before the outbreak, and multiple introductions into the nursing home before the visitor ban. The findings underscore the importance of careful outbreak investigations to understand SARS-CoV-2 transmission to develop evidence-based mitigation measures., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In general, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy is not considered to be an increased risk for severe maternal outcomes but has been associated with an increased risk for fetal distress. Maternal-fetal transmission of SARS-CoV-2 was initially deemed uncertain; however, recently a few cases of vertical transmission have been reported. The intrauterine mechanisms, besides direct vertical transmission, leading to the perinatal adverse outcomes are not well understood., Methods: Multiple maternal, placental, and neonatal swabs were collected for the detection of SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR). Serology of immunoglobulins against SARS-CoV-2 was tested in maternal, umbilical cord, and neonatal blood. Placental examination included immunohistochemical investigation against SARS-CoV-2 antigen expression, with SARS-CoV-2 ribonucleic acid (RNA) in situ hybridization and transmission electron microscopy., Results: RT-qPCRs of the oropharynx, maternal blood, vagina, placenta, and urine were all positive over a period of 6 days, while breast milk, feces, and all neonatal samples tested negative. Placental findings showed the presence of SARS-CoV-2 particles with generalized inflammation characterized by histiocytic intervillositis with diffuse perivillous fibrin depositions with damage to the syncytiotrophoblasts., Conclusions: Placental infection by SARS-CoV-2 leads to fibrin depositions hampering fetal-maternal gas exchange with resulting fetal distress necessitating a premature emergency cesarean section. Postpartum, the neonate showed a fetal or pediatric inflammatory multisystem-like syndrome with coronary artery ectasia temporarily associated with SARS-CoV-2 for which admittance and care on the neonatal intensive care unit (NICU) were required, despite being negative for SARS-CoV-2. This highlights the need for awareness of adverse fetal and neonatal outcomes during the current coronavirus disease 2019 pandemic, especially considering that the majority of pregnant women appear asymptomatic., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Lower respiratory tract (LRT) disease induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can deteriorate to acute respiratory distress syndrome (ARDS). Because the release of neutrophil extracellular traps (NETs) is implicated in ARDS pathogenesis, we investigated the presence of NETs and correlates of pathogenesis in blood and LRT samples of critically ill patients with COVID-19. Plasma NET levels peaked early after intensive care unit admission and were correlated with the SARS-CoV-2 RNA load in sputum and levels of neutrophil-recruiting chemokines and inflammatory markers in plasma samples. The baseline plasma NET quantity was correlated with disease severity but was not associated with soluble markers of thrombosis or with development of thrombosis. High NET levels were present in LRT samples and persisted during the course of COVID-19, consistent with the detection of NETs in bronchi and alveolar spaces in lung tissue from deceased patient with COVID-19. Thus, NETs are produced and retained in the LRT of critically ill patients with COVID-19 and could contribute to SARS-CoV-2-induced ARDS disease., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Summary: Here, we present an automated pipeline for Download Of NCBI Entries (DONE) and continuous updating of a local sequence database based on user-specified queries. The database can be created with either protein or nucleotide sequences containing all entries or complete genomes only. The pipeline can automatically clean the database by removing entries with matches to a database of user-specified sequence contaminants. The default contamination entries include sequences from the UniVec database of plasmids, marker genes and sequencing adapters from NCBI, an E.coli genome, rRNA sequences, vectors and satellite sequences. Furthermore, duplicates are removed and the database is automatically screened for sequences from green fluorescent protein, luciferase and antibiotic resistance genes that might be present in some GenBank viral entries, and could lead to false positives in virus identification. For utilizing the database, we present a useful opportunity for dealing with possible human contamination. We show the applicability of DONE by downloading a virus database comprising 37 virus families. We observed an average increase of 16 776 new entries downloaded per month for the 37 families. In addition, we demonstrate the utility of a custom database compared to a standard reference database for classifying both simulated and real sequence data., Availabilityand Implementation: The DONE pipeline for downloading and cleaning is deposited in a publicly available repository (https://bitbucket.org/genomicepidemiology/done/src/master/)., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press.)

The transmission of direct-acting antiviral resistance-associated substitutions (RAS) could hamper hepatitis C virus (HCV) cure rates and elimination efforts. A phylogenetic analysis of 87 men who have sex with men recently infected with HCV genotype 1a placed one-third (28/87) in a large cluster, in which 96% harbored NS5A M28V RAS., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population., Methods: Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2-specific IgG concentrations., Results: Our assay discriminated SARS-CoV-2-induced antibodies and those induced by other viruses. The assay specificity was 95.1%-99.0% with sensitivity 83.6%-95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases., Conclusions: The bead-based serological assay for quantitation of SARS-CoV-2-specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen-specific IgG determination., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

In April 2019, a suspect cluster of enterovirus cases was reported in a neonatology department in Guangdong, China, resulting in five deaths. We aimed to investigate the pathogen profiles in fatal cases, the circulation and transmission pattern of the viruses by combining metatranscriptomic, phylogenetic, and epidemiological analyses. Metatranscriptomic sequencing was used to characterize the enteroviruses. Clinical and environmental surveillance in the local population was performed to understand the prevalence and genetic diversity of the viruses in the local population. The possible source(s), evolution, transmission, and recombination of the viruses were investigated by incorporating genomes from the current outbreak, from local retrospective surveillance, and from public databases. Metatranscriptomic analysis identified Echovirus 11 (E11) in three fatal cases. Seroprevalence of neutralization antibody to E11 was 35 to 44 per cent in 3-15 age groups of general population, and the viruses were associated with various clinical symptoms. From the viral phylogeny, nosocomial transmissions were identified and all E11 2019 outbreak strains were closely related with E11 strains circulating in local population 2017-19. Frequent recombination occurred among the 2019 Guangdong E11 outbreak strains and various genotypes in enterovirus B species. This study provides an example of combining advanced genetic technology and epidemiological surveillance in pathogen diagnosis, source(s), and transmission tracing during an infectious disease outbreak. The result highlights the hidden E11 circulation and the risk of viral transmission and infection in the young age population in China. Frequent recombination between Guangdong-like strains and other enterovirus genotypes also implies the prevalence of these emerging E11 strains., (© The Author(s) 2020. Published by Oxford University Press.)

Background: The majority of infants will not be protected by maternal antibodies until their first measles vaccination, between 12 and 15 months of age. This provides incentive to reduce the age at measles vaccination, but immunological consequences are insufficiently understood, and long-term effects are largely unknown., Methods: A total of 79 infants who received early measles vaccination between 6 and 12 months age and a second dose at 14 months of age were compared to 44 children in a control group who received 1 dose at 14 months of age. Measles virus-specific neutralizing antibody concentrations and avidity were determined up to 4 years of age., Results: Infants who first received measles vaccination before 12 months of age had a long-term decrease in the concentration and avidity of measles virus-specific neutralizing antibodies, compared with infants in the control group. For 11.1% of children with a first dose before 9 months of age, antibody levels at 4 years of age had dropped below the cutoff for clinical protection., Conclusions: Early measles vaccination provides immediate protection in the majority of infants but yields a long-term decrease in neutralizing antibody responses, compared to vaccination at a later age. Additional vaccination at 14 months of age does not improve this. Over the long term, this may result in an increasing number of children susceptible to measles., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

In 2015-2016, a Zika virus (ZIKV) outbreak occurred in the Americas. In 2017, we conducted a ZIKV serosurvey in Suriname in which 770 participants were recruited from 1 urban area and 2 rural villages in the tropical rainforest. All collected samples were tested for presence of ZIKV antibodies using a ZIKV immunoglobulin G enzyme-linked immunosorbent assay and a virus neutralization assay. We found that 35.1% of the participants had neutralizing antibodies against ZIKV. In 1 remote village in the rainforest, 24.5% of the participants had neutralizing antibodies against ZIKV, suggesting that ZIKV was widely spread across Suriname., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4 viruses were first introduced into Europe in late 2014 and re-introduced in late 2016, following detections in Asia and Russia. In contrast to the 2014-15 H5N8 wave, there was substantial local virus amplification in wild birds in Europe in 2016-17 and associated wild bird mortality, with evidence for occasional gene exchange with low pathogenic avian influenza (LPAI) viruses. Since December 2017, several European countries have again reported events or outbreaks with HPAI H5N6 reassortant viruses in both wild birds and poultry, respectively. Previous phylogenetic studies have shown that the two earliest incursions of HPAI H5N8 viruses originated in Southeast Asia and subsequently spread to Europe. In contrast, this study indicates that recent HPAI H5N6 viruses evolved from the H5N8 2016-17 viruses during 2017 by reassortment of a European HPAI H5N8 virus and wild host reservoir LPAI viruses. The genetic and phenotypic differences between these outbreaks and the continuing detections of HPAI viruses in Europe are a cause of concern for both animal and human health. The current co-circulation of potentially zoonotic HPAI and LPAI virus strains in Asia warrants the determination of drivers responsible for the global spread of Asian lineage viruses and the potential threat they pose to public health.

Background: High-pathogenicity avian influenza viruses continue to circulate in poultry and wild birds and occasionally infect humans, sometimes with fatal outcomes. Development of vaccines is a priority to prepare for potential pandemics but is complicated by antigenic variation of the surface glycoprotein hemagglutinin. We report the immunological profile induced by human immunization with modified vaccinia virus Ankara (MVA) expressing the hemagglutinin gene of influenza A(H5N1) virus A/Vietnam/1194/04 (rMVA-H5)., Methods: In a double-blinded phase 1/2a clinical trial, 79 individuals received 1 or 2 injections of rMVA-H5 or vector control. Twenty-seven study subjects received a booster immunization after 1 year. The breadth, magnitude, and properties of vaccine-induced antibody and T-cell responses were characterized., Results: rMVA-H5 induced broadly reactive antibody responses, demonstrated by protein microarray, hemagglutination inhibition, virus neutralization, and antibody-dependent cellular cytotoxicity assays. Antibodies cross-reacted with antigenically distinct H5 viruses, including the recently emerged subtypes H5N6 and H5N8 and the currently circulating subtype H5N1. In addition, the induction of T cells specific for H5 viruses of 2 different clades was demonstrated., Conclusions: rMVA-H5 induced immune responses that cross-reacted with H5 viruses of various clades. These findings validate rMVA-H5 as vaccine candidate against antigenically distinct H5 viruses., Clinical Trials Registration: NTR3401.

Extra-epitopic amino acid residues affect recognition of human influenza A viruses (IAVs) by CD8+ T-lymphocytes (CTLs) specific for the highly conserved HLA-A*0201 restricted M158-66 epitope located in the matrix 1 (M1) protein. These residues are absent in the M1 protein of the 2009-pandemic IAV (H1N1pdm09). Consequently, stimulation with M1 protein of H1N1pdm09 IAV resulted in stronger activation and lytic activity of M158-66-specific CTLs than stimulation with seasonal H3N2 IAVs. During >6 years of circulation in the human population, descendants of the H1N1pdm09 virus had accumulated 4 other amino acid substitutions. However, these did not affect M158-66-specific CTL activation.

Influenza A virus (IAV) and influenza B virus (IBV) cause substantial morbidity and mortality during annual epidemics. Two distinct lineages of IBV are distinguished, based on variation in hemagglutinin (HA): B/Victoria/2/87-like (B/Vic) and B/Yamagata/16/88-like (B/Yam). Here, we show that, in humans, primary IBV infection with either lineage induces HA-specific antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. IBV infection induced antibodies specific to the HA head and stalk, but only HA stalk-specific antibodies mediated ADCC efficiently and displayed cross-reactivity with IBV of both lineages. This corresponds to recent findings that 2 points of contact between the effector and target cell (ie, HA and sialic acid, respectively, and the fragment crystallizable [Fc] domain and Fcγ receptor IIIα, respectively) are required for efficient ADCC activity and that antibodies specific for the receptor-binding site located in the head domain of HA therefore fail to mediate ADCC. Potentially, ADCC-mediating antibodies directed to the HA stalk of IBV contribute to cross-protective immunity to IBV of both lineages., (© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Treatment of blood samples from hemorrhagic fever virus (HFV)-infected patients with 0.1% detergents has been recommended for virus inactivation and subsequent safe laboratory testing. However, data on virus inactivation by this procedure are lacking. Here we show the effect of this procedure on diagnostic test results and infectious Ebola virus (EBOV) titers., Methods: Serum and whole-blood samples were treated with 0.1% or 1% sodium dodecyl sulfate (SDS) or 0.1% Triton X-100 and assayed for clinical chemistry and malaria antigen detection. Infectious EBOV titers were determined in SDS-treated plasma and whole blood from EBOV-infected nonhuman primates (NHPs). Infectious titers of EBOV or herpes simplex virus type 1 (HSV-1) in detergents-treated cell culture medium containing various serum concentrations were determined., Results: Laboratory test results were not affected by 0.1% detergent treatment of blood samples, in contrast with 1% SDS treatment. However, 0.1% detergent treatment did not inactivate EBOV in blood samples from infected NHPs. Experiments with cell culture medium showed that virus inactivation by detergents is annulled at physiological serum concentrations., Conclusions: Treatment of blood samples with 0.1% SDS or Triton X-100 does not inactivate EBOV. Inactivation protocols for HFV should be validated with serum and whole blood., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Porcine stool-associated RNA virus (posavirus), and Human stool-associated RNA virus (husavirus) are viruses in the order Picornavirales recently described in porcine and human fecal samples. The tentative group (Posa and Posa-like viruses: PPLVs) also includes fish stool-associated RNA virus (fisavirus) as well as members detected in insects ( Drosophila subobscura and Anopheles sinensis ) and parasites ( Ascaris suum ). As part of an agnostic deep sequencing survey of animal and human viruses in Vietnam, we detected three husaviruses in human fecal samples, two of which share 97-98% amino acid identity to Dutch husavirus strains and one highly divergent husavirus with only 25% amino acid identity to known husaviruses. In addition, the current study found forty-seven complete posavirus genomes from pigs, ten novel rat stool-associated RNA virus genomes (tentatively named rasavirus), and sixteen novel bat stool-associated RNA virus genomes (tentatively named basavirus). The five expected Picornavirales protein domains (helicase, 3C-protease, RNA-dependent RNA polymerase, and two Picornavirus capsid domain) were found to be encoded by all PPLV genomes. In addition, a nucleotide composition analysis revealed that the PPLVs shared compositional properties with arthropod viruses and predicted non-mammalian hosts for all PPLV lineages. The study adds seventy-six genomes to the twenty-nine PPLV genomes currently available and greatly extends our sequence knowledge of this group of viruses within the Picornavirales order.

The transmission routes and risk factors for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infections are still unknown. We used the World Health Organization questionnaire for MERS-CoV case-control studies to assess risk factors for human MERS-CoV seropositivity at a farm complex in Qatar. Nine camel workers with MERS-CoV antibodies and 43 workers without antibodies were included. Some camel-related activities may pose a higher risk of MERS-CoV infection, as may cross-border movements of camels, poor hand hygiene, and overnight hospital stays with respiratory complaints. The risk factors identified in this study can be used to develop infection prevention and control measures for human MERS-CoV infections., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Influenza A viruses can replicate in the olfactory mucosa and subsequently use the olfactory nerve to enter the central nervous system (CNS). It is currently unknown whether intervention strategies are able to reduce or prevent influenza virus replication within the olfactory mucosa and subsequent spread to the CNS. Therefore, we tested the efficacy of homologous vaccination and prophylactic oseltamivir to prevent H5N1 virus CNS invasion via the olfactory nerve in our ferret model., Methods: Ferrets were vaccinated intramuscularly or received oseltamivir (5 mg/kg twice daily) prophylactically before intranasal inoculation of highly pathogenic H5N1 virus (A/Indonesia/05/2005) and were examined using virology and pathology., Results: Homologous vaccination reduced H5N1 virus replication in the olfactory mucosa and prevented subsequent virus spread to the CNS. However, prophylactic oseltamivir did not prevent H5N1 virus replication in the olfactory mucosa sufficiently, resulting in CNS invasion via the olfactory nerve causing a severe meningoencephalitis., Conclusions: Within our ferret model, vaccination is more effective than prophylactic oseltamivir in preventing CNS invasion by H5N1 virus via the olfactory nerve. This study highlights the importance of including the olfactory mucosa, olfactory nerve, and CNS tissues in future vaccine and antiviral studies, especially for viruses with a known neurotropic potential., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: First isolated in the Netherlands in 1955 during an outbreak of acute respiratory disease (ARD) among military recruits, human adenovirus 14 (HAdV-14) has historically been considered rare. With no precedent of circulation in North America, HAdV-14 has been isolated from military and civilian cases of ARD of variable severity since 2003 in the United States., Methods: Ninety-nine isolates from military and civilian cases from different geographic locations and circulation periods were characterized by restriction enzyme analysis of viral DNA and select gene sequencing., Results: All examined viruses were found to be identical and to belong to a new genome type designated "HAdV-14p1" (formerly known as "14a"). Comparative alignments of E1A, hexon, and fiber gene sequences with other subspecies B2 HAdVs suggest that HAdV-14p1, like the closely related HAdV-11a, arose from recombination among similar HAdV-11 and HAdV-14 ancestral strains. A deletion of 2 amino acids in the knob region of the fiber protein is the only identified unique characteristic of HAdV-14p1., Conclusion: The current geographic distribution of HAdV-14p1 involves at least 15 states in the Unites States. The role of the fiber mutations in the recent emergence of HAdV-14p1 ARD in North America warrants further study.

An epizootic of avian influenza (H7N7) caused a large number of human infections in The Netherlands in 2003. We used data from this epizootic to estimate infection probabilities for persons involved in disease control on infected farms. Analyses were based on databases containing information on the infected farms, person-visits to these farms, and exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epizootic). Case definition was based on self-reported conjunctivitis and positive response to hemagglutination inhibition assay. A high infection probability was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%; 95% confidence interval [CI], 1.4%-18.9%) and active culling during depopulation (6.2%; 95% CI, 3.7%-9.6%). Low probabilities were estimated for management of biosecurity (0.0%; 95% CI, 0.0%-1.0%) and cleaning assistance during depopulation (0.0%; 95% CI, 0.0%-9.2%). No significant association was observed between the probability of infection and the exposure variables.

Background: Noroviruses (NoVs) are the leading cause of viral gastroenteritis in humans of all ages. Challenge studies that used the NoV prototype strain Norwalk virus (NV) have shown that some individuals are not susceptible to infection, suggesting the absence of a receptor. Recent studies have identified histo-blood group antigens (HBGAs) as possible receptors. Being a nonsecretor and presence of HBGA type B were associated with protection against infection with NV, a genogroup (GG) I NoV., Methods: In the present retrospective study, we investigated the association between presence of HBGAs and the risk of infection with another NoV belonging to GGI (Hu/NV/I/Birmingham/93/UK). The study was done as part of an investigation of a waterborne outbreak in a group of schoolchildren and of a cohort of healthy adults. The ABH histo-blood group phenotype was determined by use of saliva or serum samples from these individuals., Results: Presence of HBGA type B was significantly correlated with a lack of susceptibility to infection with GGI NoV and with an absence of antibodies. No correlation was found with GGII NoV. Although the infection rate in nonsecretors was lower, this difference was not statistically significant, and several children lacking HBGAs in saliva were found to be infected., Conclusions: Individuals with the HBGA type B may be protected against infection with GGI (but not GGII) NoVs. The association between susceptibility to NoV infection and being a secretor may be restricted to GGI NoV.

Poliovirus-specific immunoglobulin A (IgA) is detected after infection with wild-type virus or vaccination with live attenuated oral poliovirus (OPV) but not after vaccination with inactivated poliovirus (IPV). We examined whether the presence of IgA in serum can be used as a marker for poliovirus circulation in IPV-vaccinated populations in The Netherlands. In seronegative persons challenged with OPV, the sensitivity of this marker was 76%-86%. Results from a serosurvey showed a high seroprevalence (63%-73%) of IgA in the population born before vaccination was introduced in The Netherlands, which reflects natural exposure. The start of the vaccination program in 1957 corresponded to a reduction in the IgA seroprevalence in both vaccinated (2.1%-4.5%) and nonvaccinated groups (8.3%-11.7%). The presence of IgA-positive persons in the population could largely be explained by the occurrence of episodes of proven poliovirus circulation. We propose to use the detection of poliovirus-specific IgA as a tool to monitor virus circulation in IPV-vaccinated and nonvaccinated populations, to aid the poliovirus eradication process.