Poliovirus is known to most people in the world as the cause of polio, a devastating paralytic disease from the past. Success in polio eradication has understandably translated into stricter ...containment plans for poliovirus, coordinated by WHO. In this Personal View, we discuss the impact of recent biosafety level 3+ guidelines for handling potential poliovirus-containing diagnostic specimens, which has resulted in closure of many national WHO poliovirus reference laboratories. This reduction in laboratory capacity has a knock-on effect of capability to detect and characterise non-polio enteroviruses in samples obtained from patients with neurological symptoms. The development is of concern given the widespread circulation of non-polio enteroviruses, their role as the most common cause of meningitis worldwide, and their involvement in other severe neurological conditions, such as acute flaccid myelitis and encephalitis. These disease presentations have increased substantially in the past decade, and have been associated with major outbreaks of enterovirus D68 and enterovirus A71, leaving many who survived with lasting paralysis and disabilities. To address this growing gap in diagnostic and surveillance capability, we have established the European Non-Poliovirus Enterovirus Network (also known as ENPEN) as a supra-national, non-commercial, core reference consortium. Our consortium will develop, test, and implement generic surveillance platforms for non-polio enteroviruses and other emerging viral diseases.
Health-care workers are thought to be highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the prevalence of antibodies against SARS-CoV-2 ...in health-care workers and the proportion of seroconverted health-care workers with previous symptoms of COVID-19.
In this observational cohort study, screening was offered to health-care workers in the Capital Region of Denmark, including medical, nursing, and other students who were associated with hospitals in the region. Screening included point-of-care tests for IgM and IgG antibodies against SARS-CoV-2. Test results and participant characteristics were recorded. Results were compared with findings in blood donors in the Capital Region in the study period.
Between April 15 and April 23, 2020, we screened 29 295 health-care workers, of whom 28 792 (98·28%) provided their test results. We identified 1163 (4·04% 95% CI 3·82–4·27) seropositive health-care workers. Seroprevalence was higher in health-care workers than in blood donors (142 3·04% of 4672; risk ratio RR 1·33 95% CI 1·12–1·58; p<0·001). Seroprevalence was higher in male health-care workers (331 5·45% of 6077) than in female health-care workers (832 3·66% of 22 715; RR 1·49 1·31–1·68; p<0·001). Frontline health-care workers working in hospitals had a significantly higher seroprevalence (779 4·55% of 16 356) than health-care workers in other settings (384 3·29% of 11 657; RR 1·38 1·22–1·56; p<0·001). Health-care workers working on dedicated COVID-19 wards (95 7·19% of 1321) had a significantly higher seroprevalence than other frontline health-care workers working in hospitals (696 4·35% of 15 983; RR 1·65 1·34–2·03; p<0·001). 622 53·5% of 1163 seropositive participants reported symptoms attributable to SARS-CoV-2. Loss of taste or smell was the symptom that was most strongly associated with seropositivity (377 32·39% of 1164 participants with this symptom were seropositive vs 786 2·84% of 27 628 without this symptom; RR 11·38 10·22–12·68). The study is registered at ClinicalTrials.gov, NCT04346186.
The prevalence of health-care workers with antibodies against SARS-CoV-2 was low but higher than in blood donors. The risk of SARS-CoV-2 infection in health-care workers was related to exposure to infected patients. More than half of seropositive health-care workers reported symptoms attributable to COVID-19.
Lundbeck Foundation.
Parechovirus infections usually affect neonates and young children; manifestations vary from asymptomatic to life-threatening. We describe laboratory capacity in Europe for assessing parechovirus ...circulation, seasonality, and epidemiology. We used retrospective anonymized data collected from parechovirus infection case-patients identified in Europe during January 2015-December 2021. Of 21 laboratories from 18 countries that participated in the study, 16 (76%) laboratories with parechovirus detection capacity reported 1,845 positive samples; 12/16 (75%) with typing capability successfully identified 517 samples. Parechovirus A3 was the most common type (n = 278), followed by A1 (153), A6 (50), A4 (13), A5 (22), and A14 (1). Clinical data from 1,269 participants highlighted correlation of types A3, A4, and A5 with severe disease in neonates. We observed a wide capacity in Europe to detect, type, and analyze parechovirus data. To enhance surveillance and response for PeV outbreaks, sharing typing protocols and data on parechovirus-positive cases should be encouraged.
Enteroviruses can cause severe infections, especially in young children. Non-polio enterovirus infections are not notifiable in most countries in the EU and European Economic Area (EEA) region, and ...surveillance varies substantially between countries. We collected and analysed available enterovirus data across EU and EEA countries to assess the current epidemiological situation and need for standardising surveillance.
Aggregated data on any enterovirus detected between Jan 1, 2015, and Dec 31, 2017, through national enterovirus reference laboratories were requested from representatives in all 31 EU and EEA countries. Information collected included enterovirus types detected by month, patient age group, symptom, and specimen type. We also collected sequence data on viral capsid sequences for the three most clinically relevant enterovirus types, as identified from the data.
Aggregated data were provided by representatives from 24 (77%) of 31 countries. 9914 (66%) of 14 999 enterovirus infections with information about age were in children younger than 5 years, and 3197 (45%) of 7139 individuals for whom symptoms were reported had neurological symptoms. Other symptoms were non-specific fever (in 1607 23% patients), respiratory symptoms (in 1197 17% patients), hand, foot, and mouth disease (in 528 7% patients), and myocarditis (in 39 1% patients). 68 deaths were temporally associated with enterovirus infection. Typing for 11 559 (67%) of 17 136 specimens revealed 66 enterovirus types. Coxsackievirus A6 was the most frequently detected enterovirus type (in 1556 13% of 11 559 typed enteroviruses), and 292 (65%) of 448 patients with coxsackievirus A6 infection with available clinical data presented with hand, foot, and mouth disease. Echovirus 30 was the second most frequently detected enterovirus type, representing 1412 (12%) of 11 559 typed enteroviruses, and 384 (82%) of 467 individuals with echovirus 30 infection with available clinical data had neurological symptoms. Sequences available from 18 countries showed circulation of newly emerging strains of enterovirus A71 and enterovirus D68.
To our knowledge, this study is the largest investigation of enterovirus circulation in EU and EEA countries and confirms the availability of non-polio enterovirus data in the region. Our study highlights the wide circulation of non-polio enteroviruses in Europe, mostly affecting young children and leading to neurological symptoms. Collecting data on morbidity and mortality related to enterovirus infections, as well as harmonising case definition for surveillance, should be encouraged.
None.
Abstract
SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a ...fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21–28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15–0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.
Human parechoviruses (HPeVs) often cause severe illness among young children. National surveillance with routine testing of all cerebrospinal fluid, fecal, and tissue samples was conducted during ...January 2009-December 2012 in all counties in Denmark (6,817 samples from 4,804 children were screened for HPeV). We detected HPeV RNA in 202 (3.0%) specimens from 149 persons. Young infants were at highest risk for HPeV, and 9 (6%) of the HPeV-infected children died, probably of their HPeV illness. HPeV3 was the most common genotype identified, and 5 closely related clades of HPeV3 circulated in Denmark throughout the study period. Our study adds perspective on the prevalence and clinical and molecular virologic characteristics of HPeV infection.
•European Non-polio Enterovirus Network established.•Collect respiratory, stool and CSF samples for EV testing from patient with neurological infection.•Sensitive PCR method should be used to ...diagnose EV infection.•Sequencing of VP1 capsid protein gene is recommended for EV typing.•Standardased laboratory diagnostics and characterisation key for effective surveillancce.
Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5′noncoding regions (5′NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5′NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.
•A cohort study of wastewater workers’ exposure and systemic inflammation.•The Limulus and rFC endotoxin assays showed different exposures levels.•Inflammation was associated positively with Limulus ...and rFC endotoxin exposure.•Inflammation was associated positively with Limulus and rFC endotoxin dose.•Risk class 2 and allergenic fungi were present in workers’ exposure.
Work in wastewater treatment plants (WWTPs) can be associated with exposure to airborne microorganisms and endotoxin from the working environment. The aim of this study was to obtain knowledge about whether serum levels of the markers of systemic inflammation, C-reactive protein (CRP) and serum amyloid A (SAA), are associated with personal exposure to endotoxin, measured using the Limulus (endotoxinLimulus) and the rFC (endotoxinrFC) assays, as well as bacteria and fungi in a cohort of WWTP workers. Exposure and blood samples were collected for 11 workers over one year. Exposure to endotoxinLimulus-day and endotoxinrFC-day correlated significantly (r = 0.80, p<0.0001, n = 104), but endotoxinLimulus-day was 4.4 (Geometric mean (GM) value) times higher than endotoxinrFC-day (p<0.0001). The endotoxinLimulus-day, endotoxinrFC-day, bacteria, and fungal exposure as well as serum levels of CRP-day (GM=1.4 mg/l) and SAA-day (GM=12 mg/l) differed between workers. Serum levels of SAAday correlated significantly with CRPday (r = 0.30, p = 0.0068). The serum levels of CRPday were associated significantly with exposure to endotoxinLimulus-day. Exposure, SAA and CRP data were also analyzed as av. of each season, and SAAseason was associated positively and significantly with endotoxinLimulus-season and endotoxinrFC-season and negatively with fungalseason exposure. In conclusion, CRPday was associated with the endotoxinLimulus-day and SAAseason with endotoxinLimulus-season and endotoxinrFC-season exposure. Thus, we hereby document that WWTP workers are exposed to airborne endotoxin which seems to have a negative impact on their health.
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The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with ...rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1–G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A6) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.
Experimental evidence suggests that CDHR3 (cadherin-related family member 3) is a receptor for rhinovirus (RV)-C, and a missense variant in this gene (rs6967330) is associated with childhood asthma ...with severe exacerbations.
To determine whether rs6967330 influences RV-C infections and illnesses in early childhood.
We studied associations between rs6967330 and respiratory infections and illnesses in the COPSAC
(Copenhagen Prospective Studies on Asthma in Childhood 2010) and COAST (Childhood Origins of Asthma Birth Cohort Study) birth cohorts, where respiratory infections were monitored prospectively for the first 3 years of life. Nasal samples were collected during acute infections in both cohorts and during asymptomatic periods in COAST and analyzed for RV-A, RV-B, and RV-C, and other common respiratory viruses.
The CDHR3 asthma risk allele (rs6967330-A) was associated with increased risk of respiratory tract illnesses (incidence risk ratio IRR = 1.14 95% confidence interval, 1.05-1.23; P = 0.003). In particular, this variant was associated with risk of respiratory episodes with detection of RV-C in COPSAC
(IRR = 1.89 1.14-3.05; P = 0.01) and in COAST (IRR = 1.37 1.02-1.82; P = 0.03) children, and in a combined meta-analysis (IRR = 1.51 1.13-2.02; P = 0.006). In contrast, the variant was not associated with illnesses related to other viruses (IRR = 1.07 0.92-1.25; P = 0.37). Consistent with these observations, the CDHR3 variant was associated with increased detection of RV-C, but not of other viruses during scheduled visits at specific ages.
The CDHR3 asthma risk allele is associated specifically with RV-C illnesses in two birth cohorts. This clinical evidence supports earlier molecular evidence indicating that CDHR3 functions as an RV-C receptor, and raises the possibility of preventing RV-C infections by targeting CDHR3.
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