Drivers for a pandemic due to avian influenza and options for One Health mitigation measures.

Avian influenza viruses (AIV) remain prevalent among wild bird populations in the European Union and European Economic Area (EU/EEA), leading to significant illness in and death of birds. Transmission between bird and mammal species has been observed, particularly in fur animal farms, where outbreaks have been reported. While transmission from infected birds to humans is rare, there have been instances of exposure to these viruses since 2020 without any symptomatic infections reported in the EU/EEA. However, these viruses continue to evolve globally, and with the migration of wild birds, new strains carrying potential mutations for mammalian adaptation could be selected. If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defences against H5 viruses in humans. The emergence of AIV capable of infecting mammals, including humans, can be facilitated by various drivers. Some intrinsic drivers are related to virus characteristics or host susceptibility. Other drivers are extrinsic and may increase exposure of mammals and humans to AIV thereby stimulating mutation and adaptation to mammals. Extrinsic drivers include the ecology of host species, such as including wildlife, human activities like farming practices and the use of natural resources, climatic and environmental factors. One Health measures to mitigate the risk of AIV adapting to mammals and humans focus on limiting exposure and preventing spread. Key options for actions include enhancing surveillance targeting humans and animals, ensuring access to rapid diagnostics, promoting collaboration between animal and human sectors, and implementing preventive measures such as vaccination. Effective communication to different involved target audiences should be emphasised, as well as strengthening veterinary infrastructure, enforcing biosecurity measures at farms, and reducing wildlife contact with domestic animals. Careful planning of poultry and fur animal farming, especially in areas with high waterfowl density, is highlighted for effective risk reduction.

Avian influenza overview April - June 2023.

Between 29 April and 23 June 2023, highly pathogenic avian influenza (HPAI) A(H5N1) virus (clade 2.3.4.4b) outbreaks were reported in domestic (98) and wild (634) birds across 25 countries in Europe. A cluster of outbreaks in mulard ducks for foie gras production was concentrated in Southwest France, whereas the overall A(H5N1) situation in poultry in Europe and worldwide has eased. In wild birds, black-headed gulls and several new seabird species, mostly gulls and terns (e.g. sandwich terns), were heavily affected, with increased mortality being observed in both adults and juveniles after hatching. Compared to the same period last year, dead seabirds have been increasingly found inland and not only along European coastlines. As regards mammals, A(H5N1) virus was identified in 24 domestic cats and one caracal in Poland between 10 and 30 June 2023. Affected animals showed neurological and respiratory signs, sometimes mortality, and were widely scattered across nine voivodeships in the country. All cases are genetically closely related and identified viruses cluster with viruses detected in poultry (since October 2022, but now only sporadic) and wild birds (December 2022-January 2023) in the past. Uncertainties still exist around their possible source of infection, with no feline-to-feline or feline-to-human transmission reported so far. Since 10 May 2023 and as of 4 July 2023, two A(H5N1) clade 2.3.4.4b virus detections in humans were reported from the United Kingdom, and two A(H9N2) and one A(H5N6) human infections in China. In addition, one person infected with A(H3N8) in China has died. The risk of infection with currently circulating avian H5 influenza viruses of clade 2.3.4.4b in Europe remains low for the general population in the EU/EEA, low to moderate for occupationally or otherwise exposed people to infected birds or mammals (wild or domesticated).

Sensitivity of Detection and Variant Typing of SARS-CoV-2 in European Laboratories.

The molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key for clinical management and surveillance. Funded by the European Centre for Disease Prevention and Control, we conducted an external quality assessment (EQA) on the molecular detection and variant typing of SARS-CoV-2 that included 59 European laboratories in 34 countries. The EQA panel consisted of 12 lyophilized inactivated samples, 10 of which were SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Epsilon, Eta, parental B.1 strain) ranging from 2.5 to 290.0 copies/µL or pooled respiratory viruses (adenovirus, enterovirus, influenza virus A, respiratory syncytial virus, or human coronaviruses 229E and OC43). Of all participants, 72.9% identified the presence of SARS-CoV-2 RNA correctly. In samples containing 25.0 or more genome copies/µL, SARS-CoV-2 was detected by 98.3% of the participating laboratories. Laboratories applying commercial tests scored significantly better (P < 0.0001, Kruskal-Wallis test) than those using in-house assays. Both the molecular detection and the typing of the SARS-CoV-2 variants were associated with the RNA concentrations (P < 0.0001, Kruskal-Wallis test). On average, only 5 out of the 10 samples containing different SARS-CoV-2 variants at different concentrations were correctly typed. The identification of SARS-CoV-2 variants was significantly more successful among EQA participants who combined real-time reverse transcription polymerase chain reaction (RT-PCR)-based assays for mutation detection and high-throughput genomic sequencing than among those who used a single methodological approach (P = 0.0345, Kruskal-Wallis test). Our data highlight the high sensitivity of SARS-CoV-2 detection in expert laboratories as well as the importance of continuous assay development and the benefits of combining different methodologies for accurate SARS-CoV-2 variant typing.

External quality assessment of SARS-CoV-2 serology in European expert laboratories, April 2021.

BackgroundCountries worldwide are focusing to mitigate the ongoing SARS-CoV-2 pandemic by employing public health measures. Laboratories have a key role in the control of SARS-CoV-2 transmission. Serology for SARS-CoV-2 is of critical importance to support diagnosis, define the epidemiological framework and evaluate immune responses to natural infection and vaccine administration.AimThe aim of this study was the assessment of the actual capability among laboratories involved in sero-epidemiological studies on COVID-19 in EU/EEA and EU enlargement countries to detect SARS-CoV-2 antibodies through an external quality assessment (EQA) based on proficiency testing.MethodsThe EQA panels were composed of eight different, pooled human serum samples (all collected in 2020 before the vaccine roll-out), addressing sensitivity and specificity of detection. The panels and two EU human SARS-CoV-2 serological standards were sent to 56 laboratories in 30 countries.ResultsThe overall performance of laboratories within this EQA indicated a robust ability to establish past SARS-CoV-2 infections via detection of anti-SARS-CoV-2 antibodies, with 53 of 55 laboratories using at least one test that characterised all EQA samples correctly. IgM-specific test methods provided most incorrect sample characterisations (24/208), while test methods detecting total immunoglobulin (0/119) and neutralising antibodies (2/230) performed the best. The semiquantitative assays used by the EQA participants also showed a robust performance in relation to the standards.ConclusionOur EQA showed a high capability across European reference laboratories for reliable diagnostics for SARS-CoV-2 antibody responses. Serological tests that provide robust and reliable detection of anti-SARS-CoV-2 antibodies are available.

Influenza returns with a season dominated by clade 3C.2a1b.2a.2 A(H3N2) viruses, WHO European Region, 2021/22.

In the WHO European Region, COVID-19 non-pharmaceutical interventions continued slowing influenza circulation in the 2021/22 season, with reduced characterisation data. A(H3) predominated and, in some countries, co-circulated with A(H1)pdm09 and B/Victoria viruses. No B/Yamagata virus detections were confirmed. Substantial proportions of characterised circulating virus subtypes or lineages differed antigenically from their respective northern hemisphere vaccine components. Appropriate levels of influenza virus characterisations should be maintained until the season end and in future seasons, when surveillance is adapted to integrate SARS-CoV-2.

Spotlight influenza: The 2019/20 influenza season and the impact of COVID-19 on influenza surveillance in the WHO European Region.

BackgroundAnnual seasonal influenza activity in the northern hemisphere causes a high burden of disease during the winter months, peaking in the first weeks of the year.AimWe describe the 2019/20 influenza season and the impact of the COVID-19 pandemic on sentinel surveillance in the World Health Organization (WHO) European Region.MethodsWe analysed weekly epidemiological and virological influenza data from sentinel primary care and hospital sources reported by countries, territories and areas (hereafter countries) in the European Region.ResultsWe observed co-circulation of influenza B/Victoria-lineage, A(H1)pdm09 and A(H3) viruses during the 2019/20 season, with different dominance patterns observed across the Region. A higher proportion of patients with influenza A virus infection than type B were observed. The influenza activity started in week 47/2019, and influenza positivity rate was ≥ 50% for 2 weeks (05-06/2020) rather than 5-8 weeks in the previous five seasons. In many countries a rapid reduction in sentinel reports and the highest influenza activity was observed in weeks 09-13/2020. Reporting was reduced from week 14/2020 across the Region coincident with the onset of widespread circulation of SARS-CoV-2.ConclusionsOverall, influenza type A viruses dominated; however, there were varying patterns across the Region, with dominance of B/Victoria-lineage viruses in a few countries. The COVID-19 pandemic contributed to an earlier end of the influenza season and reduced influenza virus circulation probably owing to restricted healthcare access and public health measures.

Genetic characterization of livestock-associated methicillin-resistant Staphylococcus aureus isolated in Greece.

The interest in livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) strains is increasing due to their wide distribution and transmission even in persons without previous contact with livestock, and these strains pose a public health threat. The aim of the study was the genetic characterization of the whole genome of two epidemiologically unrelated t034 LA-MRSA strains previously isolated from the nasal cavities of a goat and a farmer in Greece. Both strains were assigned to the ST398-Vc-t034 type and they were carrying a single transposon identical to Tn6133. They harbored genes conferring resistance to several antibiotics (aminoglycosides, ß-lactams, macrolides, streptogramin B, tetracycline, and trimethoprim), and genes associated with virulence (enterotoxins, γ-hemolysins, and aureolysin). The present study can serve as baseline for further LA-MRSA epidemiological and evolutionary studies in Greece, while awareness and increased surveillance are needed to avoid their spread.

Characteristics of SARS-CoV-2 variants of concern B.1.1.7, B.1.351 or P.1: data from seven EU/EEA countries, weeks 38/2020 to 10/2021.

We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF: 1.7, 95% confidence interval (CI): 1.0-2.9; B.1.351: 3.6, 95% CI: 2.1-6.2; P.1: 2.6, 95% CI: 1.4-4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF: 2.3, 95% CI: 1.4-3.5; P.1: 2.2, 95% CI: 1.7-2.8).

COVID-19 research priorities for non-pharmaceutical public health and social measures.

Europe is in the midst of a COVID-19 epidemic and a number of non-pharmaceutical public health and social measures have been implemented, in order to contain the transmission of severe acute respiratory syndrome coronavirus 2. These measures are fundamental elements of the public health approach to controlling transmission but have proven not to be sufficiently effective. Therefore, the European Centre for Disease Prevention and Control has conducted an assessment of research gaps that can help inform policy decisions regarding the COVID-19 response. We have identified research gaps in the area of non-pharmaceutical measures, physical distancing, contact tracing, transmission, communication, mental health, seasonality and environment/climate, surveillance and behavioural aspects of COVID-19. This prioritisation exercise is a step towards the global efforts of developing a coherent research road map in coping with the current epidemic but also developing preparedness measures for the next unexpected epidemic.

Monitoring of SARS-CoV-2 infection in mustelids.

American mink and ferret are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but no information is available for other mustelid species. SARS-CoV-2 spreads very efficiently within mink farms once introduced, by direct and indirect contact, high within-farm animal density increases the chance for transmission. Between-farm spread is likely to occur once SARS-CoV-2 is introduced, short distance between SARS-CoV-2 positive farms is a risk factor. As of 29 January 2021, SARS-CoV-2 virus has been reported in 400 mink farms in eight countries in the European Union. In most cases, the likely introduction of SARS-CoV-2 infection into farms was infected humans. Human health can be at risk by mink-related variant viruses, which can establish circulation in the community, but so far these have not shown to be more transmissible or causing more severe impact compared with other circulating SARS-CoV-2. Concerning animal health risk posed by SARS-CoV-2 infection the animal species that may be included in monitoring plans are American mink, ferrets, cats, raccoon dogs, white-tailed deer and Rhinolophidae bats. All mink farms should be considered at risk of infection; therefore, the monitoring objective should be early detection. This includes passive monitoring (in place in the whole territory of all countries where animals susceptible to SARS-CoV-2 are bred) but also active monitoring by regular testing. First, frequent testing of farm personnel and all people in contact with the animals is recommended. Furthermore randomly selected animals (dead or sick animals should be included) should be tested using reverse transcriptase-polymerase chain reaction (RT-PCR), ideally at weekly intervals (i.e. design prevalence approximately 5% in each epidemiological unit, to be assessed case by case). Suspected animals (dead or with clinical signs and a minimum five animals) should be tested for confirmation of SARS-CoV-2 infection. Positive samples from each farm should be sequenced to monitor virus evolution and results publicly shared.

Very little influenza in the WHO European Region during the 2020/21 season, weeks 40 2020 to 8 2021.

Between weeks 40 2020 and 8 2021, the World Health Organization European Region experienced a 99.8% reduction in sentinel influenza virus positive detections (33/25,606 tested; 0.1%) relative to an average of 14,966/39,407 (38.0%; p < 0.001) over the same time in the previous six seasons. COVID-19 pandemic public health and physical distancing measures may have extinguished the 2020/21 European seasonal influenza epidemic with just a few sporadic detections of all viral subtypes. This might possibly continue during the remainder of the influenza season.

The role of oral microbiome in pemphigus vulgaris.

While the impact of oral microbiome dysbiosis on autoimmune diseases has been partially investigated, its role on bullous diseases like Pemphigus Vulgaris (PV) is a totally unexplored field. This study aims to present the composition and relative abundance of microbial communities in both healthy individuals and patients with oral PV lesions. Ion Torrent was used to apply deep sequencing of the bacterial 16S rRNA gene to oral smear samples of 15 healthy subjects and 15 patients. The results showed that the most dominant phyla were Firmicutes (55.88% controls-c vs 61.27% patients-p, p value = 0.002), Proteobacteria (9.17%c vs 12.33%p, p value = 0.007) and Fusobacteria (3.39%c vs 4.09%p, p value = 0.03). Alpha diversity showed a significant difference in the number of genera between patients and controls (p value = 0.04). Beta diversity showed statistical differences in the microbial community composition between two groups. Fusobacterium nucleatum, Gemella haemolysans and Parvimonas micra were statistically abundant in patients. We noticed the characteristic fetor coming out of oral PV lesions. Most of anaerobic bacteria responsible for oral halitosis are periopathogenic. Though, only F. nucleatum and P. micra were differentially abundant in our patients. Especially, F. nucleatum has been reported many times as responsible for bad breath. Furthermore, Streptococcus salivarius and Rothia mucilaginosa, species mostly associated with clean breath, were found in relative abundance in the healthy group. Consequently, the distinct malodor observed in PV patients might be attributed either to the abundance of F. nucleatum and P. micra and/or to the lower levels of S. salivarius and R. mucilanginosa in oral lesions.

Variable Sensitivity of SARS-CoV-2 Molecular Detection in European Expert Laboratories: External Quality Assessment, June and July 2020.

During the ongoing coronavirus disease 2019 (COVID-19) outbreak, robust detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key element for clinical management and to interrupt transmission chains. We organized an external quality assessment (EQA) of molecular detection of SARS-CoV-2 for European expert laboratories. An EQA panel composed of 12 samples, containing either SARS-CoV-2 at different concentrations to evaluate sensitivity or other respiratory viruses to evaluate specificity of SARS-CoV-2 testing, was distributed to 68 laboratories in 35 countries. Specificity samples included seasonal human coronaviruses hCoV-229E, hCoV-NL63, and hCoV-OC43, as well as Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and human influenza viruses A and B. Sensitivity results differed among laboratories, particularly for low-concentration SARS-CoV-2 samples. Results indicated that performance was mostly independent of the selection of specific extraction or PCR methods.

Virological surveillance of influenza viruses in the WHO European Region in 2019/20 - impact of the COVID-19 pandemic.

The COVID-19 pandemic negatively impacted the 2019/20 WHO European Region influenza surveillance. Compared with previous 4-year averages, antigenic and genetic characterisations decreased by 17% (3,140 vs 2,601) and 24% (4,474 vs 3,403). Of subtyped influenza A viruses, 56% (26,477/47,357) were A(H1)pdm09, 44% (20,880/47,357) A(H3). Of characterised B viruses, 98% (4,585/4,679) were B/Victoria. Considerable numbers of viruses antigenically differed from northern hemisphere vaccine components. In 2020/21, maintaining influenza virological surveillance, while supporting SARS-CoV-2 surveillance is crucial.

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020.

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.

Predominance of influenza virus A(H3N2) 3C.2a1b and A(H1N1)pdm09 6B.1A5A genetic subclades in the WHO European Region, 2018-2019.

BACKGROUND: The 2018/2019 influenza season in the WHO European Region was dominated by influenza A (H1N1)pdm09 and (H3N2) viruses, with very few influenza B viruses detected. METHODS: Countries in the European Region reported virus characterization data to The European Surveillance System for weeks 40/2018 to 20/2019. These virus antigenic and genetic characterization and haemagglutinin (HA) sequence data were analysed to describe and assess circulating viruses relative to the 2018/2019 vaccine virus components for the northern hemisphere. RESULTS: Thirty countries reported 4776 viruses characterized genetically and 3311 viruses antigenically. All genetically characterized A(H1N1)pdm09 viruses fell in subclade 6B.1A, of which 90% carried the amino acid substitution S183P in the HA gene. Antigenic data indicated that circulating A(H1N1)pdm09 viruses were similar to the 2018/2019 vaccine virus. Genetic data showed that A(H3N2) viruses mostly fell in clade 3C.2a (75%) and 90% of which were subclade 3C.2a1b. A lower proportion fell in clade 3C.3a (23%) and were antigenically distinct from the vaccine virus. All B/Victoria viruses belonged to clade 1A; 30% carried a double amino acid deletion in HA and were genetically and antigenically similar to the vaccine virus component, while 55% carried a triple amino acid deletion or no deletion in HA; these were antigenically distinct from each other and from the vaccine component. All B/Yamagata viruses belonged to clade 3 and were antigenically similar to the virus component in the quadrivalent vaccine for 2018/2019. CONCLUSIONS: A simultaneous circulation of genetically and antigenically diverse A(H3N2) and B/Victoria viruses was observed and represented a challenge to vaccine strain selection.

Alternating patterns of seasonal influenza activity in the WHO European Region following the 2009 pandemic, 2010-2018.

BACKGROUND: Influenza virus infections are common and lead to substantial morbidity and mortality worldwide. We characterized the first eight influenza epidemics since the 2009 influenza pandemic by describing the distribution of viruses and epidemics temporally and geographically across the WHO European Region. METHODS: We retrospectively analyzed laboratory-confirmed influenza detections in ambulatory patients from sentinel sites. Data were aggregated by reporting entity and season (weeks 40-20) for 2010-2011 to 2017-2018. We explored geographical spread using correlation coefficients. RESULTS: There was variation in the regional influenza epidemics during the study period. Influenza A virus subtypes alternated in dominance, except for 2013-2014 during which both cocirculated, and only one season (2017-2018) was B virus dominant. The median start week for epidemics in the Region was week 50, the time to the peak ranged between four and 13 weeks, and the duration of the epidemic ranged between 19 and 25 weeks. There was evidence of a west-to-east spread across the Region during epidemics in 2010-2011 (r = .365; P = .019), 2012-2013 (r = .484; P = .001), 2014-2015 (r = .423; P = .006), and 2017-2018 (r = .566; P < .001) seasons. Variation in virus distribution and timing existed within reporting entities across seasons and across reporting entities for a given season. CONCLUSIONS: Aggregated influenza detection data from sentinel surveillance sites by season between 2010 and 2018 have been presented for the European Region for the first time. Substantial diversity exists between influenza epidemics. These data can inform prevention and control efforts at national, sub-national, and international levels. Aggregated, regional surveillance data from early affected reporting entities may provide an early warning function and be helpful for early season forecasting efforts.

The possible role of oral microbiome in autoimmunity.

OBJECTIVE: The human microbiome refers to the entire habitat, including microorganisms, their genomes and the surrounding environmental conditions of the microbial ecosystem. When the equilibrium between microbial habitats and host is disturbed, dysbiosis is caused. The oral microbiome (OMB) has been implicated in the manifestation of many intra- and extraoral diseases. Lately, there has been an intense effort to investigate and specify the relationship between microbial complexes, especially that of the oral cavity and intestine and autoimmunity. This study aimed to review the current literature about the possible role of the OMB in the pathogenesis of autoimmune diseases. METHODS: We searched for published articles in English indexed in PubMed, Medline, Research Gate and Google Scholar using a search strategy that included terms for oral microbiome, autoimmune diseases, dysbiosis and next-generation sequencing. RESULTS: An important number of articles were gathered and used for the description of the possible impact of dysbiosis of OMB in the pathogenesis of Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, Behcet's disease, Crohn's disease and psoriasis. CONCLUSION: This review article draws attention to the relationship between OMB and the triggering of a number of autoimmune diseases. Although this specific topic has been previously reviewed, herein, the authors review recent literature regarding the full list of nosological entities related to the OMB, point out the interaction between the microbiome and sex hormones with regard to their role in autoimmunity and discuss novel and promising therapeutic approaches for systemic autoimmune diseases. Furthermore, the question arises of whether the OMB is associated with oral bullous autoimmune diseases.

European Pandemic Influenza Preparedness Planning: A Review of National Plans, July 2016.

Pandemic influenza A (H1N1) commenced in April 2009. Robust planning and preparedness are needed to minimize the impact of a pandemic. This study aims to review if key elements of pandemic preparedness are included in national plans of European countries. Key elements were identified before and during the evaluations of the 2009 pandemic and are defined in this study by 42 items. These items are used to score a total of 28 publicly available national pandemic influenza plans. We found that plans published before the 2009 influenza pandemic score lower than plans published after the pandemic. Plans from countries with a small population size score significantly lower compared to national plans from countries with a big population (P <.05). We stress that the review of written plans does not reflect the actual preparedness level, as the level of preparedness entails much more than the existence of a plan. However, we do identify areas of improvement for the written plans, such as including aspects on the recovery and transition phase and several opportunities to improve coordination and communication, including a description of the handover of leadership from health to wider sector management and communication activities during the pre-pandemic phase. (Disaster Med Public Health Preparedness. 2019;13:582-592).