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 September-December 2023.

Between 2 September and 1 December 2023, highly pathogenic avian influenza (HPAI) A(H5) outbreaks were reported in domestic (88) and wild (175) birds across 23 countries in Europe. Compared to previous years, the increase in the number of HPAI virus detections in waterfowl has been delayed, possibly due to a later start of the autumn migration of several wild bird species. Common cranes were the most frequently affected species during this reporting period with mortality events being described in several European countries. Most HPAI outbreaks reported in poultry were primary outbreaks following the introduction of the virus by wild birds, with the exception of Hungary, where two clusters involving secondary spread occurred. HPAI viruses identified in Europe belonged to eleven different genotypes, seven of which were new. With regard to mammals, the serological survey conducted in all fur farms in Finland revealed 29 additional serologically positive farms during this reporting period. Wild mammals continued to be affected mostly in the Americas, from where further spread into wild birds and mammals in the Antarctic region was described for the first time. Since the last report and as of 1 December 2023, three fatal and one severe human A(H5N1) infection with clade 2.3.2.1c viruses have been reported by Cambodia, and one A(H9N2) infection was reported from China. No human infections related to the avian influenza detections in animals in fur farms in Finland have been reported, and human infections with avian influenza remain a rare event. 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. The risk of infection remains low to moderate for occupationally or otherwise exposed people to infected birds or mammals (wild or domesticated); this assessment covers different situations that depend on the level of exposure.

Avian influenza overview June-September 2023.

Between 24 June and 1 September 2023, highly pathogenic avian influenza (HPAI) A(H5) outbreaks were reported in domestic (25) and wild (482) birds across 21 countries in Europe. Most of these outbreaks appeared to be clustered along coastlines with only few HPAI virus detections inland. In poultry, all HPAI outbreaks were primary and sporadic with most of them occurring in the United Kingdom. In wild birds, colony-breeding seabirds continued to be most heavily affected, but an increasing number of HPAI virus detections in waterfowl is expected in the coming weeks. The current epidemic in wild birds has already surpassed the one of the previous epidemiological year in terms of total number of HPAI virus detections. As regards mammals, A(H5N1) virus was identified in 26 fur animal farms in Finland. Affected species included American mink, red and Arctic fox, and common raccoon dog. The most likely source of introduction was contact with gulls. Wild mammals continued to be affected worldwide, mostly red foxes and different seal species. Since the last report and as of 28 September 2023, two A(H5N1) clade 2.3.4.4b virus detections in humans have been reported by the United Kingdom, and three human infections with A(H5N6) and two with A(H9N2) were reported from China, respectively. No human infection related to the avian influenza detections in animals on fur farms in Finland or in cats in Poland have been reported, and human infections with avian influenza remain a rare event. 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. The risk of infection remains low to moderate for occupationally or otherwise exposed people to infected birds or mammals (wild or domesticated); this assessment covers different situations that depend on the level of exposure.

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).

Avian influenza overview March - April 2023.

Between 2 March and 28 April 2023, highly pathogenic avian influenza (HPAI) A(H5Nx) virus, clade 2.3.4.4b, outbreaks were reported in domestic (106) and wild (610) birds across 24 countries in Europe. Poultry outbreaks occurred less frequently compared to the previous reporting period and compared to spring 2022. Most of these outbreaks were classified as primary outbreaks without secondary spread and some of them associated with atypical disease presentation, in particular low mortality. In wild birds, black-headed gulls continued to be heavily affected, while also other threatened wild bird species, such as the peregrine falcon, showed increased mortality. The ongoing epidemic in black-headed gulls, many of which breed inland, may increase the risk for poultry, especially in July-August, when first-year birds disperse from the breeding colonies. HPAI A(H5N1) virus also continued to expand in the Americas, including in mammalian species, and is expected to reach the Antarctic in the near future. HPAI virus infections were detected in six mammal species, particularly in marine mammals and mustelids, for the first time, while the viruses currently circulating in Europe retain a preferential binding for avian-like receptors. Since 13 March 2022 and as of 10 May 2023, two A(H5N1) clade 2.3.4.4b virus detections in humans were reported from China (1), and Chile (1), as well as three A(H9N2) and one A(H3N8) human infections in China. 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, and low to moderate for occupationally or otherwise exposed people.

SARS-CoV-2 in animals: susceptibility of animal species, risk for animal and public health, monitoring, prevention and control.

The epidemiological situation of SARS-CoV-2 in humans and animals is continually evolving. To date, animal species known to transmit SARS-CoV-2 are American mink, raccoon dog, cat, ferret, hamster, house mouse, Egyptian fruit bat, deer mouse and white-tailed deer. Among farmed animals, American mink have the highest likelihood to become infected from humans or animals and further transmit SARS-CoV-2. In the EU, 44 outbreaks were reported in 2021 in mink farms in seven MSs, while only six in 2022 in two MSs, thus representing a decreasing trend. The introduction of SARS-CoV-2 into mink farms is usually via infected humans; this can be controlled by systematically testing people entering farms and adequate biosecurity. The current most appropriate monitoring approach for mink is the outbreak confirmation based on suspicion, testing dead or clinically sick animals in case of increased mortality or positive farm personnel and the genomic surveillance of virus variants. The genomic analysis of SARS-CoV-2 showed mink-specific clusters with a potential to spill back into the human population. Among companion animals, cats, ferrets and hamsters are those at highest risk of SARS-CoV-2 infection, which most likely originates from an infected human, and which has no or very low impact on virus circulation in the human population. Among wild animals (including zoo animals), mostly carnivores, great apes and white-tailed deer have been reported to be naturally infected by SARS-CoV-2. In the EU, no cases of infected wildlife have been reported so far. Proper disposal of human waste is advised to reduce the risks of spill-over of SARS-CoV-2 to wildlife. Furthermore, contact with wildlife, especially if sick or dead, should be minimised. No specific monitoring for wildlife is recommended apart from testing hunter-harvested animals with clinical signs or found-dead. Bats should be monitored as a natural host of many coronaviruses.

Avian influenza overview December 2022 - March 2023.

Between 3 December 2022 and 1 March 2023 highly pathogenic avian influenza (HPAI) A(H5N1) virus, clade 2.3.4.4b, was reported in Europe in domestic (522) and wild (1,138) birds over 24 countries. An unexpected number of HPAI virus detections in sea birds were observed, mainly in gull species and particularly in black-headed gulls (large mortality events were observed in France, Belgium, the Netherlands, and Italy). The close genetic relationship among viruses collected from black-headed gulls suggests a southward spread of the virus. Moreover, the genetic analyses indicate that the virus persisted in Europe in residential wild birds during and after the summer months. Although the virus retained a preferential binding for avian-like receptors, several mutations associated to increased zoonotic potential were detected. The risk of HPAI virus infection for poultry due to the virus circulating in black-headed gulls and other gull species might increase during the coming months, as breeding bird colonies move inland with possible overlap with poultry production areas. Worldwide, HPAI A(H5N1) virus continued to spread southward in the Americas, from Mexico to southern Chile. The Peruvian pelican was the most frequently reported infected species with thousands of deaths being reported. The reporting of HPAI A(H5N1) in mammals also continued probably linked to feeding on infected wild birds. In Peru, a mass mortality event of sea lions was observed in January and February 2023. Since October 2022, six A(H5N1) detections in humans were reported from Cambodia (a family cluster with 2 people, clade 2.3.2.1c), China (2, clade 2.3.4.4b), Ecuador (1, clade 2.3.4.4b), and Vietnam (1, unspecified clade), as well as two A(H5N6) human infections from China. The risk of infection with currently circulating avian H5 influenza viruses of clade 2.3.4.4b in Europe is assessed as low for the general population in the EU/EEA, and low to moderate for occupationally or otherwise exposed people.

Avian influenza overview September - December 2022.

Between October 2021 and September 2022 Europe has suffered the most devastating highly pathogenic avian influenza (HPAI) epidemic with a total of 2,520 outbreaks in poultry, 227 outbreaks in captive birds, and 3,867 HPAI virus detections in wild birds. The unprecedent geographical extent (37 European countries affected) resulted in 50 million birds culled in affected establishments. In the current reporting period, between 10 September and 2 December 2022, 1,163 HPAI virus detections were reported in 27 European countries in poultry (398), captive (151) and wild birds (613). A decrease in HPAI virus detections in colony-breeding seabirds species and an increase in the number of detections in waterfowl has been observed. The continuous circulation of the virus in the wild reservoir has led to the frequent introduction of the virus into poultry populations. It is suspected that waterfowl might be more involved than seabirds in the incursion of HPAI virus into poultry establishments. In the coming months, the increasing infection pressure on poultry establishments might increase the risk of incursions in poultry, with potential further spread, primarily in areas with high poultry densities. The viruses detected since September 2022 (clade 2.3.4.4b) belong to eleven genotypes, three of which have circulated in Europe during the summer months, while eight represent new genotypes. HPAI viruses were also detected in wild and farmed mammal species in Europe and North America, showing genetic markers of adaptation to replication in mammals. Since the last report, two A(H5N1) detections in humans in Spain, one A(H5N1), one A(H5N6) and one A(H9N2) human infection in China as well as one A(H5) infection without NA-type result in Vietnam were reported, respectively. The risk of infection is assessed as low for the general population in the EU/EEA, and low to medium for occupationally exposed people.

Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020.

BackgroundTimely treatment with neuraminidase inhibitors (NAI) can reduce severe outcomes in influenza patients.AimWe assessed the impact of antiviral treatment on in-hospital deaths of laboratory-confirmed influenza patients in 11 European Union countries from 2010/11 to 2019/20.MethodsCase-based surveillance data from hospitalised patients with known age, sex, outcome, ward, vaccination status, timing of antiviral treatment, and hospitalisation were obtained. A mixed effect logistic regression model using country as random intercept was applied to estimate the adjusted odds ratio (aOR) for in-hospital death in patients treated with NAIs vs not treated.ResultsOf 19,937 patients, 31% received NAIs within 48 hours of hospital admission. Older age (60-79 years aOR 3.0, 95% CI: 2.4-3.8; 80 years 8.3 (6.6-10.5)) and intensive care unit admission (3.8, 95% CI: 3.4-4.2) increased risk of dying, while early hospital admission after symptom onset decreased risk (aOR 0.91, 95% CI: 0.90-0.93). NAI treatment initiation within 48 hours and up to 7 days reduced risk of dying (0-48 hours aOR 0.51, 95% CI: 0.45-0.59; 3-4 days 0.59 (0.51-0.67); 5-7 days 0.64 (0.56-0.74)), in particular in patients 40 years and older (e.g. treatment within 48 hours: 40-59 years aOR 0.43, 95% CI: 0.28-0.66; 60-79 years 0.50 (0.39-0.63); ≥80 years 0.51 (0.42-0.63)).ConclusionNAI treatment given within 48 hours and possibly up to 7 days after symptom onset reduced risk of in-hospital death. NAI treatment should be considered in older patients to prevent severe outcomes.

Avian influenza overview June - September 2022.

The 2021-2022 highly pathogenic avian influenza (HPAI) epidemic season is the largest HPAI epidemic so far observed in Europe, with a total of 2,467 outbreaks in poultry, 47.7 million birds culled in the affected establishments, 187 outbreaks in captive birds, and 3,573 HPAI virus detections in wild birds with an unprecedent geographical extent reaching from Svalbard islands to South Portugal and Ukraine, affecting 37 European countries. Between 11 June and 9 September 2022, 788 HPAI virus detections were reported in 16 European countries in poultry (56), captive (22) and wild birds (710). Several colony-breeding seabird species exhibited widespread and massive mortality from HPAI A(H5N1) virus along the northwest coast of Europe. This resulted in an unprecedentedly high level of HPAI virus detections in wild birds between June and August 2022 and represents an ongoing risk of infection for domestic birds. HPAI outbreaks were still observed in poultry from June to September with five-fold more infected premises than observed during the same period in 2021 and mostly distributed along the Atlantic coast. Response options to this new epidemiological situation include the definition and rapid implementation of suitable and sustainable HPAI mitigation strategies such as appropriate biosecurity measures and surveillance strategies for early detection in the different poultry production systems. The viruses currently circulating in Europe belong to clade 2.3.4.4b with seven genotypes, three of which identified for the first time during this time period, being detected during summer. HPAI A(H5) viruses were also detected in wild mammal species in Europe and North America and showed genetic markers of adaptation to replication in mammals. Since the last report, two A(H5N6), two A(H9N2) and one A(H10N3) human infections were reported in China. The risk of infection is assessed as low for the general population in the EU/EEA, and low to medium for occupationally exposed people.

Avian influenza overview March - June 2022.

The 2021-2022 highly pathogenic avian influenza (HPAI) epidemic season is the largest epidemic so far observed in Europe, with a total of 2,398 outbreaks in poultry, 46 million birds culled in the affected establishments, 168 detections in captive birds, and 2,733 HPAI events in wild birds in 36 European countries. Between 16 March and 10 June 2022, 1,182 HPAI virus detections were reported in 28 EU/EEA countries and United Kingdom in poultry (750), and in wild (410) and captive birds (22). During this reporting period, 86% of the poultry outbreaks were secondary due to between-farm spread of HPAI virus. France accounted for 68% of the overall poultry outbreaks, Hungary for 24% and all other affected countries for less than 2% each. Most detections in wild birds were reported by Germany (158), followed by the Netherlands (98) and the United Kingdom (48). The observed persistence of HPAI (H5) virus in wild birds since the 2020-2021 epidemic wave indicates that it may have become endemic in wild bird populations in Europe, implying that the health risk from HPAI A(H5) for poultry, humans, and wildlife in Europe remains present year-round, with the highest risk in the autumn and winter months. Response options to this new epidemiological situation include the definition and the rapid implementation of suitable and sustainable HPAI mitigation strategies such as appropriate biosecurity measures and surveillance strategies for early detection measures in the different poultry production systems. Medium to long-term strategies for reducing poultry density in high-risk areas should also be considered. The results of the genetic analysis indicate that the viruses currently circulating in Europe belong to clade 2.3.4.4b. HPAI A(H5) viruses were also detected in wild mammal species in Canada, USA and Japan, and showed genetic markers of adaptation to replication in mammals. Since the last report, four A(H5N6), two A(H9N2) and two A(H3N8) human infections were reported in China and one A(H5N1) in USA. The risk of infection is assessed as low for the general population in the EU/EEA, and low to medium for occupationally exposed people.

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.

Avian influenza overview December 2021 - March 2022.

Between 9 December 2021 and 15 March 2022, 2,653 highly pathogenic avian influenza (HPAI) virus detections were reported in 33 EU/EEA countries and the UK in poultry (1,030), in wild (1,489) and in captive birds (133). The outbreaks in poultry were mainly reported by France (609), where two spatiotemporal clusters have been identified since October 2021, followed by Italy (131), Hungary (73) and Poland (53); those reporting countries accounted together for 12.8 of the 17.5 million birds that were culled in the HPAI affected poultry establishments in this reporting period. The majority of the detections in wild birds were reported by Germany (767), the Netherlands (293), the UK (118) and Denmark (74). HPAI A(H5) was detected in a wide range of host species in wild birds, indicating an increasing and changing risk for virus incursion into poultry farms. The observed persistence and continuous circulation of HPAI viruses in migratory and resident wild birds will continue to pose a risk for the poultry industry in Europe for the coming months. This requires the definition and the rapid implementation of suitable and sustainable HPAI mitigation strategies such as appropriate biosecurity measures, surveillance plans and early detection measures in the different poultry production systems. The results of the genetic analysis indicate that the viruses currently circulating in Europe belong to clade 2.3.4.4b. Some of these viruses were also detected in wild mammal species in the Netherlands, Slovenia, Finland and Ireland showing genetic markers of adaptation to replication in mammals. Since the last report, the UK reported one human infection with A(H5N1), China 17 human infections with A(H5N6), and China and Cambodia 15 infections with A(H9N2) virus. The risk of infection for the general population in the EU/EEA is assessed as low, and for occupationally exposed people, low to medium.

Avian influenza overview May - September 2021.

The 2020-2021 avian influenza epidemic with a total of 3,777 reported highly pathogenic avian influenza (HPAI) detections and approximately 22,900,000 affected poultry birds in 31 European Countries appears to be one of the largest HPAI epidemics that has ever occurred in Europe. Between 15 May and 15 September 2021, 162 HPAI virus detections were reported in 17 EU/EEA countries and the UK in poultry (51), in wild (91) and captive birds (20). The detections in poultry were mainly reported by Kosovo (20), Poland (17) and Albania (6). HPAI virus was detected during the summer months in resident wild bird populations mainly in northern Europe. The data presented in this report indicates that HPAI virus is still circulating in domestic and wild bird populations in some European countries and that the epidemic is not over yet. Based on these observations, it appears that the persistence of HPAI A(H5) in Europe continues to pose a risk of further virus incursions in domestic bird populations. Furthermore, during summer, HPAI viruses were detected in poultry and several wild bird species in areas in Russia that are linked to key migration areas of wild waterbirds; this is of concern due to the possible introduction and spread of novel virus strains via wild birds migrating to the EU countries during the autumn from the eastern breeding to the overwintering sites. Nineteen different virus genotypes have been identified so far in Europe and Central Asia since July 2020, confirming a high propensity for this virus to undergo reassortment events. Since the last report, 15 human infections due to A(H5N6) HPAI and five human cases due to A(H9N2) low pathogenic avian influenza (LPAI) virus have been reported from China. Some of these cases were caused by a virus with an HA gene closely related to the A(H5) viruses circulating in Europe. The viruses characterised to date retain a preference for avian-type receptors; however, the reports of transmission events of A(H5) viruses to mammals and humans in Russia, as well as the recent A(H5N6) human cases in China may indicate a continuous risk of these viruses adapting to mammals. The risk of infection for the general population in the EU/EEA is assessed as very low, and for occupationally exposed people low, with large uncertainty due to the high diversity of circulating viruses in the bird populations.

Avian influenza overview February - May 2021.

The 2020-2021 epidemic with a total of 3,555 reported HPAI detections and around 22,400,000 affected poultry birds in 28 European Countries appears to be one of the largest and most devastating HPAI epidemics ever occurred in Europe. Between 24 February and 14 May 2021, 1,672 highly pathogenic avian influenza (HPAI) virus detections were reported in 24 EU/EEA countries and the UK in poultry (n=580), and in wild (n=1,051) and captive birds (n=41). The majority of the detections in poultry were reported by Poland that accounted for 297 outbreaks occurring in a densely populated poultry area over a short period of time, followed by Germany with 168 outbreaks. Germany accounted for 603 detections in wild birds, followed by Denmark and Poland with 167 and 56 detections, respectively. A second peak of HPAI-associated wild bird mortality was observed from February to April 2021 in north-west Europe. The observed longer persistence of HPAI in wild birds compared to previous years may result in a continuation of the risk for juveniles of wild birds and mammals, as well as for virus entry into poultry farms. Therefore, enhanced awareness among farmers to continue applying stringent biosecurity measures and to monitor and report increases in daily mortality and drops in production parameters, are recommended. Sixteen different genotypes were identified to date in Europe and Russia, suggesting a high propensity of these viruses to reassort. The viruses characterized to date retain a preference for avian-type receptors; however, transmission events to mammals and the identification of sporadic mutations of mammal adaptation, indicate ongoing evolution processes and possible increased ability of viruses within this clade to further adapt and transmit to mammals including humans. Since the last report, two human infections due to A(H5N6) HPAI were reported from China and Laos and 10 human cases due to A(H9N2) low pathogenic avian influenza (LPAI) virus identified in China and Cambodia. The risk of infection for the general population in the EU/EEA is assessed as very low and for occupationally exposed people low. People exposed during avian influenza outbreaks should adhere to protection measures, strictly wear personal protective equipment and get tested immediately when developing respiratory symptoms or conjunctivitis within 10 days after exposure.

An Evaluation of Hepatitis E Virus Molecular Typing Methods.

BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Better understanding of HEV subtypes involved in hepatitis E infections is essential. Investigation of sources and routes of transmission and the identification of potential clusters/outbreaks rely upon molecular typing of viral strains. A study was carried out to evaluate the ability of laboratories to undertake molecular typing with genotype and subtype determination. METHODS: A blinded panel of 11 different Orthohepevirus A strains was distributed to 28 laboratories performing HEV sequence analysis. Laboratories used their routine HEV sequencing and genotyping methods. RESULTS: Results were returned by 25 laboratories. Overall, 93% samples were assigned to the correct genotype and 81% were assigned to the correct subtype. Fragments amplified for typing ranged in size and the sequencing assays targeted both the structural and non-structural protein-coding regions. There was good agreement between the reported sequences where methods targeted overlapping fragments. In some cases, incorrect genotypes/subtypes were reported, including those not contained in the panel, and in one case, a genotype was reported for a blinded control sample containing Zika virus; collectively these data indicate contamination problems. CONCLUSIONS: In general, identification of genotypes was good; however, in a small number of cases, there was a failure to generate sequences from some of the samples. There was generally broad agreement between the use of online typing tools such as the one provided by HEVnet and curated lists of published HEV reference sequences; however, going forward harmonization between these resources is essential.