The Centers of Excellence for Influenza Research and Response (CEIRR) Risk Assessment Pipeline (RAP) integrates surveillance, phenotypic analysis, and computational modeling across six CEIRR centers to evaluate the pandemic potential of influenza A viruses. By generating coordinated data sets from wild and domestic animals and linking them to viral evolution and functional traits, CEIRR RAP supports the Centers for Disease Control and Prevention’s and the World Health Organization’s risk-assessment efforts. The RAP’s data packages thereby enable evidence-based prioritization of global influenza preparedness and response strategies.
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CEIRR Risk Assessment Pipeline executive reports on H5N1 highly pathogenic avian influenza 2.3.4.4b, swine H1 1B.2, and H9N2 low pathogenicity avian influenza B4.7.2
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SARS-CoV-2 Delta variant re-emerges in US farmed mink and free-ranging white-tailed deer in 2022-2023
American mink (Neogale vison) are susceptible to SARS-CoV-2, but little is known about virus circulation in mink since 2021. Here, in the first active surveillance study of SARS-CoV-2 in apparently healthy farmed mink in the United States, we find a ~0.9% (760/85,656) RT-PCR positivity rate among nasal swabs collected in 18 farms across six states during 2022-2023. Phylogenetic analysis of 293 viral genome sequences shows that human-adapted SARS-CoV-2 variants (e.g., Omicron) repeatedly spill over into mink. Surprisingly, the detection of a Delta lineage virus (AY.39) on a mink farm four months after its last detection in humans within the same state suggests prolonged unsampled transmission. The spread of mink-adapted AY.39 viruses from a mink farm to neighboring free-ranging white-tailed deer represents a rare instance of SARS-CoV-2 transmission between livestock and wildlife. These findings demonstrate the value of active surveillance for identifying subclinical infections and interspecies transmission between humans, mink, and wildlife.
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Highly pathogenic avian influenza (HPAI H5N1, clade 2.3.4.4b, genotype C2.1) in commercial ring-necked pheasants during the 2022 outbreak in the United States
Highly pathogenic avian influenza (HPAI) virus H5N1 clade 2.3.4.4b was introduced into North America in 2021. In 2022, clade 2.3.4.4b spilled into domestic poultry in the United States (U.S.), resulting in the largest HPAI outbreak in U.S. history. In December 2023, H5N1 2.3.4.4b was detected on an upland game bird farm in Pennsylvania. History, clinical signs, and gross lesions were suggestive of marble spleen disease. However, HPAI was identified by real-time reverse-transcriptase polymerase chain reaction; gene sequencing confirmed genotype C2.1 with phylodynamic analyses providing evidence of a wild bird introduction. Predictive mathematical modeling estimated the time of virus introduction onto the farm (15 days (95% C.I., 11-23) before the date of confirmed detection) being similar or longer than previously described for domestic poultry. Although bioexclusion measures were unable to prevent the initial exposure due to industry rearing practices, biocontainment procedures appeared to prevent spread. The lessons learned from this case may be important for other animal agriculture commodities, especially those species that are infrequently handled or observed and may have inaccurately calculated mortality levels. This well-characterized outbreak and other experiences with natural infection should be taken as opportunities to better understand the field dynamics of this virus.
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Genomic analysis reveals dynamics of SARS-CoV-2 during the initial phases of the COVID-19 outbreak in the Dominican Republic
Genomic sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely instituted during the coronavirus disease 2019 (COVID-19) pandemic to track the emergence and spread of new lineages. While this powerful tool can influence public health decisions and therapeutic development, not all regions of the world have had equal access to sequencing capacity, affecting surveillance. One such underrepresented region is the Caribbean islands, including the Dominican Republic (DR). To determine retrospectively what lineages were circulating in the DR in the first year of the pandemic, when there were strict travel restrictions imposed, we sequenced SARS-CoV-2 from nasal swab and saliva samples collected between July 2020 and February 2021. We investigated whether COVID-19 outbreaks were seeded by single or multiple introductions and established epidemiological linkages to other countries. Using 98 newly sequenced samples, we identified 16 SARS-CoV-2 lineages in the DR, indicating many independent introductions from diverse geographic areas. Further, we show that analyzing both globally prevalent and globally rare lineages within the DR highlights different aspects of international disease transmission.IMPORTANCEThis study uses genome sequencing of severe acute respiratory syndrome coronavirus 2 samples collected in an undersampled region of the world-the Caribbean, specifically the Dominican Republic-to make novel inferences about the dynamics of disease spread during a period of the coronavirus disease 2019 pandemic when many diverse lineages were co-circulating globally.
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Novel Highly Pathogenic Avian Influenza A(H5N1) Virus, Argentina, 2025
Genomic sequencing of reemerging highly pathogenic avian influenza A(H5N1) virus detected in Argentina in February 2025 revealed novel triple-reassortant viruses containing gene segments from Eurasian H5N1 and low pathogenicity viruses from South and North American lineages. Our findings highlight continued evolution and diversification of clade 2.3.4.4b H5N1 in the Americas.
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Cross-reactivity between antibodies induced by European swine influenza vaccines and Spanish swine influenza strains
BACKGROUND: Vaccination is an essential tool for controlling the severity of influenza in swine and its spillover risk to humans. Due to fast mutation rates, genomic reassortment, and the high antigenic variability of influenza A viruses (IAV), it is necessary to update vaccine strains to better match and neutralize circulating viruses.
METHODS: In this study, we analyzed the immune cross-reactivity of hemagglutination inhibition (HI) antibodies induced by currently approved European swine influenza vaccines against Spanish swine influenza viruses (SIVs) isolated from 2016 to 2021, as well as human IAV strains, using a murine model. Sera from immunized mice with monovalent (MVV) or trivalent (TVV) swine influenza vaccines were tested against Spanish representative SIVs carrying HAs from different subtypes and lineages using a HI serological assay. Amino acids in the antigenic motifs of the receptor binding site (RBS) of the IAV HA were compared and contrasted among SIV strains to detect changes that may affect protein antigenicity.
RESULTS: Sera from mice immunized with MVV or TVV showed no HI antibodies against a 2019 Eurasian avian-like H1 (EAswH1) SIV. TVV did not induce cross-reactive HI antibodies against two human seasonal H3 SIV from the 2000s (2000s-like H3) or against the human seasonal H3 vaccine strain (HuVacH3). Geometric mean (GM) HI titers of sera from TVV-immunized mice were below the protection threshold (GM < 40) against the recent human seasonal-like H1 (HUswH1) SIV, against an EAswH1 SIV, and against the human seasonal H1 vaccine strain (HuVacH1). HI antibodies induced by MVV showed high cross-reactivity with a 2019 EAswH1 SIV isolate.
CONCLUSION: Currently authorized vaccines do not induce HI antibodies against some contemporary SIV circulating in Spain, nor against human seasonal influenza vaccine strains. Updating vaccine strains to better match new SIVs emerging in Spanish swine is warranted.
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Repeated introductions and widespread transmission of human metapneumovirus in Côte d’Ivoire
In Cote d’Ivoire, the incidence rate of acute respiratory infections (ARIs) rose from 165 cases per 1000 children in 2014 to more than 200 cases per 1000 children in 2015. The genetic diversity, transmission dynamics, and epidemiology of human metapneumovirus (hMPV), a causative agent of ARIs, in Cote d’Ivoire are unknown. This information is key in comprehending the transmission patterns and the role of global strains in establishing local epidemics in the country. Demographic information and biological samples were collected from 3,899 children under five-years-old, from January 1, 2013 to December 31, 2015 through Côte d’Ivoire’s Influenza surveillance network. Phylodynamic modeling was performed on sequences of the surface and attachment glycoprotein genes (F and G, respectively). A total of 6.23% (n = 243/3899) of the samples were positive for hMPV. We observed continuous transmission of hMPV in Côte d’Ivoire throughout the year with peaks in the two dry periods from February to March and July to September. Phylodynamic modeling revealed the circulation of the two large groups of genotypes A and B as well as lineages A, B, B1, and B2. Viral introductions into Côte d’Ivoire were estimated to have occurred 2011-2015 for the F gene genotypes and 2007-2014 for G gene genotypes. Through phylogeographic modeling, we estimated at least 14 viral introductions into Côte d’Ivoire during this period frequently from regions with available sequence data (e.g., Asia). Molecular surveillance and characterization of the evolutionary mechanisms and the spread of hMPV in Côte d’Ivoire allows for differentiating the burden caused by this virus and other co-circulating respiratory viruses like RSV and influenza. Our findings may inform potential vaccine designs for hMPV similar to the recent success for RSV. Therefore, larger-scale and continuous genomic and epidemiological surveillance of hMPV globally and in Côte d’Ivoire is essential for identifying viral introductions and implementing control strategies.
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Ecology and evolution of influenza A viruses in wild waterfowl in Argentina reveals novel viral genotypes
This study investigates the genetic diversity of influenza A viruses (IAVs) in wild birds in Argentina prior to the 2023 outbreak of highly pathogenic avian influenza (HPAI) H5N1. Between 2017 and 2019, 2521 samples were collected from 39 bird species, and viral genomes (n = 44) were sequenced from nine duck species, including a newly identified host in South America, the ringed teal (Callonetta leucophrys). We detected five IAV subtypes for the first time in Argentina: H2N1, H3N8, H7N3, H8N4, and H11N9. Additionally, we identified a previously unrecognized South American H8 lineage that diverged from the North American lineage approximately 50 years ago. Phylogenetic analysis revealed a unique genetic profile: while the viruses’ core internal segments were exclusively from the South American lineage, the surface segments (hemagglutinin and neuraminidase) exhibited reassortment between North and South American lineages. This resulted in novel, Argentina-specific genotypes not observed in other countries in the region. The recent arrival of HPAI H5N1 in South America raises serious concerns about potential reassortment with these unique Argentinian strains, which could create new HPAI viruses with unpredictable characteristics. This study highlights the unique evolutionary dynamics of IAVs in Argentina and emphasizes the need for ongoing influenza surveillance in under-studied regions in South America to monitor these evolving viral populations.
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Controlling bird flu is urgent-for dairy, wildlife, poultry, pets, and people
Highly pathogenic avian influenza viruses of the H5N1 subtype have recently undergone a major geographic expansion. At the same time, these viruses have substantially broadened their host range. Typically, H5N1 circulates in poultry, waterfowl, and shorebirds, but the breadth of avian species affected has increased and spillover to mammals has become common. The recent changes in H5N1 ecology have brought die-offs in wild birds and marine mammals, a sustained outbreak in US dairy cattle, and recurring spillover into domestic cats. Maintenance of H5N1 in wild birds in North America has furthermore produced a persistent risk to US poultry. Circulation of H5N1 in domestic animals has resulted in human infections, especially among farm workers and veterinarians, events that heighten the potential for a pandemic. Through their central position in One Health, veterinarians have a critical role to play in mitigating the impact of H5N1 on animal health, agriculture, and public health.
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Persistence of SARS-CoV-2 Alpha Variant in White-Tailed Deer, Ohio, USA
Free-ranging white-tailed deer (WTD) are highly susceptible to the SARS-CoV-2 virus. Through an opportunistic sampling of WTD in northeast Ohio, USA, during January-March 2023, we identified 6 SARS-CoV-2 lineages from 36 sequences using the pangolin lineages tool, including the B.1.1.7 lineage (Alpha variant) and BQ.1.1, BQ.1.1.63, BQ.1.1.67, BQ.1.23, and XBB.1.5.35 lineages (Omicron variant). The Alpha variant, introduced by a single human-to-deer transmission event, was detected in 5 WTD in January 2023, more than 1 year after the most recent detection of the Alpha variant in humans in Ohio (August 2021). A genetically similar B.1.1.7 lineage virus from WTD in a nearby county in Pennsylvania was positioned with our Ohio deer transmission cluster, suggesting deer-to-deer transmission. The persistence of the Alpha variant in WTD in Ohio warrants continued surveillance to monitor if WTD can become a reservoir for displaced SARS-CoV-2 variants.