#17,748
The interconnected and often overlapping network of flyways for migratory birds depicted above has allowed the HPAI H5 virus to spread - albeit slowly and tentatively at first - from Southern China 20 years ago, first to Southeast Asia, Europe and the Middle East, and most recently to North and South America.
Over time, the H5 virus has evolved and diversified (via both antigenic drift and antigenic shift) into numerous clades, subclades, and genotypes.
As the virus expands geographically, it increases its opportunities to encounter, and reassort with, other influenza A viruses. Most of these hybrids fall by the wayside, unable to compete with more biologically `fit' strains, but occasionally nature produces a `better virus'.
In the mid-2000s, the emergence of clade 2.2 enabled the virus to spread more effectively via migratory birds, and heralded its arrival to Europe, the Middle East, and West Africa (see H5N1 Influenza Continues To Circulate and Change 2006 by Webster et. al.).
While other clades still exist (most notably clade 2.3.2.1c in Cambodia). clade 2.3.4.4x has dominated since it underwent a major reassortment over the summer of 2016, prior to sparking Europe's largest avian epizootic on record.Clade 2.3.2 emerged in 2009 (see EID Journal New Avian Influenza Virus (H5N1) in Wild Birds, Qinghai, China) causing large bird die offs, followed by Clade 2.3.4.4 H5 which decimated South Korea's poultry in 2014, before winging its way to North America a year later (see OIE/APHIS: HPAI H5N8 & H5N2 Detected In Washington State Wild Birds).
Often, our first clue that the HPAI H5 virus has changed significantly comes from unusually large die offs of birds, spillovers into new species, or unusual disease presentations. The type of events that we've seen with increasing frequency since 2021.
This week the CDC's EID Journal has published two reports on our evolving HPAI H5 virus. Due to their lengths, I've only posted some excerpts, so follow the links to read them in their entirety.
Our first stop is a report on a mass die off of migratory birds in Russia in 2022, and the recently acquired genetic changes observed in the virus.
Dispatch
Ivan Sobolev, Alimurad Gadzhiev, Kirill Sharshov, Olesia Ohlopkova, Kristina Stolbunova, Artem Fadeev, Nikita Dubovitskiy, Alexandra Glushchenko, Victor Irza, Maxim Perkovsky, Kirill Litvinov, Natalia Meshcheriakova, Guy Petherbridge, and Alexander Shestopalov
Abstract
In May 2022, we observed a substantial die-off of wild migratory waterbirds on Maliy Zhemchuzhniy Island in the Caspian Sea, Russia. The deaths were caused by highly pathogenic avian influenza A(H5N1) clade 2.3.4.4.b virus. Continued surveillance of influenza viruses in wild bird populations is needed to predict virus spread over long distances.
(SNIP)
On April 28, 2022, near the end of the egg incubation period, we had counted a total of 26,769 Great black-headed gull nests, 7,340 Caspian gull nests, and 5,267 Caspian tern nests on Maliy Zhemchuzhniy Island. In May, 1 week later, we detected mass deaths of waterbirds on the island comprising 25,157 Great black-headed gulls, 3,507 Caspian gulls, 5,641 Caspian terns, and 14 Dalmatian pelicans (Appendix 1 Figure 1).
Nearly all gull and tern chicks died during the nesting period. The mass death event began during hatching of Great black-headed gulls. We only found the corpses of chicks (with down but without feathers) that were similar in age. We assume that not all of the chicks actually died from disease; death of adult birds likely led to the deaths of chicks in their nests. The Caspian terns were still incubating eggs at that time; consequently, the death of adult terns led to the death of egg clutches in their nests. We did not observe live chicks on the island during the remaining 2022 nesting season.
(SNIP)
Conclusions
The HPAI H5N1 viruses detected during the mass death of birds on Maliy Zhemchuzhniy Island evolved from sequential reassortment of multiple genetic variants of LPAI and HPAI viruses (Appendix 1 Figures 3–9). The new variants probably acquired M and HA gene segments from viruses (Egyptian-like) detected in Siberia and Kazakhstan in 2020 (15).
PB2, PB1, PA, NP, and NA gene segments from HPAI viruses likely emerged as a result of reassortment with LPAI viruses during 2020–2021; NS segments likely emerged from LPAI viruses detected during 2021–2022. NS sequences closely related to those of strains isolated in the Caspian Sea regions and Romania were found in LPAI viruses predominantly circulating in Asia during 2019–2021 (Appendix 1 Figure 9). HPAI viruses with such NS sequences have been identified only in Romania and the Caspian Sea.
Gene segments of HPAI H5N1 viruses from the Caspian Sea were closely related to virus segments found in different parts of Eurasia. Specifically, PB1, PA, HA, NA, and M protein gene segments were predominantly related to those in Europe, whereas related NP and NS segments were more prevalent in Asia. In addition, the PA segment from the Caspian Sea strains was also identified in Africa, and PB2 was related to PB2 of viruses detected in the Far East (Japan, Korea, and China), Siberia (Novosibirsk region), Bangladesh, and Europe (Italy, Slovenia, and Czech Republic).
Three major flyways pass through the Caspian Sea region: the Black Sea/Mediterranean Flyway, the West Asian–East African Flyway, and the Central Asian Flyway. However, we found that gene segments of HPAI viruses from the Caspian Sea were related to variants identified in the Far East, indicating widespread distribution and exchange of influenza virus genes well beyond the major flyways. Therefore, continued surveillance and monitoring of AIVs (primarily HPAI viruses) in wild bird populations will be needed worldwide to track and predict the spread of these viruses over long distances.
Dr. Sobolev is a researcher at the Research Institute of Virology, Federal Research Center of Fundamental and Translational Medicine, Siberian Branch, Russian Academy of Sciences, Russia. His primary research interest is the molecular diagnosis and epidemiology of avian influenza viruses.
Dispatch
Neurotropic Highly Pathogenic Avian Influenza A(H5N1) Virus in Red Foxes, Northern Germany
Christine Baechlein
Abstract
In a 1-year survey of wild terrestrial predators in northern Germany, we found that 5 of 110 foxes were infected with contemporary avian influenza A(H5N1) viruses, forming a temporal cluster during January‒March 2023. Encephalitis and strong cerebral virus replication but only sporadic mammalian-adaptive viral polymerase basic 2 protein E627K mutations were seen.
Since emergence of the highly pathogenic avian influenza virus (HPAIV) H5 A/Goose/Guangdong/1/1996 (gs/GD) lineage in 1996, successors continue to circulate in waves around the world, leading to massive losses in wild bird and domestic poultry populations (1). Until 2020‒2021, gs/GD HPAIV infections in poultry holdings characteristically paralleled waterfowl migration patterns. Since then, this seasonality has virtually disappeared and gs/GD HPAIV, currently of subtype H5N1 assigned to clade 2.3.4.4b, are detected year-round in wild birds and poultry in Europe (2,3)
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The virus has been found at increasing frequency in domestic and wild living mammals, mostly affecting carnivorous species (4) and massive die-off events raised concern about potential mammal-to-mammal transmission in dense populations (5,6). HPAIV infections were regularly characterized by high viral loads in the brain and associated clinical signs of the central nervous system with corresponding morphologic changes (7–11). Although Germany has had high HPAIV infection rates in avian species, prevalence studies on HPAIV infections in terrestrial predators, which feed on (infected) waterfowl, are not available. We performed a 1 year-survey to detect HPAIV in wild terrestrial predators in northern Germany.
(SNIP)
Conclusions
Recent H5N1 virus infections with dramatic losses in sea bird breeding colonies in Europe have proven the deleterious implications of a year-round presence of HPAIV in northern Europe (13). The sustained occurrence of HPAIV outbreaks in wild birds might enhance spillover risks to wild carnivores that prey on infected birds or scavenge on their carcasses. An alimentary route of infection has been proven experimentally (14).
Our phylogenetic analyses confirm that virus strains similar to those circulating in the wild bird population have the potential to be transferred to terrestrial carnivores. Wild birds are suspected to be the most likely animal reservoirs sustaining HPAIV replication in Europe. The role of other animal species, in particular mammalian predators, is still equivocal. Clinically conspicuous cases have been reported throughout Europe in a sporadic fashion, but the true prevalence remains unknown. Our data of a 1-year survey from the Germany federal state Lower Saxony showed a temporal clustering of cases in red foxes found within the first 3 months of 2023. This period coincided with a peak in HPAIV detections in wild birds in northern Europe (4). Studies from neighboring the Netherlands also described positive cases in the winter period of 2021‒2022 (10,11). Conditions in the cold season could favor virus transmission to carnivorous mammals.
Virus variants from foxes in Germany did not form a separate phylogenetic cluster confirming independent infection events. According to several reports, gs/GD-like HPAIV shows a strong neurotropism in mammal species. This finding is true for H5N8 infections in harbor seals (9), as well as for disease outbreaks in terrestrial predators (7,8,10,11). Also, in this study, HPAIV infection of the brain was shown by high viral loads and immunohistochemical analysis. In previous studies, point mutations suspected to increase viral replication in mammals have been frequently described, especially the E627K mutation in the PB2 segment.
Ten of 14 HPAIV H5N1-positive wild carnivores detected in the Netherlands carried the mammal-adaptive variant (10,11), and those viruses replicated to higher titers in mammalian cells than in an avian cell line (10). In our study, only 1 of 4 four analyzed cases had the E627K substitution. Those results support previous observations that PB2 627K is not a prerequisite for virus replication in mammalian cells (10).
Little is known about the pathogenesis of HPAIV infection in wild mammal predators. Further virologic and serologic studies are planned and are needed to monitor those potential hosts as indicators for enhanced zoonotic spillover. Recent serologic findings of a clinically silent HPAIV H5N1 infection in a pig herd in Italy suggest that the neurologic cases seen in carnivores in Europe and elsewhere might represent just the tip of an iceberg (15). Widespread HPAIV H5N1 infection in those hosts would provide ample opportunities to further adapt to mammals, which could be associated with increased infection risks for humans.
Dr. Baechlein is a research scientist at the Lower Saxony State Office for Consumer Protection and Food Safety in Braunschweig/Hannover, Germany. Her primary research interest is characterization of zoonotic and animal disease pathogens.
