Sunday, February 09, 2025

Preprint: Pathology of Influenza A (H5N1) Infection in Pinnipeds Reveals Novel Tissue Tropism and Vertical Transmission.

 

Photo Credit Wikipedia


Note: CNN is reporting an (as yet) unconfirmed presumed positive human H5 case in Nevada (see Hogvet51's post).  Meanwhile . . . 

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While seasonal flu can occasionally cause neurological symptoms (see 2018's Neuroinfluenza: A Review Of Recently Published Studies) it is relatively rare phenomenon, and usually only results in mild, and transient symptoms.

The exact mechanisms behind these neurological manifestations are a matter of some debate, as seasonal flu viruses are generally regarded as being non-neurotropic.

Some researchers have posited that neurological symptoms may be due to neuroinflammation induced by the host's immune response. Regardless of the mechanism, we've seen seen evidence that some influenza viruses - particularly novel flu types - can be more neuroaffective than others.

Initially, H5N1 was considered primarily a respiratory disease, but in 2009 a PNAS study (see Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration ) found that the H5N1 virus was highly neurotropic in lab mice, and in the words of the authors `could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases’.
Although there had been rumors of atypical presentations of H5N1 out of Indonesia & Vietnam, 5 years (2014) later we saw Canada's first imported case; a 28 y.o. nurse who died shortly after returning from Beijing. The following year we saw a study which described her infection as `neurotropic'.
The patient presented with `. . . pleuritic chest and abdominal pain . . . , this was followed by headache, confusion and, ultimately, respiratory failure, coma and death.' After reviewing MRI imaging and histological analyses, the authors wrote: `These reports suggest the H5N1 virus is becoming more neurologically virulent and adapting to mammals'.

Also in 2015 a Scientific Reports study on the genetics of the H5N1 clade 2.3.2.1c virus Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015 – the authors warned of its neurotropic effects, and that it could pose a ` . . . significant threat to humans if these viruses develop the ability to bind human-type receptors more effectively.'

H5N1 went relatively `quiet' from 2016 to 2021, but a new subclade (2.3.4.4b) appeared in 2020 and began its world tour, reaching North America in 2021.  Since then we've seen numerous reports of enhanced neurotropism in mammals, including:
While we've been focused primarily on the H5 spillover into nearly 1,000 dairy herds across the nation, and 70+ human infections over the past 12 months, around the world a half billion birds, and (conservatively) tens of thousands of mammals, have died from the virus (see Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity).

Many have exhibited profound neurological manifestations. 

We've previously looked at the  particularly hard-hit colonies of pinnipeds (seals, sea lions,  walruses) in South America (see Preprint: Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal transmission).

Today we've preprint, which highlights the neurotropism, systemic spread -, and apparent vertical transmission - of the H5N1 virus in pinnipeds in Argentina.  This is a lengthy, and at times technical, (37-page) report, so I've just included the abstract. 

Follow the link to read it in its entirety.  I'll return with  a postscript after the break. 


Pathology of Influenza A (H5N1) infection in pinnipeds reveals novel tissue tropism and vertical transmission.

Carla Daniela Fiorito, Ana Colom, Antonio Fernandez,Paula Alonso Almorox, Marisa Andrada, Daniel Lombardo, Eva Sierra

doi: https://doi.org/10.1101/2025.02.07.636856

Preview PDF

Abstract

In 2023, an unprecedented outbreak of highly pathogenic avian influenza (HPAI) H5N1 resulted in the death of thousands of pinnipeds along the Argentinean coast, raising concerns about its ecological and epidemiological impact. Here, we present clinical, pathological, and molecular findings associated with HPAI H5N1 infection in pinnipeds from Chubut, Argentina.

Necropsies were conducted on three South American Sea Lions (SASLs) (Otaria flavescens) and one Southern Elephant Seal (SES) (Mirounga leonina), followed by histopathological, immunohistochemical and RT-sqPCR analyses. Neurological clinical signs were observed in two SASLs, with one also exhibiting respiratory distress. Neuropathological findings included lymphoneutrophilic meningoencephalomyelitis and choroiditis, neuronal necrosis, gliosis, hemorrhages, and perivascular cuffing. Viral antigen was localized in neurons, glial cells, choroid plexus epithelial cells, ependymal cells, and the neuropil.

Systemic manifestations included HPAI-related necrotizing myocarditis in the elephant seal and placental necrosis in a sea lion, with fetal tissues testing positive for HPAIV. Pulmonary lesions were minimal, limited to bronchial glands in one individual. RT-sqPCR confirmed HPAI H5 in all tested animals.

Our findings highlight the neurotropism of HPAI H5N1 in pinnipeds, and expand the known systemic effects of the virus, revealing new tissue tropism and vertical transmission.

          (Continue  . . . ) 


While there are still more questions than answers, over the years we've looked at numerous studies (see here, here, and here)  linking severe and/or repeated viral infections (including flu) to a variety of neurological diagnoses later in life.

In 2023 we looked at a study (see Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks), which found statistical linkage between viral illnesses and developing neurodegenerative diseases in the future.

Whenever we talk about long-term sequelae from influenza, the mysterious decade-long epidemic of Encephalitis Lethargica (EL) that followed the 1918 pandemic always comes to mind (see The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?).

It is estimated that between 1 and 5 million people were affected with severe Parkinson's-like symptoms. While some scientists have suggested they may have been linked to the pandemic virus, others have pointed to a post-streptococcal immune response, or believe it was an aberrant autoimmune response, and dismiss the link with the 1918 pandemic.

The cause remains a mystery.

But throughout history, there have been reports of similar outbreaks, including febris comatosa which sparked a severe epidemic in London between 1673 and 1675, and in the wake of the 1889–1890 influenza pandemic, a severe wave of somnolent illnesses (nicknamed the "Nona") appeared.
Much more recently, we've seen evidence that even a mild SARS-CoV-2 infection can sometimes produce persistent neurological manifestations (see NIH COVID-19 and the Nervous System).
So far, most of the human H5 infections in the United States over the past year have been uncharacteristically mild. 

But in a 2023 a study (see Cell: The Neuropathogenesis of HPAI H5Nx Viruses in Mammalian Species Including Humans) the authors warned that ` . . . highly pathogenic avian influenza (HPAI) H5Nx viruses can cause neurological complications in many mammalian species, including humans'.

Meaning that - until we know more - even a mild H5N1 infection is worth avoiding if at all possible.

Saturday, February 08, 2025

Australia: Victoria Reports A New Outbreak of HPAI (H7N8)

Outbreaks of H7 avian flu in 2024

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While Australia/NZ/Oceania remain free from the HPAI H5N1 virus, last year Australia's poultry industry was rocked by repeated outbreaks from 3 different subtypes of H7 avian flu (see map above).  Just over 2 months ago, New Zealand reported their first outbreak (of H7N6). 

LPAI (low path) viruses circulate worldwide. Most are considered innocuous to poultry and to humans, but when an H5 or H7 LPAI virus spills over from wild birds into poultry they can sometimes spontaneously mutate into an HPAI strain. 

After a long struggle, 5 days ago Australia's poultry industry declared themselves free of the H7 virus (see statement below):

On 3 February 2025, Australia self-declared freedom from high pathogenicity avian influenza (HPAI) H7 to the World Organisation for Animal Health, effective 23 January 2025.
HPAI H7 has been eradicated from Victoria, NSW and the ACT and there have been no new detections of HPAI H7 in Australia since 12 July 2024.
In 2024, a response to three strains of HPAI H7 took place. There were 16 infected premises including 8 in Victoria, 6 in NSW and 2 in the ACT.
But, as we've seen so many times in the past, such declarations are often fleeting. LPAI and HPAI viruses abound in nature, and new subtypes (and genotypes within subtypes) are emerging all of the time.

Today Victoria is reporting a fresh outbreak - this time of HPAI H7N8 - which is different from the two strains they reported in 2024.  First their statement, after which I'll have more on H7 viruses.

Current situation

Last updated 8 February 2025

Agriculture Victoria has confirmed the presence of avian influenza at a poultry property in northern Victoria, which has now been placed into quarantine.

Diagnostic testing performed by Australian Centre for Disease Preparedness at Geelong confirmed high pathogenicity H7N8, which is different to the strain that impacted Victorian poultry farms during 2024. Although the 2024 New South Wales/Australian Capital Territory outbreak was also an H7N8 virus, the current laboratory has advised that the current Victorian outbreak is a different virus.

The property has been placed under quarantine and a declared area is in place in the eastern two-thirds of the Strathbogie Shire to prevent movements that could spread the virus. Any suspicion of an emergency animal disease (EAD) should be immediately reported to the 24-hour EAD Hotline on 1800 675 888 or to your local vet.

Consumers should not be concerned about eggs and poultry products from the supermarkets, they do not pose a risk and are safe to consume.

While cases among humans in direct contact with animals infected with high pathogenicity avian influenza viruses are possible, the current risk to the public remains low. Find out more about avian influenza in humans from the BetterHealth Channel.

In 2024 Victoria experienced Australia’s largest avian influenza outbreak on record.

Between 22 May and 24 June, 8 properties tested positive for high-pathogenicity H7N3 and H7N9 avian influenza in south-west Victoria.

 

HPAI H7 viruses remain primarily a concern for poultry producers, with human infections up until 2013 being both rare and generally mild.  But in 2013 an LPAI H7N9 virus emerged in China in 2013 which showed us that - with the right set of mutations - an H7 virus can become  a formidable public health threat. 

H7N9 Epidemic Waves - June 14th 2017 - Credit FAO

Luckily, that deadly strain has gone to ground since China's introductions of an H5+H7 vaccine in 2017 - and while versions of it still circulate in birds - it appears to have lost much of its affinity for mammals (see EID Journal: Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017–2019).

For now, the H7 viruses popping up in Australia show no signs of posing any kind of serious public health threat.  

But, as with all influenza viruses with zoonotic potential, things can change over time. Which is why these outbreaks must be quickly contained, before something worse can happen. 

New Hampshire: DHHS Identifies New Hampshire Resident with Clade I Mpox

 

Credit WHO

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Amid the growing concerns over avian flu, a raging flu season, and fresh outbreaks of hemorrhagic fever (Marburg & Ebola Sudan) in Africa, we are also monitoring the progress of a recently emerging clade (Ib) of Mpox in Africa, and its slow, but steady, international spread. 

Last August WHO declared the Mpox outbreak in Central Africa to constitute a PHEIC (Public Health Emergency of International Concern) after reports that a new clade of the virus had begun to spread outside of the DRC (see More African Nations Reporting Mpox - Africa CDC Mpox Update (Jul 30th)).

This Ib clade is reportedly more virulent, and potentially more transmissible, than the clade II mpox virus which began its world tour in the spring of 2022. Last December, the WHO published a new, updated risk assessment, which put the risk of national and international spread as HIGH.

So far, we've seen 11 non-African nations report imported cases of this Mpox Ib clade; Sweden, Thailand, India, Germany, the United Kingdom of Great Britain and Northern Ireland, the United States of America, Canada, Pakistan, Belgium, China, and France. 

Several countries, including China, Belgium, Germany, France and the UK have reported limited secondary transmission. The UK has reported the most cases (n=9), while the United States - until yesterday - had only reported 2 (1 in California, 1 in Georgia)

Yesterday the New Hampshire DHHS reported the third case identified in the United States (h/t Shiloh & Sharon Sanders on FluTrackers).   While listed as clade I, this is most likely clade Ib. 

First the announcement, after which I'll have a bit more.

Press Release
Date: February 07, 2025

Contact
Public Information Office
(603) 271-9389 | PIO@dhhs.nh.gov
DHHS Identifies New Hampshire Resident with Clade I Mpox
Risk to Public Is Low

Concord, NH – The New Hampshire Department of Health and Human Services (DHHS), Division of Public Health Services (DPHS) has identified an adult from Merrimack County with clade I mpox. The individual recently traveled to Eastern Africa, where there is an ongoing outbreak of clade I mpox, and is currently self-isolating and recovering at home. The individual’s illness poses no current risk to the public.

The individual’s illness is likely related to their recent travel, and there is no evidence that clade I mpox is spreading from person-to-person in New Hampshire or within the United States. This is the first clade I mpox diagnosis in New Hampshire and the third clade I mpox diagnosis in the United States.

DHHS is conducting a disease investigation to identify anyone who may have had close contact with the individual. There have been no public locations identified where exposure may have occurred. The Department will facilitate appropriate care for anyone identified during the investigation.

“The mpox virus is spread primarily through direct physical contact with someone who has mpox and has developed an infectious skin rash,” said State Epidemiologist Dr. Benjamin Chan. “Public Health is working to identify and notify people who had close contact with the individual, so we can connect them with preventive vaccination and help them to monitor for symptoms of mpox.”

Mpox is a disease caused by two different genetic types of the mpox virus, called clade I and clade II. Clade II mpox has continued to circulate at low levels in the United States since a widespread outbreak occurred in 2022. More recently, clade I mpox has been causing outbreaks in Central and Eastern Africa. Both types of the virus spread primarily through direct physical contact with a symptomatic person with mpox or through contact with used items contaminated with the mpox virus. The mpox virus is not spread through the air.

People with mpox develop an infectious rash that changes over time as a person’s illness progresses. The rash can look like pimples or blisters that are painful or itchy. Over time, the rash can spread, and then slowly the skin lesions develop a scab or crust before going away over several weeks. Other symptoms of mpox can include fever, chills, headache, exhaustion, muscle aches, sore throat, or swollen lymph nodes. A person with mpox can spread the virus starting when they first develop symptoms, and they remain contagious until their rash has fully healed and a fresh layer of skin has formed.

If you are traveling to Central or Eastern Africa or if you believe you might have a risk factor for mpox, talk to your healthcare provider about whether the JYNNEOS vaccine is recommended for you.

If you have questions about mpox, please contact DPHS at 603-271-4496. For more information about mpox, visit the DHHS mpox webpage.

While the clade Ib variant of Mpox is new, concerns over the international spread of Mpox (both clade I & II) go back decades.  

In 2003 we saw a rare multi-state (Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin) outbreak when a Texas animal distributor imported hundreds of small animals from Ghana, which in turn infected prairie dogs that were subsequently sold to the public (see MMWR Update On Monkeypox 2003).

By the time that outbreak was quashed, the U.S. saw 37 confirmed12 probable, and 22 suspected human cases. Among the confirmed cases 5 were categorized as being severely ill, while 9 were hospitalized for > 48 hrs; although no patients died (cite).

 Throughout the second half of the last decade we saw repeated exported cases turning up in places like the UK, Singapore, and even Israel (see ECDC: RRA On Imported Monkeypox Cases From Nigeria). The first case imported into the United States was via a traveler from Nigeria in 2021. 

Like all viruses, Monkeypox continues to evolve and diversify, as discussed in the 2014 EID Journal article Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo, where the authors cautioned:

Small genetic changes could favor adaptation to a human host, and this potential is greatest for pathogens with moderate transmission rates (such as MPXV) (40). The ability to spread rapidly and efficiently from human to human could enhance spread by travelers to new regions.

As our collective immunity from the smallpox vaccine - which was discontinued in the late 1970s - wanes, there will be increased opportunities for emerging pox viruses to make a comeback.  We ignore them at considerable risk to global public health. 

Some other poxviruses we've looked at in recent years include:
Alaska Health Department Announces A Fatal Alaskapox Infection

A Newly Discovered Poxvirus Detected In Reindeer in Sweden & Norway

EID Journal: Novel Poxvirus in Proliferative Lesions of Wild Rodents in East-Central Texas, USA

A Novel Zoonotic Orthopoxvirus Resurfaces In Alaska

Friday, February 07, 2025

USDA Summary Of Nevada's H5N1 Genotype D1.1 Spillover Into Cattle

 

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This evening the USDA has released a summary of the initial findings on the H5N1 genotype D1.1 virus detected in several dairy herds in Nevada.  Earlier this week we learned of this spillover  (see USDA Confirms Genotype D1.1 In Nevada Dairy Cows), which is notable since the 950+ previous outbreaks were all from genotype B3.13.

For nearly a year agricultural interests have been hoping that the B3.13 spillover was a one-off event, despite research which suggested that other genotypes might spillover into cattle (see Germany: FLI Statement On Experimental Infection Of Dairy Cows With European H5N1 Virus).

As far as I can tell, the full sequences have not been publicly released, but the USDA does report detecting at least one significant mammalian mutation (D701N) in the first samples. The PB2-D701N mutation has frequently been linked to increased severity of infection (see here and here) with other avian influenza viruses.

There are still a lot of unanswered questions regarding this Nevada incident.  At least 4 herds have been affected (media reports suggest at least 2 more are pending).  While wild birds are the likely source of this spillover, whether this was due to one - or multiple - spillovers is unclear. 

How long this D1.1 genotype has been spreading in cattle, and whether it has spread to other livestock beyond this region, is unknown.  Hopefully, as testing ramps up, we'll get more answers. 

I've reproduced the USDA summary below.

 

The Occurrence of Another Highly Pathogenic Avian Influenza (HPAI) Spillover from Wild Birds into Dairy Cattle

Background

In March 2024, the USDA confirmed the first case of highly pathogenic avian influenza (HPAI) spreading between dairy cattle herds in the United States. This followed reports from dairy producers of an unusual illness in their lactating cows over the preceding 2-3 months. Virus whole genome sequencing and modeling performed by USDA suggested a single spillover of HPAI H5N1, clade 2.3.4.4b, genotype B3.13 from wild birds into dairy cattle likely occurred between October 2023 and January 2024 (1). Since then, federal, state, and industry partners have collaborated to address the HPAI threat in dairy cattle, resulting in two federal orders and the implementation of the National Milk Testing Strategy (NMTS).


States began enrolling in the NMTS in December 2024, in which they are continuing to conduct or now implementing state-wide bulk tank surveillance and/or milk processing plant silo monitoring. Nevada was among the first to participate in the National Silo Monitoring Program, which includes testing milk samples from processing plant silos for HPAI. This sampling scheme coincides with the FDA's existing regulatory program, which requires all raw milk Grade A silos to be sampled four times within 6 months.

The Detection

In Nevada, 3 of 11 silo samples collected on January 6 and 7, 2025 tested positive for HPAI via polymerase chain reaction (PCR) at the National Veterinary Services Laboratories (NVSL) on January 10. The state was notified, triggering an investigation to trace the source, as up to 12 dairies (in the same geographic region) could have contributed milk to the affected silos. On January 17, regulatory officials collected on-farm bulk milk samples from suspected dairy farms and submitted them to the Washington Animal Disease Diagnostic Laboratory (WADDL), a member of the National Animal Health Laboratory Network (NAHLN). HPAI was confirmed via PCR at NVSL on Friday, January 24, in samples from two of those dairies. NVSL completed whole genome sequencing on January 31 and identified HPAI H5N1, clade 2.3.4.4b, genotype D1.1 in samples from four different bulk tanks from one herd. A second herd also showed a partial sequence consistent with D1.1. Clinical signs were not observed in the cattle prior to the detection, but have been reported since, and the affected dairy producers reported large wild bird die-offs near the dairies.

While genotype D1.1 has been the dominant strain circulating in migratory wild birds across all four North American flyways during the winter of 2024-2025, these Nevada cases represent the first detection of a genotype other than B3.13 in U.S. dairy cattle and the second known spillover from wild birds into lactating dairy cattle.

Virus Epidemiology and Origin

Since late 2021, six separate introductions of Eurasian HPAI H5N1 clade 2.3.4.4b have been documented into the migratory wild birds in the North American flyways (genotypes A1 through A6). Genotype D1.1 is a reassortant of A3. Genotype A3 first appeared in the Pacific flyway in April of 2022 with detections only in the Pacific flyway until the fall of 2024. Since this fall, genotype A3 has been sporadically reported in migratory wild birds across all four flyways through wild bird surveillance, making up 3.3% of the overall detections to date. Genotype D1.1 retains four genes from the original A3 genotype; hemagglutinin (HA), polymerase basic 1 (PB1), matrix (M) and nonstructural (NS), with other genes originating from other North American lineage viruses found in migratory wild birds. This genotype was first detected in September 2024 and has quickly expanded to all North American flyways. D1.1 is the current predominant genotype in migratory wild birds, making up 6.07% of the total detections since 2022 despite first occurring late 2024.

The D1.1 viruses identified in dairy cattle in Nevada were found to be closely related to other D1.1 viruses recently detected in migratory wild birds across multiple North American Flyways.

Analysis of the hemagglutinin gene of the Nevada dairy cattle viruses did not identify changes predicted to impact infectivity or adaptation to mammalian hosts. However, a change of PB2 D701N commonly associated with mammalian adaptation of HPAI virus was identified in viruses sequenced from four separate dairy cattle. To date, this change has not been observed in D1.1 viruses found in wild birds or poultry and is not found in B3.13 genotype viruses detected in dairy cattle. PB2 D701N has previously been associated with mammalian adaptation because it improves RNA polymerase activity and replication efficiency in mammalian cells and has the potential to impact pathogenesis in infected mammals (2,3,4,5,6).
The change has previously been identified in human cases of HPAI H5 but with no evidence of onward transmission among humans (7,8). No other changes associated with mammalian adaptation were identified in the sequences. Of note, these D1.1 viruses sequenced from dairy cattle do not contain the PB2 - 631L marker that appeared to be fixed in dairy cattle B3.13 sequences. Following the existing public sharing process, NVSL immediately provided the D1.1 sequence information the Centers for Disease Control and Prevention and will post sequence files to the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) within 7 days of analysis, adding metadata as sequences are interpreted and quality checked in light of epidemiological information.

Summary

This detection indicates that this HPAI virus, genotype D1.1, is the second spillover event from migratory wild birds to dairy cattle following the B3.13 event in late 2023/early 2024.

Investigations are ongoing to fully characterize this event. The Nevada Department of Agriculture acted quickly, by first rapidly enrolling in the NMTS to initiate active surveillance, and then to identify and quarantine the affected dairies before cattle movements could further transmit this virus beyond the local area. This is the first instance where sampling of milk at processing plants rather than individually or directly on farm has detected a high consequence disease, demonstrating silo monitoring as an efficient method to monitor HPAI in the National dairy herd.

1. Nguyen T, Hutter C, Markin A, Thomas M, Lantz K, Killian M, Janzen GM, Vijendran S, Wagle S,Inderski B, Magstadt DR, Li G, Diel DG, Frye EA, Dimitrov SM, Swinford A, Thompson AC, Snevik KR, Suarez DL, Spackman E, Lakin S, Ahola SC, Johnson SR, Baker A, Robbe-Austerman S,  Torchetti M, Anderson TK. 2024. Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle. bioRxiv 2024.05.01.591751; doi: https://doi.org/10.1101/2024.05.01.591751

2. Li Z, Chen H, Jiao P, Deng G, Tian G, Li Y, Hoffmann E, Webster RG, Matsuoka Y, Yu K. 2005. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. The Journal of Virology 79:12058-12064.

3. Gabriel G, Abram M, Keiner B, Wagner R, Klenk HD, Stech J. 2007. Differential polymerase activity in avian and mammalian cells determines host range of influenza virus. J Virol 81:9601-4.

4. Steel J, Lowen AC, Mubareka S, Palese P. 2009. Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog 5:e1000252.

5. Gao Y, Zhang Y, Shinya K, Deng G, Jiang Y, Li Z, Guan Y, Tian G, Li Y, Shi J, Liu L, Zeng X, Bu Z, Xia X, Kawaoka Y, Chen H. 2009. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoSPathog 5:e1000709.

6. Zhou B, Pearce MB, Li Y, Wang J, Mason RJ, Tumpey TM, Wentworth DE. 2013. Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the  2009 pandemic H1N1 influenza A virus. PLoS ONE 8:e67616.

7. Le QM, Ito M, Muramoto Y, Hoang PV, Vuong CD, Sakai-Tagawa Y, Kiso M, Ozawa M, Takano R, Kawaoka Y. 2010. Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated  from humans between 2003 and 2008 in northern Vietnam. J Gen Virol 91:2485-90.

8. Zhu W, Li X, Dong J, Bo H, Liu J, Yang J, Zhang Y, Wei H, Huang W, Zhao X, Chen T, Yang J, Li Z, Zeng X, Li C, Tang J, Xin L, Gao R, Liu L, Tan M, Shu Y, Yang L, Wang D. 2022. Epidemiologic, Clinical, and Genetic Characteristics of Human Infections with Influenza A(H5N6) Viruses, China. Emerg Infect Dis 28:1332-1344.

CDC FluView Week 5: Seasonal Flu Rising Again - 1 Novel (H1N2v) Flu Case In Iowa

 


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After appearing to peak in early January (which may be an artifact of delayed reporting), flu levels are once again rising (see chart below), reaching the highest level reported in the past 5 years. 

While no new H5 cases have been reported in recent weeks, the CDC is reporting the first (swine) variant (H1N2v) detection of 2025.

Key Points
Seasonal influenza activity remains elevated and continues to increase across the country.
• During Week 5, of the 4,377 viruses reported by public health laboratories, 4,264 were influenza A and 113 were influenza B. Of the 3,458 influenza A viruses subtyped during Week 5, 1,857 (53.7%) were influenza A(H1N1)pdm09, 1,601 (46.3%) were A(H3N2), and 0 were A(H5).
• Outpatient respiratory illness is increasing and remains above baseline nationally for the tenth consecutive week. All 10 HHS regions are above their region-specific baseline.
One human infection with an influenza A(H1N2) variant (A(H1N2)v) virus was reported.
• No new influenza A(H5) cases were reported to CDC this week. To date, human-to-human transmission of influenza A(H5) virus has not been identified in the United States.
Ten pediatric deaths associated with seasonal influenza virus infection were reported this week, bringing the 2024-2025 season total to 57 pediatric deaths.
  CDC estimates that there have been at least 24 million illnesses, 310,000 hospitalizations, and 13,000 deaths from flu so far this season.
• CDC recommends that everyone ages 6 months and older get an annual influenza (flu) vaccine.1
• There are prescription flu antiviral drugs that can treat flu illness; those should be started as early as possible and are especially important for patients at higher risk for severe illness.2
• Influenza viruses are among several viruses contributing to respiratory disease activity. CDC is providing updated, integrated information about COVID-19, flu, and respiratory syncytial virus (RSV) activity on a weekly basis.

Swine variant infections are generally mild or moderate in severity, and are indistinguishable from regular flu without a lab test. Most are linked to direct or indirect contact with swine, often at agricultural exhibits and county fairs, although (as in the case of today's case), sometimes no known exposure is reported.
Novel Influenza A Virus Infections

One human infection with influenza A(H1N2) variant (A(H1N2)v) virus was reported by the Iowa Department of Health and Human Services.

The patient is ≥18 years of age and sought health care during the week ending January 18, 2025 (Week 3), was hospitalized, and has recovered from their illness. An investigation by state public health officials did not identify direct or indirect swine contact by the patent. No illness was identified among the patient's close contacts. No human-to-human transmission has been identified associated with this case.

This is the first human infection with a variant influenza virus reported during the 2024-2025 season in the United States.

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a "variant" influenza virus. Most human infections with variant influenza viruses occur following exposure to swine, but human-to-human transmission can occur. It is important to note that in most cases, variant influenza viruses have not shown the ability to spread easily and sustainably from person to person. Additional information on influenza in swine, variant influenza virus infection in humans, and guidance to interact safely with swine can be found at www.cdc.gov/flu/swineflu/index.htm.

No new human infections with A(H5) were reported to CDC this week. An ongoing outbreak of H5N1 continues in domestic dairy cows and poultry, and monitoring for additional human cases is ongoing.

Although the public health risks from swine variant viruses are considered low, the CDC advises those who are at higher risk of serious flu complications (including children under 5, adults over 65, pregnant women, and those with certain chronic medical conditions), to avoid pigs and the swine barn altogether.


In 2023 the CDC held a webinar for clinicians on recognizing, treating, and reporting zoonotic influenza cases in the community (see COCA Call : What Providers Need to Know about Zoonotic Influenza), which remains available on their website.

Since there are likely to be several more weeks of  heavy flu activity still ahead of us, there may still be value in getting the flu (and COVID) vaccines, and face masks and hand sanitizer can add prudent additional layers of protection. 

As always,  if you do get sick, stay home and call your doctor to see if an antiviral would be appropriate.

California: San Mateo County Warns Residents After Stray Cat Found With H5N1

 

Cats As Potential Vectors/Mixing Vessels for Novel Flu  

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Since the first of the year the USDA has added 21 cats to their list of mammals with H5N1, although it is generally assumed that this is just a fraction of the actual number of cases. Since last March, they have confirmed 85 domestic cats with the virus. 

In several cases, we've seen reports of multiple cat deaths in a household, but only one or two were actually tested (and counted). In other cases, cats may die unobserved in the wild - or are never tested for the virus - while others may experience mild illness and recover.  

Since the emergence of a new, more mammalian-adapted H5N1 virus in 2021, we've seen a number of outbreaks in cats around the world (see reports from Poland & South Korea). In those outbreaks, as well as several recent cases in California and Oregon, the consumption of raw meat and/or milk was the likely exposure. 

Yesterday San Mateo County, California reported HPAI H5 in a stray cat taken in by a household, and warned residents to contact their veterinarian - and monitor their own health - if their pet develops symptoms.

Overnight there was a related report in the NYTs (see C.D.C. Posts, Then Deletes, Data on Bird Flu Spread Between Cats and People). I didn't get to see that data, and can offer no additional insight beyond a review - after the break - of some recent papers on avian flu in companion animals. 

After Bird Flu Detected in Local Cat, County Health Officials Say Pet Owners Should Contact Veterinarian When Their Pets are Sick

February 6, 2025

Redwood City — State veterinary and health officials have confirmed a case of H5N1 (bird flu) in a domestic stray cat in San Mateo County. The infection, which is not related to the recent instance of bird flu in a backyard flock, was found in a stray cat in Half Moon Bay that had been taken in by a family. When it showed symptoms, they took it to Peninsula Humane Society, whose veterinarians examined it and requested testing. Lab results confirmed H5N1. It is not known how the cat was infected and it was euthanized due to its condition.

Cats may be exposed to bird flu by consuming infected bird, being in environments contaminated with the virus and consuming unpasteurized milk from infected cows or raw food. Inside domestic animals, such as cats and dogs, that go outside are also at risk of infection.​​​​​​​

According to the Centers for Disease Control and Prevention, the risk of cats spreading H5N1 to people is extremely low, though it is possible for cats to spread some strains of bird flu to people.

While there are no human cases of H5N1 related to this case, this detection in a cat highlights the importance of being proactive about preventing the spread of the virus.

Residents whose pets show signs of illness should contact their veterinarian.

Pets infected with H5N1 may experience a loss of appetite, lethargy and fever, along with neurologic signs, including circling, tremors, seizures or blindness. The illness may quickly progress to:

  • Severe depression
  • Discharge from eyes or nose
  • Other respiratory signs, such as rapid shallow breathing, difficulty breathing and sneezing or coughing
  • Pets with severe illness may die.

If a pet is showing signs of illness consistent with bird flu and has been exposed to infected (sick or dead) wild birds or poultry, residents should contact a veterinarian and monitor their own health for signs of fever or infection.

“We all want to make sure our companion animals are healthy and safe from disease,” said Lori Morton-Feazell, San Mateo County’s chief of Animal Control and Licensing. “If your pet is sick, your veterinarian can determine whether it should be tested for bird flu or any other virus or disease.”


We've known for 2 decades that cats are susceptible to HPAI H5 infection, after hundreds of large cats (lions and tigers) kept in zoos across South East Asia died from eating infected raw chicken; a tragedy we've seen repeated often, including in Vietnam last fall. 

A decade ago, in HPAI H5: Catch As Cats Can, we looked at the sporadic spillovers into felines, and in 2023 we reviewed A Brief History Of Avian Influenza In Cats, which included the outbreak of H7N2 in shelter cats in NYC, and the infection of at least two workers

Two months ago, in Emerg. Microbes & Inf.: Marked Neurotropism and Potential Adaptation of H5N1 Clade 2.3.4.4.b Virus in Naturally Infected Domestic Catswe looked at a report on the HPAI H5 infection of a house full of domestic cats (n=8) in South Dakota last April. 

Isolates from the two cats that were tested showed signs of viral adaptation to a mammalian host.  The authors wrote:

Cat H5N1 genomes had unique mutations, including T143A in haemagglutinin, known to affect infectivity and immune evasion, and two novel mutations in PA protein (F314L, L342Q) that may affect polymerase activity and virulence, suggesting potential virus adaptation.
 
Dead cats showed systemic infection with lesions and viral antigens in multiple organsHigher viral RNA and antigen in the brain indicated pronounced neurotropism.

Last November, in Eurosurveillance: (HPAI) H5 virus Exposure in Domestic & Rural Stray Cats, the Netherlands, October 2020 to June 2023, we looked at a study which found:

Of the 701 stray cats sampled, 83 had been exposed to HPAI virus, whereas only four of the 871 domestic cats. Exposure was more common in older cats and cats living in nature reserves. Some stray cats had been exposed to both avian and human influenza viruses. In contrast, 40 domestic cats were exposed to human influenza viruses.

Curiously, while we've seen no reports of HPAI H5 in European dairy cows, the authors reported finding the `. . . highest HPAI H5 seropositivity was found in cats living in nature reserves (37.8%) and on dairy farms (11.0%).'  

While the CDC continues to rank the risk to general public from avian flu as low, they do provide very specific guidance to pet owners on how to limit their risk of infection from the virus (see What Causes Bird Flu in Pets and Other Animals).

We are currently getting far less information on avian flu - both here in the United States, and from many countries around the world - than we'd like.  This is a trend which gained steam during the COVID pandemic, and has grown increasingly worse over time (see Flying Blind In The Viral Storm).

While I don't profess to understand the rationale behind these policy decisions, I do know that any short-term economic or political advantages to be had from them will pale compared to the damage we'll see should another pandemic virus emerge.

And as history tells us, sooner or later, another one will.