WHO DON Update: Avian Influenza A(H5N1) - Cambodia

#18,783

Overnight the WHO published an updated DON (Disease Outbreak News) report on the uptick in human H5N1 cases in Cambodia over the first half of 2025.  

This update only includes 11 of the 12 cases we've seen reported this year (#12, is reportedly a toddler from Takeo Province), but they note the unusual rise in cases during the month of June. 



While the same subtype, the H5N1 virus in Cambodia is an older, and more virulent, strain (clade 2.3.2.1.e) that the HPAI H5 virus currently circulating in much of the rest of the world (clade 2.3.4.4b).

Influenza viruses evolve primarily through abrupt reassortment and much slower antigenic drift. A little over a year ago we learned that this older clade had reassorted with the newer clade 2.3.4.4b virus in late 2023. 

This reassortment was recently reclassified as clade 2.3.2.1e (see WHO: Influenza at the Human-Animal Interface Report - Identifies New H5 Clade 2.3.2.1e Infections in Cambodia & Vietnam).

Although much of what is included in today's report is information we've seen previously, it provides an excellent overview of the outbreak in Cambodia over the past 6 months. 

Due to its length, I've only reproduced part of this report, including the risk assessment.  Follow the link to read it in its entirety.  I'll have more after the break.

Disease Outbreak News
Avian Influenza A(H5N1) - Cambodia
5 July 2025

Situation at a glance

Between 1 January and 1 July 2025, the World Health Organization (WHO) was notified by Cambodia’s International Health Regulations (IHR) National Focal Point (NFP) of 11 laboratory-confirmed cases of human infection with avian influenza A(H5N1) virus. Seven of the 11 cases were reported in June, an unusual monthly increase. Avian influenza A(H5N1) was first detected in Cambodia, in December 2003, initially affecting wild birds. Since then, 83 cases of human infection with influenza A(H5N1), including 49 deaths (case fatality ratio [CFR] of 59%), have been reported in the country.

While the virus continued to circulate in avian species, no human cases were reported between 2014 and 2022, after which, the virus re-emerged in humans in February 2023. Since the re-emergence of human A(H5N1) infections in Cambodia in 2023, a total of 27 cases have been reported (six in 2023, 10 in 2024, and 11 to date in 2025), of which 12 were fatal (CFR 44%).

Seventeen of the cases occurred in children under 18 years old. Avian influenza A(H5N1) is circulating in wild birds, poultry and some mammals around the world, and occasional human infections following exposure to infected animals or contaminated environments are expected to occur. In cases detected in Cambodia, exposure to sick poultry, often poultry kept in backyards, has been reported.

According to the IHR, a human infection caused by a novel influenza A virus subtype is an event that has the potential for high public health impact and must be notified to the WHO. Based on currently available information, WHO assesses the current risk to the general population posed by this virus as low. For those occupationally exposed to the virus, such as farm workers, the risk is low to moderate, depending on the measures in place. WHO routinely reassesses this risk to factor in new information.

Description of the situation

Between 1 January and 1 July 2025, the National IHR Focal Point (NFP) of the Kingdom of Cambodia notified WHO of 11 laboratory-confirmed case of human infection with avian influenza A(H5N1) virus (clade 2.3.2.1e- formerly classified as 2.3.2.1c; from cases where virus sequences are available to date) including six deaths [CFR: 54%]. These cases are reported from the provinces of Siem Reap (4), Takeo (2), Kampong Cham (1), Kampong Speu (1), Kratie (1), Prey Veng (1), Svay Rieng (1). Of the total cases reported in 2025, seven cases were reported in June 2025.

Males account for 63% of the cases. Of the 11 cases, three cases were reported in less than five-year-olds, two cases were between the age of 5 and 18 years and six cases were reported in the age group 18-65 years. All cases had exposure – handling or culling - of sick poultry, often kept in backyards.

Avian influenza A(H5N1) was detected for the first time in Cambodia in December 2003, initially affecting wild birds. Between 2014 and 2022, there were no reports of human infection with A(H5N1) viruses. However, the re-emergence of human infections with A(H5N1) viruses in Cambodia was reported in February 2023.

Since this re-emergence, Cambodia has reported 27 cases of laboratory confirmed human infection with avian influenza A(H5N1) including 12 fatalities (CFR 44%). The cases have been reported from eight provinces: Kampong Cham (1), Kampong Speu (1), Kampot (3), Kratie (3), Prey Veng (6), Svay Rieng (4), Siem Reap (5), Takeo (4).

Figure 1: Epicurve of Avian Influenza A (H5N1) cases reported in Cambodia by year from 2003- 1 July 2025

(SNIP)

WHO risk assessment

From 2003 to 1 July 2025, a total of 986 human cases of infection of influenza A(H5N1) have been reported globally to WHO from 25 countries, including this case. Almost all of these have been linked to close contact with A(H5N1) infected live or dead birds or mammals, or contaminated environments. Human infection can cause severe disease with a high mortality rate: of the 986 infections reported globally, there have been 473 deaths (CFR 48%).

In this event, cases have been reported from seven provinces in 2025. All cases have reported direct exposure to sick/dead poultry.

While human-to-human transmission cannot be ruled out, the more likely source of exposure of these cases is infected poultry of contaminated environment.

Based on information available at this time, the overall public health risk from currently known influenza viruses circulating at the human-animal interface has not changed and remains low. For those occupationally exposed to the virus, such as farm workers, the risk is low to moderate, depending on the measures in place. Additional cases in persons with exposure to sick/dead poultry is to be expected. The occurrence of sustained human-to-human transmission in this event based on currently available information is currently considered unlikely. This can, however, change and the risk assessment will be reviewed as needed if additional information becomes available.

Close analysis of the epidemiological situation, further characterization of the most recent influenza A(H5N1) viruses in both human and animal populations, and serological investigations are critical to update associated risk assessments for public health and promptly adjust risk management measures.

Current seasonal influenza vaccines are unlikely to protect humans against infections with influenza A(H5N1) viruses. Vaccines against influenza A(H5) infection in humans have been developed and licensed in some countries. WHO continues to update the list of zoonotic influenza candidate vaccine viruses (CVVs), which are selected twice a year at the WHO consultation on influenza virus vaccine composition, and on an ad hoc basis as needed. The list of such CVVs is available on the WHO website, see reference below. In addition, the genetic and antigenic characterization of contemporary animal and zoonotic influenza viruses are published here. This risk assessment will be reviewed as needed if additional information becomes available.

       (Continue . . . )


If there is one constant with influenza viruses, it is their ability to continually change and evolve. An essential trait for a virus that leaves behind a degree post-infection immunity, otherwise it would quickly run out of susceptible hosts.

Sometimes change comes gradually, through a process called antigenic drift. Drift is the standard evolutionary process of influenza viruses, and comes about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift).

More abrupt changes come from antigenic shift, aka reassortment. For shift to happen, a host (human, swine, bird) must be infected by at least two different influenza viruses at the same time (see NIAID Video: How Influenza Pandemics Occur).

These evolutionary changes can either increase or decrease the fitness, transmissibility, host range, or virulence of a virus. Evolution is not a linear process, and thankfully most reassortments end up as evolutionary dead ends. 

But we find ourselves - nearly 30 years after the first detection of an H5 A/Goose/Guangdong/1/1996 (gs/GD) lineage in China - in a world where H5's descendants have not only flourished, they have diversified into dozens of clades and subclades (many now extinct), and hundreds of genotypes, across multiple subtypes.

Early, Rapid Diversification of H5Nx

A virus that was once confined to small patch of Southeast China has spread successfully to nearly every continent, and now threatens humans, wildlife, and livestock around the globe (see Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity).

Granted, we've looked into the H5Nx abyss before, only to see the virus suddenly lose momentum. And that could certainly happen again - but as its viral diversity increases - the impact of any single negative reassortment likely diminishes. 

While we could easily be blindsided by something else percolating in the wild outside of our view - if pedigree, longevity, and past performance are worthwhile indicators - the threat posed by H5Nx is one that we simply can't afford to ignore. 

EFSA: Risk posed by the HPAI virus H5N1, Eurasian lineage goose/Guangdong clade 2.3.4.4b. genotype B3.13, currently circulating in the US

 

#18,782

Yesterday the EFSA (European Food Safety Authority) published a lengthy (55-page) risk assessment on the potential for the Bovine B3.13 genotype H5N1 virus to arrive in Europe and spread to local dairy cattle. 

While remarkably detailed, this report all but ignores the D.1. genotype which in recent months has spilled over into cattle in at least two U.S. states, has caused severe (even fatal) illness in humans, and which has spread with remarkable speed via migratory birds. 

The UK also reported an H5N1 infected Sheep earlier this year (genotype D1.2), and last summer the FLI successfully infected cattle with a contemporary European H5N1 virus, finding it replicated efficiently in bovine mammary tissue and could produce adaptive mutations (PB2 E627K) during replication.

While not mentioned, it is possible a separate risk assessment is in the works on other HPAI H5 genotypes. 

First, the EFSA press release - followed by a few excerpts from the risk assessment -  after which I'll have some comments.

Bird flu: EFSA analyses situation in US and tracks possible routes of spread 

3 July 2025
2 minutes read
 
The seasonal migration of wild birds and the importation of certain US products, such as those containing raw milk, could be potential routes for the introduction of the highly pathogenic avian influenza (HPAI) genotype currently affecting US dairy cows into Europe, a new report released by EFSA says. This virus type has not been reported so far in any country other than the USA.

 


EFSA’s scientists highlight that key European stop-overs with high-density bird congregations, such as Iceland, Britain, Ireland, western Scandinavia, and large wetlands like the Wadden Sea on the Dutch, Danish and German coasts would be useful places for early detection of the virus during the seasonal migration of wild birds.

The report also addresses the potential for the virus to be introduced into Europe through trade, concluding that the importation of products with raw milk from affected areas in the USA cannot be completely excluded and therefore could be a possible pathway. The importation of dairy cows and bovine meat could also be a potential route for virus introduction. However, the virus has rarely been found in meat, animal imports are very limited, and very strict trade regulations are in place for meat and live animals entering the EU.

EFSA’s report also provides an overview of the situation in the USA, where 981 dairy herds across 16 states were affected between March 2024 and May 2025. The report, which was reviewed by the US authorities, highlights that cattle movement, low biosecurity, and shared farm equipment contributed to the spread of the virus.

By the end of the year, EFSA will assess the potential impact of this HPAI genotype entering Europe, recommending measures to prevent its spread. 

SCIENTIFIC REPORT

Open Access

Risk posed by the HPAI virus H5N1, Eurasian lineage goose/Guangdong clade 2.3.4.4b. genotype B3.13, currently circulating in the US

European Food Safety Authority (EFSA), Julio Alvarez, Alessio Bortolami, Mariette Ducatez, Claire Guinat, Jan Arend Stegeman … See all authors

First published: 03 July 2025

https://doi.org/10.2903/j.efsa.2025.9508

Approved: 28 May 2025

Abstract

The emergence of highly pathogenic avian influenza (HPAI) A(H5N1), clade 2.3.4.4b, genotype B3.13 in U.S. dairy cattle marks a significant shift in the virus' host range and epidemiological profile. Infected cattle typically exhibit mild clinical signs, such as reduced milk production, mastitis and fever, with morbidity generally below 20% and mortality averaging 2%.

Transmission within farms is primarily driven by contaminated milk and milking procedures, while farm-to-farm spread is mainly linked to cattle movement and shared equipment. The virus demonstrates high replication in mammary glands, with infected cows shedding large quantities of virus in milk for up to 3 weeks, even in the absence of clinical signs. Shedding through other routes appears limited. Infected cattle develop virus-specific antibodies within 7–10 days, offering short-term protection, though the duration and robustness of immunity remain unclear.

Between March 2024 and May 2025, the virus was confirmed in 981 dairy herds across 16 U.S. states, with California particularly affected. Risk factors identified for between-farm spread include cattle movement, shared equipment and contact with external personnel, while biosecurity measures, including waste management and wildlife deterrence, may reduce the risk of virus introduction. In response to the outbreaks, U.S. authorities implemented strict movement controls, mandatory testing and enhanced biosecurity protocols.

Potential pathways of introduction of HPAI B3.13 virus into EU via trade from US could be the import of lactating cows and bovine meat, although strict trade regulations, absence of animal import and limited virus detection in meat, especially in muscle tissue, do not support this occurrence. Import of products containing raw milk could also be potential pathways for virus introduction.

Migratory birds – particularly waterfowl – pose potential pathways for introduction during seasonal migrations. The detection of mammalian-adaptive mutations and zoonotic cases underscores the virus' public health relevance and the need for research, surveillance and cross-sectoral preparedness.

        (Continue . . . )
 

The caveat in all of this is that much of this risk analysis is based on findings by our own USDA (see example below), whose understanding of the virus continues to evolve. 

According to the USDA, the spread of HPAI A(H5N1) virus between farms within and between States is likely linked to movement of lactating dairy cattle and shared equipment or workers between farms, while within farm spread is considered to be driven by mechanical cow-to-cow transmission, for example through contaminated milking equipment (USDA, online-b; Le Sage et al., 2024a).

While this theory is widely embraced by the USDA and many dairy farmers, there remain a great many unknowns surrounding the spread of the virus.

Two weeks ago in Preprint: Dairy Cows Infected with Influenza A(H5N1) Reveals Low Infectious Dose and Transmission Barriers, we looked at a study that was unable to duplicate the spread of the virus via contaminated milking equipment under controlled experimental conditions.

Similarly, limited surveillance and testing of humans, non-dairy cattle, and peridomestic animals in and around cattle farms has left us with huge gaps in the data (see EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA).

This EFSA report acknowledges a number of uncertainties in their analysis (see below).  

While the fall southbound bird migration from their high latitude roosting areas doesn't begin in earnest for another 45-60 days, we are already seeing sporadic cautionary reports of avian flu activity coming from Europe (see below).

Notice to the public regarding Avian Flu

From: Department of Housing, Local Government and Heritage
Published on: 3 July 2025
Last updated on: 3 July 2025

Highly Pathogenic Avian Influenza HPAI (H5N1) is currently circulating in wild birds, especially in breeding seabirds around Ireland. Over the last three weeks in particular, including following intensive surveillance by NPWS, and reports from others, there have been a number of cases of groups of dead wild sea birds washing up on shorelines in counties Kerry, Clare and Galway. A number have been tested by the Department of Agriculture, Food and Marine, and gulls and Guillemot have so far been confirmed with HPAI; and many multiples of that are likely to have HPAI. In total, 25 wild birds have tested positive for highly pathogenic avian influenza (HPAI) in 2025 (January-June).

Meaning that any lull in HPAI activity we may be enjoying during these summer months, could easily evaporate this fall. 

Stay tuned.

Cambodia MOH Reports 12th H5N1 Case of 2025

 

#18,781

A few minutes ago the Cambodian MOH announced their 12th case of H5N1 - and the 9th case in just over a month - this time involving a 5-year-old boy from Kampot Province who had contact with sick chickens. 

I've posted the screenshot, followed by a translation. 

(translation)

Kingdom of Cambodia

Nation Religion King

Ministry of Health

A case of bird flu in a 5-year-old child

The Ministry of Health of the Kingdom of Cambodia would like to inform the public: There is another case of bird flu in a 5-year-old boy who was confirmed positive for the H5N1 avian influenza virus by the National Institute of Public Health on July 3, 2025. The patient lives in Kamakor Village, Sam Lahn Commune, Angkor Chey District, Kampot Province, and has symptoms of fever, cough, shortness of breath, and difficulty breathing. 

This is the 12th case for 2025 in the Kingdom of Cambodia. The patient is currently under intensive care by medical staff. According to inquiries, the patient's family has about 40 chickens, as well as 2 sick and dead chickens. The boy likes to play with the chickens every day.

The emergency response teams of the national and sub-national ministries of health have been collaborating with the provincial agriculture departments and local authorities at all levels to actively investigate the outbreak of bird flu and respond according to technical methods and protocols, find sources of transmission in both animals and humans, and search for suspected cases and contacts to prevent further transmission in the community. They have also distributed Tamiflu to close contacts and conducted health education campaigns among residents in the affected villages.

The Ministry of Health would like to remind all citizens to always pay attention to and be vigilant about bird flu because H5N1 bird flu continues to threaten the health of our citizens. We would also like to inform you that if you have a fever, cough, sputum discharge, or difficulty breathing and have a history of contact with sick or dead chickens or ducks within 14 days before the start of the symptoms, do not go to gatherings or crowded places and seek consultation and treatment at the nearest health center or hospital immediately. Avoid delaying this, which puts you at high risk of eventual death.        

The elusive 11th case - which has yet to be publicly announced by the MOH - was identified two days ago thanks to the expert sleuthing of Lisa Schnirring at CIDRAP, whose article H5N1 sickens another in Cambodia reported:

. . .  a 19-month-old boy from Takeo province who died from his infection, according to a line list in a weekly avian flu update from Hong Kong’s Centre for Health Protection (CHP). The group said the case was reported on June 30.

Also, a weekly avian flu update from the World Health Organization (WHO) Western Pacific region office said the boy’s infection was one of two from Takeo province for the week ending June 26 and that his illness onset date was June 7. 

Reports of multiple human infections across several provinces of Cambodia all within a matter of a few weeks suggests the virus - which is reportedly a new reassortment of an older clade of the H5N1 virus recently renamed 2.3.2.1e) - is spreading rapidly through local poultry. 

So far most cases report close contact with sick or dead poultry, and there is no evidence to suggest human-to-human transmission of the virus.

But every spillover into humans is another opportunity for the virus to mutate and adapt to a human host, so we'll be watching this outbreak carefully.

 

Nature Comms: Monkeypox Virus Spreads from Cell-to-Cell and Leads to Neuronal Death in Human Neural Organoids

 

#18,780

While we are often reassured that most viral illnesses are `self-limiting' diseases, which will resolve over time, we continue to see evidence that some viral infections can produce significant long-term sequelae, including neurogenerative diseases. 

In the decade following the 1918 H1N1 pandemic - which killed tens of millions of people - the world experienced another type of epidemic; an explosion in cases of Encephalitis Lethargica, and Parkinson's disease, affecting millions (see The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?).

Its legacy was depicted in the 1990 fictionalized movie Awakenings, which was based on Oliver Sacks' 1973 memoir. In it, he described patients who had been comatose for 40 years who were treated with L-DOPA in the 1960s, and briefly recovered, only to slip back into a catatonic state.

While a direct link to the 1918 pandemic has never been established, similar outbreaks have been reported throughout history, 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 in Italy. 

Very early in the 2020 COVID pandemic we began to see concerns raised over potential long-term neurological damage due to the SARS-CoV-2 virus (see J. Neurology: COVID-19 As A Potential Risk Factor For Chronic Neurological Disorders), and 5 years later we continue to see evidence of substantial sequelae.

BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients

In early 2023, in Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks, we looked at a large study, published in Cell Neuron, which found a statistical linkage between viral illnesses and developing neurodegenerative diseases later in life.

Also in 2023 - in a Current Opinion In Neurology article (Chronic and delayed neurological manifestations of persistent infections by Pandya & Johnson) - the authors wrote:

Summary 

Viral encephalitis has been closely associated with the later development of neurodegenerative diseases and persistent viral infections of the CNS can result in severe and debilitating symptoms. Further, persistent infections may result in the development of autoreactive lymphocytes and autoimmune mediated tissue damage. Diagnosis of persistent viral infections of the CNS remains challenging and treatment options are limited.

The development of additional testing modalities as well as novel antiviral agents and vaccines against these persistent infections remains a crucial research goal.

Many people trivialize viral infections; assuming that if you survive the acute phase of the illness, no long-term damage was done. Increasingly, however, the evidence  suggests that chronic or repeated viral infections may sometimes do significant, even irreparable, harm. 

This from the NIH.

Links found between viruses and neurodegenerative diseases

At a Glance

• Researchers found associations between certain viral illnesses and the risk of Alzheimer’s and other neurodegenerative diseases. 

• The results suggest that some neurodegenerative disease might be avoided by preventing infection with influenza and other viruses.

While we have statistical linkage between these viral infections and neurodegenerative diseases, the exact mechanism(s) of how these infections damage the brain (which admittedly, is likely multifactorial) has remained elusive. 

In a breakthrough a dozen years ago, human neural organoids (aka hNOs) were first created from lab-grown stem cells, which can simulate the architecture and functionality of the human brain (cite).

This made it possible to monitor, in real time, the pathogenic impact of viral infections on `living' brain tissue (see here, here, here, and here). While not a perfect analog for the human brain, these lab grown organoids provide a useful in vitro model for studying brain development and neurological disorders. 

All of which brings us to a new study, published over the weekend in Nature Comms, which - using hNOs - describes how the Monkeypox virus can spread within these human neural organoids, and lead to neuronal death. 

While considered a relatively mild `self-limiting' disease, Mpox clade IIb infections have been linked to more serious illness (see Neurological manifestations of an emerging zoonosis-Human monkeypox virus: A systematic review by Sajjad Ahmed Khan, Surya Bahadur Parajuli, Vivek K Rauniyar )

Due to its length and complexity, I've only posted the abstract and some excerpts.  I've also posted a link and some excerpts from a press release from the University of Bern.

Monkeypox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids

Isabel Schultz-Pernice, Amal Fahmi, Francisco Brito, Matthias Liniger, Yen-Chi Chiu, Teodora David, Blandina I. Oliveira Esteves, Antoinette Golomingi, Beatrice Zumkehr, Markus Gerber, Damian Jandrasits, Roland Züst, Selina Steiner, Carlos Wotzkow, Fabian Blank, Olivier B. Engler, Artur Summerfield, Nicolas Ruggli, David Baud & Marco P. Alves

Nature Communications volume 16, Article number: 5376 (2025) Cite this article

Abstract

In 2022-23, the world witnessed the largest recorded outbreak of monkeypox virus (MPXV). Neurological manifestations were reported alongside the detection of MPXV DNA and MPXV-specific antibodies in the cerebrospinal fluid of patients. 

Here, we analyze the susceptibility of neural tissue to MPXV using human neural organoids (hNOs) exposed to a clade IIb isolate. We report susceptibility of several cell types to the virus, including neural progenitor cells and neurons. The virus efficiently replicates in hNOs, as indicated by the exponential increase of infectious viral titers and establishment of viral factories. 

Our findings reveal focal enrichment of viral antigen alongside accumulation of cell-associated infectious virus, suggesting viral cell-to-cell spread. Using an mNeonGreen-expressing recombinant MPXV, we confirm cell-associated virus transmission. We furthermore show the formation of beads in infected neurites, a phenomenon associated with neurodegenerative disorders. Bead appearance precedes neurite-initiated cell death, as confirmed through live-cell imaging.

Accordingly, hNO-transcriptome analysis reveals alterations in cellular homeostasis and upregulation of neurodegeneration-associated transcripts, despite scarcity of inflammatory and antiviral responses. Notably, tecovirimat treatment of MPXV-infected hNOs significantly reduces infectious virus loads.

Our findings suggest that viral disruption of neuritic transport drives neuronal degeneration, potentially contributing to MPXV neuropathology and revealing targets for therapeutic intervention.

       (SNIP)

Taken together, we show that human neural tissue, modeled in a complex 3D environment, is susceptible to infection with a contemporary clade IIb MPXV isolate. We show that viral replication factories are successfully established, resulting in a productive replication of MPXV within organoid cells. Furthermore, we find that viral antigen localizes not only to cell somata, but also to filaments of variable nature.

We propose that MPXV preferentially spreads from cell-to-cell, exploiting not only previously described mechanisms but also through neuritic transport, as demonstrated through live-cell imaging visualization of virus propagation dynamics. We furthermore report neuritic bead formation in virus-harboring axons and dendrites, previously documented to represent sites of virus egress and cell-to-cell transmission, as well as signs of neuronal injury.

Notably, bead formation precedes virus-induced neuronal death, which is initiated through neurite degeneration. The transcriptional landscape of MPXV-infected neural cultures suggests repurposing of tissue to favor viral propagation, characterized by disrupted cell homeostasis, limited antiviral and inflammatory responses, and upregulation of transcripts associated with neurodegenerative processes and synaptic reorganization.

Notably, tecovirimat treatment effectively limits viral spread but does not rescue the deleterious effects of neuron-to-neuron MPXV dissemination. Our findings identify a novel mechanism of MPXV spread in human neural tissue, shed light on potential factors contributing to mpox-encephalitis neuropathology, and provide a foundation for further exploration of orthopoxvirus neurobiology.

        (Continue . . . )


This press release from the University of Bern.

Can the monkeypox virus infect the human brain?

A new study led by researchers from the Institute of Virology and Immunology (IVI) and the University of Bern in collaboration with the Lausanne University Hospital and the Spiez Federal Laboratory shows that the monkeypox virus can spread efficiently in brain organoids, causing neuronal cell death. The study provides important insights into a previously unexplored aspect of MPXV infections.

(SNIP)

A team of researchers from the Institute of Virology and Immunology (IVI) and the University of Bern, in collaboration with the Lausanne University Hospital and the Spiez Federal Laboratory, has demonstrated for the first time that the MPXV can efficiently spread from cell to cell in brain organoids, leading to neuronal cell death. The study, supported by the Multidisciplinary Center of Infectious Diseases (MCID) at the University of Bern, was recently published in the journal Nature Communications.

       (Continue . . . )

One of the reasons why I get the flu shot every year, have stayed current with COVID shots - and still wear a mask in crowded indoor places - is that each year the evidence linking repeated viral infections to neurodegenerative diseases grows stronger.

While I can't do anything about my age, genetics, or past viral exposures, these proactive measures may help protect me going forward.

At least, that's the hope.  

Switzerland Unveils New Pandemic Plan

 

#18,779

During the first decade of the 21st century - when H5N1 was raging in Asia - there were huge pushes for pandemic planning, but after the relatively mild 2009 H1N1 pandemic, most were relegated to some dusty drawer, and forgotten.

The CDC/HHS updated their pandemic plans in 2017 (see CDC/HHS Community Pandemic Mitigation Plan - 2017), but around the country (and around the world), actual pandemic preparedness had been largely put on a back burner.

In August of 2019, in WHO: Survey Of Pandemic Preparedness In Member States, we saw the dismal results of a two-year survey of global pandemic preparedness.

Sadly, only just over half (n=104, or 54%) of member states responded. And of those, just 92 stated they had a national pandemic plan. Nearly half (48%) of those plans were created prior to the 2009 pandemic, and have not been updated since.

Only 40% of the responding countries reported having tested their pandemic preparedness plans - through simulated exercises - in the previous 5 years, nearly all were influenza-centric plans. 

Much like the IHR 2005 compliance (see Lancet Preprint: National Surveillance for Novel Diseases - A Systematic Analysis of 195 Countries), all of this was self-reported, and in retrospect some of their readiness appears to have been  badly `overstated'.

A few months later, the world was put to the test with a novel coronavirus, and discovered that you need more than just a glossy document in order to be prepared. 

While most of the world remains woefully unprepared for the next pandemic - with concerns rising over an invigorated H5N1 virus - we have started to see some small signs of increased preparedness. 

• Last summer both South Korea and Japan issued revised pandemic plans

• Last November Hong Kong held a Coordinated Avian Flu Drill `Amazonite'.

• Last April the ECDC published ECDC Guidance: Recommendations for Preparedness Planning for Public Health Threats,

• Over the past year, PAHO (Pan American Health Organization) has repeatedly urged its member nations to proactively prepare to deal with a potential influenza pandemic

• and recently the WHO ratified a 2025 Pandemic Agreement.

Additionally, a number of countries and regions have purchased (or arranged to purchase) limited quantities of H5N1 vaccine.

• In 2023 Japan announced plans to stockpile about 10 million doses.
• The United States ordered about 4.8 million doses last summer, enough for about 2.4 million people.
• The EU announced plans to acquire 650,000 doses
• Last December the UK announced plans to purchase 5 million doses,
• Five months ago Canada's PHAC Announced Plans To Purchase 500,000 doses Of H5N1 Vaccine.
• And 2 months ago the EU Commission Paved The Way For More H5N1 Vaccine Purchases

Yesterday Switzerland announced a major revision to their pandemic plan - the first since before the COVID pandemic.  Notably, this new plan is not influenza-specific, but focuses on `respiratory-borne pathogens' (see excerpt below). 

The current pandemic plan no longer refers to a single pathogen, but rather to the transmission routes of respiratory pathogens. The plan takes into account the requirements of the Epidemics Act, which is currently being revised, as well as the One Health approach. 

This, as you might expect, is an massive document (the summary alone is 35 pages), and the full report is spread across multiple online documents.  Most of this is of interest only to the Swiss stakeholders, so I'll forego posting excerpts here. 

Follow this link to read more.

Whether these plans - or the vaccines and antivirals being stockpiled - will be adequate or appropriate for the next global health crisis remains to be seen.  As we've seen before, No Pandemic Plan Survives Contact With A Novel Virus.

But having a framework for dealing with a crisis, and running realistic exercises, can be invaluable when the next pandemic strikes.

Most of these pandemic plans are created by - and for - national governments.  What planning may be going on at state/province/or local levels - or for the private sector - is harder to discern. 

Hopefully, more nations around the world are taking note and will act. 

But pandemic planning isn't just for governments or agencies. Ideally, businesses - both large and small - civic organizations, and even families should be making pandemic plans as well (see Does Your Company Have A CPO?).

While it may be years before the next pandemic emerges - as we've seen - the world can change literally overnight.  And once that happens, the options for preparedness rapidly wane. 

Sadly, many of the older CDC pandemic guidance documents have broken links, have been `retired', or are difficult to find.  After some searching I was able to find:

• The CDC's Get your household ready for pandemic influenza - April 2017.

• British Columbia Gov. has a 17-page Household Pandemic Preparedness Guide

• And Ready.gov also provides a pandemic preparedness section.

For more on what you and your family can do to prepare for the next global health crisis, you may wish to revisit:

A Personal Pre-Pandemic Plan

J. Virology: Genetic Resilience or Resistance in Poultry Against Avian Influenza Virus: Mirage or Reality?

2005 cover of CSIRO’s Livestock Research Magazine

#18,778

Like the creation of a truly universal flu vaccine, the quest for an avian flu-resistant chicken (and other poultry species) is one of the holy grails of influenza virology. 

Nearly 13 years ago, in CSIRO: The Quest For Flu Resistant Poultry, I featured a 2005 Livestock Research Magazine cover (above), where Cambridge University virologist Laurence Tiley had stated, “The tools to make poultry resistant to flu infection already exist”.

His bigger concern was whether they could persuade the public of the benefits of Genetically Modified (GM) poultry, which remains a touchy subject. 

By 2012, additional work had been done on the creation of transgenic chickens; which would hopefully not only be resistant to H5N1, but could pass that resistance onto their chicks (see Silencing the bird flu gene: scientists prep live hen trials in The Conversation).

But just as predictions of a commercially available universal flu vaccine being just 5 years away have thus far proved optimistic, the road to flu-resistant poultry has hit repeated roadblocks.  

Progress continues to be made, however, on both fronts (see 2023's NIH: Clinical Trial of Universal Hexavalent Flu Vaccine Candidate Begins), and today we have a lengthy - and at times highly technical - review of recent strides in developing flu resilient and/or resistant chickens.

While we appear to be getting closer to those goals, there are still a lot of obstacles to overcome.  And assuming resistant poultry can eventually be produced, there is still the matter of acceptance by the public. 

Those looking for a deep-dive will want to follow the link and read the review in its entirety (warning: pack a lunch).  I'll have a brief postscript after the break. 

Genetic resilience or resistance in poultry against avian influenza virus: mirage or reality?

Authors: Paula R. Chen, Stephen N. White, Lianna R. Walker , Darrell R. Kapczynski , David L. Suarez  david.suarez@usda.govAuthors Info & Affiliations

https://doi.org/10.1128/jvi.00820-25

 ABSTRACT

The unprecedented global spread of the highly pathogenic avian influenza (HPAI) virus in wild birds, poultry, and mammalian species has challenged our control efforts. Alternative approaches to limit avian influenza viruses (AIV) include the development of resilient or resistant chickens. Genetically resilient birds may become infected but can overcome disease, whereas resistant birds prevent virus attachment or entry and do not become infected. 

The most intensively studied host gene is myxovirus-resistance (Mx), which is expressed via the interferon pathway. Both sensitive and resistant chicken Mx genotypes have been described, but this only provides limited resilience. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been demonstrated as a host cofactor for AIV replication via interaction with the polymerase. Small nucleotide changes within this gene have demonstrated some promise for the establishment of disease resilience. Certain MHC-defined genetic chicken lines have demonstrated increased resilience with higher innate immune responses, but HPAI-infected birds still have high morbidity and mortality. 

Alternatively, gene-edited or -transgenic chickens have had some success in increasing resilience. This strategy allows flexibility to include foreign genes, modification of existing genes, or combined approaches to block critical steps in the viral life cycle. Some candidate genes include solute carrier 35A1 (SLC35A1), retinoic acid-inducible gene I (RIG-I), and toll-like receptors 3 and 7 (TLR3/7), but animal testing needs to be conducted. 

Furthermore, existing hurdles for technology transfer to commercial application from either naturally occurring resistance genes or foreign genes remain high and will require acceptance by both the poultry industry and consumers.

        (SNIP)    

CONCLUSIONS

Many groups using multiple different approaches have tried to identify genetically resistant poultry with no success. Several genes have been identified that may increase genetic resilience, but because of the high virulence and genetic variability of HPAI viruses, no genes on their own are likely to provide enduring resilience to disease.

However, other genes involved in AIV infection in chickens are likely to be identified and validated. An even greater obstacle is to introduce these genetic changes into commercial lines, where genetic trade-offs for disease resistance will need to be weighed against many other production traits.

Future work will clarify these tradeoffs in the form of the potential correlated responses to selection for naturally occurring, gene-edited, or transgenic alleles. We note that gene editing and/or transgenic approaches can be used alone, in combination with naturally occurring variants and breeding, or as the first discovery step to implement through similar natural genetic variants and selective breeding. If successful, any of these approaches would provide additional tools to combat AIV and be immensely valuable to the poultry industry.

       (Continue . . .)

 

Finding ways to make livestock innately flu resistant - without the need for repeated vaccinations or a steady diet of antivirals - is an incredibly important goal, and worthy of pursuit. 

We've seen how quickly the overuse of antivirals can lead to resistance (see Nature's China's chicken farmers under fire for antiviral abuse), and vaccines must be continually updated if they are to be effective (see J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China).

While I don't expect a `genetic solution' will become available anytime soon, we do need to be taking the `long view' on avian flu control, since pharmacological solutions are both finite and incredibly fleeting.