EXPERT REACTION: Bird flu (H7N3) detected at Victorian poultry farm

Australian Animal Health authorities have good relations with commercial poultry producers in Australia.  Producers know that if HPAI [a highly pathogenic avian influenza] is confirmed, that they will receive compensation from the government following the implementation of control and containment procedures.

This prior agreement is one of the major reasons why the control of HPAI has been so successful in Australia compared to many countries in the region  However, we now have many more households raising backyard chickens and it's important that these households ensure that they provide their chickens with treated/tap water and feed in containers inaccessible to wild birds.

Households should make sure that they contact a veterinarian or the Government Emergency Animal Disease Hotline if their birds start to show signs of illness such as: sudden death, swollen head, closed and runny eyes, lethargy and depression, lying down and unresponsiveness, lack of coordination and eating less than usual.

I work for Vaxxas which is doing research on skin patch vaccinations to potentially protect against both influenza A H7 and H5 in humans.

Bird flu is likely to soon affect Australia in a much broader sense as infected wild birds are increasingly mixing with our itinerant wild birds. Many birds especially skuas have recently died in Antarctica.  This all started with an outbreak in farmed geese in China in 1996.

Mammals that eat dead birds can be affected. Over 50 species are known to be troubled including sea lions, seals, polar bears and brown bears. Dairy cattle in the US have been affected and the virus may spread via milking machines. The US are ramping up vaccine development for cows.

Stockpiling of antivirals is again on the agenda, as is improved surveillance and testing. Australia has some onshore abilities to develop and produce appropriate vaccines - this needs more attention.

Updated comments on the recent detection of H7N3 Avian Influenza strain by Agriculture Victoria and also on the first human case of H5N1 by Victorian Health officials:

H7N3:

The H7N3 subtype of avian influenza viruses is predominantly known for its impact on domestic poultry, particularly chickens, turkeys, and ducks. Originating from wild birds, especially waterfowl, which act as natural reservoirs, the virus often circulates asymptomatically in these populations. However, when transmitted to domestic poultry, particularly in densely populated environments like poultry farms, it can spark widespread outbreaks. Transmission occurs through various routes, including direct contact between infected and susceptible birds, contamination of surfaces and equipment, and the dispersal of infectious aerosols within confined spaces. Infected birds shed the virus primarily through saliva, nasal secretions, and faeces, contributing to environmental contamination. The persistence of the virus in cooler climates further facilitates its spread and survival.

Despite its primarily avian focus, H7N3 possesses zoonotic potential, albeit limited. Human infections are rare and typically result from close contact with infected birds or contaminated environments. Human-to-human transmission has been sporadically reported but has not been sustained beyond isolated cases. However, the risk of genetic reassortment between avian and human influenza viruses raises concerns about the emergence of novel strains with enhanced transmissibility or pathogenicity.

Documented human cases of H7N3 infection serve as important markers of its zoonotic capacity. Instances such as those recorded in British Columbia, Canada, in 2004, and Jalisco, Mexico, in 2012, underscore the importance of surveillance and rapid response measures. While human cases have generally resulted in mild symptoms and full recovery, the potential for severe outcomes cannot be discounted, particularly in vulnerable populations.

Public health interventions aimed at mitigating the spread of H7N3 encompass a multi-faceted approach. Surveillance efforts involve active monitoring of both domestic poultry and wild bird populations to detect and track influenza infections. Rapid testing and reporting protocols ensure swift identification and containment of outbreaks in both avian and human populations. Biosecurity measures on poultry farms, including strict hygiene practices, movement control, and personal protective equipment for workers, are crucial for preventing transmission within and between farms. Similarly, strategies to reduce contact between wild birds and domestic poultry help minimize the risk of introduction and spread.

H5N1:

H5N1 avian influenza, a highly pathogenic strain primarily affecting birds, poses a significant public health threat due to its potential to cause severe illness in humans and its pandemic potential if it acquires sustained human-to-human transmission capabilities. While rare, human infections typically result from direct contact with infected birds or their environments, with sporadic cases reported globally, including recent occurrences in Egypt, Vietnam, and China. The virus's ability to undergo genetic reassortment or mutation heightens concerns, as mutations enabling efficient human-to-human transmission could trigger a pandemic similar to the previous ones. Monitoring efforts involve surveillance of bird populations to track virus circulation, alongside research into genetic characteristics to gauge its potential for human adaptation. The virus's rapid spread across borders through infected poultry or migratory birds underscores the importance of vigilant monitoring and containment measures. However, the public need not panic, as current surveillance and response efforts aim to detect and manage outbreaks promptly. While the possibility of H5N1 mutating to pose a greater threat to humans warrants attention, proactive monitoring and control measures mitigate the risk. Thus, while vigilance is crucial, there is no immediate cause for alarm.

Avian influenza, particularly strains like H5N1, presents significant pandemic risks due to antigenic changes. Recent cases in the US and Australia, involving 51 dairy herds, two dairy farm workers one in Texas (reported 1 April 2024) and the other in Michigan (reported 22 May 2024) who contracted it from a cow, and a 5-year-old child (reported 22 May 2024) in Victoria, highlight these concerns. The child contracted the virus in India and was detected during routine testing, sparking global health worries. No further cases linked to H5N1 have been identified through contact tracing. This case is notable for its potential to cross species barriers and affect humans more broadly.

The total number of H5N1 cases globally stands at 891 between 2003-2024, with 463 deaths. While wild migratory birds are the primary carriers, transmission can occur through cattle movements and dairy facilities. Concerns escalate if pigs become infected, potentially creating more virulent strains by mixing avian and human influenza viruses. Since 2022, H5N1 has affected various mammal species and has been found in US wastewater, suggesting potential spread to domestic animals. Cats and dogs have been found with H5N1, sparking concerns of possible human transmission due to close interactions with pets.

In Australia, a different avian influenza strain, H7N3, was identified in poultry, leading to the euthanasia of hundreds of thousands of chickens. Although less known than H5N1, H7N3 poses risks to both animal and human health. Vaccines like AUDENZ™ exist for H5N1. Vigilant global public health efforts are crucial to address these emerging zoonotic diseases, emphasizing the need for improved surveillance, diagnostics, and public health infrastructure to protect both food system workers and the general population.

Both H5N1 and H7N3 are rare in humans and human-to-human transmission has not been reported. Infections have occurred in humans via contact with infected animals.

The avian influenza or bird flu detected in a poultry farm in Victoria is of the type H7N7 H7N3 [Agriculture Victoria has initially said the strain was likely to be H7N7 but confirmed the strain was H7N3 on 23 May]. This is different to the H5N1 strain that has been devastating domestic and wild birds around the world. The H5N1 bird flu is highly pathogenic for birds, and for the small number of humans infected, the case fatality rate has been high. The current H5N1 outbreak was first detected in Europe in 2020. It has affected a wider range of bird species than previous outbreaks and has led to significant losses in both wild bird populations and poultry flocks worldwide. The disease has also spread to a wide range of wild and domestic animals including several cow herds in the USA. It is highly likely that it will eventually be detected in Australia. 

At the moment, it is people working with poultry or infected animals or hunters that have caught the disease, and there is no evidence to date of person-to-person transmission. The risk of widespread transmission among mammals and potential spillover to humans remains a concern, although at the moment the risk to humans is considered low.

There is a vaccine available against H5N1 for poultry, and the US CDC has developed candidate vaccine viruses that could quickly be used to develop vaccines for human use. The situation is being closely monitored by WHO and other authorities.

It is very reassuring that the strain identified is an H7 virus (which we have previously had outbreaks of in Australia) rather than the problematic H5N1 strain that is circulating globally. However, this should serve as an important reminder as to the need for constant vigilance regarding avian influenza and the need to report any sick or dying birds to the appropriate authorities. 

The detection of H7N7 H7N3 [Agriculture Victoria has initially said the strain was likely to be H7N7 but confirmed the strain was H7N3 on 23 May] avian influenza (bird flu) in an egg farm in Victoria is not good news. It highlights the importance of having Australia's new CDC fully resourced, and the ongoing collaboration of scientists in animal and human health ("One Health") to identify any potential zoonoses likely to cause a pandemic. For humans , H7N7 to this point has only been associated with sporadic cases of bird flu.

The feared sustained human-to-human transmission has not eventuated: yet. Currently, the bird flu strain of most concern is H5N1. Over the last couple of years, H5N1 has spread over multiple continents, presumably through migrating wild birds, but has then evolved to infect and devastate unusual populations, such as marine mammals. Most recently, H5N1 has earned notoriety by infecting herds of dairy cows in the USA. Thankfully, animal-to-human transmission of this strain of H5N1 has been rare (only one case in the US).

In Victoria, surveillance will have to be ramped up to identify other poultry populations infected with H7N7 [H7N3]; hopefully, large culls won't be needed. From a human health perspective, it is vital to terminate this H7N7 [H7N3] outbreak as soon as possible, otherwise more infections give the virus more opportunities to mutate. Infection from poultry to farmed pigs is of particular concern, as pigs can act as the perfect mixing pot of human and avian flu viruses, leading to a strain of flu that can then move between humans easily. Despite having "COVID fatigue" and not wanting to hear the word "pandemic" again, the next pandemic could be just around the corner, and a strain of bird flu is a likely candidate. Unlike the early days of COVD, at least with H5N1, there are already human vaccines and antivirals.

Avian influenza (AI) viruses are classified by a combination of two groups of surface proteins: haemagglutinin or “H” proteins, of which there are 16 (H1 to H16), and neuraminidase or “N” proteins, of which there are nine (N1 to N9). Many different combinations of “H” and “N” proteins are possible – in fact, mathematically there are 170 different combinations possible. Each combination is considered a different subtype and can be further broken down into different strains.  

AI viruses are further classified by their pathogenicity, low or high, based upon the ability of a particular virus strain to cause disease in chickens.

• Highly pathogenic avian influenza (HPAI) viruses in poultry are usually H5 or H7 subtypes of Type A influenza
• The viral strain most likely to cause human disease and fatalities is H5N1. 
• A mutation of this virus, HPAI H5N1 clade 2.3.4.4b, has been spreading globally including Antarctica), causing widespread outbreaks and deaths in bird populations. To date, very few people have died from this new strain. It has not yet been reported in Australia. 
• Australia has been relatively free of AI but, even so, this is the 9th outbreak of HPAI in Australia since 1976. None of these outbreaks involved the H5N1 strain. 

While Australia has not experienced an outbreak of the HPAI H5N1 virus, the experience gained from dealing with the outbreaks of other strains of HPAI over the last 50 years has given Australian scientists invaluable opportunities to learn how to deal with future outbreaks – even of the H5N1 variant. Surveillance of wild birds and domestic flocks, as well as contingency plans to stop an outbreak in its tracks, are not only in place but have been tested and we know they work. 

While Australia will undoubtedly experience an outbreak of H5N1 in the future, the skills to contain it are here now

Strain testing of the avian influenza virus detected in Victoria has confirmed that it is not the highly pathogenic H5N1 strain. Over the past two years, the H5N1 2.3.4.4b variant of avian influenza has spread globally, causing significant mortality in both poultry and wildlife. To date, Australia remains the only continent free of the H5N1 2.3.4.4b virus, after it reached Antarctica earlier this year. The highly pathogenic strain has been devastating worldwide, resulting in numerous wildlife deaths, particularly within seabird colonies, and has also spread to mammals. Despite confirmation that the Victorian detection is the H7N7 H7N3 [Agriculture Victoria has initially said the strain was likely to be H7N7 but confirmed the strain was H7N3 on 23 May] strain rather than H5N1, maintaining stringent quarantine procedures remains essential to prevent further spread and protect both poultry and Australian wildlife.

This is concerning, as Australia has historically been spared from avian influenza. Most avian influenza is spread by wild waterfowl (ducks, geese and swans), which migrate vast distances globally across flyways that bypass Australia. We first need to know if this is H5N1 or something else. This outbreak has been confirmed as H7N7 H7N3 [Agriculture Victoria has initially said the strain was likely to be H7N7 but confirmed the strain was H7N3 on 23 May], which is better news than if it had been H5N1. We have seen H7N7 and H7N2 in a small number of outbreaks between 2012-2020 in NSW and Victoria, which were successfully contained.  The US virus is H5N1 clade 2.3.4.4b which has swept the world since 2021 has infected a vast number of other wild birds and mammals, including in Antarctica. This means non-waterfowl birds may be spreading it along different flyways to the waterfowl, and this means Australia’s protected status may be at risk. We did a study showing that the dairy farm outbreak in the US was likely started by introduction of infection from wild non-waterfowl birds, and then spread via cattle trade and risky farming practices.

Avian flu viruses do not transmit easily in humans because they are adapted for birds, which have different receptors in their respiratory tract to ours, but they can mutate to become adapted to the human respiratory tract. That is what we fear. H5N1 clade 2.3.4.4b is the most concerning, as it has caused severe disease, including neurological damage, in animals and birds, and the statistical probability of it mutating to become transmissible in humans (and thereby cause a pandemic) as higher than any time in the past, because of the sheer scale of global infection in animals and birds and the opportunities for human adaptation. Once it gets in the food supply (meat, unpasteurised milk), that risk is even higher. A human pandemic of influenza would be much more severe that SARS-CoV-2. 

The economic impact of avian flu on farming is enormous, and this alone is cause for concern. Traditionally, outbreaks in farmed poultry have been managed by culling infected birds, and this tends to control the outbreak. Fortunately, we do not have widespread infection in Australia, so this should be a feasible strategy. There are vaccines for poultry, but they are only partially effective and can mask outbreaks. They have not been used in the past to control outbreaks, but France, for example, has such extensive infection in farmed poultry that they began using vaccination recently. Fortunately, we are well prepared for human vaccines. If a pandemic arises, once the genome sequence is known, and exact matched vaccine can be made in 6 weeks with mRNA technology and 4 months using the old egg-base methods. Australia is fortunate to have influenza vaccine and mRNA manufacturing capacity onshore, which many countries do not have. The regulatory process may take longer, but we can expect to have vaccines sooner than we did for COVID-19.

For now, we have an avian flu outbreak in farmed birds which is not the most feared strain, thankfully. Whether H5N1 can get here via wild birds remains an open question.  The current outbreak is likely be controlled quickly.  The risk of a human pandemic arising is highest in the US, the Americas and Europe, which are now the global hotspots for H5N1.

Avian influenza or bird flu is caused by a variety of influenza type A viruses that normally infect birds, especially waterfowl and shorebirds. Some are low pathogenicity avian influenza (LPAI) but others are high pathogenicity avian influenza (HPAI) strains. The difference lies in the number of basic amino acids at the cleave site of haemagglutinin (HA), a spike protein on the virus surface, which is cleaved by cellular proteases. This cleavage determination then allows the virus to infect cells of different tissues and organs in the body. So if the virus HA is more easily cleaved by proteases, it will be more pathogenic.

Identification of the genetic sequence of this virus strain and its subtype responsible for the outbreak in poultry is important. Chickens are highly susceptible to bird flu and an entire flock can be decimated overnight with HPAI. Birds shed virus in their saliva, mucous and feces. Bird flu strains have been known to infect humans but limited transmission between humans exists. Bird and human flu viruses usually have different cell receptor binding properties but some have dual binding to both avian and mammalian cells. As influenza viruses can rapidly mutate a LPAI can potentially develop into a HPAI. Therefore, surveillance of LPAIs and biosecurity measures are critical for warnings and control of virus outbreaks.

Summary:
Avian Influenza (AI), also known as bird flu, is a viral infection that mainly affects birds but can also infect humans and other animals. The viruses responsible for AI are influenza A viruses, which belong to the Orthomyxoviridae family.

Different Subtypes
Avian influenza viruses are divided into subtypes based on the combination of two surface proteins:

• Hemagglutinin (HA): There are 18 identified HA subtypes (H1 to H18).
• Neuraminidase (NA): There are 11 identified NA subtypes (N1 to N11).

The most concerning subtypes for humans include H5N1, H7N9, and H5N8.

Transmission

Avian influenza viruses spread mainly among birds through:

• Direct contact: With infected birds, their secretions, or feces.
• Contaminated environments: Such as water, soil, and surfaces.
• Migration: Wild migratory birds can carry the virus over long distances.

Transmission to humans can occur through:

• Direct contact: With infected birds or contaminated environments.
• Consumption: Of undercooked poultry products.
• Aerosols: Generated from infected birds' droppings or secretions, though this is less common.

Mutation Rate and Genetic Reassortment

Avian influenza viruses mutate quickly due to the error-prone nature of their RNA polymerase. They can also undergo genetic reassortment, where two different influenza viruses infect the same host cell and exchange genetic material, leading to new virus strains with pandemic potential.
Different Hosts
While birds are the primary hosts, avian influenza viruses can infect various species, including:

• Poultry: Such as chickens, ducks, and turkeys.
• Wild birds: Especially waterfowl.
• Mammals: Including pigs, horses, cats, dogs, and humans.

Potential Danger as the Next Pandemic Candidate

Several factors make avian influenza a potential candidate for the next pandemic:

• Wide Host Range: The ability to infect many species increases the chance of crossing the species barrier to humans.
• High Mutation Rate: Allows the virus to quickly evolve new strains that can evade existing immunity.
• Genetic Reassortment: Can create highly pathogenic strains with pandemic potential.
• High Mortality Rates: Some subtypes, like H5N1, have high mortality rates in humans.
• Global Spread: Migratory birds can spread the virus over large distances, making containment difficult.

Can different strains/subtypes of Avian Influenza jump to humans?

Avian influenza, also known as bird flu, can cross from animals to humans through several mechanisms and often requires particular mutations to adapt effectively to human hosts. Here’s an overview of the transmission pathways and necessary mutations:

Modes of Transmission

1. Direct Interaction:
   • Infected Birds: Handling live or deceased infected birds, their droppings, or secretions.
   • Contaminated Objects: Touching surfaces or materials contaminated with the virus.
2. Ingestion:
   • Undercooked Poultry: Eating poultry or poultry products that are not properly cooked.
3. Inhalation:
   • Aerosolized Particles: Breathing in dust or droplets from infected bird droppings or secretions.

Necessary Mutations for Human Adaptation
For avian influenza viruses to infect humans effectively, they generally require mutations that enable them to adapt to human cellular environments. These mutations can influence various viral characteristics:

1. Receptor Binding:
   • Hemagglutinin (HA) Protein: Avian influenza viruses typically bind to α2,3-linked sialic acid receptors found predominantly in birds. Humans have α2,6-linked sialic acid receptors in their upper respiratory tracts. Mutations in the HA protein can shift the virus’s binding preference from α2,3 to α2,6 receptors, facilitating human infection.
2. Polymerase Function:
   • PB2 Protein: The PB2 protein is part of the viral RNA polymerase complex. Mutations such as E627K in the PB2 protein can improve the virus's ability to replicate efficiently at the cooler temperatures present in human upper respiratory tracts.
3. Protein Stability:
   • Surface Proteins: Mutations that enhance the stability of viral surface proteins (HA and NA) can help the virus survive longer in the human respiratory tract environment.
4. Enhanced Replication and Spread:

• Internal Proteins: Changes in internal viral proteins, such as NP (nucleoprotein), can boost the virus’s ability to replicate in human cells.

The transmission of avian influenza from animals to humans occurs through direct interaction, ingestion, and inhalation pathways. For the virus to adapt and efficiently infect humans, specific mutations are needed, particularly in the hemagglutinin and polymerase proteins. These mutations enhance receptor binding, replication, and stability within human hosts. Monitoring these mutations is crucial for predicting and preventing potential pandemics.

What do we know about the H7N7 subtype? [Agriculture Victoria has initially said the strain was likely to be H7N7 but confirmed the strain was H7N3 on 23 May]

Potential for Human-to-Human Transmission

Currently, H7N7 has limited human-to-human transmission capability. Most human cases have been linked to direct contact with infected poultry or contaminated environments. However, the potential for mutations that enhance human transmissibility poses a risk. These changes could lead to more efficient transmission among humans, raising concerns about pandemic potential. Previous incidences of H7N7 subtype includes the 2003 Netherlands outbreak where poultry workers and their families were infected. The infections were predominantly conjunctivitis (eye infections) with some respiratory symptoms.

Public Health Implications and what should be done?

Surveillance: Continuous monitoring of H7N7 in poultry and humans is crucial to detect emerging strains with increased human adaptation.

Biosecurity: Improved biosecurity measures in poultry farms and live bird markets can reduce the risk of transmission to humans.

Preparedness: Developing vaccines and antiviral strategies targeting H7N7 can help mitigate the impact of potential outbreaks.

H7N7 avian influenza has demonstrated the ability to infect humans, primarily through direct contact with infected birds. While human-to-human transmission remains limited, the virus's potential to mutate and adapt to human hosts necessitates vigilant surveillance and preparedness to prevent and control potential outbreaks.