Tuesday, April 23, 2024

Mixed Messaging On HPAI Food Safety


Although the USDA and FDA continue to reassure the American public that the food chain (including milk) is safe from HPAI H5N1, there remain unanswered questions about how widespread the virus is in cattle, and how effective regular pasteurization is in killing the virus. 

While the extent of the spread in cattle remains unknown, 3 days ago the New York Times carried an article (see Scientists Fault Federal Response to Bird Flu Outbreaks on Dairy Farmswhere they cite (so farunverified) reports of positive tests from asymptomatic cattle in North Carolina.

Testing by the USDA of cattle has remained both limited and voluntary, and has so far only been recommended for symptomatic dairy cows (see APHIS/USDA Updated FAQ On Detection of HPAI (H5N1) in Dairy Herds).

This `don't test, don't tell' policy apparently extends to pigs as well, despite ongoing concerns that HPAI could find a home in swine herds (see EID Journal: Divergent Pathogenesis and Transmission of Highly Pathogenic Avian Influenza A(H5N1) in Swine).

An excellent overview by Jon Cohen in Science yesterday (see U.S. government in hot seat for response to growing cow flu outbreakdescribes the parsimonious release of information by the U.S. government, along with the limited evidence on the effectiveness of standard pasteurization in deactivating the virus. 

Under what I assume to be an abundance of caution, the CDC recently revised their food safety advice (see below) regarding HPAI, which now includes guidance on safely cooking beef (which, according to the USDA, are unlikely to be infected).  

  • Whole cuts of beef, veal, lamb, and pork, including fresh ham: 145°F
  • Ground meats, such as beef and pork: 160°F
  • All poultry, including ground chicken and turkey: 165°F

It is also worth mentioning that despite the mantra that `properly prepared foods are safe to consume', there may be some small risks entailed in the preparation of raw meat.  PAHO (the Pan-American Health Organization) mentions this on their Avian Influenza landing page:


The most common way for the virus to enter a territory is through migratory wild birds. The main risk factor for transmission from birds to humans is direct or indirect contact with infected animals or with environments and surfaces contaminated by feces. Plucking, handling infected poultry carcasses, and preparing poultry for consumption, especially in domestic settings, may also be risk factors.

In Asia, more than a few human HPAI H5 infections have been linked to preparing and cooking poultry.  Although it gets mentioned, far more attention needs to be paid to safe food handling practices in this time of HPAI. 

While I fully understand the USDA's desire to reassure the public about the safety of the food supply - doing so while slow rolling the release of information is a risky strategy.

Particularly when dealing with a virus with a history of repeatedly doing the unexpected.

Monday, April 22, 2024

I&ORD: Evidence of Reverse Zoonotic Transmission of Human Seasonal Influenza A Virus (H1N1, H3N2) Among Cats


My strictly indoor companion


Up until 20 years ago, cats (and dogs) were thought relatively immune to influenza A viruses.  All that changed when an equine H3N8 virus jumped to greyhounds at a racetrack in Florida in 2004, and half-way around the world, big cats in Asian zoos began to succumb to avian H5N1. 

Since then we've seen a second (avian H3N2) influenza A virus jump to dogs and begin a world tour, and dozens of reports of dogs and cats infected with a variety of (mostly novel) influenza A viruses.  

A small sampling includes:

Microorganisms: Case Report On Symptomatic H5N1 Infection In A Dog - Poland, 2023

J. Virology: Zoonotic Risk, Pathogenesis, and Transmission of Canine H3N2

Access Microbiology: Inter-Species Transmission of Avian Influenza Virus to Dogs

WHO Update & Risk Assessment On H5N1 In Cats - Poland

Nebraska Veterinary Diagnostic Center (NVDC) Report: 2 Domestic Cats Infected With HPAI H5N1

The most obvious concern is that a dog or a cat might pick up a novel influenza A virus (like H5N1) from exposure to birds, or a contaminated environment, and bring it home (zoonotic transmission). 

But it is equally possible that a companion animal (or farmed animals) could be infected by humans (aka `reverse zoonosis'), and even introduce that virus into the wild.  

Reverse zoonosis may help explain how SARS-COV ended up in North American deer and other peridomestic animals, and almost certainly how human influenza A viruses have spread so widely in swine (see Reverse zoonosis of influenza to swine: new perspectives on the human-animal interface)

While we've seen a fair number of studies on novel flu infection in companion animals, relatively little is known about the spread of seasonal flu viruses to cats.  

All of which brings us to a letter to the Editor published in Influenza & Other Respiratory Diseases, which provides details of evidence of reverse zoonotic transmission of seasonal flu viruses to cats in China, and discusses the potential for cats to serve as a `mixing vessel' . 

First, some excerpts from the letter (follow the link to read it in its entirety), after which I'll return with a postscript.

Evidence of Reverse Zoonotic Transmission of Human Seasonal Influenza A Virus (H1N1, H3N2) Among Cats

Sajid Umar, Semin Kim, Di Gao, Pu Chen
First published: 18 April 2024

Dear Editor,

Human–animal interactions are closely intertwined. The connection between animal, human, and environmental health is becoming increasingly complicated with globalization, industrialization, and climate change. Since the beginning of the 20th century, the number of domestic cats has increased rapidly worldwide, including in China. There are approximately 600 million domesticated cats worldwide, including 65 million cats in China, most of whom have close human contacts

These close contacts create more chances for pathogen spillover among humans and cats, which could lead to the emergence of new pathogenic strains or variants. Cats living in proximity to their owners carry a particular risk of catching pathogens, as they often share snuggles, kisses, dining, and beds [1, 2]. We share hundreds of pathogens with our animals, which they serve as intermediate or reservoir hosts for pathogens that affect human health. Cats, owing to their genetic similarity to humans, are more susceptible to catching diseases from their owners. Recently, it has been estimated that humans spillover far more pathogens to animals than animals transmit to humans [2, 3]. 


The high susceptibility of cats to IAVs generates the possibility of zoonotic and reverse-zoonotic transmission events and can serve as a mixing vessel for the emergence of new IAV variants (Figure 1). A large population of animals and humans makes China an ideal location for the emergence of future IAV pandemics.


IAV was detected in 2.8% of the samples (13/458), whereas influenza B virus was not detected during this study. Genetic analysis revealed the presence of A (H1N1) and A (H3N2). Among the positive strains, there were nine strains of A (H1N1) virus and four strains of A (H3N2) virus. A/H1N1 and A/H3N2 positive cats showed HAI titers against these viruses, which also supported the evidence of reverse zoonosis. Interestingly, a higher detection rate (84.61%) was observed in samples collected during autumn and winter, which could be linked to the peak flu season in Kunshan and Shanghai. Clinical signs, including sneezing, dyspnea, and coughing, varied from mild to moderate among influenza-positive cats. No deaths were reported among the positive cats.
Based on molecular and serological testing, we demonstrated human seasonal IAV-infected cats in this study. This is the first report to assess the reverse zoonotic events of influenza viruses in cats in Kunshan, China, and highlights the potential risk of catching IAV in cats living in close contact with their owners. Despite some limitations, such as the small sample size and geographical area, our study provides useful information to veterinarians, pet owners, and policymakers.

Cats could act as additional intermediate or reservoir hosts for endemic IVA evolution and thus may contribute to major public health issues. There are several reports on the natural transmission of different IAV subtypes in cats, including avian H5N1, canine H3N2, human H1N1, and H3N2 [8]. Anthroponotic spillover events for IAV have been documented among cats, suggesting close interactions between cats and owners suffering from influenza-like illness [1, 8-11]. In addition to cats, a variety of other animals (swine, dogs, turkeys, and ferrets) has been naturally infected with Influenza A/H1N1. Human-to-pig transmission of IAV is the most studied anthroponotic event. 
More IAVs jump from humans to swine than from swine to humans [1].
Several suggestions have been made to minimize the risk of IAV-reverse zoonosis.
First, flu vaccine shots are recommended to owners and susceptible cats to reduce anthroponotic events.
Second, people who are sick with seasonal flu need to modify their behaviors and should be more vigilant about the health of their cats. Pet owners can minimize reverse zoonotic transmission by keeping nasal discharges and other bodily secretions away from cats during the sickness period.
Third, owners can minimize their playing time and petting activities with their cats while they are sick.
Finally, they can also limit reverse zoonotic transmission by regularly cleaning and disinfecting the bedding area and providing fresh and healthy feed to their cats.
Reverse zoonotic events in IAV can pose significant health risks for cats and possibly human health if left unchecked. Therefore, it is important to keep the IAV under control before it imposes deadly consequences on the human population. Keeping in mind the close association of cats with humans and the high pandemic potential of IAV warrants a more integrated research approach to minimize reverse zoonoses. This could include greater testing and continuous human pathogen surveillance at the human-animal contact interface. This type of data could facilitate the mitigation, prevention, prediction, and preparation of future IAV pandemics.

          (Continue . . . .)

Twice in my lifetime (H2N2 in 1957 & H3N2 in 1968) pandemic influenza viruses have emerged from China that were a combination of avian and human flu viruses.  Presumably, some unknown host was co-infected with a seasonal flu virus and and avian flu virus, and produced a hybrid via reassortment.  

While that host might have been a human, it could just as easily have been a pig, a dog, a cat, or some other non-human host.

All reasons why, with the elevated amount of HPAI H5N1 virus in wild birds and the environment, it is more important than ever to heed the CDC's advice on how to keep your pets (and your family) safe. 

USDA Releases 239 Sequences From HPAI H5N1 Viruses

USDA - 32 Outbreaks of H5N1 in Cattle across 8 States


The USDA, which has been criticized for being slow to release genetic sequences from H5N1 viruses affecting cattle (see Helen Branswell's STAT report) - published 239 genetic sequences on Sunday evening on the SRA - NCBI (nih.gov) website.

Sequences posted are from cattle, cats, chickens, skunk, raccoon, grackle, blackbird, and goose. However, some important epidemiological details on each sample (e.g. location, collection dates, etc) are not immediately apparent (see graphic above).

Each submission contains megabytes of cryptic data, so it will take time for researchers to fully analyse them.

The USDA announcement follows:

USDA Publishes H5N1 Influenza A Virus Genetic Sequences on publicly available site
Last Modified: April 21, 2024
Today, the APHIS National Veterinary Services Laboratories made available 239 genetic sequences from the U.S. H5N1 clade influenza virus recently found in samples associated with the ongoing highly pathogenic avian influenza (HPAI) outbreak in poultry and wild birds, and the recent H5N1 event in dairy cattle. APHIS routinely publishes influenza genetic sequence data on GISAID (the Global Initiative on Sharing Avian Influenza Data); however, in the interest of public transparency and ensuring the scientific community has access to this information as quickly as possible to encourage disease research and development to benefit the U.S. dairy industry, APHIS is also rapidly sharing raw sequence data to the National Institute of Health’s National Library of Medicine, National Center for Biotechnology Information. Sequences posted are from cattle, cats, chickens, skunk, racoon, grackle, blackbird, and goose. APHIS will continue making additional raw genetic sequences available on a rolling basis at Home - SRA - NCBI (nih.gov); use the search term “WGS of H5N1”.

Sunday, April 21, 2024

A Slight Case Of Deja Flu

History Doesn't Repeat Itself, but It Often Rhymes” – Mark Twain.


While the recent spillover of HPAI H5N1 into dairy cows in at least 8 states, and the discovery of `high concentrations' of the virus in raw milk, has been called unprecedented, it isn't that far afield from the events of a decade ago, when the MERS coronavirus was found to be endemic in Arabian camels, and shed in camel's milk and urine. 

WHO Update On MERS-CoV Transmission Risks From Animals To Humans

Eurosurveillance: MERS-CoV Antibodies & RNA In Camel’s Milk – Qatar 

CIDRAP: More Evidence for Camel-to-Human MERS-CoV Transmission

Despite an abundance of scientific evidence linking camels to the carriage and likely spread of the MERS virus (see here, here, & here) the Saudi Ministry of Agriculture spent months either evading or denying the issue (see Saudi MOA Spokesman: Camel Link Unproven, MERS-CoV Is MOH Problem).

Finally, in May of 2014 the Saudi Ministry Of Agriculture Issued Warnings On Camels, urging breeders and owners to limit their contact with camels, and to use PPEs (masks, gloves, protective clothing) when in close contact with their animals.

At first, this news was not well received (see Saudi Camel Owners Threaten Over MERS `Slander’) and many people (locals and tourists) continued to defiantly expose themselves to camels (rides and `kissing') and to camel products (meat, milk, urine, etc.) without taking recommended precautions.

The good news is, despite thousands of infections and hundreds of deaths (see chart above)  MERS-CoV never did acquire full transmissibility between humans.  Most outbreaks were household or nosocomial, although a few superspreader events did occur. 

Had MERS-CoV evolved to be as easily spread as COVID, the results would likely have been far different. 

While today we are dealing with an avian influenza virus, not a coronavirus, the similarities are striking.  Both viruses were thought unlikely to infect their respective intermediate hosts (cows and camels), and both were found to shed the virus via milk and other fluids (see USDA statement below). 

Has USDA confirmed at this point that cow-to-cow transmission is a factor

Yes, although it is unclear exactly how virus is being moved around. We know that the virus is shed in milk at high concentrations; therefore, anything that comes in contact with unpasteurized milk, spilled milk, etc. may spread the virus. Biosecurity is always extremely important, including movement of humans, other animals, vehicles, and other objects (like milking equipment) or materials that may physically carry virus.  

Although the outbreak in dairy cows has only been reported in 32 herds across 8 states so far, it is likely that some spillovers have not been documented.  Testing is voluntary, and is normally limited to dairy cattle.

While no other countries have reported similar outbreaks, if H5N1 can spillover to cows here, it can probably happen in other regions of the world as well. 

As we saw in Saudi Arabia with the continued consumption of raw camel's milk, there is a strong `raw milk' movement in the United States, with the following 2017 study published in the EID Journal suggesting that > 3% of the population regularly drinks unpasteurized milk. 

Solenne Costard , Luis Espejo, Huybert Groenendaal, and Francisco J. Zagmutt


The growing popularity of unpasteurized milk in the United States raises public health concerns. We estimated outbreak-related illnesses and hospitalizations caused by the consumption of cow’s milk and cheese contaminated with Shiga toxin–producing Escherichia coli, Salmonella spp., Listeria monocytogenes, and Campylobacter spp. using a model relying on publicly available outbreak data.
In the United States, outbreaks associated with dairy consumption cause, on average, 760 illnesses/year and 22 hospitalizations/year, mostly from Salmonella spp. and Campylobacter spp. Unpasteurized milk, consumed by only 3.2% of the population, and cheese, consumed by only 1.6% of the population, caused 96% of illnesses caused by contaminated dairy products.
Unpasteurized dairy products thus cause 840 (95% CrI 611–1,158) times more illnesses and 45 (95% CrI 34–59) times more hospitalizations than pasteurized products. As consumption of unpasteurized dairy products grows, illnesses will increase steadily; a doubling in the consumption of unpasteurized milk or cheese could increase outbreak-related illnesses by 96%.

While heavily discouraged by most public health agencies (see CDC's Fast Facts: Why Is Raw Milk Unsafe?there are enough loopholes in state laws that most American can buy raw milk if they want it. 

Milk pasteurization rules in Europe are much stricter than in the United States, with most milk subjected to ultra-high temperature (UHT) pasteurization, which makes it shelf stable.  

In many other countries, however, the consumption of `raw milk' is much higher than in the US. The USDA reported in 2019:

In Mexico, half of all fluid milk goes into the processing industry for the production of yogurt, cheeses, and other products. Between 40-45 percent of consumption is of fluid drinkable milk, such as pasteurized, ultra-high temperature processed (UHT), bottled, or packaged milk. Unpasteurized, raw milk accounts for between 5-10 percent of consumption.

Beyond that, accurate estimates of the consumption of raw milk around the globe are hard to come by. But it is safe to say in that in some countries, that number is likely to greatly exceed 10%. 

There are still a great many unknowns when it comes to HPAI's spillover into cattle, including:

  • Whether the spillover of H5N1 to cows is currently limited to the B3.13 genotype found in Midwestern birds.
  • Whether non-dairy cattle are being sub-clinically infected, and if so, what the risks to public health that might pose
  • Whether standard pasteurization (as opposed to UHT) completely inactivates the virus in milk
  • Whether other milk producing animals (e.g. goats, camels, buffaloes, etc.) carry the same risk of infection as dairy cows
  • How long the virus is shed by these various milk producing species
  • And perhaps most importantly, what is the range of illness experienced by humans who consume infected milk, and can they transmit it on to others via the respiratory route?

Hopefully we'll get the answers to these, and other pressing questions, sooner rather than later.

With luck, cattle may prove to be a `dead-end' host for avian flu  - and this outbreak can be contained by the USDA/FDA and the dairy industry - but the stakes would go up considerably if we started seeing evidence of similar spillovers in other parts of the world.

Or even more ominously, if we started seeing the virus turn up in domestic pigs. A year ago, the ECDC/EFSA Avian Influenza Overview December 2022 – March 2023 warned:

The additional reports of transmission events to and potentially between mammals, e.g. mink, sea lion, seals, foxes and other carnivores as well as seroepidemiological evidence of transmission to wild boar and domestic pigs, associated with evolutionary processes including mammalian adaptation are of concern and need to be closely followed up.

While it is always possible that there is some genetic barrier that prevents HPAI H5N1 from sparking a human pandemic, over the past 3 years the virus has greatly expanded its mammalian host range.  

And that is no small concern.

Stay tuned.

Saturday, April 20, 2024

Two Recent Papers On The Evolution of H7N9 in China

H7N9 Epidemic Waves - June 14th 2017 - Credit FAO


Seven years ago - long before COVID emerged and at a time when HPAI H5N1 had all but disappeared from the map - the world held its breath and watched as China's 5th, and largest, wave of H7N9 raised pandemic concerns around the globe.   

LPAI H7N9, which had emerged in the spring of 2013, was virtually asymptomatic in poultry, but could be deadly in humans, and over 5 years had infected at least 1,500 people in China, killing roughly 40% of them.  

In late 2016, an HPAI version emerged, which threatened China's poultry industry as well as public health. Fearing the worst, China embarked on a national emergency poultry vaccination campaign with a new H5+H7 vaccine (see EID Journal: China's H5+H7 Poultry Vaccination Program, Guangdong 2017-18).

Within months human infections fell dramatically, with the last one reported in 2019.  Poultry losses plummeted, and in a 2019 report (see OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign) the authors reported:

The vaccine was associated with a 92% reduction in H7 positivity rates among poultry and a 98% reduction in human H7N9 cases.

While previous poultry vaccination programs around the world have yielded varying levels of success, China's H5+H7 poultry vaccination campaign exceeded all expectations. It even reduced the number of H5N1 & H5N6 spillovers, although China saw a rebound in H5N6 starting in late 2020. 

H7N9 remains largely suppressed in China, but it has not been eradicated, and so we check in on its continued evolution from time to time:

EID Journal: Antigenic Variant of Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2019

EID Journal: Evolution and Antigenic Drift of Influenza A (H7N9) Viruses, China, 2017–2019

This week we've seen 2 new studies published in major journals (EID & Emerging Microbes & Inf.) by Chinese researchers on the recent evolution of H7N9.  Both credit China's H5+H7 vaccination program's success, but caution that the virus continues to evolve, and that the vaccine needs to keep up.

I've only post excerpts from both studies, so follow the links to read them in their entirety. I'll have a postscript after the break. 

Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China
Yang Liu1, Yuhua Chen1, Zhiyi Yang, Yaozhong Lin, Siyuan Fu, Junhong Chen, Lingyu Xu, Tengfei Liu, Beibei Niu, Qiuhong Huang, Haixia Liu, Chaofeng Zheng, Ming Liao , and Weixin Jia


We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021–2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

From early 2013 through October 2017, a total of 5 outbreaks of avian influenza A(H7N9) virus infection occurred, resulting in 616 human deaths (1). In particular, the fifth wave of the epidemic saw a substantial increase in human fatalities. By late 2017, a total of 1,568 laboratory-confirmed cases of H7N9 virus infection in humans had been reported according to International Health Regulations guidelines (External Link). The rapid emergence, prevalence, and pandemic potential of H7N9 virus were suddenly of great concern. Since 2017, low-pathogenicity avian influenza H7N9 virus transformed into the highly pathogenic avian influenza (HPAI) A(H7N9) virus (25). 

In response, China initiated a large-scale vaccination program in the poultry industry, effectively limiting the H7N9 epidemic. Although no human H7N9 infections have been reported since February 2019, the virus is still circulating in poultry, particularly in laying hens, and remains a potential threat to poultry industry and public health (68).
Furthermore, since 2017, the H7N9 virus has undergone multiple instances of antigenic drift to evade immune pressure from vaccines (911). We investigated the genetic evolution and antigenic differentiation of the H7N9 virus in China to provide information to better control the epidemic, ensure the safety of the poultry industry, and protect public health.

This study explored the evolution and antigenic differentiation characteristics of H7N9 virus over the past decade through continuous monitoring and selection of representative sequences from all publicly available H7N9 virus sequences. However, our research still had certain limitations, and further investigation is needed to understand the relationship between the evolution of viruses under positive selection pressure and the underlying cause of antigenic variation.

In summary, influenza A viruses are highly prone to mutation and evolution, making the H7N9 virus epidemic more complex and challenging to control. This study offers vital insights into the genetic evolutionary branches and recent antigenic drift, providing crucial clues for updating the H7N9 vaccine seed virus and for disease prevention and control.     

         (Continue . . . )


While the first dispatch was more cautionary, this second report is more upbeat, describing a greatly attenuated threat from the H7N9 virus. 

Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination

Yujie HouGuohua DengPengfei CuiXianying ZengBin LiDongxue Wang


Human infections with the H7N9 influenza virus have been eliminated in China through vaccination of poultry; however, the H7N9 virus has not yet been eradicated from poultry. Carefully analysis of H7N9 viruses in poultry that have sub-optimal immunity may provide a unique opportunity to witness the evolution of highly pathogenic avian influenza virus in the context of vaccination. Between January 2020 and June 2023, we isolated 16 H7N9 viruses from samples we collected during surveillance and samples that were sent to us for disease diagnosis.
Genetic analysis indicated that these viruses belonged to a single genotype previously detected in poultry. Antigenic analysis indicated that 12 of the 16 viruses were antigenically close to the H7-Re4 vaccine virus that has been used since January 2022, and the other four viruses showed reduced reactivity with the vaccine.
Animal studies indicated that all 16 viruses were nonlethal in mice, and four of six viruses showed reduced virulence in chickens upon intranasally inoculation. Importantly, the H7N9 viruses detected in this study exclusively bound to the avian-type receptors, having lost the capacity to bind to human-type receptors. Our study shows that vaccination slows the evolution of H7N9 virus by preventing its reassortment with other viruses and eliminates a harmful characteristic of H7N9 virus, namely its ability to bind to human-type receptors.

The early H7N9 viruses bound to human-type receptors with high affinity and to avian-type receptors with low affinity [5,47,48], which is a major reason why these viruses easily infected humans. However, since 2018, the receptor-binding preference of the H7N9 viruses we detected from poultry gradually changed: their affinity for avian-type receptors has gradually increased, and their affinity for human-type receptors has gradually declined [32].

The viruses detected in this study exclusively bound to avian-type receptors. Although the underlying mechanism that has driven this receptor-binding change remains to be investigated, the fact that the surviving H7N9 viruses in vaccinated poultry have lost a key harmful trait indicates that vaccination does not cause the highly pathogenic avian influenza virus to become more dangerous to humans.

In conclusion, our study reveals the genetic evolution and biological properties of the H7N9 highly pathogenic avian influenza virus detected in recent years in China. Although antigenic differences could be easily detected between the surviving viruses and the vaccine seed strain, the lack of reassortment with other viruses and the loss of human-type receptor binding ability of existing H7N9 viruses strongly suggest that although vaccination alone cannot eradicate highly pathogenic H7N9 influenza viruses from poultry in a short time, surviving H7N9 viruses are not evolving faster or becoming more dangerous to humans.

         (Continue . . . )

Although the evolutionary trend of H7N9 appears to be away from posing a public health threat, one lucky reassortment, or a handful of of the `right' amino acid changes, could change that trajectory overnight.  

All of which makes it important that researchers in China continue to study the virus, and update the poultry vaccine. 

While H7N9 isn't anywhere near the top of my pandemic concerns today, we've seen how swiftly things can change.  And with influenza viruses, it is wise never to say `never'.

Friday, April 19, 2024

Preprint: Rapid mortality in Captive Bush Dogs (Speothos venaticus) Caused by H5N1 At A Wildlife Center In the UK

 Credit Wikipedia


Just over 13 months ago the UK government announced (see below) the deaths of 10 captive bush dogs (in November of 2022) apparently due to HPAI H5N1.  At the time it wasn't clear why there had been a 5-month delay in detecting the virus. 

Research and analysis

Confirmed findings of influenza of avian origin in captive mammals

Published 17 March 2023

Applies to England, Scotland and Wales

Details of confirmed findings of influenza of avian origin in captive mammals in Great Britain (England, Scotland and Wales).

South American bush dogs, March 2023

Ten South American bush dogs (Speothos venaticus venaticus) have tested positive for highly pathogenic avian influenza (H5N1) in March 2023.

These animals were part of a captive breeding programme at a zoological premises in England. They were tested as part of a routine investigation into an unusual mammal die-off in November 2022. Ten animals died or were euthanised in a group of 15 bush dogs, over a 9 day period.

The bush dogs had minimal clinical signs before death, and APHA cannot definitively state whether or not H5N1 caused the clinical signs. Influenza of avian origin was not suspected at the time; the virus has since been detected in postmortem samples.

There is no clear evidence suggesting mammal to mammal transmission. It is very likely all animals were exposed to the same source of infected wild birds.

Today we have a preprint from scientists at the UK's APHA and other agencies which presents a somewhat different narrative.  

  • Instead of blaming infection on exposure to `infected wild birds' we now learn these animals were most likely infected from being fed infected meat
  • Instead of exhibiting `minimal clinical signs before death' as reported above, we now learn that some of these animals exhibited neurological manifestations and histopathic examination revealed `severe acute systemic disease characterised by vasculitis, and widespread necrosis and inflammation in many organs, specifically the liver, brain, lung, and adrenal glands.'

We also learn from this preprint that - despite earlier reports of H5N1/H5N8 spillover into mammals in the UK and elsewhere in Europe (see here, here, and here) - that `Influenza A virus infection was not on the list of differentials for causative agent in this disease event'.

The preprint (excerpts below) is highly detailed, and very much worth reading in its entirety.  I'll have a bit more after the break. 

Rapid mortality in captive bush dogs (Speothos venaticus) caused by influenza A of avian origin (H5N1) at a wildlife collection in the United Kingdom

Marco Falchieri, Scott Reid, Akbar Dastderji, Jonathan Cracknell, Caroline Janet Warren, Benjamin Mollett, Jacob Peers-Dent, Audra-Lynne Schlachter, Natalie Mcginn, Richard Hepple, Saumya Thomas, Susan Ridout, Jen Quayle, Romain Pizzi, Alejandro Nunez, Alexander M P Byrne, Joe James, Ashley C Banyard

doi: https://doi.org/10.1101/2024.04.18.590032

Europe has suffered unprecedented epizootics of high pathogenicity avian influenza (HPAI) clade H5N1 since Autumn 2021. As well as impacting upon commercial and wild avian species, the virus has also infected mammalian species more than ever observed previously.
Mammalian species involved in spill over events have primarily been scavenging terrestrial carnivores and farmed mammalian species although marine mammals have also been affected. Alongside reports of detections in mammalian species found dead through different surveillance schemes, several mass mortality events have been reported in farmed and wild animals.
During November 2022, an unusual mortality event was reported in captive bush dogs (Speothos venaticus) with clade H5N1 HPAIV of avian origin being the causative agent. The event involved an enclosure of fifteen bush dogs, ten of which succumbed during a nine-day period with some dogs exhibiting neurological disease. Ingestion of infected meat is proposed as the most likely infection route.
Here we report on the infection and severe mortality within a pack of bush dogs (Speothos  venaticus) in captivity with avian origin H5N1 clade HPAIV. Bush dogs are a near  threatened species of wild canids that are of conservation concern. Wild populations of these dogs   range from northern regions of Panama (Central America) to northeastern Argentina and Paraguay;  with populations also being present in Colombia, Venezuela, the Guianas, Brazil, and eastern Bolivia  and Peru. 

This species is characterized by its small size, elongated body, small eyes, short snout, short  tail, short legs, and small and rounded ears, in addition to gregarious and diurnal behaviour (35).  

In this disease event which occurred in November 2022, two thirds of the pack of bush dogs, held  captive in a wildlife collection the UK, became clinically unwell with a disease that had a short duration and led to death and/or the need for euthanasia on welfare grounds with a range of clinical  signs including neurological disease. 

Avian influenza was not suspected at first and several tests and analysis were performed at private laboratories to ascertain cause of death and to exclude the involvement of more common canine pathogens. Overall inconclusive results led bush dog samples to be submitted retrospectively to the Animal and Plant Health Agency (APHA), Virology Department for shotgun metagenomic assessment, which detected presence of influenza type A virus sequences in internal organs. We describe the disease event, timeline, virological and pathological impact of disease and sequence analysis of the causative agent.


The exposure route to influenza A virus of avian origin in this case is hard to conclusively define. The bush dogs had been fed a diet that included frozen shot wild birds and game. In the absence of local disease events that may have been transferred to the bush dogs in the enclosure, infection through ingestion of infected meat / offal would appear to be the most likely route of  infection.

Another potential infection route is through scavenging of any wild bird carcases/any sick  wild birds landing in the un-netted pen. Other routes of infection including indirect contact (e.g., wild bird faeces) are possible but less likely and would not fit with the rapid onset of infection across a  number of dogs within a short time frame.


From the perspective of zoonotic risk, the well-established marker of mammalian adaptation (E627K) was detected in all but one of the bush dog sequences generated. This mutation alone is  insufficient to drive an increase in zoonotic risk and so the risk to human populations must be considered very low.  

          (Continue . . . )

The suspected route of infection - from being fed raw infected birds - is one we've seen repeatedly in Asia with captive big cats, going back to 2004.  The neurological manifestations reported in these bush dogs are quite similar to reports in other mammals (both in North America & Europe), including several widely reported prior to the bush dog outbreak:

CDC EID Journal: Encephalitis and Death in Wild Mammals at An Animal Rehab Center From HPAI H5N8 - UK

EID Journal: HPAI A(H5N1) Virus in Wild Red Foxes, the Netherlands, 2021

Netherlands DWHC Reports another Mammal (Polecat) Infected With H5N1

While hindsight is admittedly 20-20, it does seem as if there might have been enough clues here to at least merit testing for influenza A.  But apparently, it wasn't on the list . . . . 

Just like it wasn't on the list to test cattle, which started falling ill with a `mystery illness' last  January in Texas. 

While previously experiments (and outbreaks) had shown that cattle could be infected with influenza A (see A Brief History Of Influenza A In Cattle/Ruminants), it took weeks before anyone thought to test for it.

For years, we've watched as novel flu viruses have repeatedly `broken the rules', yet we continue to be surprised each time it happens. 

If we ever hope to get ahead of this growing threat, we need to start thinking outside of the check boxes.