Flu Virus binding to Receptor Cells – Credit CDC
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Although you'd hardly know it by some of the hyperbolic headlines in the media, but the rise of avian H5N1 to become the next pandemic is far from assured, and its purported `kill rate' of 50% is almost certainly highly inflated (see Revisiting the H5N1 CFR (Case Fatality Rate) Debate).
While the risks from avian flu are genuine, no one can say when - or even if - H5N1 will acquire the critical ability to transmit efficiently from human-to-human.
We've been on the brink before with H5N1, only for the threat to fizzle and the virus to recede. There is even some debate over whether H5 viruses are capable of sparking a pandemic (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?).
Last weekend, in How The WHO & CDC Are Developing Candidate H5N1 Vaccines, I wrote a familiar caveat:
H5N1 is obviously not guaranteed to become the next global health threat, and the next pandemic may not even arise from an influenza virus. There are plenty of other candidates, including MERS-CoV, Nipah, Langya, Lassa Fever, and even Virus X - the one we don't know about yet.
Unfortunately, the tabloid media loves simple, declarative, and often frightening headlines that induce millions of clicks.
Nuance, if it is to be found at all, comes farther down the page.
Yesterday afternoon the CDC released an `Ask the Expert' summation written by Dr. Tim Uyeki of what is known about, and being done to deal with, the potential threat of HPAI H5N1. Since it doesn't employ `click bait' adjectives in its title, it probably won't get as many clicks as it deserves.
I'll return with a brief postscript after the break.
Ask the Expert: Highly Pathogenic Avian Influenza A(H5N1) Viruses
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Ask the Experts: Highly Pathogenic Avian Influenza A(H5N1) Viruses
Dr. Tim Uyeki, Chief Medical Officer of the Influenza Division at CDC, answers common questions about highly pathogenic avian influenza A(H5N1) viruses, which have been detected in the United States in wild birds since late 2021 and commercial and backyard poultry since February 2022.
What is the extent of the current outbreak of influenza A(H5N1) in birds?
Like much of the rest of the world, the United States continues to experience outbreaks of highly pathogenic avian influenza (HPAI) A(H5N1) virus in wild birds and poultry. HPAI A(H5N1) virus has been circulating among birds and poultry in different parts of the world for many years and continuing to evolve into different groups that are referred to as clades. The current clade of H5N1 virus, called clade 2.3.4.4b, appears well-adapted to spread efficiently among wild birds and poultry in many regions of the world and was first identified in wild birds in the United States in January 2022. Since then, this current clade 2.3.4.4b HPAI A(H5N1) virus has been detected in wild birds in all 50 states and has caused bird outbreaks in 47 states affecting more than 58 million commercial poultry and backyard flocks.
What about H5N1 virus among humans?
Seven sporadic human cases associated with poultry exposures during this outbreak of contemporary HPAI A(H5N1) viruses have been reported globally since late 2021, one of which was identified in the United States. In four of these cases, no respiratory symptoms were reported. It is possible that some of these cases did not represent virus infection but rather detection of non-infectious H5N1 virus genetic material in respiratory specimens following prolonged exposure to infected birds. In three cases, severe disease occurred, including one death. No human-to-human spread of H5N1 virus was identified in any of these cases. Sporadic human infections with contemporary H5N1 viruses are not surprising, especially among people who do not take recommended precautions (such as wearing personal protective equipment, including respiratory protection, for example). Since 1997, more than 880 human cases, nearly all from previously circulating H5N1 virus clades, have been reported from 21 countries with high mortality, but very few cases have been identified worldwide since 2016. A small number of sporadic human infections with H5N1 virus does not change the risk to the general public, which CDC currently considers to be low.
What about H5N1 virus among mammals?
Although H5N1 viruses primarily infect different types of wild birds and domestic poultry, H5N1 viruses also can infect other animals. Sporadic H5N1 virus infections of mammals have been reported for more than 20 years in different countries that have experienced H5N1 outbreaks in poultry or wild birds. H5N1 viruses can infect mammals that are exposed to environments with a high concentration of virus or that eat (presumably infected) sick or dead birds or poultry, including but not limited to wild or feral animals such as foxes; stray or domestic animals such as cats and dogs; and zoo animals such as tigers and leopards. Recently, sporadic H5N1 virus infections in different mammals, including bears, wild foxes, and skunks, have been reported in Canada, the United States, and other countries, including mink in Spain and sea lions in Peru. Reports of sporadic H5N1 virus infections of predatory and scavenger mammals are not unexpected given widespread H5N1 virus infections in wild birds worldwide.
Does the detection of H5N1 viruses in farmed mink change the assessment of the risk to human health?
No. CDC and other partner agencies have characterized the H5N1 viruses from farmed mink detected in Spain and have not found any indications that would point to increased ability to infect humans. H5N1 viruses do not currently have an ability to easily infect the human upper respiratory tract, which would be needed to increase the risk of transmission to people. Although it is uncommon, H5N1 viruses can bind to receptors in the human lower respiratory tract. Mink have been shown to have two different kinds of cell receptors in their respiratory tracts, one kind of which allows for more efficient infection with H5N1 viruses. As a result, mink are much more susceptible to H5N1 virus infection than people.
If there were mink-to-mink spread of H5N1 virus (for example in the outbreak in Spain), would that change the assessment of the risk to human health?
No. While there was a genetic marker in the H5N1 viruses detected during the outbreak in mink in Spain that may have resulted in more severe disease in mink and potentially easier mink-to-mink transmission, this marker is unlikely to make it easier for infection to transmit to humans. Besides this marker, the genomic sequence of the H5N1 viruses isolated from mink was very similar to H5N1 viruses found in birds. Humans lack the type of cell receptor in the upper respiratory tract that H5N1 viruses use to cause infection. Mink, on the other hand, have two different kinds of cell receptors in their respiratory tracts, one kind of which allows for easier infection with H5N1 viruses. As a result, mink are more susceptible to infection with H5N1 viruses than people, and limited mink-to-mink spread of H5N1 virus, especially in an environment with close contact among animals, would not be surprising.
What is CDC doing to monitor these viruses in people?
CDC’s existing influenza surveillance systems are well-equipped to rapidly detect cases of avian influenza A virus infection, including H5N1 virus, in people. Influenza virus detection assays, which can detect both seasonal and novel influenza A viruses, are used in 128 public health laboratories in all 50 U.S states and 170 laboratories globally. Additionally, there are diagnostic assays to specifically detect the current H5N1 viruses available at 99 public health laboratories in all 50 U.S. states and 129 international laboratories, representing 116 countries.
CDC, along with our state and local public health partners, also continues to actively monitor people who have been exposed to infected birds and poultry for 10 days after exposure. To date, public health departments have monitored more than 6,200 people in 52 jurisdictions who were exposed to birds/poultry infected with H5N1 virus and reported this information to CDC. Of these, 161 people who were being monitored showed symptoms and subsequently were tested for novel influenza A and seasonal influenza viruses along with other respiratory viruses. H5N1 virus genetic material was only detected in a respiratory specimen from one person in Colorado who experienced fatigue from participating in poultry culling activities and was likely not infected with the virus.
Other agencies are responsible for monitoring for disease in poultry and wild birds and wildlife.
Why doesn’t this virus appear to spread from human-to-human?
H5N1 viruses currently circulating in wild birds and causing poultry outbreaks are well-adapted to spread among birds. However, these H5N1 bird flu viruses do not have the ability to easily bind to receptors in the upper respiratory tract of humans, or to transmit among people.
Is it possible this virus will cause the next pandemic?
We cannot predict when the next influenza pandemic will occur or what virus will cause the next pandemic. The origin of the 1918 H1N1 pandemic virus may have been an avian influenza A virus. The 1957 H2N2 pandemic influenza virus and the 1968 H3N2 pandemic influenza virus both resulted from a combination of genes from human and low pathogenic avian influenza A viruses. The 2009 H1N1 pandemic influenza virus resulted from a combination of genes from human, avian, and swine influenza A viruses and is believed to have emerged from pigs to transmit among people. There are many kinds of avian influenza A viruses and swine influenza A viruses that have sporadically infected people worldwide. Therefore, constant vigilance and ongoing surveillance for novel influenza viruses worldwide is needed in people and animals – especially in poultry and pigs.
Is there a vaccine to prevent bird flu infection in humans?
An H5 candidate vaccine virus (CVV) recently produced by CDC is nearly identical or, in many samples, identical to the hemagglutinin (HA) protein of recently detected clade 2.3.4.4b H5N1 viruses in birds and mammals (including the mink outbreak) and could be used to produce a vaccine for people, if needed, and would provide good protections against the circulating H5N1 viruses. This H5 CVV is available and has been shared with vaccine manufacturers.
Is there treatment available for people who get sick with bird flu?
People with avian influenza A virus infection are recommended to be treated as soon as possible with antiviral drugs that are FDA-approved for treatment of seasonal influenza. Such antiviral drugs include oseltamivir, zanamivir, peramivir, and baloxavir. Antiviral treatment works best when started as soon as symptoms begin. For patients who require hospitalization, antiviral treatment with oseltamivir is recommended as soon as possible, and clinical management is focused on supportive care of complications, including advanced organ support in an intensive care unit for patients with severe pneumonia.
Should the general public be worried about H5N1?
The current public health threat to people from H5N1 virus is low. The current H5N1 outbreak in poultry and birds continues to be mostly an animal health issue. However, people should avoid direct and close contact with sick or dead wild birds, poultry, and wild animals. People should not consume uncooked or undercooked poultry or poultry products, including raw eggs. Consuming properly cooked poultry, poultry products, and eggs is safe. Other preventive measures are available at: Bird Flu: Current Situation Summary
Tim Uyeki, MD, MPH, MPP, serves as Chief Medical Officer in the Influenza Division at CDC. He has worked at CDC on the clinical aspects, epidemiology, prevention, and control of influenza in the U.S. and worldwide since 1998, with particular interest in human infections with avian influenza A viruses, clinical management of patients with influenza, and emerging viral infectious diseases. He has participated in field investigations of human cases of H5N1 in multiple countries and contributed to World Health Organization recommendations for the clinical management of patients with seasonal and pandemic influenza, and novel influenza A virus infections, including H5N1, for many years.
While avian H5N1 deserves our attention, it is far from the only pandemic threat we face.
- Just a couple of years ago our attentions were focused heavily on a swine EA H1N1 virus in China (see PNAS: Eurasian Avian-like H1N1 Swine Influenza Virus With Pandemic Potential In China), and that threat remains in play.
- MERS-CoV continues to circulate in camels in the Middle East, occasionally spills over into humans, and is likely under-reported (see A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia).
- Monkeypox (Mpox) continues to evolve, and additional, more virulent strains are possible (see EID Journal: Monkeypox Virus Evolution before 2022 Outbreak).
- And we could easily be hit with another coronavirus - either a variant of SARS-CoV-2 - or something new, which spills over from a pig, a dog, a cat, or a bat (see Preprint: SARS-CoV-2 Exposure in Norwegian rats (Rattus norvegicus) from New York City).
I could list dozens more.
The best we can say is that we live in a threat-rich environment, and while the next pandemic threat is unknowable, another pandemic is inevitable. It's just a matter of time.
Our job is to be ready for it when it comes.
