“We are in fairly unprecedented, unchartered territory, globally in relationship to avian influenza.”
Peter Rabinowitz, MD, MPH director Center for One Health Research, University of Washington
“I think that when we know that we actually do live in uncertainty, then we ought to admit it; it is of great value to realize that we do not know the answers to different questions. This attitude of mind - this attitude of uncertainty - is vital to the scientist, and it is this attitude of mind which the student must first acquire.”
Richard P. Feynman, Ph.D., American theoretical physicist, Nobel Prize for Physics 1965
Influenza A virus subtype H5N1 (aka avian or bird flu) recently cropped up in cattle in the Southwestern U.S. It is a vicious microbe that has devastated poultry and wild bird populations worldwide. For some time, this RNA virus has been in the wings as a potential cause of the next pandemic in humans. If this were to happen, it is estimated that the human death toll from influenza A(H5N1) would surpass that from any other pathogen including Mycobacterium tuberculosis, the subject of last week’s Germ Gems post. (See April 10, 2024 Germ Gems “‘Leading Infectious Disease Killer in the World’: TB Regains the Title.”)
In this week’s post, I review briefly the the havoc already caused by influenza viruses then discuss whether avian flu will take off in humans any time soon.
Synopsis of influenza viruses. There are four types of influenza viruses: A, B, C, and D. Every winter in the U.S., influenza A and B viruses cause seasonal epidemics of disease in people. Influenza A viruses are, however, the only influenza viruses known to cause flu pandemics.
Since 1503, there have been at least 14 influenza pandemics. In the 20th century alone, there were three, the most notorious of which was the 1918-19 influenza pandemic (the “mother of all pandemics”) that killed 50 to 100 million people.
Avian flu. Bird (avian) flu is caused by different subtypes of influenza A virus. The most brutal of these subtypes is H5N1, aka as highly pathogenic avian influenza or HPAI. (The terms H5N1, HPAI and influenza A(H5N1) are often used interchangeably.)
Since H5N1 first emerged in China in 1996, it has caused a massive number of deaths in poultry and wild birds. It has targeted at least 100 bird species, spreading among wild aquatic birds especially ducks, geese, and storks as well as among domestic poultry (chickens and turkeys).
In 2021, influenza A(H5N1) emerged in North America among migratory birds. In 2022, it began spreading like wildfire to poultry farms in the U.S. killing not only 15 million domestic birds but also causing the slaughter of 193 million poultry culled as a precautionary measure to stem the epidemic.
Spillovers into mammals. Of mounting concern is the spillover of influenza A(H5N1) into mammals. In Spain, researchers have seen spillovers of influenza A (H5N1) in minks. South America has reported spillovers in dolphins. And since 2022, the U.S. Department of Agriculture (USDA) has reported influenza A(H5N1) virus detections in more than 200 mammal species including, but not limited to, foxes, otters, grizzly bears, bobcats, racoons, skunks and, in New England, grey seals.
Humans have not been spared. Since 2003, 868 cases of influenza A(H5N1) in humans have been reported worldwide. Most of these cases occurred in Asia among people who had intimate contact with poultry (mainly chickens). Of these cases, 457 were fatal, giving an astonishingly high case fatality rate of 53%.
In April 2022, the U.S. reported only one human case of influenza A(H5N1), and it was non-fatal. The afflicted person lived in Colorado and had direct exposure to poultry—the presumed source of the virus.
Recently, there’s been an emergence of influenza A (H5N1) in dairy cattle. This outbreak has alarmed public health officials.
What to know about the bird flu outbreaks in dairy cattle. On April 3, 2024, the New York Times reported that in the U.S., bird flu outbreaks had affected at least 13 dairy herds in six states. (See April 3, 2024 New York Times article “What to Know About the Bird Flu Outbreak in Dairy Cows,” by Emily Anthes and Apoorva Mandavalli.) To date, the virus has only been found in dairy cows and not in beef cattle.
Most cases were reported from dairy herds in Texas. But since then, cases in dairy cattle have been observed in New Mexico, South Dakota, North Carolina and Michigan. Fortunately, this virus—which is often fatal in birds—causes a relatively mild illness in dairy cattle.
It isn’t clear how the virus initially found its way into cattle. Contact with the feces of infected birds, however, seems, the most likely mode of transmission. At present, researchers have found no evidence that infected cattle can transmit the virus to non-infected cattle. Nonetheless, the USDA has noted that a cow-to-cow transmission cannot be ruled out.
In addition to the April 2024 outbreak of bird flu in dairy cattle, scientists were also alarmed because a Texas dairy worker became infected. This was the second case of influenza A (H5N1) in a human in the U.S. The Texas patient worked directly with sick dairy cows; he suffered a mild illness.
The U.S. Centers for Disease Control and Prevention (CDC) has been quick to point out that there has been no known human-to-human spread with the contemporary A(H5N1) viruses that currently are circulating in birds in the U.S. As a precautionary measure, however, the CDC warned doctors to be on the lookout for bird flu occurring in dairy farm workers.
What worries scientists most? Scientists worry that this virus could ultimately be passed from human-to-human and cause a pandemic. A gene mutation in influenza A(H5N1) would be required before that could happen. This has not occurred—yet.
One of the remarkable characteristics of RNA viruses is their capacity to mutate; influenza A virus is no exception. Additionally, influenza A virus is known for its reassortment ability, that is its ability to swap gene segments between different clades of the virus. In early April 2024, the United Nations Food and Agriculture Organization warned that reassortment is already happening in Asia. (See University of Minnesota Center for Infectious Disease Research and Policy April 5, 2024 newsletter, “Officials warn of H5N1 avian flu reassortment circulating in parts of Asia.”)
Fortunately, unlike SARS-CoV-2, influenza A(H5N1) it is not a novel virus. It has been on scientists’ radar screens since it first emerged in China in 1996 and has been and continues to be the subject of numerous studies. These facts have enabled the World Health Organization and the CDC to maintain lists of candidate viruses that provide protection against H5N1 and could be mass-produced in vaccines if necessary.
Living with uncertainty. It “remains difficult to predict the evolutionary direction [influenza A(H5N1)] will take in the future.” (See “European Scientists Assess Avian Flu Pandemic Risk,” Medscape April 5, 2024.) No one knows ifinfluenza A(H5N1) is ever going to decimate humans as it has vast numbers of wild birds or when this might occur. For most of us, it is just another of life’s many uncertainties that we all have learned to live with. But for epidemiologists, the evolutionary direction influenza A(H5N1) will take is an uncertainty that keeps many of them awake at night.
