“The unique feature about the influenza virus is its great potential for changes, for mutation.”
- Margaret Chan, Director-General, World Health Organization, 2007-2017
“Right now, this virus is like a kid in a candy store.”
- Richard J. Webby, PhD, virologist, St. Jude’s Children’s Research Hospital
Regular readers of Germ Gems may share the impression (quite correctly) that my weekly posts are dominated by the havoc provoked by RNA viruses. That’s because viruses with an RNA genome such as HIV, coronaviruses, filoviruses, and in the case of this week’s posting, influenza viruses, have an incredible capacity for mutation. Today I focus on the avian flu virus—the grand master of mutation.
Brief overview of influenza A viruses. Influenza A is one of four different influenza flu virus subtypes (the others being B, C and D). Influenza A viruses are characterized by two surface proteins, hemagglutinin (“H”) and neuraminidase (“N”) and are further separated into subtypes by number. There are 18 different H subtypes and 11 different N subtypes of influenza A.
Influenza A viruses cause a massive number of zoonotic infections in many animal species, especially birds. For the purposes of this post, I concentrate on one bird-adapted strain called HPAI(H5N1), which stands for highly pathogenic avian influenza virus of type A, subtype H5N1. It is more commonly known as avian influenza or “bird flu.”
What’s the big deal with influenza A H5N1? For the past year, the largest outbreak ever of the H5N1 subtype has been spreading like wildfire across farmed poultry and wild bird flocks in the U.S., Europe, and Asia. It has caused enormous mortality—with approximately 15 million domestic birds dying from bird flu in the past 18 months and more than 193 million birds being culled to stop the virus from spreading. In addition, H5N1 has been detected in a range of mammal species including mink in Spain, foxes and otters in the UK, grizzly bears, badgers, bobcats, ferrets, coyotes, racoons, skunks, and dolphins in the U.S., and seals in the Caspian Sea.
The ability of H5N1 to cross the species barrier—a biological phenomenon referred to as “species tropism”—is a matter of great concern. I am not aware of any pathogen that comes even close to H5N1 in terms of its ability to cross the species barrier. (SARS-CoV-2, the cause of COVID-19, for example, is known to infect mink, pet hamsters, and an occasional zoo animal, dog, and cat.)The factors that govern why certain animals are susceptible to infections by these viruses while others are resistant are unknown, but likely are governed by mutations in the virus’s RNA genome.
Influenza A H5N1 arrival in the U.S. By December 2021, bird flu had made its way to North America. Within a year, scientists confirmed wild bird outbreaks in 47 states, involving ducks, geese, gulls, pelicans, swans, vultures, crows, owls, eagles, and many other species of wild birds. Nearly 60 million birds in commercial and backyard flocks in 47 states died or were culled due to the virus. The impact on poultry has registered in the pocketbooks of American consumers by a stiff increase in the cost of eggs and chicken.
H5N1 infections in humans. For the most part, mammals other than humans probably become infected with H5N1 while feeding on sick or dead birds with high virus loads. Human infections with bird flu happen when the virus is in the air (in droplets and aerosols) and a person breathes it in, or possibly when a person touches something that is contaminated by the virus and then touches his own mouth, eyes, or nose.
While H5N1 infection is considered an avian disease, its threat of causing a human pandemic has never been too distant. It first appeared on the radar screen of infectious diseases specialists in 1996-1997 during an outbreak in poultry in China and Hong Kong. At that time, H5N1 infected 18 people, killing six. This virus then went on to cause more than 860 human infections with a death rate of over 50%.
Following the emergence of H5N1 bird flu in China in 1996 and human infections in Hong Kong in 1997, sporadic human infections cropped up in numerous countries. Since 2003, more than 20 countries have reported more than 860 human infections to the World Health Organization (WHO). The historic case fatality rate has been more than 50%, but this figure is thought an overestimation because many mild or asymptomatic infections may go unreported and thus are not factored into the denominator.
Human-to-human infection. Recently, an 11-year-old girl in Cambodia died from H5N1. Because the girl’s father also tested positive for avian flu, it renewed worldwide concern as to whether bird flu could spark widespread infection in people. Subsequent scientific analysis determined both the girl and her father were infected directly from birds, which quelled concerns human-to- human transmission. The Cambodian Health Ministry declared there is “no indication or evidence that there was infection from father to daughter.”
As I pointed out in my May 22, 2022, Germ Gems post, “Bird Flu: Why We Should Care,” an essential step in escalating a bird flu strain to the status of the cause of a human pandemic is the acquisition of a gene that encodes transmissibility from human-to-human. To date, human cases of influenza AH5N1 have been dead-end infections, that is, people working closely with infected poultry pick up the virus but do not pass it on to other people.
Need for increased vigilance. Public health authorities at institutions such as the WHO and Centers for Disease Control and Prevention suggest that the risk of a human influenza AH5N1 pandemic is low. Nonetheless, the fact that the virus has evolved the capacity to infect a large variety of mammals raises concern that the virus could acquire a mutation that would allow it to spread more easily between people thereby potentially triggering a pandemic.
In the back of many minds is the sobering fact that all three human influenza pandemics in the 20th century, including the “Mother of All Pandemics” in 1918-1919 that killed over 50 million people worldwide, involved influenza A bird flu strains. Therefore, calls for increased preparedness, including better zoonotic disease surveillance in humans and other mammals, have been sounded around the world.
What if bird flu takes off in humans? In an article on March 1, 2023, in the journal Nature, “How to stop the bird flu outbreak becoming a pandemic,” researchers recommend several steps. First and foremost are vaccination programs for poultry since poultry farms are a key battleground in the fight against H5N1. China has already undertaken such a vaccination program, and the U.S. is seriously considering initiating a program for vaccinating chickens. Vaccines could also help to protect certain species of wild birds, such as, bald eagles.
If bird flu does trigger a human pandemic, we already have several tools for combatting the disease. One is an approved human vaccine against avian flu that the U.S. has on hand. Although the supply is too low to be used to vaccinate the world, given the ultrarapid response of the U.S. government and pharmaceutical industry to develop a COVID-19 vaccine, it seems likely that vaccine production could be quickly ramped up. Also, it appears that the antiviral drug Tamiflu is effective against H5N1 in people, and non-pharmaceutical tools including face masks can also limit disease spread.
Pandemic preparedness. Long before the COVID-19 pandemic erupted in 2019 and the threat of an influenza A H5N1 pandemic began gathering momentum, public health experts around the world recognized that emergence of new infectious diseases challenges are inevitable. We know that an effective response to such challenges generally requires coordination of experts in public health, healthcare delivery, pharmaceutical industry, scientists, and governments. Bird flu could indeed serve as the test case for the status of our preparedness for the next pandemic.
