Avian influenza

ALSO KNOWN AS: Bird flu, avian flu, H5N1

ANATOMY OR SYSTEM AFFECTED: Blood, blood vessels, circulatory system, gastrointestinal system, heart, intestines, kidneys, lungs, muscles, musculoskeletal system, nerves, nervous system, nose, reproductive system, respiratory system, stomach, throat, urinary system

DEFINITION: Avian influenza is caused by several virus strains that attack birds; occasionally, a strain develops the ability to attack humans, sometimes triggering an epidemic. There is concern that the H5N1 strain could mutate into a form that is highly contagious among humans and result in a global pandemic.

CAUSES: Virus passed among birds and sometimes to humans

SYMPTOMS: Initially fever, appetite loss, clogged sinuses, runny nose, and muscle aches, progressing to the circulatory, nervous, reproductive, and urinary systems

DURATION: From one to five days, often fatal

TREATMENTS: Antiviral drugs

Causes and symptoms

A group of RNA viruses causes influenza in birds. Most such viruses do not attack humans, although human influenza viruses were probably derived from bird influenza viruses which made the leap from animal to human populations as a zoonotic disease. On the rare occasion that a bird flu strain achieves the ability to enter and reproduce in human cells, the human is unlikely to have effective defenses and the viral attack is likely to be severe. If the virus strain combines its ability to reproduce in humans and its highly pathogenic nature with the ability to transfer from human host to human host efficiently, then it is particularly dangerous. The most deadly human influenza pandemics in history probably began this way. Public health officials have been concerned that the avian influenza A virus strain H5N1 might undergo such a transformation and initiate such a pandemic.

Influenza virus subtypes are named for two types of their surface proteins, hemagglutinin (sixteen subtypes) and neuraminidase (nine subtypes), and all have been identified in avian influenza viruses. Each different protein is assigned a number, so that H5 in H5N1 refers to the hemagglutinin that is assigned the number five. Similarly, N1 refers to the neuraminidase assigned the number one. Hemagglutinins are responsible for attachment of the virus to host cells and entry into those cells. After the production of new viruses in the cell, neuraminidases are used by the new viruses to break out of the cell.

Influenza viruses are notorious for their ability to change their surface antigens and thereby escape host defenses, which are dependent on recognition of those antigens. The H5 and N1 surface proteins characterize the subtype causing severe human disease (since 1997) and are also antigens targeted by host defenses. Both are displayed on the surface of the membrane-like coat that surrounds the virus. The hemagglutinin (H5) is the primary target for cell defenses. If an organism has been exposed to a given hemagglutinin, then it will quickly produce antibodies that attach to that hemagglutinin, blocking the site that is normally used to attach to the organism’s cells. The virus is rendered harmless if it cannot attach to and enter a cell. If this is the organism’s first exposure to the specific hemagglutinin, however, then the response will not be as rapid. The host’s immune system will begin making antibodies against the new antigen, but they are made too slowly during this first exposure, and illness results. Most humans have had no exposure to H5 antigens and so are unprotected against H5N1.

Symptoms of avian influenza in humans include the familiar set generally caused by flu viruses. Those symptoms—fever, loss of appetite, clogged sinuses, runny nose, muscle aches, and so forth—pass in three to five days with most influenza strains, and the victim recovers. With H5N1, however, other host systems—such as the circulatory, nervous, reproductive, and gastrointestinal systems—often become involved. In approximately 60 percent of human cases reported, death occurs, sometimes within a day of the onset of symptoms.

Treatment and Therapy

The major medical solutions to avian flu infection are medications and vaccination. Antiviral medications have been difficult to develop, and few effective drugs are available. Many of the drugs prescribed for viral infections are actually used to combat secondary infections by bacteria attempting to take advantage of the host’s weakened condition. Vaccine development against influenza viruses is also problematic. The vaccines target antigens on the surface of the viruses, and the viruses mutate and change their surface antigens so frequently that new vaccines must be developed almost every year to defend against the new strains of influenza. Given these difficulties and the fact that most influenza victims recover in three to five days without treatment, drugs and vaccines against influenza have often not been a high priority compared to those against more deadly diseases such as smallpox. Periodically, however, a particularly pathogenic influenza strain has developed, and effective treatment would have saved many lives. Because the H5N1 strain is feared for its potential to be one of those strains, scientists have sought to develop both drugs and vaccines against this virus.

Several medications that act against flu viruses are available, but the virus has quickly developed resistance to the older drugs, amantadine and rimantadine. The H5N1 virus populations in Vietnam and other Southeast Asian countries are already resistant to these drugs. In those countries, the virus has been present in poultry, and occasionally in humans, a bit longer than elsewhere. Two newer drugs, oseltamivir and zanamivir, have shown effectiveness against H5N1, although the virus has sometimes been resistant to oseltamivir. The antiviral resistance of avian flu is being continuously monitored.

Progress in vaccine development has been encouraging, but no 100-percent proven vaccine is available. Even when a vaccine becomes ready for use, production of enough to meet the needs of a pandemic would be challenging. Stockpiling a vaccine in anticipation of a pandemic is possible, but the exact antigen against which it must be directed cannot be known until the virus is in the process of initiating the pandemic. Each year, experts predict the most likely antigens for an approaching flu season, and vaccines are produced in advance against those antigens. Should an influenza virus employ an antigen not anticipated by the experts, then the stockpiled vaccines would be worthless.

Vaccine production technology is also improving, but the improvements have not been fully implemented. In the standard technique, the antigenic virus to be used in the vaccine is grown in fertilized eggs—an expensive, slow, and inefficient method. Tissue culture techniques, in which the antigenic virus is grown in cells in artificial media, promise dramatic improvement in vaccine preparation once they are fully integrated into the production system.

Perspective and Prospects

The history of influenza can be traced much further back in time than the understanding of its cause. Reports describing epidemics and pandemics in which the victims showed symptoms of influenza go back to the early sixteenth century at least, but the first isolation of an influenza virus did not occur until 1933. The worst flu pandemic occurred in 1918 to 1919 (the Spanish flu), when twenty million to one hundred million people died of influenza. It was one of the deadliest diseases in history. Two more recent flu pandemics, the Asian flu (1957) and the Hong Kong flu (1968), were seriously disruptive, but not as deadly. All these pandemics were caused by influenza type A viruses, the type to which strain H5N1 and the other avian influenza viruses belong.

The concern over avian influenza type A H5N1 began in 1997 in Hong Kong, where poultry and humans came under attack. Three events associated with these infections captured the attention of epidemiologists, because together they suggested H5N1’s potential as the agent of an influenza pandemic. First, occurred from poultry to humans. Second, H5N1 proved to be highly pathogenic, as six of the eighteen infected humans died. Third, there was some indication of human-to-human transfer of the virus. If the virus maintained its pathogenic nature and its ability to move from poultry to humans, and if it added the ability to transfer efficiently from one human to another, it would almost certainly initiate another deadly pandemic.

Between 1997 and 2006, a number of human cases of avian influenza type A were documented in several countries. Not all were the result of the feared H5N1 strain, but the other strains bear watching as well. Most of the cases of human infection with H5N1 have been in Southeast Asia (Vietnam, Cambodia, Indonesia, Thailand) but also in Egypt, Iraq, Azerbaijan, and Turkey. By 2023, more than 860 people across fifteen countries in Asia, the Pacific, Europe, Africa, and the Middle East had been infected with H5N1; and more than half of those infected died. One H5N1 infection has been documented in the United States, which was reported in April 2022 in a person who worked with poultry in Colorado. Further, avian influenza virus type A H7N2 caused illness in New York, and H7N3 attacked poultry workers in Canada. No North American infection resulted in a human fatality.

A new serious strain of avian influenza type A, H7N9, was discovered in China in March 2013. By early May 2013, more than 130 people had been infected, and just over 20 percent of those infected had died. There was concern over H7N9's ability to spread more easily to mammals than other strains of bird flu, and health officials worked to develop a vaccine against this strain. None of these infections involved extensive or sustained human-to-human transmission, though a few restricted transfers between humans may have occurred. Most of the human infections were transferred from infected domestic poultry. Some may have been contracted from wild waterfowl (ducks and geese).

Human health is not the only concern regarding the H5N1 strain; there are agricultural and economic concerns as well. Poultry flocks can be destroyed by the virus. There were several poultry outbreaks around the world before 2006, in which an estimated 150 million barnyard birds either died as victims of the virus or were culled to remove the infection focus and prevent further spread of the virus. Although the governments involved often compensated individuals for their culled animals, the compensation was usually well below market value. This practice encourages farmers to hide infections that occur in their flocks, which slows the discovery of potential outbreaks and gives the virus a head start that it does not need. In addition, several governments were suspected of hiding avian flu outbreaks until they were impossible to conceal, in an attempt to protect their countries’ economic interests.

The role played by wild birds is an important piece of this puzzle as well. Wild birds, especially waterfowl, act as the reservoir for H5N1. The birds maintain the virus between epidemics. Waterfowl are known to carry the virus, release virus in their feces and oral secretions, and are usually not sickened by the virus infection. These characteristics of the reservoir indicate how easily a pandemic could start from a mutant virus in the reservoir. In Hong Kong in 2002 to 2003 and again in China in 2005, large numbers of wild birds were killed by the virus, emphasizing the virus’s tendency to mutate. Experts believe that it may take only a few mutations for the virus to gain the ability to successfully transfer between humans. If they are right, then the waterfowl reservoir is always just a step away from creating a pandemic virus strain.

Given their mobility, especially during migration, wild birds also appear to be good candidates for spreading the virus among countries and continents. However, investigations suggest that, while wild bird migration might play a role in viral geographic expansion, it is probably secondary to the role played by commercial poultry exchanges.

Avian influenza virus type A H5N1 has demonstrated its ability to transfer from wild birds to domestic poultry (and perhaps to humans), to decimate domestic poultry flocks, to be transferred from poultry to humans, and to be highly pathogenic for humans. It has not definitively demonstrated the ability to pass freely from one human to another, although the Centers for Disease Control and Prevention (CDC) indicates that a limited amount of human-to-human cases may have occurred. While for the most part, H5N1 cannot transmit effectively from person to person, if it were to add this last ability successfully to its arsenal, it would be a candidate to initiate a pandemic as deadly as the influenza pandemics of the past. The change required to introduce this ability to the H5N1 virus is not thought to be elaborate. A few simple mutations in the viral RNA might suffice.

Epidemiologists have one special concern, the potential for the H5N1 virus to use pigs for reassortment of its genes. In developing countries, pigs often share living space with chickens and other poultry. Humans often live adjacent to the animals or even share their living space. These associations are troubling because pigs host both human and bird flu viruses—for example, the H1N1 strain that caused a global pandemic between 2009 and 2010 was of swine origin, although the H1N1 virus is endemic to both birds and pigs—and the intimate association of the three species presents the two viral strains with the opportunity to invade the same pig. Together in the same host, they would be expected to exchange RNA strands. Some reassortments might produce a virus with the capability to transfer from human to human.

Governments and public health officials are between the proverbial rock and hard place. They would be criticized if they prepared for a threat that did not materialize, but more tragic results would occur if they failed to prepare and a pandemic broke out. The global chaos of the outbreak of the COVID-19 pandemic in late 2019 and early 2020 heightened concerns around the world over pandemic readiness in most countries. For the long-term struggle against avian influenza, disease patterns in animal populations might be very helpful in predicting which threats have the potential to cause human pandemics and in otherwise understanding the viruses. This possibility calls for close coordination among students of wildlife, veterinary, and human disease. That coordination will not solve all the mysteries of influenza outbreaks but should aid in understanding them, and the influenza viruses will not be controlled until they are more thoroughly understood.

In early 2022, a highly pathogenic avian influenza (HPAI) emerged in the US; by 2023, it had become the worst outbreak of avian flu in US history, resulting in the death of over 60 million barnyard and wild birds. Some experts argued that American farms should begin vaccinating commercial poultry against H5N1 to slow the spread of the virus, a practice that was already in place in China where the strain was first detected in 2010. Meanwhile, critics warned against such vaccinations, in part because of the trade restrictions they would cause. The strain was also reported to be infecting dozens of mammals living in various parts of the US, including grizzly bears, seals, and mink. Scientists found this development particularly concerning as more infections in mammals increases the odds of human infection.

In April 2024, amid an ongoing outbreak of H5N1 in the US states of Texas and Michigan, government officials announced that the disease had spread from poultry to cattle. Additionally, a human worker caught the disease from one of the cows infected with the virus. This outbreak was notable not only because it was a rare instance of the disease being transmitted from poultry to cattle; more importantly, this marked the first confirmed time the disease had made the jump from a mammal to a human. By that time, H5N1 had been identified in wild birds in every US state.

As H5N1 outbreaks continued to emerge across the US, some epidemiologists warned that inadequate testing measures may have resulted in human cases of H5N1 going undiagnosed. These concerns grew after workers dealing with infected cows in different US states reported influenza-like symptoms but were not tested for H5N1. To address these gaps and oversights, some medical experts called for an expanded testing system that included proactive testing of local populations in areas where avian influenza had spread to humans.

By May 2024 the US government had also ramped up its efforts to fund the development of an effective avian influenza vaccine. However, this decision attracted some controversy. Some critics of this effort argued that spending significant money to develop and produce these vaccines was a waste of resources, due to the relatively low risk of avian influenza mutating enough to spread at high levels among human beings. However, other people, including a number of medical experts, felt the risk was significant enough to justify doubling down on efforts to develop an effective and safe vaccine due to the challenges and long timelines involved in vaccine development.

The following month, the World Health Organization (WHO) announced the first confirmed case of the avian flu strain H5N2 in humans after a patient in Mexico died from complications resulting from an H5N2 infection. However, the WHO announced that it believed the overall threat that H5N2 posed to the public to be low, as the agency had yet to observe human-to-human transmission.   

Bibliography

"Avian Influenza A(H5N2) - Mexico." World Health Organization, 5 June 2024, www.who.int/emergencies/disease-outbreak-news/item/2024-DON520. Accessed 26 June 2024.

"Avian Influenza A (H7N9) Virus." World Health Organization. WHO, 2016. 29 Apr. 2013.

Beigel, John, and Mike Bray. “Current and Future Antiviral Therapy of Severe Seasonal and Avian Influenza.” Antiviral Research 78 (2008): 91–102. Print.

"Bird Flu." MedlinePlus. National Institutes of Health, 2 Oct. 2014. Web. 29 Apr. 2016.

Clark, Larry, and Jeffrey Hall. “Avian Influenza in Wild Birds: Status as Reservoirs, and Risks to Humans and Agriculture.” Current Topics in Avian Disease Research: Understanding Endemic and Invasive Diseases. Ed. Rosemary K. Barraclough. Washington: Amer. Ornithologists’ Union, 2006. Print.

Cohen, Jon. "Bird Shots." Science, 6 Apr. 2023, www.science.org/content/article/bird-shots-vaccinating-poultry-best-defense-deadly-bird-flu. Accessed 26 Apr. 2023.

Davis, Mike. The Monster at Our Door: The Global Threat of Avian Flu. New York: New, 2005. Print.

Green, Jeffrey. The Bird Flu Pandemic. New York: Dunne, 2006. Print.

"H5N1 Bird Flu: Current Situation Summary." Centers for Disease Control and Prevention, 19 Apr. 2023, www.cdc.gov/flu/avianflu/avian-flu-summary.htm. Accessed 26 Apr. 2023.

"Influenza Type A Viruses." Centers for Disease Control and Prevention, 9 Mar. 2022, www.cdc.gov/flu/avianflu/influenza-a-virus-subtypes.htm. Accessed 26 Apr. 2023.

Murphy, Sean. "What to Know About the Latest Bird Flu Outbreak in the US." The Associated Press, 3 Apr. 2024, apnews.com/article/bird-avian-flu-chickens-eggs-03793b5b1cb7429ce293e8577aef0358. Accessed 11 Apr. 2024.

Sfakianos, Jeffrey N. Avian Flu. New York: Chelsea House, 2006. Print.

Stein, Rob. "Launching an Effective Bird Flu Vaccine Quickly Could be Tough, Scientists Warn." NPR, 3 May 2024, www.npr.org/sections/health-shots/2024/05/03/1248092856/bird-avian-flu-vaccine-human-pandemic. Accessed 15 May 2024.

Stone, Will. "The U.S. May Be Missing Human Cases of Bird Flu, Scientists Say." NPR, 2 May 2024, www.npr.org/sections/health-shots/2024/05/02/1248538298/the-u-s-may-be-missing-human-cases-of-bird-flu-scientists-say. Accessed 15 May 2024.