Recent reports about the detection of highly infective avian influenza (HPAI) in US livestock (a young goat, herds of dairy cattle) and even an individual in Texas have raised the specter of the SARS-COV2 pandemic, leading some to ask whether a new global incident is just around the corner. In today’s Tulane Medicine Digest, we will discuss the current state of the avian influenza outbreak, the CDC’s thoughts on risk to humans, and the available options for prevention and treatment of HPAI.

A Brief History of Avian Influenza

Avian influenza was first identified over a century ago, with initial reports dating back to 1878, but outbreaks remained sporadic and contained throughout most of the twentieth century. Beginning in the 1990s, the increasing density of poultry populations (as a result of intensive farming) has resulted in longer, more frequent waves. H5N1—the strain of highly pathogenic avian influenza A (HPAI) at the heart of current reports—was first detected in 1996. Like many viruses, avian influenza undergoes genetic reassortment—a process in which viruses exchange genetic material between variants over time—leading to mutations that can alter infectivity and transmission.. The current H5N1 outbreak began in 2020 in chickens and wild birds and likely occurred due to such mutations. Cases in North America began in late 2021, but were primarily restricted to domestic poultry and wild birds, with occasional cases in wild mammals.

The recent detection in U.S. non-poultry farm animals, and limited transmission to humans, has understandably led to some public concern. It is important to note that in the US, the only known cases so far involve a poultry worker in Colorado in 2022 and a cattle worker in Texas in April of 2024. In both cases, symptoms were mild and resolved after only a few days. While infections can potentially cause severe illness, the risk of a large outbreak remains low due to the difficulty of human-to-human transmission. A 2023 case in a Chilean man briefly raised alarms due to the presence of a mutation known to increase viral replication, but several further mutations would have been necessary for the virus to easily spread between humans. Overall, the Centers for Disease Control and Prevention (CDC) has thus maintained its judgment that the current strain of H5N1 poses little direct threat to humans. 

Environmental and Agricultural Impact of HPAI

A greater concern has been the potential impact of viral spread on livestock and endangered species. In addition to the direct deaths from avian influenza, large numbers of animals often need to be isolated or culled in order to prevent spread. Such measures can lead to large fluctuations in the prices of products – such as eggs or milk – due to disrupted supply chains and increased costs of surveillance. It is currently unknown exactly how the disease transmits, so this is the main question that would impact a potential future mammalian spread. Airborne transmission—a large factor in the rapid spread of SARS-COV2—would pose the greatest threat. However, a recent study observed that the highest concentration of virus in dairy cattle was found in the milk itself, suggesting that the primary route of spread between cows may be due to direct contact with contaminated gloves or milking machinery, rather than by breathing. While this indicates presence of the virus in milk, pasteurization has been shown to destroy the pathogen. Despite this data, out of an abundance of caution the FDA has recommended discarding products from symptomatic animals to further reduce risk.

Whether transmission is direct or airborne, the most effective method of combatting further spread is likely to be a widespread vaccination. However, many livestock producers are reluctant to employ vaccination due to difficulties in exporting vaccinated animals and concerns over spread via asymptomatic carriers. Thus, a concerted effort is necessary to develop other effective methods of containing infection, increase efficacy of vaccines, and work to change policy to facilitate global use of preventative –  rather than reactive – measures. 

Stopping the Spread: Prevention and Treatments for Avian Influenza

Health authorities including the CDC and World Health Organization (WHO) actively monitor outbreaks of avian flu, and such vigilance has been heightened in light of recent human cases. Public health measures implemented include surveillance, monitoring of exposed individuals, and stringent biosecurity measures to prevent further spread. The CDC emphasizes that the first lines of defense are avoiding contact with sick or dead animals, handling animal products with care, and ensuring food products like milk are pasteurized before consumption​. For individuals who are infected, antiviral treatments such as oseltamivir are recommended for both mild and serious cases, and are especially effective if administered early. It is perhaps also comforting to know that the CDC already maintains a stockpile of candidate vaccine viruses to aid in faster development of specific vaccines in the event of an outbreak. 

In addition to established treatments, researchers are also developing novel techniques with potential to combat HPAI infection and spread. USDA scientists recently discovered a protein that increases cellular antiviral response to various strains of avian influenza. Gene-editing techniques to increase expression of this protein could be leveraged to provide greater innate protection against avian influenza in poultry. Tulane researchers James McLachlan, PhD and Lisa Morici, PhD, have developed a novel vaccine adjuvant shown to increase vaccine efficacy against various pathogens. The adjuvant increases immunity at mucosal surfaces, such as those of the nose and mouth, which are often the source of both initial infection and airborne transmission. A team at Georgia State University is exploring the potential of 4′-fluoridine as a novel antiviral for treatment of influenza. As rapid mutations in influenza viruses can increase their resistance against existing antivirals, the compound could provide greater effectiveness against novel challenging variants of the virus. 

The Importance of Global Cooperation

While the threat to humans remains low at present, controlling infection and spread of a rapidly mutating and ubiquitous pathogen such as avian influenza requires concerted efforts on the part of scientists, governments, and agricultural producers. The World Organisation for Animal Health states in its One Health approach that international collaboration is critical, and that individuals and institutions must work together to prevent future pandemics and remove barriers to effective containment. In a timely podcast on avian flu, Tulane University’s Chad Roy, PhD, answers many questions about the disease and stresses that in order to prevent future pandemics there must be a paradigm shift away from simply responding to existing dangers as they arise, and towards proactive prevention of future pathogenic risks.

In conclusion, while the recent detections of HPAI raise concern, they are unlikely to signal the onset of a global outbreak akin to SARS-COV2. The CDC’s assessment underscores that the current risk to human health remains low, largely due to the virus’s limited ability to transmit between humans. Nonetheless, continued vigilance will be important, including enhanced surveillance, biosecurity measures, and ongoing research into effective treatments and preventive strategies. Taking into account lessons learned during the COVID pandemic, a comprehensive approach that involves global cooperation will be vital for managing current risks and preparing for future threats, ensuring the health of humans and the safety of our global food supply.

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Special thanks to James Zanewicz, JD, LLM, RTTP and Elaine Hamm, PhD for copy-editing assistance.