H5N1's Early Impacts Credit WHO
#18,454
Nearly 30 years ago H5 A/Goose/Guangdong/1/1996 (gs/GD) lineage emerged in South East China, causing up to 40% mortality in farmed geese. It was originally subtyped as H5N4, but retyped as H5N1 in 1997 (cite).
Roughly a year later Hong Kong reported outbreaks in poultry, and in May of 1997 the 1st human infection was reported (see Influenza A (H5N1) in Hong Kong: an overview). In November and December, 17 more cases were detected (6 fatal), raising international alarm and sparking the eradication of Hong Kong's poultry.
While HPAI H5 viruses were occasionally reported in Chinese wild birds, the HPAI H5N1 virus went to ground for nearly 6 years, resurfacing again in 2003 in Hong Kong in 2 residents who had recently visited Fujian Province. Notably, other family members reportedly died, but were never tested (see WHO Announcement).
For the next two years HPAI H5N1 remained primarily a South East Asia concern, with outbreaks in poultry, and spillovers into humans and captive big cats (often fed raw poultry), spreading from China into Vietnam, Thailand, Cambodia and Indonesia.
But the virus continued to mutate, spawning new clades and genotypes. Some were more biologically `fit' than others, but each served as a stepping stone in the virus's evolution.
In the spring of 2005, pictures of a massive die off of migratory birds at Qinghai Lake, Tibet went viral (see H5N1 Influenza Continues To Circulate and Change 2006 by Webster et. al.). A new clade (2.2) had emerged, which was particularly pathogenic in some species, while other migratory birds were better able to transport it over long distances.
This sparked the first major diaspora of the virus, with H5N1 turning up in Europe, then the Middle East, and Africa, within a matter of months (see H5N1 Virus Evolution in Europe—An Updated Overview).
That was twenty years ago, and today the descendants of H5 A/Goose/Guangdong/1/1996 (Gs/Gd) are more diverse, more widespread, and more impactful than ever (see Nature Reviews: The Threat of Avian Influenza H5N1 Looms Over Global Biodiversity).
Today we've got a fascinating, and highly detailed review article that traces the evolution and spread of H5Nx from those early years to where we are today, with clade 2.3.4.4b's recent conquest of the Western Hemisphere, and its rapidly expanding host range.
Those looking for a deep-dive will find this 21-page review is well worth reading in its entirety. Due to its length, I've only reproduced the link and a brief excerpt below. I'll have a brief postscript after the break.
Review Article Open Access
Alejandro J. Aranda1, Gabriela Aguilar-Tipacamú1,2, Daniel R. Perez3, Bernardo Bañuelos-Hernandez4, George Girgis5, Xochitl Hernandez-Velasco6, Socorro M. Escorcia-Martinez6, Inkar Castellanos-Huerta7 and Victor M. Petrone-Garcia8
Published: 25 April 2025 https://doi.org/10.1099/jgv.0.002081
Conclusion
A wide range of factors promote the environmental permanence of AIV, considering natural reservoirs, as well as seasonal migration patterns intra- and intercontinental, facilitating the introduction and emergence of the virus in various geographical regions. The breeding area in Siberia plays a key role in the spread of the main epidemiological events caused by H5NX viruses descended from the Gs/Gd lineage since not only the main migratory routes from all continents are interconnected, but it also is a region where 200 000–400 000 wildlife birds converge during the breeding season [263].
However, factors like globalization also contributed to the increased activity of the poultry industry, which led to the emergence of HPAIV and the local spread of AIV worldwide. The leap between different species has been an observable phenomenon in Gs/Gd lineage viruses by acquiring mutations involved with pathogenicity, transmissibility and adaptability due to the participation of potential intermediary or bridge hosts that allow the permanence of these mutations.
Based on the eco-epidemiological review of the outbreaks caused by the Gs/Gd virus, it is of interest to evaluate whether the acquisition or permanence of the mutations involved in adaptation to a new host. As well, evaluate the implementation of biological tools such as vaccination to safeguard wildlife populations that are suffering from a never-before-seen imbalance and the potential risk presented for Antarctic and Greenland wildlife which have reported cases of H5NX virus of the Gs/Gd lineage for the first time, as would be the spread of the virus to Oceania through pelagic species, which is increasingly becoming a target continent in the spread of the virus, since in March 2024 the first case of H5N1 clade 2.3.2.1a was reported in a human [264], opening the window of a possible third intercontinental incursion of Gs/Gd lineage viruses, mediated by ecological and human activity factors.
Despite our growing concerns over H5N1, we probably won't know if H5Nx avian influenza is capable of sparking a pandemic until we actually see it happen. While I wouldn't bet good money against it, it is probably fair to call it a long-shot (at least in the near-term).
But H5Nx is only one of scores of avian and swine influenza A viruses in the wild with pandemic potential (see CDC IRAT scores).
All are continually evolving (via antigenic drift and antigenic shift), and many are spilling over into new mammalian species where they may pick up host adaptations. A few (of many) recent examples:
While individually they may all be long-shots to spark a pandemic (and some would undoubtedly be worse than others) - when you have that many threats rolling the genetic dice - it makes it all but inevitable that one of them will eventually succeed.
We now live in an age (see The Third Epidemiological Transition) where the the number, frequency, and intensity of pandemics are only expected to increase over the next few decades.
BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events
PNAS Research: Intensity and Frequency of Extreme Novel Epidemics
Since predicting the next pandemic is a mug's game, our best option is to make sure we are prepared for the next global public health crisis.
Regardless of the source.
