Epidemiologists (those who study the spread of diseases) often find themselves in a most unenviable position. A new, highly transmissible disease is identified and they feel compelled to warn of the dangers of an impending pandemic. Such was the position that virologist Robert Webster found himself in, in 2003. A new and potentially highly pathogenic virus of the H5N1 flu strain had developed in birds in Asia between 1996 and 2002. First discovered in a goose from Guangdong, and known as avian influenza, or more simply bird flu, it had decimated domesticated bird stocks and proved able to jump the species boundary and kill a variety of vertebrate species. A relative of the dreaded “Spanish flu” that killed between 30 and 50 million people in 1918-19, H5N1 looked like an imminent threat. “The world is teetering on the edge of a pandemic that could kill a large fraction of the human population,” Webster warned in an article in American Scientist.
Two years later, in 2005, Webster’s call was amplified by another expert on bird flu, who stated that an outbreak among humans could kill between 50 and 150 million people. The politicians began listening, and in 2006 billions were spent researching H5N1, developing vaccines and planning responses to an outbreak. The plans included widely publicised and dramatic rehearsals of responses to outbreaks in places like airports, and health ministers began warning that a pandemic could wreak more damage than a terrorist attack. The public was thus on high alert, and governments and companies were poised to commence mass production of vaccines. And then – no pandemic eventuated.
A heightened state of alert can only be maintained for so long, and by 2019 little if any public memory of the preparations of 2006 remained. Governments and populations were thus caught unawares when, in December 2019, news of a new respiratory virus started coming out of Wuhan, China. The disease had nothing to do with bird flu. Instead it was a coronavirus – a relative of the common cold – soon to become known as Covid-19. Within months the globe was in turmoil. International travel all but ceased, populations were locked down, hospital systems were overwhelmed, governments were again spending billions, and pharmaceutical companies were again working on vaccines. Despite it all, the pandemic raged for several years and killed at least 7 million people.
While public attention was focused on Covid, however, a new, concerning variant of H5N1 had emerged. Spreading globally since 2020, this new variant was increasingly in the news by late 2023, and talk of a new pandemic was rising. The cost to the poultry industry was high, possibly in the billions globally. Heightened public awareness stemmed from the fact that the disease had been detected in penguins in the Antarctic in October 2023, and then had quickly spread to seals. H5N1 is a subtype of the influenza A virus. The dominant strain that arose in 1996 continues to be watched closely. It can infect many, very different species, including valuable livestock, and it can be highly pathogenic in people.
Bird flu has been around for a long time and can be caused by many different subtypes of influenza A. It has been recorded in over 100 species of birds and many strains are known. The problem with H5N1 is that it is an HPAI – highly pathogenic avian influenza – meaning it has great potential to cause disease. And if the virus does jump the species boundary into humans, the results could be catastrophic. The World Health Organisation (WHO) estimates that around 60 per cent of people infected with avian influenza H5N1 die of the infection. Indeed, in the last 20 years we know of 878 human cases of HPAI H5N1, with a 52 per cent mortality rate in 23 different countries. There are those, however, who think it is probably far less lethal than that, arguing that it’s mostly very sick people who seek treatment, and that many others, who have mild symptoms, do not seek treatment and so are not recorded as recovering from the infection.
The strain of H5N1 currently in the news is prosaically known as clade 2.3.4.4b. It’s an unusual virus that is able to infect marine mammals and birds. It is also known in foxes, bears, cats, dogs and most recently in dairy herds in the US. There are only a handful of human infections recorded to date, one of whom was a dairy worker whose only symptoms were red and inflamed eyes, and who made a full recovery. Clade 2.3.4.4b doesn’t appear to be able to spread readily between people – yet. But it’s concerning how many different mammal species can be infected.
The threat posed by the diversity of mammal species infected is twofold. First, it increases the range of animals in closer contact with humans, in particular livestock and domestic pets. Second, the more animal species infected with H5N1, the greater the potential for H5N1 to mix with other flu subtypes in a process called reassortment. The genetic material of an influenza A virus exists as eight separate segments inside the viral cell. When two different flu viruses infect the same animal, there is the opportunity for them to exchange segments and this can produce new, potentially dangerous strains.
In 2009 the world saw a reassortment event, not in bird flu, but in human flu. A new variant of the H1N1 flu subtype emerged that contained genes from swine, bird and human flu virus, and it quickly spread among humans leading to the so-called swine flu pandemic. Because of the novel genetic make-up of the H1N1 strain, people were immunologically naive to the virus, and unable to mount an effective defence, and thus the disease easily spread across the globe.
Because pigs host subtypes of bird, human and swine flu, they are the perfect cocktail shakers to produce new viral reassortant strains with pandemic potential. Webster’s concern about bird flu in particular arises because, if a variant easily transmissible between humans did emerge, in a pig for example, then there are several factors that suggest a pandemic would be very damaging. The high mortality rate seen in rare human cases is one. Another is that the time period between infection and becoming infectious is short. In another subtype of bird flu, known as H9N2, poultry can transmit the virus as quickly as six hours after they are infected. A high rate of transmission would produce a rapidly evolving pandemic with the potential to overwhelm health services. The H5N1 subtype of bird flu is prevalent in wild birds that migrate long distances. In addition to a rapid temporal spread, H5N1 also poses concern because of the potentially wide geographical spread outside human control. Indeed, in October 2023 H5N1 arrived in Antarctica where it has since killed hundreds of elephant seals, and late last year a polar bear was found to have died of the virus in Alaska.
For all this concern, the threat alert by the WHO remains low, and not without good reason. Since the discovery of the HPAI H5N1 lineage in that goose in Guangdong in 1996, human-to-human transmission has been exceptionally rare and only one case of human-to-human-to-human spread has ever been recorded. Those contracting bird flu are typically poultry farmers, and those few secondary infections, carers of those farmers. It is the potential for what could happen that justifies the fear, and it is for this reason that many countries have a pandemic preparedness plan for H5N1, with small amounts of vaccine stockpiled that cover a range of different strains. In comparison to Covid-19, the creation and upscaling of vaccine production would be more rapid, because pandemic preparedness for flu has been developing over many years. There are doubts around the infrastructure for distribution though, and we must hope that global governments have learned lessons from our last pandemic to better respond to future ones.
In a world of spiralling threats, from escalation of conflict in the Middle East, to climate change, governments everywhere struggle to prioritise spending and focus. In this context, bird flu presents a most lamentable amalgam of characteristics – of uncontrollable spread in wild species, high mortality rates among humans, but low chances of becoming a human pandemic. The chances of the government getting the response right in these circumstances are low. But the consequences of getting it entirely wrong are dire indeed. The one thing that’s certain is that as we endure pandemics we learn valuable lessons, and our response becomes ever more agile.
[See also: The age of danger]
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