The unfolding of a pandemic (2)

Part 1 here:

INFLUENZA viruses generated and proliferating in pig populations have been a serious pandemic threat to the human population for a long time, but research into their potential has been neglected compared with other kinds of influenza such as pathogenic avian influenza viruses.

As discussed in The unfolding of a pandemic (1), confirmed human infections with swine influenza are now being reported far from the original outbreak in Mexico; it is now taken flight to well over 25 countries with several thousand clinical cases and over 50 deaths. The clusters of milder infections in the US suggest the virus is spreading readily and the US Center for Disease Control and Prevention (CDC) says this strain is so different from existing human flu viruses that most people have no immunity to it; currently there are no specific vaccine to this new human flu virus.

New & emerging disease watchers are waiting to see if this particular virus undergoes any further genetic reassortment in the months or years to come.

Some virologists say we should have seen this emergence coming! This type of virus [pig-associated influenza] emerged in the US in 1998 and has since become well-established on intensive pig farms across North America. That 1998 virus was a re-engineered influenza virus with components of influenza genes from pigs, birds and human viruses, and it was shown to be evolving rapidly.

Influenza viruses infect many different species of animal, including waterfowl, pigs, horses and humans. It wasn’t all that long ago that the cross-species transfers of viral infections were thought to be exceptional and unusual; not any longer! The long genetic evolution, in comparative isolation, of influenza viruses in birds and mammals has to some extent prevented bird flu viruses transferring to people. But the 1997 and 2003 detection of a highly pathogenic avian-derived influenza virus (A/H5N1) in humans was a worrying portent of the brave new world of possible pandemics.

Influenza specialists have known that the mixing of flu viruses between what are called synanthropic hosts (like pigs, companion animals, rodents and birds), can lead to newly genetically engineered viruses. For example if bird-derived influenza viruses pass to pigs, which also have their own flu strains, the intensively housed pigs can catch two kinds of flu at once. The pig is like the laboratory crucible or mixing vessel, and hybrid flu viruses can emerge with genes from both parent viruses.

That happened in the United States in 1998. Swine flu is now endemic in the USA and intensively housed American pigs regular contacted ‘winter flu’, just like humans.  These swine flu strains are genetically mutated forms of virus from the great human pandemic of 1918, which killed pigs as well as at least 50 million people worldwide. The swine flu strains are members of the H1N1 Influenza A family. The terms “H” and the “N” classify these viruses according to the surface proteins haemagglutinin (H) and neuraminidase(N) on influenza virus. Influenza viruses can remain genetically stable for long periods and continue to circulate as mild infections in certain animal populations. That was the case for swine flu up to the late 1990’s when a re-engineered influenza virus in pigs emerged.

And sometimes these evolving viruses get the chance to try out in another new host on top!

Let’s go back to some important history to explain this. In 1976 swine-derived flu caused an outbreak of H1N1 influenza in people at a military camp in New Jersey, USA with at least one death. That particular virus didn’t spread efficiently from person-to-person and the outbreak soon stopped.

But in 1998, the swine-derived H1N1 hybridised with human and bird viruses, resulting in a three-way re-assortment of the viral genes - the “triple reassortant” viruses caused flu outbreaks in intensive piggeries in three US states [Minnesota, Iowa and Texas]. These viruses initially had genes that produced human-derived surface proteins and swine internal viral proteins, with the exception of three genes that made up the RNA polymerase, the crucial enzyme the virus uses to replicate in its host. Two of these internal processing genes were from bird influenza viruses and the third from human flu virus. Virologists believe that these bird polymerases allow the virus to replicate faster than those with the human or swine versions, making it more virulent and potentially deadlier.

By 1999, these reassorted influenza viruses became the dominant flu strain infecting pigs in North America and, unlike the swine flu virus they replaced, the new ones were actively evolving. There were many versions with different pig or human surface proteins, including one, very similar to the Mexican flu spreading now, with H1 and N1 determinants from the original swine virus.

All these new viruses contained the avian and human polymerase genes and they outcompeted the other swine influenza viruses that don’t have these genes.  Like all rapidly evolving influenza viruses they are undergoing small changes in their genes that antigenically change surface proteins to evade the pigs’ immunity. And just like human flu in some parts of the world, ‘pig flu’ in North America is no longer seasonal.

Virologists in 2004 warned that pigs in the US were an increasingly important reservoir of viruses with human pandemic potential. One in five pig workers in USA have antibodies to swine flu, showing they have been infected with the virus; in contrast most people in the general populace have no immunity to these viruses.

Generally it is the haemaggultinin protein (H) type which determines our immune response and makes the difference between mild and severe influenza outbreaks. Because the Mexican influenza virus carries the swine version of H, the antibodies most of us have to circulating human H1N1 influenza viruses will not recognise it. Even the CDC warned last year that swine H1N1 represented a pandemic threat if these viruses began circulating in humans. 

The insertion of the avian polymerase genes are especially worrying, as similar genes make A/H5N1 bird flu lethal in mammals and also made the 1918 human pandemic virus so lethal in people. The H5 surface protein are totally new to humans, and whilst human-to-human spread has not been a feature of bird flu, this virus has killed more than half of the people it infected.

Up until this Mexican flu outbreak, the major focus has been on this H5N1 virus or another bird influenza virus as a potential source of the next human flu pandemic. Any influenza virus that has undergone reassortment from any of these new haemagglutinin families - H5, H7 or H9 - only needs to become readily contagious to go pandemic.

So where did the new Mexican influenza virus originate? Veratect (see The unfolding of a pandemic (1)) based in Washington State USA monitors world press and government disease reports to provide early disease warnings for its clients, which includes the US, Centre for Disease Control. Their first inkling of the disease was a 2 April report of a surge in respiratory disease in a town called La Gloria, east of Mexico City, which resulted in the deaths of three young children. Only on 16 April - after Easter week, when millions of Mexicans travel to visit relatives - did reports surface elsewhere in the country. Local reports in La Gloria blamed industrial pig farms in nearby Perote, a subsidiary of US pork producer Smithfield Foods. These farms produce nearly one million pigs a year.

Smithfield Foods has insisted there were “no clinical signs or symptoms” of swine flu in its pigs or its farm workers in Mexico. That is unsurprising, as the company routinely administers influenza virus vaccination to swine herds. US Department of Agriculture researchers know that while vaccination keeps pigs from getting sick, it does not block infection or stop pigs from shedding of the virus. The evidence suggests that ‘swine flu’ was a disaster waiting to happen. Swine flu virus research has received little research attention, perhaps because it caused only mild infections in people which didn’t spread well between people. Now one swine flu virus has stopped being so well-behaved and has begun to spread effectively between humans and has now gone global.

David Obendorf

David Obendorf

So where did the new Mexican influenza virus originate? Veratect (see The unfolding of a pandemic (1)) based in Washington State USA monitors world press and government disease reports to provide early disease warnings for its clients, which includes the US, Centre for Disease Control. Their first inkling of the disease was a 2 April report of a surge in respiratory disease in a town called La Gloria, east of Mexico City, which resulted in the deaths of three young children. Only on 16 April - after Easter week, when millions of Mexicans travel to visit relatives - did reports surface elsewhere in the country. Local reports in La Gloria blamed industrial pig farms in nearby Perote, a subsidiary of US pork producer Smithfield Foods. These farms produce nearly one million pigs a year.

Smithfield Foods has insisted there were “no clinical signs or symptoms” of swine flu in its pigs or its farm workers in Mexico. That is unsurprising, as the company routinely administers influenza virus vaccination to swine herds. US Department of Agriculture researchers know that while vaccination keeps pigs from getting sick, it does not block infection or stop pigs from shedding of the virus. The evidence suggests that ‘swine flu’ was a disaster waiting to happen. Swine flu virus research has received little research attention, perhaps because it caused only mild infections in people which didn’t spread well between people. Now one swine flu virus has stopped being so well-behaved and has begun to spread effectively between humans and has now gone global.