Since at least 1918, when the "Spanish Flu" swept across the world, leaving a trail of corpses in its wake, Americans have blamed influenza outbreaks on other countries. These days we like to point fingers eastward, invoking images of ancient agricultural practices and chaotic live animal markets in China and Southeast Asia. With a whiff of smugness, we tell ourselves that those are obviously the kinds of places where we can expect the next global flu pandemic to make the leap into humans.

Unless it happens in Maryland, that is. As public health officials reported recently in MMWR:

On September 17, 2017, the Maryland Department of Agriculture (MDA) was notified by fair and 4-H officials of ill swine at agricultural fair A, held September 14–17. That day, investigation of the 107 swine at fair A revealed five swine with fever and signs of upper respiratory tract illness. All five respiratory specimens collected from these swine tested positive for influenza A virus at the MDA Animal Health Laboratory, and influenza A(H3N2) virus was confirmed in all specimens by the U.S. Department of Agriculture National Veterinary Services Laboratory (NVSL). On September 18, MDA was notified by fair and 4-H officials that swine exhibitors were also ill.

By the time the outbreak burned out, H3N2 swine flu had infected at least 40 people at three fairs around the state. Over 1/3 of the patients had only indirect contact with pigs. In one case, a child who had simply been wheeled through the exhibit hall in a stroller caught it. Fortunately nobody died, though two children infected by this virus had to be hospitalized.

This spillover event didn't set off the next 1918-scale flu disaster, but it certainly had a lot of the necessary elements.

Flu viruses have a unique and complex ecology. Birds are the main reservoirs for influenza, and the avian strains of it don't grow very well in humans. Bird flu can infect poultry workers who are exposed to lots of the virus, but it seldom spreads to other people. We're dead-end hosts for it. However, if it first makes an intermediate stop in pigs it can mutate and adapt to mammalian lungs. The resulting swine flu strains can more easily infect humans.

Once a flu strain becomes established in humans, it spreads seasonally and accumulates minor mutations, a process called genetic drift. That's how it evades the antibodies people built up against it the previous year, allowing it to re-infect the same hosts again. Occasionally an entirely new strain will make the leap from animals (usually pigs) to humans, and displace one of the strains that was circulating before. These genetic shifts are where major flu pandemics come from. That's why flu virologists are so intensely interested in pigs.

Indeed, the Maryland outbreak isn't the first time this particular strain of swine flu, called variant H3N2, has come to the attention of public health officials.

Flu strains are classified by their two major antigenic proteins, hemagglutinin (H) and neuraminidase (N). Different H and N proteins reassort as flu strains evolve. The current flu vaccine, based on the strains seen circulating in humans, contains both a H1N1 and a H3N2 virus. Variant H3N2 swine flu, as the name implies, is a bit different from the regular H3N2 strain. Specifically, it has picked up a gene from the 2009 pandemic H1N1 flu strain. Veterinarians first found it in pigs in 2010, and it's caused sporadic outbreaks among humans ever since.

What's different this time is the patient population. Past outbreaks of variant H3N2 have mostly affected people who had direct contact with pigs. At the Maryland fairs, however, it seems to have spread a lot more easily. It's not clear why.

What is clear is that the next big influenza outbreak could start anywhere poultry, pigs, and people come together. China is certainly a possibility, but so are the local 4-H club, the county fair, and Old MacDonald's Organic Farm and Petting Zoo. It could even make a multi-step journey, moving from birds into pigs in one place, and then from pigs to humans somewhere else. Even the dreaded Spanish flu might very well have originated on farms in Kansas, then spread to Europe with American troops deployed to the Great War.

As Walt Kelly famously said, we have met the enemy, and he is us.

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