Pandemic
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Influenza viruses originate in wild waterfowl and have long spilled over and adapted to other species, including humans. There are three types. Type B and type C influenza viruses are human-adapted pathogens, which cause mild seasonal flu. Type A are those viruses that have remained in their original reservoirs: ducks, geese, swans, gulls, terns, and waders.39
Occasionally, type A viruses spill over into domesticated poultry flocks. It’s especially common in southern China, where traditional farming practices allow domesticated ducks and wild waterfowl to easily mingle, providing ample opportunities for influenza to spread into the domesticated flocks. But the domesticated birds, unlike the wild ones, have no immunity to flu viruses. The pathogen replicates with abandon in their bodies, evolving new, more deadly strains called “highly pathogenic avian influenza” or HPAI.40 The process is so reliable that scientists can reproduce it in the lab, creating more deadly strains of avian influenza simply by passing the virus repeatedly through chickens.41
One important check on the spread of highly pathogenic avian influenza is the size of the domesticated bird flocks they infect. Infected chickens shed the virus in their feces for just a handful of days before the virus kills them. Without masses of susceptible poultry around, transmission dies out on its own within a couple weeks, as mathematical models show. In low-density poultry-raising regions, the basic reproductive number of these deadly viruses is less than 1.42 That’s why, up until 2000, scientists considered avian influenza the way they considered Ebola before it emerged in densely crowded West Africa in 2014, as an “infection of minor importance.”43
But then the number and size of poultry farms in China started to grow. By 2009, nearly 70 percent of China’s “broilers”—domesticated chickens raised for meat, as opposed to those raised for the eggs they lay—were reared on farms with more than two thousand other birds. Even larger farms became more common, too: between 2007 and 2009, the number of large farms with more than one million birds grew by nearly 60 percent.44 The pace of international trade in poultry picked up. Twenty times more chickens were shipped across national borders in 2008 than in 1970.45
With bigger flocks and more poultry on the move, contact increased between poultry and wild bird territory and flyways, precipitating more frequent spillovers of flu from the wild birds to the domesticated ones. These spillovers in turn led to more frequent emergence of highly pathogenic avian influenza viruses, which were able to cause longer and bigger outbreaks in the larger flocks they infected. As a result of these changes, the deadly viruses crossed the threshold to become self-sustaining epidemic pathogens in poultry. According to mathematical models, the basic reproductive number of avian influenza viruses, in places where poultry farming is intense, is more than 10.46
As the virus’s basic reproductive number increased, so did the frequency and scale of the outbreaks it caused. Between 1959 and 1992, outbreaks of deadly avian influenza had occurred roughly every three years. Most affected fewer than five hundred thousand birds. Between 1993 and 2002, outbreaks occurred once every year, and between 2002 and 2006, they occurred every ten months. About half of these outbreaks affected millions of birds at a time.47
For years, the growing viral menace posed by our supersized poultry farms escaped public notice, mostly because highly pathogenic avian influenza viruses were restricted to birds. They didn’t infect humans. Then, in 1996, a wild bird flu crossed over into domesticated geese on a small farm in Guangdong province, one of the largest poultry-producing regions in China.48 The virus, dubbed “H5N1,” evolved two never-before-seen capacities. Unlike other avian influenzas, which were rarely found in wild birds, this virus struck a wide variety of wild species, including migratory ones. It also could infect humans.49
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People were exposed to H5N1 through close contact with infected birds. Normal flu symptoms would turn into severe pneumonia, and for some, organ failure. More than half—59 percent—of those infected perished.50 And the virus spread. The international poultry trade carried H5N1 into poultry flocks in at least eight countries, including Thailand, Indonesia, Malaysia, and Cambodia.51 Migratory birds ferried H5N1 into the Middle East and Europe.52 As of this writing, North America has been spared, because few bird species migrate between North America and the H5N1-afflicted parts of the Old World. But that could change. The virus has intermittently been found in migratory birds in Siberia, who mingle with the ducks, geese, and swans that migrate across the Bering Sea into North America. If the latter birds get infected, North America could face H5N1 as well.53
Of all the new pathogens emerging today, novel influenza viruses like H5N1 are the ones that keep the most virologists up at night. If H5N1 or any other novel avian influenza evolved to transmit effectively between humans, the death toll would be swift and substantial. Even with low mortality rates, seasonal flu viruses carry off huge numbers of victims, simply because they are so good at spreading widely among us. Every year seasonal influenza kills up to half a million people around the world. That’s the toll of flu viruses that have already adapted to us, and we to them. A novel influenza virus that could spread as well as the seasonal flu with an even marginally higher mortality rate could level millions.
For now, H5N1 is a zoonotic pathogen. It can’t easily spread from one person to another, which is why of the tens of thousands of people who’d likely been exposed to the virus by the summer of 2014, only 667 cases in humans had been reported.54 But as it evolves, H5N1’s transmissibility in humans could improve. So far, the virus has evolved into at least ten distinct lineages, or “clades,” all with varying abilities and proclivities.55 Some have already mutated in ways that scientists think could boost the effectiveness of H5N1’s transmission in humans. A distinct clade in Egypt, for example, appears better than any other at binding with human cells. That is probably why, between 2009 and 2013, more than half of those who sickened with H5N1 came from Egypt.56
And the virus continues to evolve. If an avian influenza like H5N1 does graduate from a zoonotic pathogen into a human-adapted one, the necessary adaptations will likely occur inside the bodies of people who work intimately with infected birds. I flew to Guangzhou to get a sense of the openings and obstacles the virus would encounter in their bodies. On the plane, it was apparent that flu season had descended upon us. Indeed, a couple weeks earlier, H5N1 had killed a thirty-nine-year-old bus driver in Guangdong province, setting off a massive slaughter of poultry in Hong Kong, many of which had been reared in southern Chinese provinces. The entire aircraft seemed to be coughing, creating an orchestra of high coughs, low coughs, long coughs, short coughs, wet coughs, and dry coughs. The habit of coughing into elbows had not caught on among my fellow passengers. People leaned down and let it all out. The tall young man sitting next to me studied the newspaper avidly during the flight. After we landed, he held a vomit bag to his face, coughed up a wad of mucus, spit it out, and stuffed the bag back into the seat pocket.57
When I arrived at the Jiangcun poultry market in Guangzhou, an open-air wholesale operation where thousands of chickens, ducks, and geese are reared in mesh-wire enclosures, there was no warning about the ongoing H5N1 outbreak, or the death of the bus driver. The birds seemed healthy enough, although according to a 2006 study, one out of every hundred was in fact infected with H5N1.58 If the workers at Jiangcun were aware of this factoid, they didn’t show it. In the United States, poultry workers handling birds infected with highly pathogenic avian influenza viruses wear the same elaborate protective gear that clinicians wear to fight Ebola.59 The workers at Jiangcun were bare-handed and unmasked, wearing simple rubber boots and aprons. The middle-aged couples who managed each enclosure—about the size of the typical monkey cage at a zoo—used long metal hooks to grab the birds by the neck, unceremoniously stuffing them into plastic bins, which were then loaded onto trucks. The dead ones they simply stuffed into a tightly lidded blue plastic barrel. One of these stood beside every enclosure.
Their nonchalance
stemmed, I figured, from the learned indifference of proximity. The workers lived bathed in the viral-contaminated excreta of the birds they tended. They spent their days in the enclosures, grew vegetables in the trash-strewn empty lot behind the caged birds, and retired each night to the low, stained cement-block flats just hundreds of yards away on the same property. A cloud of dust—bits of feathers, sand, and desiccated bird shit—had settled over everything: the lines of damp gray laundry strung over the concrete paths and the sagging cardboard boxes of packaged noodles and biscuits in the little shops across from the enclosures. The windows in the workers’ flats were opaque with it.
The ragpickers who tended the market were similarly exposed. They lived in hand-built shacks covered with tarps just outside the market’s fence. I saw them ambling through the market, shovels slung over their shoulders, collecting wet mush from the bird enclosures into eight-foot-tall piles. Piles of the stuff lay next to their shacks, too.
Any virus in bird excreta at Jiangcun poultry market enjoyed bountiful, unfettered access to the workers there. It could enter the human body as freely as a stream flows into the sea.
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Precisely how H5N1 gained the ability to infect humans is not clear. Some experts speculate that another crowd of livestock—pigs—may have played a role. One of the biological barriers to the spread of bird influenzas in humans is the fact that bird-adapted viruses bind to sialic acids in birds that are not present in humans. Theoretically, H5N1 or some other bird-adapted virus could spontaneously mutate in such a way that allows it to bind to human sialic acids. But there’s another, much faster way for novel flu viruses to acquire that ability, through what’s called reassortment. This is when a virus acquires a chunk of new genes from another virus, and with the newly acquired genes, all of the capabilities those new genes confer. An avian influenza virus could reassort with one that was already good at infecting people, for example one of the many influenza viruses already adapted to humans, such as the relatively mild ones that cause seasonal flu. Then the novel avian influenza virus could acquire the ability to transmit efficiently in humans, too.
Reassortment of this kind could happen only in cells coinfected with both viruses at the same time. But since human influenzas bind to human sialic acids, and avian influenzas to avian sialic acids, people aren’t easily infected with bird influenzas, and birds aren’t easily infected with human influenzas. Thus, even with the massive flocks of poultry moving across international borders and thousands of people exposed to bird excreta across southern China and elsewhere, opportunities for human and avian flu viruses to directly exchange genes are slim.
This is where the pigs come in. Pigs have both humanlike sialic acids on the surfaces of their cells as well as avian-like ones. That means that both kinds of virus can bind to their cells. (This is also true of quails, but given the small scale of quail farming does not seem to play much of a role in the epidemiology of influenza.) Pigs living in proximity to both humans and poultry flocks or wild waterfowl could be the mysterious missing link between bird viruses and human influenza pandemics. Virologists call them the perfect “mixing vessel” for novel influenza strains.60
And just as poultry flocks have grown in China, so have the size of pig farms, increasing the probability that an avian influenza could spill over into pigs.61 Up until 1985, 95 percent of China’s pigs were raised in rural households that reared only one or two pigs a year.62 By 2007, more than 70 percent of China’s pigs were reared in farms where hundreds of pigs are crowded together. By 2010, China was the world’s largest producer of pork, raising 660 million pigs, half of all the pigs raised in the world, and more than five times the production of countries such as the United States.63
A few days after visiting Jiangcun, I arrived in Laocun, Gongming, an illegal pig-farming colony in a sparsely populated industrial area about an hour outside Shenzhen. About one thousand pig farmers live there, along with thousands of pigs, in long, low shacks made of scrap metal and bamboo, paying rent for the government-owned land, illicitly, to the son of a Communist Party member. Along the lanes, groups of hens and a few sickly pigs turned out from the herds roamed freely. The pig farmers wore tall boots, preparing the refuse that they collect from restaurants and elsewhere into viscous stews, steaming in tubs, to feed to the pigs.
We drove around slowly, trying not to arouse attention, until we happened upon a ruddy-cheeked couple, who beckoned us into their shack. It was here that I saw how easily pig, bird, and human influenza viruses could mingle. The couple had divided the dirt-floored structure, rich with the odor of the pigs, into several dark enclosures sparsely furnished with old mattresses, some sticks, and used plastic bags. In one, a young woman hunched beside a smoky fire ringed by stones, a bucket of water by her side, vegetables floating atop. The family’s laundry hung alongside one low wall. A pair of improbably bright red sneakers was stashed on a high wooden shelf.
About ten yards away, under the same roof, hundreds of pigs shuffled and snorted. There were at least three hundred pigs there, packed into long, narrow pens with a two-foot mud track in between them. Each weighed two hundred pounds or more, and most were huddled on top of one another, fast asleep, bodies caked with dung and the remains of their meals. Their heads, with their heavy chins and long, floppy ears, seemed immense atop their squat bodies.
As we made our way through the pig shack, we could see just beyond it a wide, shallow pond. The farmers told us they used this as a manure lagoon in which to store pig waste and raise fish. It was as still and shallow as the ornamental duck ponds that American developers build outside suburban malls. It undoubtedly attracted passing waterfowl. Their viral-contaminated droppings, as they flew overhead, could easily land in one of the many pig troughs that dotted the colony. In the summer, the farmers removed the scrap metal roofs on their shacks to let in the breeze, exposing pigs and their feed to the open air.
Seeing that lagoon, I could easily imagine a pig at Laocun coming down with both an avian influenza and a human one. In that animal’s body, the next pandemic flu virus could hatch.
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Whether or not H5N1 evolves into a human pathogen or fades away into oblivion, the risk of novel influenza viruses remains, as the growing crowds of people, birds, and pigs continue to hatch new strains with pandemic potential. Over the course of writing this book, at least two novel influenza viruses are known to have emerged, both with newly evolved capacities to infect humans.
A variant of H3N2, a virus that normally infects pigs, started spreading into people in the United States in the summer of 2012. (Scientists categorize influenza viruses by the type of proteins on their surfaces. Each has one of sixteen subtypes of the protein hemagglutinin (H) and one of nine subtypes of the enzyme neuraminidase (N) on its surface.)64 People were infected with the pig virus at state fairs, where hundreds of pigs from across the state were gathered together in pig barns. The crowds of pigs created what the virologist Michael Osterholm called “airborne clouds of virus” inside the barns, which were readily inhaled by local people.65
I saw these firsthand at my local state fair in Maryland. People passed in and out of the pig barns, and the airborne clouds of virus that wafted inside them, as nonchalantly as the poultry workers and pig farmers lived amid infected bird excreta in south China. Onlookers walked freely among the small dusty pens in which the pigs slept, holding plastic cups of beer and leaning over to fondle the animals. Giant fans blew the barn’s hot, dusty air around, ruffling visitors’ hair. “Look at the piggy!” I overheard a teenage girl say to her friends, her shoes caked with pig muck. “He’s so cute! Look how beefy he is!” Some of the pig handlers had annexed some of the pigs’ pens, in lieu of a pricey hotel room. In one pen, a couple with two small girls had set up folding chairs and were munching on potato chips; in another, a pile of saggy mattresses sat atop bales of hay, covered with blankets and pillows. Whoever slept there inhaled the virus-laden air all night long.
Betwee
n 2011 and 2012, H3N2v from pigs managed to infect 321 people.66 It’s not a huge number of people, but for a pig virus that had never previously infected humans, H3N2v’s progress into Homo sapiens was “unprecedented,” Osterholm said. The virus had surmounted the species barrier and with repeated exposures could produce mutants with the ability to replicate inside humans. “We’re tempting fate,” Osterholm said.67
Another new influenza strain started infecting humans in February 2013, in eastern China. This virus, H7N9, was discovered in three patients hospitalized for severe pneumonia. Phylogenetic analyses suggested that the new virus was the product of multiple reassortment events involving viruses from ducks, chickens, and wild migratory birds that had occurred over the previous year somewhere near Shanghai. The changeling virus then likely amplified in poultry flocks.
Virologists worried about the spread of H7N9 because there’d been no glimmer of disease in the poultry themselves. Human cases of H5N1 were accompanied by concomitant outbreaks in domesticated flocks, providing a crude sort of advance warning. There’d been no such warning for H7N9. Because infected birds didn’t get sick, the infections in people appeared as if out of nowhere. The virus seemed to have the capacity to spread silently, without manifesting in disease, in people, too. One study found that more than 6 percent of poultry workers harbored antibodies to H7N9, despite having no history of suffering an infection.
In the fall, a second wave of human infections began, this time over a much wider region, including southern China as well as eastern China. Since most of the people who caught the virus had been exposed to live poultry, it’s likely that birds were the stealthy culprits behind its spread. By February 2015, H7N9 had infected more than six hundred people.
Like H5N1 and H3N2, it has not achieved the easy transmissibility among people that would make it a candidate for a pandemic—yet. Whether one of these novel viruses, or any of the other ones that continue to emerge from our supersize poultry and pig farms, will end up with the right genetic combination to do that remains to be seen.68