Is This a Pandemic Being Born?

Here’s how it would happen. Children playing along an urban river bank would spot hundreds of grotesque, bloated pig carcasses bobbing downstream. Hundreds of miles away, angry citizens would protest the rising stench from piles of dead ducks and swans, their rotting bodies collecting by the thousands along river banks. And three unrelated individuals would stagger into three different hospitals, gasping for air. Two would quickly die of severe pneumonia and the third would lay in critical condition in an intensive care unit for many days. Government officials would announce that a previously unknown virus had sickened three people, at least, and killed two of them. And while the world was left to wonder how the pigs, ducks, swans, and people might be connected, the World Health Organization would release deliberately terse statements, offering little insight.

It reads like a movie plot — I should know, as I was a consultant for Steven Soderbergh’s Contagion. But the facts delineated are all true, and have transpired over the last six weeks in China. The events could, indeed, be unrelated, and the new virus, a form of influenza denoted as H7N9, may have already run its course, infecting just three people and killing two.

Or this could be how pandemics begin.

On March 10, residents of China’s powerhouse metropolis, Shanghai, noticed some dead pigs floating among garbage flotsam in the city’s Huangpu River. The vile carcasses appeared in Shanghai’s most important tributary of the mighty Yangtze, a 71-mile river that is edged by the Bund, the city’s main tourist area, and serves as the primary source of drinking water and ferry travel for the 23 million residents of the metropolis and its millions of visitors. The vision of a few dead pigs on the surface of the Huangpu was every bit as jarring for local Chinese as porcine carcasses would be for French strolling the Seine, Londoners along the Thames, or New Yorkers looking from the Brooklyn Bridge down on the East River.

And the nightmarish sight soon worsened, with more than 900 animal bodies found by sunset on that Sunday evening. The first few pig carcass numbers soon swelled into the thousands, turning Shanghai spring into a horror show that by March 20 would total more than 15,000 dead animals. The river zigzags its way from Zhejiang province, just to the south of Shanghai, a farming region inhabited by some 54 million people, and a major pork-raising district of China. Due to scandals over recent years in the pork industry, including substitution of rendered pig intestines for a toxic chemical, sold as heparin blood thinner that proved lethal to American cardiac patients, Chinese authorities had put identity tags on pigs’ ears. The pig carcasses were swiftly traced back to key farms in Zhejiang, and terrified farmers admitted that they had dumped the dead animals into the Huangpu.

Few Chinese asked, "What killed the pigs?," because river pollution is so heinous across China that today people simply assume manufacturing chemicals or pesticides fill the nation’s waterways, and are responsible for all such mysterious animals demises. The Yangtze, which feeds Shanghai’s Huangpu, has copper pollution levels that are 100 times higher than U.S. safety standards, and leather tanning facilities along the river have notoriously been responsible for toxic waste, including chromium. And across China — especially in Beijing — air pollution was so bad in January and February that pollution particulate levels routinely peaked at higher than 10 times the U.S. safety standards set by the Environmental Protection Agency. When I was in Beijing in late January, the air pollution was so thick that it visually looked like fog, obscuring all sunlight and even skyscrapers located less than three city blocks away. So, hideous as the pig carcasses might be, Shanghai residents tended to shrug them off as yet another example of the trade-offs China is making, pitting prosperity against pollution.

But 12 days after the first Shanghai porcine death flow was spotted, pig carcasses washed up along the shores of Changsha’s primary river, the Xiang — also a Yangtze tributary, this one located hundreds of miles west of Shanghai. Known as "the Sky City" for its 2,749-foot-tall central tower, Changsha is home to more than 7 million people and capital of Hunan province. Along with some 50 dead pigs, authorities collected a few thousand dead ducks from the Xiang on March 22 and 23.

Two days later, another mass duck and swan die-off was spotted, this time along the Sichuan River hundreds of miles to the north, near Lake Qinghai. The lake is the most important transit and nesting site for migratory aquatic birds that travel the vast Asia flyway, stretching from central Siberia to southern Indonesia. In 2005, a mass die-off of aquatic birds in and around Lake Qinghai resulted from a mutational change in the long-circulating bird flu virus, H5N1 — a genetic shift that gave that virus a far larger species range, allowing H5N1 to spread for the first time across Russia, Ukraine and into Europe, the Middle East and North Africa — it has remained in circulation across the vast expanse of Earth for the last seven years.

On March 25, Chinese authorities seized manufactured pork buns that were found to be made from Zhejiang pigs that had died of the mysterious ailment. The possibly contaminated pork was in the Chinese food supply. By the end of March, at least 20,000 pig carcasses and tens of thousands of ducks and swans had washed upon riverbanks that stretch from the Lake Qinghai area all the way to the East China Sea — a distance roughly equivalent to the span between Miami and Boston. Nobody knows how many more thousands of birds and pigs have died, but gone uncounted as farmers buried or burned the carcasses to avoid reprimands from authorities.

While environmental clean-up and agricultural authorities scrambled to remove the unsightly corpses and provide the anxious public with less-than-believable explanations for their demise, a seemingly separate human drama was unfolding. On Feb. 19, a man identified by Xinhua, China’s state news agency, only as Li, an 87-year old retiree, was hospitalized in Shanghai with severe respiratory distress and pneumonia. On March 4, Li went into severe cardio-respiratory failure and succumbed.

On Feb. 27, a man identified only as Wu, a 27-year-old butcher or meat processor, fell ill with respiratory distress, was hospitalized, and died on March 10. The day Wu succumbed a third individual, a 35-year-old woman identified as Han, was hospitalized in the city of Nanjing, though she came from distant Chuzhou City, in Anhui province, about 300 miles northwest of Shanghai. Han is reportedly in critical condition, in intensive care. To date, no connection between the three individuals has been found.

The elderly Li may have been part of a family cluster of illness, as his 55-year old son died of pneumonia in March, and another 67-year-old son suffered respiratory distress, but has survived.

On March 31 — Easter in the United States — China’s newly created National Health and Family Planning Commission (which includes the former Ministry of Health) announced that 87-year-old Li, Wu, and Han all were infected with a form of influenza denoted as H7N9 — a type of flu never previously known to infect human beings. The commission insisted that Li’s two sons (one dead, the other a survivor) were not infected with the flu virus — their ailments were reportedly coincidental, though they occurred at the same time as the elder Li’s demise.

So much for the backstory: What is going on?

According to Chinese authorities, some of the dead pigs tested antibody-positive for circoviruses, or PCV-2, and samples of the virus were isolated from Huangpu River. The implication was that the Shanghai pigs died of PCV-2, a type of virus that is harmless to human beings, as well as birds. Photographs of the carcasses reveal that the animals were large adult hogs, but PCV-2 does not kill adult pigs — it is lethal to fetuses and newborn piglets.

The Chinese health authorities have to date offered no cause of death for the ducks and swans, failed to describe any unusual genetic features that might have turned the PCV-2 into an adult pig-killer virus, and insisted there is no connection between the pigs, people, and birds. Though the surviving woman, Han, had some contact with live chickens, according to Xinhua, neither Li nor Wu had any known contact with birds. Wu has been identified variously as a butcher, meat processor, and employee of a meat plant — all of which might imply he had contact with pigs.

Influenzas are named according to the specific nature of two proteins found on the virus — the H stands for hemaggluntinin and the N for neuraminidase. These proteins play various roles in the flu-infection process, including latching onto receptors on the outside of the cells of animals to transmit the virus into their bodies. Those receptors can vary widely from one species to another, which is why most types of influenza viruses spreading now around the world are harmless to human beings. As far as any scientists know, the H7N9 forms of flu have never previously managed to infect human beings, or any mammals — it is a class of the virus found exclusively in birds. It is therefore extremely worrying to find two people killed and one barely surviving due to H7N9 infection.

One very plausible explanation for this chain of Chinese events is that the H7N9 virus has undergone a mutation — perhaps among spring migrating birds around Lake Qinghai. The mutation rendered the virus lethal for domestic ducks and swans. Because many Chinese farmers raise both pigs and ducks, the animals can share water supplies and be in fighting proximity over food — the spread of flu from ducks to pigs, transforming avian flu into swine flu, has occurred many times. Once influenza adapts to pig cells, it is often possible for the virus to take human-transmissible form. That’s precisely what happened in 2009 with the H1N1 swine flu, which spread around the world in a massive, but thankfully not terribly virulent, pandemic.

If the pigs, people, and birds have died in China from H7N9, it is imperative and urgent that the biological connection be made, and extensive research be done to determine how widespread human infection may be. Shanghai health authorities have tested dozens of people known to have been in contact with Wu and Li, none of whom have come up positive for H7N9 infection. Assuming the tests are accurate, the mystery of Li and Wu’s infections only deepens. Moreover, if they are a "two of three," meaning two dead, of three known cases, the H7N9 virus is very virulent.

"At this point, these three are isolated cases with no evidence of human-to-human transmission", the WHO representative in China, Dr. Michael O’Leary, told reporters on Monday. But, O’Leary added, the possibility of a family cluster of illness could not be ruled out, and, "We don’t know yet the causes of illness in the two sons, but naturally, if three people in one family acquire severe pneumonia in a short period of time, it raises a lot of concern."

But Hong Kong authorities, smarting from years of outbreaks spread from mainland China including H5N1 (1997) and SARS (2003), have put the territory on health alert. "We will heighten our vigilance and continue to maintain stringent port health measures in connection with this development," the Centre for Health Protection in Hong Kong stated in a press release on Monday.

The Chinese National Influenza Center has posted the H7N9 genetic sequences of viruses from Li, Wu, and Han on the WHO flu site. A number of H7N9 sequences found in birds over the last few years are also posted: The human and bird strains do not match, though none of the birds strains were obtained from animals in 2013.

The mystery is deep, the clock is ticking, and the world wants answers.

If we were imagining how a terrible pandemic would unfold, this could certainly serve as an excellent script.

Timeline of Events