Is China covering up another flu pandemic -- or getting it right this time?
- By Laurie GarrettLaurie Garrett is senior fellow for global health at the Council on Foreign Relations and a Pulitzer Prize winning science writer.
We are at a mysterious fork in the road. One path leads to years, perhaps decades, of spread of a new type of influenza, occasionally making people sick and killing about 18 percent of them. It’s not a pleasant route, strewn as it is with uncertainties, but no terror seems to lurk on its horizon. The other path, however, wrenches the gut with fear, as it brings worldwide transmission of a dangerous new form of flu that could spread unchecked throughout humanity, testing global solidarity, vaccine production, hospital systems and humanity’s most basic family and community instincts.
There may be some minor footpaths along the way, heading to other alternatives, but they can’t be discerned at this moment. At this writing, 108 cases of H7N9 flu, as the new virus has been dubbed, have been confirmed, and one asymptomatic carrier of the virus has been identified. Twenty-two of the cases have proven fatal, and nine people have been cured of the new flu. The remainder are still hospitalized, many in severe condition suffering multiple organ failures. As the flu czar of the World Health Organization (WHO), Dr. Keiji Fukuda, tersely put it to reporters last week, "Anything can happen. We just don’t know."
On this tenth anniversary of China’s April 2003 admission that the SARS virus had spread across that country — under cloak of official secrecy, spawning a pandemic of a previously unknown, often lethal disease — Beijing finds itself once again in a terrible position via-a-vis the microbial and geopolitical worlds. In both the SARS and current H7N9 influenza cases, China watched the microbe’s historic path unfold during a period of enormous political change. And the politics got in the way of appropriate threat assessment.
On Nov. 16, 2002, the first human case of SARS staggered in search of a doctor the very day that top Communist Party leaders were meeting behind closed doors, naming Hu Jintao and Wen Jiabao the new leaders of the world’s most populous country. Determined to experience China’s first peaceful transition of power in living memory, without public strife between political factions, the party leaders vowed that nothing could rock the ship of state until March of 2003, when the National People’s Party Congress would convene and officially anoint Hu and Wen. In the meantime, "stability" was the nervous watchword. President Jiang Zemin and his close Shanghai allies were jockeying to maintain control of key assets, including the military, while Hu and his backers hoped to squash the Shanghai billionaire bloc that they felt had amassed too much wealth and power.
Fang Lin, a country bumpkin who had made his way to the Shenzhen metropolis near Hong Kong and found work in a restaurant that served exotic animal meats, was the first November SARS victim. By December 2002 that first case of a new, mysterious respiratory disease had expanded into a full-fledged epidemic in Guangdong province, and Dr. Zhong Nanshan and his colleagues at the Guangzhou Institute of Respiratory Diseases were overwhelmed. Amid health-care worker panic and great mystery regarding the cause of the outbreak, Zhong led a valiant clinical effort that was largely unknown to the outside world, even nearby Hong Kong. Indeed, Guangdong provincial and party authorities and their Guangzhou municipal counterparts did not even officially notify Beijing of their outbreak until Feb. 8, 2003, after it was winding down. One of the Guangzhou patients fled the province on Feb. 21, checked into the Hotel Metropole in Hong Kong’s Kowloon district, and passed his virus onto a cluster of travelers staying on the same hotel floor. Those individuals, unknowingly infected, went on to spawn outbreaks in Hanoi, Singapore, Toronto, Hong Kong, China’s Shanxi Province, and from there to Beijing.
Even as the WHO and health departments around the world struggled over the next five weeks to understand and control the new pandemic, the transitional government in Beijing was mum, denying any claims that SARS was of Chinese origin and that it lurked around the country, including in its capital. After retired People’s Liberation Army surgeon Jiang Yanyong courageously leaked information to Western reporters about dying patients in a Beijing hospital, the fresh Hu/Wen regime, newly ratified by the People’s Party Congress, secretly on April 17 decided to publicly attack the epidemic. Three days later the nation’s minister of health — a Jiang ally — and Hu’s colleague, the mayor of Beijing, were unceremoniously sacked, placing shared blame on both factions of the Communist Party. The government publicly acknowledged the epidemic, and the People’s Republic set course on an all-out war against SARS.
I covered the SARS epidemic in Hong Kong and throughout mainland China, and there are more than a few aspects of the current H7N9 situation that provoke feelings of déjà vu. As was the case in 2003, Beijing now has new leaders, President Xi Jinping and Premier Li Keqiang, who assumed office on March 14, 2013. As was the case with SARS in 2003, information regarding the new H7N9 flu did not start to flow publicly until after safe installation of the new leadership. And during the months between the Communist Party’s closed meetings that selected Xi and Li and March 14th, the country was rocked by scandals, including murder and billions of dollars’ worth of financial shenanigans, pitting one Communist Party faction against another. Both the SARS and H7N9 outbreaks unfolded in atmospheres of political intrigue and secrecy.
Today, with the future path of the new influenza still uncertain, Beijing faces conundrums similar to those it confronted after publicly admitting to SARS. May Day, one of China’s biggest travel holidays, is approaching. Travel restrictions might be warranted to prevent nationwide spread if the virus is now thought to be geographically confined, and if further evidence shows that people can act as carriers and transmitters of H7N9. But the economic and geopolitical consequences of clamping down on social mobility are profound, particularly now that China’s economic growth is slowing.
In 2003, Beijing warned the public to limit travel, but did not actually barricade the capital and set up health checkpoints in all of the nation’s train, bus, shipping, and air travel stations until it was too late. I watched tens of thousands of fearful migrant workers and students — impelled by rumors of forced quarantines targeting those without permanent Beijing residency papers — flee the capital by trains over the days between the April 20 admission and May Day holiday, taking the SARS virus to every region of the country. Having lost control of geographic spread, China had no choice but to assume the entire country was infected, and create an extraordinarily expensive, nationwide response. I witnessed construction of Xiaotangshan SARS Hospital, a 1,500-bed quarantine facility erected in only eight days, complete with isolation rooms, dedicated sewer and water filtration systems, negative air pressure flow, and state-of-the-art nursing stations. That astounding feat was repeated all over the country, with quarantine hospitals built in five to 10 days in every region. As I traveled around China by car, I was stopped roughly every 50 miles by police and subjected to thermometer checks. Any individual anywhere in the country that evidenced a fever was immediately placed in one of the newly erected quarantine facilities, and would remain there indefinitely — no visitors allowed. In Beijing, such fever stations were ubiquitous: Anybody with an abnormal temperature was immediately packed off to a military-run quarantine site or Ditan Hospital for Infectious Diseases, where even the doctors and nurses were on lockdown, forbidden to see their families for weeks. Knowing that the virus was spreading inside of hospitals, terrified physicians and nurses jumped out of
windows and patients hid in their homes until May 15, when the central government declared it a high crime, punishable even by death, to hide or spread SARS cases.
That is how by July 5, 2003, China stopped SARS — with a nationwide find-the-fever campaign that could not possibly be executed in a country that places civil liberties above the rights of the state. I have often thought about the fever stations I encountered in the mountains of Shanxi, where coal truck drivers were compelled to submit to fever checks while people in bio-containment space suits sprayed antimicrobials all over their vehicles’ cabs. I’ve tried to imagine such fever stations positioned along America’s superhighways: Visions of angry drivers pulling shotguns on public health nurses and highway patrol officers always dance thru my head. Few countries could today manage a nationwide fever/quarantine campaign akin to China’s SARS effort.
Indeed, I’m not sure the China of 2013 could pull off the feat it executed in 2003. Thanks to Weibo, China’s equivalent of Twitter, and dozens of other Internet-posting possibilities, very little about this flu outbreak has remained secret for long. Any perceived violation of patients’ rights or individual dignity is getting a virtual shout-out. And though President Xi and top health officials have already noted that travel over May Day might be unwise, and Hong Kong has signaled anxiety about the pending tsunami of mainland visitors, possibly bringing H7N9 their way, it seems unimaginable that today’s government could close the perimeter of any major city, let alone Shanghai, the epicenter of H7N9, with population of some 23 million people.
The path not taken?
Staring down that fork in the H7N9 road, Beijing’s options are limited to waiting, watching and hoping that the path the new virus takes more closely resembles the route of H5N1 ("bird flu"), with the microbe circulating in birds for decades, occasionally causing terrible illness (though usually death) in isolated human victims, but never erupting into a full-fledged human epidemic. The other path — what might more closely mirror the 2009 H1N1 "swine flu" pandemic — is almost too terrible to think about.
In 2008, a type of influenza that had circulated in pigs for decades underwent some key mutations as it passed through commercial hog farms in the American Midwest. A few isolated cases of nonfatal human infection turned up, among pig farmers and kids that visited county fairs in the United States. Late in 2008, more medically ominous, yet still isolated, cases turned up in children in Texas and California, offering hints that the new form of H1N1 could spread from person to person (rather than pig to person). Dutifully reported by health officials, the cases were logged by the Centers for Disease Control (CDC). But it wasn’t until the virus jumped the border into Mexico, probably via infected travelers or farmworkers, that the global swine flu pandemic was born in March 2009. And BOOM, it spread around the world with breathtaking speed, despite every kind of control measure officials in given countries could dream up — including grounded flights from Mexico, forced quarantine, and school closures. No vaccines were available for more than six months, and the world’s richest countries bought rights to all supplies manufactured before 2010. Most of the population of the planet never received an H1N1 vaccine, and the lions’ share that did get immunized had already been exposed to the pandemic, or even toughed out the flu.
So that H1N1-like path in this forked flu road is frightening because the world’s capacity to respond to a true pandemic hasn’t really improved since 2009/10. In China, many of the find-fever-and-quarantine policies of SARS were executed against H1N1 patients, but proved ineffective, as that flu was far more contagious than the SARS coronavirus. But Beijing had clearly learned lessons from SARS: Within hours after the WHO declared H1N1 a pandemic, Premier Wen held a high-level meeting devoted to influenza control, and just two days later an unprecedented disease-focused Politburo meeting on H1N1 was chaired by President Hu.
What spared the world catastrophe during that swine flu outbreak was the relative weakness of the virus; many human populations experienced it as no more virulent, even less so, than normal seasonal flu. Biologically, the H1N1 experience showed that an animal influenza can adapt to humans, mutating to be able to latch onto receptors in our lungs, but fail to carry the genetic firepower to sicken and slay most of its Homo sapiens victims. That’s the hopeful news. But politically, the take-home message from H1N1 swine flu was more foreboding: Solidarity between countries and economic powers, corporations, even many health authorities will yield in a pandemic to nationalism, company and private interests, and jockeying for power, profit and influence.
The H7N9 flu now evolving before Humanity’s eyes in China has killed 18 percent of the 108 people with lab-confirmed infections as of April 22. That’s a lethality about nine times the mortality rate of the Great Influenza of 1918-19, which claimed at least 50 million lives by lowball estimate, and up to 100 million based on extrapolation from colonial-era records in India and African countries. (There is no consensus regarding how many people perished in China in 1918.) More worrying, only about 9 percent of the confirmed H7N9 cases in China have walked out of hospital, cured of their infections; one has been asymptomatic; and the remainder are still hospitalized, many suffering multiple organ failure and illnesses from which they are unlikely to recover.
Reflecting on his experiences with SARS in the April 16 South China Morning Post, Zhong, the Guangdong doctor, said of H7N9 flu, "It’s too early to rule out the possibility of human-to-human transmission. We think the virus is still adapting, so such a possibility exists. SARS was not as transmittable in its early stages but it evolved and got stronger. We can only say that based on the evidence so far, no human-to-human transmission has been detected. But that does not mean it is not possible."
In a 2011 paper published in Health Affairs, the head of China’s CDC, Zijian Feng, warned that despite "tremendous progress" in his country in the post-SARS era, "To advance the detection and control of emerging infectious diseases, China must now invest far more in pathogen-based surveillance. An enhanced disease-detection system in China will help prevent and contain outbreaks before they cause substantial illness and death in China and other countries." In other words, improvements had been made, but a genuine early-warning system to detect outbreaks and prevent epidemics wasn’t yet realized.
In the weeks since H7N9 was first publicly reported in China, Zijian Feng and his CDC colleagues have struggled with disease detection and surveillance, evidencing genuine difficulty in identifying pieces of the flu puzzles that are key to assessing its threat to human beings. For example, until April 17 the agency repeatedly stated that there was no evidence for transmission of the virus between human beings. People, the Chinese CDC insisted, were getting H7N9 somehow from birds. But on April 17 the agency admitted that at least three clusters of human-to-human transmission had likely occurred, including the first known cases of the virus in Shanghai. The CDC’s Zheng Guang then said, "people infected with H7N9 can transmit virus…they could possibly infect others." Worried about the public response to that news, Zheng hastily added, "People don’t need to panic, because such limited human-to-human transmission won’t pr
ompt a pandemic."
Most troubling, Zheng added, "Forty percent of the patients had no contact with poultry or environments where birds were located," and most of those categorized as "having contact" merely bought or ate poultry in exactly the manner that tens of millions of Chinese do daily.
More than 88,000 birds, both wild and domestic, have been tested in China for the H7N9 infection: 39, at this writing, have tested positive. None of the birds has been ill. If this is a bird virus, it is unlike any avian influenza seen before.
In contrast, the H5N1 avian flu whipped through poultry populations like a conflagration, spreading and killing up to 100 percent of exposed animals within days. In 2008, I visited farms in Bangladesh that had been hit by the virus, hearing tales of overnight obliteration of flocks. One farmer led me to his computer, weeping as he shared photos of his suffering chickens, their coxcombs and feet purple with hemorrhage, heads bowed, feathers molting. That bird flu is so contagious that farmworkers can unintentionally infect entire commercial flocks merely by carrying the virus on the soles of their shoes, from one contaminated poultry center to a virus-free one. H5N1 is a real avian flu — spectacularly infectious and deadly as it spreads among birds.
In nature, H5N1 viruses carry a set of gene mutations that render them fully adapted for bird-to-bird spread, and, conversely, ill-suited to spreading to or among humans. In 2004, University of Iowa team tested duck hunters in the United States for evidence of bird-flu infection. At the time, an epidemic of another type of avian flu was circulating in mallard ducks — no hunters had illness, and only three showed hints of exposure in their blood. A National Institute of Hygiene and Epidemiology in Vietnam survey of people infected with H5N1 found that few worked in the poultry industry. Most were peasant families that slaughtered and consumed a chicken that had been sick — the direct blood exposure presumably involved a very high dose of H5N1 viruses. When an individual in Guangzhou, China, came down with H5N1, local health officials rounded up birds from the patient’s live animal market and tested all the market workers: While about 10 percent of the birds were sick with the virus, only 1 out of 110 humans working in the market had any blood evidence (in the form of antibodies) of exposure to H5N1. In 2005/6, when H5N1 was epidemic in birds in Thailand, health officials tested hundreds of hospitalized respiratory disease patients for the virus; none was infected. Similarly, Cambodian health officials tested more than 300 villagers for H5N1 when an epidemic spread among their poultry, killed 60 percent of the birds and one man; none of the people, other than the deceased farmer, was infected. Italy’s Istituto Zooprofilattico Sperimentale delle Venezie reviewed all practices used to stop spread of H5N1 within poultry flocks, concluding that in the absence of an effective vaccine there were few means to stop the virus from spreading like wildfire — among the birds.
Overall, the evidence from H5N1 is that a true avian flu is brutally contagious and deadly to vulnerable bird species, but rarely infectious to, or between, mammals. Isolated H5N1 cases have been found in dogs and felines (including domestic cats and tigers) that attack or eat infected birds. Some Indonesian studies have found isolated H5N1-infected pigs. And since 1997, 640 people have been diagnosed with H5N1 disease in 15 countries, 377 of whom have died. There is significant dispute regarding how many additional people may have suffered mild or asymptomatic H5N1 infections, but most flu experts agree that H5N1 is among the deadliest viruses on Earth today, killing roughing 60 percent of humans it infects.
In contrast, the new H7N9 virus is officially designated by the U.N.’s Food and Agriculture Organization LPAI, or "low pathogenicity avian influenza" because it causes no apparent life-threatening disease in birds. The new Chinese virus seems to have transitioned from avian flu to something else: an infection of minor consequence to birds, but often lethal for human beings.
1985, researchers showed that two key mutations in bird flu viruses occurring simultaneously could switch them to forms capable of spreading among mammals. When H5N1 appeared in Hong Kong in 1997, local flu experts took some comfort in discovery that the virus had not made those mutational changes, so spread among people was unlikely. And since that time the WHO has nervously monitored strains of the virus emerging worldwide, looking for evidence that these mutations had been made. Thankfully, they have not. But in 2012, two labs working independently — one in the Netherlands, the other in the United States — controversially deliberately made those mutations in H5N1 under controlled conditions, confirming that a bird virus with those gene switches could spread from one ferret to another, through the air coughed between them.
The H7N9 virus now circulating in China has those mutations. As Ron Fouchier, the Dutch researcher who did the ferret experiment told me, "This virus really doesn’t look like a bird virus anymore; it looks like a mammalian one."
Whence came this new flu?
Usually, an influenza that newly jumps from birds to pigs, or people, emerges in rural settings, spreading among farm chickens or ducks. And typically the first human cases are village children that frolic among family fowl. When scientists isolate the new virus from such infected individuals, it’s usually a clear recombination of two or three old flu strains — a sort of genetic swap that resulted in a mosaic of bits from other viruses. The most important mosaic pieces are those for the H (hemaggluntinin) and N (neuraminidase), the proteins influenza uses to infect target animals, and spread inside their bodies. Virologists designate flu viruses according to their H and N types, but the crucial mutations that determine whether or not a virus can spread among people can only occur in certain types of Hs and Ns.
Or so we thought. H7N9 was supposed to be one of the exclusively bird forms of flu, unable to spread to mammals. That has, of course, proven wrong.
According to the WHO’s Chinese Influenza Center, the new H7N9 is a recombinant of a type of influenza (H2N9) that has been spreading for a few years among wild aquatic birds in South Korea and China, an H7N3 found in wild Chinese ducks in 2011, and an H9N2 identified last year in Chinese brambling birds. The new virus is, therefore, a triple recombination.
When these three influenzas blended, the two "mammalian" mutations somehow occurred. One, dubbed ingloriously E627K, changed the virus’s temperature tolerance from 40 degrees Celsius — the normal temperature of a bird body — to 33 C, typical human body heat. The other mutation, Q226L, switched the virus’s hemaggluntinin protein from a form that latches onto a bird’s respiratory tract, which is rich in sialic acids, to a type that locks onto galactose-rich receptors found in the throats and lungs of human beings. (These are the same mutations that Fouchier and a separate lab led by Yoshiro Kawaoka at University of Wisconsin inserted into the H5N1 virus, transforming it into a mammal-to-mammal spreader.)
There is a missing link. For the new virus to have acquired these key mutations, it must be infecting a mammalian species of some kind, besides human beings. It had to have picked up those mutations inside a mammalian host. But to date no infected pigs or other mammals have been found, according to the Chinese CDC.
This is a mystery. And here is
another: Nearly all known bird-to-human flu jumps have occurred in rural settings, unfolding on and around farms. But not this H7N9: This may well be the first truly urban influenza in history. No infected rural flocks or farmers have been found in China. This outbreak started in one of the most modern, densely populated metropolises in the world: Shanghai.
The SARS pandemic of 2003 had its first index case – a term epidemiologists use to define the starting point of an outbreak — Fang Lin, identified Nov. 16, 2002. From his isolated illness grew the outbreak that five weeks later raged across Guangdong province. This H7N9 outbreak may have four index cases in Shanghai — three of them, members of the same Li family. In the Li household lived three men, a father aged 87 and his two sons, aged 55 and 69. On Feb. 14, the elder Li went to Shanghai’s Hospital No. 5, suffering breathing difficulty. He was examined, and sent home. Ten days later the elder returned to the hospital, suffering from pneumonia, and was admitted.
Two days later, on Feb. 27, the local hospital admitted 55-year old Li and its emergency room treated a 27-year-old butcher suffering "flu" who had no connection to the Li family. Recognizing it had two family members with pneumonia, the hospital notified the Shanghai CDC. Over the next four days, the third Li family member and the young butcher were all admitted to Hospital No. 5, now suffering Acute Respiratory Distress Syndrome (ARDS).
There was considerable concern that the Li family had SARS, or perhaps the new SARS-like coronavirus that was discovered in late 2012 in Saudi Arabia. ARDS is the key symptom of SARS, and is its usual cause of death. The local CDC used a SARS test that came up negative, but only the Beijing CDC could execute lab work for the novel Saudi coronavirus; the Shanghai CDC would not send samples to Beijing, however, until March 20. This delay would prove damaging, and hard to understand.
Hospital workers all over China fretfully recall the rapid spread of SARS within medical facilities in 2003, and the high death toll the virus took among doctors and nurses. As the condition of the Li family worsened, health-care workers in Hospital No. 5 demanded protective gear, such as N95 masks, to keep them from acquiring the unknown disease. They were rebuffed.
Meanwhile, events were unfolding that were rattling national nerves. Air-pollution levels in the Chinese capital and about 10 percent of the nation exceeded U.S. Environmental Protection Agency’s maximum allowable standards nearly 40-fold; thousands of pig carcasses floated down Shanghai’s central Huangpu River; thousands more dead ducks, carefully wrapped in bags, floated on other rivers; numerous chemical pollution incidents sent Weibo users into frenzies. The national atmosphere was agitated, but official government reaction was mute, amid China’s high-level government transition.
On March 4, the elder Li died of the mysterious disease.
The following day, March 5, the National People’s Party Congress convened in Beijing, officially anointing Xi Jinping and Li Keqiang as president and premier of China. The do-not-rock-the-boat period was finally at its end.
And on March 6, someone posted on Weibo, "Ask the hospital to tell the truth." The anonymous posting went on to detail that a Shanghai family shared a terrible flu, and a 27-year-old man with similar symptoms had recently checked in. The Weibo user appeared to be a Hospital No. 5 employee, as he or she noted the lack of protective gear for doctors and nurses and expressed personal fear.
Over the next 24 hours the conditions of 55-year-old Li and the young butcher dramatically worsened. Both would soon succumb. When the butcher’s family got a Hospital No. 5 bill for 100,000 RMBs — roughly $12,500 — for their son’s failed treatment, cries of outrage surfaced on Weibo and a Shanghai municipal blog site. One blogger who goes by the moniker "Fisherman" indignantly commented on the payments demanded of the butcher’s family, and noted that none of the remaining patients was under quarantine. Doctors and nurses are "terrified," blogger Fisherman wrote, as no protective gear has been provided. The Shanghai CDC and administration of Hospital No. 5 posted their own reactive accounts on Weibo the following day, essentially confirming the four mysterious cases, but ignoring complaints over the costs of care and staff safety.
Yet no national alarm bell was rung: Beijing CDC had yet to learn of the unfolding mess in Shanghai. And when a 35-year-old housewife was admitted to a hospital in Anhui Province, suffering identical symptoms, doctors there had no idea what was transpiring 300 hundred miles away in Shanghai.
By March 20, the Shanghai CDC had exhausted its battery of clinical and laboratory tests. Samples from the Li family and the young butcher tested positive for influenza A, but negative for the dreaded H5N1. Unable to figure out what kind of flu virus might be responsible, samples were forwarded to the WHO Influenza Collaborating Center in Beijing, part of the national CDC. After ruling out SARS and the novel Saudi virus, for several days the Beijing lab struggled to identify the influenza, never imagining it could be a H7N9 subtype — humans had never faced such a strain, and no standard H7N9 lab test existed.
On March 30, the Chinese scientists extracted and identified H7N9 in three patient samples. As Westerners celebrated Easter the official Chinese news service, Xinhua, on March 31, announced:
"Avian influenza has been detected recently in humans in Shanghai and Anhui Province, and two of them have died, the other being in a critical condition, the National Health and Family Planning Commission said. The victims include an 87-year-old male in Shanghai who got sick on 19 Feb 2013 and died on 4 Mar 2013, a 27-year-old male in Shanghai who became ill on 27 Feb 2013 and died on 10 Mar 2013 and a 35-year-old female in Chuzhou City, Anhui province who became ill on 9 Mar 2013 and is now in a critical condition."
According to the Xinhua release, 88 close contacts of the three dead had been scrutinized, and all were well. But that wasn’t exactly true. One Li family member was still in Hospital No. 5, battling pneumonia.
For several days, Chinese health authorities insisted "so far it is still a bird virus, not a human virus," and no human-to-human transmission had transpired. But on March 31, the WHO’s Beijing representative Mike O’Leary insisted, "if three people in one family acquire severe pneumonia at the same time, it raises concern" that spread between people has occurred.
By April 2, the official case toll had reached seven, spread across three provinces along the Yangtze River, and the search was on for the virus’s host. The total number of infections now stands at 109, and cases have been confirmed as far north as Beijing, and south 800 miles to Zhejiang, in cities with a combined population of more than 70 million people.
Which path will H7N9 take?
Much about this virus remains too strange to permit easy prediction. Markets are jittery, especially in Hong Kong and Shanghai. Airline, chicken and hotel stocks are down, and China’s commercial poultry industry has lost some $3 billion since April 1. Financial forecasters feel nervous.
The absence of a genuine epidemic in birds — less than 0.005 percent have tested positive for infection — means this is no longer an avian flu, if it ever was. The host species for H7N9 has yet to be identified. Whatever animal harbors the virus, it must be an urban-adapted creature, and ubiquitous from China’s nearly tropical south to its wintry north. And because of the presence of those two crucuial "mammalian" mutations, it must have an internal ecology permissive to mammal-infectious forms of flu — which would seem to exclude birds, insects, amphibians — all but mammals.
A few infected — but not ailing — birds have been found in Chinese markets, implying that the mysterious host can pass its influenza onto birds, and that it inhabits marketplaces. The University of Wisconsin in 2006 did its now classic "Trojan Chicken Study," sprinkling a powder visible only with UV light on one chicken at a county fair and watching the powder — a surrogate for flu viruses — spread over four days from the feet of that Trojan. In the end, the UV light revealed that 8.5 percent of the people working around the fair had the Trojan Chicken’s surrogate virus on their hands. The study revealed that direct physical contact by one species to another (in this case, chicken-to-human) isn’t necessary to spread virus. The "infected" chicken feet could just as well have been mouse paws, cow hoofs, or pig snouts.
The age distribution of H7N9 human cases is striking — quite unlike any other flu outbreak. Flu generally infects males and females equally, but H7N9 has struck twice as many males as females. (In the over-60 age group, three times as many males, versus females, have been infected.) Bird flus tend to afflict children in large numbers because the youngsters play among ducks and chickens. More than 80 percent of confirmed H5N1 cases, for example, have been in youngsters under 17 years of age. But very few kids have come down with H7N9, and by far the majority of cases have been in adults over 60 years of age. It is unlikely this is due to a unique vulnerability in the bodies of over-60 males. Rather, this may be another clue to the identity of the mysterious viral host — behaviorally, elderly Chinese urban men are engaged in some activity that puts them at greater contact with the unknown carrier creature.
A few infected pigeons have been found, but Chinese cities are not havens for flocks of plaza-hounding pigeons, as is the case in Paris, Rome, or New York. Because pigeon meat is prized in China, most such birds are caged and sold for food; only one infected wild pigeon has been discovered to date. Chinese agricultural officials have tested pigs, some of the floating hog carcasses, and fresh pork — all reportedly were negative for the virus. No information regarding other urban denizens, such as rats, cats, and mice, has been provided.
Two weeks ago, Weibo users in Nanjing posted gruesome photos of sidewalks strewn with dead swallows that had bizarrely "fallen out of the sky," as one micro-blogger put it. Officials insisted that whatever killed those swallows, it wasn’t H7N9. On April 21, the Vietnamese government put Long An Province on special alert after more than 5,000 swallows similarly dropped dead out of the sky, and tested positive for the other bird flu, H5N1. Chinese officials have not indicated whether those Nanjing swallows had H5N1. It would be ominous if the H5N1 and H7N9 viruses were co-circulating in China, as it would both confuse the investigation and present the possibility of yet another deadly recombination of the influenzas. On April 22, German agricultural officials announced that H5N1 had broken out among turkeys in that country, prompting Hong Kong to place an immediate ban on all importation of poultry products from Germany.
It’s not yet clear what the incubation time is for this virus, which makes tracking the host all the more difficult. Investigators have been monitoring hundreds of individuals known to have had contact of some kind with identified flu patients, and three possible clusters of human-to-human transmission — including the Li family in Shanghai — are now subjects of special scrutiny. But triangulating people and a mysterious host is tough when the time lag between exposure and first symptoms is unknown.
To date, only one asymptomatic human carrier — a 4-year-old child in Beijing — has been found, and just a handful of patients have had mild flu disease. Nine of the 108 identified cases have been cured — 99 have either died or still suffer some influenza. These startling clinical numbers point to a very dangerous, lethal virus — but one that is still hard for people to get, or to spread to other people.
So a forecaster might reasonably conclude that H7N9 is likely to follow a H5N1-like path, causing only occasional but frightening cases in people, and never spawning a human pandemic.
But there are reasons to believe the numbers of human cases, especially milder ones, are wildly wrong, directing our eyes to that dicey H1N1-like path.
The Chinese are using a state-of-the-art nucleotide test, known as RT-PCR, to test people and animals for the virus. The method is highly specific, and if any viruses are in a drop of blood, the test will find them. But such PCR assays will not come up positive if an individual or animal was exposed — even ailing — but successfully fought off the infection and cleared the virus from its body. To find those people or animals, investigators need to test for the presence of anti-H7N9 antibodies in their blood.
In the absence of mass antibody screening, Chinese investigators are instead trying to find milder cases by relying on interviews with the close contacts of patients, asking over the phone, "Have you had any of these symptoms?" Given what transpired with SARS in 2003 and swine flu in 2009, few individuals are motivated to mention mild symptoms — they don’t want to be locked in quarantine. (On Monday, a woman identifying herself only as Gu crashed a flu press conference in Shanghai and demanded that authorities tell her where her father is. Gu said her mother died of H7N9 on April 3, and her father was diagnosed with flu and placed in quarantine on April 13. Since then, Gu declared to the press gathering, she has not been allowed to communicate with her father or get medical updates from his physicians. In a country where public denunciations of politicians can get one locked up Gu’s actions signal desperation, and echo the sorts of cries for help I encountered from families during the SARS pandemic.) And since the Shanghai butcher’s family revealed the enormous debt incurred by his treatment, many Chinese are also reluctant to report ailments. The government now says that all H7N9 flu care will be free, but many Chinese recall the under-the-table payments demanded by some hospitals and physicians during the SARS epidemic, and remain deterred. Indeed, Anhui provincial authorities this week said that only 80 percent of treatment and hospitalization costs will be covered, and the remainder of H7N9 care must be paid for by patients’ families — a tall order for intensive care costs in any country.
People’s Liberation Army Col. Dai Xu insisted via Weibo and on China’s CCTV that the fearfulness felt by the Chinese in the face of H7N9 flu is part of an elaborate American conspiracy — one first executed in the creation of SARS: "The national leadership should not pay too much attention to it," he wrote. "Or else, it’ll be like in 2003 with SARS! At that time, America was fighting in Iraq and feared that China would take advantage of the opportunity to take other actions. This is why they used bio-psychological weapons against China. All of China fell into turmoil and that was exactly what the US wanted. Now, the US is using the same old trick. China should have learned its lesson and should calmly deal with the problem. Only a few will die, but that’s not even a one-thousandth of those who die in car crashes in China."
Famous for his nationalistic comments, Xu reportedly gained 30,000 Weibo followers in the 24 hours following this comment. He also drew criticism, to which Xu responded that his detractors were working with "American devils," adding, "It is common knowledge that a group of people in China have been injected wi
th mental toxin by the U.S. I will not retreat even half a step."
Just as the virus stands at the fork of a bifurcated road, so does the Chinese Communist Party. Though hardliners within the party may share Xu’s extremist views, the leadership this week took a remarkable step down a different, enlightened path, sending H7N9 test kits and viral samples to Taiwan. If China hopes to avoid the shame it experienced after covering up the SARS epidemic a decade ago, the government and the party will take the high road — that’s the one that shares samples with Taiwan and timely information transparently with the entire world.