The Economic Consequences of Chinese Pandemic Un-Preparedness

The population of China plays a significant role in the world economy.  Low cost manufacturing in China drives the larger economies of many other nations.  As a benchmark for this influence, recent reports put 80% of Walmart's manufacturing capacity in China. (Though the folks Newsweek, unsurprisingly, can't make up their minds and corrected an original report to say only 6%.)  While not every global firm relies so heavily on China, a bit of everything we buy is made there, or was made using machine tooling produced there. 

The health and productivity of workers responsible for China's manufacturing power is therefore of critical interest.  On a longer timescale, as China grows into a market on which western companies depend, the health of more than a billion consumers will also play a crucial role in the world economy.  These observations set up a series of questions about the capabilities of China’s public health system.  The answers to those questions in turn, through the role of the Chinese population as manufacturers and consumers, help determine the impact on the global economy of a pandemic Avian Flu outbreak within China.

I've just returned from a scenario planning exercise run by the GBN called "China's Choices".  I was able to ask journalists, professors, and corporate planners with experience in country about some of these issues.  The answers were not encouraging.  I will get into the details below, but there is already cause for concern.

Over at Recombinomics, Henry Niman continues to bang the drum about human cases of the Avian Flu in Asia, now citing local reports from China about a number of unexplained deaths that he asserts are due to the Flu.  He is evidently unsatisfied with the WHOs correspondence with the Chinese government in which all reports of human cases are denied.  Given Niman's language, I have to wonder if he is fanning the flames of panic.  But if there is in fact the beginnings of an outbreak in China then everyone had better pay attention right now.  However, I have a feeling that even in the event of a real outbreak it will take quite a while for anyone to figure out what is going on.  One of the things to come out of "China's Choices" is that even the central government can't trust data coming in from rural areas, and that you have to be on the ground gathering your own information.  This is primarily because China is an enormous country, and local officials are now rewarded based on what they report to be true about local conditions and production levels, rather than rewarded based upon standard metrics.  Can the Chinese government know to trust local reports of human cases of Avian Flu, let alone trust the denials?

We can at least try to get an idea of how they might handle an outbreak.  Worldwide flu vaccine production capacity is only a few hundred million doses per year, concentrated primarily in Western Europe and the U.S.  It is truly hard to dig up numbers for how much flu vaccine is produced and administered in China, but as far as I can tell, Chinese domestic flu vaccine production is no more than 10-20 million doses.  China Daily reported at the end of 2003 that demand for flu vaccines was only 15 million doses that year, growing at 15% annually.  Most of the vaccine used in the country is purchased from the US and Europe, as reported last summer in the China Chemical Industry News;

In 2003, the 13 Chinese domestic vaccine business only shared 30 per cent of the market. And the remaining 70 per cent of flu vaccine was imported from France, America and other countries. Huge technique differences exist between China vaccine manufacturers and their foreign counterparts.

Because the vast majority of humanity is immune naive for H5 viruses, the consensus seems to be that two doses of any vaccine will be required to generate an immune response.  This means there is probably only enough vaccine to take care of Beijing, or perhaps a selected population in many of the big cities.  Where does that leave the rest of the population?  At "China's Choices" last week, it was pointed out that when the rural population starts to revolt regimes tend to change in China.  Launching completely into the realm of speculation, I am led to wonder if the lack of a flu vaccine might be another tipping point.  Everything depends on the response of the government, and I don't think anyone -- inside or outside China -- is prepared to deal with a pandemic.

Keep in mind that WHO hasn't been getting samples of recent human H5N1 isolates from Asia, the vaccine takes some months to produce once samples are shipped and a strain is identified, and a vaccine based on that strain (modified, in this case, to be less lethal) may not actually confer immunity.  It is thus unlikely that China will have effective vaccine ready to go anytime soon, and they can't expect help from us because we don't have one either.

So much for setting the stage.  What happens if a flu pandemic hits China?

Inside the country, areas may be quarantined and people may stay away from populations centers to avoid infection, thereby depriving manufacturers of labor.  If the outbreak is severe, enough people may be sick that productivity is seriously impacted.

Outside the country, even if governments understand that quarantines will only marginally slow the spread of the  virus, populations will likely demand limitations on travel and trade.  Estimates of the economic costs of SARS range from USD 50 Bn (Bio-ERA) to 150 Bn (CDC) in lost trade and tourism revenues, while less than 800 people succumbed to the disease.  Thus fear of the disease caused considerably more economic damage than did the disease itself.  There is no reason to expect the response to an Avian Flu pandemic will be less severe.  Whether or not production of goods is actually slowed within China, shipping probably will be.  That is, the manufacturing capacity relied on by much of the global economy may go dark for up to several years.

While the domestic impact of a Chinese Flu pandemic depends on factors such as the availability of vaccines and anti-viral drugs, the stability of the public health system, and the willingness of the government to communicate with its citizens and the outside world, the global impact of a Chinese Flu pandemic depends on when it happens.  Aside from issues of whether the virus might escape the borders and find its way into other countries, aside from whether the Chinese government learned from the SARS outbreak and shares epidemiological information, the global impact of a pandemic confined entirely within China's borders could be severe.  If an outbreak happens soon, the consensus of folks I spoke to at the GBN meeting was that investment would move elsewhere, diversifying manufacturing capacity into India, for example.  There would be short term pain, but not that much economic damage would result.

But if the pandemic hits at point when the consumer market within China is significant, then it won't just be low cost manufactured goods that go missing; a reduction in shipping could mean the sudden loss of hundreds of millions of consumers.  We live in a globalized economy wherein goods and services are provided based on the availability of credit and upon cash flow.  If western economies start to rely on capital flow out of China, a pandemic could be far more severe than people are planning for now.

In the short term, if this system starts to break down, it just isn't clear that critical products -- gloves, surgical masks, disposable plastic lab ware -- are going to make it where they are needed.  What fraction of the medical disposables we use are manufactured in China?  If a pandemic flu outbreak occurs in China, do we have reserves or replacement capacity? 

Masks were in short supply during the SARS crisis, and I wonder if all the right people are making sure masks and similar necessities are not only stockpiled for the next crisis, but that the manufacturing and supply lines will remain open.  A flu outbreak could come in multi-month long waves, with the challenge to the global system of health care providers, critical goods manufacturers, and the overall economy lasting several years.

These questions point the way to considering how restriction in trade with China may begin to impact local economies to the point that they have difficulty mounting domestic responses to a pandemic.  I have no answers after all of this, just more questions.

WHO doesn't have recent flu strains.

Catching up on Avian Flu news of the past week, I find that Nature is reporting (subscription required), "it is nearly eight months since the World Health Organization (WHO) last saw data on isolates from infected poultry in Asia".  And worse, "From the dozens of patients who caught the deadly H5N1 strain this year, the WHO has managed to obtain just six samples.  Affected countries are failing, or refusing, to share their human samples with the WHO's influenza programme in Geneva".

And this just when "trends suggest that the virus is becoming less virulent and more infectious -- two characteristics typical of pandemic flu strains".  Lovely.

The report continues, "The WHO's flu programme was last given access to a sample in October 2004, so it has no idea how the virus is changing in birds."

The upshot of the story is that countries wherein the virus is present are concerned about "losing control over information", want to develop their own vaccines, and are worried about intellectual property issues.  These points in particular are remarkable given that none of the countries affected is in much of a position to produce significant quantities of vaccine, which means that in order to protect their populations they will need outside assistance anyway.  Not to mention the affects on the rest of the world should an outbreak spread because local authorities were unprepared to deal with it. 

Evidently, "Some countries have provided samples but stipulated that the information can't be shared with the wider community".  Hmmm.  Excellent time to feel nationalistic.

Here are questions this story prompts me to ask:

Is anyone comparing the sequences of strains from human cases?  The answer would seem to be "no", which means we can't know whether more than one strain able to survive in humans is emerging, nor how those strains are changing over time at the molecular level.

How in the hell can anyone expect to prepare a vaccine against a bug we aren't getting samples of?  Who (WHO?) thinks we are actually prepared for any kind of widespread emerging infectious disease, let alone one as obvious a threat as H5N1?

The report ends by suggesting that discussions are underway to remedy the lack of cooperation and material transfer.  Somehow this doesn't make me feel any more comfortable.

"Preparing for the Next Pandemic"

Michael Osterholm, director of CIDRAP, has an excellent perspective piece in last week's New England Journal of Medicine, "Preparing for the Next Pandemic".

Here are some notes and highlights:

•    Typical annual US domestic death toll from flu is 30,000 to 50,000, with global toll 20-30 times higher.
•    “Today, making the 300 million doses of influenza vaccine needed annually worldwide requires more than 350 million chicken eggs and six or more months.”
•    Even if we develop a more capable, faster alternative, we must assure the production capacity for sufficient doses for a global population.
•    If a pandemic hit tomorrow, vaccine production in the following six months would be limited to at most one billion monovalent doses.  Because effective vaccination often requires two doses, we could thus protect at most only 500 million people.
•    Just in time economics also used to plan critical care facilities and equipment.  We do not have sufficient numbers of ventilators, for example, to handle a surge of flu victims.
•    “We have no detailed plans for staffing the temporary hospitals that would have to be set up in high school gymnasiums and community centers – and that might need to remain in operation for one or two years.  Health care workers would become ill and die at rates similar to, or even higher than, those in the general public.  Judging by our experience with [SARS], some health care workers would not show up for duty.  How would communities train and use volunteers?  If the pandemic wave were spreading slowly enough, could immune survivers of an early wave, particularly health care workers, become the primary response corps?”
•    No significant planning about use of antiviral agents.  (From my work with Bio-ERA, it is clear that there are even contradictions in the way US and Canada are stockpiling Tamiflu and vaccine.  The US has minimal stockpiles of the antiviral drug, but has already ordered large numbers of vaccine doses, while Canada has stockpiled lots of Tamiflu but is waiting on the vaccine.  I have to wonder how this might affect epidemiolgical dynamics across the border.)
•    “The current system of producing and distributing influenza vaccine is broken, both technically and financially.  The belief that we can greatly advance manufacturing technology and expand capacity in the normal course of increasing our annual vaccination coverage is flawed.  At our current pace, it will take generations for meaningful advances to be made.”
•    Osterholm argues for cell culture based vaccine production.
•    Notes that in 1968, during most recent pandemic, China’s population of humans was only 760 million, of pigs only 5.2 million, and of poultry only 12.3 million.  Current populations are humans 1.3 billion; pigs 508 million; and poultry 13 billion.  “Similar changes have occurred in the human and animal populations of other Asian countries, creating an incredible mixing vessel for viruses."

Well done, Dr. Osterholm.

Heinz Feldmann on Marburg

Heinz Feldmann, head of the Level 4 labs at the National Microbiology Laboratory of the Public Health Agency of Canada, was in town this week to give a couple of talks on the Marburg virus.  He just returned from field work in Uige, the center of the current outbreak.

Here are a few notes:

  • There are claims that up to 80% of the highland Gorillas in the area have been felled by Ebola, but Feldmann expressed some skepticism and noted that none of the cases had been lab confirmed.  Evidently, there is  discussion of using experimental vaccines in the Gorillas to try to preserve the population.  This is more than can be done for the humans, because the vaccines have yet to undergo even safety testing.
  • Feldmann and others are working on vaccines for Marburg and Ebola, and adenovirus vectors don't work very well due to extensive seroprevalence in the population of neutralizing antibodies.
  • However, his lab is using VSV as a vector and this is working extremely well in monkeys.  When the GP protein from Marburg is included in VSV Virus Like Particles (VLPs), 100% of monkeys survive exposure with cross strain protection, including the "POP" strain thought to have been weaponized by the Soviets.  Ebola is a slightly different story, with 100% protection for any given strain, slightly less protection across strains, and zero cross species protection.

I am increasingly interested in the possibility of VLPs as the foundation of a synthetic and distributed vaccine production infrastructure.  Ralph Baric was in town a few weeks ago, and he said he was having success with VLP vaccines for Noroviruses.  So your next ocean cruise could well be diarrhea free.

Marburg in Angola

I'm catching up on the news, and trying to sort out what to make of the Marburg virus outbreak in Angola.

The 11 April, 2005 New York Times story reports;

The race to contain the outbreak of Marburg, a deadly relative of the better-known Ebola virus, is centered here in the town of Uíge (pronounced weezh), where health officials fear the makings of a public health disaster that could spread elsewhere in Angola and beyond.

The number of victims is already the largest ever recorded from a Marburg outbreak, and there is no effective treatment. Nine out of 10 people who get the virus die, usually within a week.

...The virus is named for the town in Germany where it was first identified in 1967 after laboratory workers were infected by monkeys from Uganda.

Scientists do not know the source of the virus or how this outbreak began. But the Centers for Disease Control and Prevention in Atlanta confirmed the first Marburg case in Uíge on March 8. That suggests that two months more of illness and deaths lie ahead.

It's a nasty bug, no question about it.

The 10 April, 2005 New York Times story by Sharon Lafraniere, "To Contain Virus in Angola, Group Wants Hospital Closed", contains other interesting tidbits.  The article begins;

UIGE, Angola, April 9 - An international medical charity battling a hemorrhagic fever that so far has killed 181 Angolans has urged the government to close the regional hospital here, at the center of the outbreak, saying the medical center itself is a source of the deadly infection.

Doctors Without Borders, the global relief organization that runs an isolation ward at the hospital for victims of the deadly fever, Marburg virus, told Angolan officials on Friday that the hospital should be closed if the rapidly spreading epidemic was to be contained.

Two other hospitals within 60 miles of Uige may also have to be shut down, said Monica de Castellarnau, the organization's emergency coordinator in Uige, the provincial capital, where the outbreak was first reported.

That possibility raises the prospect of a second health care crisis, one in which hundreds of thousands of people already facing a disease that is almost always fatal may suddenly have no access to hospital care. But in an interview in the streets of Uige, where an intensive effort is under way to find and isolate new cases of the virus, Ms. Castellarnau said there might be no alternative.

"The hospital has been the main source of infection," she said. "We have to break that chain somehow. It is a massive public health decision, and it must be taken by the government."

No doubt this ought to make people think hard about contingencies in an Avian Flu pandemic.  If we have to start implementing quarantines on hospitals and clinics because they are concentrated sources of virus, what happens to ongoing medical and emergency care?  Hopefully, the folks at Effect Measure are pondering this.

I also have, sitting on my desk, a preprint describing how both Ebola and Marburg employ mechanisms that suppress the human anti-viral response.  Since the article is not published, I can't describe the details here.  Essentially, both viruses specifically down-regulate key genes known to play a role in anti-viral reactions, down-regulate coagulation related gene expression, and also appear to suppress the ability of liver cells to regenerate clotting factors.

Reuters and the AP are both carrying stories about how local customs have led to the spread of the disease from corpses to family members, and about how hard it is to change those cultural practices.  The Marburg Wiki has similar information.

The AP story ends with the following tidbit, which is both interesting and troubling;

Angola's protracted civil war, which ended in 2002, wrecked the country's public infrastructure, including hospitals and roads.

Uige still bears the scars of that war: some houses are still partial ruins with bullet holes and smashed walls. When the outbreak began, the hospital didn't have a single pair of medical gloves, officials said.

Once again, this reminds us how carefully we have to watch the Avian Flu outbreak in SE Asia, particularly in the areas hit by the tsunami (see my post, A Confluence of Concerns).

1957 Flu Redux (...almost...)

The AP carried a story today that announced a recomendation (order?) from the WHO to destroy shipments of flu strains sent to labs around the world as part of an ongoing testing program.

The problem, it seems, is that the test kit contained the 1957 pandemic flu strain, which no one has been vaccinated against since 1968.  The story reports that, "It was not immediately clear why the 1957 pandemic strain, which killed between 1 million and 4 million people -- was in the proficiency test kits routinely sent to labs."  The story continues;

Most of the samples were sent starting last year at the request of the College of American Pathologists, which helps labs do proficiency testing. The last shipments were sent out in February.

Dr. Jared Schwartz, an official with the pathology college, said a private company, Meridian Bioscience Inc. of Cincinnati, Ohio, is paid to prepare the samples. The firm was told to pick an influenza A sample and chose from its stockpile the deadly 1957 H2N2 strain.

Regardless of the wisdom of this choice, it is interesting that it was caught at all -- one of the labs correctly identified the 1957 strain.  That bodes well for infectious disease surveillance, but note that this was a test kit sent to the labs, not an environmental sample that they had to test completely blind.

Note also that the strain is now out in the world again, and could thus be kept as a potential weapon.  Most of the kits were shipped to labs in the US, and the College of American Pathologists has requested confirmation in writing that all the test kits have been incinerated.  Which is great.  Except that the bug is still now out in the world.  Even if this was an accident -- especially if this was an accident -- the incident highlights how ill prepared the global community is for biological surprises.

UPDATE (14 April 05): Effect Measure has nice coverage of this incident.

Bio-ERA: Thinking Ahead

Bio Economic Research Associates has now published its first report examining possible outcomes of a flu pandemic, Thinking Ahead: Anticipating Early Impacts of an Avian Influenza Pandemic.  The report, and the associated research service, are designed to help answer the following questions:

  • What key indicators and signposts should the business community be watching with respect to pandemic influenza?
  • If human transmissible H5N1 broke out in Asia, what specific actions (travel advisories, quarantines, travel restrictions, etc.) should we expect to be implemented by governments and public health authorities?
  • How would these actions impact regional and global economies, and businesses operating within and/or interconnected with, affected regions?
  • How would these developments affect investors and financial markets?

ProMED-mail

If you want up to the minute information about emerging diseases, ProMED-mail is a service run by the International Society for Infectious Diseases and the Federation of Americal Scientists (FAS).  The FAS also runs ahead/ILIAD, which specifically tracks infectious animal and zoonotic diseases.

There is also link in the "Navigation" bar of the ProMED-mail site to recent medical product and food recalls and medical alerts.

This is good stuff.  But don't read it just before going to bed.