Bird Flu: An ill wind from the East Options

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http://www.atimes.com/atimes/Global_Economy/GG01Dj01.html

Bird flu: An ill wind from the East

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Countries Hit by Bird Flu Have Little Medicine to Treat Humans

By Alan Sipress

JAKARTA, Indonesia -- As highly lethal avian influenza circulates among poultry in East Asia, posing the prospect of a worldwide human pandemic, most of the countries now affected have virtually no stocks of the medicine needed to treat the virus, according to officials in the region.

To view the entire article, go to http://www.washingtonpost.com/wp-dyn/conte...er=emailarticle

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http://www.voanews.com/english/2005-07-06-voa19.cfm

UN Releases 'Blueprint' for Fight Against Bird Flu in Asia

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http://www.voanews.com/english/2005-07-05-voa28.cfm

Millions Needed for Global Plan to Halt Bird Flu

[Gabrielle]

This is an excellent piece on the coming pandemic.
Preparing for the Next Pandemic
Michael T. Osterholm
From Foreign Affairs, July/August 2005

Summary: If an influenza pandemic struck today, borders would close, the global economy would shut down, international vaccine supplies and health-care systems would be overwhelmed, and panic would reign. To limit the fallout, the industrialized world must create a detailed response strategy involving the public and private sectors.

This post has been edited by Gabrielle: Jul 6 2005, 03:12 PM

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http://www.washingtonpost.com/wp-dyn/conte...5070601967.html

Deadly Flu Strain Shows Up in Migratory Birds
Scientists' Discovery Gives Rise to Fears the Virus Could Spread Beyond East Asia

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http://www.usatoday.com/news/health/2005-0...htm?POE=NEWISVA

Bird Flu may spread, harm people, scientists warn

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http://www.alertnet.org/thenews/newsdesk/SP268006.htm

First case of bird flu hits Phillippines

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http://thestaronline.com/news/story.asp?fi...ec=Worldupdates

Killer bird flu virus erupts again in Thailand

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http://www.voanews.com/english/2005-07-20-voa20.cfm

Indonesia Reports First Human Bird Flu DeathsIndonesia Reports First Human Bird Flu Deaths
By Nancy-Amelia Collins
Jakarta
20 July 2005

Indonesia has reported its first human deaths attributed to bird flu. Health officials still do not know how the victims contracted the virus.

The Indonesian Health Ministry says tests in Hong Kong indicate a father and his two daughters died earlier this month in Jakarta from the virulent H5N1 bird flu virus.

Health minister Siti Fadillah Supari said test results on the father led her to conclude that all three died of bird flu.

But the World Health Organization's representative in Indonesia, Georg Peterson, said only the father tested positive for the virus. "What we know so far is that three people of the same family died of influenza-like illnesses and that they confirmed H5N1 is the father in the family. We do not yet know what the exposure could be or the source of infection could be," he said.

Mr. Peterson said there is no evidence yet any of the three had contact with infected poultry, but signs do not point to human-to-human transmission. "What is happening is all contact with these people are being monitored closely for fever and influenza symptoms and if no one is getting sick in the next few days it's most likely that there's no human-to-human transmission here," he said.

Millions of chickens have been slaughtered since the H5N1 bird flu virus first started infecting poultry populations across Asia in late 2003.

Dozens of people have died from the virus in Thailand, Vietnam and Cambodia, with health experts saying most of those who died caught bird flu from contact with infected poultry.

But the WHO has warned the virus may mutate into a form more easily transmitted between humans.

[Gabrielle]

This is the best all around article I've read on avian influenza. It discusses the virus and the reasons why scientists say we're brewing for another pandemic. Chinese population growth as well as the growth of chicken farming in China has made the situation ripe for the emergence of an H5N1 virus that's transmitted from human to human.

The Next Pandemic
Laurie Garrett
From Foreign Affairs, July/August 2005

Summary: Since it first emerged in 1997, avian influenza has become deadlier and more resilient. It has infected 109 people and killed 59 of them. If the virus becomes capable of human-to-human transmission and retains its extraordinary potency, humanity could face a pandemic unlike any ever witnessed.

Laurie Garrett is Senior Fellow for Global Health at the Council on Foreign Relations and is the author of The Coming Plague and Betrayal of Trust.

PROBABLE CAUSE

Scientists have long forecast the appearance of an influenza virus capable of infecting 40 percent of the world's human population and killing unimaginable numbers. Recently, a new strain, H5N1 avian influenza, has shown all the earmarks of becoming that disease. Until now, it has largely been confined to certain bird species, but that may be changing.

The havoc such a disease could wreak is commonly compared to the devastation of the 1918-19 Spanish flu, which killed 50 million people in 18 months. But avian flu is far more dangerous. It kills 100 percent of the domesticated chickens it infects, and among humans the disease is also lethal: as of May 1, about 109 people were known to have contracted it, and it killed 54 percent (although this statistic does not include any milder cases that may have gone unreported). Since it first appeared in southern China in 1997, the virus has mutated, becoming heartier and deadlier and killing a wider range of species. According to the March 2005 National Academy of Science's Institute of Medicine flu report, the "current ongoing epidemic of H5N1 avian influenza in Asia is unprecedented in its scale, in its spread, and in the economic losses it has caused."

In short, doom may loom. But note the "may." If the relentlessly evolving virus becomes capable of human-to-human transmission, develops a power of contagion typical of human influenzas, and maintains its extraordinary virulence, humanity could well face a pandemic unlike any ever witnessed. Or nothing at all could happen. Scientists cannot predict with certainty what this H5N1 influenza will do. Evolution does not function on a knowable timetable, and influenza is one of the sloppiest, most mutation-prone pathogens in nature's storehouse.

Such absolute uncertainty, coupled with the profound potential danger, is disturbing for those whose job it is to ensure the health of their community, their nation, and broader humanity. According to the Centers for Disease Control and Prevention (CDC), in a normal flu season about 200,000 Americans are hospitalized, 38,000 of whom die from the disease, with an overall mortality rate of .008 percent for those infected. Most of those deaths occur among people older than 65; on average, 98 of every 100,000 seniors with the flu die. Influenza costs the U.S. economy about $12 billion annually in direct medical costs and loss of productivity.

Yet this level of damage hardly approaches the catastrophe that the United States would face in a severe flu pandemic. The CDC predicts that a "medium-level epidemic" could kill up to 207,000 Americans, hospitalize 734,000, and sicken about a third of the U.S. population. Direct medical costs would top $166 billion, not including the costs of vaccination. An H5N1 avian influenza that is transmittable from human to human could be even more devastating: assuming a mortality rate of 20 percent and 80 million illnesses, the United States could be looking at 16 million deaths and unimaginable economic costs. This extreme outcome is a worst-case scenario; it assumes failure to produce an effective vaccine rapidly enough to make a difference and a virus that remains impervious to some antiflu drugs. But the 207,000 reckoning is clearly a conservative guess.

The entire world would experience similar levels of viral carnage, and those areas ravaged by HIV and home to millions of immunocompromised individuals might witness even greater death tolls. In response, some countries might impose useless but highly disruptive quarantines or close borders and airports, perhaps for months. Such closures would disrupt trade, travel, and productivity. No doubt the world's stock markets would teeter and perhaps fall precipitously. Aside from economics, the disease would likely directly affect global security, reducing troop strength and capacity for all armed forces, UN peacekeeping operations, and police worldwide.

In a world where most of the wealth is concentrated in less than a dozen nations representing a distinct minority of the total population, the capacity to respond to global threats is, to put it politely, severely imbalanced. The majority of the world's governments not only lack sufficient funds to respond to a superflu; they also have no health infrastructure to handle the burdens of disease, social disruption, and panic. The international community would look to the United States, Canada, Japan, and Europe for answers, vaccines, cures, cash, and hope. How these wealthy governments responded, and how radically the death rates differed along worldwide fault lines of poverty, would resonate for years thereafter.


WHAT ONCE WAS LOST

Nearly half of all deaths in the United States in 1918 were flu related. Some 675,000 Americans -- about 0.6 percent of the population of 105 million and the equivalent of 2 million American deaths today -- perished from the Spanish flu. The average life expectancy for Americans born in 1918 was just 37 years, down from 55 in 1917. Although doctors then lacked the technology to test people's blood for flu infections, scientists reckon that the Spanish flu had a mortality rate of just less than one percent of those who took ill in the United States. It would have been much worse had there not been milder flu epidemics in the 1850s and in 1889, caused by similar but less virulent viruses, which made most elderly Americans immune to the 1918-19 strain. The highest death tolls were among young adults, ages 20-35.

The Spanish flu got its name because Spain suffered from an early and acute outbreak, but it did not originate there. Its actual origin remains uncertain. The first strain was mild enough to prompt most World War I military forces to dismiss it as a pesky ailment. When the second strain hit North America in the summer of 1918, however, the virus caused a surge of deaths. First hit was Camp Funston, an army base in Kansas, where young soldiers were preparing for deployment to Europe. The virus then spread swiftly to other camps and on troop ships crossing the Atlantic, killing 43,000 U.S. military personnel in about three months. Despite the entreaties of the military's surgeons general, President Woodrow Wilson ordered continued shipments of troops aboard crowded naval transports, which soldiers came to call "death ships." By late September 1918, so overwhelmed was the War Department by influenza that the military could not assist in controlling civic disorder at home, including riots caused by epidemic hysteria. Worse, so many doctors, scientists, and lab technicians had been drafted into military service that civilian operations were hamstrung.

Under these conditions, influenza swept from the most populous U.S. cities to extraordinarily remote rural areas. Explorers discovered empty Inuit villages in what are now Alaska and the Yukon Territory, their entire populations having succumbed to the flu. Many deaths were never included in the pandemic's official death toll -- such as the majority of victims in Africa, Latin America, Indonesia, the Pacific Islands, and Russia (then still in the throes of revolution). What is known about the toll in these regions is staggering. For example, influenza killed 5 percent of the population of Ghana in only two months, and nearly 20 percent of the people of Western Samoa died. The official estimate of 40-50 million total deaths is believed to be a conservative extrapolation of European and American records. In fact, many historians and biologists believe that nearly a third of all humans suffered from influenza in 1918-19 -- and that of these, 100 million died.

In the last years of the nineteenth century and the early years of the twentieth, a series of important scientific discoveries spawned a revolution in biology and medicine and led pioneers such as Hermann Biggs, a New York City doctor, to create entire legal and health systems based on the identification and control of germs. By 1917, the United States and much of Europe had become enthralled by the hygiene movement. Impressive new public health infrastructures had been built in many cities, tens of thousands of tuberculosis victims were isolated in sanatoriums, the incidences of child-killing diseases such as diphtheria and typhoid fever had plummeted, and cholera epidemics had become rare events in the industrialized world. There was great optimism that modern science held the key to perfect health.

Influenza's arrival shattered the hope; scientists still had virtually no understanding of viruses generally, and of influenza in particular. The hygienic precautions and quarantines that had proved so effective in holding back the tide of bacterial diseases in the United States proved useless, even harmful, in the face of the Spanish flu. As the epidemic spread, top physicians and scientists claimed its cause was everything from tiny plants to old dusty books to something called "cosmic influence." It was not until 1933 that a British research team finally isolated and identified the influenza virus.

Most strains of the flu do not kill people directly; rather, death is caused by bacteria, which surge into the embattled lungs of the victim. But the Spanish flu that circulated in 1918-19 was a direct killer. Victims suffered from acute cyanosis, a blue discoloration of the skin and mucous membranes. They vomited and coughed up blood, which also poured uncontrollably from their noses and, in the case of women, from their genitals. The highest death toll occurred among pregnant women: as many as 71 percent of those infected died. If the woman survived, the fetus invariably did not. Many young people suffered from encephalitis, as the virus chewed away at their brains and spinal cords. And millions experienced acute respiratory distress syndrome, an immunological condition in which disease-fighting cells so overwhelm the lungs in their battle against the invaders that the lung cells themselves become collateral damage, and the victims suffocate. Had antibiotics existed, they may not have been much help.


OOPS

In January 1976, 18-year-old Private David Lewis staggered his way through a forced march during basic training in a brutal New Jersey winter. By the time his unit returned to base at Fort Dix, Lewis was dying. He collapsed and did not respond to his sergeant's attempts at mouth-to-mouth resuscitation.

In subsequent weeks, U.S. Army and CDC scientists discovered that the virus that had killed Lewis was swine flu. Although no other soldiers at Fort Dix died, health officials panicked. F. David Matthews, then secretary of health, education, and welfare, promptly declared, "There is evidence there will be a major flu epidemic this coming fall. The indication is that we will see a return of the 1918 flu virus that is the most virulent form of flu. In 1918, a half million people died [in the United States]. The projections are that this virus will kill one million Americans in 1976."

At the time, it was widely believed that influenza appeared in cycles, with especially lethal forms surfacing at relatively predictable intervals. Since 1918-19, the United States had suffered through influenza pandemics in 1957-58 and 1968-69; the first caused 70,000 deaths and the second 34,000. In 1976, scientists believed the world was overdue for a more lethal cycle, and the apparent emergence of swine flu at Fort Dix seemed to signal that another wave had come. The leaders of the CDC and the Department of Health, Education, and Welfare (HEW) warned the White House that there was a reasonably high probability that a catastrophic flu pandemic was about to hit. But opinion was hardly unanimous, and many European and Australian health authorities scoffed at the Americans' concern. Unsure of how to gauge the threat, President Gerald Ford summoned the polio-fighting heroes Jonas Salk and Albert Sabin to Washington and found the long-time adversaries in remarkable accord: a flu pandemic might truly be on the way.

On March 24, 1976, Ford went on national television. "I have just concluded a meeting on a subject of vast importance to all Americans," he announced. "I have been advised that there is a very real possibility that unless we take effective counteractions, there could be an epidemic of this dangerous disease next fall and winter here in the United States. ... I am asking Congress to appropriate $135 million, prior to the April recess, for the production of sufficient vaccine to inoculate every man, woman, and child in the United States."

Vaccine producers immediately complained that they could not manufacture sufficient doses of vaccine in such haste without special liability protection. Congress responded, passing a law in April that made the government responsible for the companies' liability. When the campaign to vaccinate the U.S. population started four months later, there were almost immediate claims of side effects, including the neurologically debilitating Guillain Barré Syndrome. Most of the lawsuits -- with claims totaling $3.2 billion -- were settled or dismissed, but the U.S. government still ended up paying claimants around $90 million.

Swine flu, however, never appeared. The head of the CDC was asked to resign, and Congress never again considered assuming the liability of pharmaceutical companies during a potential epidemic. The experience weakened U.S. credibility in public health and helped undermine the stature of President Ford. Subsequently, an official assessment of what went wrong was performed for HEW by Dr. Harvey Fineberg, a Harvard professor who is currently president of the Institute of Medicine.

Fineberg concluded:"In this case the consequences of being wrong about an epidemic were so devastating in people's minds that it wasn't possible to focus properly on the issue of likelihood. Nobody could really estimate likelihood then, or now. The challenge in such circumstances is to be able to distinguish things so you can rationally talk about it. In 1976, some policymakers were simply overwhelmed by the consequences of being wrong. And at a higher level [in the White House] the two -- likelihood and consequence -- got meshed."

Fineberg's warnings are well worth remembering today, as scientists nervously consider H5N1 avian influenza in Asia. The consequences of a form of this virus that is transmittable from human to human, particularly if it retains its unprecedented virulence, would be disastrous. But what is the likelihood that such a virus will appear?


DEVOLUTION

Understanding the risks requires understanding the nature of H5N1 avian flu specifically and influenza in general. Influenza originates with aquatic birds and is normally carried by migratory ducks, geese, and herons, usually without harm to them. As the birds migrate, they can pass the viruses on to domesticated birds -- chickens, for example -- via feces or during competitions over food, territory, and water. Throughout history, this connection between birds and the flu has spawned epidemics in Asia, especially southern China. Aquatic flu viruses are more likely to pass into domestic animals -- and then into humans -- in China than anywhere else in the world. Dense concentrations of humans and livestock have left little of China's original migratory route for birds intact. Birds that annually travel from Indonesia to Siberia and back are forced to land and search for sustenance in farms, city parks, and industrial sites. For centuries, Chinese farmers have raised chickens, ducks, and pigs together, in miniscule pens surrounding their homes, greatly increasing the chance of contamination: influenza can spread from migrating to domestic birds and then to swine, mutating and eventually infecting human beings.

Ominously, as China's GDP grows, so do the expensive appetites of the country's 1.3 billion people, more of whom can afford to eat chicken regularly. Today, China annually raises about 13 billion chickens, 60 percent of them on small farms. Chicken farming is quickly morphing into a major industry, with some commercial poultry plants rivaling those in Arkansas and Georgia in scale -- but lagging behind in hygienic standards. These factors favor rapid influenza evolution. By the close of the twentieth century, at least two new types of human-to-human flu spread around the world every year.

Influenza viruses contain eight genes, composed of RNA and packaged loosely in protective proteins. Like most RNA viruses, influenza reproduces sloppily: its genes readily fall apart, and it can absorb different genetic material and get mixed up in a process called reassortment. When influenza successfully infects a new species -- say, pigs -- it can reassort, and may switch from being an avian virus to a mammalian one. When that occurs, a human epidemic can result. The transmission cycles and the constant evolution are key to influenza's continued survival, for were it to remain identical year after year, most animals would develop immunity, and the flu would die out. This changing form explains why influenza is a seasonal disease. Vaccines made one year are generally useless the following.

Among the eight influenza genes there are two, dubbed H and N, that provide the code for proteins recognized by the human immune system. Scientists have numbered the many types of H and N proteins and use this system to classify a virus. A different viral combination of H and N proteins will trigger a different human immune response. For example, if a strain of H2N3 influenza circulates one year, followed by a different variety of H2N3 the next year, most people will be at least partially immune to the second strain. But if an H2N3 season is followed by an outbreak of H3N5 influenza, few people will have any immunity to the second virus, and the epidemic could be enormous. But a widespread epidemic need not be a severe or particularly deadly one: a virus' virulence depends on genes other than the two that control the H and N proteins.

Scientists first started saving flu virus samples in the early twentieth century. Since that time, an H5N1 influenza has never spread among human beings. According to the World Health Organization (WHO), "No virus of the H5 subtype has probably ever circulated among humans, and certainly not within the lifetime of today's world population. Population vulnerability to an H5N1-like pandemic virus would be universal." As for virulence, within about 48 hours of infection, H5N1 avian influenza kills 100 percent of infected chickens -- although the virulence of a potential human-to-human transmissible H5N1 is impossible to predict.

A team of Chinese scientists has been tracking the H5N1 virus since it first emerged in Hong Kong in 1997, killing 6 people and sickening 18 others. The strain came out of southern China's Guangdong Province, where it apparently was carried by ducks, and hit Hong Kong's chicken population hard. After authorities there killed 1.5 million chickens -- almost every single one in Hong Kong -- the outbreak seemed to stop. But the virus had not disappeared; rather, it had retreated to China's Guangdong, Hunan, and Yunnan provinces, spreading once again to aquatic birds.

From 1998 to 2001 the virus went through multiple reassortments and moved back to domestic birds, spreading almost unnoticed in Chinese chicken flocks. It continued to evolve at high speed: 17 more reassortments occurred, and in January 2003 the "Z" virus emerged, a mutant powerhouse that had become tougher, capable of withstanding a wider range of environmental challenges. The Z virus spread to Vietnam and Thailand, where it evolved further, becoming resistant to one of the two classes of antiflu drugs, known as amantadines, or M2-inhibitors.

In early 2004, it became supervirulent and capable of killing a broad range of species, including rodents and humans. That permutation of the virus was dubbed "Z+." In the first three weeks of January 2004, Z+ killed 11 million chickens in Vietnam and Thailand. By April 2004, 120 million chickens in Asia had died of flu or been exterminated to slow the influenza brushfire. The avian epidemic stopped for a while, but in July another 1 million chickens died from the disease. The Z+ virus was causing massive internal bleeding in the birds. By the beginning of 2005, with chickens dying and customers shying away from what remained, the Asian poultry industry had lost nearly $15 billion.

By April 2005, the H5N1 virus had also moved to pigs. Scientists isolated the disease from swine in a part of Indonesia where pigs are raised underneath elevated wood-slatted platforms that house chickens. Less rigorous investigations had previously indicated that pigs in China and Vietnam may also have been infected by H5N1 influenza. The discovery in Indonesia provided disturbing evidence that the virus was infecting mammals, although it was not yet known how widely the swine disease had spread or how lethal it was for the animals.


HARD TO KILL

Over the course of this brief but rapid evolution, the H5N1 virus developed in ways unprecedented in influenza research. It is not only incredibly deadly but also incredibly difficult to contain. The virus apparently now has the ability to survive in chicken feces and the meat of dead animals, despite the lack of blood flow and living cells; raw chicken meat fed to tigers in Thailand zoos resulted in the deaths of 147 out of a total of 418. The virus has also found ways to vastly increase the range of species it can infect and kill. Most strains of influenza are not lethal in lab mice, but Z+ is lethal in 100 percent of them. It even kills the very types of wild migratory birds that normally host influenza strains harmlessly. Yet domestic ducks, for unknown reasons, carry the virus without a problem, which may explain where Z+ hides between outbreaks among chickens.

Traditional Asian methods of buying, slaughtering, and cooking meat make it hard to track the spread of an influenza virus -- and tracking it is critical to preventing the disease from spreading. In Asia, consumers prefer to buy live chickens and other live animals at the market, slaughtering them in home kitchens. Asians thus have a high level of exposure to potentially disease-carrying animals, both in their homes and as they pass through the markets that line the streets of densely packed urban centers. For someone trying to trace a disease, Asia is a nightmare: with people daily exposed to live chickens in so many different environments, how can a sleuth tell whether an ailing flu victim was infected by a chicken, a duck, a migratory heron -- or another human being?

Although most of the 109 known human H5N1 infections have been ascribed to some type of contact with chickens, mysteries abound, and many cases remain unsolved. "The virus is no longer causing large and highly conspicuous outbreaks on commercial farms," a 2005 WHO summary of the human Z+ cases states. "Nor have poultry workers or cullers turned out to be an important risk group that could be targeted for protection. Instead, the virus has become stealthier: human cases are now occurring with no discernible exposure to H5N1 through contact with diseased or dead birds."

If proximity to infected animals is the key, why have there been no deaths among chicken handlers, poultry workers, or live-chicken dealers? The majority of the infected have been young adults and children. And there has been one documented case of human-to-human transmission of the Z+ strain of the H5N1 virus -- in late 2004, in Thailand. Several more such cases are suspected but cannot be confirmed. According to the WHO, there is "no scientific explanation for the unusual disease pattern."

Assessing and understanding H5N1's virulence in humans has also proved elusive. When it first appeared in Hong Kong in 1997, the virus killed 35 percent of those it was known to have infected. (Less severe cases may not have been reported.) The Z strain of the disease, which emerged in early 2003, killed 68 percent of those known to have been infected. In H5N1 cases since December 2004, however, the mortality has been 36 percent. How can the fluctuation over time be explained? One disturbing possibility is that H5N1 has begun adapting to its human hosts, becoming less deadly but easier to spread. In the spring of 2005, in fact, H5N1 infected 17 people throughout Vietnam, resulting in only three deaths. Leading flu experts argue that this sort of phenomenon has in the past been a prelude to human influenza epidemics.

The medical histories of those who have died from H5N1 influenza are disturbingly similar to accounts of sufferers of the Spanish flu in 1918-19. Otherwise healthy people are completely overcome by the virus, developing all of the classic flu symptoms: coughing, headache, muscle pain, nausea, dizziness, diarrhea, high fever, depression, and loss of appetite. But these are just some of the effects. Victims also suffer from pneumonia, encephalitis, meningitis, acute respiratory distress, and internal bleeding and hemorrhaging. An autopsy of a child who died of the disease in Thailand last year revealed that the youth's lungs had been torn apart in the all-out war between disease-fighting cells and the virus.


BAD MEDICINE

According to test-tube studies, Z+ ought to be vulnerable to the antiflu drug oseltamivir, which the Roche pharmaceuticals company markets in the United States under the brand name Tamiflu. Yet Tamiflu was given to many of those who ultimately succumbed to the virus; it is believed that medical complications induced by the virus, including acute respiratory distress syndrome, may have prevented the drug from helping. It is also difficult to tell whether the drug contributed to the survival of those who took it and lived, although higher doses and more prolonged treatment may have a greater impact in fighting the disease. A team of Thai clinicians recently concluded that "the optimal treatment for case-patients with suspected H5 infection is not known." Lacking any better options, the WHO has recommended that countries stockpile Tamiflu to the best of their ability. The U.S. Department of Health and Human Services is doing so, but supplies of the drug are limited and it is hard to manufacture.

What about developing a Z+ vaccine? Unfortunately, there is only more gloom in the forecast. The total number of companies willing to produce influenza vaccines has plummeted in recent years, from more than two dozen in 1980 to just a handful in 2004. There are many reasons for the decline in vaccine producers. A spate of corporate mergers in the 1990s, for example, reduced the number of major international pharmaceutical companies. The financial risk of investing in vaccines is also a key factor. In 2003, the entire market for all vaccines -- from polio to measles to hepatitis to influenza -- amounted to just $5.4 billion. Although that sum may seem considerable, it is less than two percent of the global pharmaceutical market of $337.3 billion. Unlike chemical compounds, vaccines and most other biological products are difficult to make and can easily become contaminated. There is also a large and litigious antivaccine constituency -- some people believe that vaccines cause harmful side effects such as Alzheimer's disease and autism -- adding considerable liability costs to manufacturers' bottom lines.

The production of influenza vaccines holds particular drawbacks for companies. Flu vaccines must be made rapidly, increasing the risk of contamination or other errors. Because of the seasonal nature of the flu, a new batch of influenza vaccines must be produced each year. Should sales in a given year prove disappointing, flu vaccines cannot be stockpiled for sale in a subsequent season because by then the viruses will have evolved. In addition, the manufacturing process of flu vaccines is uniquely complex: pharmaceutical companies must grow viral samples on live chicken eggs, which must be reared under rigorous hygienic conditions. Research is under way on reverse genetics and cellular-level production techniques that might prove cheaper, faster, and less contamination-prone than using eggs, but for the foreseeable future manufacturers are stuck with the current laborious method. After cultivation, samples of the viruses must be harvested, the H and N characteristics must be shown to produce antibodies in test animals and human volunteers, and tests must prove that the vaccine is not contaminated. Only then can mass production commence.


The H5N1 strain of avian flu poses an additional problem: the virus is 100 percent lethal to chickens -- and that includes chicken eggs. It took researchers five years of hard work to devise a way to grow the 1997 version of the H5N1 virus on eggs without killing them; although there have been technological improvements since then, there is no guarantee that an emerging pandemic strain could be cultivated fast enough.

In the current system, all influenza vaccines must be quickly made following a WHO meeting of flu experts held every February. At that gathering, scientists scrutinize all available information on the flu strains known to be circulating in the world. They then try to predict which strains are most likely to spread across every continent in the next six to nine months. (This year the WHO committee chose three human flu strains, of types H3N2 and H1N1, to be the basis of the next vaccine.) Samples of the chosen strains are delivered to pharmaceutical companies around the world for vaccine production, and the vaccines are hopefully available to the public by September or October -- a few months after influenza typically strikes Asia, in the early summer. Europe and the Americas are usually hit shortly after, in September. Because viruses constantly change themselves, the process cannot be executed earlier in the year.

Although new technology may allow an increase in production capacity, manufacturers have never made more than 300 million doses of flu vaccine in a single year. The slow pace of production means that in the event of an H5N1 flu pandemic millions of people would likely be infected well before vaccines could be distributed.


GLOBAL REACH

The scarcity of flu vaccine, although a serious problem, is actually of little relevance to most of the world. Even if pharmaceutical companies managed to produce enough effective vaccine in time to save some privileged lives in Europe, North America, Japan, and a few other wealthy nations, more than six billion people in developing countries would go unvaccinated. Stockpiles of Tamiflu and other anti-influenza drugs would also do nothing for those six billion, at least 30 percent of whom -- and possibly half -- would likely get infected in such a pandemic.

Resources are so scarce that both wealthy and poor countries would be foolish to count on the generosity of their neighbors during a global outbreak. Were the United States to miraculously overcome its vaccine production problems and produce ample supplies for U.S. citizens, Washington would probably deny the vaccine to neighbors such as Mexico, since governments tend to reserve vaccine supplies for their own citizens during emergencies. Were the United States to falter, it would probably not be able to rely on Canadian or European generosity, as it did just last year. When the United Kingdom suspended the license for the Chiron Corporation's U.K. production facility for flu vaccine due to contamination problems, Canada and Germany bailed the United States out, supplying additional doses until the French company Sanofi Pasteur could manufacture more. Even with this assistance, however, the United States' vaccine needs were not fully met until February 2005 -- the tail end of the flu season.

In the event of a deadly influenza pandemic, it is doubtful that any of the world's wealthy nations would be able to meet the needs of their own citizenry -- much less those of other countries. Domestic vaccine purchasing and distribution schemes currently assume that only the very young, the elderly, and the immunocompromised are at serious risk of dying from the flu. That assumption would have led health leaders in 1918 to vaccinate all of the wrong people. Then, the young and the old fared relatively well, while those aged 20 to 35 -- today typically the lowest priority for vaccination -- suffered the most deaths from the Spanish flu. And so far, H5N1 influenza looks like it could have a similar effect: its human victims have all fallen into age groups that would not be on national vaccine priority lists, and because H5N1 has never circulated among humans before, it is highly conceivable that all ages could be susceptible. Every year, trusting that the flu will kill only the usual risk groups, the United States plans for 185 million vaccine doses. If that guess were wrong -- if all Americans were at risk -- the nation would need at least 300 million doses. That is what the entire world typically produces each year.

There would thus be a global scramble for vaccine. Some governments might well block foreign access to supplies produced on their soil and bar vaccine export. Since little vaccine is actually made in the United States, this could prove a problem for Americans in particular. Facing such limited supplies, the U.S., European, and Japanese governments might give priority to vaccinating heads of state around the world in hopes of limiting social chaos. But who among the elite would be eligible? Would their families be included? How could such a global triage be executed justly?

A similar calculus might be necessary for countries engaged in significant military operations. Troop movements would certainly help spread the disease, just as World War I aided the growth of the 1918-19 Spanish flu. Back then, the flu wreaked havoc on combatant nations. In the summer of 1918, influenza killed far more soldiers than did bombs, bullets, or mustard gas. By October, some 46 percent of the French army was off the field of battle -- ailing, dying, or caring for flu victims. Influenza death tolls among the various military forces generally ranged from 5 to 10 percent, but some segments fared even worse: historian John Barry has reported that 22 percent of the Indian members of the British military died.

In the event of a modern pandemic, the U.S. Department of Defense, with the lessons of World War I in mind, would undoubtedly insist that U.S. troops in Iraq and Afghanistan be given top access to vaccines and antiflu drugs. About 170,000 U.S. forces are currently stationed in Iraq and Afghanistan, while 200,000 more are permanently based elsewhere overseas. All of them would potentially be in danger: in late March, for example, North Korea conceded it was suffering a large-scale H7N1 outbreak -- taking place within miles of some 41,000 U.S. military forces. It is impossible to predict how such a pandemic influenza would affect U.S. operations in Iraq, Afghanistan, Colombia, or any other place.

Armed forces throughout the world would face similar issues. Most would no doubt pressure their governments for preferential access to vaccine and medications. In addition, more than a quarter of some African armies and police forces are HIV positive, perhaps making them especially vulnerable to influenza's lethal impact. Social instability resulting from troop and police losses there would likely be particularly acute.

Such a devastating disease would clearly have profound implications for international relations and the global economy. With death tolls rising, vaccines and drugs in short supply, and the potential for the virus to spread further, governments would feel obliged to take drastic measures that could inhibit travel, limit worldwide trade, and alienate their neighbors. In fact, the Z+ virus has already demonstrated its disruptive potential on a limited scale. In July 2004, for example, when the Z+ strain reemerged in Vietnam after a three-month hiatus, officials in the northern province of Bac Giang charged that Chinese smugglers were selling old and sickly birds in Vietnamese markets -- where more than ten tons of chickens are smuggled daily. Chinese authorities in charge of policing their side of the porous border, more than 1,000 kilometers long, countered that it was impossible to inspect all the shipments. Such conflicts are now limited to the movement of livestock, but if a pandemic develops they could well escalate to a ban on trade and human movement.

Although there is little evidence that isolation measures have ever slowed the spread of influenza -- it is just too contagious -- most governments would likely resort to quarantines in a pandemic crisis. Indeed, on April 1, 2005, President George W. Bush issued an executive order authorizing the use of quarantines inside the United States and permitting the isolation of international visitors suspected of carrying influenza. If one country implements such orders, others will follow suit, bringing legal international travel to a standstill. The SARS (severe acute respiratory syndrome) virus, which was less dangerous than a pandemic flu by several orders of magnitude, virtually shut down Asian travel for three months.

As great as they would be, the economic consequences of travel restrictions, quarantines, and medical care would be well outstripped by productivity losses. In a typical flu season, productivity costs are ten times greater than all other flu-related costs combined. The decline in productivity is usually due directly to worker illness and absenteeism. During a pandemic, productivity losses would be even more disproportionate because entire workplaces -- schools, theaters, and public facilities -- would be shut down to limit human-to-human spread of the virus. Workers' illnesses also would likely be even more severe and last even longer than normal. Frankly, no models of social response to such a pandemic have managed to factor in fully the potential effect on human productivity. It is therefore impossible to reckon accurately the potential global economic impact.


AILING

The potential for a pandemic comes at a time when the world's public health systems are severely taxed and have long been in decline. This is true in both rich and poor countries.

The Bush administration recognized this weakness following the anthrax scare of 2001, which underscored the poor ability of federal and local health agencies to respond to bioterrorism or epidemic threats. Since that year, Congress has approved $3.7 billion to strengthen the nation's public health infrastructure. In 2003, the White House also took several steps to improve the nation's capacity to respond to a flu pandemic: it increased funding for the CDC's flu program by 242 percent, to $41.6 million in 2004; gave the National Institutes of Health an additional 320 percent in funds for flu-related research and development, for a total of $65.9 million; increased spending on the Food and Drug Administration's licensing capacity for flu vaccines and drugs by 173 percent, to $2.6 million; and spent an additional $80 million to create new stockpiles of Tamiflu and other anti-influenza drugs. On August 4, 2004, the Department of Health and Human Services also issued its pandemic flu plan, detailing further steps that would be taken by federal and state agencies in the event of a pandemic. Several other countries have released similar plans of action.

But despite all this, a recent event underscored the United States' tremendous vulnerability. In October 2004, the American College of Pathologists mailed a collection of mystery microbes prepared by a private lab to almost 5,000 labs in 18 countries for them to test as part their recertification. The mailing should have been routine procedure; instead, in March 2005 a Canadian lab discovered that the test kits included a sample of H2N2 flu -- a strain that had killed four million people worldwide in 1957. H2N2 has not been in circulation since 1968, meaning that hundreds of millions of people lack immunity to it. Had any of the samples leaked or been exposed to the environment, the results could have been devastating. On learning of the error, the WHO called for the immediate destruction of all the test kits. Miraculously, none of the virus managed to escape any of the labs.

But the snafu raises serious questions: If billions have been spent to improve laboratory capabilities since 2001, why did nobody notice the H2N2 flu until about six months after the kits had been shipped? Why did a private company possess samples of the virulent flu? Why was the sample included in the kits? In the aftermath of the September 11, 2001, attacks and the anthrax scare, many countries reclassified 1957-58 and 1968-69 influenza strains as Level 3 pathogens, requiring extreme care in their handling, distribution, and storage -- why did the United States still consider H2N2 to be a mere Level 2 pathogen, a type frequently mailed and studied? Finally, around the world, what other labs -- public and private -- currently possess samples of such lethal influenza viruses? The official CDC answer to these questions is, "We don't know."

Even with all of these gaps, probably the greatest weakness that each nation must individually address is the inability of their hospitals to cope with a sudden surge of new patients. Medical cost cutting has resulted in a tremendous reduction in the numbers of staffed hospital beds in the wealthy world, especially in the United States. Even during a normal flu season, hospitals located in popular retirement areas have great difficulty meeting the demand. In a pandemic, it is doubtful that any nation would have adequate medical facilities and personnel to meet the extra need.

National policymakers would be wise to plan now for worst-case scenarios involving quarantines, weakened armed services, and dwindling hospital space and vaccine supplies. But at the end of the day, effectively combating influenza will require multilateral and global mechanisms. Chief among them, of course, is the WHO, which since 1947 has maintained a worldwide network that conducts influenza surveillance. The WHO system oversees laboratories all over the world, chases (and sometimes refutes) rumors of pandemics, pushes for government transparency regarding human and avian flu cases, and acts as an arbiter in negotiations over vaccine production, trade embargoes, and border disputes. Its companion UN agency, the Food and Agriculture Organization (FAO), working closely with the World Organization for Animal Health, monitors flu outbreaks in animal populations and advises governments on culling flocks and herds, cross-border animal trade, animal husbandry and slaughter, and livestock quarantine and vaccination. All of these organizations have published lengthy guidelines on how to respond to a pandemic flu, lists of answers to commonly asked questions, and descriptions of their research priorities -- most of which have been posted on their Web sites.

The efforts of these agencies should be bolstered, both with expertise and dollars. The WHO, for example, has an annual core budget of just $400 million, a tiny increment of which is spent on influenza- and epidemic-response programs. (In comparison, the annual budget of New York City's health department exceeds $1.2 billion.) An unpublished internal study estimates that the agency would require at least another $600 million for its flu program were a pandemic to erupt. It is in every government's interest to give the WHO and the FAO the authority to act as impartial voices during a pandemic, able (theoretically) to assess objectively the epidemic's progress and rapidly evaluate research claims. The WHO in particular must have adequate funding and personnel to serve as an accurate clearinghouse of information about the disease, thereby preventing the spread of false rumors and global panic. No nation can erect a fortress against influenza -- not even the world's wealthiest country.

Few members of the U.S. Congress or its legislative counterparts around the world were alive when the great Spanish flu swept the planet. There may be some who lost parents, aunts, or uncles to the 1918-19 pandemic, and perhaps even more have heard the horror stories that were passed down. But politics breeds shortsightedness, and for decades the threat of an influenza pandemic has been easily forgotten, and therefore ignored at budget time. Politicians and health leaders made many serious errors in 1918-19; some historians say that President Wilson sent 43,000 soldiers to their deaths by forcing them aboard crowded ships to join a war he had already won. But in those days, human beings had no understanding of their influenza foe.

In 1971, the great American public health leader Alexander Langmuir likened flu forecasting to trying to predict the weather, arguing that "as with hurricanes, pandemics can be identified and their probable course projected so that warnings can be issued. Epidemics, however, are more variable [than hurricanes], and the best that can be done is to estimate probabilities."

Since Langmuir's time a quarter of a century ago, weather forecasting has gained a stunning level of precision. And although scientists cannot tell political leaders when an influenza pandemic will occur, researchers today are able to guide policymakers with information and analysis exponentially richer than that which informed the decisions of President Ford and the 1976 Congress. Whether or not this particular H5N1 influenza mutates into a human-to-human pandemic form, the scientific evidence points to the potential that such an event will take place, perhaps soon. Those responsible for foreign policy and national security, the world over, cannot afford to ignore the warning.

[Gabrielle]

This is another nice article from Foreign Affairs. It urges businesses to start preparing for the near certain pandemic.

Preparing for the Next Pandemic
Michael T. Osterholm
From Foreign Affairs, July/August 2005

Summary: If an influenza pandemic struck today, borders would close, the global economy would shut down, international vaccine supplies and health-care systems would be overwhelmed, and panic would reign. To limit the fallout, the industrialized world must create a detailed response strategy involving the public and private sectors.

Michael T. Osterholm is Director of the Center for Infectious Disease Research and Policy, Associate Director of the Department of Homeland Security's National Center for Food Protection and Defense, and Professor at the University of Minnesota's School of Public Health.

FEAR ITSELF

Dating back to antiquity, influenza pandemics have posed the greatest threat of a worldwide calamity caused by infectious disease. Over the past 300 years, ten influenza pandemics have occurred among humans. The most recent came in 1957-58 and 1968-69, and although several tens of thousands of Americans died in each one, these were considered mild compared to others. The 1918-19 pandemic was not. According to recent analysis, it killed 50 to 100 million people globally. Today, with a population of 6.5 billion, more than three times that of 1918, even a "mild" pandemic could kill many millions of people.

A number of recent events and factors have significantly heightened concern that a specific near-term pandemic may be imminent. It could be caused by H5N1, the avian influenza strain currently circulating in Asia. At this juncture scientists cannot be certain. Nor can they know exactly when a pandemic will hit, or whether it will rival the experience of 1918-19 or be more muted like 1957-58 and 1968-69. The reality of a coming pandemic, however, cannot be avoided. Only its impact can be lessened. Some important preparatory efforts are under way, but much more needs to be done by institutions at many levels of society.


THE BACKDROP

Of the three types of influenza virus, influenza type A infects and kills the greatest number of people each year and is the only type that causes pandemics. It originates in wild aquatic birds. The virus does not cause illness in these birds, and although it is widely transmitted among them, it does not undergo any significant genetic change.

Direct transmission from the birds to humans has not been demonstrated, but when a virus is transmitted from wild birds to domesticated birds such as chickens, it undergoes changes that allow it to infect humans, pigs, and potentially other mammals. Once in the lung cells of a mammalian host, the virus can "reassort," or mix genes, with human influenza viruses that are also present. This process can lead to an entirely new viral strain, capable of sustained human-to-human transmission. If such a virus has not circulated in humans before, the entire population will be susceptible. If the virus has not circulated in the human population for a number of years, most people will lack residual immunity from previous infection.

Once the novel strain better adapts to humans and is easily transmitted from person to person, it is capable of causing a new pandemic. As the virus passes repeatedly from one human to the next, it eventually becomes less virulent and joins the other influenza viruses that circulate the globe each year. This cycle continues until another new influenza virus emerges from wild birds and the process begins again.

Some pandemics result in much higher rates of infection and death than others. Scientists now understand that this variation is a result of the genetic makeup of each specific virus and the presence of certain virulence factors. That is why the 1918-19 pandemic killed many more people than either the 1957-58 or the 1968-69 pandemic.

A CRITICAL DIFFERENCE

Infectious diseases remain the number one killer of humans worldwide. Currently, more than 39 million people live with HIV, and last year about 2.9 million people died of AIDS, bringing the cumulative total of deaths from AIDS to approximately 25 million. Tuberculosis (TB) and malaria also remain major causes of death. In 2003, about 8.8 million people became infected with TB, and the disease killed more than 2 million. Each year, malaria causes more than 1 million deaths and close to 5 billion episodes of clinical illness. In addition, newly emerging infections, diarrheal and other vector-borne diseases, and agents resistant to antibiotics pose a serious and growing public health concern.

Given so many other significant infectious diseases, why does another influenza pandemic merit unique and urgent attention? First, of the more than 1,500 microbes known to cause disease in humans, influenza continues to be the king in terms of overall mortality. Even in a year when only the garden-variety strains circulate, an estimated 1-1.5 million people worldwide die from influenza infections or related complications. In a pandemic lasting 12 to 36 months, the number of cases and deaths would rise dramatically.

Recent clinical, epidemiological, and laboratory evidence suggests that the impact of a pandemic caused by the current H5N1 strain would be similar to that of the 1918-19 pandemic. More than half of the people killed in that pandemic were 18 to 40 years old and largely healthy. If 1918-19 mortality data are extrapolated to the current U.S. population, 1.7 million people could die, half of them between the ages of 18 and 40. Globally, those same estimates yield 180-360 million deaths, more than five times the cumulative number of documented AIDS deaths. In 1918-19, most deaths were caused by a virus-induced response of the victim's immune system -- a cytokine storm -- which led to acute respiratory distress syndrome (ARDS). In other words, in the process of fighting the disease, a person's immune system severely damaged the lungs, resulting in death. Victims of H5N1 have also suffered from cytokine storms, and the world is not much better prepared to treat millions of cases of ARDS today than it was 85 years ago. In the 1957-58 and 1968-69 pandemics, the primary cause of death was secondary bacterial pneumonias that infected lungs weakened by influenza. Although such bacterial infections can often be treated by antibiotics, these drugs would be either unavailable or in short supply for much of the global population during a pandemic.

The arrival of a pandemic influenza would trigger a reaction that would change the world overnight. A vaccine would not be available for a number of months after the pandemic started, and there are very limited stockpiles of antiviral drugs. Plus, only a few privileged areas of the world have access to vaccine-production facilities. Foreign trade and travel would be reduced or even ended in an attempt to stop the virus from entering new countries -- even though such efforts would probably fail given the infectiousness of influenza and the volume of illegal crossings that occur at most borders. It is likely that transportation would also be significantly curtailed domestically, as smaller communities sought to keep the disease contained. The world relies on the speedy distribution of products such as food and replacement parts for equipment. Global, regional, and national economies would come to an abrupt halt -- something that has never happened due to HIV, malaria, or TB despite their dramatic impact on the developing world.

The closest the world has come to this scenario in modern times was the SARS (severe acute respiratory syndrome) crisis of 2003. Over a period of five months, about 8,000 people were infected by a novel human coronavirus. About ten percent of them died. The virus apparently spread to humans when infected animals were sold and slaughtered in unsanitary and crowded markets in China's Guangdong Province. Although the transmission rate of SARS paled in comparison to that of influenza, it demonstrated how quickly such an infectious agent can circle the globe, given the ease and frequency of international travel. Once SARS emerged in rural China, it spread to five countries within 24 hours and to 30 countries on six continents within several months.

The SARS experience teaches a critical lesson about the potential global response to a pandemic influenza. Even with the relatively low number of deaths it caused compared to other infectious diseases, SARS had a powerful negative psychological impact on the populations of many countries. In a recent analysis of the epidemic, the National Academy of Science's Institute of Medicine concluded: "The relatively high case-fatality rate, the identification of super-spreaders, the newness of the disease, the speed of its global spread, and public uncertainty about the ability to control its spread may have contributed to the public's alarm. This alarm, in turn, may have led to the behavior that exacerbated the economic blows to the travel and tourism industries of the countries with the highest number of cases."

SARS provided a taste of the impact a killer influenza pandemic would have on the global economy. Jong-Wha Lee, of Korea University, and Warwick McKibbin, of the Australian National University, estimated the economic impact of the six-month SARS epidemic on the Asia-Pacific region at about $40 billion. In Canada, 438 people were infected and 43 died after an infected person traveled from Hong Kong to Toronto, and the Canadian Tourism Commission estimated that the epidemic cost the nation's economy $419 million. The Ontario health minister estimated that SARS cost the province's health-care system about $763 million, money that was spent, in part, on special SARS clinics and supplies to protect health-care workers. The SARS outbreak also had a substantial impact on the global airline industry. After the disease hit in 2003, flights in the Asia-Pacific area decreased by 45 percent from the year before. During the outbreak, the number of flights between Hong Kong and the United States fell 69 percent. And this impact would pale in comparison to that of a 12- to 36-month worldwide influenza pandemic.

The SARS epidemic also raises questions about how prepared governments are to address a prolonged infectious-disease crisis -- particularly governments that are already unstable. Seton Hall University's Yanzhong Huang concluded that the SARS epidemic created the most severe social or political crisis encountered by China's leadership since the 1989 Tiananmen crackdown. China's problems probably resulted less from SARS' public health impact than from the government's failed effort to allay panic by withholding information about the disease from the Chinese people. The effort backfired. During the crisis, Chinese Premier Wen Jiabao pointed out in a cabinet meeting on the epidemic that "the health and security of the people, overall state of reform, development, and stability, and China's national interest and image are at stake." But Huang believes that "a fatal period of hesitation regarding information-sharing and action spawned anxiety, panic, and rumor-mongering across the country and undermined the government's efforts to create a milder image of itself in the international arena."

Widespread infection and economic collapse can destabilize a government; blame for failing to deal effectively with a pandemic can cripple a government. This holds even more for an influenza pandemic. In the event of a pandemic influenza, the level of panic witnessed during the SARS crisis could spiral out of control as illnesses and deaths continued to mount over months and months. Unfortunately, the public is often indifferent to initial warnings about impending infectious-disease crises -- as with HIV, for example. Indifference becomes fear only after the catastrophe hits, when it is already too late to implement preventive or control measures.

READY FOR THE WORST

What should the industrialized world be doing to prepare for the next pandemic? The simple answer: far more. So far, the World Health Organization and several countries have finalized or drafted useful but overly general plans. The U.S. Department of Health and Human Services has increased research on influenza-vaccine production and availability. These efforts are commendable, but what is needed is a detailed operational blueprint for how to get a population through one to three years of a pandemic. Such a plan must involve all the key components of society. In the private sector, the plan must coordinate the responses of the medical community, medical suppliers, food providers, and the transportation system. In the government sector, the plan should take into account officials from public health, law enforcement, and emergency management at the international, federal, state, and local levels.

At the same time, it must be acknowledged that such master blueprints may have their drawbacks, too. Berkeley's Aaron Wildavsky persuasively argued that resilience is the real key to crisis management -- overly rigid plans can do more harm than good. Still, planning is enormously useful. It gives government officials, private-sector partners, and the community the opportunity to meet, think through potential dilemmas, purchase necessary equipment, and set up organizational structures for a 12- to 36-month response. A blueprint forces leaders to rehearse their response to a crisis, preparing emotionally and intellectually so that when disaster strikes the community can face it.

Influenza-vaccine production deserves special attention. An initiative to provide vaccine for the entire world must be developed, with a well-defined schedule to ensure progress. It is laudable that countries such as the United States and Vietnam are pursuing programs with long-term goals to develop and produce H5N1 vaccine for their respective populations. But if the rest of the world lacks supplies, even the vaccinated will be devastated when the global economy comes to an abrupt halt. Pandemic-influenza preparedness is by nature an international issue. No one can truly be isolated from a pandemic.

The pandemic-related collapse of worldwide trade and its ripple effect throughout industrialized and developing countries would represent the first real test of the resiliency of the modern global delivery system. Given the extent to which modern commerce relies on the precise and readily available international trade of goods and services, a shutdown of the global economic system would dramatically harm the world's ability to meet the surging demand for essential commodities such as food and medicine during a crisis. The business community can no longer afford to play a minor role in planning the response to a pandemic. For the world to have critical goods and services during a pandemic, industry heads must stockpile raw materials for production and preplan distribution and transportation support. Every company's senior managers need to be ready to respond rapidly to changes in the availability, production, distribution, and inventory management of their products. There is no model for how to revive the current global economy were it to be devastated.

To truly be complete, all planning on international, regional, national, and local levels must consider three different scenarios: What if the pandemic begins tonight? What if it starts one year from now? What if the world is so fortunate as to have an entire decade to prepare? All are possible, but none is certain.


STARTING TONIGHT

What would happen today in the office of every nation's leader if several cities in Vietnam suffered from major outbreaks of H5N1 infection, with a five percent mortality rate? First, there would be an immediate effort to try to sort out disparate disease-surveillance data from a variety of government and public health sources to determine which countries might have pandemic-related cases. Then, the decision would likely be made to close most international and even some state or provincial borders -- without any predetermined criteria for how or when those borders might be reopened. Border security would be made a priority, especially to protect potential supplies of pandemic-specific vaccines from nearby desperate countries. Military leaders would have to develop strategies to defend the country and also protect against domestic insurgency with armed forces that would likely be compromised by the disease. Even in unaffected countries, fear, panic, and chaos would spread as international media reported the daily advance of the disease around the world.

In short order, the global economy would shut down. The commodities and services countries would need to "survive" the next 12 to 36 months would have to be identified. Currently, most businesses' continuity plans account for only a localized disruption -- a single plant closure, for instance -- and have not planned for extensive, long-term outages. The private and public sectors would have to develop emergency plans to sustain critical domestic supply chains and manufacturing and agricultural production and distribution. The labor force would be severely affected when it was most needed. Over the course of the year, up to 50 percent of affected populations could become ill; as many as five percent could die. The disease would hit senior management as hard as the rest of the work force. There would be major shortages in all countries of a wide range of commodities, including food, soap, paper, light bulbs, gasoline, parts for repairing military equipment and municipal water pumps, and medicines, including vaccines unrelated to the pandemic. Many industries not critical to survival -- electronics, automobile, and clothing, for example -- would suffer or even close. Activities that require close human contact -- school, seeing movies in theaters, or eating at restaurants -- would be avoided, maybe even banned.

Vaccine would have no impact on the course of the virus in the first months and would likely play an extremely limited role worldwide during the following 12 to 18 months of the pandemic. Despite major innovations in the production of most other vaccines, international production of influenza vaccine is based on a fragile and limited system that utilizes technology from the 1950s. Currently, annual production of influenza vaccine is limited to about 300 million trivalent doses -- which protect against three different influenza strains in one dose -- or less than one billion monovalent doses. To counter a new strain of pandemic influenza that has never circulated throughout the population, each person would likely need two doses for adequate protection. With today's limited production capacity, that means that less than 500 million people -- about 14 percent of the world's population -- would be vaccinated within a year of the pandemic. In addition, because the structure of the virus changes so rapidly, vaccine development could only start once the pandemic began, as manufacturers would have to obtain the new pandemic strain. It would then be at least another six months before mass production of the vaccine.

Even if the system functions to the best of its ability, influenza vaccine is produced commercially in just nine countries: Australia, Canada, France, Germany, Italy, Japan, the Netherlands, the United Kingdom, and the United States. These countries contain only 12 percent of the world's population. In the event of an influenza pandemic, they would probably nationalize their domestic production facilities, as occurred in 1976, when the United States, anticipating a pandemic of swine influenza (H1N1), refused to share its vaccine.

If a pandemic struck the world today, there would be another possible weapon against influenza: antiviral medicine. When taken daily during the time of exposure to influenza, antivirals have prevented individuals from becoming ill. They have also reduced the severity of illness and subsequent complications when taken within 48 hours of onset. Although there is no data for H5N1, it is assumed antivirals would also prevent H5N1 infection if taken before exposure. There is no evidence, however, that current antiviral influenza drugs would help if the patient developed the kind of cytokine storm that has characterized recent H5N1 infections. But barring this complication, H5N1 should be treatable with Tamiflu (oseltamivir phosphate), which is manufactured by the Roche pharmaceuticals company in a single plant in Switzerland.

In responding to a pandemic, Tamiflu could have a measurable impact in the limited number of countries with sizable stockpiles, but for most of the world it would not be available. Although the company plans on opening another facility in the United States this year, annual production would still cover only a small percentage of the world's population. To date, at least 14 countries have ordered Tamiflu, but the amount of these orders is enough to treat only 40 million people. The orders take considerable time to be processed and delivered -- manufacturing can take up to a year -- and in an emergency the company's ability to produce more would be limited. As with vaccines, countries would probably nationalize their antiviral supplies during a pandemic. Even if the medicine were available, most countries could not afford to buy it. Critical antibiotics, for treatment of secondary bacterial infections, would also be in short supply during a pandemic. Even now, supplies of eight different anti-infective agents are limited in the United States due to manufacturing problems.

Aside from medication, many countries would not have the ability to meet the surge in the demand for health-care supplies and services that are normally taken for granted. In the United States, for example, there are 105,000 mechanical ventilators, 75,000 to 80,000 of which are in use at any given time for everyday medical care. During a routine influenza season, the number of ventilators being used shoots up to 100,000. In an influenza pandemic, the United States may need as many as several hundred thousand additional ventilators.

A similar situation exists in all developed countries. Virtually every piece of medical equipment or protective gear would be in short supply within days of the recognition of a pandemic. Throughout the crisis, many of these necessities would simply be unavailable for most health-care institutions. Currently, two U.S.-based companies supply most of the respiratory protection masks for health-care workers around the world. Neither company would be able to meet the jump in demand, in part because the component parts for the masks come from multiple suppliers in multiple countries. With travel and transportation restricted, masks may not even be produced at all.

Health-care providers and managed-care organizations are also unprepared for an outbreak of pandemic influenza today. There would be a tremendous demand for skilled health professionals. New "hospitals" in high school gymnasiums and community centers would have to be staffed for one to three years. Health-care workers would probably get sick and die at the same rate as the general public -- perhaps at an even higher rate, particularly if they lack access to protective equipment. If they lack such fundamental supplies, it is unclear how many professionals would continue to place themselves in high-risk situations by caring for the infected. Volunteers who are naturally immune as a result of having survived influenza infection would thus have to be found and employed. That means that the medical community's strong resistance to using lay volunteers, which is grounded in both liability concerns and professional hubris, would need to be addressed.

Other unpleasant issues would also need to be tackled. Who would have priority access to the extremely limited antiviral supplies? The public would consider any ad hoc prioritization unfair, creating further dissent and disruption during a pandemic. In addition, there would not even be detailed plans for handling the massive number of dead bodies that would soon outstrip the ability to process them. Clearly, an influenza pandemic that struck today would demand an unprecedented medical and nonmedical response. This requires planning well beyond anything devised thus far by any of the world's countries and organizations.

A YEAR FROM NOW

Even if an H5N1 pandemic is a year away, the world must plan for the same problems with the same fervor. Major campaigns must be initiated to prepare the nonmedical and medical sectors. Pandemic planning must be on the agenda of every school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor in the United States and beyond. There is an urgent need to reassess the vulnerability of the global economy to ensure that surges in demand can be met. Critical heath-care and consumer products and commodities must be stockpiled. Health professionals must learn how to better communicate risk and must be able to both provide the facts and acknowledge the unknowns to a frightened or panicked population.

If there is a year of lead-time before an H5N1 pandemic, vaccine could play a more central role in the global response. Although the world would still have a limited capacity to manufacture influenza vaccine, techniques that could allow scientists to get multiple doses from a current single dose may increase the supply. In addition to further research on this issue, efforts are needed to ensure the availability of syringes and equipment for delivering vaccine. There must also be an international plan for how the vaccine would be allocated. It is far better to struggle with the ethical issues involved in determining such priorities now, in a public forum, rather than to wait until the crisis occurs.

Prevention must also be improved. Priority should be placed on early intervention and risk assessment. And an aggressive and comprehensive research agenda must be launched immediately to study the ecology and biology of the influenza virus and the epidemiologic role of various animal and bird species.


TEN YEARS LATER

If developed countries begin to transform radically the current system of influenza-vaccine production, an influenza pandemic ten years from now could have a much less devastating outcome. The industrialized world must initiate an international project to develop the ability to produce a vaccine for the entire global population within several months of the start of a pandemic. The initiative must be a top priority of the group of seven industrialized nations plus Russia (G-8), because almost nothing could inflict more death and disruption than a pandemic influenza.

The current BioShield law and additional legislation recently submitted to Congress will act to enhance the availability of vaccines in the United States. This aim is laudable, but it does little to address international needs. The ultimate goal must be to develop a new cell-culture vaccine or comparable vaccine technology that works on all influenza subtypes and that can be made available on short notice to all the people of the world.


WHAT COURSE TO TAKE?

The world must form a better understanding of the potential for the emergence of a pandemic influenza strain. A pandemic is coming. It could be caused by H5N1 or by another novel strain. It could happen tonight, next year, or even ten years from now.

The signs are alarming: the number of human and animal H5N1 infections has been increasing; small clusters of cases have been documented, suggesting that the virus may have come close to sustained human-to-human transmission; and H5N1 continues to evolve in the virtual genetic reassortment laboratory provided by the unprecedented number of people, pigs, and poultry in Asia. The population explosion in China and other Asian countries has created an incredible mixing vessel for the virus. Consider this sobering information: the most recent influenza pandemic, of 1968-69, emerged in China, when its population was 790 million; today it is 1.3 billion. In 1968, the number of pigs in China was 5.2 million; today it is 508 million. The number of poultry in China in 1968 was 12.3 million; today it is 13 billion. Changes in other Asian countries are similar. Given these developments, as well as the exponential growth in foreign travel over the past 50 years, an influenza pandemic could be more devastating than ever before.

Can disaster be avoided? The answer is a qualified yes. Although a coming pandemic cannot be avoided, its impact can be considerably lessened. It depends on how the leaders of the world -- from the heads of the G-8 to local officials -- decide to respond. They must recognize the economic, security, and health threat that the next influenza pandemic poses and invest accordingly. Each leader must realize that even if a country has enough vaccine to protect its citizens, the economic impact of a worldwide pandemic will inflict substantial pain on everyone. The resources required to prepare adequately will be extensive. But they must be considered in light of the cost of failing to invest: a global world economy that remains in a shambles for several years.

This is a critical point in history. Time is running out to prepare for the next pandemic. We must act now with decisiveness and purpose. Someday, after the next pandemic has come and gone, a commission much like the 9/11 Commission will be charged with determining how well government, business, and public health leaders prepared the world for the catastrophe when they had clear warning. What will be the verdict?

[Gabrielle]

The Human-Animal Link
William B. Karesh and Robert A. Cook
From Foreign Affairs, July/August 2005

Summary: Recent outbreaks of avian flu, SARS, the Ebola virus, and mad cow disease wreaked havoc on global trade and transport. They also all originated in animals. Humanity today is acutely vulnerable to diseases that start off in other species, yet our health care remains dangerously blinkered. It is time for a new, global approach.

William B. Karesh is Director of the Field Veterinary Program at the Wildlife Conservation Society and Co-chair of the World Conservation Union's Veterinary Specialist Group. Robert A. Cook is Vice President of and Chief Veterinarian at the Wildlife Conservation Society.

ONE WORLD, ONE HEALTH

In recent years, outbreaks of diseases such as avian flu, severe acute respiratory syndrome (SARS), the Ebola virus, and mad cow disease have frightened the public, disrupted global commerce, caused massive economic losses, and jeopardized diplomatic relations. These diseases have also shared a worrisome key characteristic: the ability to cross the Darwinian divide between animals and people. None of these illnesses depends on human hosts for its survival; as a result, they all persist today, far beyond the reach of medical intervention.

Meanwhile, humanity has become vulnerable to cross-species illnesses, thanks to modern advances such as the rapid transportation of both goods and people, increasing population density around the globe, and a growing dependence on intensified livestock production for food. The global transport of animals and animal products, which includes hundreds of species of wildlife, also provides safe passage for the harmful bacteria, viruses, and fungi they carry, not to mention the prion proteins that cause insidious illnesses such as mad cow disease and chronic wasting disease in deer and elk.

Adding to the risks is the fact that while many people in the developed world would scarcely recognize meat if it did not come wrapped in clear plastic, the vast majority of people on the planet today still slaughter animals for meat themselves or buy it fresh, salted, or smoked in open-air markets. These markets generally go uninspected by health officials, and consumers rarely have access to good health care, education on hygiene, common vaccines, or antibiotics.

Not only is local and national health care often a problem; internationally, no agency is responsible for, or capable of, monitoring and preventing the myriad diseases that can now cross the borders between countries and species. More specifically, no organization has the mandate to pursue policies based on a simple but critically important concept: that the health of people, animals, and the environment in which we all live are inextricably linked.

Thus, for example, the U.S. Department of Agriculture works to protect only the U.S. livestock industry and has scaled back the attention it pays to animals outside the United States over the last two decades. Despite new concerns about terrorist attacks on the U.S. food supply, Washington has still made little attempt to research and reduce diseases overseas before they reach U.S. shores. Nor does the United Nations direct the resources necessary to do a better job. The UN Food and Agriculture Organization, for example, is mandated to monitor the production of livestock and crops but does little to track threats to and dangers from wild plants and animals. The World Animal Health Organization has a volunteer committee that considers wildlife-related diseases, but it consists of just six people and meets only three days a year. And the World Health Organization (WHO) can only get involved in a country if officially invited, leaving it helpless to intervene in countries with governments that either do not know about or do not want to reveal the presence of a disease within their borders. The U.S. Centers for Disease Control and Prevention (CDC) must similarly wait for an invitation before extending their reach outside the United States.

What all this means is that no government agency or multilateral organization today focuses on the numerous diseases that threaten people, domestic animals, and wildlife alike. Nor does any one body collect and collate data from across the scientific spectrum, to ensure that health solutions are based on the input of professionals from all the various health fields working with humans, domestic animals, and wildlife.

Yet diseases pay no regard to the divisions among species or academic disciplines, and the failure to recognize this truth is placing humanity in great peril. As a recent outbreak of avian influenza reminded the world, what happens in one part of it -- and to one species -- can have a deadly serious impact on others. The planet clearly needs a new health paradigm that not only integrates the efforts of disparate groups but also balances their respective influences, to help bridge the gaps between them. This is especially so since the immediate effects of a particular illness are often the least of the problem. Diseases that attack people and animals also cause poverty and civil unrest, disrupt "free" ecosystem services such as drinking water and plant pollination, and threaten otherwise well-planned and sustainable economic development efforts, such as low-impact tourism. In short, the failure to adopt a planetwide and cross-species approach to health is getting costlier by the day; humanity cannot afford to pay the price much longer.


THE WORLD WE WERE GIVEN

According to recent analysis, more than 60 percent of the 1,415 infectious diseases currently known to modern medicine are capable of infecting both animals and humans. Most of these diseases (such as anthrax, Rift Valley fever, bubonic plague, Lyme disease, and monkeypox) are "zoonotic," meaning that they originated in animals but have crossed the species barrier to infect people. The others, which receive less attention, are "anthropozoonotic," meaning they are typically found in humans but can and do infect animals as well (examples include the human herpes virus, tuberculosis, and measles). Dividing infectious agents into these two groups is convenient for teaching purposes. But it overlooks the critically important fact that all of them can move back and forth among species, mutating and changing their characteristics in the process. Avian influenza -- which started in birds but is now infecting humans as well -- has recently highlighted the need for a more holistic view of disease.

It is probably just luck that has so far allowed scientists to maintain these distinctions. One of the greatest medical success stories of the last century was the eradication of smallpox. But this achievement was largely due to the fact that smallpox survives in only one host species, namely humans. If even one more type of animal had been able to harbor the disease, there is a good chance that eradication would not have been accomplished, despite the Herculean global effort. When a pathogen can find refuge or a place to mutate in a range of hosts, controlling it becomes far more complex, requiring an integrated -- and much more difficult -- approach.

To get a sense of the breadth and the seriousness of the issue, consider HIV/AIDS, which most scientists now think arose in Africa as a result of the human consumption of primates that were infected with simian immunodeficiency viruses. Or consider the Ebola virus, which has a similar history. The disease first came to international attention in 1976, when it appeared around the Ebola River in what was then called Zaire. The virus infects people, gorillas, chimpanzees, and monkeys, causing severe internal and external hemorrhaging and leading to death in up to 90 percent of its human victims. Human infection spreads quickly, especially via caregivers and people who flee an area to escape the illness. Since the disease first appeared, successive human outbreaks have been recorded in Côte d'Ivoire, Gabon, Sudan, and Uganda. But humans have not been the only victims; lowland gorillas and chimpanzees in Gabon and Congo and chimpanzees in western equatorial Africa have been decimated by the sickness. Other forest animals, such as duikers (small antelopes) and bush pigs may also be affected. When subsistence hunters discover a sick or dead animal in the forest, they view it as good fortune and bring it home to feed their families or trade with their neighbors. The Ebola virus then easily infects those handling the meat, and a chain of contacts and infections ensue. Each of the human outbreaks in central Africa during the late 1990s and the first years of this century was traced to humans handling infected great apes.

SARS also arose from contact with wild animals. The illness first appeared in late 2002 in China's Guangdong Province, where people began complaining of high fever, cough, and diarrhea, and eventually developed severe pneumonia. The unknown disease was very contagious; within a matter of weeks, a visitor to Hong Kong helped spread it to five continents. By July of 2003, the WHO had tallied 8,437 cases and 813 deaths. Due mostly to a lack of understanding of the new disease, global travel and trade were disrupted as fear spread.

After four months, scientists eventually discovered that the mystery disease was caused by a coronavirus (a family of viruses found in many animal species). The virus, in turn, was traced back to a small mammal called the palm civet, which is farmed in the Guangdong region and sold for human consumption. Later, evidence of the virus was also found in raccoon dogs, ferrets, and badgers being sold in Guangdong's wildlife markets, as well as in domestic cats living in the city. Epidemiological studies confirmed that the first human infections had indeed come through animal contact, although the exact species responsible has not been definitively identified.

In the months after SARS first appeared, the Chinese government closed down its live wildlife markets. Within ten days of linking the disease to the wild animal trade, the government also confiscated close to a million animals, many of which had been brought into the area from other parts of the world and which hosted a variety of exotic viruses and bacteria. But the damage had already been done. Prior to the government action, the animals were often housed together, exposed to one another's waste, and sometimes even fed to one another. For a virus or bacteria capable of jumping between species, the markets had provided the perfect place to reproduce.


THE WORLD'S NOT FLAT, IT'S A MIXING BOWL

China, however, is far from the only country where people risk infection from animal-borne diseases. The West is also in danger, as was discovered in late May 2003, when the first cases of a mysterious illness were reported in hospitals in Illinois, Indiana, and Wisconsin. Patients, many of whom had been in close contact with pet prairie dogs, started coming down with skin ulcers and fevers. It was soon discovered that a prairie-dog dealer in Wisconsin had let a number of his animals mix with rodents recently imported from Ghana that happened to be carrying the monkeypox virus. An animal distributor had then sold the infected prairie dogs to pet stores in Milwaukee and at an animal swap meet in northern Wisconsin. Within about a month, 71 human cases of monkeypox in six Midwestern states had been reported to the CDC; luckily, no one died.

It remains unknown how or where waste from the infected prairie dogs was dumped or whether owners released any infected prairie dogs into the wild during the scare. Moreover, U.S. laws remain dangerously lax. At the time of the monkeypox outbreak, it was legal to import any nonendangered African rodent into the United States as a pet -- despite the fact that the risk of bringing in foreign diseases in the process was predictable and could have been avoided through international surveillance and information-sharing programs. (Wildlife health experts and human health workers in central Africa have long associated human monkeypox infections with rodent and squirrel contact.) Since the U.S. outbreak, Washington has imposed restrictions on the import of African rodents, but it remains legal to bring in rodents from other continents, and many other species from around the world continue to be shipped into the United States and many other countries, largely without oversight.

Determining the exact scale of the global wildlife trade is impossible, since the operations range from the extremely local to the international, and are often illegal and informal. Part of the picture, however, can be glimpsed from figures compiled by the Wildlife Conservation Society from a variety of sources. According to these numbers, the annual global trade in live wild animals includes roughly 4 million birds, 640,000 reptiles, and 40,000 primates. Following the SARS outbreak that began in 2002, the Chinese government reportedly confiscated 838,500 wild animals from the markets of Guangdong. But every year, tens of millions of wild mammals, birds, and reptiles continue to flow through these and other trading centers, where they make contact with humans and dozens of other species before being shipped elsewhere, sold locally, or sometimes freed back into the wild -- often carrying new and dangerous pathogens. The number of these animals that end up as food is staggering; indeed, experts estimate that in central Africa alone consumers eat 579 million individual wild animals a year, for a total of more than a billion kilograms of meat. Meanwhile, people in the Amazon basin are thought to consume between 67 and 164 million kilograms of wild animal meat a year, accounting for between 6.4 million and 15.8 million individual mammals alone.

Before these animals (with whatever diseases they may be carrying) are eaten, they encounter -- and possibly transmit pathogens to -- hunters and marketers. They also risk infecting domestic animals and wild scavengers in villages and market areas that consume the remnants and waste of wildlife eaten by humans. All considered, at least a billion direct and indirect contacts among wildlife, humans, and domestic animals result from the handling of wildlife and the wildlife trade annually.

Such contact does not just endanger humans and their pets; the pathogens inadvertently transported around the globe can also devastate local wildlife, disrupting the environment and causing enormous economic harm. In October 2004, avian flu (specifically, the H5N1 type A influenza virus) was detected in two mountain hawk-eagles that were smuggled from Thailand into Belgium in airline carry-on baggage. Last year, another deadly virus entered Italy via a shipment of Pakistani parrots, lovebirds, and finches. Chytridiomycosis, a fungal disease responsible for the extinction of 30 percent of the world's amphibian species, has been spread by the international trade and subsequent release of African clawed frogs (a popular laboratory animal). Tuberculosis originating from domestic cattle has now infected herds of wild bison in Canada, deer in Michigan, and cape buffalo and lions in South Africa. In 1999, rinderpest, a disease originally introduced to Africa by the importation of domestic cattle from India, killed more wild buffalo in Kenya than had been slain by poachers during the previous two decades.

The increasing movement of animals and humans around the world and their greater exposure to the many diseases that dance between them have also placed domesticated livestock at increasing risk. This is especially so since the ravenous international demand for animal meat has turned livestock production into an ultraintensive industry, with swine, poultry, and cattle operations now packing huge numbers of animals into limited spaces. Moreover, projections by the International Food Policy Research Institute indicate a doubling of animal production in developing countries over the next 20 years. Although modern factory-farm practices maximize food production, they also make livestock more susceptible to illness. Infection spreads quickly through crowded animal pens, and growing antibiotic resistance makes fighting disease more difficult. Many farms now routinely mix antibiotics with animal feed to avoid transmitting illnesses, and selective breeding for specific traits often predisposes animals to conditions requiring repeated antibiotic treatment. Such increased antibiotic use is helping to create dangerous drug-resistant superbugs that may endanger both animals and humans.

High-volume food production has also prompted the livestock industry to adopt other dangerous practices, which have already led to at least one high-profile disaster: the outbreak of bovine spongiform encephalopathy (BSE), or mad cow disease, in the United Kingdom. Mad cow disease is a chronic, degenerative disorder that affects the central nervous system of cattle. The disease, known as scrapie in sheep, had existed for hundreds of years without infecting other species. It only crossed over to cattle when British farmers started feeding infected sheep byproducts to their herds in the 1980s. Once BSE jumped to cows it started spreading rapidly, with 182,745 documented cases occurring between 1986 and 2002 in the United Kingdom. In response to the outbreak, European countries banned all imports of British cattle. But BSE has nonetheless been found in Europe, Canada, and the United States since then. It has also jumped to people, and a new human variant of the illness, known as Creutzfeldt-Jakob disease, is believed to be responsible for 150 deaths since 1995.

Malaysia has also fallen victim to a disease spread by new farming techniques: the Nipah virus, which appeared in the country's pig and human populations in 1998, killing 105 people and forcing the Malaysian government to cull more than one million pigs to stop the spread. Five species of fruit bats were later also found to carry the virus, suggesting a wide prevalence of the pathogen among healthy bats. It seems that people had acquired the virus from handling infected pigs, which had contracted the disease from bats feeding in fruit trees standing in newly developed pig farms.

The Nipah outbreak highlights what can happen when people and domestic animals modify previously undisturbed wild habitats. Within natural ecosystems, microbes and wildlife tend to exist more or less in balance. But the introduction of new species -- such as cows, pigs, dogs, or humans -- can allow pathogens to jump into these new hosts, which may have no natural immunity or evolved resistance. The results, predictably, can be devastating.

In addition to the direct health damage they have caused people and animals, animal-related pathogens have destabilized international trade and caused hundreds of billions of dollars of economic damage globally. The report of the U.S. National Intelligence Council's 2020 Project, Mapping the Global Future, has identified a global pandemic as the single most important threat to the global economy. In early 2003, the UN Food and Agriculture Organization reported that more than one-third of the global meat trade was being embargoed as a result of mad cow disease, avian influenza, and other livestock illnesses. According to Bio Economic Research Associates, the rash of emerging or reemerging livestock diseases that have cropped up around the world since the mid-1990s (illnesses that include mad cow disease, foot-and-mouth disease, avian influenza, swine fever, and others) has caused losses of an estimated $100 billion; SARS alone cost the global economy half that amount. The pain caused by such crises, moreover, has spread far beyond those responsible; wildlife market traders were not the ones who paid for the SARS outbreak, and the African rodent importer in Texas did not reimburse the U.S. and local governments for the millions of dollars spent to contain monkeypox in 2003.

Nor can these dollar figures adequately reflect the often devastating effect outbreaks can have on some of the poorest people on the planet. Since 2003, for example, efforts to control the spread of avian influenza in Asia have required the culling of more than 140 million chickens. In countries such as Thailand and Vietnam, the vast majority of these animals were not owned by large, industrial producers but by small farmers and peasants. Losing their livestock was painful indeed, especially since financial compensation schemes for rural poultry owners are rare to nonexistent in much of Southeast Asia. Not only did this lack of compensation increase the damage done by the disease; it also created a serious disincentive for bird owners to report suspicious illnesses among their flocks.

RISING TO THE OCCASION

As many of these examples suggest, preventing or controlling future outbreaks of animal-borne diseases and mitigating their impact will require a far broader approach than has so far been attempted by the generally isolated health systems of highly developed countries. Too often, the global response to new pathogens has been driven by fear, which has only magnified the economic and other costs of disease control.

That said, a few brave individuals have already begun the process of creating a new international and interdisciplinary approach to disease control. Working in some of the most remote places on earth, they have slowly established knowledge-sharing networks, such as the World Conservation Union's Veterinary Specialist Group. And their contributions have already been significant. For example, when avian influenza first appeared, much attention was mistakenly directed at controlling its spread among wild birds in Northeast and Southeast Asia. It was these new informal participants in health discussions -- such as conservation biologists and veterinarians working with the Wildlife Conservation Society in Cambodia and linked to staff at the Food and Agriculture Organization -- who were the first to point out that the migratory routes and timing of wild birds did not actually correspond with the spread of the disease and that domestic birds were more likely the culprit. Without this insight, valuable resources would have been wasted trying to control the disease among the wrong animal population.

As important as such contributions have been, however, many individuals trying to develop a new global approach to health-care work for nongovernmental organizations or for local governments lack the resources and a larger, formal network that could fill in the gaps in health care as it relates to wildlife and humanity. Were their resources improved, the results would be enormously beneficial; building bridges across disciplines to solve health problems can have simple but profound effects.

For example, studies in South America have shown that, contrary to common opinion, livestock diseases pose many more threats to wildlife than the other way around. In much of the world, reducing disease in domestic animals would benefit several industries, improve human health and livelihoods, and help safeguard wild animals. As this suggests, strategically increasing protections in one area of health care can benefit another. For example, gorillas and chimpanzees in central Africa have little to no immunity to common human diseases, and so they are endangered by contact with local people and tourists. This risk could be dramatically reduced by implementing good preventive health programs and practices in local villages, which would benefit both people and wildlife. Already, work with the Ebola virus in gorillas and chimpanzees has shown that investments in wildlife health can protect urban human populations; in Africa, animal health workers detected the presence of Ebola in wildlife months before the first human cases occurred, providing critical lead-time to warn villagers not to hunt or handle the animals that were a source of the infection. Such a broad, "one health" approach to disease can be much more effective and inexpensive than the traditional "quarantine and stamping out" strategy for fighting an illness after an outbreak has already begun. Specialists in human and animal health, in conjunction with wildlife conservation professionals, have already developed a set of guiding concepts on these themes, called the Manhattan Principles. But the ideas still need much broader acceptance to be more effective.

To further improve the chances of heading off and limiting the effect of animal-related diseases, a number of additional steps are necessary. To begin with, better worldwide surveillance to detect infectious diseases among wildlife is needed to improve response time and reduce the costs of new outbreaks. Such surveillance differs from traditional hypothesis-driven disease research because it involves very broad searching rather than attempts to answer a highly focused question. Investment in gathering advance information can pay off handsomely; early warning of how diseases work and of their normal characteristics among animals can help limit the damage when the illnesses start to spread.

New public-private partnerships could also be hugely helpful. Currently, the failure of public-sector programs to comprehensively monitor, prevent, and respond to unusual diseases is being compensated for by the private sector. Coordination between these efforts and governments remains limited -- in some cases due to regulations and restrictions that prevent such collaboration. For example, under its agreement with member states, the World Animal Health Organization cannot accept information on wildlife diseases in a country unless that information has been submitted officially by a national agricultural authority -- few of which are mandated or organized to monitor wildlife diseases. These policies should be reformulated to facilitate cooperation among governments, corporations, and nonprofit organizations, and formal mechanisms for sharing information should be established.

It would also help to shift responsibility for the costs of outbreak prevention and control to animal traders, since this would provide them with incentives for reducing disease and would lower the costs of disease surveillance, control, and prevention by third parties. One way to force traders to shoulder more of the costs would be to require them to buy disease outbreak insurance on all animal imports or shipments. Doing so would discourage dangerous activities among animal traders by hitting them where it hurts: in their wallets.

Financial incentives are not enough, however; the World Trade Organization and other appropriate international bodies must also start requiring governments to better regulate the health aspects of international trade in wild and domestic animals. Individual states also need to implement new laws to prevent the spread of diseases within their borders. There is now plenty of evidence to suggest that human trade and consumption of wildlife have led to global health disasters; governments must therefore immediately start making serious efforts both to reduce and to regulate properly the trade of such animals internationally, regionally, and even locally.

On the health-care side, decisions still tend to be made without sufficient input from all appropriate stakeholders. For example, the decision of a Southeast Asian government in 2004 to control avian influenza by culling wild migratory birds failed to identify the real source of the problem (domestic livestock) or to recognize that the wild birds were protected by at least two separate international conventions. Involving experts in public health, agriculture, and environmental conservation, as well as legal counsel, in such decisions would help governments avoid repeating these mistakes and adopt more sound strategies in the future.

Finally, greater bilateral and multilateral aid is needed for efforts to gather, evaluate, and share information on infectious diseases that affect the wide range of living organisms present around the world. Too often, health experts focus on human health and agriculture alone, missing a huge part of the picture. More money must be spent on initiatives that include wildlife health and conservation in discussions of human health care; more money would also help stimulate the development of holistic efforts in areas of the world where they are most critically needed.

The obstacles to identifying, understanding, and sharing information about all infectious diseases on the planet may appear daunting. But they are no excuse for not trying. New, holistic approaches should be started at local and regional levels; such efforts are already proving efficient and cost-effective and are advertising the benefits of the new paradigm. Such small- and medium-scale efforts can be built up over time and run in parallel with higher-order, global coordination.

The time to launch such initiatives is now, before the next global pandemic occurs. Bridges must be built between different scientific disciplines, and trade in wildlife must be dramatically reduced and, like the livestock industry, properly regulated. Global health will not be achieved without a philosophical shift from the expert-controlled, top-down paradigm that still dominates both science and medicine. A broader, more democratic approach is needed, one based on the understanding that there is only one world -- and only one health.

[Snuffysmith]

Unknown Illness Kills Nine Chinese Farmers

By Philip P. Pan

BEIJING, July 23 -- An unidentified disease has killed nine farmers and sickened 11 others in a rural part of China's western Sichuan province, prompting the government to dispatch an emergency team of researchers to investigate whether the deaths are related to bird flu, a Health Ministry...

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[Gabrielle]

Avian influenza

Malign influences

Jul 21st 2005
From The Economist print edition

More deaths from bird flu in Asia

THE first human deaths from avian influenza in Indonesia were announced on July 20th by the country's health minister, Siti Fadillah Supari. She said that three members of a family living on the outskirts of Jakarta had been killed in the past ten days. Human cases of bird flu in Indonesia have been reported since June, but these are the only known fatalities.

Normally, people who catch the virus, which has been rampaging through the domestic fowl of South-East Asia since 2002, do so directly from birds. In this case, although the World Health Organisation had yet to confirm Dr Supari's announcement when The Economist went to press, its officials are worried there is no obvious avian source for the infection. That, plus the fact that the victims lived together, raises the possibility that one of them gave it to the others. Dr Fadillah was keen to play down the idea of such human-to-human transmission, but more than 300 people who have had contact with the three victims are being tested for the virus just in case, and plans are under way to test animals within a 20km radius and slaughter those that are infected.

Virologists have long been concerned about bird flu, worrying that the virus which causes it might mutate in a way that allowed it to be transmitted easily from person to person. This, they fear, might result in a catastrophic epidemic among humans, similar to the one just after the first world war that killed 20m-40m people.

It is by no means certain that such a mutation has happened in the Jakarta cases, even if they do turn out to have been transmitted between family members. According to Ian Jones, a professor of virology at the University of Reading, in England, it is possible that there could have been transmission between humans simply because one of the family members was carrying unusually large amounts of the unmutated virus.

In addition, Dr Fadillah says that the genetic sequence of the virus in question has been obtained, and that it was indeed a conventional one. However, some virologists urge sceptical caution. Peter Openshaw, head of respiratory infections at the National Heart and Lung Institute in London, said that he would want to see any statement about the genetic sequence of the virus—and its difference from other isolates—coming from a scientist rather than a politician.

On top of this, a paper in this week's Proceedings of the National Academy of Science reported a different sort of mutation. It suggested that the virus circulating in the avian population has been evolving into a form less lethal to birds. That raises concerns that birds which have survived the disease may act as a reservoir—and that if migratory wildfowl caught it, they could carry it out of South-East Asia.

The British government, meanwhile, announced it would stockpile 2m doses of a vaccine against the strain of bird flu currently in circulation. It is hoped these would confer resistance to any human virus that might emerge and could be used to protect medical workers in an outbreak.

[Snuffysmith]

Bird Flu Deaths Sow Panic In Wealthy Jakarta Suburb

By Alan Sipress

SERPONG, Indonesia -- When Iwan Siswara Rafei, a government auditor, and his two young daughters died suddenly this month, there was panic in their middle-class suburb along with reports that they were Indonesia's first casualties of bird flu.

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[Snuffysmith]

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Will we be ready?
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Most Americans consider bird flu a distant threat, but U.S. health officials are preparing for a potential pandemic.

By Melissa Healy
Times Staff Writer

July 25 2005

In the perennial conflict between germs and humans, the influenza virus has a distinguished roster of battlefield victories. But now, far from America's shores, a new round of hostilities is brewing. For the first time, scientists and public health officials are preparing to fight back.

The complete article can be viewed at:
http://www.latimes.com/features/health/la-...=la-home-health

[Snuffysmith]

http://www.voanews.com/english/2005-07-27-voa16.cfm

Death Toll From China's Latest Disease Continues to Rise
By Naomi Martig
Hong Kong
27 July 2005

An infectious disease that has killed two dozen people in Southwestern China has sparked fears that bird flu or SARS (Severe Acute Respiratory Syndrome) has resurfaced. The World Health Organization says it is not disputing China's contention that a known pig-borne bacteria has caused the latest deaths, but says the high mortality rate is alarming.

The Chinese Ministry of Health says a bacteria (streptococcus suis) that regularly infects pigs has killed at least 24 people in Sichuan Province since last month, mainly farmers, and has infected more than 100.

Bob Dietz is a spokesman for the Western Pacific region of the World Health Organization. He says that if the numbers are accurate, the situation will mark the first time the WHO has seen such large numbers of people infected by this particular bacteria.

Mr. Dietz said it is still too early to say if a serious outbreak of the disease is imminent. "We do see a steady increase in numbers in reported cases, and a slow but steady rise of deaths. But these types of hard figures are still not reliable enough to make a prediction of course," he said.

The Ministries of Agriculture and Health say they have seen no indication that the bacteria is spreading by person-to-person contact. Mr. Dietz says the current situation, however, is still very disconcerting, because of the unusually large numbers of victims involved. "We don't understand why there are so many people getting ill. [Normally] when this disease appears, one or two, maybe three people get ill, in contact with pigs. Why all of a sudden are we seeing 117 cases of this? That is not clear to us and we don't know why that is happening," he said.

China has been hard hit by infectious diseases in the past several years. SARS, or Severe Acute Respiratory Syndrome, started in Southern China in late 2002 and spread around the world, killing almost 800 people. Bird flu, caused by a virus that can be lethal to human beings, has affected flocks of chickens and wild birds in many parts of the country.

Mr. Dietz says the WHO is monitoring the situation. Chinese authorities, meanwhile, have taken steps to keep the bacteria from spreading, including prohibiting farmers from slaughtering or processing infected pigs.

[Snuffysmith]

Dangerous Bird Flu Strain Found in Russia
July 29, 2005 10:06 AM EDT
MOSCOW - Investigators have determined that a strain of bird flu virus infecting fowl in Russia is the type that can infect humans, the Agriculture Ministry said Friday.

The virus caused the deaths of hundreds of birds in a section of Siberia this month, but no human infections have been reported.

In a brief statement, the ministry identified the virus as avian flu type A H5 N1.

"That raises the need for undertaking quarantine measures of the widest scope," the statement said. Ministry officials could not immediately be reached for elaboration.

Strains of bird flu have been hitting flocks throughout Asia and some fatal human cases have been reported there.

[Snuffysmith]

World Not Set To Deal With Flu

By David Brown

Public health officials preparing to battle what they view as an inevitable influenza pandemic say the world lacks the medical weapons to fight the disease effectively, and will not have them anytime soon.

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