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September 20th, 2005
H5N1 - Killer Flu
Essay: The Next Pandemic?

The Next Pandemic?
by Laurie Garrett
Excerpted from the July/August 2005 issue of FOREIGN AFFAIRS


A fighting cock before a match. Trade in these birds may be implicated in the flu’s spread.
Credit: Photo Credit: Thirteen/WNET/Blue Ice Pictures, Inc.

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….

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….

[The most virulent strain of the H5N1 virus] 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 [an avian influenza] 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….

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…. 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…. 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.

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….

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….

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 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.

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. The full version of this article can be found on the FOREIGN AFFAIRS website.

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