Unarmed against a flu pandemic

WASHINGTON - 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.

Public health specialists and manufacturers are working frantically to develop vaccines, drugs, strategies for quarantining and treating the ill, and plans for international cooperation, but these efforts will take years. Meanwhile, the most dangerous strain of influenza to appear in decades - the H5N1 "bird flu" in Asia - is showing up in new populations of birds, and occasionally people, almost by the month, global health officials say.

If the virus were to start spreading in the next year, the world would have only a relative handful of doses of an experimental vaccine to defend against a disease that, history indicates, could potentially kill millions. If the vaccine proved effective and every flu vaccine factory in the world started making it, the first doses would not be ready for four months. By then, the pathogen would probably be on every continent.

Theoretically, antiviral drugs could slow an outbreak and buy time. The problem is that only one licensed drug, oseltamivir, appears to work against bird flu. At the moment, not enough is stockpiled for widespread use. Nor is there a plan to deploy the small amount that exists in ways that would most effectively slow the disease.

The public, conditioned to believe in the power of modern medicine, has heard little of how poorly prepared the world is to confront a flu pandemic, which is an epidemic that strikes several continents simultaneously and infects a substantial portion of the population.

Since the current wave of avian flu began sweeping through poultry in Southeast Asia more than 18 months ago, international and U.S. health authorities have warned of the danger and tried to mobilize. Research on vaccines has accelerated, efforts to build drug supplies are under way, and discussions take place regularly on developing a coordinated global response.

The U.S. Department of Health and Human Services will spend $419 million in pandemic planning this year. The National Institutes of Health's influenza research budget has quintupled in the past five years.

"The secretary or the chief of staff - we have a discussion about flu almost every day," said Bruce Gellin, head of Health and Human Services' National Vaccine Program Office. This week, a committee is to give health secretary Mike Leavitt an updated plan for confronting a pandemic.

Despite these efforts, the world's lack of readiness to meet the threat is vast, experts say.

"The only reason nobody's concerned the emperor has no clothes is that he hasn't shown up yet," Harvey V. Fineberg, president of the National Academy of Sciences' Institute of Medicine, said recently of the world's efforts to prepare for pandemic flu. "When he appears, people will see he's naked."

The most outspoken is Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. In writing and in speeches, Osterholm reminds his audience that after public calamities, the United States usually convenes blue-ribbon commissions to pass judgment. There will be one after a flu pandemic, he believes.

"Right now, the conclusions of that commission would be harsh and sad," he said.

In hopes of slowing a pandemic's spread, public health specialists have been debating proposals for unprecedented countermeasures. These could include vaccinating only children, who are statistically most likely to spread the contagion; mandatory closing of schools or office buildings; and imposing "snow day" quarantines on infected families - prohibiting them from leaving their homes.

Other measures would go well beyond conventional boundaries of public health: restricting international travel, closing transit systems and nationalizing supplies of critical medical equipment, such as surgical masks.

Osterholm argues such measures would fall far short. He predicts a pandemic would cause widespread shutdowns of factories, transportation and other essential industries. To prepare, he says, authorities should identify and stockpile a list of perhaps 100 crucial products and resources that are essential to keep society functioning until the pandemic recedes and the survivors go back to work.

Since late 2003, 109 people are known to have been infected with the emerging H5N1 virus in Asia. About half - 55 - have died.

Ironically, for the current H5N1 strain of avian flu to gain "pandemic potential," it will have to become less deadly. Declining lethality is a key sign that the microbe is adapting to human hosts. That is one reason the 34 percent mortality observed in the most recent outbreak - a cluster of cases in northern Vietnam - worries scientists.

Pandemic influenza is not an unusually bad version of the flu that appears each winter. Those outbreaks are caused by flu viruses that have been circulating for decades and change slightly year to year.

Pandemics are caused by strains of virus that are highly contagious and to which people have no immunity. Such rare strains arise from the chance scrambling and recombination of an animal flu virus and a human one, resulting in a strain whose molecular identity is wholly new.

In the 20th century, pandemics occurred in 1918, 1957 and 1968. Although the 19th-century record is less certain, there appear to have been four flu pandemics - in 1833, 1836, 1847 and 1889. On a purely statistical basis, the nearly 40 years since the last one suggests the time might be ripe.

The microbe called influenza A/H5N1 appeared in East Asia in 1996 and has flared periodically since. It is highly contagious and lethal in chickens, but it can be carried without symptoms in some ducks - a combination that helps keep it in circulation.

Birds occasionally infect humans, and scientists recently found evidence that the virus is sometimes passed from person to person. That form of transmission is now difficult and rare, but the virus could evolve so it becomes easy and common.

If H5N1 never becomes easily transmissible in human beings, it will never become a pandemic. If it does become transmissible, the consequences are difficult to imagine. But history provides some clues.

The "Spanish flu" in 1918 and 1919 was the biggest and, along with AIDS, the most important infectious disease outbreak of the 20th century. It is on the short list of great disasters in human history.

At least 50 million people, and possibly as many as 100 million, died when the world's population was 1.9 billion people, one-third its current size.

Tests are under way at three U.S. hospitals on an experimental vaccine against H5N1. But it is not the first H5N1 vaccine.

When a slightly different strain of the virus surfaced in Hong Kong in 1997, killing thousands of chickens and a half-dozen people, researchers used viruses from birds and people to make experimental vaccines. But neither offered much protection in lab tests, and nobody knows why.

Instead of working on the problem, researchers dropped it. First SARS (severe acute respiratory syndrome), and then a different avian flu strain that arose in Europe (H7N7), took their attention.

"The urgency around this issue kind of dissipated," said John Treanor, a physician at the University of Rochester and one of the leaders of the vaccine project. "I think it's an example of how unpredictable things are. We got distracted."

As the first, small hedge against disaster, the government last fall ordered 2 million doses of H5N1 vaccine from Sanofi Pasteur, one of the country's three flu vaccine makers, even though nobody yet knows whether it works.

A half-dozen other countries are working on pandemic vaccines. But making enough to fight an outbreak is a tall order.

About 300 million flu shots are made worldwide each year. The vaccine protects against three flu strains. If the global production capacity were directed to make only H5N1 vaccine, the output could be 900 million shots.

Unfortunately, virologists are almost certain people will need two doses about a month apart to mount a successful immune response against a wholly new strain such as H5N1. That would cut the theoretical number of recipients worldwide to 450 million. If each shot requires a larger-than-usual amount of vaccine to work, the number will be even smaller.

Because nearly all flu vaccine is made by growing the virus in fertilized chicken eggs, special factories and a steady supply of eggs are required. Consequently, a key element of pandemic planning is getting more people to get yearly flu shots, which will give companies a larger market and an incentive to expand their plants.

Around the world, flu vaccine production has risen by just one-third in the past decade. New plants in Brazil, South Korea and the Netherlands soon will boost global production by 25 percent.

In theory, even a modest amount of vaccine might be useful. Fighting disease outbreaks is like fighting fires. You do not have to hose down the whole world to put the fire out, but you do have to hose down the perimeter to keep it from spreading. It might be possible to contain an H5N1 outbreak at its source if the surrounding population were immediately vaccinated.

Would the United States, Europe and Japan be willing to donate their precious vaccine supply to mount such a long-shot defense? This is perhaps the biggest unanswered question in pandemic flu planning - and one likely to be answered only at the moment of truth.

"If it was done in consultation with the WHO [World Health Organization] - and with other governments that would make contributions, as well - we would be more likely to consider it," said Gellin at the Department of Health. But observers both in and out of the government said, not for quotation, that they doubt the U.S. government would ever send a significant amount of its vaccine stockpile overseas.

In the absence of vaccine, the only pharmaceutical bulwark against H5N1 is a drug called oseltamivir. It can shorten the illness's duration, and if taken immediately after exposure, it can prevent infection. But the world's supply is limited.

Sold as Tamiflu, it is manufactured by one company, the Swiss giant Roche, in a laborious, expensive process that takes eight months.

Twenty-five countries have ordered oseltamivir to stockpile, and five others have expressed interest, a Roche spokesman, Terence J. Hurley, said recently.

The United States has a stockpile, but it is enough to treat less than 1 percent of the population. The government has ordered enough to treat 3 million more people, or about 2 percent total.

At a congressional hearing in May, the company's medical director, Dominick A. Iacuzio, said it will begin producing oseltamivir in the United States soon. The company says it could supply 13 million more courses of treatment in 2006 and an additional 70 million in 2007 - provided the government orders them.

In a study published last year, Ira M. Longini Jr. of Emory University ran a mathematical model of what might happen if a pandemic such as the 1957 Asian flu, which was caused by a virus far milder than bird flu, hit the United States.

He and his colleagues estimated that with no vaccine or antiviral drugs, there would be 93 million cases and 164,000 deaths. Vaccinating 80 percent of people younger than 19 - the group most responsible for spreading the virus - "would reduce the epidemic to just 6 million total cases and 15,000 total deaths in the country."

Giving that group eight weeks of oseltamivir would have the same effect, at least temporarily. But it would take the equivalent of 190 million courses of treatment - more than anyone thinks the country will have in the next few years.

Somewhat more realistic is sending the drug to where the outbreak begins. One researcher, Neil M. Ferguson of Imperial College in London, said in an interview that results of his not-yet-published mathematical modeling "are encouraging."

But unless antiviral drugs squelch a pandemic at the outset, their ultimate usefulness will be small. Without widespread immunity through vaccination or infection, the virus will move into a population when the drugs run out.

WASHINGTON - An emerging bird flu pandemic with the potential to kill millions of people around the world could be nipped in the bud if it were discovered within a week or two of its initial eruption and battled intelligently with drugs and quarantines, according to the first computer models to show how the disease would spread and what it would take to stop it.

The computations offer a modicum of hope amid a din of alarming predictions about the catastrophic outbreak now thought to be brewing in South Asia.

"The models show that if you combine well-directed, targeted treatment with some social interventions like closing schools, ideally together with some vaccination, it's conceivable you'd be able to stop the epidemic," said Anthony Fauci, chief of infectious diseases at the National Institutes of Health, which funded much of the work through its National Institute of General Medical Sciences.

The plan would work only if authorities recognized very quickly that the flu virus had morphed into the contagious form that can trigger a pandemic.

It would work only if health officials around the world immediately shipped to the outbreak area as many as 30 million tablets of the one medication scientists expect could be helpful.

It would work only if local agencies managed to distribute those drugs to the vast majority of people who might have had recent contact with the victims - schoolmates and work mates at a minimum but, better yet, anyone who may have gone to the same restaurants, ridden the same buses or shopped or prayed in the same venues.

And it would work only if most residents over a potentially sprawling region obeyed orders to stay home as the emergency blossomed.

"If we get to the point where there are thousands of cases, we just have no chance of containing it," said Neil Ferguson of Imperial College London, lead author of one of the studies, which appears in today's issue of the journal Nature.

"Basically, you contain it at the source or you fail," agreed Ira Longini, a biostatistician at Emory University's Rawlins School of Public Health in Atlanta, who led the other study, published in today's online edition of the journal Science.

At issue is the H5N1 strain of avian flu virus that is spreading through birds and other animals in Asia. The virus has killed half of the roughly 100 people it has stricken in the past 18 months, but has the potential to cause global devastation if, as many scientists expect, it gains the ability to spread easily from person to person.

No vaccine exists against the virus, though experimental versions are being raced into development. The one drug that seems able to prevent infection and reduce the virus's spread is oseltamivir (sold as Tamiflu). More than two dozen countries and the World Health Organization are stockpiling the drug. But supplies are so limited today that it would be impossible to treat everyone in the event of an outbreak.

Deadly avian flu keeps N.J. on edge

Friday, September 16, 2005

There's flu, and then there's Flu.

This year, doctors are on the lookout not just for seasonal influenza, but also for the possible arrival, later on, of a lethal and highly contagious strain of avian flu from Southeast Asia.

"Basically, bird flu has the same symptoms as regular flu, except you don't get better," said Dr. Barry Prystowsky, a pediatrician in Nutley. Prystowski is one of about two-dozen doctors in New Jersey designated by the state as "sentinel physicians," who keep a watchful eye for signs of pending epidemics.

"You quickly dehydrate and get pneumonia at the same time. You would need hospitalization within a few days, then end up on a respirator and probably die," Prystowsky said.

It's a dire diagnosis, but New Jersey health officials believe the state is ready.

Sentinel physicians are one component of a comprehensive early detection and response system outlined in a draft of the state's 2005 Influenza Pandemic Plan. An updated version of the plan, first conceived in 2002, is posted online. It will be revised to keep up with emerging infectious diseases, officials said.

A pandemic is an epidemic that can spread across a country and to other parts of the world. Bird flu, which emerged last year in Vietnam and Thailand and moved recently to Russia, has killed more than 50 people, mainly poultry workers. What has not happened, but what health officials fear, is that the avian flu virus - known as H5N1 - will be spread further by migratory birds.

The even bigger fear is that the virus will combine genetically with a human viral strain that can be transmitted person to person.

That new strain would be highly contagious and deadly, scientists say.

Some experts have predicted darkly that, if such a strain develops, the world could face a pandemic like the so-called Spanish flu of 1918 that killed more than 20 million people. There is no way to say if and when bird flu will hit the United States, but European officials worried this summer that they will have to deal with it sooner rather than later. One British scientist told reporters bird flu presents "a national emergency. ... Many people are threatened by a virus that can decimate a country."

As it is, New Jersey health officials estimate that an eight-week pandemic would cause 1.5 million outpatient visits and nearly 41,000 hospital admissions, including 9,553 patients in intensive care and 4,775 on respirators. There would be 8,141 deaths, they estimate.

Across the United States, officials predict that a pandemic could kill upward of 207,000 and hospitalize 733,000, compared with 36,000 deaths and 114,000 hospitalizations in an average flu season.

Sentinel doctors

Sentinel physicians such as Prystowsky are on the outlook for increasing numbers of patients with symptoms such as sore throat, fever and cough. The doctors file a weekly report with New Jersey's Local Information Network and Communication System and state health officials analyze the data for spikes in the numbers.

If a suspicious illness appears, the sentinel physician may send a sample to the state labs in Trenton to be tested and forwarded to the federal Centers for Disease Control and Prevention, which oversees the sentinel program.

New Jersey's Pandemic Plan is a "generic" defense against any invading microbe, said Dr. Eddy Bresnitz, the state epidemiologist.

"The approach would be the same whether for bird flu or other flu," Bresnitz said. "This is flu. We're going to test it. When we do surveillance, we don't presuppose for what. If we knew what strain it was, we wouldn't have to test for it."

New Jersey will also monitor any "influenza-like illness" reported by hospitals, nursing homes and elementary schools, as well as the amount of over-the-counter drugs sold by pharmacies, as possible early indicators of flu.

Also, six cities - Paterson, Jersey City, Elizabeth, Newark, Trenton and Camden - are among 120 cities nationally that will tell the CDC each week how many death certificates involved pneumonia and influenza.

New Jersey's response to a flu pandemic would include informing the public about supplies of vaccine and antiviral medication - such as Tamiflu, an effective prescription flu treatment if used shortly after symptoms appear - school and business closings, suspended public meetings, travel restrictions and quarantines. More than 3,000 crisis counselors would be deployed.

The state is a lot better prepared since Sept. 11 and the subsequent anthrax and bioterrorism scares, Bresnitz said. "We've really improved all our capabilities of responding to emerging infections," he said.

In months to come, New Jersey will stage a flu-pandemic exercise similar to the simulated bio-terrorism attack drills held at hospitals in the spring, Bresnitz said. The state Department of Agriculture also has an avian-flu detection and response plan, including the culling of infected poultry flocks if necessary.

Flu is airborne

Bresnitz said there is more than just a whimsical distinction between sentinel physicians who gather information, and the so-called sentinel chickens used by health officials in years past to detect the presence of West Nile virus-infected mosquitoes.

But surveillance is only a tool for early detection and might not stop a pandemic, Bresnitz said.

"Influenza is an airborne disease spread very efficiently, with a short incubation, so we'd have to depend on other things," he said. This includes common sense personal hygiene such as hand washing and covering coughs and sneezes.

Seasonal influenza and flu pandemics have many similar public health issues, such as potential vaccine shortages, Bresnitz said. Federal scientists, for example, announced this month they had successfully tested a potentially effective bird-flu vaccine in people, but are unsure whether they can produce enough of it in time.

"But a pandemic is a different beast," Bresnitz cautioned. "A novel virus strain that nobody is experienced with has higher mortality and greater number of people infected."

New Jersey will also encourage hospitals statewide to develop "surge capacity" guidelines, similar to ones issued during last year's flu-vaccine shortage, to accommodate the anticipated crush of thousands of pandemic patients. They will have to decide whom to admit and whom to send home.

"I think they're all as prepared as they can be," Aline Holmes said of the New Jersey Hospital Association's 105 members.

"Everyone has their plans in place to work closely with the Health Department," said Holmes, a nurse and the association's flu liaison with the state.

Prystowsky, the Nutley sentinel physician, is less sanguine.

If bird flu combines with a human viral strain and begins to spread, he said, "I think it's going to be devastating."

"I think thousands of people are going to die, especially the fragile, the elderly, the very young, the babies. I don't think we'll have the vaccine supply because they won't be able to produce it. If it hits, hopefully we'll have enough Tamiflu to save some of us."

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