Henry, I read an article yesterday that kind of dovetailed with my sense of the way things might work in a pandemic that are more hopeful than most of what we are reading about the bird flu. What is your opinion of this, if you don't mind?
Quick action may head off global epidemic
By Paul Wiseman, USA TODAY
BANGKOK — After poring over old medical records, studying census data and cranking out mathematical models, scientists and health officials are beginning to believe they have a chance to stop a bird flu pandemic before it kills millions of people worldwide.
The key: detecting an outbreak early and rushing powerful antiviral drugs to the source to throttle a pandemic at birth before it can bust out of Southeast Asia, carrying sickness and death around the globe. "It is the first time in the history of mankind that anyone has thought about keeping a worldwide pandemic at bay," says William Aldis, the top World Health Organization (WHO) official in Thailand.
But the window of opportunity could close quickly, and the world is not yet prepared to take advantage of it, researchers say. Rich countries are stockpiling antiviral drugs, but there is little available in the impoverished backwaters of Southeast Asia where an outbreak is likely to begin.
"The world is not dealing with this with sufficient attention," says Supamit Chunsuttiwat, disease control expert at the Thai Ministry of Public Health. "If we join hands, we might be able to stop the pandemic."
"We are not prepared," says Marc Lipsitch, an epidemiologist at the Harvard School of Public Health. "It is critical to scale up preparations on the home front, but equally urgent ... to prevent the start of a new pandemic in Asia."
Avian influenza, an infectious disease of birds caused by type A strains of the influenza virus, jumped to humans in 2003. The H5N1 strain that has infected people has killed 54 of the 98 people infected, a 55% death rate. The WHO, a United Nations health agency coordinating the bird flu battle, warned in a January report about the potential for a pandemic: widespread infection — and death.
"Never before had so many countries been so widely affected by avian influenza in poultry in its most deadly form," the report said. "Never before had any avian influenza virus caused such extremely high fatality in humans."
The clock seems to be ticking. Vietnam on May 23 reported its 38th bird flu death, a 46-year-old man who succumbed May 19. Chinese officials quarantined parts of remote Qinghai Province and rushed 3 million doses of bird flu vaccine for use in poultry, not humans, after an outbreak among migratory birds. There have been no confirmed human cases in China.
The WHO in May expressed concern that strains of the deadly H5N1 bird flu virus circulating in northern Vietnam are becoming more infectious to humans.
The nightmare scenario: The virus mutates into a type that can pass easily from human to human, something that apparently has not happened yet. If it does, the world could face a pandemic like the one that killed at least 40 million people in 1918-19. The WHO warns that an uncontained bird flu pandemic could kill 2 million to 50 million people worldwide.
But researchers are beginning to believe the tragedy could be stopped if the world responds aggressively to the first signs of a pandemic outbreak. "It's an opportunity not to be missed," says Scott Dowell, Bangkok-based director of a joint program between Thai health officials and the U.S. Centers for Disease Control and Prevention. "In 1918, they didn't stand a chance. But we're not in 1918. We're in 2005."
The lessons of 1918
In contrast to previous pandemics, researchers this time know what to watch for: the lethal H5N1 avian influenza virus, which first showed up in humans eight years ago in Hong Kong and which mutates rapidly.
So countries in the regions have been training their health workers to identify bird flu and to isolate patients who have it. If a pandemic strain begins, they will notice clusters of human cases — for example, 20, 30, 40 cases in a single village. That has not happened yet.
Researchers at the Harvard School of Public Health found the flu virus that generated the 1918-19 pandemic was less contagious than believed. Their conclusions, published last December in the journal Nature, suggest another influenza pandemic might be easier to contain than previously feared. The Harvard team studied influenza deaths in 45 U.S. cities during the 1918-19 pandemic. Using old medical records and sophisticated mathematical models, the team concluded that each influenza victim infected two to four people, not up to 20, as researchers had previously suspected.
Why do researchers care about this arcane statistic, known as the "reproductive number"? Because the disease will quickly die out if health officials can intervene aggressively enough with some combination of antiviral drugs, vaccines and low-tech measures such as travel restrictions and quarantines. The goal: to push the reproductive number below 1, the point at which each victim infects less than one more person.
Cutting the reproductive number below 1 from 4 is still difficult, but it's a lot easier than the "almost impossible" task of getting it there from 20, says Harvard's Lipsitch, a co-author of the study. "It means that there is a good chance that very intense control measures could work, and we should take it."
A human vaccine would be the best way to stop a bird flu pandemic. But creating a vaccine for a pandemic strain of virus that doesn't exist yet would take at least several months. In the meantime, researchers are becoming more confident that antiviral drugs, designed to treat the flu once people get sick, can be used to prevent a pandemic viral strain from spreading. Unlike vaccines, antivirals have a shelf life of up to five years, can treat a range of viruses and can be stockpiled well in advance of a pandemic.
Ira Longini, a professor of biostatistics at Atlanta's Emory University, and a team of numbers crunchers have created statistical models to calculate the effectiveness of antiviral drugs in stopping a bird flu pandemic.
In a telephone interview, Longini says the results, which will appear in a paper submitted to the journal Nature and are expected to be published this month, are promising: Health officials in rural Southeast Asia would have more time and would need less antiviral medicine to stop a pandemic. The team created a model of a 3,500-square-mile area populated with 500,000 people in rural Thailand, where the pandemic is likely to emerge.
If it did break out there, Longini says, health officials would have two to three weeks, and perhaps as long as a month, to intervene with antivirals and quarantines before the disease broke loose and began spreading. The reason for the time lag: People in rural Southeast Asia don't travel very often or very far; the disease is unlikely to spread quickly beyond their communities.
By targeting the source of the outbreak, not distributing antivirals across an entire country, health officials can limit the amount of drugs they need. "We are putting the drug where the transmission is and not wasting it," Longini says.
Antivirals pose their own problems. The most effective antiviral drug is oseltamivir, a tablet developed by Swiss pharmaceutical giant Roche and Gilead Sciences of Foster City, Calif., and marketed by Roche as Tamiflu.
A protein on the surface of the flu virus called neuraminidase lets the virus move from one cell to another. Tamiflu prevents the neuraminidase from doing its job and stops the virus from infecting new cells.
The supply problem
The U.S. Food and Drug Administration approved Tamiflu for treating adults in 1999 and for prevention (in people older than 12) in 2000. Tamiflu helped control an outbreak of the H7N7 avian flu strain that caused one death in the Netherlands two years ago.
But Tamiflu takes a year to manufacture and is expensive. At U.S. pharmacies, it costs about $6.50 per capsule, though Roche is offering undisclosed discounts to governments that stockpile the drug and has donated about 120,000 10-capsule treatments to the WHO, Roche spokesman Terence Hurley says. The recommended dosage is 10 (two a day for five days) for treatment; and at least five (one a day for five days) for prevention, WHO spokesman Peter Cordingley says. So the cost can add up, especially in a country such as Laos where the annual per capita income is less than $2,000.
As the bird flu threat has grown, wealthy countries have started stockpiling Tamiflu. The United Kingdom has amassed 14.6 million 10-capsule treatments, enough to cover a quarter of its population. The United States last year had stockpiled 2.3 million treatments, enough for less than 1% of the population, according to Roche.
Supplies are scarce in the countries where a pandemic is likely to emerge. The WHO has sent just 2,500 treatments to Vietnam and 500 treatments to Cambodia. It has a stockpile, mostly donated by Roche, of more than 120,000 treatments at its regional offices in Manila and New Delhi, ready to be delivered by courier anywhere a pandemic emerges.
Health experts say at least some of the Tamiflu should be diverted from rich Western countries to Southeast Asia, where it's needed.
"Several million courses sent to Thailand would be more effective than hoarding for nearly 300 million people" in the USA, Emory's Longini says. "If you stop the spread at the source, it's much better."
In fact, Longini believes that as few as 120,000 treatments — the amount the WHO has stockpiled in Asia — might be enough to stop a bird flu pandemic in its tracks. But he still says individual Southeast Asian countries should have their own stockpiles to react if necessary to multiple outbreaks.
"We should be moving quickly on regional stockpiling," the WHO's Aldis says. "If I were a donor country and I heard that there was a way to switch off a pandemic before it happened, I'd have my checkbook out."
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