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It's that time of year again--avian flu panic season. As the weather turns colder in the northern hemisphere and the flu starts making its annual rounds, the media and their anointed health experts are chirping and squawking once again about how we could be blindsided by a pandemic that some have estimated could kill a billion persons worldwide. New books like The Coming Avian Flu Pandemic join last year's The Monster at Our Door: The Global Threat of Avian Flu.
A year ago in these pages I clucked at all this, laying out the evidence that the alarmists were wrong, that avian influenza type H5N1 would not become readily transmissible from human to human and therefore not become pandemic--meaning a global epidemic. (See "Fuss and Feathers: Pandemic Panic over the Avian Flu," November 21, 2005.) Some of the arguments I made have quietly caught on. For instance, health officials, including National Institute of Allergy and Infectious Diseases director Dr. Anthony Fauci, no longer talk about an "overdue pandemic" (because there is no pattern to when pandemics occur; they are never "due" or "overdue"). But the damage has been done. A Harvard School of Public Health survey of adults who have children revealed that 44 percent think it "likely" or "somewhat likely" there will be "cases of bird flu among humans in the U.S. during the next 12 months." Less than a fifth of respondents considered it "not at all" likely.
Not coincidentally, an avian flu bureaucracy has become entrenched. Like all bureaucracies, it will fight to survive and thrive, egging on governments to provide ever more money. The alarmingly titled 2006 Guide to Surviving Bird Flu is published by no less than the Department of Health and Human Services. Never mind that no one in this country has yet even contracted bird flu. Congress last year allocated $3.8 billion to prevent the ballyhooed catastrophe (Bush requested almost twice that amount). The latest "scary news," promulgated in the November 23 issue of the New England Journal of Medicine by über-alarmist Robert Webster of St. Jude Memorial Children's Hospital, is that human cases of H5N1 contracted from birds are continuing to increase. Indeed, confirmed cases for 2006 are running ahead of those for last year. But the difference is slight; 97 worldwide for all of last year versus 111 through the end of November 2006. This difference could be entirely explained by better surveillance. Moreover, the real concern is not sporadic bird-to-human transmission, but human-to-human transmission. Far more people die of tuberculosis in an hour than all those known to have died from H5N1.
So it's time to revisit the allegations and show that as small as the risk was a year ago, it's nevertheless dropped considerably since.
Mutation and Reassortment
A flu pandemic can come about in two ways. One way is for the virus to randomly mutate to become easily transmissible between humans. "Randomly" is the key word here. There are no evolutionary pressures to make H5N1 adapt better to humans. Given enough time, H5N1 might mutate so that it could under the right conditions become pandemic. But that could take millions of years, during which time it would be more likely to mutate itself out of existence. H5N1 was first identified in Scottish chickens in 1959. It has been flying around the globe for close to half a century and hasn't done a number on us yet. There's absolutely no reason to think it will pick this year or next to do so.
Another scenario is that somebody with human flu could contract avian flu at the same time and the two flus could "reassort" into hybrid avian-human flu. The last two flu epidemics in the 20th century--1957-58 and 1968-69--were caused by such hybrids. We can help reduce this possibility by vaccinating as many people as possible (especially Southeast Asian poultry farmers) against human flu, thus reducing the potential number of "mixing vessels." Programs underway to keep farmers away from poultry droppings and spittle (birds don't sneeze or cough) will also help.
Ferreting Out the Truth
A fascinating study in the August 8, 2006, issue of Proceedings of the National Academy of Sciences would seem to indicate we're already pretty safe from a human-avian hybrid. Researchers from the U.S. Centers for Disease Control and Prevention conducted three separate studies with ferrets, which are among the few animals known to suffer from and transmit human flu. The ferrets were infected with several H5N1 strains in addition to a common human influenza virus (H3N2) that circulates almost every year. The infected animals were then either placed in the same cage with uninfected ferrets to test transmissibility by close contact or in adjacent cages with perforated walls to test spread of the virus from respiratory droplets.
The research showed that the H3N2 virus passed easily by droplets (ferrets do sneeze and do not use handkerchiefs) but the H5N1 virus did not spread--the same thing we're seeing in humans infected with H5N1 from birds.
Separately, the scientists used gene splicing to create a hybrid H5N1/H3N2 virus. In other words, rather than letting nature take its course and seeing if the viruses would reassort, they guaranteed that reassortment occurred. They found these hybrids also did not pass easily between the animals. Moreover, ferrets injected with the reassorted virus showed symptoms less severe than those with the pure avian flu. Reassortment appears to have weakened the virus.
In a final study, CDC researchers passed a hybrid virus through a series of ferrets to see if it would accumulate genetic changes necessary to transmit more easily. This tested the mutation factor. The scientists found this introduced only one genetic change in the virus but didn't enhance its transmissibility.
Other researchers have found the explanation for a phenomenon that was already clear but unexplained--that H5N1 virtually never spreads from human to human and, if it does, it's only after prolonged contact. This contrasts with human flu, which can be contracted via a single cough or sneeze. A Nature magazine study published last March found that while avian flu can infect human lungs, it cannot infect most of the cells lining the nose, throat, and sinuses. Moreover, it tends not to penetrate deeply into the lungs. "It has been an enigma why people get sick and die from H5N1 avian flu virus, but the virus does not spread well in humans," study leader and University of Wisconsin virologist Yoshihiro Kawaoka told WebMD. "Our finding explains it."
That Allegedly Horrendous Death Rate
Ersatz experts like Laurie Garrett, a renowned pandemic panic-monger, warn of a horrific mortality rate from the bird flu virus. "Right now in human beings, it kills 55 percent of the people it infects," she told ABC News's Primetime last year. St. Jude's alarmist Webster referred to a similar death rate in his New England Journal of Medicine article, and the media routinely parrot it. By comparison, the devastating 1918-1919 Spanish flu is believed to have killed 2.5 percent to 5 percent of those it infected. The death rate in a typical flu season is less than 1 percent. It's true that, of bird flu cases recorded by the World Health Organization, 59 percent have died. But this is a mere artifact with an obvious explanation: Only people with the most severe cases go to the hospital and become part of the dataset.
As to what the true mortality rate is, over a three-month period in 2004, Swedish and Vietnamese researchers studied 45,478 residents in a rural district in Vietnam that had H5N1 outbreaks to find out how many had contact with sick birds and how many had flu-like illnesses. They published their results in January 2006 in the Archives of Internal Medicine. They found that of 8,149 who had a flu-like illness, 650 to 750 probably caught it from birds. Yet for all of 2004, the World Health Organization data indicated only 29 Vietnamese cases with 20 deaths. Thus what might seem to be a horrific mortality rate of almost two in three, or 69 percent, appears to be actually around one in 140 or 0.71 percent. This, in the rural portion of a Communist country with a state-run medical system. That 0.71 percent is in the same range as seasonal human flu.
More good news from Vietnam, incidentally, is that it has reported zero cases in 2006. Why? As I wrote last year, "Vietnam appears to be making a heroic effort to inoculate all of its poultry." If you can keep poultry from getting flu, you've knocked down the chance of a human pandemic from close to zero to absolute zero.
Antivirals: Preventing Infection, Preventing Spread
Another risk-reducing development over the past year is the increased availability and evident reliability of Roche's Tamiflu and GlaxoSmithKline's drug Relenza. These drugs interfere with neuraminidase (the 'N' in H5N1), a protein on the surface of the virus that must multiply in order for the virus to multiply. Research at St. Jude's has shown that H5N1 appears to express the highest level of neuraminidase of any flu since 1957, and studies continue to appear showing both drugs can kill two birds with one stone. That is, they are effective both in preventing a person from getting the flu and, if they do get it, from transmitting it.
A review of four of these studies appeared online in the American Journal of Epidemiology in November. It showed that preventive administration of Relenza, which is given with an inhaler, reduced the chance of becoming infected by 75 percent, reduced the chance of transmission by 19 percent, and reduced the severity of illness by 52 percent. For Tamiflu, taken as tablets or liquid, preventive administration reduced the chance of becoming infected by 81 percent, reduced the chance of transmission by 80 percent, and reduced the severity of illness by 56 percent. Mind you, these were tests against human seasonal flu strains. But because H5N1 expresses such high levels of neuraminidase, there's an excellent chance it would be even more vulnerable to these two antivirals than is human flu. Last year three cases of Tamiflu-resistant H5N1 set off warning bells, but there have been no such cases reported this year.
Naturally all this is great news if you have the drug and take it in time. But the drugs can also be used to prevent a pandemic outbreak. Even a year ago, the World Health Organization had a program in place to quickly detect any outbreak of human avian flu, offering hope of smothering it with antivirals. Writing in Nature, researchers predicted that such an outbreak in the area most likely to have one, Southeast Asia, could be snuffed with "a stockpile of 3 million courses" depending on "how quickly cases are diagnosed and the speed with which antiviral drugs can be distributed." The World Health Organization had such a stockpile by early 2006, and assuredly it's much larger now.
A year ago, people and governments were flocking to get Tamiflu in the same way they've recently stampeded to get the new Sony PlayStation. But according to maker Roche, production will have been expanded to a rate of 400 million treatment courses annually by the end of this year, a more than ten-fold increase since 2004. Currently there are only 10,000 treatments of Relenza available in pharmacy channels, says a company spokesman, "However, next year we will have approximately 20 million treatments available. The deliveries will begin in January 2007 and the majority of the initial shipments will be for the U.S. government pandemic stockpiling efforts."
Vaccines: Birds in the Bush and in the Hand
Although much of the $3.8 billion Congress allocated to fight pandemic H5N1 will be a complete waste, legislators wisely dedicated a billion of that to developing an entirely new way of making flu shots. (Although vaccine makers might have done the same with their own funds at the same pace.) This entails growing the vaccine in mammalian cell cultures rather than eggs. Six companies are now working on such vaccines using federal funds. Cell cultures can cut the usual nine-month period for making vaccine batches in chicken eggs to a mere 90 days. Although the current rabies vaccine has been grown from a cell culture since 1980 and two drug companies have cell-cultured H5N1 vaccines in clinical trials, such vaccines have not yet received FDA or E.U. approval.
In fact, no human H5N1 vaccine has yet received official approval, but companies are pumping them out anyway in the confidence that their drugs will be found both safe and effective. Switzerland has ordered enough vaccine from GlaxoSmithKline for one inoculation of each of its eight million citizens if a pandemic erupts. The U.S. government has ordered 2.7 million doses from three makers, which would be enough to vaccinate first responders so they could take care of those who did become ill. Eventually the country plans to stockpile 20 million doses and then presumably will increase that as well, but since the vaccines aren't yet available, even that amount is still academic.
It's common to hear that stockpiling vaccines is futile since it's impossible to say what the effectiveness of a vaccine based on the virus presently in humans exposed to birds will be when it's altered to a point where it's going from human to human. But there was already evidence last year that such a mutation shouldn't be a problem. Scientists tested blood from people who had received an experimental vaccine against a 1997 strain of H5N1 and found it provoked a powerful cross-reaction from a strain that killed several Vietnamese in 2004.
Newer research by Dr. John Treanor and colleagues at the University of Rochester, presented on October 13 at a meeting of the Infectious Diseases Society of America supports these findings. Treanor's team studied people who'd been vaccinated against the Hong Kong strain of the H5N1 virus in 1998. Each was vaccinated again this year with a booster shot to fight the strain found in Vietnam. A second test group received only shots for the Vietnam strain in 2005. Those who received shots back in 1998 developed better protection than those with just the 2005 vaccination. Thus for all the talk about how rapidly H5N1 mutates, injections from 1998 were still protective. On the other hand, a seasonal human flu injection from 1998 would be worthless.
This is both evidence that H5N1 is not mutating like gangbusters and that we can quite possibly amass enough vaccine to protect every reachable person on the planet without having to build a new stockpile each year. Hysteria over an avian flu pandemic has been very good for the Chicken Little media, authors, ambitious health officials, drug companies, and even Bush bashers. (An alarmist fantasy published by Nature magazine in May 2005 concluded by predicting a pandemic outbreak in December of last year, laying the blame entirely at the president's feet.) But even as many of the panic-mongers have begun to lie low, the vestiges of hysteria remain--as do the misallocations of billions of dollars from more serious health problems. Too bad no one ever holds the doomsayers accountable for the damage they've done.