February 02, 2004
Bird Flu Virus Outbreak Has Infectious Disease Experts Worried

The A(H5N1) strain of avian influenza that has spread to many Asian countries and caused 7 deaths out of 11 known human cases has a lot of disease experts on edge. The fear is that the avian virus and the human H3N2 strain currently spreading in Asian could coinfect either a human or a bird and the avian and human viral DNA could recombine in the same infected cell to create a new virus strain that could spread rapidly in humans with fatal results. A World Health Organization (WHO) official says a combined human/avian flu strain could kill millions worldwide.

Shigeru Omi, director of the UN agency's Western Pacific office, warned last week that millions of people around the world could die if the H5N1 strain of bird flu mixes with the human H3N2 virus that was headed towards Asia.

The fear is for a reprise of the 1918 flu pandemic which killed 1% to 2% of the world's population.

Dr. Klaus Stöhr of the WHO says so far the pattern of human cases of bird flu fit the previous patterns of bird flu outbreak in Hong Kong.

Because the virus apparently "vanished" after causing the cluster of infections, Dr. Stöhr said, his agency does not consider the possible person-to-person spread a major public health threat. Similar transmission, limited to a short chain of people and with a definite end, occurred in earlier avian influenza outbreaks in Hong Kong, he said.

The fact that the bird flu virus has not rapidly spread from existing human cases suggests it hasn't mutated yet to be easily spreadable in humans.

The fact that just a handful of human cases have been reported this time despite the bird flu being around for several weeks was also fairly encouraging.

Government cover-ups and insufficient testing have allowed bird flu to spread for months before being detected.

W.H.O. first learned about the mutated A(H5N1) strain in January through reports from Vietnam, then learned that birds had begun getting infected elsewhere in Asia as early as April 2003. In addition to Vietnam, the affected countries are Cambodia, China, Indonesia, Japan, Laos, South Korea and Thailand. "We have no clue which species of bird first spread it," Dr. Stöhr said.

Better surveillance procedures are needed in many countries. Plus, there is not enough money to kill the chickens in countries where the bird flu is spreading. This increases the chance that bird flu viruses will combine with human viruses to produce a virus capable of killing millions in a human outbreak.

All flu viruses probably originate in birds, and the best environment for making the jump to humans is one where densely packed people live closely with birds and animals.

"In Asia we have a huge animal population, a huge bird population and two-thirds of the world's people living there,'' said Klaus Stohr, chief influenza scientist at the World Health Organisation.

The population of China alone is bigger than that of the whole of Africa, and 80 percent of the new human flu strains the last few decades appeared in China first.

Growth in egg and chicken consumption in Asia has increased the capacity of chickens to be hosts for avian influenza strains.

From the early 1970s to the early 1990s, per capita consumption of meat, eggs and milk grew about 50 per cent in developing countries, leading to big increases in animal herds. Over the last 25 years, the fastest growth has been in the numbers of chickens and pigs, the FAO says.

Asians' fondness for shopping at live animal markets also adds to the chances for flu jumping species, experts say.

The problem with vaccines is that they take too long to develop and manufacture. The method of growing vaccines in eggs takes months and requires that large numbers of the proper kinds of eggs and egg-growing facilities be available. It simply is not possible to scale up that quickly and it takes months to do so. Even worse, bird flu poses a special difficulty because unmodified avian influenza virus would kill the egg and therefore stop the growth process short.

The extra complication where bird flu is involved, Professor Gust says, is that the virus cannot be grown in eggs, as is usual practice in making vaccines, because it would simply kill the eggs. Instead it has to be put through a process known as reverse genetics technology to engineer a strain that both grows in eggs and protects against the bird virus.

Even if the manufacturers were ready to go when a human-to-human virus appeared, it would still take at least six months for a vaccine to be widely available. And in that time, the virus would be likely to have made its way very quickly around the world and caused many deaths.

Whether the bird flu strain currently spreading in Asia will mutate into a form easily transmittable in humans remains to be seen. But if this particular outbreak in chickens doesn't turn into a major human pandemic some flu strain will eventually mutate into a very deadly strain and could kill millions. What we need are much faster ways to develop and produce vaccines.

One bright light on the horizon if the development of cell culture techniques for growing vaccine viruses. Chiron Corporation CEO Howard Pien claims that Chiron cell culture flu vaccine will be able to halve the production time for flu vaccine.

A: The general estimate for a vaccine product is that it takes five to six years to develop it for the market. It is entirely possible we will do this faster, but that is assuming our test is very, very positive. Currently, it takes four months to make flu vaccine in chicken eggs. We believe that time can be reduced by 50%. The net effect will be to increase output.

Chiron says they will go into Phase III clinical trials for the cell culture version of their vaccine in 2004.

Chiron expects to enter Phase III studies for its flu cell-culture vaccine this year.

The US government is trying to accelerate development of faster virus production technologies but some doubt cell culture methods will be faster.

Health and Human Services Secretary Tommy Thompson says federal officials want to urge companies to move toward newer technologies that would allow faster production of vaccine, which currently takes at least six months from egg to vaccine.

In mid-December, Thompson said he hopes some of the expected $50 million in new federal funding for flu research will be used to encourage new companies to start making vaccine using newer, egg-free technologies.

A switch to cell culture technology, which Aventis already uses to make vaccines against polio and other diseases, wouldn't speed production of flu vaccine, says Michael Decker, vice president for scientific and medical affairs at Aventis. "Let's suppose we had no chickens and no eggs. Then, cell culture is faster." But for companies with established supplies of chicken eggs, there's no advantage. "The virus takes the same time to grow in either."

The use of either cell culture grow viruses to make killed-virus vaccines is not the only imaginable approach for more rapid vaccine production. DNA vaccines could probably be produced more quickly.

Another approach is the use of DNA vaccines. Here, the gene for a pathogen protein is introduced into human cells and is then expressed to produce the protein inside the body. There are many advantages to the DNA vaccination method. For example, it is much cheaper to produce and distribute large amounts of DNA than it is to produce and distribute large amounts of protein. Also, the same strategy can be used to tackle virtually any pathogen, so multiple vaccinations are possible. Technical hurdles that need to be overcome include finding efficient ways of getting the DNA into human cells, making sure the gene is expressed once it is inside the cell, and making sure the DNA does not integrate into the genome and disrupt our own genes. There are many DNA vaccines in clinical and pre-clinical trials, including vaccines for HIV, herpes, hepatitis and influenza.

Until it becomes possible to develop and produce hundreds of millions of vaccine doses in a matter of weeks the human race is going to continue to live under the threat of a repeat of the 1918 pandemic with tens or even hundreds of millions killed. Research aimed at developing types of vaccines that can be produced more quickly ought to be a higher priority.

Share |      Randall Parker, 2004 February 02 11:47 PM  Dangers Natural Bio

Marika said at June 3, 2004 4:00 PM:

Hello, June 3, 2004
My name is Marika, and I am 12 years old. Today I went to a friends house and we found a small blue egg on the ground. I couldn't find anyone else to Email so I Emailed you.I dont know but I think its either a robin's egg or a bluejays egg. I need some quick info. First of all do you think the egg will even hatch? I wrapped it up and brought it out in the sunlight so it would be nice and warm. My friend said it had been outside on the ground for about 2/3 days. Another thing I want to know is what to feed it if it does hatch. And where should I keep it? I mean I have to go to school all day long. How do I watch it? And finally I know I'd have to eventually let it free if it hatched. How would I free it. I don't know if it'd go free. Please Email me back quick. My Email is bluebookworm6@hotmail.com. Hurry!

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