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Wednesday, October 19, 2005

Bird Flu Vaccines - Science In Action

As you may or may not know, the current tests on vaccine without adjuvants have showed that two doses of 90mcg each were required to induce decent immunity (not even great immunity). This means that the worldwide capacity for vaccine production would amount to vaccines for only 75 million out of a world population of more than 6 billion.

That means that after a year of full-out vaccine production we would only have enough to vaccinate about 1 out of every 85 people. Worse yet, the strain that has been used to develop the test vaccine is quite different from some of the currently circulating strains of H5N1, so it might not confer much protection on those immunized.

The trivalent flu vaccine contains three strains of vaccine of 15 mcg each for a total one time dose of 45mcg.

Tests on adjuvants to make smaller doses of vaccine produce a better immune response are proceeding, and work on new methods of designing vaccine is leaping ahead. This thread in CurEvents.com contains links to several articles about various strategies that may work. The bottom line, however, is that you can't expect an effective and available vaccine against a human strain of H5N1 within the next two years.

With that in mind, doesn't it seem rational to shift a lot of public health resources to the third world? If nothing else, we could sample and test the strains currently circulating in Asia so that we had a good library with which to use the new techniques of designing vaccines.

As for issues about vaccinating birds, see this CurEvents.com thread. A lot of people don't agree with my theories (I'm MM2), so this way you can get the criticism directly from them. I believe that vaccinating poultry in Asia with ineffective vaccines is what produced the Qinghai strain.

If I'm right, the very last thing we want to do is use a poorly designed vaccine to pre-vaccinate the human population. It's okay if it's only a few people, but not for widespread use. Flu strains change very rapidly in large populations during outbreaks, so vaccinating a bunch of people beforehand might produce an antigenic shift that would tend to make the entire population more vulnerable.

The reason that I bring this up is that work on producing a vaccine that's supposed to be effective against all flu strains is proceeding. I doubt it will succeed and my bet is that the attempt would be dangerous, because it would force the evolution of currently circulating strains toward virulence.

I believe the high-pathogenic strains of bird flu evolved due to the interaction of vaccinated populations of domestic birds and wild birds. The domestic birds had partial immunity by vaccination, so a more infectious strain evolved that could overcome the partial immunity (IMO in India). If the virus were isolated in the domestic population, it would evolve into a low-pathogenic variety, because high-pathogenic varieties would quickly be eliminated by culling. But given that it also has the wild birds to infect, the high pathogenic strains are being produced by the forces of natural selection and the interactions of these two populations.

Domestic birds and swine are bred for characteristics other than resistance to disease. Wild birds are selected for resistance to infection. The interaction between a susceptible population and a carrier population is what is driving this.

The reason you see the sudden occurrence of disease when migratory birds arrive in an area is the stress of migration. While they are eating and getting fat, their natural resistance keeps their viral count relatively low. After they have flown for long distances, the stress on their immune system allows the virus to replicate rapidly. At their new stopping place, large amounts of virus are disseminated on the ground and in the water from their droppings. It is then picked up by non-migratory wild birds (and now mammalian populations), who convey it to domestic flocks.

The domestic flocks with partial immunity succumb to strains that are very virulent and are able to evade the partial immunity. These strains pass back into the wild birds and rodents, and when the migratory birds fly in some of them pick up the new strain.

It's a giant mixing bowl selecting for virulence and antigenic change.

The Indonesian researchers seem to have noted the same phenomenon about vaccinations in domestic fowl - that the virus was mutating rapidly when birds had been given non-specific vaccinations.

Now, there is a huge wild bird population that has not yet been infected, and there is an ever-renewable population of domestic birds in which a new strain of the virus can romp, so I don't see any equilibrium developing any time soon. Instead, I would say that the same conditions that produced the Qinghai strain will continue to produce new variants, and the interaction between domestic birds and wild birds will continue just as it is now.

To boot, now you have added the pig/rat vector. I expect more pathogenic strains than the Qinghai to appear in the next two years, because of the broad range of hosts and the culling efforts.

As for why I don't think trying to cull wild birds is useful, eventually the wild bird populations (non or short-migrating populations) will develop an equilibrium-adapted strain that is incredibly infectious yet not very harmful to its host, and that will serve as an inoculation. The migrating birds will eventually carry that strain around the world. But you are looking at at least a decade before that happens, and probably two. The human strains will long since have emerged and subsided.

The only thing I can see that one could do to change this is to stop culling and vaccinating domestic populations, and let the survivor birds breed. This would take a decade or more to produce results and in the meantime a large number of people would probably starve to death, so it's not likely to happen. The birds which would survive to breed would be slower-growing and slower-laying, so they would inevitably be selected back out of the domestic population again.

In any case, the circumstances that produced the exceptionally and abnormally virulent strains of H5N1 are still extant and will produce other viruses with the same characteristics. It is not the small bird/swine/human type of farming that produced this. That has been around forever. It is the practices of modern farming that did, especially vaccinating poultry.

Killing all the birds and shit reminds me of this story: Back in Jolly Old when the Plague hit London, somebody noticed that hundreds of thousands of cats had infiltrated the city. The smart guys knew that it was infected cats causing the Plague. So they killed all the cats.

Now here's a little something: the use of silver. I'll post something on it tomorrow, but just so you know; the term: "born with a silver spoon in his mouth" comes from the fact that in Jolly Old the only persons not getting the Plague were the rich. It was only the rich that could afford silver eating utensils and dishes, and it had been known for centuries that silver prevented contamination in almost everything..
Howard - I think silver only works against bacteria, but it does work. This is still used in veterinary medicine at times!

I have wondered lately if the answer to bacterial drug resistance might not be that.

Killing wild birds won't help at all.
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