Before I ask
you to believe anything I write, I should start with my credentials.
At one time I was Chief, Laboratory of Virology & Rickettsiology,
Division of Biologics Standards, National Institutes of Health
(for more detail check my Curriculum Vitae on my web site:
www.drtauraso.com ). The Division, which
is now the Bureau of Biologics, FDA, was the regulatory agency
concerned with, among other things, overseeing the manufacture,
safety, potency, and efficacy of all biologic products, including
vaccines. During the last few years of my tenure there, I
was the principal officer in charge of ALL aspects of influenza
vaccine control. It is important to note that, at the time,
there were 6 United States influenza vaccine manufacturers
(presently in 2006 there is only one!).
It was during
the influenza epidemic known at the time as “The Hong Kong
Flu” in 1967/68 that my laboratory was able to revamp and
update the methods of determining influenza vaccine potency.
Up until that time such tests were dreadfully inadequate.
It is my feeling
today that epidemiologists -- scientists who study how epidemics
develop and how to control them -- have either forgotten history
or are asleep at the wheel.
When we examine
how many contagious diseases were controlled (prevented or
cured) in the past, it was good epidemiology which did it.
Cholera and dysentery, once scourges in many countries, were
eliminated when we cleaned up the water supply by separating
sewage from clean water. In those countries where the water
supply is not cleaned up by public health methods, these diseases
still occur from time to time.
which killed many people in this hemisphere, preventing the
French from completing the Panama Canal , was virtually eliminated
once Dr. Gorgas controlled the mosquitoes which carried the
virus. Many do not know that the largest viral epidemic killing
tens of thousand of people in Philadelphia in the mid 1850's
was caused by Yellow Fever. Today this viral disease just
does not occur here nor anywhere in the Western Hemisphere
. Although there is now a Yellow Fever Vaccine, what eliminated
the disease was a public health measure of getting rid of
the mosquito vector.
of course, was the great “wonder drug” in the 1940's which
cured many bacterial diseases such as strep throat (and its
related scarlet fever and complicating rheumatic fever), bacterial
pneumoniae of various kinds, urinary tract infections, and
many more too numerous to list here.
We should not
belittle the contribution of vaccines which can be credited
in virtually eliminating polio, measles, mumps, rubella, whooping
cough, and tetanus, again to name a few.
of this article is to evaluate the use of influenza vaccine
in preventing epidemics and to suggest a novel new approach
to the prevention of the much dreaded “Bird Flu.”
VACCINE REALLY WORK?
At one time
when I was the Influenza Vaccine Control Officer working at
the Division of Biologics Standards, I was skeptical about
the value of influenza vaccine in preventing influenza epidemics.
The influenza virus is complex and the vaccine must be made
correctly, it must contain adequate potency, and sufficient
numbers of individuals must be immunized to achieve “herd
immunity” or it will not work. Another problem is the fact
that the virus mutates (changes) and a new vaccine must be
made with each change which occurs quite frequently. Additionally,
there might not be sufficient time to make enough vaccine
in time to distribute among the population at risk before
the epidemic hits.
and we do not really know why, a new strain emerges in the
Far East . The subsequent epidemic migrates to the West. The
degree and seriousness of the epidemic is usually related
to how different the new strain is from the previous strain.
But the vaccine
is the best and only thing we have at this time, and it behooves
us to determine how we can make it work for us.
earlier, the influenza virus is complex as viruses go. It
contains two proteins which stimulate the body to make antibodies
to them. The Hemagglutinin (shortened with the letter “H”)
and the Neuraminidase enzyme protein (shortened with the letter
“N”). So the virus is identified by these two proteins: H5N1
as in the case of the bird flu virus.
strains of influenza A
pandemic of 1918
pandemic of "Asian" flu
pandemic of " Hong Kong " flu
A/New Jersey /7 H1N1
swine flu in recruits
some strains had similar subtypes this did not prevent them
from resulting in epidemics as in the case with the three
H2N2 strains listed here. It would also appear that those
viruses with N2 seem to cause more human pandemics of influenza
than strains with other N subtypes. Although there was a great
scare when swine flu hit in 1976, it really did not produce
any significant epidemic among the population. What caused
more problems was the high incidence of Guillian Barre syndrome
– a paralytic disease -- resulting in individuals getting
the “bad” vaccine.
** Some have
believed the 1918 pandemic was cause by a bird-type influenza.
Others believed it was caused by a swine strain. The fact
is that at this time we really are not sure.
DATA ARE KNOWN ABOUT INFLUENZA?
B and C viruses are known to cause disease in humans. Although
influenza B and C viruses are strictly human pathogens, influenza
A viruses are readily isolated from avian species, pigs and
other animals. Influenza A viruses are divided into subtypes
based on differences in their surface glycoprotein antigens,
hemagglutinin (H) and the enzyme, neuraminidase (N). There
are 14 recognized H subtypes and 9 recognized N subtypes.
All of these subtypes have been isolated in birds but only
3 different H and two different N subtypes have been isolated
in humans (See TABLE II)
II: Influenza Subtypes
viruses are unique amongst the respiratory viruses in that
they undergo significant antigenic variation. Antigenic drift
involves minor antigen changes from one season to the next
and may result in epidemic spread of the new strain. Antigenic
shift involves major antigenic changes of the H and N molecules
and occurs only with Influenza A viruses. These changes can
result in the appearance of pandemic viruses. (a pandemic
is an epidemic which is widespread throughout the world)
believe individuals who survived the 1918 flu pandemic have
antibodies to H1, others suggest it was H5, and so it is assumed
that they were infected with a virus of similar protein composition.
Was the virus which caused the 1918 pandemic of bird origin?
Who really knows? We have named the present flu strain H5.
Could the H5 then have been of swine origin or some other
animal? This is unimportant to our present discussion. What
ever the origin might have been the pandemic resulted in very
many deaths world wide. So we must take this very seriously.
suggests that the vaccine must induce the production of antibodies
to both the H an N proteins
to be efficacious. In the case of the swine influenza vaccine
over 20 years ago, something happened to destroy the N protein
during the inactivation process with formalin (formaldehyde).
But, this not well known fact was withheld from the public.
Public health officials were in a bind. President Gerald Ford
publicly stated that we had to immunize the entire population.
And so we embarked on this great program to immunize the public
with a worthless vaccine. I was in private practice as a Pediatrician
at the time and I refused to give it my patients, many of
whom later thought I was a genius for this vaccine resulted
in a very high incidence of the ascending paralysis known
as Guillian Barre Syndrome. I, of course, took the credit
but no one, including me, knew this complication was to occur.
All I knew was the vaccine was no good, so why take the risk?
When one observes
how chickens are penned up like sardines in the production
houses in Asia and South East Asia – and in the United States
--, it is little wonder that this virus originated there.
I have seen pictures of these birds so crowded they are unable
to move in any direction. These are both chicken
production houses .
Bird flu is
a disease of birds and under normal situations infects mostly
birds and spreads easily from bird to bird and does not seem
to care what species of bird it infects, for it has been found
in chickens, ducks, geese, swans, etc. The fact that it infects
migratory birds is particularly important because migratory
birds have been one of the principal means of spread from
country to country. Although bird flu can spread from bird
to humans, since humans are not the natural host, the infection
usually does not spread from human to human. It has recently
been shown that the bird flu has a particularly difficult
time penetrating the respiratory mucosal cells of humans.
And I believe there is a reason for this.
But let us
not forget that the flu virus may mutate very easily to a
strain somewhat related to but different from the originating
strain. The new mutated strain is usually sufficiently different
to make it contagious to the general public. This very important
fact that flu virus can mutate makes it most formidable and
is the reason why influenza epidemics occur every year or
so. I am concerned if and when the Bird Flu virus ever mutates
into H5N2. What we do not know is whether an H5N2 strain will
be as serious a pathogen to humans as H5N1 is to birds. It
could be that the N5N2 strain might not be contagious as we
strains listed in the TABLES, it would appear that humans
seem to be susceptible only to H2-containing strains. Remember
what was stated above that the bird flu has a difficult time
penetrating the respiratory mucosal cells in the human. It
has been believed that the neuraminidase
enzyme is responsible for how the influenza virus initially
penetrates the cell and perhaps why the Swine flu vaccine
was not effective because it lacked the capacity to elicit
neuraminidase antibodies. Additionally the Swine flu never
progressed into a full blown epidemic, probably because it
contained N1 and not N2.
a potential mutation of H5N1 to N5N2, a vaccine containing
both antigens would be what is needed to prevent this potential
it can mutate the flu virus poses a real threat to humans.
SHOULD WE DO?
waiting until the Bird Flu virus mutates to become a full
fledged human pathogen able to transmit from human to human,
why not anticipate this event. Prepare a vaccine containing
the H5H1 antigens and begin a prospective vaccination program
in humans. Since this would be prospective, we would have
sufficient time to make this happen during a 1 - 1 ½
year time period.
This bold approach
would be worth it considering the potential of Bird Flu causing
such a serious pandemic. In initial smaller immunization programs
of giving the H5N1 vaccine to individuals in Asia at risk
of getting the virus directly from birds. But, I urge not
to delay the larger program of immunizing individuals world
A better approach
would be to prepare a vaccine containing the following bivalent
influenza strains: Bird Flu (H5H1), 500 CCA Units; the current
A strain of H3N2, 500 Units; and not include any B influenza
strain. High risk individuals in South East Asia should receive
a similar vaccine. This is a most unique approach, for we
usually do not prepare and administer a vaccine for a strain
of virus which does not yet exist. But considering the potential
harm we are anticipating if and when the Bird Flu is able
to spread from human to human.
can be administered either one cc subcutaneously or 0.1 cc
intradermally, which we have been shown to be as effective
in eliciting antibodies.
We still have
adequate time to accomplish this. Unfortunately, as things
usually move in government, committees are slow in making
and executing decisions. I urge that in this case decisions
are made quickly to prevent the spread of what might be a
devastating disease -- “Human/Bird Flu.”
c. Tauraso, M.D.
Laboratory of Virology and Rickettsiology, Division of Biologics
Standards, National Institutes of Health