ISIS Press Release 18/05/06
What Can You Believe About Bird Flu?
Dr. Mae-Wan Ho looks
behind the propaganda and expert pronouncements that frighten you and give false
reassurance in turn
A fully referenced version
of this article is posted on ISIS members’ website. Details here
Is the bird flu pandemic imminent?
Anyone following the streamers of headlines on bird flu in the popular media
will be thoroughly bewildered. Experts and politicians have been telling us
that a bird flu pandemic is bound to happen; all it takes is for the deadly
H5N1 Asian strain of bird flu that kills more than half of its human victims
to mutate so it can pass from human to human instead of from infected chickens
to humans. That could happen at any time; a state of emergency is declared,
and drugs and vaccines are being stockpiled around the world; all to the benefit
of the pharmaceutical industry (see “Where’s
the bird flu pandemic?” this series).
The
arrival of a dead swan in Fife Scotland at the beginning of April 2006 that tested positive
for H5N1 was met with due alarm. Bird flu is spreading to Britain, and
the pandemic is surely just around the corner.
A
week later, however, the British government’s
chief scientific adviser sir David King said the chances of bird flu virus
mutating into a form that spreads between human are “very low”, and any suggestion
that a global flu pandemic in humans was inevitable was “totally misleading”
[1].
Anyway, no more wild
birds have tested positive, and that seemed to have given false reassurance
to those who believe bird flu is transmitted by wild migrating birds.
Bird flu is not a food safety issue?
There has been little mention
that infected meat and other poultry products could bring the dreaded virus to our supermarket
shelves and farms. But people know that anyway. Sales of poultry products
have plummeted so much that the EU has already announced payments to compensate
the industry.
The pundits have
been out in force giving reassurances that the pandemic is not going to happen
after all, despite the alarm raised previously, which has already delivered
great profits to the drug industry, so now they’ll have to protect the food
industry.
The
chief executive of UK Medical Research Council Colin Blakemore said on BBC
radio, “There is no evidence of transmission to people by eating cooked
eggs or chicken”, adding that the only food
risk he could see was from “drinking swans’ blood”.
A journalist in Nature reporting on the debate among scientists
commented that Blakemore and others have downplayed the risk of catching bird
flu from eating chickens and eggs, for fear of damaging public confidence
and the poultry industry [2].
The European Food
Safety Authority (EFSA) published a prominent scientific risk assessment paper
in March 2006, advising that poultry products are safe to eat and have “not
been implicated in the transmission of the H5N1 avian influenza virus to humans.”
It stated that, “humans who have acquired the infection have been in direct
contact with infected live or dead birds.”
This same EFSA has been criticised recently by the European Commission for
“GMO bias” in giving overwhelmingly positive opinions on genetically modified
food and feed, and often ignoring evidence of hazards (see “European
Food Safety Authority Criticised for GMO bias”, this issue).
Many scientists disagree
with the opinion of the EFSA on bird flu, as they have on GMOs. There simply
is insufficient evidence to say that eating infected poultry would not transmit
the virus. As Masato Tashiro, a virologist at the National Institutes of Infectious
Diseases in Tokyo said, “Direct evidence of oral infection is
lacking, but so too is proof against.”
Furthermore, there
is no guarantee that people would always cook the products sufficiently well,
or take hygienic precautions while preparing food to prevent uncooked meat
contaminating other food items that are eaten raw.
Albert
Osterhaus, a virologist at the Eramus Medical Centre in Rotterdam,
said available evidence suggests that the gastro-intestinal tract in humans is a portal of entry for H5N1. He
was part of a team of scientists that showed cats became infected with H5N1
after being fed infected chickens. They exposed cats to H5N1 virus by three
different routes: intrathecally (injection into the fluid surrounding the
brain and spinal cord), feeding on infected chickens, or close contact with
respiratory-infected cats. They found that regardless of the route of exposure,
the virus replicated in the respiratory tract as well as in other tissues
of the cats; and infected tissues contained the viral antigens wherever there
is severe necrosis (tissue death) or inflammation. Inflammation association
with H5N1 infection was found in the nerve tissue of the gut wall only in
cats that had eaten virus-infected chickens, suggesting a new portal of entry
for influenza viruses in mammals [3].
All of the cats excreted virus through the respiratory tract as well as the
digestive tract. In humans, shedding of the virus in the faeces has been observed,
and therefore the possibility of faecal-oral transmission should be taken into
account.
An EFSA spokesperson
said the agency stands by the report’s conclusions [2]. Les Sims, a consultant
for the UN’s Food and Agriculture Organization (FAO) said avian influenza
“has never been and should never have been seen as a food safety issue.” Bird
flu concerns over food “have a devastating impact on the livelihood of millions
of farmers globally and demonstrate that risk communication on this has been
a total failure.”
But Jody Lanard,
a physician and risk-communication consultant based in Princeton,
New Jersey, USA, disagreed. She said such advice shows little has been learnt
about risk communication since the British agriculture minister publicly fed
his young daughter a hamburger at the height of the BSE (bovine spongiform
encephalitis) crisis.
The pundits can’t be trusted
A 2005
European Commission poll showed that almost half of European citizens believe
the authorities favour economic interests over consumer health, and
they no longer believe what the regulators say. In many cases, they believe
just the opposite of what the regulators tell them, which is why the poultry
industry is suffering.
As for the fear that
the Asian bird flu will damage the industry, the first outbreak of bird flu
was reported in Norfolk Britain 27 April 2006. Some 35 000 birds
had to be culled. The dreaded H5N1 was not the culprit, but another, H7 strain
[4], later identified to be H7N3 [5], which does not cause serious disease
in humans, but Japan has promptly slapped a ban on imports of UK poultry.
This outbreak highlights
the fact that bird flu is already endemic in commercial farms in Europe
as it is in the United States. Officials from the Department of the Environment,
Food and Rural Affairs admitted that an H7 strain of avian flu was last detected
in Britain in 1987 [4], and outbreaks of H7 avian flu have since occurred
throughout the world. In 2003, 31 million birds had to be culled in the Netherlands
after an outbreak of the H7N7 strain of bird flu. In 2002, H7N7 broke out
on poultry farms in Virginia USA, and 4 million turkeys and chickens were
slaughtered. The only comfort is that H7 infections in humans are mild, and
only one vet working on the outbreak in the Netherlands died after developing
pneumonia.
The outbreak is also a grim reminder that factory farms are the breeding grounds,
reservoirs and incubators of bird flu viruses, not wild migrating birds or backyard
farms (see “Fowl
play in bird flu”, this series)!
Is it safe to eat poultry products?
The existing evidence does
suggest that eating infected poultry runs the risk of contracting the virus,
as the cat feeding study shows. Not only can cats catch the virus by eating
infected dead birds, they can then pass it on to other cats [6]; there is
also unconfirmed evidence of human to human transmission, according to a report
from the World Health Organization (WHO) Global Influenza Program Surveillance
Network [7]. A cat was found with the H5N1 virus on the German Baltic island
of Rügen near where 100 birds have died from the H5N1 virus [6, 8], which
confirms the laboratory findings.
Furthermore, back
in October 2004, 147 tigers out of 441 died or were
killed after some of them become infected with H5N1 from eating raw chicken
carcases; subsequent investigation found that at least some tiger-to-tiger
transmission of the virus had occurred [8].
Thus, eating meat and eggs that are not sufficiently cooked
is definitely not a good idea, especially if you do not know where the meat
and eggs have come from.
Now
is the time to buy locally from organic free-range farms, which may need all
our support lest they become victims of politically motivated propaganda.
The genetic evidence
Influenza A viruses, of which H5N1 is a member, cause diseases in many other
species including humans, pigs, horses, mink, cats, and marine animals. They
have a genome that comes in 8 segments of RNA, and apart from the usual mutations
and recombinations of which viruses are prone, different strains of influenza
A viruses can exchange segments (a process referred to as re-assortment). This
makes it easy, at least in principle, to create a new deadly virus that causes
epidemics (see “Fowl
play in bird flu”, this series).
H5N1 first emerged
in Hong Kong in 1997, where it caused the deaths of 6 of 18
infected persons [9]. The virus was believed eradicated by the slaughter of
all poultry in Hong Kong, but new types of H5N1 continued to emerge in poultry
in Hong Kong in 2000 and 2001; and in 2003, antigenically and biologically
novel H5N1 killed one of two infected humans.
The World Health
Organization Global Influenza Program Surveillance Network analysed the genomes
of H5N1 viruses taken from birds and humans in Asia [7] and
showed that all the genes in the viruses are of avian influenza origin. So
reassortment of genome segments between human and bird influenza A viruses
was not involved in the current epidemic, as in earlier ones.
Of the three influenza
pandemics in the last century, the 1957 H2N2 and 1968 H3N2 pandemic viruses
were avian-human reassortments in which three and two of the eight avian gene
segments respectively got into an already circulating human-adapted virus.
The origin of the genes of the 1918 influenza virus H1N1, estimated to have
killed about 50 million worldwide, is still unknown [10].
Researchers found that the H5N1 viruses separate out into two clades (distinct
genetic lineages) with non-overlapping geographic distributions. Viruses isolated
from the Indochina peninsula form a tight cluster within clade 1, whereas those
from several surrounding countries - China, Indonesia, Japan and South Korea
– form a more divergent (less tightly clustered) clade 2. Clade 1 viruses were
isolated from both humans and birds in Vietnam, Thailand and Cambodia, but only
from birds in Laos and Malaysia. They are resistant to the adamantine drugs
but sensitive to neuraminidase inhibitors (see “Where
is the bird flu pandemic?” this series). Viruses isolated from birds and
humans in Kong Kong in 2003 and 1997 make up clades 1’ and 3 respectively.
Most H5N1 isolated from
humans are antigenically homogeneous and distinct from avian viruses circulating
before the end of 2003. Some viruses isolated in 2005 show antigenic drift
(genetic mutation), but the HA genes from viruses isolated from humans are
nevertheless closely related to the HA from H5N1 viruses of avian origin,
retaining the specificity for bird-type cell surface receptor, and differing
from the nearest gene in bird isolates of the same year in 2-14 nucleotides.
These findings are consistent with the epidemiologic data that suggest humans
acquired their infections by direct or indirect contact with poultry or poultry
products. Both clades of H5N1 from the 2004-5 outbreak have a multiple basic
amino acid motif at the cleavage site, which is a defining feature of highly
pathogenic avian influenza viruses. Among all H5N1 isolated collected in east
Asia since 1997, only those in clades 1, 1’ and 3 appear to be associated with
fatal human infections.
Taken together, the results indicate that the H5N1 viruses from human infections
and the closely related avian viruses isolated in 2004 and 2005 belong to a
single genotype, often referred to as genotype Z, and can be traced back to
viruses isolated in 1997 in Hong Kong and from geese in China.
Thus, viruses from
the 1997 H5N1 epidemic may have been circulating in Asia since
without causing any reported human infections until the two confirmed cases
in Hong Kong in February 2003. Where and how have they been circulating?
Intensive poultry farming & bird flu
In an earlier study, researchers
found that H5N1 influenza viruses were isolated from apparently healthy domestic
ducks in Mainland China from 1999 to 2002; and these viruses
were becoming progressively more pathogenic for mammals as time passed [9].
Twenty-one viruses
isolated were confirmed to be H5N1 subtype, and antigenically similar to the
virus that was the source of the 1997 Hong Kong bird flu haemagglutinin
gene, and all were highly pathogenic in chickens (most causing 100% mortality,
although the earliest isolates were less lethal). The viruses were increasingly
pathogenic for mice the later they were isolated. The earliest seven isolates
were non-pathogenic or of low pathogenicity, the next seven of relatively
more pathogenic, and the last four highly pathogenic. All pathogenic viruses
replicated in the lung.
The genetic findings suggest that H5N1 had been circulating among domestic
fowl in Asia since the 1997 epidemic in Hong Kong. And while circulating in domestic
ducks, H5N1 viruses gradually acquired the characteristics that make them lethal
in mammals including humans. One possible explanation is the transmission of
duck H5N1 viruses to humans, the selective evolution of the viruses in humans,
and their subsequent transmission back to ducks.
Thus, commercial factory farming could be the reservoir, breeding ground and
incubator for deadly epidemic viruses like H5N1, as consistent with other evidence
(see “Fowl play
in bird flu”, this series).
How likely is the bird flu pandemic?
Many experts are saying
that the only barrier between a pandemic of bird flu among birds and one among
humans is if the H5N1 mutates its HA gene to recognize the human-type cell
surface marker rather than the bird type.
As it turned out,
human cells deep in the lower respiratory tract do have the bird-type receptor,
which is why the virus can enter those cells and cause severe pneumonia; although
the progeny virus is less easy to pass on than if, like human influenza viruses,
it could enter and replicate in the cells of the upper respiratory tract as
well [11]. Is that the only barrier that keeps away the bird flu pandemic?
Things are not that
simple, according to the team of researchers in Erasmus Medical
Center in Rotterdam, the Netherlands. Left
to its own devices, successful species jumps in nature are relatively rare.
That is because complex adaptations
are needed for a virus to get established in a new species and transmit from
host to host within that species [12]. These complex
adaptations including genetic differences constitute biological barriers between species, which can only
be breached by genetic modification. That is why genetic modification is dangerous,
as I, and others have been warning since genetic engineering began. The
SARS virus of the last pandemic did breach species barriers and was highly
infectious as it passed from one human host to numerous others, it made many
more people ill and caused many more deaths. There is indeed evidence
that extensive genetic engineering of corona viruses may have been contributed
to creating the SARS virus [13, 14].
What are the barriers
preventing a virus to get into a new host [12]?
First of all, there are barriers to prevent the virus from entering the body,
such as mucus, alveolar macrophages, and epithelium (linings of organs and tissues).
There are specific receptors governing the entry into cells. The HA on the viral
coats of the avian influenza viruses preferentially bind to carbohydrate chains
attached to the receptor protein ending in a sialic acid in a-2,3 linkage to a galactose, whereas the HA on human influenza
viruses prefer an a-2,6 linkage. The lower respiratory tract cells in humans
have carbohydrate chains on receptors ending in SA-a-2,3-gal, however, which is why fatal pneumonia can occur
in humans infected with the virus.
Once within the cell, the virus must replicate. Many avian influenza viruses
can infect mouse cells but not replicate; often because the viral polymerase
differs between avian and mammalian influenza viruses in residue 627 of the
polymerase protein PB2, which is usually glutamic acid in avian viruses and
lysine in mammalian viruses. So this might be another barrier. In experimentally
infected mice, a glutamic acid to lysine mutation at this position in the PB2
protein of H5N1 virus results in increased virulence and in the ability of the
virus to invade organs other than the lungs. Both H5N1 virus from human patients
in Asia and H7N7 virus from a fatal human case in the Netherlands possess a
lysine at this site. Lysine is also in the PB2 in H5N1 viruses isolated from
the thousands of dead wild water-fowl in mid-2005 from Qinghai Lake in China.
The replicated virus must be released from the host cell to infect more cells
or be shed from the host. In influenza, progeny virus particles are bound to
host cell receptor carbohydrate chains by their haemagglutinin. Viral neuraminidase
cleaves these carbohydrate chains, thus releasing the newly produced virus from
the cell surface. Like the respective haemagglutinins, neuraminidases from avian
influenza viruses have a preference for the SA-a-2,3-gal-terminated chains, whereas those from many human
influenza viruses prefer the a-2,6 linkage.
Even if progeny virus exits one host cell, host innate immune responses may
hinder the infection of other cells. Interferons may induce uninfected cells
to enter an antiviral state that inhibits viral replication. The viral NS1 polypeptide
acts as an antagonist to interferon induction in infected cells by sequestering
double-stranded RNAs or suppressing host post-transcriptional processing of
mRNAs. NS1 also may help the virus to replicate in interferon-treated cultured
cells.
In order to spread
from the respiratory tract to other susceptible tissues, the virus needs to
enter the lymph and/or blood system, and be successfully transported to other
tissues. In poultry, whether infection is localised or systemic depends on
the amino acid sequence at the cleavage site of HA. The cleavage is required
for the haemagglutinin to become fully functional. Low pathogenic influenza
viruses require extracellular proteases that are limited to the respiratory
and gastrointestinal tracts to cleave the precursor haemagglutinin, whereas
highly pathogenic avian influenza viruses have changes in the cleavage site
that allow the precursor HA to be processed by ubiquitous intracellular proteases,
resulting in fatal systemic infection. The HAs of H5N1 viruses all have this
change, which is a motif of basic amino acids.
From their sites of replication, viruses need to be transmitted to new hosts.
Dissemination of progeny viruses form the infected host occurs through shedding
in respiratory, enteric, or urogenital secretions. Human influenza viruses replicate
mainly in the upper respiratory tract and are usually readily transmitted via
droplets formed during coughing or sneezing. By contrast, H5N1 virus typically
infects human cells in the lower respiratory tract and so may be less easily
shed from the infected patient.
Finally, it is well established in epidemiology theory that, as the proportion
of susceptible hosts in the population, s, drops (as individuals become
infected, then recover, or die), the number of secondary cases per infection,
R, also drops, R = sR0. If R<1, as
is currently the case for H5N1, an infection will not cause a major epidemic.
But if R is even modestly greater than one, a novel infection may spread
locally, with potential for further spread in the absence of control.
For novel infections that jump species, there is no pre-existing specific immunity.
(Although as many others have pointed out, boosting our natural innate immunity
through good nutrition will give us the best protections yet against any new
disease agent.) Pre-existing immune protection can sometimes reduce the number
of susceptible hosts, and hence R. For instance, humans who had previously
encountered an influenza virus with the N2 neuraminidase may have been partially
protected in the 1968 H3N2 pandemic that followed the global circulation of
H2N2 viruses. In addition, cross-reactive T cells (which kill virus-infected
cells) also may contribute to immunity against other subtypes of influenza viruses.
Influenza is difficult to control because a long infectious period coincide
with a period of transmission before symptoms become apparent and quarantine
measures can be taken; as opposed to SARS, in which the transmission period
coincides with the appearance of symptoms.
Faulty replication of RNA viruses within an individual can generate mutants
that by chance have the capability of being transmitted. This was highlighted
in January 2006 when samples from a patient infected with H5N1 virus in Turkey
was found to have a mixed population of viruses, some of which expressed haemagglutinin
with an amino acid sequence associated with an increased affinity for SA-a-2.6-Gal.
Conclusion
It would
be foolish to be complacent about eating infected poultry products. On the
other hand, the bird flu pandemic is not just around the corner, though it
could happen if we do not address the real cause of bird flu: the ever-expanding
intensive poultry farming and the globalised food trade.
All the evidence
summarised in this and other articles in the series points to intensive poultry
farming as the reservoir and incubator for deadly bird flu viruses, while
the globalised trade in live birds and poultry products are the main routes
of disease transmission.
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