The Institute of Science in Society

Science Society Sustainability
http://www.i-sis.org.uk

This article can be found on the I-SIS website at 
http://www.i-sis.org.uk/WTBFP.php

ISIS Press Release 11/05/06

Where's the Bird Flu Pandemic?

The hype over bird flu pandemic has greatly profited the drug 
industry with little sign of an effective vaccine or cure

Dr. Mae-Wan Ho

Sources for this report are available in the ISIS members site.

Bird flu pandemic could kill up to 150 million and lose US$800 billion

Top UN public health expert Dr. David Nabarro of World Health 
Organisation (WHO) warned in September 2005 that a mutated bird flu 
virus pandemic could kill up to 150 million people [1]. He was just 
taking up his appointment as the new UN coordinator to lead a global 
drive to counter a human flu pandemic. Nabarro said that with the 
"almost certainty" of another influenza pandemic soon, and with 
experts saying there is a high likelihood of the H5N1 virus mutating, 
it would be "extremely wrong" to ignore the serious possibility of a 
global outbreak.

The 1918 influenza pandemic killed more than 40 million; the range of 
deaths in the next pandemic could be anything "between 5 and 150 
million, " Nabarro said.

The World Bank issued its own dire warning that economic losses due 
to pandemic bird flu could top US $800 billion [2].

In a letter to the nation, president George W. Bush announced his 
National Strategy for Pandemic Influenza Preparedness and Response 
[3], which is determined to detect outbreaks that occur anywhere in 
the world, to protect the American People by stockpiling vaccines and 
antiviral drugs, and improve the US' ability to rapidly produce new 
vaccines against a pandemic strain, and to be ready to respond at the 
federal, state and local levels in the event that a pandemic reaches 
the USA.

Because a pandemic could strike at any time, President Bush requested 
$7.1 billion in emergency funding , which includes $251 million to 
detect and contain outbreaks before they spread around the world; 
$2.8 billion to accelerate development of cell-culture technology; 
$800 million for development of new treatments and vaccines; $1.519 
billion for the Departments of Health and Human Services and Defense 
to purchase influenza vaccines; $1.029 billion to stockpile antiviral 
medications; and $644 million to ensure that all levels of government 
are prepared to respond to a pandemic outbreak.

In January 2006, the United States announced in Beijing China that it 
would provide $334 million to support the global campaign against the 
avian flu virus [4]. This funding is part of a broader commitment of 
the United States that totals £3.98 billion recently appropriated by 
Congress.

"There is no pandemic flu in Louisiana"

But by 15 April 2006, Dr. Julie Gerberding, head of the Centers for 
Disease Control and Prevention, told a conference of 1 200 of mostly 
health department officials from across the state of Georgia gathered 
in Tacoma that [5] there is no evidence bird flu will be the next 
pandemic and there is "no evidence it is evolving in a direction that 
is becoming more transmissible to people."

This was in sharp contrast to the November letter from President 
Bush, which encouraged the public to prepare the nation and the world 
"to fight this potentially devastating outbreak of infectious 
disease." The president's letter created so much anxiety that the 
audience at the Tacoma conference wanted to know about buying 
surgical masks and stockpiling food at question time.

Gerberding and other federal officials said H5N1 bird flu is likely 
to reach the United States; but when that happens, "it does not 
signal the start of a pandemic" or a threat to the food supply, said 
Richard Raymond, an undersecretary at the US Department of 
Agriculture.

Less than a week later, a press release for the 'Louisiana State 
Summit' carried the headline: "There Is No Pandemic Flu in Louisiana" 
[6]. "Flu season is coming to an end, and there have not been any 
widespread outbreaks of the flu in Louisiana. Nor have there been any 
confirmed cases of avian flu in human in the United States. Finally, 
although there has been much attention, there has not been a flu 
epidemic, much less a flu pandemic."

The flu pandemic is yet to happen. The number of human cases of bird 
flu has been rather modest so far – 204 with 113 deaths over three 
years (see Box 1) - in comparison with the most recent pandemic SARS, 
which made 8439 ill and killed 812 in just four months in 2003 [7]. 
Part of the reason is that while SARS was transmitted from 
person-to-person, bird flu is still transmitted from infected poultry 
to people.

But we are told that this could change at any time. The H5N1 virus 
could gain the ability for human transmission by mutation or by 
picking up the right genes (see "Fowl play in bird flu", this series).

Box 1

Global status of bird flu [8, 9]

Domestic poultry

There have been 4253 outbreaks since 2003 in 28 countries in Asia, 
Europe, and Africa: Topping the list are: Vietnam (2 312, 54.4 
percent), Thailand (1 078, 25.3 percent), Indonesia (209, 4.9 
percent), Turkey (176, 4.1 percent) Russia (121, 2.8 percent), and 
People's Republic of China (79, 1.9 percent).

Human

There have been a total of 204 cases of H5N1 bird flu resulting in 113 deaths.

Country

Cases

Deaths




Vietnam

93 42

Indonesia

32 24

Thailand

22 14

China

17 12

Turkey

12 4

Egypt

12 4

Azerbaijan

8 5

Cambodia

6 6

Iraq

2 2



Total

204

113

The bird flu hoax

Dr. Joseph Mercola, who runs a popular health website, has been 
referring to "the bird flu hoax" [10] ever since Bush first announced 
his National Strategy in early October 2005. The hoax was 
perpetrated, Mercola and others claim, to justify the huge sums of 
money given away to pharmaceutical corporations to make vaccines and 
antiviral drugs.

There is currently no effective vaccine against H5N1, or indeed 
against any new strain of viruses such as the influenza virus, which 
mutates and evolves rapidly. Last August, the US National Institutes 
of Health (NIH) announced preliminary results of a H5N1 vaccine trial 
[11]. But the vaccine was only effective at such large doses of the 
flu antigen (90 m g compared to the usual 15 m g) that critics said 
even if the entire US vaccine production capacity were employed, it 
could produce enough only for 15 million people, or barely 5 percent 
of the US population .

But the US government had already bought 2 million of the H5N1 
vaccine from the company Sanofi Pasteur based in Pennsylvania; and 
intended to buy 20 million more. The test results meant that would 
provide protection for 333 000 to 3.4 million people, far short of 
the original 20 million goal.

So, it is down to treatments with antiviral drugs such as ribavirin 
(action not understood) and inhibitors of the viral neuraminidase - 
oseltamivir and zanamivir – sometimes used in combination with 
corticosteroids. Other drugs such as amantadine, which targets the 
viral protein M2, an ion channel needed for the viral particle to 
become uncoated once it is taken into the cell [12], are often not 
effective [13]. The presence of amino acid residue Asp31 in the M2 
protein of H5N1 virus invariably confers resistance to amantadine 
treatment, so oseltamivir or Tamiflus (brand name) appears to be 
about the only treatment (see Box 2). It does not cure or prevent the 
disease, however.

Recently, H5N1 viruses with an aminoacid substitution in neuramindase 
that confers high-level resistance to oseltamirvir have been isolated 
from two of eight Vietnamese patients, and both died despite early 
initiation of treatment in one patient.

Nevertheless, US Defence Secretary Donald Rumsfeld, for one, has made 
more than $5 million out of bird flu by selling shares in the biotech 
firm that discovered and developed Tamiflu [14]. Tamiflu is being 
bought up in massive amounts by governments all over the world in 
anticipation of a pandemic. More than 60 countries have ordered large 
stocks.

Box 2

What is Tamiflu?

Tamiflu is practically the only drug against bird flu. A website run 
by Swiss drug giant Roche describes Tamiflu as "The #1 
doctor-prescribed flu medicine", recommended to be taken within the 
first two days from the onset of flu symptoms [15].

Tamiflu is the brand name for oseltamivir, an antiviral that acts by 
inhibiting the viral enzyme neuraminidase as an analogue of it 
substrate, thereby preventing new viruses emerging from infected 
cells [16]. It does not cure or prevent the disease, but claims to 
prevent death.



The drug was developed by a California biotech company, Gilead 
Sciences, and is now made and sold by pharmaceutical giant Roche, 
which pays a royalty on every tablet sold, amounting to about a fifth 
of its price.

Rumsfeld was on the board of Gilead from 1988 to 2001, and was its 
chairman from 1997. He left to join the Bush administration in 2001, 
but retained a huge shareholding. The firm made a loss in 2003, the 
year before concern about bird flu started. Then revenues from 
Tamiflu almost quadrupled to $44.6 million. Sales almost quadrupled 
again, to $161 million last year and the share price trebled.

Rumsfeld sold some of his Gilead shares in 2004, resulting in capital 
gains or more than $5 million, according to the financial disclosure 
report he is obliged to make each year, which also showed that he 
still held up at least $25 m worth of shares.

Roche's sale of Tamiflu was forecast to reach £1 billion by 2007. 
Patients will need two 75 mg capsules a day for five days, costing a 
total of £60-£100 [17].

Britain has ordered 14.6 million courses at £180 m, enough for a 
quarter of the population. Germany has ordered 6m doses. France, New 
Zealand and Norway planned to purchase enough to treat 20 to 25 
percent of their population.

Indeed, "experts are still predicting that the world will soon face a 
flu pandemic," and 'summits' such as the one in Baton Rouge, 
Louisiana, are held in each state to ensure the entire country is 
ready for a widespread outbreak of the flu [6].

To reinforce this message, an article was published online 28 April 
2006 in Nature , on strategies for mitigating an influenza pandemic 
based on simulations with a mathematical model [18]. The researchers 
found that border restrictions and/or internal travel restrictions 
are unlikely to delay spread by more than 2-3 weeks unless they are 
more than 99 percent effective. Closing schools during the peak of a 
pandemic can reduce the peak attack rates by up to 40 percent, but it 
would have little impact on overall attack rates. Case isolation, or 
household quarantine could have a significant impact on reducing 
overall attack rates. Treatment of clinical cases can reduce 
transmission, but only if antivirals are given within a day of 
symptoms starting.

The researchers also found that given enough drugs for 50 percent of 
the population, household-based prophylaxis (taking drugs in advance 
of being ill) coupled with school closure could reduce clinical 
attack rates by 40 to 50 percent. Vaccine stockpiled in advance of a 
pandemic could significantly reduce attack rates even if the vaccines 
are of low (70 percent) efficacy.

Those results are good news for the drug companies; the bird flu hoax lives on.

Bird flu disease in humans

Highly pathogenic avian influenza virus subtype H5N1 first caused 
disease in 18 patients with 6 deaths in Hong Kong in 1997.

A family of five from Hong Kong visited Fujian province in Mainland 
China on 26 January 2003. The two year-old daughter developed high 
fever and respiratory symptoms two days after arriving there and died 
of a pneumonia-like illness seven days after the onset of symptoms. 
The family returned to Hong Kong on 9 February. The father, a 33 
year-old, was admitted on 11 February after suffering fever and 
malaise for four days, as well as sore throat, cough with 
blood-stained sputum and bone pain. He had low lymphocyte count and 
evidence of consolidation in the right lower-lobe of the lung. He 
died six days after admission. Influenza A subtype H5N1 was 
identified, and autopsy revealed oedema, haemorrhage and other 
evidence of lung disease characteristic of severe pneumonia. No other 
organ showed signs of disease.

On 12 February, the family's previously healthy 8-year-old son was 
admitted after three days with an influenza-like illness and symptoms 
similar to the father. He said he had close contact with live 
chickens during his visit to China. He recovered.

The patients with H5N1 disease had unusually high serum levels of 
chemokines (signalling molecules of the immune system), and fits in 
with a previous report that the H5N1 virus induces large amounts of 
pro-inflammatory cytokines from macrophage cultures, suggesting that 
cytokine dysfunction, a 'cytokine storm' contributes to the H5N1 
disease [18, 19].

According to conventional wisdom, avian influenza viruses generally 
have little affinity for human respiratory tissues, because the 
haemagglutinin (HA) on the surface of the virus prefers carbohydrate 
side chains on the cell surface receptors that end in SA- a -2,3-gal, 
whereas the HA of human influenza viruses prefer those terminating in 
SA- a -2,6-gal.

Genetic analysis indicates that H5N1 is basically an avian virus 
[20], and its HA has affinity for SA- a -2,3-gal, although isolates 
from birds and humans show genetic differences indicating that the 
virus has changed on infecting humans.

In mammals including humans, influenza A viruses that can replicate 
are generally recovered only from the superficial epithelium of the 
respiratory tract, reflecting the anatomical distribution of 
trypsin-like proteases that cleave the viral haemagglutinin, which is 
an essential step for making new replicating viruses in the 
infectious process. In contrast, cleavage of the H5 haemagglutinin 
tends to be independent of the anatomical distribution of protease, 
because of the insertion of a run of basic amino acids at the 
cleavage site. This is characteristic of the HA of all highly 
pathogenic avian influenza viruses, and may contribute to the 
tendency of H5N1 viruses to localize to the brain [19].

It turns out that H5N1 can cause infection of the lower respiratory 
tract and severe pneumonia in humans because the virus binds to 
several kinds of cells in the human lung and lower respiratory tract 
[22]. These cells have surface receptors with carbohydrate chains 
ending in SA- a -2,3-gal instead of SA- a -2,6-gal typical of human 
cells.

Many scientists consider H5N1 dangerous enough as it is, as it has 
killed more than 50 percent of the people infected. They also believe 
that if H5N1 should mutate or pick up a HA gene that enables it to 
recognize SA- a -2,6-gal instead of SA- a -2,3-gal, then the virus 
would replicate rapidly in human hosts and become transmitted from 
person to person. Then, there would be no stopping a flu pandemic 
reminiscent of the one in 1918 estimated to have killed 40 million 
worldwide.

How dangerous is the H5N1 infecting poultry? Should we worry about 
consuming infected poultry products? How likely is the virus to 
become the agent of the next flu pandemic? Read the next article in 
this series, "What can you believe about bird flu?"



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