Science in Society Archive

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

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?”

Article first published 11/05/06



References

  1. “WHO: Mutated bird flu could kill up to 150 million people”, USA Today , 20 September 2005, http://www.usatoday.com/news/health/2005-09-29-flu-pandemic_x.htm
  2. World Bank Avian flu: economic losses could top US$800 billion. World Bank News and Broadcast 8 November 2005, http://web.worldbank.org/WBSITE/EXTERNAL/NEWS/0,,contentMDK:20715408~pagePK:642357043~piPK:437376~the SitePK:4607,00html
  3. Pandemic Flu Preparing and Protecting Against Avian Influenza. The White House, 1 November 2005, http://www.whitehouse.gov/infocus/pandemicflu/
  4. Statement on U.S. pledge of $334 million in global fight against bird flu. The White House, 18 January 2006, http://www.whitehouse.gov/news/releases/2006/01/20060118-6.html
  5. “Bird flu threat not so grave, CDC chief says”, M. Alexander Otto, The News Tribune 15 April 2006, http://www.thenewstribune.com/news/local/story/5663788p-5080102c.html
  6. “There is no pandemic flu in Louisiana”, Press Release. Department of Health and Hospitals, Louisiana, 21 April 2006, http://www.dhh.state.la.us/news.asp?Detail=855
  7. Ho MW. SARS virus genetically engineered? Science in Society 2003, 19, 36-38, http://www.i-sis.org.uk/isisnews.php
  8. Update on avian influenza in animals. Alerts – Disease Information, Organisation Mondiale de la Santé Animale, 21 April 2006, http://www.oie.int/downld/AVIAN%20INFLUENZA/A_AI-Asia.htm
  9. Confirmed human cases of avian influenza A (H5N1) Reported to WHO, 21 April 2006, http://www.who.int/csr/disease/avian_influenza/country/en/index.html
  10. Bird flu epidemic is a hoax. Dr. Joseph Mercola, http://www.mercola.com/2005/oct/25/avian_flu_epidemic_is_a_hoax.htm
  11. “Bird flu vaccine not up to scratch”, Declan Butler, News@nature.com , 10 August 2005, doi:10.1038/news050808-9
  12. Amantadine. Wikipedia, http://en.wikipedia.org/wiki/Amantadine
  13. Henter J-I, Chow C-B, Leung C-W Lau Y-L. Cytotoxic therapy for severe avian influenza A (H5N1) infection. Lancet 2006, 367, 870-3.
  14. “Donald Rumsfeld makes $5 million killing on bird flu drug”, Geoffrey Lean and Jonathan Owen, Independent on Sunday , 12 March 2006, http://www.commondreams.org/headlines06/0312-06.htm
  15. Tamiflu: the #1 doctor-prescribed flu medicine. Tamiflu, http://www.tamiflu.com/
  16. Oseltamivir. Wikipedia, http://en.wikipedia.org/wiki/Tamiflu
  17. “Roche sees £1bn Tamiflu sales”. Alan Hall, Evening Standard , 18 October 2005, http://www.thisismoney.co.uk/news/article.html?in_article_id=404429&in_page_id=2
  18. Ferguson NM, Cummings DAT, Fraser C, Cajka JC, Cooley PC and Burke DS. Strategies for mitigating an influenza pandemic. Published online, 28 April 2006, Nature , doi:10.1038/nature
  19. Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, Ng T<, Chan KH, Lai ST, Lim WL, Yuen KY, Guan Y. Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 2004, 363, 617-9.
  20. Doherty PC, Turner SJ, Webby RG and Thomas PG. Influenza and the challenge for immunology. Nature Immunology 2006, 7, 449-55.
  21. The World Health Organization Global Influenza Program Surveillance Network. Evolution of H5N1 avian influenza viruses in Asia. Emerging Infectious Diseases 2005, 11, 1515-21
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  23. Van Riel D, Muster VJ, de Wit E, Rimmelzwaan GF, Fouchier RAM, Osterhaus AbDME, Kuiken T. H5N1 virus attachment to lower respiratory tract. Science 2006, 312, 399.

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