What Is Avian Flu?

The cause of the ongoing 2004 Asian outbreak of avian (bird) influenza (also called “chicken cholera” and “bird plague”) is the “H5N1 influenza type A virus” (henceforth H5N1). Researchers first identified H5N1 in terns, which are birds, in South Africa in 1961. H5N1 is extremely contagious in birds and rapidly fatal, with a mortality approaching 100%. Birds can die on the same day that ruffled feathers, diarrhea, and other symptoms and signs first appear.

Sick bird with ruffled feathers
Source: Getty Images Korea Times, available from: http://archive.wn.com/birdflutoday

The most important control measures once authorities detect an outbreak of H5N1 avian flu is rapid destruction (called “culling” or “stamping out”) of all infected and exposed birds, proper disposal of carcasses, and the quarantining and disinfection of poultry farms. (1)

http://www.zonaeuropa.com/weblog20040111.htm Disposal of bird carcasses.

http://www.zonaeuropa.com/weblog20040111.htm Disposal of bird carcasses.

Not all avian flu virus strains are as nasty as H5N1. Thus, learning which avian virus strain is causing a given poultry outbreak is important to determine the risk to human health (as we shall see below, H5N1 has developed the ability to infect humans). For example, the weakly pathogenic H5N2 (not H5N1--notice the difference) strain, which does not cause human disease, caused an outbreak of avian influenza in Taiwan, and H7 and H9 avian flu strains caused a recent outbreak in Pakistan.

Among its numerous distinctive qualities, H5N1 is now known to have the ability to jump species, e.g., from birds to humans. This jump first occurred during the 1997 Hong Kong avian flu outbreak. Diseases (e.g., salmonella and rabies) that are shared by, and transmitted between, humans and animals, are called zoonoses (more on this below). Of the eighteen persons who required hospitalization for laboratory-proven H5N1disease in the 1997 Hong Kong avian flu outbreak, six died. The source of their infection in all cases was traced to contact with diseased birds on farms (1 case) and in live poultry markets (17 cases). (1)

City of Hong Kong
http://www.askasia.org/image/photos/i000127.htm

Even more grave in the 1997 Hong Kong avian flu outbreak was the identification of one case of “probable”transmission ofH5N1 between humans. This case involved “prolonged, unprotected, intimate exposure to a child who was dying of unconfirmed but highly suspected H5N1 infection.” (2) Inter-human spread of H5N1 worries world public health authorities because H5N1 is highly pathogenic and could potentially ignite a worldwide human pandemic that could not be stopped, but only mitigated through various interventions, such as rapid poultry culling, as described above.

In December2003 (one year ago), a much wider outbreak of avian flu caused by the H5N1 strain began simultaneously in multiple Asian countries. As of October 25, 2004 (two months ago), 44 humans in Viet Nam and Thailand have been infected with the H5N1 avian flu, and 32 have died (a very high mortality rate indeed), according to the World Health Organization, which reports only laboratory-confirmed cases. (3)

Map of most recent avian flu outbreak (January 2004)
http://www.zonaeuropa.com/01058.htm

Has any human-to-human transmission been identified in the 2003-2004 Asian avian flu outbreak? The answer is “maybe”. On September 27, 2004, Thai health officials announced “possible” human-to-human transmission in a family cluster of H5N1 flu. Specifically, a mother could have acquired the infection either from some environmental source or while caring for her daughter.

Why are world public health authorities so concerned about an H5N1 pandemic if human-to-human transmission so far appears rare? The answer involves influenza virus mutations. Research has shown that certain avian influenza virus strains, initially of low pathogenicity, can rapidly mutate (within 6 to 9 months) into a highly pathogenic strain if allowed to circulate in poultry populations. (1)

In addition, “[S]cientists have learned that avian and human influenza viruses canexchange genes when a person is simultaneously infected with viruses from both species. This process of gene swapping inside the human body can give rise to a completely new subtype of the influenza virus to which few, if any, humans would have natural immunity. Moreover, existing vaccines, which are developed each year to match presently circulating strains and protect humans during seasonal epidemics, would not be effective against a completely new influenza virus.

“If the new virus contains sufficient human genes, transmission directly from one person to another (instead of from birds to humans only) can occur. When this happens, the conditions for the start of a new influenza pandemic will have been met. Most alarming would be a situation in which person-to-person transmission resulted in successive generations of severe disease with high mortality, which was the situation during the great influenza pandemic of 1918–1919, when a completely new influenza virus subtype emerged and spread around the globe, in around 4 to 6 months. Several waves of infection occurred over 2 years, killing an estimated 40–50 million persons.” (1)

Scientists working in several countries have developed a vaccine prototype for H5N1 using the 2003 strain. This was not easy. H5N1 in its natural form kills the chicken eggs upon which viruses are normally grown to produce vaccines. To address this, the world scientific community used “reverse genetics” 1) to lower the pathogenicity of H5N1 to chickens and 2) to obtain a high yield of the altered virus in egg cultures from which a vaccine could then be prepared. Specifically, researchers removed “a stretch of 4 or 5 basic amino acids at the hemagglutinin cleavage site that allows the virus to replicate in every organ of a chicken's body, rather than respiratory and gut tissue normally infected.” (4).

Unfortunately, the H5N1 vaccine prototype used the 2003 strain of H5N1, and cannot be used to expedite vaccine development in the case of an erupting pandemic. The reason is the initial analysis of the 2004 H5N1 virus (not the 2003 H5N1 virus), conducted by laboratories in the WHO network (see below), demonstrated significant virus mutation.

The WHO is so convinced that the H5N1 phenomenon presents a serious risk to human health that it is strongly encouraging the development of “pandemic preparedness” in all countries. “ The first priority, and the major line of defense, is to reduce opportunities for human exposure to the largest reservoir of the virus: infected poultry. This is achieved through the rapid detection of poultry outbreaks and the emergency introduction of control measures, including the destruction all infected or exposed poultry stock, and the proper disposal of carcasses.” (1)

Do presently available “get-yours-now!” human flu vaccines contribute to averting an influenza pandemic with H5N1? WHO experts reply: “Yes, in a precisely targeted way. Current vaccines, when administered to high-risk groups, such as poultry cullers, protect against circulating human strains and thus reduce the risk that humans at high risk of exposure to the bird virus might become infected with human and avian viruses at the same time. Such dual infections give the avian and human viruses an opportunity to exchange genes, possibly resulting in a new influenza virus subtype with pandemic potential. Annual vaccines are produced for routine use in protecting humans during seasonal epidemics of influenza. They offer no protection against infection with the H5N1 avian virus.” (1)

How exactly is year-to-year influenza vaccine composition determined? “ Circulating influenza viruses in humans are subject to permanent antigenic changes which require annual adaptation of the influenza vaccine formulation. Updates in influenza vaccine composition should ensure the closest possible match between the influenza vaccine strains and the circulating influenza strains; ensuring this match is one of the foundations for influenza vaccine efficacy.” (5) The Global Influenza Surveillance Network, administered by the WHO since 1948, currently consists of 112 national influenza centers in 83 countries and four WHO Collaborating Centers for Reference and Research on Influenza located in Atlanta, United States (the CDC); London, United Kingdom; Melbourne, Australia; and Tokyo, Japan.

“The 112 national influenza centers sample patients with influenza-like illness and submit representative isolates to WHO Collaborating Centers for immediate strain identification. In addition to genetic and antigenic analyses of influenza viruses, the WHO Collaborating Centers jointly with key national laboratories involved in registration and quality control of influenza vaccines (Australia, the United Kingdom, and the United States) collaborate annually on serological studies to obtain evidence as to whether the current vaccines induce satisfactory antibody levels to new epidemic strains.

World Health Organization convenes vaccine recommendation meeting.
http://www.who.int/csr/disease/influenza/vaccinerecommendations/en/

“Twice a year, WHO organizes a consultation with the Directors of the WHO Collaborating Centers and representatives of key national laboratories to review the results of these laboratory and clinical studies and make recommendations on the composition of the influenza vaccine (February: northern hemisphere; September: southern hemisphere). Immediately after this consultation, WHO informs representatives of pharmaceutical companies on its decisions which are published in the press and the WHO Weekly Epidemiological Record. The WHO collaborates with key national licensing agencies on the provision of viruses for vaccine production as well as vaccine potency testing reagents. More than 250 million vaccine doses are produced annually based on the WHO recommendations. Since 1972, WHO has recommended 39 changes in the influenza vaccine formulation.” The (5)

What does the prescription for influenza vaccine for the Northern hemisphere in 2004-2005 look like? The WHO authorities wrote: “It is recommended that vaccines to be used in the 2004-2005 northern hemisphere influenza season contain the following:

• “an A/New Caledonia/20/99(H1N1)-like virus
• an A/Fujian/411/2002(H3N2)-like virus a
• a B/Shanghai/361/2002-like virus b

a The currently used vaccine virus is A/Wyoming/3/2003. A /Kumamoto/102/2002 is also available as a vaccine virus.

b Candidate vaccine viruses include B/Shanghai/361/2002 and B/Jilin/20/2003 which is a B/Shanghai/361/2002-like virus.” (5)

Editor’s Note: The H5N1 phenomenon is part of an ancient pattern of zoonotic diseases, which naturally infect both humans AND animals and which can be transmitted between them. The World Health Organization has defined an emerging zoonosis as a "zoonosis that is newly recognized or newly evolved or that has occurred previously but shows an increase in incidence or expansion in geographical, host or vector range." (6) When the H5N1 virus jumped from chickens to humans in 1997 in Hong Kong, an emerging zoonosis was born. New zoonoses comprise 75% of emerging infectious diseases. Where did this 75% figure come from?

In a remarkable study published in 2001, a group of researchers at the University of Edinburgh identified risk factors for human disease emergence. (7) During their comprehensive literature review, they catalogued the existence of 1,415 organisms known to infect humans. The authors further classified these 1,415 infectious organisms as follows:

Of these 1,415 organisms known to infect humans, 868 (61%)infect animals, too, which qualifies them as zoonotic organisms. Moreover, of these 1,415 organisms known to infect humans, 175 are associated with the so-called “emerging diseases” such as West Nile and SARS. Of the 175 infectious organisms associated with the emerging diseases in humans, 132 (75%) also infect animals. This is the source of the 75% figure in the statement “New zoonoses comprise 75% of emerging infectious diseases” (see above).

This “75%” finding has practical importance in directing the search for the cause of new types of human illness when they appear suddenly and are associated with high mortality. This finding also has the effect of conflating the human and veterinary fields, and inflating the need for experts with simultaneous knowledge of the two disciplines.

Comments are welcomed. Please send to moleary@semp.us.

Sources:

1. World Health Organization: “Avian influenza frequently asked questions.” Available at: http://www.who.int/csr/disease/avian_influenza/avian_faqs/en/.

2. Hien TT, De Jong M, Farrar J: “Avian influenza—a challenge to global health care structures.” In New England Journal of Medicine. Vol. 351, No. 23, December 2, 2004, p 2364.

3. World Health Organization: “Cumulative Number of Confirmed Human Cases of Avian Influenza A(H5N1) since 28 January 2004.” Available at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2004_10_25/en/.

4. BioMed Central: Available at: http://www.biomedcentral.com/news/20040129/05.

5. World Health Organization: “Recommendations for influenza vaccines.” Available at: http://www.who.int/csr/disease/influenza/vaccinerecommendations/en/ .

6. Marano N, Pappiaoanou M: “Historical, New, and Reemerging Links between Human and Animal Health: in Emerging Infectious Diseases Vol. 10, No. 12, December 2004. Available at: http://www.cdc.gov/ncidod/EID/vol10no12/04-1037.htm.

7.Kruse H, Kirkemo A-M, Handeland K. “Wildlife as source of zoonotic infections.” In Emerging Infectious Disease [serial on the Internet], Dec 2004. Available at: http://www.cdc.gov/ncidod/EID/vol10no12/04-0707.htm.