The avian influenza (AI) virus—a type A influenza adapted to an avian host— is a pathogen most noted for its debilitating effect on the global poultry industry. The infection dates back to Europe in the 1870s, although the cause of the outbreaks of highly pathogenic strains of avian influenza (HPAI) was unknown then (1). Research in H5N1, having gained more attention in the modern age, has led to major advancements in the identification and control of flu outbreaks. Today, the threat of one specific strain of avian influenza—of mammoth virulence and mortality—threatens humanity: H5N1. H5N1 has wreaked havoc among poultry-dependent communities in southeastern Asia, but it presently infects only birds. However, the virus has the potential to mutate and initiate a deadly pandemic capable of devastating the human population with airborne human-to-human transmission. In response to this threat, as well as past and present outbreaks, we have witnessed a political, social and economic response, differing in gravity with location. A HPAI strain such as H5N1 could define the future of humanity, and recent research has proven through genetic modification that it very possible for H5N1 to mutate and facilitate transmission. The controversy is grounded in whether to publish the studies on the successful genetic modification of H5N1. We should pursue research on the virus in preparation for an “inevitable” outbreak or event of bioterrorism. This research would be invaluable in furthering our understanding of modern virology and genetics. Here, the benefits surely outweigh the risks. These risks, however, are large and should not be treated lightly. Most notably, there lies potential for bioterrorism should a virulent strain of the virus fall into the wrong hands, or be generated by a terrorist organization. Further understanding through research is imperative and would aid in preparation for a pandemic strain of highly pathogenic avian influenza through the mutation of the H5N1 virus; such a mutation could occur at any moment, due to a characteristic of the influenza virus known as host adaptation.
Why is the potential H5N1 influenza outbreak such a threat to the modern world? How could it be worse than the 1918 flu pandemic, which killed 3 to 5% of the world’s population? The world now is much more densely populated, and if an HPAI pandemic were to occur with the virulence it affects birds with, it would spread more easily, especially since AI has many respiratory symptoms conducive to contagion, such as coughing and sneezing (1). Today, the average lifespan is much longer, and there are more chronically ill and immunodeficient people than there were in 1918. The elderly have a higher chance of becoming infected with influenza. Also, the AIDS pandemic had no bearing in 1918, but in our present day, there are plenty of cases globally that would increase the virulence of H5N1 because immunodeficiency would allow for easier infection (1). In our modern age, there is extensive commercial plane travel, which influences the ability of the virus to get around the world quickly, as well as infect in close quarters. The virus would be able to get to places it previously could not. This would lead to the delocalization of the disease, and could, in theory, lead to many epicenters of pandemic influenza (1). Lastly, this virus is much more lethal than the 1918 strain, and with such a higher mortality rate (about 60%), it could wreak havoc upon the global population (1). Recently, scientists have also uncovered that HPAI H5N1 influenza can enter the central nervous system, causing significant and irreparable damage to cognitive functions. Neurodegeneration is also possible, as well as brain hemorrhages. These cerebral symptoms are much more severe than typical flu symptoms, and are potentially more fatal (2). The projections if an H5N1 pandemic took place are startling: around 360 million deaths (3).
With such a sobering future outlook, the various political, societal and economic factors are worthy of examination due to the potential global catastrophe inherent to the spread and propagation of the H5N1 virus. The past responses to outbreaks of AI are especially fascinating because these cases offer insights into greater dilemmas concerning animal health, production, public health and disease prevention. To address these issues, there has been an immense effort to utilize public funds in various nations, for the sake of preparedness (4).
In 2005, President George W. Bush spoke on behalf of the growing global insurgence of H5N1 to the United Nations. He remarked that the U.S. was taking this very seriously in a post-9/11 world; threats to U.S. homeland security could arise from bioterrorism with infectious disease (5). Consequently, the United Nations began thinking about possible predicaments that could arise with a deadly pandemic: how would the governments of the world respond and how would national and international organizations respond and collaborate (6)? At this time, H5N1 was just being noticed in Europe, and fear of the “imminent” catastrophe provoked governmental action. In the United States, President Bush called for a plan to prepare for a global outbreak of HPAI H5N1. His plan called for a total 7.1 billion dollar expenditure, of which, 2 billion would be allocated for the purpose of stockpiling antiviral medications and 20 million doses of an experimental vaccine against avian flu (7). 2.7 billion dollars would be dedicated to vaccine research and upgrading our methods of vaccine manufacture (7). Federal funding for state and federal public health agencies would also be increased (1,7). President Bush justified his plan through the lens of homeland security; we cannot be too careful after 9/11, and that U.S. security and preparedness should be our prerogative. It is more imperative to prepare the countries in which H5N1 is actually concentrated. Bush failed to recognize that the greatest threat of H5N1 creating a virulent pandemic lies in the control and handling of outbreaks in Asia today (8).
As John Barry argued in his book, The Great Influenza, hospital infrastructure and medical training is imperative in handling a pandemic. Barry argues that the medical training revolution prior to the 1918 influenza pandemic (i.e. increased medical requirement of World War 1) readied the world for such an outbreak, and without that revolution, the pandemic would have been much worse (9). We should apply Barry’s logic to Bush’s plan as well. Critics of the plan say that it “doesn’t provide for improving hospital infrastructure for disaster response” (1). This is where the money should be focused, not on the stockpiling of an experimental vaccine. Due to the fast mutation of Influenza A, it is likely that an effective vaccine against HPAI will no longer be effective in the long term, as the virus will have mutated to a new strain unaffected by the vaccine so it is important money be focused elsewhere, like on lasting improvements in hospital infrastructure and technology (10).
However, the public response will most likely call for essential government intervention. Besides the normal flu pandemic precautions—face masks, hand washing, isolation, healthy eating— the public will likely want the government to intervene and protect their citizens. Public health organizations will fill the void here and make a difference in the handling of an avian influenza pandemic. These organizations will hear the rallying cry of the people, and come to the rescue. (4). Already, the World Health Organization (WHO), has established the Global Influenza Programme (1952); a network of national influenza centers and laboratories vital in the ongoing monitoring of influenza, virus sampling, and the distribution of flu shots (6). This program is useful in the monitoring of avian flu, but now that we are faced with a greater threat on the horizon, people have looked to the WHO to prepare the world for potential disaster. This has been evident in the call to stockpile anti-virals. The United States is the only nation that is adequately prepared in terms of resources to combat a deadly flu pandemic (6). Elsewhere, no one seems to have given a single preventative thought. There are 16 experimental H5N1 vaccines in development, but it is projected that if a pandemic was to occur, 12 months after the initial outbreak there would only be 500 million vaccines developed in a world with over 6 billion people. Another public health movement calls for non-pharmaceutical ways to prepare for a pandemic of avian influenza, emphasizing public education and communication, in addition to the monitoring and reporting of flu cases (4).
In examining the economic factors of this disease, it is apparent that a very similar response is evoked from each affected nation at the time of an outbreak. For the purpose of exploring the economic response of an outbreak of HPAI, we will concentrate on the outbreak in Thailand in late 2003. Like most epidemics of AI in southeastern Asia, the Thailand outbreak began isolated in domestic poultry operations who had reported mass deaths (6). The outbreaks were met with disease eradication efforts like the mass culling of birds, but they were ultimately unsuccessful. This epidemic brought about the first human cases and deaths from avian influenza Thailand had ever seen (11). The outbreak was seen as a strong economic threat, and concerns stemmed from the containment policies that could be put in place to control the spread of disease (12,13). The containment policies were: to cull all susceptible poultry within a 5km radius of a confirmed outbreak, to burn all infected materials, to disallow movement of any infected matter within 50km of an infection site, and to ban the exportation of poultry products for 90 days (6). This last measure was the most significant. Although redundant—for most bordering countries had already banned trade with Thailand during the outbreak— this policy had the most crippling effect economically on Thailand (11). Some of these bans, in fact, remained in effect until 2008 (6). This effect is particularly severe, and similar constraints have been put in place on other nations with regard to HPAI outbreaks. The economic scar this outbreak has left on Thailand has been very difficult for the nation to return from, especially in the poultry industry.
At first, while researchers were still unraveling the cause of the H5N1 virus they speculated that the virus’ spread could reflect the migratory patterns of birds. Before mid-2005, migratory wild birds have been widely considered to be the primary source of the dispersal of H5N1 outside Asia. This claim was based on the discovery that hundreds of wild birds had died at Lake Quinghaihu, on a high plateau in China. It is now clear that the dispersal of the virus does not correspond with to the main migration routes of wild birds. The global network of migration routes conceals the cause of the virus’ globalization— of the commercial exchanges of poultry with the West, the more likely mechanism for disease spread (14).
So where do we stand now with the global pandemic situation of H5N1? The threat H5N1 is still very real; 2000 ducks were killed just this past week from the virus in northwest Cambodia. Since 2003, H5N1 has killed or forced the culling of more than 400 million domestic poultry and caused an estimated 20 billion dollars in economic damage across the globe before it was eliminated from most of the 63 countries infected at its peak in 2006. The HPAI H5N1 virus remains endemic in six nations (15). The number of outbreaks in domestic poultry and wild bird populations shrank steadily from 2003 to mid-2008. The number of outbreaks rose progressively from mid-2008 to mid-2011 but has decreased since then. Although HPAI H5N1 continues to be a global threat for poultry and humans, most countries rely on clinical surveillance based on the reporting of cases in poultry. As a result, outbreak information is underreported and inaccurate (3). Active surveillance in poultry and wild bird species therefore needs to be maintained by governments in endemic countries and countries at risk globally. A number of endemic countries are now implementing active surveillance measures for H5N1 with the help of the Food and Agriculture Organization (15).
The next logical step in preparing the world for a pandemic of HPAI H5N1 is the development of a vaccine capable of combating this virulent strain. Currently, there are three main U.S. manufacturers responsible for producing the 80 million doses of the seasonal flu vaccine, and resources for vaccine production are currently stretched thin (1). In 2005, public demand and paranoia fueled scientists to pursue their search for a vaccine for H5N1. Using a virus isolated from a Vietnamese patient in 2004, researchers successfully created a vaccine effective against the H5N1 virus (6). The National Institute of Allergy and Infectious Disease (NAID) has shown the vaccine “to be safe and to induce an immune response that is predictive of being protective” (1). If a human HPAI H5N1 pandemic were to occur, the goal would be to produce 300 million doses of the vaccine in six months (6). This target, however, is unrealistic, for the current industry in the United States lacks the resources and means to produce such a profound quantity of vaccines. To be able to reach this target number, it would take about three to five years (1). This is much too long, for in such dire circumstances as an influenza pandemic, the virus would have already done too much damage before vaccine distribution would take effect. The difficulty in creating a vaccine for H5N1 lies in the high virulence of the strain, for in the process of making the vaccine, the virus is actually lethal to the chicken embryos that compose a vital role in the vaccine development process (1). This poses a major question in how prepared we truly are for a pandemic of H5N1. Based on our current infrastructure and vaccine development capabilities, I would argue that a virulent human transmissible strain would have devastating consequences on modern mankind.
In our contemporary world, where terrorism remains a tangible threat globally, “weaponizing” this virus remains a top concern. When dealing with such a volatile genetic scenario as that associated with pandemic AI, there are bound to be experiments trying to genetically manipulate the virus into a human-transmissible variety. The University of Wisconsin-Madison and Erasmus University of the United States and the Netherlands both succeeded in similar genetic manipulation of the H5N1 virus. The studies describe a series of five mutations that are necessary to make the avian flu virus spread airborne among ferrets (16). Two of the five mutations necessary for human transmission occur commonly in the H5N1 virus in the wild, one has been shown to occur rarely in nature, and the other two have never been found in H5N1 but have in H2 and H3 strains (16). Their results did show one interesting revelation contrary to original thinking: the adapted virus showed less fatality as it became more contagious.
In January 2012, researchers trying to publish these papers were met with fierce opposition from the United States government who “frantically acted to block the full publication of research that successfully mutated the H5N1 virus to be highly contagious” (17). The National Science Advisory Board for Biosecurity asked that details be removed before the papers were published. Controversy ensued when just a few months later, a panel convened by the World Health Organization recommended that the papers be published, uncensored (16). This has led to a disagreement on how to proceed in the handling of the publishing issue. Proponents of publishing, like David R. Franz, a former commander in the U.S. Army Medical Research Institute of Infectious Diseases, believe “this H5N1 experience gives us an opportunity to reset the way we think about infectious disease, infectious disease research, the tools and the knowledge of biotechnology that have become so powerful, and responsibility in life sciences research” (18). Advocates simply believe that the benefits of studying the mutated strain outweigh the risks of keeping such a virulent strain around. Conversely, opponents of publishing the papers believe that bioterrorism is a very real threat in our modern age, and that the accidental release of the disease, or an event of biological warfare utilizing such a deadly virus is very realistic (18). The terrorist organization, Al Qaeda, is known to recruit experienced microbiologists and biochemists, and with the right conditions, could be able to reproduce the published experiments (17). However, for this to occur, the terrorist group would need the correct training, pristine conditions and an extremely well outfitted lab; an unlikely scenario. Both of the research groups ended up publishing their papers, with their data uncensored. By publishing their findings, future researchers can use their experiments in application to different viruses. There is much to still learn about virology, and in using what we have just recently uncovered, there is potential to find cures for deadly viral diseases that plague humanity to this day.
Our modern world has seen an increase in natural disasters over the past few decades. There is no ignoring that the Earth is changing, and that disasters such as a highly pathogenic pandemic is not out of the realm of possibility. It seems that mankind is truly the virus; problems such as overpopulation, global warming, and the prevalence of natural disasters are just symptoms of the human plague on Earth. Our battle isn’t exactly man versus nature, but rather man versus ourselves. In our dealings with H5N1 and other infectious diseases, we should be wary of the consequences our own actions may have, for in studying the possibility of that crucial mutation of H5N1, we may, in fact, lose control and begin the next era of superior infectious diseases. For now, there is no present danger of Highly Pathogenic Avian Influenza H5N1, but we must use our experience thus far to further our understanding of virology, for we will then be more prepared when the next plague hits; an inevitable event in our future.
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