The Coming Influenza Pandemic Part V

In Parts I-IV I discussed the biology, morphology, etiology, genetics and ecology of influenza, the various influenza pandemics that have occurred over the past century and the current socioeconomic factors that increase the likelihood and potential severity of another deadly flu pandemic. In Part V, I further examine these socioeconomic factors and propose some solutions.

Over the past several decades there has been a dramatic decline in public health funding and infrastructure which could exacerbate any pandemic. Vaccine technology has changed little since the 1950s, and is still done in eggs, a slow process that is prone to contamination.³⁽¹³⁹⁾ Even with modern technology, however, we have lost much ground in the last 30 years. In 1976, there were thirty-seven flu vaccine manufacturers in the U.S. Today there are less than four.^3(p140)  Worldwide, there are only 12 flu vaccine manufacturers and 95% of the stock goes to the wealthiest countries, even though the majority of victims will likely be in the developing world.^3(p159)

The war on terror has taken funding that could be used for critical pandemic research and redirected it toward research on rare or non-existent diseases such as smallpox. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, said that a flu pandemic was greater threat than a bioterrorist attack.^3(p171) 758 researchers, including 2 Nobel laureates, signed a petition claiming that the war on terror, and it’s obsession with exotic pathogens had caused a 27% decline in federal grants for research on immediate threats such as tuberculosis, malaria and influenza, that kill millions of people each year.^3(p170)

As a result of HMO streamlining, many hospitals have been closing. Those remaining open have reduced the number of unused beds to as close to 0 as possible, thus leaving no space for new patients in a disaster, terrorist attack or pandemic (but maximizing profits). Between 1990 and 1997, for example, Los Angeles lost 17% of their available hospital beds due to streamlining, while a 2003 survey of hospitals found that 90% of U.S. emergency rooms were “seriously understaffed and overcrowded.”^3(p132) Additionally, millions of American remain uninsured or lack paid sick leave, which results in sick people continuing to work where they infect their coworkers.

Lastly, there is a growing anti-vaccination hysteria that threatens us all by discouraging people from getting vaccinated. Yet flu vaccines typically produce strong immune responses in 70-90% of those who have been vaccinated.¹¹ However, there are several caveats to this. Flu vaccines take up to two weeks to stimulate complete immunity.¹¹ For some patients, particularly young children, up to two doses may be required.¹¹ In the time it takes to develop immunity, a person can be infected and become sick. This might lead one to believe that the vaccine made them sick. In reality, influenza made them sick before the vaccine was able to protect them. Therefore, getting vaccinated early, before the height of flu season, is critical to self-protection. Also, if a high enough percentage of the population is vaccinated, there will be very little, if any, of the pathogen circulating in the population, thus further reducing the chances of infection. This is called herd immunity and occurs when 70% of population is immunized.^13(p792) 

One reason people fear vaccines is that there have been several notable correlations documented between vaccines and alarming side-effects. However, correlation does not equate to cause, and in virtually every case, the correlations were coincidental; not causative.

In 1976, several people developed Guillain-Barre syndrome (GBS) after getting vaccinated for swine flu. Many people assumed that the vaccine was responsible. Guillain-Barre is a neurological autoimmune disease that sometimes follows infection with Campylobacter jejuni and influenza.¹¹ It is also very rare, occurring in approximately 1 out of every 100,000 people. The number of people who contracted GBS during the 1970s swine flu vaccination program was not significantly higher than normal. The CDC believes that there may have been 1 additional GBS case per 100,000 during the 1976 vaccination program, yet no scientific evidence has confirmed this.¹¹ The most likely explanation is that the few cases of GBS that did occur, would have occurred anyway.

Even when vaccines are available and desired, poor Americans have less access. Only 39% of African American seniors get vaccinated annually, while 71% of white seniors get vaccinated. This is one reason why seasonal flu is still so deadly in the U.S.^3,(p35-6)

From Wikipedia

What Can Be Done?

While another deadly pandemic is likely, there is much we can do now that was not possible in 1918. Vaccine, antiviral and antibacterial technology is far more advanced than it was then. With sufficient funding, we should be able to develop vaccines against Highly Pathogenic Avian Influenza (HPAI) strains like H5N1 and make them available to people throughout the world. We also need to provide more funding for antibiotic development to fight the various bacteria that cause deadly secondary infections associated with influenza and governments should stockpile Tamiflu and provide it to people early, when it is effective at stopping influenza.

Governments also need to invest in the rebuilding of public health infrastructures, including an increase in available beds and emergency room capacity. However, they also need to do a better job of educating the public on the benefits and safety of vaccines. Lastly, the rich countries need to provide support for better veterinary surveillance in the developing world and all governments need to be completely open and honest about HPAI outbreaks in their backyards.

Image from Wikipedia

 Tamiflu is only known drug that can fight H5N1 influenza. Rapid stockpiling of Tamiflu (enough for 25% of the population of each country) is essential for averting catastrophic losses of human life. ^3(p145) Japan has purchased enough Tamiflu for 20% of their population, while Australia only has enough for 5% of their population, and the U.S. only has enough for only 1% of their population.^3(p144) Poor countries have asked permission to produce their own generic versions of Tamiflu, but the U.S. and France vetoed the proposal because it would eat into Roche’s profits.³ 

Rebuilding public health infrastructures necessarily involves providing affordable and accessible health care to all and the ability to stay home when ill. Short of this lofty goal, hospitals could be required to maintain sufficient unused beds for disasters or pandemics. Effective public health media campaigns, along the lines of anti-smoking advertisements, could be used to educate the public specifically about the safety and benefits of vaccinations  and how to protect oneself against influenza (e.g., frequent hand washing, staying home when sick, coughing into elbow). Much more funding needs to go into influenza research, as well as the development of new antibacterial drugs.

Asian Bird Cull (from Wikipedia)

 While the U.S. monitors its own flocks for HPAI, many developing countries do not.  Most sub-Saharan countries have closed their flu monitoring systems due to lack of financial resources (only South Africa and Senegal still monitor).^3(p24)  Monitoring must be dramatically improved in areas with histories of HPAI outbreaks, such as Vietnam, Thailand and China. When there is any indication of an HPAI outbreak, the WHO must be notified immediately. Samples must be provided to experts for identification and, if it is a HPAI strain, the birds should be culled immediately to prevent the spread.

In the developing world, poverty, corruption and poor infrastructure all hamper such efforts. Developing countries also have valid reasons for not cooperating with the international community, even when they have detected an outbreak. For example, they are less able to deal with the financial and nutritional losses caused by a large chicken cull than developing countries. There are also cultural challenges, such as the value of chickens as pets, future dowries, hedges against famine, or, in the case of prize fighting cocks, as ongoing sources of income.

Lastly, the wealthy nations need to move away from the lifeboat ethic that currently dominates their public health planning and recognize that the front line of any deadly influenza pandemic will be the poorest and most socially isolated communities in the world. It will be impossible to contain influenza in these communities and it will spread throughout the world. Providing free or low-cost vaccines and Tamiflu to developing countries will help protect us all.

References

1. AVERT, 2009, AVERTing AIDS website, October 28, 2009: http://www.avert.org/worldstats.htm
2. Bartlett, Donald L.,  and James B. Steele, 2004, “The Health of Nations,” New York Times, Oct 24,
3. Davis, Mike, 2005, The Monster at Our Door, The New Press, New York
4. Enserink, Martin, 2004, Science, 306, Dec ember 17, 2004
5. Kash, John C., Tumpey, Terrence M., Proll, Sean C., Carter, Victoria, Perwitasari, Olivia, Thomas, Matthew J., Basler, Christopher F., Palese, Peter, Taubenberger, Jeffery K., García-Sastre, Adolfo, Swayne, David E., and Katze, Michael G., 2006, “Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus,” Nature. October 5; 2006, 443(7111): 578–581.
6. Soares, Christine, 2009, “Pandemic Payoff,” Scientific American, November, 2009, p19-20
7. Various Authors, 2009, “Influenza:,” from Wikipedia, accessed November 7, 2009, http://en.wikipedia.org/wiki/Influenza
8. Various Authors, 2009, “Cytokine Storm,” from Wikipedia, accessed November 7, 2009: http://en.wikipedia.org/wiki/Cytokine_storm
9. Various Authors, 2009, “Black Death,” from Wikipedia, accessed November 8, 2009: http://en.wikipedia.org/wiki/Black_Death
10. Various Authors, 2009, “1918 flu pandemic,” from Wikipedia, accessed November 8, 2009: http://en.wikipedia.org/wiki/1918_flu_pandemic
11. Various Authors, 2009, “Seasonal Influenza: the Disease,” Centers For Disease Control and Prevention website, accessed November 14, 2009: http://www.cdc.gov/flu/about/disease/
12. Wallace, Amy, 2009, “An Epidemic of Fear: How Panicked Parents Skipping Shots Endangers Us All,” Wired, October 19, 2009: http://www.wired.com/magazine/2009/10/ff_waronscience/
13. Willey, Joanne M., Sherwood, Linda M., and Woolverton, Christopher J.,  2009, Prescott’s Principles of Microbiology, New York, NY, McGraw Hill
14. Various Authors, 2009, “Pearl River Delta” from Wikipedia, accessed November 14, 2009: http://en.wikipedia.org/wiki/Pearl_River_Delta
15. Various Authors, 2009, “Cortisol,” from Wikipedia,  accessed November 16, 2009: http://en.wikipedia.org/wiki/Cortisol
16. California Newsreel, 2008, “Unnatural Causes,”  video.  Transcript accessed November 16, 2009: http://www.unnaturalcauses.org/assets/uploads/file/UC_Transcript_1.pdf
17. President’s Council of Advisors on Science and Technology, 2009, “Report to the President on U.S. Preparations for 2009-H1N1 Influenza,” August 7, 2009: http://www.whitehouse.gov/assets/documents/PCAST_H1N1_Report.pdf

The Coming Influenza Pandemic Part IV

In Parts I, II and III I discussed the biology, morphology, etiology and genetics of influenza and the various influenza pandemics that have occurred over the past century. In Part IV I will discuss the social, political and economic factors that influence influenza ecology and increase the likelihood and potential severity of another deadly flu pandemic.

So far we have dodged many bullets. There are several highly pathogenic avian strains circulating among poultry and other fowl that cannot yet easily infect humans. The number of these HPAI strains appears to be growing. There are several socioeconomic factors that contribute not only to the proliferation of HPAI strains, but also create opportunities for them to mix and reassort with human and porcine strains. Further, some of these socioeconomic factors could make a modern pandemic just as devastating, or worse, than 1918. These factors include the growth of mega farms, in which tens of thousands of animals are crammed into relatively small areas; the growth of mega slums, such as those found in Mumbai and Nairobi, where hundreds of thousands of people live closely together in squalor; the industrialization of Southern China, where mega farms and mega slums collide with migrating water fowl that harbor novel influenza strains; and the decline in public health and veterinary surveillance systems which can monitor and quash outbreaks before they turn into pandemics.

Mega farms are an enormous threat to public safety. They pollute the air, land and water with animal wastes and they use up an inordinate amount of water. However, the most dangerous aspect of mega farms may be the fact that so many animals are cramped together that they easily spread diseases to each other, forcing farmers to overuse antibiotics and other drugs to avert infections and massive die-offs. This creates an ideal environment for genetic reassortment and antigenic shift of influenza viruses.

20-30 years ago, mega farms were relatively rare in the U.S. and virtually nonexistent in the third world. Ranches typically had a few hundred or, if really large, a few thousand head of cow or swine. The percentage of U.S. hogs raised on factory farms with more than 5000 pigs has increased from 18% of all U.S. swine farms in 1993 to 53% in 2003.^3(p90) Western Arkansas and Northern Georgia, alone, slaughter over one billion chickens per year.^3(p83) One swine farm in Utah produces more raw sewage than the entire city of Los Angeles.^3(p84) The U.S. giant of poultry farming, Tyson, slaughters more than two billion chickens per year in the U.S.^3(p83) Mega farms are also starting to grow throughout the world. Charoen Pokphond (CP), the Asian analog of Tyson, has factory farms all over Thailand & China. CP won the very first permit to operate a private enterprise in China, during the economic reorganization initiated by Deng Xiaoping.^3(p103-105) In 2003, during the height of a Thai H5N1 outbreak, rather than cull their flocks, CP increased their rate of slaughter and sent diseased chicken meat abroad^3(p103-105) 

Wadala Slum, Mumbay (from Wikipedia)

 During the 1918 Spanish Flu pandemic, the poor and hungry were the hardest hit, both in morbidity and mortality.^3(p28) Germany had a high mortality due to war famine.^3(p28) Iran was recovering from several years of cholera, typhus, drought and famine, which contributed to the highest relative influenza mortality (up to 22%) in the world.^3(p29) India had a high mortality rate due to famine and concurrent infection with malaria.^3(p28) The pandemic hit India during harvest season, exacerbating the famine. Today, the problem of poverty and famine may be worse. In 1918, there were only 25 million slum dwellers worldwide. In 2005, there were over 1 billion, and this is expected to double by 2020.^3(p152) As you can see from the table below, some of the world’s densest slums surpass the international average by almost two orders of magnitude.

Poverty affects health and immunity in several ways. Malnutrition deprives the body of nutrients and calories necessary for homeostasis. Poverty creates uncertainty about survival, which leads to stress and the overproduction of cortisol, which can lead to diabetes, heart disease, hypertension, and impaired immune response.¹⁶ Poverty also forces people to live in overcrowded conditions that facilitate the spread of germs. In many slums, there may be as many as 1000 people sharing a single latrine.³ Slum dwellers are less likely to have adequate (if any) clean drinking water. They have less access to doctors and may be less inclined to take stay home to recuperate from influenza for fear of losing income or their jobs. People who are already ill are much more likely to contract and die from influenza. This is even more true for those with compromised immune systems. In Africa, 27 million people are infected with HIV. Combined with poverty, malnutrition, and poor influenza surveillance and vaccination, Africa will likely be hit hard by an influenza pandemic.^3(p160)

Deforestation, over-farming and overfishing have forced many subsistence workers to flee the countryside for the cities throughout the developing world. These practices also deprive people of protein in their diets and encourage the consumption of exotic meats such as civets, in China, the hypothesized source of the SARS virus, or monkeys, in Africa, the likely origin of HIV.^3(p58) Deforestation, in particular, brings people in closer contact with wild animals that may harbor novel diseases, such as Ebola. In China, deforestation, over-farming, massive urbanization have led to increased contact with flu carriers, such as wild water fowl in the Pearl River Delta and increased genetic mixing between these vectors of influenza and domesticated pigs, chickens and ducks.³

Image from Wikipedia

Influenza A is endemic in ducks and geese from Siberia and Canada. As many as one-third of young ducks and geese harbor the virus.^3(p9) It infects their gut and is shed in their feces into the same water they drink and from which they feed. It is usually harmless to them, but it is spread rapidly, permitting considerable exchange of genetic material.^3(p9) One study in Alberta found 27 different subtypes in one community of ducks.^3(p9) During their migrations to the Gulf Coast and southern China, they may continue to shed influenza for as long as one month.^3(p9)

Downtown Guangzhou with Slum in Foreground (Image from Wikipedia)

Siberian and Canadian ducks and geese, which form the natural reservoir for influenza and serve as vectors that transmit the disease to swine and people, fly south for the winter, primarily to the Pearl River Delta, in Southern China. The Pearl River Delta is one of the largest conglomerations of humans on Earth. It is home to several large cities including Guangzhou (10 million), Shenzhen (8.4 million), Hong Kong (7 million), Dongguan (6.9 million), Foshan (6.7 million), and three other cities of over 1 million people.¹⁴ Macau is also located in the delta and has a population density of more than 18,000 people per square kilometer.¹⁴ Much of the region resembles Europe during industrial revolution due to rapid industrialization. There are huge, overcrowded slums, rampant pollution, poverty, all in close proximity to dense poultry and swine farms. The percentage delta residents living in urban settings grew from 32% in 1978 to 70% by 2002.^3(p58-9) Air pollution in the delta is 24 times higher than rest of China and 50% of the residents cannot afford medical attention when ill.^3(p58-9) 

Wet Market (image from Wikipedia)

While poverty is high, those who can afford meat are buying it more than ever before.. This has led to the proliferation of wet markets (where live animals are sold from cages), that serve as swap meets for influenza genes. Poultry consumption in China more than doubled since 1980. There are 700 million chickens in Guangdong province and many of the chicken cages sit atop pig pens, allowing the pigs to eat infected chicken feces. 2003 study of the Guangdong area found 500 different flu strains in wild & domestic birds (53 subtypes of H9, alone).^3(p62-63) 

Stay tuned for Part V, tomorrow, when I will discuss how crumbling public health infrastructures also increase the chances of another deadly pandemic and the consequences. 

References

1. AVERT, 2009, AVERTing AIDS website, October 28, 2009: http://www.avert.org/worldstats.htm
2. Bartlett, Donald L.,  and James B. Steele, 2004, “The Health of Nations,” New York Times, Oct 24,
3. Davis, Mike, 2005, The Monster at Our Door, The New Press, New York
4. Enserink, Martin, 2004, Science, 306, Dec ember 17, 2004
5. Kash, John C., Tumpey, Terrence M., Proll, Sean C., Carter, Victoria, Perwitasari, Olivia, Thomas, Matthew J., Basler, Christopher F., Palese, Peter, Taubenberger, Jeffery K., García-Sastre, Adolfo, Swayne, David E., and Katze, Michael G., 2006, “Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus,” Nature. October 5; 2006, 443(7111): 578–581.
6. Soares, Christine, 2009, “Pandemic Payoff,” Scientific American, November, 2009, p19-20
7. Various Authors, 2009, “Influenza:,” from Wikipedia, accessed November 7, 2009, http://en.wikipedia.org/wiki/Influenza
8. Various Authors, 2009, “Cytokine Storm,” from Wikipedia, accessed November 7, 2009: http://en.wikipedia.org/wiki/Cytokine_storm
9. Various Authors, 2009, “Black Death,” from Wikipedia, accessed November 8, 2009: http://en.wikipedia.org/wiki/Black_Death
10. Various Authors, 2009, “1918 flu pandemic,” from Wikipedia, accessed November 8, 2009: http://en.wikipedia.org/wiki/1918_flu_pandemic
11. Various Authors, 2009, “Seasonal Influenza: the Disease,” Centers For Disease Control and Prevention website, accessed November 14, 2009: http://www.cdc.gov/flu/about/disease/
12. Wallace, Amy, 2009, “An Epidemic of Fear: How Panicked Parents Skipping Shots Endangers Us All,” Wired, October 19, 2009: http://www.wired.com/magazine/2009/10/ff_waronscience/
13. Willey, Joanne M., Sherwood, Linda M., and Woolverton, Christopher J.,  2009, Prescott’s Principles of Microbiology, New York, NY, McGraw Hill
14. Various Authors, 2009, “Pearl River Delta” from Wikipedia, accessed November 14, 2009: http://en.wikipedia.org/wiki/Pearl_River_Delta
15. Various Authors, 2009, “Cortisol,” from Wikipedia,  accessed November 16, 2009: http://en.wikipedia.org/wiki/Cortisol
16. California Newsreel, 2008, “Unnatural Causes,”  video.  Transcript accessed November 16, 2009: http://www.unnaturalcauses.org/assets/uploads/file/UC_Transcript_1.pdf
17. President’s Council of Advisors on Science and Technology, 2009, “Report to the President on U.S. Preparations for 2009-H1N1 Influenza,” August 7, 2009: http://www.whitehouse.gov/assets/documents/PCAST_H1N1_Report.pdf