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<H4>Major Topic about [Your Pathogen]</H4>
   
In 1995, work on reconstructing the 1918 H1N1 virus began. Researchers obtained RNA fragments from preserved tissue samples and the cadaver of a victim found buried in the Alaskan permafrost.  Using these RNA sequences, cloned segments of DNA were produced and introduced into cells.  The sequencing of the genome was completed in 2005.  <BR><BR>
 
The 1918 virus is believed to have originated entirely in birds (as opposed to co-infecting a host along with a human virus), although there are elements in the viral genome that do not appear in avian viruses.  The “rescued” 1918 virus was used to infect mice.  The mice lost thirteen percent of their body weight in two days, an indication of the virulence of the 1918 flu.<BR><BR>
 
Most of the victims of the 1918 pandemic died from pneumonia.  By inserting genes from the 1918 virus into a modern viral strain, three genes were implicated in this effect.  Normally, influenza infects only the upper respiratory tract of its host.  The PA, PB1 and PB2 as well as a nucleoprotein from the 1918 virus allowed common modern flu viruses to multiply deep in the lung tissue of lab ferrets, who died of pneumonia.
<H3>Responses to the Spanish Flu</H3>
The Spanish Flu affected many countries.  Across the entire globe, the number of deaths was estimated to be as high as 100 million. The flu hampered military operations during the last year of World War 1: Germany, Turkey, Austria-Hungary, and France all suffered major casualties among troops and the civilian population. Every country reacted differently to the disease and its effects on the population. <BR><BR>
 
Though the virus was confined to military camps for most of the summer of 1918, the flu reached Philadelphia by September. The government ordered mandatory vaccinations and all influenza cases were to be reported to the health department. The flu began to spread rapidly through the country, causing the police to close schools, churches, and other public places in order to quarantine the population. The quick spread of the epidemic gave little time for preventive measures to be taken. Scientific studies of prevention plans show that San Francisco, Milwaukee, Kansas City, and St. Louis had the most effective responses. St. Louis actually began its prevention plan two weeks before Philadelphia, the hardest hit city initially. <BR><BR>
 
In Canada, the influenza pandemic had a positive impact on Canada’s public health system. The Canadian Medical Association had been pushing for federal health regulations since 1900. In 1919, the Department of Health Act was passed, and funds were finally available to expand hospitals and health care.  The influenza epidemic also forced officials to cancel the Stanley Cup Playoffs.  With the series between the Montreal Canadiens and the Seattle Metropolitans tied, several players from Montreal became severely ill with the flu, and one later died.  The remainder of the series was cancelled.<BR><BR>
 
A worldwide trend of declining pregnancies and live births was generally seen in the amount of during the early 1920s that can largely be attributed to influenza deaths.  (This contrasts with the “baby boom” after World War II).  Pregnant women appeared more susceptible.  About 20-50% of pregnant women struck by the flu died during the epidemic.  In most European countries, the total fertility rate dropped 7%, with Norway being an exception showing an increase in birth rate.
<H3>Treatment of the Spanish Flu</H3>
The Spanish Flu was very virulent, and quick to kill. With so many people dying, treatments had to be found as quickly as possible.  Unfortunately, there were few effective means of combating the disease.  Out of desperation, doctors even tried bleeding patients, a long discredited and abandoned practice, but to no effect.  Oxygen was also given to those who were ill without success. Doctors and researchers tried to develop new vaccines as well.  With any strain of flu, it is difficult to make a vaccine and none of them appeared to have significant positive effect.  Despite their efforts, medical personnel found that the only thing that could be done was to allow the disease to run its course, giving plenty of fluids and allowing the patient to rest.  This is still the treatment for most cases of flu.<BR><BR>
 
Other than rest and fluids, blood transfusions seemed to be the only truly effective form of treatment. Transfusions of whole blood, plasma, or serum from survivors of the flu were given to people who were very ill.  The treatment was effective because the survivors had developed antibodies which were transferred with their blood.  Even this treatment was not completely effective, though it appeared to reduce mortality rates by up to 50%.  It is unclear how effective transfusion would be as a treatment for a modern flu epidemic.
<H3>Historical Remembrance and Contemporary Relevance</H3>
The 1918 influenza pandemic holds a unique place in the history of epidemics.  Compared to other influenza epidemics, it had death rates 5 – 20 times higher than expected.  Between 50 and 100 million people lost their lives, including a surprisingly high number of healthy individuals and an unexpected number of youths, neither of which were the traditional victim groups for influenza.<BR><BR>
 
In America, despite the unusual potency and unique victim groups of the Spanish Flu, it has become the “forgotten epidemic”.  Several theories attempt to explain this historical amnesia.  The most important explanations include the epidemic’s close proximity to World War I and the relative rapidity of the Spanish Flu, which would move in unexpectedly on communities, wreak havoc, and then disappear shortly afterwards.  <BR><BR>
 
Whether Americans remember the 1918 Pandemic or not, the causal H1N1 virus has continued to play a role in history.  Indeed, all “Influenza A pandemics since that time…have been caused by descendants of the 1918 virus, including ‘drifted’ H1N1 viruses and reassorted H2N2 and H3N2 viruses…making the 1918 virus indeed the "mother" of all pandemics”.<BR><BR>
 
The contemporary influenza threat, however, comes from the H5N1 avian flu strain (see below), which is only distantly related to H1N1.  Though both strands are avian in origin, they appear to have arisen through different evolutionary pathways.  Many scholars who believe the world is “overdue” for a cyclical influenza outbreak believe H5N1 is the leading contender.  The importance of remembering the Spanish Flu pandemic today may be its usefulness for comparisons to hypothetical modern outbreaks.<BR><BR>
 
Recent studies of the 1918 outbreak in America imply that some actions taken by city authorities, such as quarantines – which were previously thought rather unsuccessful on the whole – and the wearing of masks were effective in mitigating the damage of the epidemic.  Problems arose, however, when these sanctions were lifted too soon and the Spanish Flu returned in subsequent waves.  In the highly mobile modern world, state-imposed isolation appears a far-fetched and nearly unenforceable intervention.  Requiring face masks in public, though more plausible, could also prove difficult to implement in the current individual-based culture.  Plus, the original state-intervention measures required a consensus among authorities over the best course of action, quick decision making, and a large amount of public support.  In 1918, America was embroiled in the First World War and the citizenry was largely willing to allow extra governmental power in hopes of ending the epidemic.  In contrast, the citizenry today seems far less likely to grant additional authority to the state.  Regardless of these non-pharmaceutical interventions, doctors seem to be in agreement that a vaccine would still be the primary focus of health authorities if an avian flu epidemic were to strike.  


<H4>References</H4>
<H4>References</H4>

Revision as of 16:36, 9 February 2010

The Biology of [Your Pathogen]

Subtopic 1

Discuss the structure and function of your pathogen.

The History of [Your Pathogen]

Discuss onset of outbreaks. Is your disease episodic or chronic? Where, when, and how do cases occur and spread?
Sample image of your pathogen:

Flu-Picture1.png



References

“Avian Influenza or Bird Flu: Reference Summary.” (2008) “X-Plain Avian Influenza or Bird Flu,” http://www.nlm.nih.gov/medlineplus/tutorials/avianflu/id509103.pdf
Bakalar, N. (2007) “How (and How Not) to Battle Flu: A Tale of 23 Cities” New York Times http://www.nytimes.com/2007/04/17/health/17flu.html
Baum, L. (2006) “The Deadliest Fall,” http://ideaexplore.net/news/041116.html
Billings, M. (2005) “The Influenza Pandemic of 1918.” http://www.stanford.edu/group/virus/uda/
Borenstein, S. (2007) “Research on monkeys finds resurrected 1918 flu killed by turning the body against itself,” http://www.usatoday.com/tech/science/discoveries/flu-research.htm?POE=NEWISVA
Center for Infectious Disease Research and Policy, University of Minnesota, http://id_center.apic.org/cidrap/content/influenza/panflu/biofacts/panflu.html
Cummings, S. “Spanish Influenza Outbreak, 1918” http://history-world.org/spanish_influenza_of_1918.htm
Duffy, M. (2002) “The Influenza Pandemic” First World War: The War to End All Wars. http://www.firstworldwar.com/atoz/influenza.htm
"Influenza Epidemic of 1918–19" (2009) Encyclopædia Britannica Online http://www.britannica.com/EBchecked/topic/287805/influenza-epidemic-of-1918-19
Kindt, T.J., R.A. Goldsby and B.A. Osborne (2007) Kuby Immunology, 6th Revised Ed, WH Freeman and Co, NY; p 302
Lamb, R.A, and D. Jackson (2005) “Extinct 1918 virus comes alive,” Nature Med 111154 – 1156
Mamelund, S.-E. (2001) “Effects of the Spanish Influenza pandemic on fertility and nuptiality in Norway” http://www.iussp.org/Brazil2001/s30/S34_P01_Mamelund.pdf
Morens, D.M., and A.S. Fauci (2007) “The 1918 Influenza Pandemic: Insights for the 21st Century,” J Infect Dis 195:1018-1028
Parsons, D. (2006) “The Spanish Lady and the Newfoundland Regiment” WWI: The Medical Front. Dr. Geoffrey Miller” http://www.vlib.us/medical/parsons.htm
Osterholm, M.T. (2005) “Preparing for the Next Pandemic,” New Eng J Med 352:1839-1842
Osterholm; M.T., and A.L. Petrosino (2005) “Cytokine Storm and the Influenza Pandemic,” http://www.cytokinestorm.com/
Researchers unlock secrets of 1918 flu pandemic” (2008) http://www.reuters.com/article/newsOne/idUSTRE4BS56420081229?pageNumber=1&virtualBrandChannel=0
Schoenstadt, A. (2008) “Spanish Flu” http://flu.emedtv.com/spanish-flu/spanish-flu.html
Taubenberger, JK., and D.M. Morens “1918 Influenza: The Mother of All Pandemics.” The Center for Disease Control. 2005. Emerging Infectious Diseases. 8 April 2009. <http://www.cdc.gov/ncidod/eid/vol12no01/05-0979.htm#cit>.
“The Great Pandemic: The United States in 1918 – 1919.” http://1918.pandemicflu.gov/the_pandemic/04.htm
“The Threat of Pandemic Influenza: Are We Ready?” National Academies of Science Workshop Summary (2005) http://www.nap.edu/openbook.php?record_id=11150&page=1
“The Deadly Virus: The Influenza Epidemic of 1918” National Archives and Records Administration http://www.archives.gov/exhibits/influenza-epidemic/
“The 1918 Flu Virus is Resurrected” (2005) Nature 437:794-795.
“1918 Spanish flu treatment may also be effective for current avian influenza patients,” http://www.news-medical.net/?id=19832

Other Influenza Epidemics

The Asian Flu 1957-1958

The 1957-1958 Asian flu pandemic was not as virulent as the 1918 pandemic. There were far fewer deaths and cases of the flu, but it was important for two reasons. First, the incidence rate was highest for children; second, it was the first pandemic for which a vaccine was available. The pandemic was responsible for an estimated 2 million deaths worldwide. Those most affected by the pandemic were school children, young adults, pregnant women, and the elderly

The pandemic had two waves. It began in China in February 1957. By June it had spread to Asia, Europe, and America, affecting primarily school age children. A second wave occurred in January and February, 1958 and affected the elderly more than children. The first wave was attributed to children going back to school in the Fall of 1957. The close contact with other children helped spread the disease. The average age of those affected was 6-12. Schoolchildren then helped spread the flu by taking it home to their families. Many schools closed for a time to combat the spread of the pandemic, a measure that was somewhat effective. Although the infection rate in the first wave was highest for children and adolescents, the elderly had the highest death rate. The lower incidence in the elderly may have been due to partial immunity because most had been exposed to the Spanish flu of 1918. They had a higher death rate however because of their age.

Because of medical advances since the 1918 Spanish flu, the virus responsible for this new epidemic was quickly identified as a H2N2 type, and a vaccine was quickly made. This was the first vaccine available for a flu pandemic. It was available by May of 1957, it became generally accessible to the U.S. by August and by October in Britain. Despite availability, in the U.S., less than half of the 60 million doses were used.

References:

http://cns.miis.edu/flu_watch/history.htm
“Influenza: A Short History of the Disease,” http://lhncbc.nlm.nih.gov/apdb/phsHistory/health_news.html
“Pandemic Influenza,” http://www.globalsecurity.org/security/ops/hsc-scen-3_pandemic-influenza.htm
“1957: British public gets 'Asian Flu' vaccine,” http://news.bbc.co.uk/onthisday/hi/dates/stories/october/1/newsid_3086000/3086843.stm

The Hong Kong Flu 1968-1969

The Hong Kong virus, an H3N2 strain, evolved from the Asian Flu virus, which circulated from 1957 to 1968. (3, 7) The Hong Kong flu was probably a result of antigenic drift, meaning that the original virus was an Asian Flu virus with an advantageous mutation that kept the human immune system from recognizing it as a pathogen. Because Hong Kong Flu evolved from Asian Flu, many people who had Asian Flu were immune or partially immune, largely due to the overlapping N2 subtype. Mortality worldwide was 500,000 to 750,000 from 1968 to 1969. The United States recorded 34,000 deaths. The Hong Kong Flu reappeared in 1970 and in 1972 but has not been seen since.

Hong Kong Flu appeared in the United States in September of 1968, possibly brought by soldiers returning from Vietnam. The incidence escalated through December and into January, the month with the highest number of fatalities. This is a slightly atypical timeline. Flu season typically begins in early October and goes through March, with the highest number of cases in occurring in February. The Hong Kong Flu peaked several weeks earlier. The height of the infectious period coincided with schools’ winter breaks. Children, who suffered the highest incidence of infection, were at home where they were more isolated than if they had been at school. This may have lowered the number of people exposed to contagious patients and stunted the flu’s spread. Many schools closed which likely also helped keep the pandemic from worsening. The US Department of Health and Human Services called it “the mildest pandemic of the twentieth century.”

Hong Kong Flu was first recognized in July of 1968 and the World Health Organization (WHO) determined its H3N2 type on August 16th. The WHO provided antibiotics, though as is always the case with a viral infection, they were ineffective. Vaccines were manufactured in the United States, but they were not finished in time to prevent the disease from spreading.

References

http://medicine.science-tips.org/health/diseases-and-conditions/hong-kong-flu.html http://cns.miis.edu/flu_watch/history.htm
“Pandemics and Pandemic Scares in the Twentieth Century,” http://www.hhs.gov/nvpo/pandemics/flu3.htm
Earn, D.J.D., J. Dushoff and S.A. Levin (2002) “Ecology and evolution of the flu,” Trends Ecol Evol 17:334-340.
http://www.medterms.com/script/main/art.asp?articlekey=26429
Harder, T.C., and W. Ortrud (2006) “Avian Influenza,” in Influenza Report, ed. B.S. Kamps, C. Hoffmann and W.Preiser, Flying Publisher (www.flyingpublisher.com), Ch. 2
http://www.cdc.gov/flu/about/season/flu-season.htm
http://www.pandemicflu.gov/general/historicaloverview.html
http://www.publications.parliament.uk/pa/ld200506/ldselect/ldsctech/88/8805.htm

Avian Influenza A, H5N1

Introduction

Avian influenza A (H5N1) is an influenza virus subtype that occurs primarily in bird populations. The current form of virus does not typically infect humans unless there is direct, extensive contact with infected poultry or other contaminated surfaces (1). Fewer than 500 human cases of H5N1 influenza have been reported worldwide in the 5 years since the virus first crossed the species barrier from birds to humans. Nonetheless, there is cause for concern because the H5N1 virus has caused the largest number of cases of severe disease and death in humans of any avian flu virus. At present, human-to-human spread of the virus has been “limited, inefficient and unsustained” (2). Even without human-to-human transmission, fatality rates are over 50%, far higher than from any other flu epidemic in history (2,3). By comparison, the fatality rate for recent pandemics has been about 0.1% while the Spanish flu of 1918-1919 had a fatality rate of about 2.5%. This high rate for the H5N1 virus is presumably because there is little preexisting immunity to its (4). Should the virus develop an improved ability to spread from person-to-person, a devastating pandemic could occur. It should be noted that the fatality rate data collected by the WHO may be skewed because it is the most severe cases that are reported. Cases that are not as severe go unreported to the WHO, thus making it seem as if there are a disproportionate number of fatalities (5).

History

The highly pathogenic H5N1 virus was first isolated in 1996 from farmed geese in Guangdong Province, China near Hong Kong. T he following year, the first confirmed cases of human infection with H5N1 were reported in 18 patients in Hong Kong with 6 fatalities (6). By 2004, the virus had spread through the bird populations of East Asia, becoming endemic. Widespread human cases were reported for the first time.

The virus has predominantly affected humans in Vietnam and Indonesia and China with fewer cases in other Southeast Asian countries (see Table). Egypt has also shown a number of cases with a very high fatality rate. Over the last several years the H5N1 virus has become increasingly endemic in bird populations further and further from Hong Kong. Infections in birds have been confirmed throughout most of Asia and the Middle East, with human cases reported as well in countries as far from Hong Kong as Nigeria (2).

Human Incidence of H5N1 by Country (2)

Country Cases Deaths
Azerbaijan 8 5
Bangladesh 1 0
Cambodia 8 7
China 38 25
Djibouti 1 0
Egypt 63 23
Indonesia 141 115
Iraq 3 2
Laos PDR 2 2
Myanmar 1 0
Nigeria 1 1
Pakistan 3 1
Thailand 25 17
Turkey 12 4
Vietnam 110 55
Total 417 257

Treatment

As for all influenza strains, there are several antiviral drugs available to reduce the duration and severity of flu caused by the H5N1 virus. A popular drug for treating this strain of flu is the neuraminidase inhibitor Oseltamivir (marketed as Tamiflu). This drug is potentially efficacious because it not only targets proteins that are common to all influenza A strains but also targets proteins especially important in the H5N1 genetic structure (7).

However, due to rapid mutation of the H5N1virus (8) and poor agricultural practices, there already are viral strains that are immune to some drugs. Drugs targeting M2 viral coat protein (amantadine or rimantadine) are generally cheaper than neuraminidase inhibitors like Tamiflu, although less effective. They were therefore originally chosen by the World Health Organization (WHO) to combat H5N1. When the drugs were found to be ineffective, it was discovered that poultry farmers in South China commonly administered these drugs to poultry, thus allowing H5N1 to evolve to become immune to this particular class of drugs. As a result in 2005, pharmaceutical company Hoffman-La Roche donated 3 million doses of Tamiflu to the WHO to prevent a pandemic (7,8).

Pandemic Prevention

Currently, the WHO conducts extensive monitoring for the H5N1 virus. In 2005, the WHO released a document recommending a number of “strategic actions” to prevent a pandemic from H5N1, and should it occur, to contain it as best as possible (9). One of the pre-pandemic objectives is to “reduce the opportunities for human infection” (9) through vaccinating all at-risk workers (9). This would significantly reduce the most likely transmission route by which the H5N1 virus could become a virus capable of human to human transmission (8). Over time, as more people are infected, the chances of a genetic exchange between human flu virus and avian flu virus will increase, thus allowing the avian flu virus more opportunities to create a transmissible human flu virus. Should a pandemic virus emerge, the WHO has plans to take steps to “contain or delay spread at the source. As part of this goal of slowing evolution of the virus, approximately 150 million birds either infected or at extreme risk of infection have been “destroyed” since 2003 (8).

The most pressing concern is that the extremely virulent H5N1 avian virus could acquire one of the hemagglutinins reactive with human cells and thus be carried by humans. The most straightforward way for this to occur would be for a human flu virus and the H5N1 avian flu virus to exist at the same time in a pig. Pigs have sugar chains necessary for both the human virus and the avian virus to flourish and whenever both viruses inhabit a pig at the same time there is a chance that the viruses will trade genes resulting in a human form of the H5N1 avian flu (10).

Several countries are in the process of developing human vaccines against the H5N1 virus, which would significantly hinder disease progress. However, typical seasonal flu can change significantly from year to year rendering previous vaccines ineffective, and the H5N1 virus mutates at an even higher rate. Thus by the time a vaccine is implemented the virus may have changed sufficiently to render the vaccine less than fully effective (8). This makes H5N1 especially dangerous as there is currently no technology capable of keeping up with its natural evolution.

According to the WHO, the risk of pandemic H5N1 is serious (8). Two of the three criteria for a pandemic as described by the WHO have been met: H5N1 is a new virus subtype and it causes serious human illness. The last criterion, that it can spread easily and sustainably from person-to-person, has not yet occurred. If it does, another pandemic, even more deadly than the “Spanish flu” pandemic, could occur.

References

1. “Evolution of H5N1 Avian Influenza Viruses in Asia.” http://www.cdc.gov/ncidod/EID/vol11no10/05-0644.htm
2. “Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO,” http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_04_08/en/index.html
3. Taubenberger, JK., and D.M. Morens “1918 Influenza: The Mother of All Pandemics.” The Center for Disease Control. 2005. Emerging Infectious Diseases. 8 April 2009. <http://www.cdc.gov/ncidod/eid/vol12no01/05-0979.htm#cit>.

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