Avian Influenza 1
Running head: AVIAN INFLUENZA
Review of Recent Literature Concerning Avian Influenza
and Associated Risks to Human Populations
Chris Stotelmyer
Professor Lynée Lewis Gaillet
English 3090
March 3, 2005
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Abstract
The total mortality of the 1918 influenza pandemic was roughly 30 million people
worldwide. Although subsequent pandemics occurred in Asia in 1957 and 1968, their
mortality rates were far less than the 1918 outbreak. The recent emergence of highly
virulent strains of avian influenza in Asia has been of increasing concern to public health
officials. Scientists believe that another pandemic is inevitable, and that these avian
strains may pose the greatest threat of a new, worldwide outbreak of influenza. The
shortage of flu vaccine in 2004 has heightened public awareness of a possible pandemic
and, as a result, several articles were published in the past year concerning the emerging
threat of avian influenza. This review examines those articles to collect and summarize
the latest research on the avian influenza threat.
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Review of Recent Literature Concerning Avian Influenza
And Associated Risks to Human Populations
Introduction
Influenza has long been present in human populations. The name “influenza,” in fact,
is the result of early Renaissance superstition. Astrologers in Renaissance Florence
attributed an outbreak of the virus to the malignant “influences” of certain configurations
of stars and planets (Collier & Oxford 2000). Science has obviously improved since the
Renaissance and our current knowledge of the influenza virus is growing rapidly. The
purpose of this paper is to review the most recent (2004-05) literature concerning the
possibility of a large-scale outbreak. Scientists have been particularly concerned with the
increasing threat of Asian strains of avian influenza or “bird flu.” This paper will focus
on those concerns.
The Influenza Viruses
Influenza viruses are grouped into three major types: influenza A, B, and C. Only
influenza A and B regularly infect humans and, between those two, type A is the more
significant pathogen (Collier et al. 2000). Influenza A is further categorized by subtype.
Two proteins, hemagglutin (H) and neuramidase (N), on the surface of the virus provide
scientists with a useful means of identification. Researchers have elucidated fifteen
different varieties of the H protein and nine varieties of the N protein. Therefore, a
subtype of influenza A is given a specific designation based on these proteins: H1-H15
and N1-N9 (Trampuz, Prabhu, Smith, & Baddour 2004). Furthermore, influenza A is a
common pathogen to many mammals including birds, swine, and horses; however, only
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subtypes with H1 or H3 proteins are currently active in human populations (Stöhr &
Esvald 2004).
Pathogenicity of Influenza A
A number of influenza A subtypes constantly circulate in human populations without
incident because immunity has been established by repeated exposure to the viruses.
However, influenza A has demonstrated a remarkable ability to undergo subtle, and
sometimes significant, genetic mutations. In fact, annual epidemics arise when these
common subtypes undergo enough genetic mutation to produce new strains (Collier et al.
2000). Influenza pandemics, on the other hand, are caused by the rare emergence of a
completely new subtype for which the population has no immunity. Klaus Stöhr and
Marja Esveld of the World Health Organization (WHO) believe these new viruses are
probably derived from the many influenza A subtypes which are known to circulate
widely in animals but do not infect humans (2004). If an animal influenza virus manages
to cross the species barrier and infect humans, a pandemic may result.
Scientists believe that the devastating influenza pandemic of 1918 was probably
caused by an animal influenza subtype that had crossed the species barrier. Human
populations, therefore, lacked any immunity to this new virus. The new virus’ ability to
produce serious illness – its virulence – combined with the fact that the population was
immunologically defenseless allowed it to spread rapidly worldwide in only four to six
months (World Health Organization 2004, p.79). Interspecies transmission of influenza
is also thought to be the cause of the “Asian flu” pandemic of 1957 and the “Hong Kong
flu” pandemic of 1968 (Kaye & Pringle 2005).
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Avian Influenza A
Avian influenza has become a significant concern among scientists. In 1997, 18
people in Hong Kong were hospitalized due to a particularly virulent form of influenza.
Six of those individuals died as a result of their illness (Weir et al 2004). Scientists
determined that these individuals had been infected with the avian influenza subtype
H5N1 and that direct bird to human transmission occurred (Peiris et al. 2004). The
significance of the outbreak in Hong Kong is that it was the first documented case of such
a transmission.
The WHO has been monitoring a highly pathogenic avian influenza (HPAI) H5N1
subtype that has been responsible for an increased number of outbreaks on Asian poultry
farms since late 2003 (2004, p.79). H5N1 spreads rapidly in birds and mortality rates can
approach 100% (Capua & Alexander 2004). What concerns scientists most is the fact
that influenza A subtypes have demonstrated the ability to exchange genetic information
when two different viruses have infected the same host. If a human subtype of influenza
and an avian strain such as H5N1 were to be present in the same host, genetic interaction
can occur. Kaye & Pringle have hypothesized that an intermediate host animal such as
swine could provide the means for this kind of genetic exchange (2005).
Human Infections with Avian Influenza A Subtypes in 2004
The following is a summary of documented human infections with avian influenza
subtypes reported in the literature in 2004:
British Columbia
Tweed et al. describe two cases of human illness caused by the H7N3 subtype of
influenza. A low-mortality outbreak of subtype H7N3 occurred on a poultry farm in
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British Columbia on February 6, 2004. The virus was transmitted to an adjacent farm
with a dramatic increase in mortality. 2,000 chickens died on this farm in two days.
Farm workers were provided with personal protective equipment and were monitored for
flu-like symptoms. During the monitoring period 57 workers demonstrated a flu-like
illness, and two of those workers tested positive for the H7N3 virus (2004).
Thailand
In October of 2004 the Ministry of Public Health in Thailand reported that a 9-yearold girl in northern Thailand died of respiratory failure after having been hospitalized
with a flu-like illness. The Ministry tested the girl for influenza and found that she had
been infected with H5N1. The Thai authorities determined that the girl had been exposed
to infected chickens at her home while preparing recently killed birds for cooking. In
addition, Thailand had already confirmed 16 cases of human infection with H5N1
between January and October 2004. Eleven of those cases were fatal (World Health
Organization 2004, p.377).
Viet Nam
In January of 2004 the WHO received reports from Hanoi concerning three cases of
H5N1 infection in humans. Two children and one adult suffering from a severe
respiratory illness were admitted to a hospital in Hanoi. All three patients died of
respiratory failure. The Influenza Center of Hong Kong tested samples from the three
patients and confirmed that their illness was caused by H5N1 (World Health
Organization 2004, p.13).
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Discussion
Reports of human infection with highly pathogenic H5N1 have slowly increased since
the first documented case in 1997. However, two things should be kept in mind when
considering these reports. First, advances in technology over the past decade have
improved our ability to rapidly and accurately identify this new virus. Second, the WHO
has become increasingly vigilant since 1997 and has encouraged Asian countries to
carefully document influenza outbreaks. These two factors might explain the increase in
the number of cases that have been reported in the literature. In other words, H5N1 may
have been present in these countries long before 1997, but cases of human infection went
unrecognized.
Regardless of how long H5N1 has been present in Asia, the WHO has become
increasingly concerned. Outbreaks of H5N1 on poultry farms have been increasing, often
with devastating economic repercussions to developing countries – countries whose
economies rely heavily on agriculture (WHO 2004, p.78). Developing countries also
have fewer resources to deal with outbreaks and to protect agricultural workers from
possible infection. Add to this the fact that Asian countries have very high population
densities, and it is understandable that the WHO considers H5N1 a significant health
concern.
Concerns about H5N1 have made the production of a vaccine a priority to the WHO.
Vaccines have traditionally been the best defense against influenza; however, no vaccine
for H5N1 exists. Attempting to produce a vaccine after a pandemic has erupted would
likely be of limited use. Stöhr and Esvald assert that it is political and economic
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obstacles, not technological ones, that are responsible for the absence of an H5N1
vaccine:
Uncertainty over a viable market prevents companies from investing in pandemic
vaccine development, and many governments see no reason to step in, as
availability of pandemic vaccines is not considered a public health good (2004,
p.2196).
In other words, governments and pharmaceutical companies are unwilling to invest in
“hypothetical” threats.
Fortunately, science has progressed to the point that rapid development of a reference
vaccine virus has become a reality. Webby et al. were able to produce such a virus in less
than four weeks (2004). Although their research is ongoing and still in its initial stages,
the results are encouraging. Research similar to Webby et al. is, at present, the most
promising avenue for a rapid response to the avian influenza problem, and further
research needs to be encouraged. This technology could also lead to advances in vaccine
development for other viruses. All that remains is to convince governments and
pharmaceutical companies that a short-term expenditure could avert a significantly
greater one in the future.
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References
Capua, I., & Alexander, D. J. (2004). “Avian influenza: recent developments.” Avian
Pathology. 33, 393-404.
Collier, L., & Oxford, J. (2000). Human Virology. New York: Oxford.
Hirst, M., et. al. (2004). “Novel avian influenza H7N3 strain outbreak, British
Columbia.” Emerging Infectious Diseases. 10, 2192-95.
Kaye, D., & Pringle, C. R. (2005). “Avian influenza viruses and their implication for
human health.” Clinical Infectious Diseases. 40, 108-12.
Peiris J. S. M., et. al. (2004). “Re-emergence of fatal human influenza A subtype H5N1
disease.” The Lancet. 363, 617-19.
Stöhr, K., & Esveld, M. (2004). “Will vaccines be available for the next influenza
pandemic?” Science. 306, 2195-96.
Trampuz, A., Prabhu, R. M., Smith, T. F., Baddour, L. M. (2004). “Avian influenza: A
new pandemic threat?” Mayo Clinic Proceedings. 79, 523-30.
Tweed, S. A., et. al. (2004). “Human illness from avian influenza H7N3, British
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