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Viral Infections
Medical Options in the Event of an Influenza Pandemic
a report by
John H Beigel, MD
Staff Clinician, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH)
‘Avian armageddon’; ‘crisis’; ‘nightmare.’ A variety of phrases have been 2–3-linked sialic acids.
2
This difference in influenza binding domains may
used to describe the threat of avian influenza and an influenza pandemic. serve as a barrier to the efficient transfer of viruses across species.
3
These phrases suggest a helplessness, an inevitability of doom. Are there
really no ways to mitigate this disease? Currently, there are four licensed Avian influenza viruses currently cause sporadic zoonotic infections. The
antiviral medications: amantadine and rimantadine (both available as majority of recognized cases have been H5N1, though human infections
generic drugs), zanamivir (Relenza), and oseltamivir (Tamiflu). Additionally, with H7N3, H7N7, H9N2, and H10N7 have also occurred in relatively fewer
there are several novel antiviral compounds in development. While the cases. It is not known what barriers exist to the transfer of viruses across
optimal antiviral strategy is not clear, several medical options currently exist species and the efficient replication needed for a pandemic virus.
for treatment during an influenza pandemic. Discussions of potential influenza pandemic viruses should consider that any
of these viruses or other influenza viruses may have the potential to acquire
the ability for sustained human-to-human transmission, and thus any of
these viruses could be a pandemic virus.
While the optimal antiviral strategy
Pathophysiology
is not clear, several medical options The pathophysiology of avian influenza is not fully elucidated. Proposed
currently exist for treatment during
mechanisms of the high fatality rate seen in humans infected with
avian influenza include severe pathophysiology due to viral tropism,
an influenza pandemic. hypercytokinemia/dysregulation, and high levels of replication of the avian
influenza virus with associated tissue damage.
It has been widely thought that the largest hurdle to a pandemic of H5N1
The Spectrum of Influenza virus is its limited ability to attach to the α-2,6 sialic acid on human
Avian influenza currently represents an episodic zoonotic disease. If this epithelial cells. However, in evaluations of host cell binding sites, the
virus acquires the ability for sustained human-to-human transmission, it α-2,3 sialic acid configuration could be detected on type II pneumocytes
could become a pandemic virus. Previous outbreaks would suggest that in the alveoli.
4
Furthermore, H5N1 viruses have been shown to bind
pandemic influenza viruses displace the circulating seasonal influenza A directly to type II pneumocytes.
5
Type II pneumocytes are progenitor cells
strain(s) and, thereafter, are present as seasonal influenza viruses. Thus, that can differentiate into new squamous type I pneumocytes following
discussions of therapeutics should consider avian influenza, pandemic most types of lung injury.
6–8
Thus, avian influenza, specifically
influenza, and seasonal influenza as points on a spectrum, rather than as demonstrated for H5N1, may bind to the very cells of the lung
unique disease entities. responsible for repair after severe infections. This may be responsible for
the described incidence of acute respiratory distress syndrome (ARDS) in
This is not to imply that these are similar diseases with similar
pathophysiological features. While the pathophysiology of mild seasonal
John H Beigel, MD, is a Staff Clinician at the National Institute
influenza is well described, and some insight into the pathophysiology of
of Allergy and Infectious Diseases at the National Institutes of
avian influenza from animal and limited human experience exists, the Health (NIH) in Bethdesa. His research interests are primarily
pathogenesis of pandemic influenza is not known.
focused around clinical research and therapeutics in emerging
infectious diseases, including influenza. After a several-month
secondment to the Global Influenza Program at the World
Avian Influenza Heath Organization (WHO) in Geneva, his recent research
Influenza A viruses can be classified based on surface glycoproteins:
activities have included clinical protocols for early phase I/II
work on novel influenza therapeutics, as well as the
hemagglutinin (HA) or neuraminidase. Viral HA binds to sialic acid
development of international clinical protocols for the study of severe influenza, including avian
conjugated glycoproteins on host cells.
1
This binding is necessary for viral influenza. Dr Beigel received his medical training at the Medical College of Ohio. After completing
replication. The sialic acid configuration varies from species to species.
his residency at the University of Cincinnati, he completed a fellowship in critical care medicine at
the NIH and a fellowship in infectious disease at the Massachusetts General Hospital, Boston.
Human influenza viruses have been thought preferentially to bind to 2–6-
linked sialic acids on airway epithelium, and avian influenza viruses bind to
© T OUCH BRIEFINGS 2007
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