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Writing Committee of the Second World Health Organization Consultation on Clinical Aspects
of Human Infection with Avian Influenza A (H5N1) Virus. N Engl J Med 2008;358:261-273
Pandemic
According to the
World Health Organization (WHO), a
pandemic can start when three
conditions have been met:
The Journal of Immunology
E-
pub (www.jimmunol.org)
Published online 6
January 2008
Nature Biotechnology
Influenza virus particles mostly
spherical/ovoid, 80-120nm diameter
haemagglutinin (HA), a
135Å trimer
neuraminidase (NA), a 60Å
Paul Digard, Dept of
tetramer
Pathology,
University of Cambridge
Host Range
Species barrier between birds
and human:
Replication
PB2, PB1
and PA
Ns-
1
Hemaggluti Neuraminid M
nin ase 2
Hemagglutinin
Determine species
specificity for
avian α 2,3 –linked or
human α 2,6 –linked sialic
acid
Residues
Epidemiology of Human
Infections
Transmission
Handling of dead and sick poultry during the
week before the onset of illness –
Incubation Period
2-5 days
Increases in human cases of H5N1 have been observed during cooler months.
Infection rate and case fatality is more prevalent among younger individual ( age 40 or below )
Most
Probably Yes
Healthy Human Subjects Have CD4 T
Cells Directed Against
H5N1 Influenza Virus
Immunological memory
Immunological memory
- After infection
(antigen) is cleared
majority of effector
cells die by apoptosis
(programmed cell death).
- However, a significant
number persist as
memory cells –
immunological
memory.
- Immunological
memory ensures
rapid response on a
second encounter
with a pathogen, and
thereby usually
Pathogenesis
Viral Factors
Viral Replication
•Bronchiolar and alveolar cells, upper and
lower respiratory track
•Viral RNA persists in the respiratory track
upto 3 months
Pathological Findings
•Diffuse alveolar damage, inflammatory cells
and apoptosis in alveolar cells
Host Responses
•Increased level of imflammatory
cytokines IFN-γ, TNF-α, IL-5,IL-13.
H5N1 binds to α2,3-linked sialic acid
receptor on avian cells
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tion11
biochemical,
An integrated
analytical and data
mining approach demonstrates
that from the human-adapted H1N1
and H3N2 viruses, but not H5N1 (bird
flu) viruses, specifically bind to long
α2-6 sialylated glycans with this
Clinical
features Severe pneumonia/
Acute respiratory distress
syndrome
Other syndromes (listed in the
Laboratory diagnostic
•
VIRAL LATENCY
/OPPORTUNISTIC
INFECTION
Prevention
Increased Virus threat