H1N1

1
The reason we are so concerned about a pandemic
is the experience of the 1928 pandemic of
influenza.
1918
H1N1
2
Mortality in the 1918 pandemic was so great that
the life expectancy in the United States dropped
dramatically in that period.
3
Usually flu deaths are in the very young and the
very old, usually because of secondary bacterial
pneumonia
The dotted line shows the expected mortality from
influenza that is normally seen with deaths in
the very young and the elderly. These patients
usually died in the second week of illness due to
secondary bacterial pneumonia.
4
The 1918 virus resulted in severe, often fatal
primary viral pneumonitis.

• In 1918 the big difference was deaths in young
  adults between the ages of 15 and 40.
• These patients died of acute viral pneumonia and
  died between 24 and 48 hours of onset of
  symptoms.
• This is what is reported from Mexico City and
  what has been seen with bird (avian) flu. This
  is the reason for major concern.

5
1928 epidemic rate of progression across the
United States
This map shows how rapidly the 1928 epidemic
progressed across the United States at a time
when there was no air travel, few cars, and only
the railroad. You can see it all happened in
four short weeks. It started in the ports where
the soldiers from World War I were returning, and
spread rapidly to the rest of the country. This
is a lesson about the efficiency of the spread of
influenza virus.
6
This is an electron micrograph of the influenza
virus. You will see that it has a coat with
spikes. These spikes are the Hemagglutinin (H)
and the Neuraminidase (N) of the virus. These
are the H and the N we hear about. These are the
proteins against which our bodies make
antibodies. These antibodies protect us against
influenza.
Influenza virus
7
(No Transcript)
8
Note H16 recently identified in black-headed
gulls
9
Epidemic vs. Pandemic
1918, Swine flu, Bird flu
Major mutation pandemic
Regular winter flu
Minor mutation epidemics
10
Reassortment (in humans)
Migratory water birds
PANDEMICS
SHIFT
Source WHO/WPRO
11
Reassortment (in pigs) SHIFT
Migratory water birds
Source WHO/WPRO
12
The Role of The Pig
The original avian virus hemagluttinin (H5) can
only attach to bird cells which have a2,3
receptors in their respiratory and
gastrointestinal tracts
a2,3
a2,3
a2,3
a2,6 and a2,3
a2,6
The virus reassorts in pigs which have a2,3 AND
a2,6 receptors. When it does this it may aquire
the ability to attach to a2,6 human respiratory
tract cells
13
However, the human respiratory tract does have
some a2,3 linkages of sialic acid residues to
galactose particularly lower down in the tract.
Green a2,6
Red a2,3
Kyodo Shinya et al. Nature 2006
14
(No Transcript)
15
Pulmonary histology of infected mice
1918 clone A necrotising bronchiolitis
severe alveolitis B severe alveolar edema
histiocytic alveolitis scattered
neutrophils C alveolitis (neutrophilic)
hemorrhage 1918 53 Tx/91 D moderate
alveolitis moderate edema Tx/91 HA1918 E
mild peribronchial inflammation
minimal alveolitis Tx/91 F paucicity of
lesions
Tumpey et al, Science 200531077-80
16
Anti-influenza Drugs

• Neuraminidase Inhibitors
• Target - NA
• ZanamivirRelenza?
• OseltamivirTamiflu?

• M2 blockers
• Target - M2
• AmantadineSymmetrel
• RimantadineFlumadine
• Most 2004 H5N1 are resistant against
  M2-blockers

Slide courtesy of Erich Hoffmann, Division of
Virology, Department of Infectious Diseases,
St.Jude Childrens Research Hospital Memphis, TN,
USA
17
Safe and effective vaccines are likely to be the
single most important public health tool.