Transcript Influenza 1999 - University of Washington

Pandemic Influenza:
A Zoonotic Infection
Kathleen M. Neuzil, MD, MPH
PATH
University of Washington
School of Medicine
April 27, 2009
Questions
 What is the epidemiology of human
influenza?
 What is the role of animals in influenza
epidemiology?
 When do we worry about a pandemic?
Excess mortality:
Hallmark of epidemic influenza
 1837: Robert Graves, Dublin.
 1847: William Farr, London.
 1887-1956: Selwyn Collins, USA.
Influenza: An epidemic respiratory disease
associated with “excess” deaths
“Conductor turns away man because he is
not wearing his anti-flu mask.”
“Hunt up your wood-workers and
cabinet-makers and set them to
making coffins. Then take your street
laborers and set them to digging
graves. If you do this you will not
have your dead accumulating faster
than you can dispose of them.”
Amer J Public Health 1918; 8: 787.
20th Century Influenza Pandemics
Influenza pandemics: Mutations of animal
viruses, or viral reassortants
1918
Spanish
(H1N1)
Avian mutated
H1N1
40-50 million
deaths
1957
Asian flu
(H2N2)
Human H1N1
Avian H2N2
H1N1
disappeared
1968
Hong Kong
(H3N2)
Human H2N2,
avian H3Nx
H2N2
disappeared
1977
Russian
(H1N1)
Virus identical to Benign —
human strains
H1N1, H3N2
circulate
Surface antigens of the Influenza A virus
Hemagglutinin
Neuraminidase
M2
PB2
PB1
NS
PA
HA
NA
M
NS
PB2
PB1
NS
PA
HA
NA
M
NS
Epidemic human
virus A(H2N2)
Avian virus
A(H3N?)
1968 Pandemic
New epidemic virus
A(H3N2)
PB2
PB1
NS
PA
HA
NA
M
NS
Steinhoff MC. Epid and Prev
of Influenza. In: Infectious Dis
Epidemiology. Nelson et al.
Incidents with limited spread before 1997
1976 Swine flu NJ: Enzootic in
H1N1
swine herds.
One death in
military camp.
1986
One adult with
severe pneumonia.
H1N1
Netherlands:
Swine virus from
avian source.
1988 Swine flu Wisconsin:
H1N1
Swine virus.
Pregnant woman
died.
1993
H3N2
Netherlands:
Two children; mild
Swine — human
disease.
H3N2, avian H1N2.
1995
H7N7
UK: Duck virus.
One adult —
conjunctivitis.
What is the role of pigs?
H5N1 – Where did it start?
 1996: First detected in
geese in Guangdong
Province, China.
 1997: First recognized in
humans: Hong Kong,18
human cases, 6 fatal.
 H5N1 viruses isolated from
birds at wholesale and
retail markets in Hong
Kong.
 No further cases following
widespread culling of
chickens.
2003-2005 Avian Influenza A (H5N1)
outbreak in humans
 Vietnam, Thailand,
Cambodia
 55 cases, 42 deaths
 Predominantly children
and young adults.
 Rural Asia: Households
maintain free-ranging
poultry for income, food.
 Children play near
poultry; families slaughter
birds for food.
 Pathogenesis: high and
disseminated viral
replication and intense
inflammatory response.
N Engl J Med 2005: 353; 25
N Engl J Med 2004; 350: 1179
H5N1: How did it spread?
 1997-May 2005: largely
confined to SE Asia.
 Infected wild birds in Qinghai
Lake, China; rapidly spread
westward.
 Death of swans and geese
marked spread into Europe,
India and Africa.
 Ducks may be “stealth carriers.”
 Wild mallard ducks do not
always show signs of disease
when infected with highly
pathogenic H5N1 viruses.
N Engl J Med 2006; 355: 2174
Number of confirmed human H5N1 cases
by month as of 2009-01-27
Source: World Health Organization
H5N1: Human-to-human transmission?
 Infection after close contact with infected child leading
to illness and death.
 Evidence of antibodies to H5 in health care workers
who cared for patients in Hong Kong in 1997.
 Intensified surveillance (PCR) with contacts has led to
detection of mild cases, more infections in older
adults, and increased numbers of family clusters in
Vietnam.
 Family clusters in Indonesia.
NEJM 2005; 353;13.
NEJM 2006; 355: 2186.
So…
 H5N1 is a novel virus with ability to infect and cause
disease in humans
 Limited human to human transmission at present
 Total number of cases small; case fatality rate high
 Exposure and risk of future cases increasing with
increasing spread of virus among birds
 Is avian influenza worth the investment of resources,
and if so, what can/should be done?
WHO: Pandemic alert
 Influenza A virus with a novel HA or novel HA
and NA — substantial proportion of the
population has little or no antibody to the
novel virus.
 Novel virus demonstrates ability to cause
disease in humans.
 Novel virus demonstrates ability to spread
easily among humans.
Updated WHO guidance will be available in 2009
Revised Pandemic Phases
Source: World Health Organization
WHO Strategic Actions
 The objectives of the strategic actions correspond to the principal
opportunities to intervene and are likewise phase-wise.
 Phase: pre-pandemic
 1. Reduce opportunities for human infection
 2. Strengthen the early warning system
 Phase: emergence of a pandemic virus
 3. Contain or delay spread at the source
 Phase: pandemic declared and spreading internationally
 4. Reduce morbidity, mortality, and social disruption
 5. Conduct research to guide response measures
www.who.int
So what should be done,
pre-pandemic (now!)?
 Improve surveillance
worldwide.
– All types of influenza.
– All types of respiratory
disease.
– Easier, more reliable, less
expensive diagnostics.
– Year-round surveillance.
– Clinical research on human
cases/ populations.
Reduce opportunities for human infection
 Education about human behaviors.
 Control spread in birds/animals (collaboration
between animal and public health sectors).
 Improve approaches to environmental detection
of virus.
General emergency preparedness
 Clearly-defined plans, leadership structure.
 Responsibility/accountability.
 Communications.
 Surge capacity — Mass delivery mechanisms
for drugs/vaccines/health services.
 Stockpiles of essential medical supplies.
 Table-top exercises.
Preventing/minimizing morbidity and mortality
 Pandemic vaccines – Supplies, equitable
access, developing country manufacturers,
novel ways to use less antigen (make limited
supply go further).
 Antivirals – International stockpiles, supplies,
equitable access, developing country
manufacturers, international clinical trials
networks.
 Community mitigation strategies –
Quarantines/border or school closures.
Flu vaccine supply: Inadequate, inequitable


>95% of world flu vaccine comes from 9 countries
4 European companies produce 65% of world supply
Fedson DS. Vaccine Development for an Imminent Pandemic. Human Vaccines 2006: 2(1)38-42.
Dennis C. Flu-vaccine makers toil to boost supply. Nature 440:1099. Apr 2006.
Near term strategy: Is real-time response viable?
Real time response is not a viable solution in the near-term since existing
infrastructure would only serve a small portion of the world’s population
within 6 months of outbreak.
Real-time Global Pandemic Capacity – “Best Case”
7.0 B
Global Demand = 6.8B
6.0 B
Pandemic
Courses
Filled in
6 Month
Timeframe
5.0 B
4.0 B
2.8 B
3.0 B
2.0 B
1.2 B
1.2 B
2007
2008
1.8 B
1.9 B
2.0 B
2.0 B
2009
2010
2011
2012
2013
~1.3yrs
~1.3yrs
~1.3yrs
~1yr
1.0 B
0.0 B
Availability Timeframe
~2yrs
for Global Need
~2yr
~1.4yrs