Epidemiology

1
Epidemiology Mitigation, History Current
Threat
Pandemic Influenza
(90 slides commemorating the 90th anniversary of
The Second Wave) Comments to estarbuck_at_savechildr
en.org pleaseCreated April 24, 2006 Last
Updated Feb. 17, 2009 (Animation in 5 slides
requires PowerPoint presentation mode)

• Slides adapted (with thanks) from
• Johns Hopkins University (www.pitt.edu/super1/lec
  ture/lec21431/index.htm)
• WHO Maps (www.who.int/csr/disease/avian_influenza/
  en/index.html)
• WHO WPRO Graphs (http//www.wpro.who.int/sites/csr
  /data/)
• And others

2
Topics Covered

• Links between avian, pandemic, seasonal flu
• Meaning of H N links to virulence
  immunity
• Natural reservoirs of Influenza A evolution
  into pandemic strains
• Modes of person-to-person transmission, serial
  interval, reproductive number, incubation period,
  etc.
• Pandemics of the 20th century, esp. 1918 waves,
  attack rate, mortality, risk groups
• Current distribution, spread, control of H5N1
  HPAI
• Human H5N1  Distribution, transmission,
  clusters, treatment, mortality
• Current pandemic threat, WHO Phases of Pandemic
  Alert, containment strategy
• Immunization, anti-virals, non-pharmaceutical
  interventions (NPIs)
• Potential pandemic social economic impact,
  key unpredictables.

3
Three Different Kinds of Influenza
Related to each other, but public health
implications of each is very different
Pandemic Influenza A Pandemic
Avian Influenza Bird Flu
Seasonal Influenza The Flu
(Not very seasonal in the warmest climates)
4
Influenza Type A Virus The Cause of All Avian
Pandemic Flu Much of the Seasonal Flu
Hemagglutinin (H) protein facilitates viral
attachment onto our cells for invasion
replication
8 RNA gene segments The extent of illness in
birds humans is due to the expression of
several genes in combination
Neuraminidase (N) protein facilitates virus
detachment
(H N are recognized by our immune system)
5
Circulating Seasonal Influenza A Sub-Typesfrom
Pandemics of the 20th Century
1918/19 H1N1
1957/58 H2N2
1968/69 H3N2
1 - 4 million deaths
1 4 million deaths
40-100 million deaths
H3N2 Seasonal Flu
H2N2
1977 lab escape?
H1N1 Seasonal Flu
H1N1 Seasonal Flu
1920 1940 1960 1980 2000
4 pandemics since 1889, with 11 to 39 years
(average 30 years) between each 3 annual
risk of pandemic onset (but likely higher now)
6
1918, 1957, 1968 US UK Overall Clinical
Attack Rates Range 23 39. (Slide from
UK Dep. of Health)
7
Case Fatality Attack Rates in the US in 1918,
1957, 1968, Projected US Mortality of a
Modern Pandemic (CDC, Feb. 2007)
8
Camp Funston, Kansas, March 1918 Sadly, the
comparatively benign first wave was
not at all predictive of what was to come
9
Every Community Should Expect 1 3 Waves /
Outbreaks, Each Lasting 6 12 Weeks (Over a
Duration of 1.5 Years Max.?)

• The second wave was the killer that swept around
  the world, causing death due to (?)
• Primary viral pneumonia Acute Respiratory
  Distress Syndrome (ARDS),
• Secondary bacterial infections, particularly
  pneumonia

10
And, as the Second Wave Swept Around the World
Called the Spanish Influenza because of
extensive press coverage of it in Spain. The
King got it neutral Spain had no press
censorship.
11
Published Pandemic Mortality Estimates for
Selected Countries (Johnson NPAS Mueller J.
Bulletin of the History of Medicine (2002)
76105-15) (1918 28 of current global
population. http//birdfluexposed.com/resources/N
IALL105.pdf)
Russia/USSR 450,000
British isles 249,000
Canada 50,000
Japan 388,000
Afghan. 320,000
Spain 257,000
USA 675,000
Egypt 139,000
Philip. 94,000
Bangl./ India/ Pak. 18.5 million
Guatemala 49,000
Nigeria 455,000
Indonesia 1.5 million
Kenya 150,000
Brazil 180,000
Australia 15,000, in 1919 only
South Africa 300,000
Chile 35,000
Global Total 50 100 million (WHO 20-50
million)
Sequestration completely protected American
Samoa, Australia from the 2nd wave, while
Western Samoa lost 22 of its population
12
typical for seasonal flu
(Also had some shift in deaths to younger adults
in 1957 1968)
Next Pandemic
Risk groups for severe fatal infection cannot
be predicted with certainty, but are likely to
include infants, the elderly, pregnant women,
persons with chronic or immunosuppressive
conditions (HHS)
U.S. life expectancy dropped by 12 years
13
Origin of Pandemic Influenza
(All human flu pandemics come from bird flu by
1 of 2 mechanisms)
Migratory water birds
H 1-16
Domestic pig
N 1-9
Domestic birds
14
(type A)
H16
XXXXXX
15
1. Constant Mutation Small random changes in
viral RNA during replication sometimes cause
important change in shape of H, N, etc., in
transmission or virulence, are then propagated
through continuing infections of new individuals
Virus (Can only replicate inside animal cells)
New H shape allows attachment to human cells
or avoidance of antibodies
Human Cells
16
2. Re-Assortment Bird human viral RNA
segments exchanged in pig or human infected with
both human avian flu at once, causes
instantaneous big change in virus
Migratory Water Birds
Pig or Human
17
Origin of Pandemic Strains Mutation
Reassortment

• Belshe RB. N Engl J Med 200535321
• Reassortment likely to happen fairly soon if
  there is a good match??
• The right combination of several mutations more
  likely after several years??

18
H5N1s Global Genetic Roulette Table
Persistence spread of H5N1 is
historically unprecedented for HPAI
62 countries (incl. Nepal in 2009)
19
Current Global Spread c/o Trade in Bird Products
Bird Migration
Highly Pathogenic H5N1 Influenza Virus in
Smuggled Thai Eagles, Belgium (CDC)
20
Controlling Highly Pathogenic Avian Influenza
(HPAI)

• Clean disinfect farms
  live markets
• Control movement of birds, workers, potentially
  contaminated materials
• Segregate different species batches of poultry
  from each other, from pigs waterfowl
• Vaccination
• Disease surveillance
• Rapid culling of infected at risk poultry, with
  incentives to farmers

21
Continuing Widespread H5N1 HPAI Continuing
Serious Pandemic Threat
Less H5N1 HPAI in wild migratory birds in
2007/2008 than in 2006
H5N1 HPAI in poultry is now endemic in several
countries, including Egypt Indonesia.
28 countries in 2007, 23 countries in
2008 (www.oie.int/eng/info_ev/en_AI_factoids_1.htm
)
22
Expect human cases in all areas with substantial
human exposure to HPAI H5N1 birds
Expect human cases in all areas with substantial
human exposure to H5N1 HPAI birds
As of February 16, 2009 407 lab.-confirmed
cases in 15 countries, including 254 deaths (Case
Fatality 62)
23
This case-fatality distribution among H5N1 cases
is reminiscent of those observed during previous
pandemics, particularly in 1918 (WHO, June 2006,
re. a similar distribution)
70
77
45
73
57
50 37
(9 serological studies have found very few
sub-clinical infections mild illnesses.)
24
Should the virus improve its transmissibility by
acquiring, through a reassortment event, internal
human genes, then the lethality of the virus
would most likely be reduced. However, should
the virus improve its transmissibility through
adaptation as a wholly avian virus, then the
present high lethality could be maintained during
a pandemic. (page 15) some modelling studies
have suggested that pandemic spread could not be
fully sustained in the presence of very high
mortality. All such matters remain difficult
to predict. (page 16)
25

• In 2007, the US Centers for Disease Control
  started conducting agency-wide simulations of
  pandemic spread to the US, with initial case
  fatality of 20. 
• If CFR stayed at 20, there would be 12 24
  million deaths in the US alone (assuming the
  expected 20 - 40 attack rate).

26
Is this strong seasonal pattern because flu
transmission is favored by lower temperature
and/or lower humidity?
27
(From Responses to Avian Influenza State of
Pandemic Readiness Fourth Global Progress
Report. UN System Influenza Coordinator The
World Bank, October 2008, page 9.)
The threat of an influenza pandemic remains
unchanged.
28
1/4 of cases are in clusters www.fluwikie.com
45 clusters in 10 countries
This kind of a distribution of illness onset
dates would be suggestive of person- to-person
transmission.
R02, v5.5 days
http//h5n1flu.blogspot.com/

• 1 Feb. 2003 Hong Kong family visiting
  Fujian, China
• 44 Dec./Jan. 08/09 Mother daughter in
  Shanxi, China.
• Clusters indicate possible person-to-person
  transmission
• Or common exposure to an environmental source,
  like birds.
• Here, a cluster is defined as 2 or more persons
• Who have been in contact with each other,
• Who became very sick with a respiratory disease,
  
• At least 1 of whom is a WHO lab-confirmed H5N1
  case.

29
H5N1 in Humans Remains RareCurrently Implicated
ExposuresSource of infection is unclear in 25
of cases.Environmental exposure? (Visiting live
poultry markets. Fomites? Fertilizer?
Aerosolized Feces?) Very few cases in presumed
high-risk groups (Commercial poultry workers,
workers at live poultry markets, cullers,
veterinarians, health staff caring for patients
without using protective equipment)
Preparing or disposing of diseased birds
Handling fighting cocks
90 of clusters involve blood relatives, some due
to person-to-person transmission (genetics?)
Handling poultry, esp. asymptomatic ducks
Consuming uncooked duck blood ( undercooked
poultry?)
30
One theory is that most people have bird-like
receptors only on cells deep in their lungs,
while some families have more in their upper
airways (though things may be more complex).
31
(http//birdflubook.com/resources/Ungchusak333.pdf
)
established in 1812 January 27, 2005
vol. 352 no. 4 Probable Person-to-Person
Transmission of Avian Influenza A (H5N1) Kumnuan
Ungchusak, M.D., M.P.H., Prasert Auewarakul,
M.D., Scott F. Dowell, M.D., M.P.H., Rungrueng
Kitphati, M.D., Wattana Auwanit, Ph.D., Pilaipan
Puthavathana, Ph.D., Mongkol Uiprasertkul, M.D.,
Kobporn Boonnak, M.Sc., Chakrarat
Pittayawonganon, M.D., Nancy J. Cox, Ph.D.,
Sherif R. Zaki, M.D., Ph.D., Pranee Thawatsupha,
M.S., Malinee Chittaganpitch, B.Sc., Rotjana
Khontong, M.D., James M. Simmerman, R.N., M.S.,
and Supamit Chunsutthiwat, M.D., M.P.H.

• Thailand, Sep. 2004
• 11 year old girl died in Kamphaeng Phet province
  without H5N1 test.
• Mother from BKK visited daughter in hospital,
  H5N1 without poultry exposure, died.
• Aunt H5N1, recovered

32

• April /May 2006 Karo, N. Sumatra cluster
• Limited WHO/MOH containment activities
• No transmission beyond this family
• Local people resist chicken culling demand
  departure of WHO team

"Thank God, the result came back negative," MOH
official on 1 of 4 nurses with flu symptoms after
caring for H5N1 cases, Jakarta Post, June 4,
2006. (3 cases in health workers trouble)
33
If you think H5N1 is out of the headlines or the
pandemic threat has evaporated, maybe youre
just reading the wrong papers!
Human cases of avian influenza A(H5N1) in NWFP,
Pakistan, OctoberNovember 2007 The Peshawar
family cluster Conclusion . evidence
supports a chain of transmission beginning with
poultry-to-human transmission followed by
human-to-human transmission for 3 generations of
transmission. Despite thorough investigation and
active surveillance, there was no evidence of
sustained transmission in the community.
34
Three Requirements for a Flu Pandemic
H5N1 in 1997 Since 2003

• Novel flu virus for humans Yes
• Ability to replicate in humans Yes
  cause illness
• Ability to pass easily Not Yet
  from person to person
  (signaled by growing
  clusters / outbreaks
  of human
  cases)

The question remains open what is needed for
the H5N1 virus to transmit efficiently from one
human to another? Overall, the genetic controls
of cross-species infectivity and transmissibility
of influenza viruses are complex and not yet
fully understood. WHO, Nov. 2006.
35
Proposed New WHO Phases of Pandemic Alert (WHO
phases apply to the whole world. Key to Phases
3 4 The size growth of clusters of human
cases)
Geographic spread
Phases 5-6
Predominantly animal Infections Limited
transmissibility among people
5 - 6
Post Peak
Post Pandemic
4
Sustained H-2-H transmission
1 - 3
Time
(www.who.int/csr/disease/influenza/PPWGupdate_WHOW
ebVersion.pdf - See notes below)
36
WHO Interim Protocol Rapid
Operations to Contain the Initial Emergence of
Pandemic Influenza Updated October 2007 ..
containment of a pandemic might be possible at
the initial stages . Emphasis within the
Containment Zone Antivirals for treatment
prophylaxis Movement restrictions in out
Non-pharmaceutical interventions Emphasis in both
zones Surveillance laboratory testing
Communications social mobilization

• WHO has a stockpile of 3 million 10-capsule
  courses of Tamiflu for this.
• But containment may be more likely to delay
  onset than prevent a pandemic.
• News of this warning of high risk of imminent
  pandemic onset

37
Rapid transition from Phases 3 to 4, followed by
quick spread around the world, may leave us
little time to prepare.
Border closures travel restrictions are likely,
may delay spread of the
virus, but are unlikely to stop it.
38
(Hypothetical scenario of severe pandemic onset
trigger for international evacuation)

• How much will international airline travel be
  affected?
• For how long?
• What will the triggers be for governments for
  airlines?
• Will ports of entry be closed?
• Will US citizens have the right of return?

39
Flu Pandemic Gravest Threat to UK Security
Could Claim Up to 750,000 Lives
Friday, 8 August 2008
40
Potential Impact Beyond Flu-Related Mortality
In 1918, Worker Absenteeism Led to Social
Economic Disruption
41
In the 21st CenturyPandemic Wave Peak
Worker-Absenteeism 50 (?) Long Supply Lines
Just-In-Time Delivery of Goods Big Impact on
Availability of Goods Services?
(www.cidrap.umn.edu/index.html)
42
CATEGORIES OF RISK AVIAN PANDEMIC INFLUENZA
UNSIC
Livelihoods

• Food income loss from poultry deaths, culling
  decreased economic activity

• High illness potentially high death rates
• Overstretched health facilities
• Disproportionate impact on vulnerable

Human Health

• Increased demand for governance security
• Higher public anxiety
• Reduced capacity due to illness death

Governance Security

• Deterioration of coping support mechanisms
• Interruption in public services
• Quarantine policies

Social Humanitarian Needs

• Trade commerce disruptions
• Degraded labour force
• Interruption of regular supply systems

Economic Systems
43
A Whole-of-Society ApproachTo Pandemic
Preparedness(WHO slide, May 2008)
Business continuity Surge capacity Critical
interdependencies Clear command and control
Social distancing
44
(Health Sector)
45
Current (1950s!) flu vaccine technology
requires slow production in eggs targets
strain-specific surface antigens ( Recent
progress includes growth of virus in cell
cultures instead of in eggs)
A Strain of Type B
Seasonal Vaccine Antigens
A Strain of Type ASubtype H1N1
A Strain of Type ASubtype H3N2
46
Annual Process of Development, Manufacturing,
Distribution of Seasonal Flu Vaccine
The time lag between vaccine production
seasonal flu outbreaks (often 6 months or more)
can result in a mismatch between the vaccine
the circulating virus.
47
(In millions of courses for the US market)
(for USA)

• Global flu vaccine production capacity can meet
  only a small fraction of global need.
• The US goal is to be able to immunize the entire
  US population within 6 months of pandemic onset
  by 2011

(Long-term goal is a universal influenza A
vaccine)
48

• WHO, 2/16/07
• 16 manufacturers from 10 countries developing
  prototype H5N1 pandemic vaccines.
• For the first time, vaccines can bring about
  a potentially protective immune response against
  strains of H5N1 virus found in a variety of
  geographical locations.
• Some .. work with low doses of antigen, which
  means that significantly more vaccine doses can
  be available in case of a pandemic.

Vietnam Thailand Cambodia
Vietnam/JP14/05
ck/Cambodia/013LC1b/05
Vietnam/1194/04
Clade 1
Vietnam/1203/04
Vietnam/HN30408/05
Thailand/16/04
Vietnam/JPHN30321/05
Hong Kong/213/03
Indonesia/CDC523/06
Indonesia/CDC699/06
Indonesia/CDC326/06
Indonesia/5/05
Clade 2.1
Indonesia/CDC184/05
Indonesia/7/05
dk/KulonProgoBBVET9/04
Indonesia
ck/Indonesia/CDC25/05
Indonesia/6/05
ck/Brebes/BBVET2/05
Indonesia/CDC625/06
Indonesia/CDC594/06
Karo cluster
ck/Dairi/BPPVI/05
ck/Yunnan/374/04
ck/Yunnan/115/04
dk/Guangxi/13/04
Strains in yellow Vaccine strains
ck/Guangxi/12/04
ck/Yunnan/493/05
ck/Yunnan/447/05
whooping swan/Mongolia/244/05
bar headed gs/Qinghai/1A/05
Clade 2.2
Turkey/65596/06
Turkey/15/06
Iraq/207NAMRU3/06
Middle east Europe Africa
ck/Nigeria/641/06
mld/Italy/332/06
turkey/Turkey/1/05
Egypt/2782NAMRU3/06
Djibouti/5691NAMRU3/06
ck/Nigeria42/06
migratory dk/Jiangxi/2136/05
gs/Kazakhstan/464/05
ck/Krasnodar/01/06
Azerbaijan/011162/06
swan/Iran/754/06
dk/Laos3295/06
Anhui/1/05
Clade 2.3
Anhui/2/05
Japanese white-eye/Hong Kong/1038/06
ck/Malaysia935/06
China Laos
Vietnam/30850/05
Guangxi/1/05
dk/Hunan/15/04
qa/Guangxi/575/05
dk/Vietnam/Ncvdcdc95/05
migratory dk/Jiangxi/1653/05
Hong Kong/156/97
There are many strains of H5N1 HPAI
gs/Guangdong/1/96
49
(Injectable Peramivir has completed phase-1
trials)
Tamiflu! (oral)
Ralenza (inhaled)
(Older drugs)
(Viral resistance to these is more common)
50
In Seasonal Flu, Early Treatment with Tamiflu
Reduces the number of viral particles released
from infected cells, thereby

• Decreasing viral
• shedding

• Decreasing the duration of uncomplicated illness
  
• Reducing lower respiratory tract complications,
  antibiotic use, hospitalizations.
• But, H1N1 is increasingly Tamiflu resistant,
  worldwide.

51
Use of Antivirals for H5N1

• From Osterholm, 2/14/06
• H5N1 1918 H1N1 cause a very different disease
  than H3N2 (seasonal flu).
• Virus storm may lead to cytokine storm
  (particularly in those with strongest immune
  response?)
• From WHO, September 2007

• Tamiflu reduces mortality if given in early
  stages of illness.
• May need to double dosage, and/or double duration
  of treatment.
• Optimal dose regimen is uncertain.
• Viral resistance to Tamiflu may develop.

(For close contacts of H5N1 cases, WHO recommends
Tamiflu or Ralenza prophylaxis. This would have
big drug supply implications in a pandemic.)
52
Pandemic Flu Prevention Treatment Challenge
(nothing like SARS)
2 day incubation period for seasonal flu is
expected for pandemic flu also
High levels of virus, some person-to-person
transmission, 1 day before symptoms!
Transmission up to 7 days after fever ends
longer in kids immune suppressed
Peak transmission
53
March 2005 H5N1 viral pneumonia / ARDS survivor
in Hanoi. Supportive care, incl. ventilator, O2,
hydration, antibiotics for secondary
bacterial infections are important.
54

• Modes of Person-to-Person Transmission Close
  Exposure (1 - 2 meters / 3 - 6 feet)
• Large droplets from coughing, sneezing,
  talking, to others eyes, nose, or mouth
• Contact direct (hand-to-hand) indirect
  (hand-to-surface-to-hand less common?)
• ? Airborne / aerosol / droplet nuclei By
  aerosol-generating medical procedures in shared
  air spaces with poor air circulation? Can remain
  suspended in air for longer, but NOT long
  distance or in ventilation systems?

Courtesy of CDC
55
In 1918, Some of the Guidance to the Public (
Even Some of the Advertising) Reflected a Good
Understanding of the Modes of Transmission
56
Infection Prevention (To reduce risk of
infection in spite of close exposure)
(How much better will we be in the 21st century?)
1957 (no longer recommended)
Current focus for the general public
57
In 1918, Masks Were Popular in Many Areas,
Required in Some
Schoolgirls wear masks to protect against the flu
in Tokyo
Seattle, Nov. 1918 No mask, no ride.
58

• Medical masks (surgical / procedure) help protect
  against droplets
• N95 also for aerosols (important for suctioning,
  nebulizer treatment, etc.), but should be
  fit-tested using a kit
• Neither protect eyes or prevent contact
  transmission
• Better on cases than on uninfected?
• Neither tested for influenza
• Must discard after dirty or moist
• Will likely be in short supply
• Woven cloth masks Little data

(Institute of Medicine, US National Academy of
Sciences, 4/27/06 proof, http//www.nap.edu/catalo
g/11637.html)
1918 ( 21st Century?)
59
Even full PPE with N-95 mask may not always be
completely protective
(Good hand hygiene minimizing exposure are also
important.)
60
Community Mitigation Multiple Layered
Non-Pharmaceutical Interventions (NPIs)(To
reduce contacts between potentially infectious
susceptible persons)
(Because No Single NPI is Effective Enough)
61
(R0 the average number of secondary cases of
disease generated by a typical primary case in
a susceptible population.)
Flu From 1 to a cluster of 15 cases in 9 days,
2,047 by Day 30!
Explosive flu outbreaks are due to this short
generation time (due to short incubation period
peak infectivity early in illness.)
(Nothing like SARS Ro 3, v 9 days From 1
to 4 cases in 9 days, 40 by Day 30)
(Reproductive Number R0 for flu
1.5 3.0, but higher in closed settings
among children.)
62
NPIs Can Reduce R0 by Reducing the Number of
Contacts Between Infectious Susceptible Persons
(In both scenarios, above, ¼ of contacts become
ill.)
63
Effect of R0 on the Epidemic Curve
2.7
64
Good Understanding of Modes of Transmission Led
to Non-Pharmaceutical Interventions But Guidance
in the US was Inconsistent Communities Made
Very Different Decisions
65
Protective Sequestration in Gunnison, Colorado
1 of only 7 U.S. towns residential
institutions to escape the 2nd wave (Escape
Community Digital Document Archive, Center for
the History of Medicine, Univ. of Michigan
www.med.umich.edu/medschool/chm/influenza/)

• Non-Pharmaceutical Interventions
• Barricades on roads for 4 months
• Rail travel restricted
• Quarantine of arrivals jailing of those in
  violation
• Isolation of suspected cases
• Schools all institutions closed
• No public gatherings, per state law

Site Small mountain town, far from
major population centers, but on a major rail
line. Population 1,329 in town Flu Cases 0
in town Flu Deaths 0 in town
66
Current modeling (with uncertain assumptions),
analysis of 1918 data, suggest that early
sustained use of multiple partially effective
non-pharmaceutical interventions (NPIs), can

• Delay the outbreak peak
• Reduce peak burden on hospitals infrastructure
  
• Modestly reduce total of cases deaths.

NPIs 16 days after 1st case
NPIs 2 days after 1st case
Excess pneumonia flu mortality over 19131917
baseline in Philadelphia St. Louis, Sep.
8Dec. 28, 1918 (Hatchett RJ, Mecher CE, Lipsitch
et al. Public health interventions
epidemic intensity during the 1918
influenza pandemic. PNAS 2007 http//www.pnas.org
/cgi/content/abstract/0610941104v1)
(US CDC, Feb., 2007 http//www.pandemicflu.gov/p
lan/community/mitigation.html)
67
200,000 crowd to see the biggest parade in the
citys history, 2 weeks after the first civilian
cases, the day after 200 were admitted to
hospital!
By mid-October Philadelphia was reeling. ..
the city had to secure five supplementary
morgues. .. Many families, especially in the
slums, had no adult well enough to prepare food
in some cases had no food at all because the
breadwinner was sick or dead. Alfred Crosby
68
In Philadelphia the number of dead quickly
overwhelmed the citys ability to handle bodies.
It was forced to bury people, without coffins,
in mass graves and soon began using steam shovels
to dig the graves.
(John Barry, The Great Influenza)
69
Oct. 7 Mayor closes theaters, moving picture
shows, schools, pool billiard halls, Sunday
schools, cabarets, lodges, societies, public
funerals, open air meetings, dance halls,
conventions, until further notice.
Oct. 5 First cases in civilians reported
Nov. 14 Closing order withdrawn (but was again
re-instituted)
Source Hatchett R, Mecher C, Lipsitch M.
(www.pnas.org/cgi/reprint/104/18/7582)
70
The Situation in Saint Louis During the Peak of
the Second Wave Never Approached that in
Philadelphia
In St. Louis, Missouri, the Red Cross Motor Corps
transports a flu victim from a house at Etzel
Page Avenues (St. Louis Post Dispatch file photo)
71
Goal of 21st Century Preparedness Efforts
Community Mitigation (St. Louis County Dep. of
Health, 2006 www.pandemicprep.org/)
Lower
Raise
72
Non-Pharmaceutical Interventions for Pandemic
Influenza National Community Measures. WHO,
Jan. 2006. (www.cdc.gov/ncidod/eid/vol12no01/05-13
71.htm)
1918 NPIs for the 21st Century!

• WHO recommendations,
• based on limited data, vary
• by transmission pattern,
• by illness severity extent.
• Ill persons should remain home, but forced
  isolation quarantine are ineffective
  impractical
• Nonessential travel to affected areas should be
  deferred
• Mask use should be based on setting risk
• Hand respiratory hygiene should be routine
• Contaminated household surfaces should be
  disinfected
• If the pandemic is severe, social distancing
  measures, such as school closures, should be
  considered.

73
Most Countries Now have Plans in Place to
Implement NPIs But in Most, Logistical
Legislative Provisions are Unclear
(From Responses to Avian Influenza and State of
Pandemic Readiness - Fourth Global Progress
Report. UN System Influenza Coordinator The
World Bank, October 2008, page 58.)
74
Community Strategies by Pandemic Flu Severity
(1) From U.S. CDC ( 15 Other Federal Agencies!)
Feb. 1, 2007
75
Community Strategies by Pandemic Flu Severity
(2) (www.pandemicflu.gov/plan/community/mitigation
.html)
76
How feasible are these NPIs going to be for real
people to practice?
(if the net holds up)
77
School Closing Warrants Special Consideration

• Immediate community-wide impact from a single
  policy decision?
• But data on benefits of school closing is very
  limited.
• Mathematical models suggest closing will reduce
  transmission,
• If kids stay home away from friends.
• But, closing will cause substantial adverse
  socio-economic impacts. (How many health workers
  will stay home with their kids because schools
  are closed?) Nutrition?
• Pros cons must be considered.

78
Intervals in Local Epidemic Curves Triggers for
Community Mitigation
Different communities will be at different
intervals during national waves/ epidemics
Detect cases clusters early

• Implementing interventions before the local
  outbreak will likely result in economic social
  hardship without public health benefit,
  intervention compliance fatigue.
• Implementing after extensive local spread will
  likely limit the public health benefits.
• The geopolitical trigger should be defined as a
  cluster of cases occurring within a U.S. State or
  proximate epidemiological region (e.g., a
  metropolitan area that spans more than one
  State). (US HHS/CDC, Feb. 2007)

(Adapted from US CDC slide)
79
Effective Communication Will Be Important

• Trust Communicate in ways that builds,
  maintains, or restores trust. Acknowledge
  uncertainty avoid excessive reassurance.
• Transparency People are more likely to
  over-estimate the risk if information is
  withheld. Public panic is rare when people are
  candidly informed.

• Start early to prevent rumors misinformation,
  to prepare the public for the crisis.
  Acknowledge that early information may change.
• Understanding the public is critical to effective
  communication. Thus, crisis communication should
  be a dialogue.

www.who.int/csr/resources/publications/WHO_CDS_200
5_28/en/index.html
80
In 2006, 2007, 2008, US Health Secretary Mike
Leavitt noted at pan flu state planning summits
around the country that, Any community that
fails to prepare with the expectation that the
federal government will at the last moment be
able to come to the rescue will be tragically
wrong, not because the federal government lacks
will, not because we lack wallet, but because
there is no way in which 5,000 different
communities can be responded to simultaneously,
which is a unique characteristic of a human
pandemic.
81
In Connecticut local health departments ..
currently note, somewhat incredulously, that, in
the event of Pandemic Flu, they are responsible
for

• Community quarantine isolation .......
• Instituting .. social distancing
• Mass Care, i.e., taking care of those too ill to
  be at home .. when the hospitals have exhausted
  surge capacity shut their doors
• Mass Fatalities, i.e., collecting large numbers
  of bodies when the ordinary medical examiner
  mortuary processes have collapsed
• without any assistance from any outside
  source, as it is assumed that every community is
  undergoing the same crisis.
• (From a local health department in Connecticut,
  Feb. 2007)

82
Few countries have the staff, facilities,
equipment, hospital beds needed to cope .
(WHO, Oct. 2005)
(Hospital surge capacity is now a hot topic, 90
years later.)
Pandemic A total of 20 to 40 of everyone on
earth gets sick with the flu.
(John Barry. The Great Influenza.)
83
A Critical Gap in WHO HHS Guidance

• During the pandemic, most ill people will be
  cared for at home.
• In some families, all caretakers will be ill at
  the same time.
• Woodsons 17-page guide fills a critical gap for
  the US setting
• Preventing or treating dehydration in people
  with flu will save more lives than any other
  intervention during the influenza pandemic.
• Guidelines for families community health
  workers are needed for resource-poor settings.

(August 29, 2006)
(www.BirdFluManual.com)
84
Common illnesses, such as HIV, TB, diarrhea,
malaria, particularly pneumonia, will need
treatment CHWs may be good for this in some
settings
In the northwestern mountains of Nepal in 1987, a
CHW (who uses antibiotics to treat childhood
pneumonia) takes the respiratory rate of an
infant using a sand timer. In a pandemic, should
he also treat pneumonia in older kids adults?
See Reducing Excess Mortality from Common
Illnesses During an Influenza Pandemic WHO
Guidelines for Emergency Health Interventions in
Community Settings www.who.int/diseasecontrol_em
ergencies/common_illnesses2008_6.pdf
85
Generic Content for Basic Community Health
Response in Developing Countries
12/11/08 draft for in-country adaptation. Health
Working Group, Humanitarian Pandemic Preparedness
(H2P) Initiative (Based on the document, Health
Interventions, Tools, Modules available at
www.coregroup.org/h2p/)
86
WHO is Now Developing Important New / Detailed
Guidance
87
Conclusions (1)Key Unpredictables

• Will it come from H5N1
  or from another subtype?
• Will we move from Phase 3
  to Phase 6 overnight or over months?
• Will it hit next week, next year, or next decade?
• What roles will immunization anti-virals play?
• How high will mortality be? (1968, 1918, H5N1?)
• How much economic social disruption?

88
1918, 1957, 1968 were each quite different,
H5N1 has been unprecedented
Expect the Unexpected Keep Plans Actions
Flexible Based on Current Best Evidence
89
Conclusions (2)

• Bird flu is NOT a substantial
  direct threat to public
  health
  (pandemic flu is)
• Pandemic flu onset severity are signaled by
• WHO updates on phases of pandemic alert
• The size growth of human clusters,
• Due to H5N1 or another new flu subtype,
• Anywhere in the world,
• Severity of illness in these human cases,
• NOT by the arrival of H5N1 in birds in any
  country.
• However, the current threat will likely continue
  as long as H5N1 causes disease in humans in
  poultry.

90
Conclusions (3)

• All concerned should keep in mind that no health
  emergency on the scale of a severe influenza
  pandemic has confronted the international
  community for several decades.

• "the present threat to international public
  health is sufficiently serious to call for
  emergency actions calculated to provide the
  greatest level of protection preparedness as
  quickly as possible.
• (WHO Strategic Action Plan for Pandemic Influenza
  20062007, page 4. WHO, 2006)
• So far, there are no silver bullets ( nobody
  will come riding to our rescue).
• We need to prepare, now, as best we can
• www.coregroup.org/H2P
• www.savethechildren.org/publications/technical-res
  ources/avian-flu/

91
(No Transcript)
92
(WHO phases apply to the whole world. Phases 4
5 may be skipped altogether - they assume gradual
evolution of the virus.)
Key to Phases 3 - 6 The size growth of
clusters of human cases
(See notes below)
93
Spread of H2N2 Pandemic in 1957
94
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95
Some Current Controversies
(1957)

• Which non-
• pharmaceutical
• interventions, under
• which circumstances,
• to reduce person-to-
• person transmission? Benefits vs. negative
  consequences, feasibility.
• Importance of airborne transmission in
  person-to-person flu transmission implications
  for control (surgical vs. N-95 masks, etc.).
• Relative roles of migratory birds vs. trade in
  poultry products in spread of High Path. H5N1.

96
Low Pathogenic Highly Pathogenic Avian
Influenza in Migratory Water Birds Poultry
Reservoir
LPAI
Only H5N1 HPAI is transmitted back to migratory
birds then on to poultry in other areas (?)
HPAI (H5/H7)
Mutation
LPAI (H1-16)
97
The age-specific incidence per 10 million
population (below), indicates that the
distribution of cases by age (left) partly
reflects the young population of Viet Nam.
(Indonesia has higher incidence in the young.)

• Median age 18 yrs.
• 90 age 40 or less

• Higher incidence in the young may be due to
• Greater exposure to the virus,
• More severe disease, and/ or,
• More thorough investigation of pneumonia,
• in the young?

98
Most Cases Not Hospitalized in Time to Get
Maximal Benefit of Tamiflu
mean 4.6 days
maximum Tamiflu efficacy
76 case fatality rate (CFR)
46 CFR
22 CFR
cases deaths
human H5N1 cases and deaths
Days between symptom onset and hospitalization
Lab-confirmed H5N1 cases in humans reported to
WHO between November 2003 and November 12, 2007
for which there is symptom onset and health
status data.
99
(No Transcript)
100
(September 2007 Slide)
101
(September 2007 Slide)
102
(No Transcript)
103
If 2 lt R0 lt 3, and v 3 Days (each mouse click)
104
NPIs Can Reduce R by Reducing the Number of
Contacts Between Infectious Susceptible Persons
105
Pandemic Influenza Preparedness, Response,
Recovery Guide for Critical Infrastructure Key
Resources (Sep. 2006)
106
Spheres of Progress in Influenza Research
Points of overlap among the three circles
illustrate how the findings in each area have
implications for the other two areas. The major
challenges within each area of research are noted
around the periphery of that circle. (R Salomon
RG Webster. Cell, Feb. 6, 2009)