Emergency Health and Nutrition Training Epidemiology,
Prevention, Treatment, History, & Current Threat Pandemic
Influenza Last Updated June 18, 2007
Slide 3
Three Different Kinds of Influenza Seasonal Influenza The Flu
Seasonal Influenza The Flu Avian Influenza Bird Flu Avian Influenza
Bird Flu Pandemic Influenza A Pandemic Pandemic Influenza A
Pandemic Related to each other, but public health implications of
each is very different
Slide 4
Influenza Type A Virus The Cause of All Avian & Pandemic
Flu & Much of the Seasonal Flu Neuraminidase (N) protein
facilitates virus detachment Hemagglutinin (H) protein facilitates
viral attachment onto our cells for invasion & replication
Slide 5
H16 XXXXXX (type A)
Slide 6
Origin of Pandemic Influenza Migratory water birds H 1-16 N 1-9
Domestic pig Domestic birds (All human flu pandemics come from bird
flu by 1 of 2 mechanisms)
Slide 7
Circulating Seasonal Influenza A Sub-Types from Pandemics of
the 20 th Century 19201940196019802000 H1N1 Seasonal Flu H2N2 H3N2
Seasonal Flu 1918/191957/581968/69 40-100 million deaths ~2 million
deaths~1 million deaths 4 pandemics since 1889, with 11 to 39 years
(average ~30 years) between each = ~3.3% annual risk of pandemic
onset (but likely higher now)
Slide 8
Camp Funston, Kansas, March 1918: Sadly, the comparatively
benign first wave was not at all predictive of what was to
come
Slide 9
(John Barry. The Great Influenza.)
Slide 10
Slide 11
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)
Slide 12
Published Pandemic Mortality Estimates for Selected Countries
(Johnson NPAS & Mueller J. Bulletin of the History of Medicine
(2002) 76:105-15) (1918: 28% of current global population.
http://birdfluexposed.com/resources/NIALL105.pdf )
http://birdfluexposed.com/resources/NIALL105.pdf USA: 675,000
Bangl./ India/ Pak.: 18.5 million Nigeria: 455,000 Egypt: 139,000
Guatemala: 49,000 Afghan.: 320,000 Indonesia: 1.5 million Philip.:
94,000 Japan: 388,000 Brazil: 180,000 South Africa: 300,000 Kenya:
150,000 Global Total: 50 100 million (WHO: 40 million +)
Russia/USSR: 450,000 Spain: 257,000 Canada: 50,000 Chile: 35,000
Australia: 15,000, in 1919 only British isles: 249,000
Slide 13
(Also had some shift in deaths to younger adults in 1957 &
1968) typical for seasonal flu U.S. life expectancy dropped by 12
years
Slide 14
Modes of Person-to-Person Transmission: 1.Large droplets from
coughing, sneezing, & talking, to others eyes, nose, or mouth;
2.Contact: direct (hand-to-hand) & indirect
(hand-to-surface-to-hand less common?); 3.? Airborne / aerosol /
droplet Courtesy of CDC
Slide 15
Decent Understanding of Modes of Transmission Led to
Non-Pharmaceutical Interventions But Guidance in the US was
Inconsistent & Communities Made Very Different Decisions
Slide 16
Gunnison, Colorado 1 of 7 U.S. towns & residential
institutions to escape the 2 nd wave Flu Cases: 0 in town; 2 in
county Flu Deaths: 0 in town; 1 in county Non-Pharmaceutical
Interventions Barricades on roads for 4 months; Rail travel
restricted; Quarantine of arrivals to county, & jailing of
those in violation; Isolation of suspected cases; Schools & all
institutions closed; No public gatherings, per state law
Slide 17
(For SARS, R o = 3, v = 9 days: From 1 to 4 cases in 9 days,
& 40 by Day 30) Flu: From 1 to a cluster of 15 cases in 9 days,
& 2,047 by Day 30! (Reproductive Number: R 0 for flu = 1.5 3.0,
but higher in closed settings & among children.) Explosive flu
outbreaks are due to this short generation time (due to short
incubation period & peak infectivity early in illness.)
Slide 18
Expect human cases in all areas with substantial human exposure
to HPAI H5N1+ birds 313 lab.-confirmed cases with 191 deaths (61%)
in 12 countries Expect human cases in all areas with substantial
human exposure to H5N1 HPAI + birds (So far, limited serological
surveys suggest that sub- clinical infection & mild illness
remain rare.)
Slide 19
Slide 20
Tamiflu! (oral) Ralenza (inhaled) (Older drugs) (Viral
resistance to these is more common) (Injectable Peramivir has
completed phase-1 trials)
Slide 21
WHO, May 2006: In patients with confirmed or strongly suspected
H5N1 infection, clinicians should administer oseltamivir treatment
as soon as possible (strong recommendation, very low quality
evidence). (Evidence = seasonal flu clinical trials in humans &
H5N1 animal data). clinicians might administer a combination of
neuraminidase inhibitor & M2 inhibitor (weak recommendation,
very low quality evidence). (Resistance to Tamiflu is a
concern.)
Slide 22
Slide 23
Pandemic Flu Prevention & Treatment Challenge ~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
Slide 24
Oseltamivir Therapy in H5N1 Thailand and Vietnam, 2004-2005
Oseltamivir Treatment Number Patients Number (%) Survivors Yes256
(24%) No123 (25%) Writing Committee. N Engl J Med.
2005;353:1374-1385. Tamiflu treatment often started late Dosage too
low? Poor absorption of oral Tamiflu? Course of treatment too
short? Some H5N1 resistance to Tamiflu
Slide 25
Case-Fatality by Age WHO Data on 256 Confirmed Cases, 11/03 -
11/06 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)
Slide 26
H5N1 in Humans Remains Rare: Currently Implicated Exposures
(Source of infection is unknown in many cases. Very few cases are
in presumed high-risk groups: Commercial poultry workers, workers
at live poultry markets, cullers, veterinarians, & health staff
caring for patients without using protective equipment) Some cases
are in family clusters, some due to person-to-person transmission
(genetics?) Preparing or disposing of diseased birds Handling
fighting cocks Handling poultry, esp. asymptomatic ducks Consuming
uncooked duck blood (& undercooked poultry?)
Slide 27
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.
(http://birdflubook.com/resources/Ungchusak333.pdf)http://birdflubook.com/resources/Ungchusak333.pdf
Thailand, Sep. 2004: A.11 year old girl died in Kamphaeng Phet
province without H5N1 test. B.Mother visited daughter in hospital
from BKK, H5N1+ without poultry exposure, & died. C.Aunt H5N1+,
recovered
Slide 28
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
Viet Nam: No human cases, 2006
Slide 29
Three Requirements for a Flu Pandemic: 1.Novel flu virus for
humans Yes 2.Ability to replicate in humans Yes & cause illness
3.Ability to pass easily Not Yet from person to person (signaled by
growing clusters / outbreaks of human cases) H5N1 in 1997 &
Since 2003:
Slide 30
* Key to Phases 3 - 6: The size & growth of clusters of
human cases (WHO phases apply to the whole world. Phases 4 & 5
may be skipped altogether - they assume gradual evolution of the
virus & an R 0 < 1.0.) (See notes below)
Slide 31
Current (~1950s!) flu vaccine technology requires slow
production in eggs * * Recent progress in growth of virus in cell
cultures instead of in eggs
Slide 32
(for USA) (In millions of courses for the US market) 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
Slide 33
Medical masks (surgical / procedure) help protect against
droplets N95 masks (should be fit- tested) Neither protect eyes or
prevent contact transmission Neither tested for influenza Must
discard after dirty or moist Will likely be in short supply Woven
cloth masks: Little data 1918 (& 21 st Century?)
Slide 34
Analysis of 1918 data: 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. (US CDC, Feb., 2007: http://www.pandemicflu.g
ov/plan/community/mitigat ion.html) http://www.pandemicflu.g
ov/plan/community/mitigat ion.html (* see photos in Barry, The
Great Influenza) Excess pneumonia & flu mortality over 19131917
baseline in Philadelphia & St. Louis, Sep. 8Dec. 28, 1918 NPIs
16 days after 1 st case NPIs 2 days after 1 st case
Slide 35
Community Strategies by Pandemic Flu Severity (1) From U.S. CDC
(& 15 Other Federal Agencies!) Feb. 1, 2007 Pandemic Severity
(Based Mostly on Case Fatality Ratio) Interventions by
SettingSeasonal Flu1957 / 19681918 or Worse Workplace/Community
Adult social distancing decrease number of social contacts (e.g.,
encourage teleconferences, alternatives to face-to-face meetings)
Generally not recommended ConsiderRecommend increase distance
between persons (e.g., reduce density in public transit, workplace)
Generally not recommended ConsiderRecommend modify, postpone, or
cancel selected public gatherings to promote social distance (e.g.,
stadium events, theater performances) Generally not recommended
ConsiderRecommend modify workplace schedules and practices (e.g.,
telework, staggered shifts) Generally not recommended
ConsiderRecommend
Slide 36
Community Strategies by Pandemic Flu Severity (2)
(http://www.pandemicflu.gov/plan/community/mitigation.html)http://www.pandemicflu.gov/plan/community/mitigation.html
Pandemic Severity (Based Mostly on Case Fatality Ratio)
Interventions by SettingCFR < 0.1%0.1% -