Emergency Health and Nutrition Training

Epidemiology, Prevention, Treatment, History, & Current Threat

Pandemic Influenza

Last Updated June 18, 2007

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

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

H16 XXXXXX

(type A)

Origin of Pandemic Influenza

Migratory water birds

H 1-16

N 1-9

Domestic pig

Domestic birds

(All human flu pandemics comefrom bird flu by 1of 2 mechanisms)

Circulating Seasonal Influenza A Sub-Typesfrom Pandemics of the 20th Century

1920 1940 1960 1980 2000

H1N1 Seasonal Flu H1N1 Seasonal Flu

H2N2

H3N2 Seasonal Flu

1918/19 1957/58 1968/6940-100 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)

Camp Funston, Kansas, March 1918: Sadly, the comparatively benign first wave was not at all predictive of what was to come

(John Barry. The Great Influenza.)

“In Philadelphia the number of dead quickly overwhelmed the city’s 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)

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)

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

SouthAfrica: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, in1919 only

British isles:249,000

(Also had some shift in deaths to younger adults in 1957 & 1968)

typical for seasonal flu

U.S. life expectancy dropped by 12 years

Modes of Person-to-Person Transmission:

1. Large droplets from coughing, sneezing, & talking, to other’s 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

Decent Understanding of Modes of Transmission Led to Non-Pharmaceutical InterventionsBut Guidance in the US was Inconsistent & Communities Made Very Different Decisions

Gunnison, Colorado

1 of 7 U.S. towns & residential institutions to escape the 2nd 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

(For SARS, Ro

= 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: R0 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.)

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.)

Tamiflu! (oral)

Ralenza (inhaled)

(Older drugs)

(Viral resistance to these is more common)

(Injectable Peramivir hascompleted phase-1 trials)

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.)

Pandemic Flu Prevention & Treatment Challenge

~2 day incubation period for seasonal flu is expected for pandemic flu also

High levels of virus, & someperson-to-person transmission,

1 day before symptoms!

Transmission up to 7 days after fever ends – longer inkids & immune suppressedPeak

transmission

Oseltamivir Therapy in H5N1 Thailand and Vietnam, 2004-2005

Oseltamivir Treatment Number Patients Number (%)

Survivors

Yes 25 6 (24%)

No 12 3 (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

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)

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 duckblood (& undercooked poultry?)

established in 1812 January 27, 2005 vol. 352 no. 4

Probable Person-to-Person Transmissionof 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)

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

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

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:

* 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 R0 < 1.0.)

(See notes below)

Current (~1950’s!) flu vaccine technology requires slow production in eggs *

* Recent progress in growth of virus in cell cultures instead of in eggs

(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

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 (& 21st Century?)

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.gov/plan/community/mitigation.html

)

(* see photos in Barry, The Great Influenza)

Excess pneumonia & flu mortality over 1913–1917 baseline in Philadelphia & St. Louis, Sep. 8–Dec. 28, 1918

NPIs 16 daysafter 1st case

NPIs 2 days after 1st case

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 Setting Seasonal Flu 1957 / 1968 1918 or Worse

Workplace/CommunityAdult social distancing

–decrease number of social contacts (e.g., encourage teleconferences, alternatives to face-to-face meetings)

Generally not recommended

Consider Recommend

–increase distance between persons (e.g., reduce density in public transit, workplace)

Generally not recommended

Consider Recommend

–modify, postpone, or cancel selected public gatherings to promote social distance (e.g., stadium events, theater performances)

Generally not recommended

Consider Recommend

–modify workplace schedules and practices (e.g., telework, staggered shifts)

Generally not recommended

Consider Recommend

Community Strategies by Pandemic Flu Severity (2)(http://www.pandemicflu.gov/plan/community/mitigation.html)

Pandemic Severity(Based Mostly on Case Fatality Ratio)

Interventions by Setting CFR < 0.1% 0.1% - <1% CFR = 1% +

Home

Voluntary isolation of ill at home (adults and children); combine with use of antiviral treatment as available and indicated

Recommend Recommend Recommend

Voluntary quarantine of household members in homes with ill persons (adults and children); consider combining with antiviral prophylaxis if effective, feasible, and quantities sufficient

Generally not recommended

Consider Recommend

School

Child social distancing–dismissal of students from schools and school-based activities, and closure of child care programs

Generally not recommended

Consider:≤ 4 weeks

Recommend:≤ 12 weeks

–reduce out-of-school contacts and community mixing

Generally not recommended

Consider:≤ 4 weeks

Recommend:≤ 12 weeks

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(See Danbury News,Oct. 1918, for details)

(Isolating the ill is also very important)

A Critical Gap in WHO & HHS Guidance

During the pandemic, most ill people will be cared for at home.

Woodson’s 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)

Pandemic influenza preparedness and mitigation in refugee and displaced populations

WHO training modules for humanitarian agencies

www.who.int/diseasecontrol_emergencies/training/influenza/en/

Module 5: Case ManagementObjectives:

A. How to manage patients at home

B. How to manage patients in facilities

C. What to stockpile

D. How to prioritize resources like antibiotics and antivirals

A Sobering Call to Action

“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 and preparedness as quickly as possible."

WHO Strategic Action Plan for Pandemic Influenza 2006–2007, page 4

“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.” (3/20/06)

---Mike Leavitt, US Secretary of Health and Human Services

Pandemic Planning Assumptions and Uncertainties

1. Another pandemic will occur

but we don’t know when

1. Approximately 20-40% of everyone on earth will become ill

but we can’t predict the severity CFR in seasonal flu: <0.1%

CFR in 1918 pandemic: ~2.2%

CFR with current H5N1: ~59%

Save the Children’s Pandemic Flu Preparedness Goals

1. Protect the health of SC staff and their families worldwide

Save the Children’s Pandemic Flu Preparedness Goals

2. Continue key agency functions

•Payroll

•Communications Technology

•Essential staff roles backfilled

•Human Resources

Save the Children’s Pandemic Flu Preparedness Goals

3. Protect the health and well-being of children and families

Preparedness Efforts

Oct 05 Influenza Working Group formed, 2 VPs assigned as co-leaders

Jan 06 Boston Summit, Pandemic Simulation exercise

Feb 2 HQ staff re-assigned to 50% LOE each

March Track I, Track II preparedness roll-out

Regular updates with SC President

Staff preparedness sessions begin

April/May Influenza Point Person (IPP) regional trainings

Preparedness Efforts

June Country Office Influenza plans submitted, reviewed

July Business Continuity Planning

August Agency-wide BCP finalized

Dec 90K distributed to country offices forpreparedness

Jan 07 external website live and regularly updated

Ongoing: staff preparedness sessions in headquarters and country offices