Transcript SARS Severe Acute Respiratory Syndrome

Avian Influenza
Shoreland, Inc.
April 2006
Taipei ‘Wet Market’
China--Backyard Farms
Pandemic Influenza
• Next pandemic inevitable in the near term
– Wide agreement by WHO, CDC, others
– Current H5N1 “bird flu” or another strain
• Worldwide spread within 2-3 months possible
• Initial quarantine may close borders for weeks to months
• Highly contagious
– Humans have no immunity to new strains
• Vaccine availability will lag by months
– Insufficient anti-viral drugs currently available
• Significant mortality
– 1% of world’s population (30 million) died in 1918 pandemic
– 1-2 million died in 1957 & 1968 pandemics
– Similar mortality possible if no effective intervention
H5N1: Confirmed Cases
in Humans, Wild Birds, & Poultry
(April 4, 2006)
H5N1: Confirmed Cases in Humans
192 cases / 109 deaths
WHO counts only lab-confirmed cases
The 2 Mechanisms Whereby Pandemic Influenza
Originates
WHO Pandemic Phases
• Inter-Pandemic Period
– Phase 1: Animal virus present; no human transmission
– Phase 2: Animal virus with features posing risk of human transmission
• Pandemic Alert Period
– Phase 3: Human infection through animal contact but no human-to-human spread (rarely,
spread to a close contact)
– Phase 4: Small clusters of limited human-to-human transmission; highly localized
– Phase 5: Larger clusters of human-to-human transmission but still localized
• Pandemic Period
– Phase 6: Worldwide human-to-human infection; increased and sustained transmission in
general population
Terminology: Pathogenic Avian Serotypes
(defined according to disease caused in birds)
• Influenza A has many subtypes, classified according to 16 “H” and 9
“N” proteins
• Poultry cases
– H5 (generally highly pathogenic)
– H7 (high or low pathogenic varies by strain)
– H9 (always low pathogenic)
• Human cases
– H5 (generally severe)
– H7 (mild disease even if highly pathogenic in birds)
– H9 (mild disease; only 3 cases documented)
Avian Influenza A (H5N1)
• Occurs primarily in poultry, waterfowl, or other birds
• Mammals are susceptible to infection--ingested chicken
– Become ill and die
– Thus far don’t serve as natural carriers
– 2004: pigs (China); tigers & domestic cats (Thailand)
– 2006: domestic cat, stone marten (Germany)
• Emerged in Asia sometime before 1997 in poultry
• 1997 - Mutated into highly pathogenic form
– Infected 18 humans (6 deaths) in Hong Kong
• 2003 - Re-emerged in poultry
– Mutated slightly to “Z” strain
• Current wave of bird to human cases since Dec. ‘03
Reasons for Concern for Pandemic H5N1
• H5N1 can infect many avian and animal species
– Facilitates geographic spread
• Recombination event is not necessary for a pandemic
– 1918 strain pure avian virus that underwent ~10 spontaneous mutations, became infective for humans,
and was exceptionally virulent
– Several similar mutations present in currently circulating H5N1 virus
– NS1 gene possible virulence factor:
one variant of a specific NS1 gene present in all AI isolates
(plus 1918 strain), but no human influenza A
H5N1 Outbreaks in Birds
Countries with H5N1 Outbreaks in 2005-06
Asia
Cambodia
China *
Hong Kong
Indonesia
India
Kazakhstan
Malaysia
Mongolia
Pakistan (H5)
Russia
Thailand
Viet Nam
Georgia**
Burma (Myanmar)
Africa
Cameroon
Egypt
Niger
Nigeria
Burkina Faso
Mid-East
Azerbaijan
Iran**
Iraq
Israel
Jordan
Turkey
Europe
Albania
Austria **
Bosnia & Herzegovina **
Bulgaria **
Croatia
Denmark
France
Germany
Greece**
Hungary
Italy**
Poland**
Romania
Serbia & Montenegro
Slovakia
Slovenia **
Sweden
Switzerland**
Ukraine
United Kingdom**
* Cases were reported in birds in the following provinces or autonomous regions during 2005 and/or 2006: Anhui, Guizhou, Hubei, Hunan, Inner Mongolia, Jiangxi, Liaoning, Ningxia, Qinghai, Shanxi, Sichuan, Xinjiang, Xizang (Tibet),
and Yunnan.
† H5 confirmed in poultry with further tests pending; however 1 human case has been confirmed as H5N1.
‡
Affected birds exclusively wild/migratory species to date.
Countries with outbreaks in 2003 and/or 2004 but not in 2005-06: Japan, Korea, Laos
Transmission
• Spread by domestic ducks, poultry, wild migratory birds
• Transmitted bird to human through:
– Direct contact with sick / infected birds
– Surfaces contaminated with droppings, respiratory secretions, ocular
secretions
– Possibly: eating under-cooked eggs & poultry, duck blood
• Human-to-human transmission non-existent or rare with existing
H5N1 strain
• Incubation period unknown -- 2-8 days
– Pandemic virus (after human adaptation) likely 1-4 days
Transmission (cont’d)
• Mainly large droplet spread
– 3 feet
– Emphasis on social distancing
• Environmental contact (H5N1 viruses can survive for up to 6 days)
• Airborne transmission possible?
– Isolate first cases with airborne precautions
• Infectious period
– 1 day before onset of symptoms to 5 days after in adults and 3 weeks in young children
– Big contrast to SARS
• Seasonally unclear; winter may be still be higher
H5N1 Clinical -- Symptoms
• Initially cannot differentiate from other cases of severe influenza
• Presents with fever and influenza-like symptoms, cough, sore throat, rhinitis,
muscle aches, headache
• Conjunctivitis
• Rapid onset of viral pneumonia, ARDS
– H5N1 mouse studies indicate diffuse extrapulmonary involvement, macrophage activation,
cytokine storm effect
• Severest mortality in young adults
• Other symptoms, e.g., severe diarrhea, encephalitis, etc. (see notes)
Use of Antivirals
• Stand-by treatment
– For use (after medical consultation) after becoming ill in an
outbreak situation
• Dosing as per treatment regimen on “Treatment of Avian Influenza” slide
• Prophylaxis
– In an outbreak situation, antivirals to be taken as instructed before
becoming ill
Types of Antivirals
• Oseltamivir (Tamiflu) -- recommended
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Active against H5N1 in vitro and likely effective in vivo (mice)
Shelf life: at least 5 years
Supplies limited; not currently in retail stores
Until this year 2 million doses per year
U.S. current stockpile of antiviral drugs: 5.5 million treatment courses
– an additional 12.4 million treatment courses of Tamiflu and 1.75 million treatment courses of Relenza
due by Sept 2006
– ? production issues
• Zanamivir (Relenza) -- may also be effective
• Taken via inhalation - less convenient to use
• Amantadine, rimantadine: H5N1 is resistant to these drugs
Treatment of Avian Influenza
• Need to start antiviral treatment in first 48 hours
– Reduce mortality / complications
• Non-severe cases
– 75 mg oseltamivir (Tamiflu) po bid for 5 days
• 2 Vietnamese cases with oseltamivir-resistant mutation developing during therapy with death.
– Higher dosing may be necessary
– Resistant virus not necessarily infectious
OR
– 10 mg zanamivir (Relenza) inhaled bid for 5 days
• Almost none currently available
• Severe cases
– 150 mg oseltamivir po bid for 7-10 days
– Consider adding inhaled zanamivir (Relenza)
– Consider po/IV ribavirin
Prophylaxis of Avian Influenza
• Oseltamivir 75 mg po once daily during period of exposure and for 710 days after last exposure
– If staying in an area of on-going epidemic with no vaccine available, this
could mean taking prophylaxis for 2 months or longer.
• Prophylaxis of general public not in current HHS plan
Prevention for the Traveler:
Pre-travel
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Check for any travel restrictions
Prohibit travel with a fever to/from H5N1 areas
Educate & provide handout on avian influenza
Provide travel health kit
Supply antivirals (e.g., oseltamivir) if traveling to H5N1-affected area (Freedman DO,
Leder K. J Trav Med 2005; 12: 36-44)
• Vaccinate with conventional influenza vaccine
– Does not protect against H5N1 but may decrease chance of confusing human
influenza with H5N1
• Identify in-country health care resources
Education: Preventive Measures During Travel
• Avoid contact with birds, animal markets / farms, bird droppings or secretions,
and potentially contaminated surfaces
• Frequent thorough hand washing
– Carry and use alcohol hand sanitizer / wipes
– Need for paper towels in washrooms
– After shaking hands
• Ingestion of eggs and poultry that are well cooked
• Good respiratory hygiene
– When possible, change of airplane seats to avoid travelers with respiratory symptoms; masks
when appropriate
• Seek early medical consultation for any fever or influenza-like symptoms during
or after travel to H5N1 areas
Travel Kit for H5N1 Areas
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First aid and medical supplies
Oral thermometer and probe covers
Household disinfectant
Disposable gloves and plastic storage bags
Alcohol-based wipes / hand sanitizer
Masks (2- or 3-ply surgical, N95, others)
Consider antivirals (e.g., oseltamivir)
Masks
• Surgical masks 2- or 3-ply
• Benefit controversial but may be cultural mandate
• N-95 masks
• Fit testing required; some limitations but may be good stand-by protection and useful on
airplanes
• N-95 or N-100 with exhalation valve
• Alternative to N-95
• Exhalation valve increases comfort, temperature, and “wetness” of mask
• May be difficult to ensure compliance unless high risk exists
Employees/Visitors After Return from H5N1 Areas
• Employees/visitors with fever or respiratory illness < 10 days
from H5N1-affected area should inform appropriate contact
point by telephone and have their illness assessed by the
corporate or other health care provider before going into the
workplace
Pandemic Planning Assumptions
• Two or more waves in same year or in successive flu seasons
• Second wave may occur 3-9 months later; may be more serious
than first (seen in 1918)
• Each wave lasts about 6 weeks in a given community
30% Attack Rate; 10% of Workforce
Community-based Containment Measures
• Slow spread locally; allow for preparation
• Slow spread to other communities
• Local containment plan
– Care, food, services to the isolated or quarantined
– Legal preparedness
– Flu/fever clinics hotlines
• Community communication & cooperation
– Voluntary quarantine can work
Pandemic Public Health Measures
• Respiratory etiquette
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Cover mouth/nose with sneeze/cough
Use tissues
Dispose of tissues
Immediate hand hygiene
• Avoid large gatherings
• Surgical masks in public controversial
– Social distancing (3 feet) more effective
• Symptomatic individuals to wear masks
• Snow days; Closure of public places
– “Cordon sanitaire”
Avian Vaccines - Poultry
• Avian vaccines used in poultry
– Used extensively in several locales, including China
– Feb 2004 to Jan 2005: China inoculated 2.68 billion birds
• Not currently thought to be an effective control measure
Avian Vaccines - Human
Human monovalent H5N1-only vaccines undergoing trials in U.S. and elsewhere
– Sanofi: 2 doses were needed at 90 µg given 1 month apart--only 50% of subjects protected (seasonal flu vaccine
contains 15 µg)
– GSK: Human trials have begun in Europe with low antigen content vaccines with adjuvants
– 8 million H5N1 doses on hand by 2/06 (4 million people)
– NIH long-term project (MedImmune) to develop seed virus strains against all known H types, including H5N1
• Egg technology: Long time-line (3-6 months) for additional doses once decision made, current capacity 5
million doses / month
• Cell culture techniques; new investment, several years off
• Priority plans: HCWs at top
– 50% of the population that are healthy and 2-64 years at bottom
• Current flu vaccines do NOT include avian strains and offer no partial or cross-protection
Eliminate pandemic virus strain at source?
• Recent mathematical models of massive antiviral administration in a
localized epidemic situation
• “Ring eradication” feasible if:
– Low to moderate transmissibility (R0 < 1.8)
– Chemoprophylaxis of 90% of population within 1-3 weeks
• 1-3 million courses of oseltamivir needed
– Movement restrictions; high compliance
Recombined pandemic H5N1 strain vs. SARS
• Much more explosively contagious than SARS
– Airborne spread
– Easy in-flight spread compared to SARS
• More difficult to contain with simple quarantine measures than SARS
• Will still more rapidly lead to definitive international travel
prohibition
• May not be seasonal