Transcript Calculation of High Risk Population and Potential Impacts

Alameda County
Influenza Update
Rosilyn Ryals, M.D.
Division of Communicable Disease
Control & Prevention
Alameda County Public Health Department
November 2005
Outline
Influenza
 The Pandemic Threat

What is Influenza?
Contagious, acute, febrile, respiratory
illness caused by viruses
 Epidemics of influenza occur during winter
months in temperate regions, like the U.S.
 Every year in the United states:

» 5 to 20% of the population get flu
» >200,000 people are hospitalized from flu
complications
» Approximately 36,000 people die from flu
(primarily high risk persons)
High Risk Population
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Adults >65 years
Children 6-23 months
Persons aged 2-64 yrs. with chronic lung, heart or
metabolic disorders:
- heart disease (ever diagnosed)
- asthma (taking medication)
- diabetes (ever diagnosed)
Persons with hemoglobinopathies or
immunosuppression
Children and adolescents on long-term aspirin
therapy
Women pregnant during influenza season
High Risk Population (continued)
Adults and children who have any condition that
can compromise respiratory function.
 Residents of nursing homes and other chronic-care
facilities
Plus those in close contact with high risk persons:
 Household members and out-of-home care givers
of infants under the age of 6 mos.
 Healthcare workers who provide direct, hands-on
care to patients
- ambulatory health care services
- hospitals
- nursing and residential care facilities

High Risk Group Impact on
Alameda County
Alameda County has a population of about
1.5 million people
 The high risk groups identified comprise
approximately 1/3 of the county population

High Risk Groups
2-64 - chronic
disease
36%
>=65
32%
HH w/ infants
12%
nursing homes
1%
HCW
6%
pregnant women
6%
6-23 mos.
7%
Symptoms of Influenza
Fever
 Headache
 Malaise
 Cough
 Sore Throat
 Runny or stuffy nose
 Myalgia
 GI symptoms (nausea, vomiting, and
diarrhea) – primarily in children

Influenza-Course
Incubation: 1-4 days, averagely 2 days
 Adults can be infectious from the day
before symptoms until about 5 days after
onset
 Children may be infectious > 10 days
 Severely immunocompromised persons may
shed virus for weeks or months
 Uncomplicated influenza illness typically
resolves in 3-7 days

Influenza- Complications
Pneumonia – usually secondary bacterial
 Dehydration
 Exacerbation of chronic conditions
 Sinus and ear infections (children)
 Febrile seizures in children

Biology of Influenza
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Influenza viruses belong to the family
Orthomyxoviridae
There are 3 distinct types of influenza: A, B and C
Influenza A and B are the two types that cause
epidemic human disease
Influenza A is further categorized into subtypes on
the basis of two surface antigens: hemagglutinin
(H) and neuraminidase (N)
Type A Influenza has 16 different Hs and 9
different Ns
Human disease with Influenza A has historically
been caused by three subtypes of H (H1, H2, and
H3) and two subtypes of N (N1 and N2)
Biology of Influenza (continued)


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All known subtypes of influenza A can be found in
birds
Influenza B viruses are not categorized into
subtypes.
Standard nomenclature for influenza viruses
includes: (1) Influenza type, (2) Place of initial
isolation, (3) Strain designation, and (4) Year of
isolation, and (5) H and N subtypes for Influenza
A. For example, influenza A isolated in a
California patient in 2004 would be written as:
A/California/7/2004 (H3N2)
Biology of Influenza (continued)
 Influenza A viruses
are the most
worrisome of all the well-established
infectious diseases:
» Mutate rapidly
» In addition to humans, they infect pigs, horses, sea
mammals, and birds
» They have a large number of subtypes maintained in
aquatic birds, providing a perpetual source of
viruses and a huge pool of genetic diversity
Biology of Influenza (continued)

Influenza A viruses are described as
“sloppy, capricious, and promiscuous”
because:
– They lack a proof-reading mechanism to detect and
correct small errors that occur when the viruses copy
themselves.
– This allows for constant stepwise changes in their
genetic makeup termed antigenic drift
– Though small, these slight variations keep populations
susceptible to infection (This explains need for a new
vaccine for each winter season)
Biology of Influenza (continued)
– The genetic content of influenza viruses is segmented
into 8 genes
– This facilitates the swapping of gene segments during
co-infection with hman and avian influenza viruses,
thereby creating a new virus subtype that will be
entirely or largely unfamiliar to the human immune
system.
– If this “novel strain” contains a mix of genes causing:
severe disease and allowing easy human-to-human
transmission, a pandemic is ignited. This is termed:
antigenic shift.
Biology of Influenza (continued)
Usually a single strain of influenza virus
prevails during an epidemic
 Occasionally, two different strains within a
single subtype (e.g. A/Victoria/3/75
(H3N2)or A/Texas/1/77 (H3N2) or two
different influenza A subtypes (H1N1 and
H3N2) may circulate simultaneously.

InfluenzaTransmission
Primarily transmitted person-to-person by
large virus-laden droplets (as generated by
cough or sneezing within 3 feet of
susceptible person)
 Direct or indirect contact with virus-laden
respiratory secretions followed by touching
the eyes, nose or mouth of a susceptible
person

Laboratory Diagnosis

It is difficult to diagnose based on clinical
symptoms alone. Similar symptoms can be
caused by other illnesses, e.g.
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Mycoplasma peumoniae
Adenovirus
Respiratory Syncytial Virus
Rhinovirus
Parainfluenza Viruses
Legionella
Laboratory Diagnosis
TEST
Time for Results
 Viral culture*
3-10 days
 Serology
>2 weeks
 Rapid antigen testing:
<30 minutes
 PCR
1-2 days
 Immunofluorescence assays 2-4 hours
*Only culture isolates can provide specific information:
circulating strains and subtypes
Prevention of Influenza
Inter-pandemic Period
VACCINATION
Inactivated Influenza Vaccine

Influenza vaccine can be given to people 6
months of age and older. It is recommended
for people who are at risk of serious
influenza or its complications, and for
people who can spread influenza to those at
high risk (including all household
members)
Live Attenuated Influenza
Vaccine
Live, attenuated influenza vaccine
(L.A.I.V.) was licensed in 2003. L.A.I.V.
contains live but attenuated (weakened)
influenza virus. It is sprayed into the
nostrils rather than injected into the muscle.
It is recommended for healthy children and
adults from 5 through 49 years of age, who
are not pregnant.
Recipients may shed virus.
Influenza Vaccination
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Influenza viruses are constantly changing.
Therefore, influenza vaccines are updated every
year, and annual vaccination is recommended.
For most people influenza vaccine prevents
serious illness caused by the influenza virus. It
will not prevent “influenza-like” illnesses caused
by other viruses.
It takes about 2 weeks for protection to develop
after vaccination, and protection can last up to a
year.
2005-2006 Influenza
Vaccine
•
Inactivated Influenza Vaccine
A/New Caledonia/20/99 (H1N1)
A/New York/55/2004 (H3N2)
B/Jiangsu/10/2003
•
Live attenuated Influenza Vaccine (LAIV)
A/New Caledonia/20/99 (H1N1)
A/California/7/2004 (H3N2)
B/Jiangstu/10/2003
Pneumococcal Vaccination
There are two licensed vaccines:
(1) Pneumococcal Conjugate Vaccine, and
(2) Pneumococcal Polysaccharide Vaccine.
 Recommendations for Pneumococcal
Vaccine include population at high risk
for influenza and its complications.

Prevention of Influenza
Antivirals
Antiviral therapy and
prophylaxis
Adamantine Derivatives:
(1) Amantadine
(2) Rimantadine
Neuraminidase Inhibitors:
(1) Zanamivir
(2) Oseltamivir (Tamiflu)
Antivirals for Treatment
Any person with life-threatening influenzarelated illness
 Any person at high-risk for serious
complications of influenza and who is
within the first 2 days of illness onset

Antivirals for Prophylaxis
All persons who live or work in institutions
caring for people at high risk of
complications from influenza should be
given antiviral medication in the event of an
institutional outbreak
 Persons at high risk of serious influenza
complications should be given antivirals if
they are likely to be exposed to others
infected with influenza.

Impacts of Antiviral Drug Therapy
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Adamantanes
– Reduce duration of illness (1 day)
– No studies on severity or complications
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Oseltamivir (neuraminidase inhibitors)
– Reduce duration of illness
– Pooled analysis of randomized controlled trials*
» Decreased hospitalization by 59% (p = .02)
» Decreased lower resp tract illness by 55% (p <.001)
» Decreased antibiotic use by 27% (P <.001)
*Kaiser, Arch Intern Med 2003
Prevention of Influenza
Infection Control
Infection Control
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Encourage annual Influenza vaccine for Health
Care workers
Use of Standard Precautions:
(1) Handwashing
(2) Gloves
(3) Mask, Eye Protection, Face Shield: when patient care
activities are likely to generate splashes or sprays
(4) Gown: protect skin and prevent soiling of clothing in patient
care activities that are likely to generate splashes or sprays
(5) Patient-Care Equipment
(6) Environmental Control
(7) Linen
(8) Occupational Health and Bloodborne Pathogens
(9) Patient Placement: private room or cohorting
Infection Control
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Droplet Precautions:
(1) Patient Placement: Private room; cohort; or maintain at least 3
feet spatial separation
(2) Mask: as per Standard precautions and when working within
3 feet of an infected patient
(3) Patient transport: limit to essential purposes only; minimize
dispersal of droplets by masking patient, if possible.
Infection Control
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Contact Precautions:
(1) Patient Placement
(2) Gloves and handwashing
(3) Gown
(4) Patient transport
(5) Patient-Care Equipment
Infection Control

Airborne Precautions (smaller particles than
respiratory droplets); may result from
procedures like endotracheal intubation,
suctioning, nebulizer treatment, or
bronchoscopy. These procedures can result
in dissemination of airborne droplets over
long distances; requires use of special airhandling and ventillation.
Infection Control
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Airborne Precautions (continued):
(1) Patient placement: negative air pressure with 6-12 air
exchanges per hour, and appropriate discharge of air
outdoors; keep door closed; can also cohort if private room
not available.
(2) Respiratory protection: wear an N95 respirator when entering
room
(3) Limit movement and transport of patient to essential purposes
If transport or movement is necessary, use mask for patient, if
possible.
Infection Control
In Doctor’s Offices and Clinics, in addition
to standard precautions and annual influenza
immunization of health care workers:
(1)
(2)
Encourage patients with respiratory and other symptoms consistent
with influenza to call in advance of coming in.
Encourage the use of masks by symptomatic patients or the use of
tissues to cover coughs/sneezes
Goals of Influenza Surveillance
in the U.S.
» Find out when and where influenza activity is
occurring
» Determine what type of influenza viruses are
circulating
» Detect changes in the influenza viruses
» Track influenza-related illness
» Measure the impact influenza is having on deaths in
the U.S.
U.S. Influenza Surveillance
System
(1) 75 WHO and 50 NREVSS Collaborating Labs
throughout U.S. report: # specimens tested, # positive
for influenza A or B
(2) U.S. Influenza Sentinel Providers Network: 1000
providers around the country report number of
persons seen, and number with influenza-like illness
by age group
(3) 122 Cities Mortality Reporting systems report # of
pneumonia or influenza deaths
(4) State and Territorial Epidemiologists report the level
of influenza activity in the state
(5) Influenza-associated pediatric mortality report labconfirmed influenza deaths in children <18 years old
U.S. Influenza Surveillance
System
(continued)
(6) Emerging Infections Program conducts surveillance for
lab-confirmed influenza-related hospitalizations in persons
less than 18 years of age in 57 counties throughout U.S.
(covering 10 states)
(7) New Vaccine Surveillance Network provides populationbased estimates of lab-confirmed influenza hospitalization
rates for children <5 years who live in 3 U.S.
counties(Ohio, Tennessee, and New York)
Pandemic Influenza: A
Harbinger of Things to Come
Pandemic Influenza
Worldwide outbreak of a novel strain
 Associated with high morbidity, excess
mortality, and social and economic
disruption
 First recorded pandemic that fits influenza
profile occurred in 1580

Pandemic Influenza in the 20th
Century

1918-19 Spanish Flu (H1N1)
» 20-50 million deaths worldwide
» >500,000 U.S. deaths
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1957-58 Asian Flu (H2N2)
» 70,000 U.S. deaths
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1968-69 Hong Kong Flu (H3N2)
» 50,000 U.S. deaths
Avian H5N1 in Asia
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Continuing presence in Asia since 1996
– Documented direct avian to human transmission, Hong
Kong,1997
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Enzootic and epizootic of unprecedented size and
complexity
– 9 countries with ongoing outbreaks (most recently in Malaysia)
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Ongoing human cases with high case fatality, mostly in
healthy children and young adults
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Ongoing evolution of the virus’ antigenic, genetic and
functional properties
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No sustained human to human transmission to date
Why are We Concerned?
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Increasing countries/areas with avian influenza
– Uncertainties on progress of control
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Ongoing human infection with avian H5N1
– Limited implementation of protective measures
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Co-Circulating human influenza viruses
– Risk of genetic reassortment leading to pandemic strain
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Majority of human population would have no
immunity
H5N1 resembles the 1918-19 pandemic influenza in
that healthy young persons are affected and a deadly
feature is a primary viral pneumonia.
Human Infections
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H5N1 - severe
–
–
–
–
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1997 Hong Kong: 18 cases; 6 deaths
2003 Hong Kong: 2 cases; 1 death
2004 Vietnam and Thailand: 40 cases; 29 deaths
2005 Hunan (China): 3 cases, 2 deaths
H9N2 - mild
– 1999 Hong Kong: 2 cases (mild)
– 2003 Hong Kong: 1 case (mild)
17 Human Cases
12 Deaths
94 Human Cases
42 Deaths
4 Human Cases
4 Deaths
4 Human case
3 Deaths
CIDRAP, 8/2005
Influenza H5N1: expanded host
range?
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Domestic poultry
Wild birds
– infected
– reservoir
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Humans
Swine (China)
Cats? (Netherlands)
The natural hosts of the
influenza A virus
People, Pigs and Poultry in China
1968
2004
People
790 million
1.3 billion
Pigs
5.2 million
508 million
12.3 million
13 billion
Poultry
Understanding Pandemic Influenza
• Recent studies in mice using genetically
engineered influenza strains similar to the
1918 H1N1 pandemic strain suggest that
macrophage activities with high levels of
cytokine production maybe a factor in the
lung and other organ damage (cytokine
storm). Kobasa et al; Nature 2004;431:703
• The clinical picture and epidemiology, as
well as current studies of H5N1 cases in
SE Asia suggest a similar “cytokine
storm” phenomena. Peiris et al; Lancet 2004;363:617
Requirements for a Pandemic
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Isolation from humans of a novel influenza A
virus
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Little or no immunity in the population
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Demonstrated ability of the virus to replicate
and cause disease
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Efficient person-to-person transmission
H5N1
All prerequisites met for start of pandemic
except efficient human-to-human transmission
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More pathogenic than most avian strains
– Progressively more pathogenic in poultry
– Larger number of animal species affected
Ducks are asymptomatic but excrete virus, so
sustainable reservoir
 Pigs shown to be infected in China
 Human cases concentrated in previously
healthy children and young adults
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National Level Command and
Control for Pandemic Influenza
Lead Departments:
Medical Response:
DHHS
Veterinary Response:
Dept. Agriculture
International Activities: State Department
Overall domestic incident management and
federal coordination is through the
Department of Homeland Security.
Criteria for success of initial control
Rapid identification of initial cluster
 Rapid case detection, isolation, and treatment
 Rapid prophylaxis of targeted population
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– Sufficient drug available
– No antiviral resistance
School and work closures
 Population cooperation with strategies
After 4-5 weeks, it will be impossible to contain

Containing an Initial Outbreak of
Novel Influenza – Can this be done?
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Hong Kong accomplished this in 1997
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2004 H5N1 situation much more challenging
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Large areas affected in a large number of countries
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Slow and incomplete reporting of H5N1 findings
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Poor public health infrastructure
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Complex political and economic situations
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International action required: support for antivirals
WHO phase of Pandemic Alert
Phase 1: Inter-pandemic phase: Low risk of human cases
Phase 2: New virus in animals, no human cases: Higher risk of human
cases
Phase 3: Pandemic Alert, New Virus causes human cases: No or very
limited human-to-human transmission
Phase 4: Pandemic Alert, New virus causes human cases: Evidence of
increased human-to-human transmission
Phase 5: Pandemic Alert, New virus causes human cases: Evidence of
significant human-to-human transmission
Phase 6: PANDEMIC: Efficient and sustained human-to-human
transmission
According to WHO, the world is presently in phase 3.
WHO Outbreak Control Measures
Pre pandemic
Pandemic
Phase 4
Phase 5
Phase 6
Yes
Yes
Yes
Symptomatic persons
Yes
Yes
Yes
Exposed persons
Consider
Consider
Consider
Persons seeking care
Yes
Yes
Yes
Tracing and follow up--contacts
Yes
Yes
No
Voluntary quarantine--healthy contacts
No
Yes
No
Antiviral Prophylaxis--Contacts
Yes
Yes
No
Voluntary home confinement of
symptomatic persons
Yes
Yes
Yes
Closure of schools
No
Consider
Consider
Population-wide measures (e.g. close
workplaces)
No
Consider
Consider
Confinement of cases
Face masks
U.S., State, and Local Control
Measures

Currently under development
Problems Anticipated in Surge
Capacity

Beds
– Emergency regulations, increase in beds in existing
facilities, alternative facilities, tents, home care
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Personnel
– Medical Reserve Corps; citizens volunteers; scope of
practice changes
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Equipment/Infection Control Supplies
Vaccine
Medications
Vaccine Crisis
• Current “standard” vaccine reflects 1950’s
technology
– grown in chicken eggs
– takes 6 months or more to produce
– use of “reverse genetics” to develop prototype
vaccine virus
• Need an immediate and comprehensive
international program to develop a cell
culture system for vaccine production with
surge capacity
Influenza Vaccine Crisis
• Current annual international capacity for
influenza vaccine production using egg
culture is approximately 300 million trivalent
doses (900 million monovalent)
• Almost all of the world’s influenza vaccine is
produced in nine countries (12% of the
world’s population)
• Production capacity will NOT increase
significantly in the next several years
• New and more timely methods for
production are desperately needed and
Prototype Vaccine
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Hungary has developed and tested a H5N1
vaccine on 150 persons
Claims it is effective “beyond doubt”
Set to be approved by European Medicines
Agency
Sold at $5-6 per dose
Ready to begin production
LIMITATION: In that vaccine must be developed
based upon pandemic strain
Advisory Committee Recommendation for
Vaccine
 Federal
government should purchase all
influenza vaccine during a pandemic
H5N1 Vaccine for U.S. Stockpile
Sanofi Pasteur $100 million for H5N1
vaccine
 Chiron 10,000 doses for testing
 HHS plans to buy vaccine for 20 million
 MedImmune developing multiple subtypes

Antiviral Stockpile (oseltamivir)
Recommedations of Advisory Group

40 million courses minimum
– 133 million courses to treat all infected and prophylaxis
HCWs and patients at highest risk of infection
Status of Antivirals for U.S. Stockpile
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Currently 2 million courses of Tamiflu
Orders for 6 million courses
Plans for 20 million courses
GlaxoSmithKline $2.8 million for 84,300 treatment courses
of zanamivir (Relenza)
Request for funds to cover up to 50% of population
Antivirals – Not A Panacea
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Global production capacity limited; high cost
Ability to use antivirals to limit spread depends on
rapid case detection and contact tracing
Need to start treatment early
Effectiveness on serious illnesses and mortality
unknown
Prophylaxis may require ongoing use for 6 weeks or
longer
Antiviral resistance and side effects may limit use
Tamiflu produced outside of U.S.
Ten Things to Know About
Pandemic Influenza
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Pandemic Influenza is different from Avian Influenza
Influenza pandemics are recurring events
The world may be on the brink of another pandemic
All countries will be affected
Widespread illness will occur
Medical supplies will be inadequate
Large numbers of deaths will occur
Economic and social disruption will be great
Every country must be prepared
WHO will alert the world when the pandemic threat
increases
For the first time mankind is
watching a potential pandemic
unfolding.
World Health Organization