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JIT: The Impact of Pandemic Influenza on Public Health

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Sneezing generates particles. of varying sizes. 10-100 m. Chotani, GIDSAS ... droplets that may become aerosolized when people sneeze, cough, laugh, or exhale. ... – PowerPoint PPT presentation

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Title: JIT: The Impact of Pandemic Influenza on Public Health


1
JIT The Impact of Pandemic Influenza on Public
Health
Rashid A. Chotani, MD, MPH Director, Global
Infectious Disease Surveillance Alert
System Johns Hopkins Bloomberg School of Public
Health 410-502-3116/410-322-7469 rchotani_at_jhsph.ed
u
2
Part I Basics
3
Influenza Virus
  • RNA, enveloped
  • Viral family Orthomyxoviridae
  • Size
  • 80-200nm or .08 0.12 µm (micron) in diameter
  • Three types
  • A, B, C
  • Surface antigens
  • H (haemaglutinin)
  • N (neuraminidase)

Credit L. Stammard, 1995
4
Influenza Virion
5
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6
The Burden of Influenza
  • Seasonal Influenza
  • Globally 250,000 to 500,000 deaths per year
  • In the US (per year)
  • 35,000 deaths
  • gt200,000 Hospitalizations
  • 37.5 billion in economic cost (influenza
    pneumonia)
  • Pandemic Influenza
  • An ever present threat

7
Contagiousness
  • Influenza is a highly contagious disease
  • Typical incubation 2 days (range 1-4 days)
  • Individuals are contagious for 1 to 4 days before
    the onset of symptoms and about 5 days after the
    first symptoms
  • Peak viral shedding - first 3 days of illness
  • Subsides usually by 5-7th day in adults
  • can be 10 days in children
  • Approximately 50 of infected people do not
    present any symptoms but are still contagious

8
Spread of Influenza
  • Most human influenza infections are spread by
    virus-laden respiratory droplets that are
    expelled during coughing and sneezing.
  • Influenza viruses range in size from 0.08 to 0.12
    µm.
  • They are carried in respiratory
  • secretions as small-particle
  • aerosols (particle sized lt10µm).
  • Sneezing generates particles
  • of varying sizes
  • 10-100 µm

9
Modes of Transmission
  • The 3 modes of transmission include
  • Droplet transmission
  • Airborne transmission, and
  • Contact transmission

10
Droplet Transmission
  • Droplet transmission occurs when contagious
    droplets produced by the infected host through
    coughing or sneezing are propelled a short
    distance and come into contact with another
    persons
  • conjunctiva,
  • mouth, or
  • nasal mucosa.

11
Airborne Transmission
  • Airborne transmission occurs when viruses travel
    on dust particles or on small respiratory
    droplets that may become aerosolized when people
    sneeze, cough, laugh, or exhale.
  • They can be suspended in the air much like
    invisible smoke.
  • They can travel on air currents over considerable
    distances.
  • With airborne transmission, direct contact with
    someone who is infected is not necessary to
    become ill.

12
Contact Transmission
  • Two Types
  • Direct involves body-to-body surface contact
  • Indirect occurs via contact with contaminated
    intermediate objects, such as contaminated hands,
    or inanimate objects (fomites), such as
    countertops, door knobs, telephones, towels,
    money, clothing, dishes, books, needles etc.

13
Survival of Influenza Virus on Surfaces
  • Hard non-porous surfaces 24-48 hours
  • Plastic, stainless steel
  • Recoverable for gt 24 hours
  • Transferable to hands up to 24 hours
  • Cloth, paper tissue
  • Recoverable for 8-12 hours
  • Transferable to hands 15 minutes
  • Viable on hands lt5 minutes only at high viral
    titers
  • Potential for indirect contact transmission
  • Humidity 35-40, temperature 28C (82F)

Source Bean B, et al. JID 198214647-51
14
Affects of humidity on infectivity influenza,
Loosli et al, 1943
15
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16
Definitions
  • Epidemic a located cluster of cases
  • Pandemic worldwide epidemic
  • Antigenic drift
  • Changes in proteins by genetic point mutation
    selection
  • Ongoing and basis for change in vaccine each year
  • Antigenic shift
  • Changes in proteins through genetic reassortment
  • Produces different viruses not covered by annual
    vaccine

17
Reassortment (in humans)
Migratory water birds
Source WHO/WPRO
18
Reassortment (in pigs)
Migratory water birds
Source WHO/WPRO
19
Mutation (in humans)
Source WHO/WPRO
20
From birds to humans
Migratory water birds
  • Hong Kong, SAR China 1997, H5N1
  • Hong Kong, SAR China 1999, H9N2
  • The Netherlands 2003, H7N7
  • Hong Kong, SAR China 2003, H5N1

Source WHO/WPRO
21
Part II History
22
Spanish Flu A(H1N1) 1918-19
Approximately 20-40 million people died
worldwide, and over 500,000 in US.
23
The big pandemic of 1918
24
Images from the 1918 Influenza Epidemic National
Museum of Heath and Medicine
25
The big pandemic of 1918
26
Images from the 1918 Influenza Epidemic National
Museum of Heath and Medicine
27
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28
Asian Flu A(H2N2) 1957-58
During the 1957-58 Asian flu epidemic, a school
child in Islington, London, gargles to keep the
virus at bay. More than a million people died
worldwide and about 70,000 in US.
29
Spread of H2N2 Influenza in 1957 Asian Influenza
30
Hong Kong Flu A(H3N2)1968-69
Members of the Red Guard in China covered their
mouths against flu germs in 1968 on the orders of
Chairman Mao. The Hong Kong flu of 1968-69
killed more than 1 million people worldwide, and
34,000 in US.
31
Timeline of Emergence of Influenza A Viruses in
Humans
Avian Influenza
H7
H9
H5
Russian Influenza
H5
H1
H3
H2
H1
1918
1957
1968
1977
1997
2003
1998/9
Spanish Influenza H1N1
Asian Influenza H2N2
Hong Kong Influenza H3N2
32
Recorded Influenza Pandemics
33
Part III H5N1 Avian Outbreaksfrom July 2004
34
Current Pandemic Concerns
35
Countries Reporting Confirmed Occurrence of H5N1
Influenza in Poultry and Wild Birds Since 2003
As of May 30, 2006. Source WHO/WPRO
36
Countries Reporting Confirmed Occurrence of H5N1
Influenza in Poultry and Wild Birds Since 2006
As of May 30, 2006. Source WHO/WPRO
37
In Cats???
  • 7 March 2006, Rome Following the finding of the
    H5N1 avian influenza virus in a dead cat on the
    island of Rügen in Germany, the European
    Commission has advised its member states to take
    specific measures regarding cats and dogs in the
    infected areas. The general public and cat owners
    especially have increasingly shown concern and
    are consulting veterinarians for advise.

38
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39
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40
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41
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42
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43
Dept of Health and Human Services
www.pandemicflu.gov
44


45
Current Pandemic Concerns
46
Current Pandemic Concerns
47
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48
Part IV H5N1 Human Outbreaks
49
Avian Influenza A(H5N1), 1997
Avian Influenza A(H5N1) caused 18 cases of
influenza with 6 deaths in the Hong Kong area.
Experts are concerned that the virus may acquire
a mutation encouraging human-to-human
transmission.
50
The H5N1 Influenza Pandemic Threat
  • Avian infection in 9
  • countries
  • 34 human cases and
  • 23 deaths (68)
  • Culled gt100 m
  • chickens
  • Avian infection in
  • Hong Kong
  • 18 human cases and
  • 6 deaths (33)
  • Culled poultry
  • Avian infection in 4
  • countries
  • 7 human cases and
  • 6 deaths (86)
  • Person-to-person?
  • Ongoing avian H5N1 infections

2003
2004
1997
1998
1999
2000
2001
2002
51
Affected Countries with Confirmed Human Cases of
H5N1 Influenza since 2003
As of May 24, 2006. Source WHO/WPRO
52
Affected Countries with Confirmed Human Cases of
H5N1 Influenza since 2006
As of May 24, 2006. Source WHO/WPRO
53
Geographic Location of the North Sumatra Cluster
and cases Confirmed on May 29, Indonesia, 2006
54
Cumulative Number of Confirmed Human Cases of
Avian Influenza A/(H5N1) since 26 December 2003
to 24 May 2006
Source WHO
As of May 24, 2006.
55
Cumulative Number of Confirmed Human Cases of
Avian Influenza A/(H5N1) since 26 December 2003
to 24 May 2006
Mortality 43
Mortality 65
Mortality 70
Mortality 100
Source WHO
As of May 24, 2006.
56
Cumulative Number of Confirmed Human Cases of
Avian Influenza A/(H5N1) since 26 December 2003
to 24 May 2006
Source WHO
As of May 24, 2006.
57
Avian Human H5N1 Identified in No. of Countries
(Since 26 December 2003 to 24 May 2006)
Source WHO
As of April 24, 2006.
58
Nations With Confirmed Cases H5N1 Avian
Influenza (May 19, 2006)
Dept of Health and Human Services
www.pandemicflu.gov
59
Part V Interventions
60
WHO Global Influenza Surveillance Network
Makes recommendations on influenza vaccine
formulation
Serologic Studies National Licensing Agencies
Antigenic Genetic Analysis WHO CC
Diagnostic Reagents Vaccine Strains Potency
Testing Reagents
Isolation of Representative Strain from Clinical
Sample National Influenza Centers
Disease Epidemiology Data
Source WHO Global Influenza Program
61
Influenza Vaccine Development
Source WHO Global Influenza Program
62
Influenza Pandemic Vaccine
Lag between pandemic strain detection and full
scale vaccine production
Optimistic Projection
Today
Clinical batch production Testing 1-2
months????
Vaccine Prototype Development 1-2 months
2
4
6
0
Months
Source WHO Global Influenza Program
63
Key bottlenecks
  • Purity of strain
  • Production requirements
  • Production system EGG
  • Biosecurity
  • Clinical data allowing increase in vaccine
    availability

Reverse genetics
Clinical data allowing increase in vaccine
availability
Clinical Trials
Source WHO Global Influenza Program
64
Vaccine Production Capacity
Source WHO Global Influenza Program
65
Vaccine Consumption - 2000
Source WHO Global Influenza Program
66
Vaccine
  • Challenges
  • H5 HA is poorly immunogenic as compared to H3N2
    or H1N1 viruses
  • To date vaccines against H5 have required 2 doses
    or an adjuvant to induce necessary level of
    neutralizing antibodies
  • Influenza virus has a high error rate making it
    evolve continuously
  • There are already two clades of HPAI H5N1 virus
    circulating
  • Manufacturing capacity is limited and licensing
    requirements are stringent

67
Vaccine
  • September 16, 2005 HHS
  • News Headlines
  • US DHHS buying 100 million of avian vaccine
  • Vaccine has not been approved by FDA
  • Proper dosage being determined
  • Protection for 2 to 20 million Americans

68
Vaccine
  • Inactivated vaccine candidate
  • Sanofi Pasture has developed an unadjuvanted,
    inactivated H5N1 vaccine candidate
  • Prospective, randomized, double-blind trials
    (450 adults, 18-64 years) established the need
    for two doses (neutralizing titer 140)
  • Now being tested in children and elderly
  • Live, attenuated vaccine candidate
  • MedImmune will develop (under US contract) will
    develop at least one vaccine for each of the 16
    HA
  • Candidate vaccine has been developed for H5 H9
    (phase 1 clinical trials)

69
Vaccine
  • Sanofi Pasture has developed an unadjuvanted,
    inactivated H5N1 (virus isolated in Southeast
    Asia in 2004) vaccine candidate. Reported in NEJM
  • The higher the dosage of vaccine, the greater the
    antibody response produced.
  • Of the 99 people evaluated in the 90-mcg,
    high-dose group, 54 percent achieved a
    neutralizing antibody response to the vaccine at
    serum dilutions of 140 or greater
  • Only 22 percent of the 100 people evaluated who
    received the 15-mcg dose developed a similar
    response to the vaccine.
  • Generally, all dosages of the vaccine appeared to
    be well tolerated
  • Almost all reported side effects were mild
  • The second dose of vaccine did not cause more
    local or systemic symptoms than the first
  • Systemic complaints of fever, malaise, muscle
    aches, headaches and nausea occurred with the
    same frequency in all dosage groups as in the
    placebo group
  • Lab tests did not reveal any clinically
    significant abnormalities

70
Vaccine
  • A new genetically engineered vaccine created by
    scientists at the CDC, is egg-independent and
    adjuvant-independent.
  • Hoelscher MA at al. Lancet. 2006 Feb
    11367(9509)475-81.
  • A similar vaccine, adenovirus-based influenza A
    virus vaccine directed against the hemagglutinin
    (HA) protein of the A/Vietnam/1203/2004 (H5N1)
    (VN/1203/04) strain isolated during the lethal
    human outbreak in Vietnam from 2003 to 2005.
  • Gao W et al. Protection of mice and poultry from
    lethal H5N1 avian influenza virus through
    adenovirus-based immunization. J Virol. 2006
    Feb80(4)1959-64.

71
Chemotherapy
  • Prevent membrane fusion (M2 Inhibitors)
  • Amantidine (Symmetrel)
  • Remantidine (Flumadine)
  • Neuraminidase inhibitors
  • Zanamivir (Relenza)
  • US buying 2.8 million (could treat 84,300
    people)
  • Oseltamivir (Tamiflu)
  • Peramivir (more potent in vitro)???

72
Chemotherapy
  • Relenza
  • Reduced the incidence of the disease in both
    young and older populations
  • First Study In participants 18 years of age or
    older, the proportion of people who developed
    symptoms confirmed to be flu was 6.1 for the
    placebo group and 2.0 for the Relenza group.
  • The second community study enrolled people 12 to
    94 years of age (56 of whom were older than 65
    years).
  • In this trial, the percent of people who
    developed symptoms confirmed to be flu were
    reduced from 1.4 of the participants on placebo
    to 0.2 for those who used Relenza.

73
Types of protective masks
  • Surgical masks
  • Easily available and commonly used for routine
    surgical and examination procedures
  • High-filtration respiratory mask
  • Special microstructure filter disc to flush out
    particles bigger than 0.3 micron. These masks are
    further classified oil proof oil resistant
    not resistant to oil
  • The more a mask is resistant to oil, the better
    it is
  • The masks have numbers beside them that indicate
    their filtration efficiency. For example, a N95
    mask has 95 efficiency in filtering out
    particles greater than 0.3 micron under normal
    rate of respiration.
  • The next generation of masks are called
    Nanomasks. These boast of latest technologies
    like 2H filtration and nanotechnology, which are
    capable of blocking particles as small as 0.027
    micron.

74
Food Safety
  • Conventional cooking (temperatures at or above
    70C in all parts of a food item) will inactivate
    the H5N1 virus.
  • Properly cooked poultry meat is therefore safe to
    consume.
  • The H5N1 virus, if present in poultry meat, is
    not killed by refrigeration or freezing.
  • Home slaughtering and preparation of sick or dead
    poultry for food is hazardous this practice must
    be stopped.
  • Eggs can contain H5N1 virus both on the outside
    (shell) and the inside (whites and yolk). Eggs
    from areas with H5N1 outbreaks in poultry should
    not be consumed raw or partially cooked (runny
    yolk) uncooked eggs should not be used in foods
    that will not be cooked, baked or heat-treated in
    other ways.
  • There is no epidemiological evidence to indicate
    that people have been infected with the H5N1
    virus following consumption of properly cooked
    poultry or eggs.
  • The greatest risk of exposure to the virus is
    through the handling and slaughter of live
    infected poultry.
  • Good hygiene practices are essential during
    slaughter and post- slaughter handling to prevent
    exposure via raw poultry meat or cross
    contamination from poultry to other foods, food
    preparation surfaces or equipment

75
Survival of Influenza Virus on Surfaces
  • (WHO) recommends that environmental surfaces be
    cleaned by
  • disinfectants such as Sodium hypochloride 1
    in-use dilution, 5 solution to be diluted 15 in
    clean water for materials contaminated with blood
    and body fluids
  • bleaching powder 7 gram/liter with 70 available
    chlorine for toilets and bathrooms and
  • 70 alcohol for smooth surfaces, tabletops and
    other surfaces where bleach cannot be used.
  • Environmental cleaning must be done on a daily
    basis.

Source World Health Organization. Highly
pathogenic avian influenza (HPAI) Interim
infection control guidelines for health care
facilities.
76
New laboratory test
  • The FDA has approved a new laboratory test
    developed by the CDC to diagnose H5 strains of
    influenza in patients suspected to be infected
    with the virus.
  • The product the Influenza A/H5 (Asian lineage)
    Virus Real-time RT-PCR Primer and Probe Set
    provides preliminary results on suspected H5
    influenza samples within four hours once a sample
    is tested.
  • If the presence of the H5 strain is identified,
    then further testing is conducted to identify the
    subtype.
  • If clinicians suspect a patient may be infected
    with an avian influenza virus, they should
    contact their state or local health department.
  • For more information
  • CDC. New laboratory assay for diagnostic testing
    of avian influenza A/H5 (Asian lineage). MMWR.
    200655(RR5)127.

77
Part VI Where are we ..
78
CURRENT WHO PHASE of PANDEMIC ALERT
Inter-Pandemic Phase New Virus in Animals, NO Human Cases Low Risk of Human Cases 1
Inter-Pandemic Phase New Virus in Animals, NO Human Cases High Risk of Human Cases 2
Pandemic ALERT New Virus Causes Human Cases No or Very Limited Human-to-Human Transmission 3
Pandemic ALERT New Virus Causes Human Cases Evidence of Increased Human-to-Human Transmission 4
Pandemic ALERT New Virus Causes Human Cases Evidence of Significant Human-to-Human Transmission 5
PANDEMIC Efficient Sustained Human-to-Human Transmission 6
WHO May 23 reported a cluster of 8 individuals
(Sumatra is ) of one extended family raising
questions of potential Human-to-Human transmission
Source WHO Global Influenza Program
79
THE NEXT PANDEMIC?
  • Potential impact of next pandemic (CDC)
  • 2-7.4 million deaths globally
  • In high income countries
  • 134-233 million outpatient visits
  • 1.5-5.2 million hospitalizations
  • 25 increase demand for ICU beds, ventilators,
    etc.

80
Planning Assumptions US Healthcare
  • 50 or more of those who become sick will seek
    medical care
  • Number of hospitalization and deaths will depend
    upon the virulence of the pandemic virus

Moderate (1957-like) Severe (1918-like)
Illness 90 million (30) 90 million (30)
Outpatient medical care 45 million (50) 45 million (50)
Hospitalization 865,000 9,900,000
ICU care 128,750 1,485,000
Mechanical ventilation 64,875 745,500
Deaths 209,000 1,903,000
81
What Needs to be Done?
  • Surveillance
  • Culling
  • Domestic poultry vaccine issues
  • Quarantine
  • Ring??
  • Vaccination against circulating flu
  • H5N1 vaccine development
  • Stockpiling of antivirals
  • Quicker laboratory testing
  • Stringent infection control practices
  • Handwashing Disinfection, Masks etc
  • Masks
  • Education
  • Vaccination, antivirals, masks, food safety,
    handwashing, disinfection, etc
  • Coordination
  • Through planning preparedness

82
US Pandemic Influenza Plan Funding 2006
Appropriations HHS Allocations (3.3B)
Dollars in Millions
Dept of Health and Human Services
www.pandemicflu.gov
83
Take-home messages
  • The threat to public health will remain so long
    as the virus continues to cause disease in
    domestic poultry
  • The outbreaks in poultry are likely to take a
    very long time to control
  • Should the final prerequisite for a pandemic be
    met, the consequences for human health around the
    world could be devastating
  • Regardless of how the present situation evolves,
    the world needs to be better prepared to respond
    to the next influenza pandemic

84
Timing has a lot to do with the outcome of a rain
dance
The only thing more difficult than planning for
an emergency is having to explain why you didnt.
Be Proactive NOT Reactive!!!!
We have to prepare for the next pandemic!!!
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