Title: Influenza, novel H1N1 (swine flu), H5N1 (avian influenza) and Occupational Infection
1Influenza, novel H1N1 (swine flu), H5N1 (avian
influenza) and Occupational Infection
- Stephen Born MD, MPH
- University of California, San Francisco
- Division of Occupational and Environmental
Medicine
2Influenza
- An acute viral disease of the respiratory tract
characterized by fever, headache, myalgia,
prostration, coryza, sore throat and cough.
Cough is often severe and protracted, but other
manifestations are usually self-limited, with
recovery in 2-7 days. - From Control of Communicable Diseases Manual 17th
edition
3Influenza
IS IT A COLD OR THE FLU? (Adapted from the CDC)
4nH1N1 Symptoms
- Broad clinical spectrum from mild upper
respiratory tract illness with or without fever
to acute respiratory distress syndrome (ARDS) - Some patients present with gastro-intestinal
symptoms of vomiting or diarrhea - Many with severe illness have underlying diseases
such as asthma. Obstructive airways disease,
diabetes, immunodeficinecy cardiovascular
disease, renal failure, malignancy and morbid
obesity. Also, pregnant women, especially 3rd
trimester (13 fold increased risk of
hospitalization). - See PMID 19790188
5Influenza A Nomenclature
Influenza type
Hemagglutinin subtype
Year of isolation
A/Sydney/5/97 (H3N2)
Geographic source
Isolate number
Neuraminidase subtype
6What name for the current Pandemic Influenza?
- The World Health Organization has struggled
mightily to avoid the ethnic monikers given the
Spanish, Hong Kong and Asian flus, instructing
its representatives to shift from swine flu to
H1N1 to A (H1N1) S-O.I.V. (the last four
initials stand for swine-origin influenza
virus) to, recently, Pandemic (H1N1) 2009. - http//www.nytimes.com/2009/05/01/health/01name.ht
ml - IOM refers to nH1N1
- Aka H1N1v
7What Influenza? What Name?
- A/California/7/2009 (H1N1) virus
- According to WHO update 65 dated 11 September
2009 - Pandemic (H1N1) 2009 influenza virus continues to
be the predominant circulating virus of
influenza, both in the northern and southern
hemisphere. Allviruses analyzed to date have
been antigenically and genetically similar to
A/California/7/2009-like pandemic H1N1 virus
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9nH1N1
- On August 24, the Presidents Council of Advisors
on Science and Technology said that H1N1 could
infect up to half the U.S. population, result in
the hospitalization of 1.8 million people, and
cause 30,000 to 90,000 deaths in addition to the
30,000 to 40,000 deaths from a typical flu
season.
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11Influenza
- Hemagglutinin (HA) spike
- Governs virus binding and entry into cells
- 15 Subtypes, H1 to H15
- In pandemics, a novel subtype arises
- Only H1, H2, and H3 have circulated in humans in
the past century - All 15 HA subtypes are found in free-flying birds
- WHO Avian influenza assessing the pandemic
threat
12Influenza
- Neuraminidase (NA) governs the release of the
newly formed virus from infected cells - There are 9 subtypes, N1 to N9
- Immunity to NA subtype reduces the amount of
virus released from a cell, resulting in less
severe disease - All 9 types found in free-flying birds
- Only N1 N2 in stable human lineages
- WHO Avian influenza assessing the pandemic threat
13Influenza
- Influenza A
- Virus mutates rapidly
- Infects pigs, horses, sea mammals and birds
- Large number of subtypes/huge pool of genetic
diversity - Only Influenza A known to cause pandemics
- Many genetic replication errors due to lack of a
proof reading mechanism - Constant small changes result in antigenic drift
- WHO Avian influenza assessing the pandemic
threat
14Influenza
- Influenza B and C
- Essentially human viruses
- Influenza B causes sporadic outbreaks of severe
respiratory disease - Nomenclature
- B/Shanghai/361/2002
- Also prone to mutation
- Influenza C causes no or very mild symptoms
- Few mutations
- WHO Avian influenza assessing the pandemic threat
15Influenza
- Antigenic Changes
- Drift
- Same subtype, minor changes often involving point
mutations - Shift
- New subtype, major changes, may involve genetic
recombination between different viruses - Likely responsible for pandemics
- Pigs often thought of as the crucible for genetic
recombination since they may be infected with
both human and avian types of viruses
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18Improvements on Nature
- Concentrated animal feeding operations (CSFOs)
- During the later stages of the 1918 pandemic,
farmers noted that their pigs were getting sick
and called the disease hog flu. - Generally milder than human disease
- One 2007 study showed that CAFO workers were 50
times more likely and their spouses were 25 times
more likely to have elevated H1N1 antibodies
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20Avian Influenza
- Avian influenza viruses are excreted in feces and
secretions - Wild birds contaminate ponds/lakes
- Domestic foul become infected
- Chicken coops often above pig pens or pigs may be
fed bird carcasses - China is often thought of as a major area of risk
for genetic recombination since pigs, chickens,
ducks and humans often live in close proximity - WHO Avian influenza assessing the pandemic
threat
21Influenza
- Instances of Avian Influenza in Humans
- N5H1, Hong Kong 1997
- 18 people hospitalized/6 died
- 1.5 million chickens killed to stop outbreak
- H9N2, China and Hong Kong 1999
- 2 children infected
- H7N2, Virginia 2002
- One person had serologic evidence of infection
- H5N1 China and Hong Kong 2003
- Ongoing worldwide
- Many, many other sporadic examples
22Influenza
- Since 2003 62 countries/territories have
experienced outbreaks of HPAI H5N1 - FAO AIDE News May 2009
- Jumped species to tigers in Thailand with 147 out
of 418 captive tigers developing severe symptoms
after being fed chicken carcasses in October 2004 - WHO Avian influenza assessing the pandemic threat
23Influenza
- H5N1
- Inefficient human to human transmission
24HPAI H5N1
- H5N1 affects the young, in the prime of life,
similar to the 1918 pandemic strain - H5N1 causes viral pneumonia, like the 1918
strain, without evidence of bacterial pneumonia - Why has H5N1 not shown sustained human to human
transmission? - Is it only a matter of time?
- Is there something that is preventing
reassortment? - NEJM January 27, 2005 Editorial
25Mortality Associated with Influenza Pandemics and
Selected Seasonal Epidemic Events, 1918-2009
Morens D et al. N Engl J Med 2009361225-229
26Genetic Relationships among Human and Relevant
Swine Influenza Viruses, 1918-2009
Morens D et al. N Engl J Med 2009361225-229
27Influenza
- Three prerequisites for a pandemic
- A novel virus subtype
- The general population will have little or no
immunity - The virus must be able to replicate in humans and
cause serious disease - The new virus must be efficiently transmitted
from one human to another - The first two conditions have been met by the
H5N1 avian strain but have been met by nH1N1 - WHO Avian influenza assessing the pandemic
threat
28Influenza
- The 1918 Spanish Flu pandemic (H1N1) killed
about 40-50 million people worldwide in less than
one year, with 500,000 US deaths2.5 estimated
case fatality rate - The young and healthy were especially affected
- First wave simultaneously in Europe and USA in
March 1918Spring and Summer - Second wave in Augustten fold increase in
fatality rate - Some reports of being healthy in the morning,
dead by night - The total military deaths in WW1 were 8.3 million
over 4 years - WHO Avian influenza assessing the pandemic
threat
29Pandemic Influenza
- 1957-1958 H2N2 Asian Flu caused 70,000 US
deaths - 1968-1969 H3N2 Hong Kong Flu caused 34,000 US
deaths - Relatively mild, only 11 years after the previous
pandemic with the same N2 subtype which may have
conferred some protection - One constant feature A rapid surge in cases
with exponential increases in a matter of weeks - A severe pathogenic pandemic influenza is likely
to overwhelm ED and hospital bed capacity - WHO Avian influenza assessing the pandemic
threat
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31Influenza
- Vaccine development
- Usually produced in fertilized chicken eggs
- (H5N1 kills chicken embryos)
- Modified seed viruses are in development using
recombinant genetic technology to remove lethal
genes - Process of producing vaccine using this
technology takes monthspandemic basically over
when vaccine was available in quantity in 1957
and 1968 - A few companies are developing cell culture
production techniques - WHO Avian influenza assessing the pandemic
threat
32Seasonal Influenza Vaccine
- The vaccines to be used in the 2009-2010
influenza season in the U.S. contain the
following - an A/Brisbane/59/2007 (H1N1)-like virus
- an A/Brisbane/10/2007 (H3N2)-like virus
- a B/Brisbane/60/2008-like virus.
- A/Brisbane/59/2007 is a current vaccine virus
A/South Dakota/6/2007 (an A/Brisbane/59/2007-like
virus) is a current vaccine virus used in live
attenuated vaccines.A/Brisbane/10/2007 and
A/Uruguay/716/2007 (an A/Brisbane/10/2007-like
virus) are current vaccine viruses. - http//www.fda.gov/BiologicsBloodVaccines/Guidance
ComplianceRegulatoryInformation/Post-MarketActivit
ies/LotReleases/ucm162050.htm
33nH1N1 Vaccine
- Two recent studies of vaccines derived from the
A/California/7/2009 (H1N1) virus - A single 15 microgram dose of the 2009 H1N1
vaccine was immunogenic in adults, with mild to
moderate vaccine-associated reactions. PMID
19745216 - A single 7.5 microgram dose of the
MF59-adjuvanted vaccine was effective. PMID
19745215
34Live Attenuated Influenza Vaccine
- Aka FluMist
- Derived from a live influenza A and B virus
strains modified by cold adaptation creating a
Master Donor Virus - Cold adapted
- Temperature Sensitive
- Attenuated
- The MDV is updated annually with hemagglutinin
(HA) and neuraminidase (NA) genes from
contemporary flu viruses - See PMID 19453395
35LAIV
- Replicates primarily in the ciliated epithelial
cells of the nasopharyngeal mucosa to induce
immune responses. - Does not replicate well in warmer temperatures
found in the lower airways and lung - In adults, studied in ages 18-64. Studies
evaluated the effectiveness in preventing any
febrile illness. Post hoc analysis in adults
50-64 years old failed to show effectiveness. As
a result, not approved for use in adults gt50 in
the United States. - See PMID 19453395
36LAIV
- Cross protection among antigenically distinct
viruses within the same subtype may be induced by
LAIV - See PMID 19768402
- LAIV may work better in populations that have not
received multiple influenza vaccinations - See PMID 19464536
37Influenza
- Antiviral Drugs
- M2 inhibitors including amantadine and
rimantadine are ineffective against H5N1 and
nH1N1, but work against seasonal H1N1 - Neuraminidase inhibitors include oseltamivir and
zanamivir are effective against nH1N1 with
sporadic resistance - Better safety profile
- More expensive
- Negligible capacity for surge production
- Resistance does develop (summer camps)
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39Influenza
- Short incubation-1 to 3 days
- Individuals infectious before symptoms develop
- Transmitted by person-to-person contact, fomites
and droplets gt10 microns - Probable transmission by droplet nuclei, lt5
microns (airborne) - Disease may not present with full clinical
symptoms, but can be spread by the affected person
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41DHS Office of Biotechnology Activities Notice of
Proposed Changes September 22, 2009
- Designation of human H2N2 viruses that circulated
from 1957-8, the fully reconstructed 1918-1919
H1N1 and HPAI H5N1 as Risk Group 3 agents. - Requires enhanced biosafety practices, including
uses of powered air purifying respiratiors and
other PPE - Recombinant work using any genes/segments from
the above strains will require BSL 3 enhanced
containment - Federal Register/Voll 74, No. 182/Tuesday
September 22, 2009/Notices
42ACIP Recommends Five Groups as Priority Targets
for H1N1 Vaccination
- The CDCs Advisory Committee on Immunization
Practices (ACIP) has recommended which U.S.
population groups should be targeted to receive
H1N1 influenza vaccine when it becomes available.
People over 65 have the lowest priority. - The 15-member ACIP says these five groups should
be targeted - pregnant women
- household contacts of infants under 6 months
- healthcare and emergency-services workers
- young people between 6 months and 24 years of
age - and nonelderly adults with underlying risk
conditions, such as diabetes and chronic lung
disease.
43 J. Cohen Science 325, 1328-1329 (2009)
Published by AAAS
44CDC Recommended Respiratory Protection
- Occupational (non-health care)
- No novel H1N1 in community Facemask/respirator
not recommendedFacemask - Novel H1N1 in community Facemask/respirator not
recommended but could be considered under certain
circumstances - Occupational (health care)
- Caring for persons with known, probable or
suspected novel H1N1 or influenza-like illness
Respirator. - Use respirator and consider temporary
reassignment for employees at high risk. - http//www.cdc.gov/h1n1flu/masks.htm
45PUSHBACK!
- Much disagreement with CDC and OSHA guidelines
- Who needs a respirator when surgical masks are
cheaper and are thought by some to be equally
effective against droplet spread? - Examples CCSF DPH and SFGH ID
46Institute of Medicine Report 9/1/09
- (1) Healthcare workers who are in close contact
with individuals with nH1N1 or ILI should use fit
tested N95 respirators - (2) Increase research on Influenza transmission
and personal respiratory protection - Investigate relative importance of aerosol vs
airborne transmission - See http//www.nap.edu/catalog/12748.html
47Influenza Transmission changes with Humidity and
Temperature
- Cold and Dry conditions favor in the guinea pig
host model - PMID 17953482 PMCID PMC2034399
- Same PI hypothesizes that transmission of
influenza virus in temperate zones is
predominantly by aerosol, in the tropics by
contact - Also hypothesize that current summertime
transmission in North America is by contact.
48I had a little bird, Its name was Enza. I
opened the window, And in-flu-enza.
49Indications for Hand Hygiene
- When hands are visibly dirty, contaminated, or
soiled, wash with non-antimicrobial or
antimicrobial soap and water. - If hands are not visibly soiled, use an
alcohol-based handrub for routinely
decontaminating hands.
Guideline for Hand Hygiene in Health-care
Settings. MMWR 2002 vol. 51, no. RR-16.
50Efficacy of Hand Hygiene Preparations in Killing
Bacteria
Better
Good
Best
Antimicrobial soap
Plain Soap
Alcohol-based handrub
51Influenza
- Past pandemics have typically hit world
populations like a flash flood. They have
started abruptly and explosively, swept through
populations, and left considerable damage in
their wake. They could not be stopped but peaked
rapidly and then subsided almost as abruptly as
they began. The emergence of human cases of
avian influenza A H5N1 virus infection in Asia is
an unprecedented warning - NEJM January 27, 2005 Editorial
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53 J. Cohen Science 325, 1328-1329 (2009)
Published by AAAS
54Bottom Line Influenza Mortality
- Each year 36,000 US citizens die from seasonal
influenza which has generally has a mortality
rate of less than .2 - This year we can expect many more deaths because
many more people will be infected although the
mortality rate is less than that of typical
seasonal influenza
55Table. Model input parameters and outcome
estimates
56Flu Deaths
- The former model uses a high projected mortality
rate and estimates that the need for mechanically
assisted ventilation may be increased by 33
above US baseline in the upcoming influenza
season - See RRN_at_ncbi.nlm.nih.gov RRNID RRN1009.1
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58Emergence of Influenza A (H1N1) Viruses from
Birds and Swine into Humans
Zimmer S and Burke D. N Engl J Med
2009361279-285
59Acknowledgements and References
- References as noted on each slide
- WHO and CDC Websites especially useful
- CDC H1N1 Website http//www.cdc.gov/h1n1flu/
- California DHS for the color influenza
slides--available on line - http//www.dhs.ca.gov/ps/cdic/cdcb/pds/cpe/Documen
ts/09020420Handouts.ppt - Unofficial blog for the latest news
www.promedmial.org - Photos from 1918 http//nmhm.washingtondc.museum/c
ollections/archives/agalleries/1918flu/1918flu.htm
l - For CAFO references Environmental Health
Perspectives September 2009 - Check out Emerging Infectious Diseases Journal
(EID)
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