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InfluenzaWALEED JAVAID, MD, FACPHOSPITAL EPIDEMIOLOGISTDIRECTOR OF INFECTION CONTROL
Introduction� Acute febrile illness � Varying Outbreaks� Attack rates 10% to 40%� Possibly causing Epidemics for past 400 years
ClassificationInfluenza A Influenza B Influenza C
Gene segments 8 8 7
Viral Proteins 10 11 9
Unique M2 NB HEF
Host Humans, swine, equine, avian, marine mammals Humans only Humans and swine
Epidemiology Antigenic shift and drift Antigenic drift only Antigenic drift only
Clinical May cause large pandemics
Severe disease generally confined to older adults or persons at high risk
Mild disease without seasonality
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Neuraminidase helps in Release
From CellB. Entering Cell C. ReplicationHemagglutinnin
Binding to Sialic Acid
Pathology of Influenza Infection
Antigenic DriftInefficient proof reading by vRNA
polymerase
High incidence of transcription errors
Changes in amino acid substitutions in the HA and NA
New variants evade preexisting humoral immunity
IntrapandemicOutbreaks
Antigenic Drift
Antigenic Drift
RNA
Hemagglutinin
NeuraminidaseAntibodies
Sialic acid
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Antigenic ShiftHost (Human or Pig)
Recombination of vRNA Segments
New reassorted Virus
Pandemic Influenza
Human InfluenzaVirus
Avian Influenza Virus
Antigenic Shift
Antigenic Shift
Influenza Pandemics and Epidemics
Introduction ofhypotheticalA HxNx virus
Significant minor variation A HxNx may occur at anyof these points. Epidemics may or may not beassociated with such variations
Introduction of hypotheticalA HyNy major (new subtype)variant A HxNx disappears
Dis
ease
Inci
den
ce
Mea
n P
op
ulat
ion
Ant
ibo
dy
Lev
el
Pandemic
EpidemicEpidemic
Pandemic
Interpandemic Period
Epidemic
Time in Years
1 2 3 4 5 6 7 8 9 10 11 12
Incidence of clinically manifest influenzaMean level of population antibody vs A HxNxMean level of population antibody vs A HyNy
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0.6 0.4 0.57.5
98.3
0
20
40
60
80
100
120
<1 y 1 - 4 y 5 - 49 y 50 - 64 y 65+ y
Age Group
Res
pira
tory
& C
ircul
ator
y D
eath
s P
er 1
00,0
00 P
erso
n Ye
ars
Influenza-Associated Deathsby Age Group, 1976-1999
Adapted from Thompson W et al. JAMA. 2003;289:179-186.
US Life Expectancy1900-1990
Age
(y)
1900 1930 1950 1970 1990
70
60
50
40
30
1918Flu Epidemic
Year
Date Name of pandemic Deaths Case fatality
rateSubtype involved
Pandemic Severity Index
1889–1890 Asiatic or Russian Flu 1 million 0.15%
possibly H3N8or H2N2
N/A
1918–1920 Spanish flu 20 to 100 million 2% H1N1 5
1957–1958 Asian Flu 1 to 1.5 million 0.13% H2N2 2
1968–1969 Hong Kong Flu
0.75 to 1 million <0.1% H3N2 2
1977–1978 Russian flu N/A N/A H1N1 N/A
2009–2010 Swine Flu 18,000 to 284,500 0.03% H1N1/09 N/A
1976-77 to 2006-07
Annual flu virus deaths (USA only)
3.00 to 46,000 N/A N/A N/A
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Influenza Is the Leading Cause of US Vaccine-Preventable Disease Deaths
Disease Cases DeathsInfluenza (millions) ~500,000 Pneumococcal diseases (millions) ~120,000Hepatitis A 282,650 1013Hepatitis B 146,644 9694Measles 60,189 132Mumps 24,075 7Rubella 4412 21Pertussis 53,634 65Tetanus 486 77
CDC. MMWR. 2006;55;511-515. Thompson W et al. JAMA. 2003;289:179-186.Felkin D et al. Am J Public Health. 2000;90:223-229.
VPD Cases & Deaths, US 1989-1998
Naming convention for influenza viruses� The antigenic type (e.g., A, B, C)� The host of origin (e.g., swine, equine, chicken, etc. For human-origin viruses, no host of origin designation is given.)� Geographical origin (e.g., Denver, Taiwan, etc.)� Strain number (e.g., 15, 7, etc.)� Year of isolation (e.g., 57, 2009, etc.)� For influenza A viruses, the hemagglutinin and neuraminidase antigen description in parentheses (e.g., (H1N1), (H5N1)
A/Texas/50/2012 (H3N2)
A / Texas / 50 /2012 (H3N2)
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Annual reformulations of the influenza vaccine� Since 1999 WHO provides annual recommendations for influenza vaccine formulations� Northern Hemisphere� Southern Hemisphere
� Since 2012-13 recommendations included additional B strain for quadrivalent vaccine
Influenza Vaccines A Trivalent Defense
CDC. MMWR Recomm Rep. 2005;54(RR-8):1-40.
Influenza Vaccines A Quadrivalent Defense
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H1N1 H3N2 B-strain QIV
1998–1999 A/Beijing/262/95(H1N1 A/Sydney/5/97(H3N2) B/Beijing/184/93 N/A
1999– 2000 A/Beijing/262/95 (H1N1) A/Sydney/5/97 (H3N2) B/Shangdong/7/97 N/A
2000–2001 A/New Caledonia/20/99 (H1N1) A/Moscow/10/99 (H3N2) B/Beijing/184/93 N/A
2001–2002 A/New Caledonia/20/99(H1N1) A/Moscow/10/99(H3N2) B/Sichuan/379/99 N/A
2002–2003 A/New Caledonia/20/99(H1N1) A/Moscow/10/99(H3N2) B/Hong Kong/330/2001 N/A
2003–2004 A/New Caledonia/20/99(H1N1) A/Moscow/10/99(H3N2) B/Hong Kong/330/2001 N/A
2004-2005 A/New Caledonia/20/99(H1N1) A/Fujian/411/2002(H3N2) B/Shanghai/361/2002 N/A
2005-2006 A/New Caledonia/20/99(H1N1) A/California/7/2004(H3N2) B/Shanghai/361/2002 N/A
2006-2007 A/New Caledonia/20/99(H1N1) A/Wisconsin/67/2005 (H3N2) B/Malaysia/2506/2004 N/A
H1N1 H3N2 B-strain QIV
2007-2008 A/Solomon Islands/3/2006 (H1N1)A/Wisconsin/67/2005 (H3N2) B/Malaysia/2506/2004 N/A
2008-2009 A/Brisbane/59/2007 (H1N1) A/Brisbane/10/2007 (H3N2) B/Florida/4/2006 N/A
2009-2010 A/Brisbane/59/2007 (H1N1) A/Brisbane/10/2007 (H3N2) B/Brisbane/60/2008 N/A
2010-2011 A/California/7/2009 (H1N1) A/Perth/16/2009 (H3N2) B/Brisbane/60/2008 N/A
2011-2012 A/California/7/2009 (H1N1) A/Perth/16/2009 (H3N2) B/Brisbane/60/2008 N/A
2012-2013 A/California/7/2009 (H1N1) A/Victoria/361/2011 (H3N2) B/Wisconsin/1/2010 B/Brisbane/60/2008
2013-2014 A/California/7/2009 (H1N1) A/Victoria/361/2011 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008
2014-2015 A/California/7/2009 (H1N1) A/Texas/50/2012 (H3N2) B/Massachusetts/2/2012 B/Brisbane/60/2008
•Influenza A H3N2•Oct 1 – Nov 22, 2014
•48% antigenically "like" the 2014-2015 influenza A (H3N2) vaccine •52% were antigenically different (drifted) from the H3N2 vaccine virus
•December 3, 2014, 16:00 ET (4:00PM ET)
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� Surveillance data indicate that influenza A (H3N2) viruses have predominated � 85 influenza A (H3N2) viruses collected � 44 (52%) are significantly different (drifted) from
A/Texas/50/2012� Detected in late March 2014� Drifted H3N2 viruses are A/Switzerland/9715293/2013� Susceptible to both oseltamivir and zanamivir.
Adjusted vaccine effectiveness estimates for influenza seasons from 2005-2015
10
21
52
37
5660
47 49 51
19
0
10
20
30
40
50
60
70
2004-05 2005-06 2006-07 2007-08 2009-10 2010-11 2011-12 2012-13 2013-14 2014-15
Adjusted Overall VE (%)
http://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm
For patients with ILI these studies compare odds ofVaccination & Lab confirmed Influenza : Vaccination & Negative Influenza
Influenza Surveillance in the United States� Virological Surveillance� Surveillance for Novel Influenza A Viruses
� Outpatient Illness Surveillance� U.S. Outpatient Influenza-like Illness Surveillance Network
(ILINet)� Mortality Surveillance� 122 Cities Mortality Reporting System� National Center for Health Statistics (NCHS) mortality
surveillance data� Influenza-Associated Pediatric Mortality Surveillance System
� Hospitalization Surveillance� Influenza Hospitalization Network (FluSurv-NET)
� Summary of the Geographic Spread of Influenza
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Influenza-like Illness (ILI)
� ILI is defined as:� Fever (temperature of 100°F [37.8°C] or greater)� A cough and/or a sore throat � Without a KNOWN cause other than influenza.
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Google Flu Trends
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Flu Vaccination
� All persons aged 6 months and older are recommended for annual vaccination� Exceptions� Children less then 6 months of age� Allergies to Flu Vaccine or ingredients
Types of flu shots� Trivalent:� Standard-dose trivalent shots: virus grown in eggs.
given a jet injector, for persons aged 18 through 64 years� Intradermal trivalent shot: Which is injected into the
skin approved for people 18 through 64 years of age.� High-dose trivalent shot, approved for people 65
and older.� Trivalent shot virus grown in cell culture, which is
approved for people 18 and older.� Recombinant trivalent shot that is egg-free,
approved for people 18 years and older.
Types of flu shots
� Quadrivalent� A quadrivalent flu shot.� A quadrivalent nasal spray vaccine, approved for
people 2 through 49 years of age (recommended preferentially for healthy children 2 years through 8 years old when immediately available and there are no contraindications or precautions)
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Emergency Department Utilization During Outbreaks of Influenza� The American College of Emergency Physicians (ACEP) recommends: � Close coordination between:� Emergency physicians� Health care facilities� Public health entities� Educate the public regarding appropriate physician
referrals and emergency department (ED) utilization for presumptive influenza.
Emergency Department Utilization During Outbreaks of Influenza� Ensure that emergency care and critical care providers are immunized against influenza. � Implement rapid screening and appropriate respiratory infection control interventions for all individuals arriving in the ED.
Emergency Department Utilization During Outbreaks of Influenza� End the practice of boarding admitted patients in the ED when no inpatient beds are available� Develop robust communication methods with the Centers for Disease Control and Prevention (CDC)
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Emergency Department Utilization During Outbreaks of Influenza� Require hospitals and communities that are severely affected by influenza to postpone elective admissions and to develop strategies to increase surge capacities, including floor and isolation beds, until the crisis abates. � Engage emergency physician participation in city, state, and national public health response planning.
Emergency Department Utilization During Outbreaks of Influenza� Develop hospital-based and regional emergency response plans � Create regional command centers to monitor ambulance diversion status and local inpatient and ED capacity, and to coordinate regional ED response.
ED Evaluation
� Infection Control Measures� Isolation of patients� Wearing appropriate protective equipment
� Knowledge of current local prevalence of disease� Strategic management plans
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Clinical Pathway for patients who present to ED with ILI and Low regional Prevalence of disease
ILI and low regional prevalence
Is the patient at high risk for complications
Yes
Influenza testing
Positive
Initiate antiviral treatment
Negative
Supportive Care
No
Supportive Care
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Clinical Pathway for patients who present to ED with ILI and High regional Prevalence of disease
ILI and High regional prevalence
Is the patient at high risk for complications
Yes
Influenza testing
Positive
Initiate antiviral treatment
Negative
Supportive Care
No
Supportive Care
Influenza like illness Outpatient visits
0
10000
20000
30000
40000
50000
60000
70000
80000
1 152943 5 193347 9 233751132741 3 173145 7 213549112539 1 152943 5 193347 9 233751132741 3 173145 72003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Influenza-like Illness Outpatient Visits
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
1 4 7 1013161941444750 1 4 7 1013161941444750 1 4 7 1013161941444750 1 4 7 1013161941444750 1 4 7 10132011 2012 2013 2014 2015
Average of AGE 0-4Average of AGE 5-24Average of AGE 25-64Average of AGE 25-49Average of AGE 50-64Average of AGE 65
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Laboratory confirmed influenza hospitalizations
0
50
100
150
200
250
300
350
1 4 7 10 13 16 41 44 47 50 1 4 7 10 13 16 41 44 47 50 1 4 7 10 13 16 41 44 47 50 1 4 7 10 13 16 41 44 47 50 53 3 6 9 122011 2012 2013 2014 2015
0-4 yr18-49 yr50-64 yr5-17 yr65+ yr
Influenza Differential Diagnosis� Fever + Cough� Mycoplasma� Adenovirus� Respiratory syncytial virus� Rhinovirus� Parainfluenza virus� Legionella� Others
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Respiratory Viral Panel� At Upstate� Influenza A – H1, H3, 2009 H1� Influenza B� Respiratory Syncytial Virus� Human Metapneumovirus� Human Parainfluenza Virus 1, 2, 3, 4� Adenovirus� Rhinovirus / Enterovirus� Coronavirus – HKU1, NL63, OC43, 229E� Bordetella pertussis� Mycoplasma pneumonia� Chlamydophilia pneuminae
Treatment
� Neuraminidase Inhibitors� Oseltamivir� Zanamivir
� Adamantanes� The current circulating virus is not sensitive to these� Amantadine� Rimantadine
That’s All