PUBH501, Fall 2015: Topics in

Community and Preventive

Medicine

Seasonal and Pandemic

Influenza
(Avian Influenza)
Page 53
onwards

Learning Objectives
Discuss the characteristics of seasonal
influenza
Discuss the differences between seasonal and
pandemic influenza
Discuss the status of the current concern over
avian influenza (H5N1) and the novel H1N1
(swine) influenza
2

CPM Influenza

Age-Adjusted Mortality Rate (All Causes),

United States, 1900-2005

Deaths per 1,000 Pop.

26

19.5

13
6.5

0
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000
Year
Source: National Center for Health Statistics

CPM Influenza

The Burden of Seasonal Influenza

Globally: 250,000 to 500,000 deaths / year
United States each year:
>200,000 hospitalizations
36,000 deaths
(80%90% in persons 65 years)

CPM Influenza

Influenza-Associated Hospitalizations
by Age Group
Hospitalizations per 100,000

600

450

472

300

150
115

90

22

0
0-4 Yrs

5-49 Yrs

50-64 Yrs

Age Group
CPM Influenza

65 Yrs
Source: Thompson, unpublished data, 2004 5

Influenza versus Flu

Not everything called the flu is influenza
Influenza = acute viral disease of the
respiratory tract characterized by fever,
headache, myalgia, prostration, coryza, sore
throat, cough
Importance derives from
rapidity with which epidemics evolve
widespread morbidity
seriousness of complications, especially
pneumonia
Source: CCDM, 18th ed. 6

CPM Influenza

Influenza Virus:
Two Important Types and Hosts

Type A
Most virulent group, causes epidemics
Multiple hosts

Humans
Birds, both wild and poultry
Swine
Horses

Subtyped by surface antigens (glycoproteins)

Hemagglutinin (H or HA)
Neuraminidase (N or NA)

Type B

Humans

CPM Influenza

Is this how you get it?

CPM Influenza

Influenza A
Surface Antigens and Subtypes

16 Hemagglutinins (HA)
Sites of attachment to host
cells

9 Neuraminidases (NA)

Helps release newly formed

virions from infected cell

Current human subtypes: H1N1, H3N2

Many strains of each subtype, e.g.,

A/New Caledonia/20/99 (H1N1); B/Hong Kong/330/2001

CPM Influenza

Distribution of Influenza A Subtypes

in Humans, Swine, Horses, and Birds
Haemagglutinin subtype

H1
H2
H3

H1
H3

H3

H7

H1
H2
H3
H4
H5
H6
H7
H8
H9
H10
H11-H16

Neuraminidase subtype

N1
N2

N1
N2

N7
N8

N1
N2
N3
N4
N5
N6
N7
N8
N9

10

CPM Influenza

Antigenic Changes in HA and NA

Antigen drift
Minor mutations in flu virus

Antigenic shift
Much larger immunologic change (reassortment)

11

CPM Influenza

Antigenic Drift
Point mutations in the HA gene cause minor
antigenic changes to HA protein
Gradual, continuous process
Immunity against one strain may be limited
Vaccine strains must be updated each year
Antigenic drift causes seasonal epidemics

12

CPM Influenza

Antigenic Shift
Emergence of new human influenza type A virus
subtype (new HA subtype) through:
Genetic reassortment (human and animal viruses)
Direct animal (poultry) to human transmission

Pandemic can occur if efficient and sustained virus

transmission occurs among humans (sustained
person-to-person transmission)
Pandemic can result in substantial morbidity and
mortality worldwide
13

CPM Influenza

Prevention of Influenza: Influenza Vaccine

Biannual WHO strain selection
Northern hemisphere countries begin production in
spring for following season
Trivalent:
Type A: H1N1, H3N2
Type B

68 months to produce vaccine for U.S.

Inactivated for intramuscular injection
Live, attenuated, intranasal spray

14

CPM Influenza

2009-2010 Influenza Vaccines

Seasonal Influenza Vaccine (Trivalent)
Composition
H1N1: A/Brisbane/59/2007 (H1N1)-like virus
H3N2: /Brisbane/10/2007 (H3N2)-like virus
B: B/Brisbane/60/2008-like virus
Availability: early Fall

Novel H1N1 (swine) Influenza Vaccine

Commercial production just beginning- available now

World Health Organization

CPM Influenza

15

Recommended Annual Influenza Vaccination,

2009-2010 (United States)

All persons 6 months to 18 years

Persons 50 years
Persons 6 months with certain chronic conditions*
All pregnant women during influenza season
Persons living or caring for high-risk* persons, including
all health-care personnel
Household contacts and caregivers of children 59 months
old, adults 50 years, and high-risk* persons

* High-risk = 65 years; residents of nursing home or chronic care facility;

chronic pulmonary or cardiovascular conditions; chronic metabolic
diseases, renal dsyfunction, hemoglobinopathies, immunosuppressed;
children 6 months to 18 years receiving chronic aspirin therapy;
pregnant women during influenza season

83% of population!
CPM Influenza

16

Pandemics Do Occur
Spanish flu

Deaths per 1,000 Pop.

26

19.5

13
6.5

0
1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000
Year
National Center for Health Statistics

CPM Influenza

17

Camp Funston, Kansas, 1918

Source: PBS The American Experience

CPM Influenza

18

Pandemic of 19181919
Began with first cases in March 1918 in Europe,
USA
In Spring, highly contagious, but not
deadly
Virus probably traveled between Europe/USA
on troop ships
Land, sea travel to Africa, Asia
Warning signal missed

19

CPM Influenza

Pandemic of 19181919
August, 1918 simultaneous explosive outbreaks in in
France, Sierra Leone, USA
Fall 1918 Winter 1918-1919
25-35% of world infected
10-fold increase in death rate
Highest death rate ages 15-35 years
Leading cause of death among WW I soldiers
Deaths from primary viral pneumonia, secondary
bacterial pneumonia
Deaths within 48 hours of illness
20

CPM Influenza

Pandemic of 19181919
Came to be known as Spanish Flu, even though
probably originated in U.S.
Substantial morbidity and mortality
20-50 million deaths worldwide
>500,000 U.S. deaths
In many communities, so many deaths occurred so quickly that bodies
buried in mass graves
43,000 U.S. military deaths (out of ~100,000 U.S. troop casualties during
WW I)

21

CPM Influenza

22

CPM Influenza

Avian Influenza H5N1

Since December 2003, 30+ countries reported
H5N1 among domestic poultry and wild birds
Largest outbreak of avian influenza ever described
Over 150 million birds died or destroyed

Virulence
Asymptomatic in most wild birds and domestic ducks
Highly fatal in domestic poultry
Felines and other mammals can be infected

23

CPM Influenza

Avian Morbidity/Mortality from H5N1

Approaches 100%
in commercial
poultry flocks
Deaths within 2
to 12 days after
first signs of illness
Survivors in
poor condition
24

CPM Influenza

Epidemiology of H5N1 Cases, 2003-2006

Infrequent, sporadic avian-to-human transmission,
previously healthy children, young adults
WHO review of 205 H5N1 cases:

Median age: 20 years (range: 6 mo. to 75 yrs.)

90% < 40 years old
Mortality highest in 10-19 year olds (73%)
Mortality lowest in 50 year olds (18%)
Median time, onset to death: 9 days

25

CPM Influenza

Confirmed Human Cases of Avian Influenza

200

No. Cases

150

Lived
Died

100

50
0
2003

2004

2005

2006
Year

CPM Influenza

2007

2008

2009
WHO, 1 July 2009 26

Situation in Animals and Humans

Panzootic among poultry and birds
Enormous agricultural and economic impact
Global, not regional problem

Primarily a zoonotic disease among humans

Very rare human disease among exposed humans
Key to reducing the public health threat is to control
the problem in poultry

27

CPM Influenza

Proportion of H1N1 (S-OIV)

to other Influenza subtypes

http://www.who.int/csr/disease/swineflu/Virologicaldata2009_12_04.pdf

28

CPM Influenza

World Health Organization Pandemic Phases

Inter-pandemic phase
New virus in animals, no human
cases

Pandemic alert
New virus causes human cases

Pandemic

Low risk of human cases

Higher risk of human cases

No or very limited human-to-human

transmission

Evidence of increased human-to-human

transmission

Evidence of significant human-to-human

transmission

Efficient and sustained human-to-human

transmission

29

CPM Influenza

Global Strategies To Date

Reduce threat of avian influenza (H5N1) to
agriculture
Surveillance, culling, vaccination of poultry

Protect people exposed to infected poultry

Surveillance, prevent high risk behavior through education, antiviral drugs

Prepare for potential future pandemic

National planning, strengthen early warning systems, vaccine
development efforts

30

CPM Influenza

H5N1 Influenza in Humans: Summary

Pandemic Requirements:
A new human influenza A subtype

AND
Causes serious illness

AND
Spreads easily from human-to-human

2 of 3 requirements for pandemic met;

opportunities for the third, as long as human and
bird infections continue
H5N1 will not be eradicated soon
Preparedness planning is essential
31

CPM Influenza

Swine Influenza A (H1N1):

Introduction
Swine Influenza (swine flu) =
respiratory disease of pigs, regularly
cause outbreaks of influenza among
pigs
Swine flu viruses do not normally
infect humans, however, human
infections with swine flu do occur,
Most commonly, human cases of
swine flu occur in people who are
around pigs but swine flu viruses
can be spread from person to
person
Source: Chotani Supercourse lecture

CPM Influenza

32

Swine Influenza A (H1N1):

History in U.S.
Jan-Feb 1976, Fort Dix, NJ:
Swine flu cases in military
recruits: 13 severe illness, 1
death
Fall 1976: > 40 million people
were vaccinated; program
stopped because of >500 cases
(30 deaths) of GBS
Sept 1988, previously healthy 32 y.o. pregnant woman in
Wisconsin hospitalized for pneumonia after being infected
with swine flu and died 8 days later.
Dec. 2005 Feb. 2009: 12 human infections with swine
influenza reported from 10 states in the United States
CPM Influenza

33

Swine Influenza A (H1N1):

Transmission to Humans
Through contact with infected pigs or
environments contaminated with swine
flu viruses
Through contact with a person with
swine flu
Human-to-human spread of swine flu
has been documented also and is
thought to occur in the same way as
seasonal flu, through coughing or
sneezing of infected people
Source: Chotani Supercourse lecture

CPM Influenza

34

Swine Influenza A(H1N1):

MarchApril 2009
March, early April 2009: Mexico experienced
outbreaks of respiratory illness and influenza-like
illness (ILI) in several areas of the country
April 12: outbreak of ILI in a small community in
the state of Veracruz reported to PAHO
April 17: case of atypical pneumonia in Oaxaca
State prompted enhanced surveillance throughout
Mexico
April 23: several cases of severe respiratory
illness confirmed as influenza A(H1N1) virus
infection were communicated to the PAHO
Sequence analysis revealed that the patients were
infected with the same strain detected in 2 children
residing in California
Samples from the Mexico outbreak match
swine influenza isolates from patients in the
United States
Source: Chotani Supercourse lecture

35

CPM Influenza

Novel Influenza A(H1N1)

Number of Cases by Age Group, Mexico, 11 May
2009
No. Confirmed Cases

600

549

538

450

391

300
223

183

150

121
37

0-9

10-19

20-29

30-39

40-49

50-59

60+

NA

Age Group

Source: Secretaria de Salud, Mexico 36

CPM Influenza

Novel Influenza A(H1N1)

10

100

7.5

75

50

2.5

25

16.1 17.9
3.6

1.8

3.6

3.6

7.1

12.5

5.4

10.7 12.5
1.8

1.8

Case-Fatality (%)

No. of Deaths

Case-Fatality Rate by Age Group, Mexico, 11 May

2009
Deaths
%

1.8

0
>75

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

15-19

10-14

5-9

1-4

<1

Age Group

Overall Case-Fatality Rate = 2.7%

CPM Influenza

Source: Secretaria de Salud, Mexico37

Swine Influenza A(H1N1):

MarchApril 2009

Virus described as new subtype of A/H1N1 not

previously detected in swine or humans
CDC determines that this virus is contagious and
is spreading from human to human
The virus contains gene segments from 4 different
influenza types:

North American swine

North American avian
North American human
Eurasian swine

38

CPM Influenza

World Health Organization Pandemic Phases

Low risk of human cases
Inter-pandemic phase
New virus in animals, no
Higher risk of human cases
human cases

Pandemic alert
New virus causes
human cases

Pandemic

1
2

No or very limited human-to-human

transmission

Since
2004

Evidence of increased human-tohuman transmission

April 27

Evidence of significant human-tohuman transmission

April 29

Efficient and sustained human-tohuman transmission

June 11
Source: WHO

CPM Influenza

39

Pandemic Influenza A(H1N1)

Status Update
Region

Deaths

WHO Regional Office for Africa (AFRO)

108

WHO Regional Office for the Americas (AMRO)

5878

WHO Regional Office for the Eastern Mediterranean (EMRO)

392

WHO Regional Office for Europe (EURO)

at least 918

WHO Regional Office for South-East Asia (SEARO)

766

WHO Regional Office for the Western Pacific (WPRO)

706

Total

at least 8768

Source: WHO, 29 November 2009 40

CPM Influenza

I know how not to get AIDS.

I do not know how not to get the flu.
Alfred W. Crosby, influenza historian

Source: Gina Kolata, Flu

CPM Influenza

41

Influenza A(H1N1)
General Population Prevention Guidelines
Cover nose and mouth with tissue
when coughing or sneezing
Dispose of tissue in trash after use

Handwash with soap and water

Especially after coughing or sneezing.

Clean hands with alcohol-based hand

cleaners
Avoid close contact with sick people
Avoid touching eyes, nose or mouth
with unwashed hands
If sick with influenza, stay home from
work or school and limit contact with
others to keep from infecting them
Source: Chotani Supercourse lecture

CPM Influenza

42

Influenza A(H1N1)
Treatment

Vaccine available
Antivirals for treatment and/or prevention (?) of
infection:
Oseltamivir (Tamiflu) or
Zanamivir (Relenza)

Use of anti-virals can make illness milder and

recovery faster; may also prevent serious flu
complications
For treatment, antiviral drugs work best if started
soon after getting sick (within 2 days of symptoms)
Source: CDC

CPM Influenza

43

Influenza A(H1N1)
Other Protective Measures
separation
of symptomatic
patents either inpatents
the home or
separation
of
symptomatic
Isolation:
hospital so that they will not infect others
either in the home
or hospital
so that
they
not
separation
of asymptomatic
persons
thatwill
may have
been exposed
to infection
infect
others
Quarantine: separation from of asymptomatic persons that may have been
exposed to infection

non-quarantine measures that reduce contact between persons,

such as closing ofnon-quarantine
schools or prohibiting
gatherings
measureslarge
that reduce
contact between
Social-Distancing:
persons, such as, closing of schools or prohibiting large gatherings

Source: CDC

CPM Influenza

44

Influenza A(H1N1)
Summary

WHO alert level Phase 6

Highly communicable, now global
Overall case-fatality rate <1%, but higher in Mexico
(1.2%) and elsewhere
Majority of cases reported in health young adults
Majority (but not all) of deaths had underlying conditions

Vaccine available
Anti-virals available

45

CPM Influenza

Requirements for Pandemic

Requirements for Pandemic

H5N1

Novel
H1N1

New human influenza A subtype

Causes serious illness

Spreads easily from human-to-human

46

CPM Influenza

Comparison to 1918 Pandemic

Characteristics of 1918 Pandemic

H5N1

Novel
H1N1

Spring: mild illness but easily

transmissible from person to person
Influenza A avian-type virus
Affects mostly younger people
Kills millions of people in
the Fall
CPM Influenza

X
47

Its only flu

48

CPM Influenza