Dr.

Jagadish Nuchin
MD,MBA

June 10, 2009 1

 Problem statement - In pigs
Swine flu or pig flu or hog flu or
SIV
Endemic (H1N1 and H3N2) in most
of the countries- worldwide- OIE
 25 percent of animals show
antibody evidence of infection.
(51% in north-central America)
Occurs all the months
Outbreaks usually occur in cold
season
H1N1 strains are circulating in pig
population since 1930 and H3N2
June 10, 2009 2
Transmission of swine
influenza virus from
pigs to humans is not
common
( Zoonotic swine flu)-
very rare
So far only few such
cases have been
occurred globally with
no man to man
transmission (WHO)
Pigs have been
described as ‘mixing
vessels’ for the various
influenza
June 10, 2009 virus strains- 3
 Problem statement in Man
Influenza is an ARTI caused by
influenza viruses
Occurs in all the countries affecting
5-15% of the global population,
resulting in severe illness in 3-5
million patients and causing 250,000-
500,000 deaths worldwide.
In addition to these annual
epidemics, the influenza A virus has
caused three major global pandemics
during the 20th century: the Spanish
June 10, 2009 4
 Year Deaths CFR Influenza PSI
(Millions)
A
subtype
Asiatic
1889–1890 1 NA Possibly H2N2 ?
( Russian)
flu
Spanish 1918 20-100 2.5 H1N1 5
flu
Asian flu 1957 2 0.1 H2N2 2
Hong 1968 1 0.1 H3N2 2
Kong
 Epidemiologic
al features

June 10, 2009 6

It may occur in several forms- as
 Subclinical cases – being manifest
only by serological surveys (1/3 of the
total)
 Pandemics- every 10-15 years once
(due to major antigenic changes)
 Epidemics –tend to occur at intervals of
2-3 years in case of Influenza A and 4-
7 years in case of Influenza B. this
periodicity is not regular like measles
June 10, 2009
and diphtheria 7
Unique features of influenza
epidemics
Epidemic starts in a characteristic
way.
Begins with a few cases, soon
followed by sudden outburst of
disease - indicated by
 rise in the incidence of febrile respiratory
illness in children and old- high attack rates-
10-50%
 Increased hospitalization of cases

 Sickness-absenteeism in schools/working
June 10, 2009 8
Factors contributing to easy
and fast spread of the disease
Short incubation period
Large number of mild and
subclinical cases
High proportion of susceptible
population
Short duration of immunity
Absence of cross-immunity (sub-
type specific)
June 10, 2009 9
Influenza viruses
They are RNA viruses
Infect mammals and birds and cause
ARTI
The name influenza comes from the
Italian influenza, meaning "influence"
(Latin: influentia).
The word influenza was first used in
English in 1743
Virus was first discovered in pigs by
Richard Shope in 1931.
June 10, 2009 10
Morphology
Influenza viruses have a very similar
structure.
The core consists of RNA
The influenza viruses are classified
into A,B, and C serotypes based on
type of RNA (M1 and NP internal
antigens)
The envelope has an inner protein
layer and an outer lipid layer
June 10, 2009 11
 Influenza viruses
Belong to Orthomyxoviridae family, which
comprises five genera:
Influenza virus A –Birds (mainly wild aquatic
birds) and mammals
Influenza virus B – exclusively humans and
rarely seals
Influenza virus C – man and pigs
Isa virus -infect salmon
Thogoto virus-infect vertebrates and
invertebrates, such as mosquitoes and sea lice.

June 10, 2009 12

Two types of spikes
(peplomers) are projected from
the
envelope – Haemagllutinin
( more in number) and
Neuraminidase (less in
number)
The virus particle is 80–120
June 10, 2009 13
Influenza virus A

• Wild aquatic birds are the natural

hosts for a large variety of
influenza A.
• Occasionally, viruses are
transmitted to other species and
may then cause devastating
outbreaks in domestic poultry or
give rise to human influenza
pandemics
June 10, 2009 14
Influenzavirus B
• Influenza B almost exclusively infects
humans and seals
• Is less common than influenza A.
• Mutation takes place very slowly (less
genetically diverse), with only one influenza
B serotype.
• immunity to influenza B is usually acquired
at an early age.
• However, influenza B mutates enough that
lasting immunity is not possible.
• 10,pandemics
June 2009 are less likely 15
Influenzavirus C
Infects humans and pigs and
can cause severe illness and
local epidemics.
However, influenza C is less
common than the other types
and usually seems to cause mild
disease in children.
June 10, 2009 16
 Influenza A
H1N1

June 10, 2009 17

Classification of Influenza A
Influenza A viruses are further classified,
based on the viral surface proteins
hemagglutinin (HA or H) and
neuraminidase (NA or N).
Sixteen H subtypes (or serotypes) and
nine N subtypes of influenza A virus have
been identified but only H 1, 2 and 3, and
N 1 and 2 are commonly found in humans
(CDC)
Influenza A virus strains are assigned an
H number and an N number based on,
June 10, 2009 18
 The Influenza A
genome
encodes 11
proteins:
hemagglutinin
(HA),
neuraminidas
e (NA),
nucleoprotein
(NP), M1, M2,
NS1, NS2(NEP),
PA, PB1, PB1-F2
and PB2.
June 10, 2009 19
 • HA and NA are large glycoproteins on
the outside of the viral particles.
• HA is a lectin that mediates binding
of the virus to target cells and entry
of the viral genome into the target
cell, while NA is involved in the
release of progeny virus from
infected cells, by cleaving sugars that
bind the mature viral particles.
• Thus, these proteins are targets for
June 10, 2009 20
The Influenza A serotypes that have been
confirmed in humans, ordered by the number of
known human pandemic deaths, are:
• H1N1, which caused Spanish flu in 1918 and has been identified as
the serotype of the 2009 outbreak of swine flu originating from
Mexico
• H2N2, which caused Asian Flu in 1957
• H3N2, which caused Hong Kong Flu in 1968
• H5N1, a pandemic threat in the 2007–08 flu season
• H7N7, which has unusual zoonotic potential
• H1N2, endemic in humans and pigs
• H9N2
• H7N2
• H7N3
• H10N7
• In 2009, a recombinant influenza virus
derived in part from H1N1 was first
detected in Mexico and the United
States.
June 10, 2009 21
 New Strain- Influenza A
(H1N1)
Origin-not known. But researchers say that
the new H1N1 strain first evolved around
September 2008 and circulated in the
human population for several months
before the first cases were detected.
First confirmed case- April 13th 2009
( Women died of pneumonia) in Oaxaca,
Mexico.

June 10, 2009 22

 Reassortment
The mixing of the genetic material of two
similar viruses infecting the same cell.
In particular, reassortment occurs among
influenza viruses, whose genomes consist of
eight distinct segments of RNA.
These segments act like mini-chromosomes,
and each time a flu virus is assembled, it
requires one copy of each segment.
The new reassortant strain will share
properties of both of its parental lineages.
June 10, 2009 23
 Reassortment

June 10, 2009 24

June 10, 2009 25
H1N1

June 10, 2009 26

The Influenza A H1N1 virus contains
the gene segments from 4 viruses
North American swine
North American Avian
North American human
 Eurasian swine

June 10, 2009 27

As on today
8 June 2009 -- As of 06:00 GMT, 8 June 2009,
73 countries have officially reported 25,288
cases of influenza A(H1N1) infection, including
139 deaths.

June 10, 2009 28

June 10, 2009 29
June 10, 2009 30
India as on 8 June
th

June 10, 2009 31

 Phase 1- no influenza viruses
circulating among animals have
been reported to cause infections in
humans.
Phase II- an animal influenza virus
circulating among domesticated or
wild animals is known to have
caused infection in humans, and is
therefore considered a potential
June 10, 2009 32
 3) Phase III-an animal or human-animal
influenza reassortant virus has caused
sporadic cases or small clusters of disease in
people, but has not resulted in human-to-
human transmission sufficient to sustain
community-level outbreaks.
4) Phase IV- human-to-human transmission of
an animal or human-animal influenza
reassortant virus able to cause “community-
level outbreaks.”

June 10, 2009 33

 5) Phase V-human-to-human spread of the virus
into at least two countries in one WHO region.
6) Phase VI- community level outbreaks in at
least one other country in a different WHO
region in addition to the criteria defined in
Phase 5. Designation of this phase will
indicate that a global pandemic is under way.

June 10, 2009 34

June 10, 2009 35
Why concern
 A novel strain
 Man to man transmission
 Virulence
 No natural or artificial immunity

June 10, 2009 36

 Source of infection- A case or a
subclinical case
Period of infectivity- the virus is
present in the nasopharynx from
1-2 days before to 3-7 days after
the onset of symptoms

June 10, 2009 37

Immunity
All the three are antigenically unrelated,
hence no cross protection and it is
subtype-specific
Antibodies appear 5 days after infection
reach the peak in 2 weeks. After 8-12
months, the titre drops to preinfection
level
Antibodies against HA- neutralizes the
virus
( inhibits initiation of infection)
Antibodies against NA-reduces the disease
June severity
10, 2009 and decreases the ability to 38
 Antibodies against
ribonucleoprotein are type
specific- useful in typing viral
isolates as A or B.
Serum antibodies persist for
many months whereas secretory
(IgA) antibodies in nasal
secretions are short lived.
June 10, 2009 39
Season
epidemics usually occur in
winter months in Northern
hemisphere and in winter or rainy
season in the Southern
hemisphere. In India, epidemics
often occurred in summer

June 10, 2009 40

Mode of transmission
By three ways-
1) by direct transmission- when an infected
person sneezes mucous into eys, nose or
mouth.
2) by aerosols produced by infected people
coughing, sneezing and spitting and
3) through hand-to-mouth transmission from
either contaminated surfaces (Fomites) or
direct personal contact, such as a hand-shake.

June 10, 2009 41

 Influenza can also be transmitted by contact
with infected bird droppings (in case of avian
influenza), saliva, nasal secretions, feces,
blood and with contaminated surfaces.
 Airborne aerosols have been thought to
cause most infections, although which
means of transmission is most important is
not absolutely clear.

June 10, 2009 42

Survival of virus
Influenza viruses can be inactivated by sunlight,
disinfectants and detergents

1) Hard non-porous surface-

-Transferable to hands up to 24 hrs

- recoverable for >24 hrs
2) Cloth and paper-
Transferable to hands up to 15 minutes
recoverable for 8-12 hrs
3) On hands- viable up to 5minutes only at high viral
titre
Required humidity is 35-40% and
temperature 28 degree Celsius
June 10, 2009 43
 Overcrowding enhances the
transmission
Portal of entry- RT
Incubation period- 18-72 hrs
( up to 7 days-WHO)

June 10, 2009 44

Pathogenesis
The virus enters the RT, causes inflammation
and necrosis of superficial epithelium of
tracheal and bronchial mucosa, followed by
secondary infection.
There is no vireamia

June 10, 2009 45

 Clinical
symptoms are
similar to
seasonal
influenza -chills,
fever, running
nose, sore
throat, muscle
pains, severe
headache,
coughing,
weakness,
general
discomfort,
shortness of
June 10, 2009 46
Risk group/factors
Risk group (associated with more serious disease
and increased mortality from influenza-
complications are more like pneumonia, bronchitis,
sinus, and ear infections)
 Young children
 Weak
 Old
 With chronic pulmonary diseases
 Smoking

June 10, 2009 47

 Contrast to seasonal flu, here the symptoms
are severe, last longer and complications are
common with high mortality
The most dreaded complication is pneumonia
( especially in children and old), which should
be suspected if fever persists beyond 4-5 days
or recurs abruptly after convalescence.

June 10, 2009 48

Laboratory diagnosis
1) Virus isolation- Specimen- Nasopharyngeal
secretions are the best specimens as they
contain the large amounts of virus-infected cells.
Egg inoculation of virus may be required

 Real time RT PCR

 The virus can also be
detected by Fluorescent
antibody technique
June 10, 2009 49
 2) Paired Sera-
First sample- in acute phase, not later
than 5th day
Second sample- in convalescent
phase- 10-15 days after the onset of disease

Fourfold rise- Diagnostic

At least 2-5ml of serum should be
sent
June 10, 2009 50
Where to send in India
NIV Pune
NICD new Delhi
Govt. of India, Influenza centre, Pasteur
institute, Coonoor.
Haffkine Institute, Mumbai
School of Tropical Medicine, Kolkata
AIIMS, New Delhi
Armed Forces Medical College, Pune

June 10, 2009 51

Case definitions
Suspect Case
 Defined as an individual with an acute febrile
respiratory illness (fever >38°C) with onset of
symptoms:
– Within 7 days of travel to affected areas; or
– Within 7 days of close contact with a
confirmed or probable case of Swine Influenza A
(H1N1)

June 10, 2009 52

 Probable Case
 Defined as an individual with an acute febrile
respiratory illness (fever >38°C) with an
influenza test that is positive for Influenza A
but is un-subtypeable by reagents used
to detect seasonal influenza virus infection,
OR;
 an individual with a clinically compatible
illness or who died of an unexplained acute
respiratory illness who is considered to be
epidemiologically linked to a probable or a
confirmed case.
June 10, 2009 53
 Confirmed Case
Defined as an individual with laboratory
confirmed Swine Influenza A (H1N1) virus
infection by one or more of the following
tests:
Real-time RT-PCR; Viral culture;
 Four-fold rise in Swine Influenza A (H1N1)
virusspecific neutralizing antibodies

June 10, 2009 54

Treatment- oseltamivir and
zanmivir
Oseltamivir- both for treatment and prophylaxis

Infants Dosage Duration

<3 months 12 mg BD 5 days

3-5 months 20mg BD 5 days

6-11 months 25mg BD 5 days

Others

<15kg 30mg BD 5 days

15-23kg 45mgBD 5 days

24-40kg 60mgBD 5 days

>40kg 75mg BD 5 days

June 10, 2009 55
Dose and
duration can
be modified
as per clinical
condition.
Also
available as
syrup
(12mg/ml)
June 10, 2009 56
Prevention and Control

June 10, 2009 57

Less successful

During the outbreak-

Use of masks- in
cases and contacts
Use of hand
kerchief while
sneezing/coughing
If you don't have a
tissue, cough or
sneeze into your
sleeve.
June 10, 2009 58
Hand washing with disinfectants
Avoid touching mouth, nose or
eyes with hands unless you
wash your hands.

June 10, 2009 59

 Avoid overcrowding
Good ventilation of building
Stay at home at the first sign of
influenza
No travelling to affected
countries/areas
Screening at air/sea port

No risk of flu
June 10, 2009 60
Vaccines
Right now no vaccines for this new strain
WHO/CDC assured a vaccine in another 6-8
months now

June 10, 2009 61

Bottlenecks for
vaccination
 Influenza epidemics are unpredictable
 Because of antigenic variation, new vaccines
are constantly required- A vaccine formulated
for one year may be ineffective in the
following year, since the influenza virus
evolves rapidly, and different strains become
dominant.
 Right now no vaccine for current strain, may
take several months for manufacturing huge
quantity(CDC)

June 10, 2009 62

 Than
k you
all
June 10, 2009 63