DEFINITION

HISTORY
EPIDEMIOLOGY
PROGNOSIS
MORPHOLOGY
CLASSIFICATION
TYPES
CAUSES
SIGN & SYMPTOMS

WHAT IS INFLUENZA ?
Known as the flu
More severe disease than common
cold
An infectious
disease of birds and mammals
Caused by RNA viruses of the
family Orthomyxoviridae

HISTORY
ETHYMOLOGY
~The word Influenza comes from
the Italian language meaning
"influence and refers to the cause of
the disease
~Changes in medical thought led to its
modification to influenza del freddo,
meaning "influence of the cold".

~ The word influenza was first used in English to refer to the

disease we know today in 1703 by Hugger of the University
Of Edinburgh.
~Archaic terms for influenza include epidemic catarrh,
grippe (from the French, first used by Molyneaux in
1694) sweating sickness, and Spanish fever (particularly for
the 1918 flu pandemic strain).

PANDEMIC
~human influenza were clearly described by Hippocrates
roughly 2,400 years ago.
~disease may have spread from Europe to the Americas
as early as the European colonization of the Americas.
~The first convincing record of an influenza pandemic was
of an outbreak in 1580, which began in Russia and
spread to Europe via Africa.
~The most famous and lethal outbreak was the 1918 flu
pandemic (Spanish flu pandemic) (type A
influenza, H1N1 subtype), which lasted from
1918 to 1919.

~symptoms in 1918 were so unusual that initially

influenza was misdiagnosed as dengue, cholera, or
typhoid
~The etiological cause of influenza, was first discovered
in pigs by Richard Shope in 1931
~The first significant step towards preventing influenza
was the development in 1944 of a killed-virus vaccine for
influenza by Thomas Francis, Jr..

Known flu pandemics

Deaths

Case fatality
rate

Subtype
involved

Pandemic
Severity
Index

Asiatic
(Russian) Flu 18891890

1 million

0.15%

possibly H3
N8

NA

1918 flu
pandemic 19181920
(Spanish flu)

20 to 100
million

2%

H1N1

0.13%

H2N2

<0.1%

H3N2

0.03%

H1N1

NA

Name of
pandemic

Date

Asian Flu

19571958

Hong Kong
Flu

19681969

1 to 1.5
million
0.75 to 1
million

2009 flu
pandemic

20092010

18,000

EPIDEMIOLOGY
Influenza can be traced as far back as 400BC
In Hippocrates of the Epidemics, he describes a cough
outbreak that occurred in 412 BC in modern-day Turkey at
the turn of the autumn season

18th century: Between 1781=1782, an influenza epidemic infected 2/3 of

Romes population and of Britains population
Disease spread to North America, West Indies and South
America

Spread of pandemic culminated in New England,

New York and Nova Scotia in 1789.

1781 marked the beginning of the 10-40 year cycle of

influenza epidemics and pandemics.

PROGNOSIS
~most people will recover completely in
about one to two weeks, but others will
develop life-threatening complications
(such as pneumonia).
~ Influenza, thus can be deadly,
especially for the weak, young
and old, or chronically ill.

~People with a weak immune system and suffer from

particularly severe disease.
~Other high-risk groups include pregnant women and young
children.
~Smoking is another risk factor.
~Even healthy people can be affected, and serious problems from
influenza can happen at any age.

MORPHOLOGY

Types A, B, C
Diameter 80 - 120 nm
Pleomorphic, spherical, filamentous particles
Single-stranded RNA
Segmented genome, 8 segments in A and B
Hemagglutinin and Neuraminidase on surface of
virion

STRUCTURE OF INFLUENZA VIRUS

contains seven different structural
proteins.
Three major proteins (PB1, PB2, and
PA) bound to RNA viruses and are
the cause of the transcription and
replication of RNA
Envelope consists of Haemagglutinin
and Neuraminidase (H and N), which
determines variants of influenza virus

CLASSIFICATION
~ influenza viruses are RNA viruses that make up
three of the five genera of the family Orthomyxoviridae : Influenza virus A
Influenza virus B
Influenza virus C
~They are only distantly related to the human parainfluenza
viruses, which are RNA viruses belonging to the paramyxovirus
family that are a common cause of respiratory infections in
children such as croup, but can also cause a disease similar to
influenza in adults.

TYPES
Influenza virus A
~This genus has one species, influenza A virus.
~Wild aquatic birds are the natural hosts.
~viruses are transmitted to other species and may then cause
devastating outbreaks in domestic poultry or give rise to human
influenza pandemics.
~most virulent human pathogens among the three influenza
types and cause the most severe disease.
~can be subdivided into different serotypes based on the antibody
response to these viruses.

~The 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 Swine Flu in 2009
*H2N2, which caused Asian Flu in 1957
*H3N2, which caused Hong Kong Flu in 1968
*H5N1, which caused Bird Flu in 2004
*H7N7, which has unusual zoonotic potential
*H1N2, endemic in humans, pigs and birds
*H9N2
*H7N2
*H7N3
*H10N7

Influenza B
~This genus has one species, influenza B virus.
~exclusively infects humans and is less common
than influenza A.
~ animal susceptible to influenza B infection are
the seal and the ferret.
~ influenza B mutates at rate 23 times slower
than type A and consequently is less genetically
diverse, with only one influenza B serotype.

~ As a result , a degree of immunity to influenza B is usually

acquired at an early age.
~However, influenza B mutates enough that lasting immunity
is not possible.
~This reduced rate of antigenic change, combined with its limited
host range (inhibiting cross species antigenic shift), ensures
that pandemics of influenza B do not occur

Influenza virus C
~This genus has one species,
influenza C virus, which infects
humans, dogs and pigs, some times
causing both severe illness and
local epidemics

~However, influenza C is less common

than the other types and usually only
causes mild disease in children.

COMPARISON OF INFLUENZA A, B AND C

TYPE A

TYPE B

TYPE C

Severity of illness

++++

++

Animal reservoir

yes

no

no

Human pandemics yes

no

no

Human epidemics yes

yes

no (sporadic)

Antigenic changes shift, drift

drift

drift

Segmented
genome

yes

yes

yes

Amantadine,
rimantidine

sensitive

no effect

no effect

Zanamivir
(Relenza)

sensitive

sensitive

Surface
glycoproteins

(1)

~Variants of flu virus are sometimes named

according to the species the strain is endemic in
or adapted to
~main variants named using this convention are:
Bird Flu
Human Flu
Swine Flu
Horse Flu
Dog Flu

COMPARISON OF SEASONAL AND PANDEMIC FLU

SEASONAL
PANDEMIC
Outbreaks follow predictable seasonal patterns;

Occurs rarely (a few times a century)

occurs annually, usually in winter, in temperate

No previous exposure; little or no pre-existing

climates

immunity

Usually some immunity built up from previous

Healthy people may be at increased risk for

exposure

serious complications

Healthy adults usually not at risk for serious

Health systems may be overwhelmed

complications; the very young, the elderly and those

Vaccine probably would not be available in the

early stages of a pandemic

with certain underlying health conditions at increased

risk for serious complications
Health systems can usually meet public and patient
needs
Vaccine developed based on known flu strains and
available for annual flu season

From CDC

Effective anti-virals may be in limited supply

Number of deaths could be quite high (e.g., U.S.
1918 death toll approximately 675,000)

Adequate supplies of anti-virals are usually

Symptoms may be more severe and

available

complications more frequent

Average U.S. deaths approximately

May cause major impact on society (e.g.

36,000/yr

widespread restrictions on travel, closings

Symptoms: fever, cough, runny nose,

of schools and businesses, cancellation of

muscle pain. Deaths often caused

large public gatherings)

by complications, such as pneumonia.

Potential for severe impact on domestic

Generally causes modest impact on

and world economy

society (e.g., some school closing,

encouragement of people who are sick to

stay home)
Manageable impact on domestic and world
economy

CAUSES
~ the air by coughs or sneezes, creating aerosols
containing the virus.
~ Airborne aerosols
~ direct contact with bird droppings or nasal secretions
~ contact with contaminated surfaces or water .
~ Influenza viruses can be inactivated by sunlight,
disinfectants and detergents.
~ frequent hand washing reduces the risk of infection.

Signs and Symptoms

Fever, usually over 100F
Cough with little or no sputum

Chills and/or sweats

Nasal congestion
Headache
Muscle aches
Sore throat
Chest soreness, light sensitivity, and eye pain

The Life Cycle of the Influenza

Virus
Influenza is a contagious viral infection of the
respiratory system causing illnesses in animals
and people.
Because the influenza virus reproduces quickly,
can mutate easily and is easy to contract, it can be
difficult to prevent the spread of infection.

Initial
Infection

Cellular
Stage

Genetic
Reproductio
n

Infectious
Stage

Extracellular
Activity

Initial Infection
Influenza is spread primarily in tiny
droplets expelled during coughing or
sneezing.
They can be easily inhaled or may come
in contact with objects that a potential
host may touch, thereby transmitting the
disease.

Cellular Stage
Once the virus has entered the host, it
will fuse to the plasma membrane of a
permissive cell within the respiratory
tract, particularly in the nose, mouth and
throat.

Genetic Reproduction
The virus will enter the cytoplasm of the
cell and then proceed to the nucleus.
Once the virus enters the nucleus, it
deposits genetic material, replicates its
genome and forms new gene particles.

Extracellular Activity
The new virus particles will then leave the
cell and invade surrounding tissues to
infect other cells.
This process will be repeated until the
virus has proliferated throughout the
body.

Infectious Stage
The virus will then be shed from the
mucous membranes into the saliva
and nasal discharge of the host.
Sneezing or coughing will then
spread the disease to other potential
hosts.

INFLUENZA REPLICATION
Viruses can replicate only in living cells
Influenza virus replicates is a multi-step
process:
1st , the virus has to bind to and enter
the cell,
2nd , deliver its genome to a site where
it can produce new copies of viral
proteins and RNA,
3th , assemble these components into
new viral particles, and,
4th , exit the host cell.

ST
1 STEP
Viruses binds onto sialic acid sugars on
the surfaces of epithelial cells
through hemagglutinin.

WHAT IS THAT :
Sialic acid sugars ; sialoglycoprotein
Sialic Acid : Derivative of
Neuraminic acid
Glycoprotein : Sugar and protein.

Then, the hemagglutinin is cleaved by

a protease, the cell imports the virus
by endocytosis.

ND
2 STEP
The acidic conditions in the endosome cause two events to happen:
First, part of the hemagglutinin protein fuses the viral envelope with the
vacuole's membrane,
then the M2 ion channel allows protons to move through the viral
envelope and acidify the core of the virus, which causes the core to
dissemble and release the viral RNA and core proteins into the cytoplasm.

FACT: Amantadine drugs works by blocking the M2 ion channel to prevent

infection.

 Once the vRNA is in the cytoplasm it travels to the nuclues n

enter the nucleus thru the nuclear pore
The nucleus will decode the vRNA for protein productions
The ribosome will synthesized viral proteins which will :
Either enter nucleus to bind vRNA and form new viral
genome particles
Or will secreted through the Golgi apparatus onto the cell
surface ( Hemagglutinin and neuraminidase molecules)

RD
TH
3 & 4 STEP

The vRNA and viral core proteins leave the nucleus and enter
this membrane protrusion
The newly synthesized vRNA and other viral proteins are
assembled into a virion.
Hemagglutinin and neuraminidase molecules cluster into a
bulge in the cell membrane.
After the release of new influenza viruses, the host cell dies.

REPLICATION OF INFLUENZA VIRUS

INFLUENZA PATHOLOGY
Influenza virus replicates in the epithelial cells throughout the respiratory tree, with virus
being recoverable from both the upper and lower respiratory tract of people naturally or
experimentally infected .As histologic changes are nonspecific, histologic analysis alone is
insufficient to make a specific diagnosis diagnosis typically requires supporting diagnostic
tests such as viral isolation, rapid diagnostic tests serologic studies, or a biopsy or autopsy
tissue section confirmed by immunohistochemical techniques Non-fatal influenza viral

infections predominantly involve the upper respiratory tract and trachea, but fatal cases of
influenza usually show evidence of pneumonia.

Figure 1. Sites of influenza entry in the respiratory tract. (A) The anatomical and functional structures of
the human airways are shown. Influenza first infects the upper airway and the ciliated cells in the
bronchus and bronchioli. Resulting clinical syndromes include tracheitis, bronchitis, bronchiolitis, and
bronchopneumonia. The adaptive immune response is initiated in lymph nodes along the airways. (B)
The respiratory epithelia is especially equipped to defend from incoming pathogens by a layer of mucus
(bronchus), ciliated cells (bronchus and bronchioli), and alveolar macrophages (alveoli).

The pathogenicity and virulence of the influenza virus is determined by several

interacting factors:

Host factors:
Presence of target receptors on host cells
Availability of enzymes in host cells which are essential for viral entry and replication
State of immunocompetence of the individual host
Specific immunity against certain viral epitopes in the individual host and target
population
Ability of the immune system to control the viral replication effectively without
causing serious collateral damage for the host by its inflammatory response

Viral factors:
Ability to bind to host cells

Ability of virus shedding

Restriction of cytopathogenic effects to allow for an appropriate balance
between viral replication and control by the host
Escape from immunosurveillance by evolution of antigenic variation driven by
selective pressure of the immune response

Escape from immunosurveillance by recombination with different virus strains

from zoonotic disease
Modulation of the immune response to attenuate effective host defense
mechanisms

A recent paper compiled data from a number of studies in which

human volunteers were given influenza virus, and the production of
virus and flu-like symptoms were recorded. The results are
summarized in this graph

Figure 2: Replication cycle of influenza A virus. Binding and entry of the virus,
fusion with endosomal membrane and release of viral RNA, replication within
the nucleus, synthesis of structural and envelope proteins, budding and
release of virions capable of infecting neighboring epithelial cells (Modified
from Cox & Kawaoka 1997)

TREATMENT &
PREVENTION OF
INFLUENZA
VIRUS

vaccination
Influenza vaccines have been used since 1945.
Available Vaccines:
Product: Agriflu (TIV)
Manufacturer: Novartis
Year licensed: 2009
Indications: For persons ages 18 years of age and older.
Product: Fluzone High Dose (TIV)
Manufacturer: Sanofi Pasteur
Year Licensed: 2009
Indications: For persons ages 65 years and older.
Product: Afluria (TIV)
Manufacturer: CS Limited
Year Licensed: 2007
Indications: For persons 6 months of age and older.

Who should not receive influenza vaccine:

Infants younger than six months of age.

People who have had an anaphylactic reaction (allergic reactions
that cause difficulty breathing, which is often followed by shock) to
eggs, egg products, or other components of the flu vaccine. There
are antiviral agents which doctors can prescribe as an alternative
for preventing influenza in such people.
People with acute serious illness with fever
People who are moderately or severely ill should consult with their
physician before receiving any vaccine
People with a history of asthma or other reactive airway diseases
should not be given LAIV.
People with chronic underlying medical conditions that may
predispose them to severe influenza infections should also not be
given LAIV. For these people, TIV is indicated.
LAIV should not be given to pregnant women.
(LAIV=trivalent influenza virus vaccine )

Effectiveness of the vaccines :

The vaccine protects between 45% and 90% of healthy
children from getting influenza.
Studies indicate that the older and healthier children who
have received the influenza vaccine are, the more likely they
will be protected.
Influenza vaccination has also been shown to decrease
middle ear infections among young children by about 30%.

Diagnosis
There are several influenza tests available that may be used to help make diagnosis :

Rapid influenza diagnostic test (RIDT)

used to detect the virus in nasal secretions and one of the most common methods
used to diagnose this infection.
Direct fluorescent antibody stain (DFA)
detects influenza A or B virus in samples of nasal secretions. This method of testing is
more specific than RIDT but requires specialized equipment.
Viral culture
It can be used for confirmation of a positive rapid test result. In this test, the influenza
virus is actually grown and identified in the laboratory. It has the advantage of identifying
which viruses (A, B, or another respiratory virus) and which strains of virus are present.

 Influenza A or B antibody tests

these are blood tests performed to detect the body's immune response to an influenza
infection.

What does the test result mean?

If a flu test is positive, it means that the affected person most likely has influenza A
or B, and treatment with antiviral medication may be prescribed to minimize
symptoms. However, it may not tell the doctor which strain of influenza is causing
the infection, how severe the symptoms are likely to be, or whether or not a person
may experience any secondary complications.
A negative influenza test may mean that the person has something other than
influenza, that the test is not detecting the influenza strain, or that there is not
sufficient virus in the specimen to allow it to be detected.

MEDICATION
Influenza A & B:
Oseltamivir (Tamiflu)
Zanamivir

Influenza A:
Amantadine
Rimantadine

HOME TREATMENT
Bed rest
Drink extra fluids at least one full glass of water or juice every hour.
Acetaminophen (Tylenol), or Ibuprofen can relieve head and muscle
aches. Aspirin should be avoided for children.

When To Call A Health Professional

After three days of fever over 102 F.
If cough brings up heavy mucus.
If there is increasing difficulty in breathing.
When a patient seemingly gets better, then gets worse again.
If flu-like symptoms occur 10 days to three weeks.