INTRODUCTION
Influenza, commonly referred to as the flu, is
an infectious viral disease caused by RNA
viruses of the family Ortho-myxoviridae (the
influenza viruses),
affects birds and mammals. that
Common symptoms are chills, fever, sore
throat, muscle pains, severe headache, coughing,
fatigue and general discomfort.
Although confused with other influenza-like illnesses,
especially the common cold, influenza is a more severe
disease .
DEFINITION
WHO : Influenza is a viral infection that
affects mainly the nose, throat, bronchi and,
occasionally, lungs. Infection usually lasts
for about a week, and is characterized by
sudden onset of high fever, aching muscles,
headache and severe malaise, non-
productive cough, sore throat and rhinitis.
HISTOR
Y
Influenza can be traced as far back as 400 BC
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
17th century:-
• Between 1781-1782, an influenza epidemic infected 2/3 of Rome’s
population and ¾ of Britain’s population. Later, 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 of influenza epidemics
and
pandemics
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American Red Cross nurses keep the flu patients in
temporary wards set up inside the Oakland municipal
Auditorium.
EPIDEMILOGICAL
DETERMINANTS
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AGENT
Influenza viruses are classified within the family
of Ortho-myxoviridae.
There are three viral sub–types, namely influenza
type A, type B and type C.
These three viruses are antigenically distinct.
There is no cross–immunity between them.
Of importance are the influenza A and B viruses
which are responsible for epidemics of disease
throughout the world.
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CONTD..
I. Both influenza A and B viruses have two
distinct surface antigens – the
Hemoglutinin (H) and the
Neuraminidase (N) antigens.
II. The H antigen initiates infection
following attachment of the virus to
susceptible cells. The N antigen is
responsible for the release of the
virus from the infected cell.
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I. The influenza A virus is unique among
the viruses because it is frequently
subject virus to antigenic variation, both
major and minor.
I. When there is a sudden, complete or
major change, it is called a shift, and
when the antigenic change is gradual,
over a period of time, it is called a drift..
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CONTD..
. Antigenic shift appears to result from
genetic recombination of human with
animal or avian virus, providing a major
antigenic change.
This can cause a major epidemic or
pandemic involving most or all age
groups.
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CONTD..
.
Antigenic drift involves “Point
mutation” in the gene owing to selection
pressure by immunity in the host
population.
Antigenic changes occur to a lesser
degree in the B group influenza viruses.
Influenza C appears to be antigenically
stable.
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• Since the isolation of the virus A in
1933, major antigenic changes have
occurred twice
– once in 1957 (H2N2) and then again
in
1968 (H3N2).
• Strains occurring between 1946 and 1957
have been called H1N1 strains. The shift in
1968 involved only the H antigen.
• In 1977, a new antigenic type appeared in
China and the USSR and the virus was
identified as A (H1N1). Within a year, it had
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• Curiously, this was an earlier virus which has
appeared after a lapse of over 20 years.
• In the past, the emergence of a new, influenza
A sub–type led to the prompt disappearance of
the previously prevalent sub–type. In the 1977
episode, however, this did not happen.
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The prevailing A (H3N2) was not displaced.
Dual infection with both viruses were
reported.
As of now, three types of influenza viruses
– A (H1N1), A (H3N2) and B exist.
Influenza viruses of the H1N1 sub–type have
caused epidemics of the disease in two periods
of this century – from about 1946 up until
1957, and from 1977 until the present.
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STRUCTURE OF VIRION
HA - hemagglutinin
NA - neuraminidase
helical nucleocapsid (RNA plus
NP protein)
lipid bilayer membrane
polymerase complex
M1 protein
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RESERVOIR OF INFECTION
It has become increasingly evident that a
major reservoir of influenza virus exists in
animals and birds.
Many influenza viruses have been isolated
from a wide variety of animals and birds
(e.g. swine, horses, dogs, cats, domestic
poultry, wild birds, etc.)
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CONTD..
.
Some of these include the major H and
N antigens related to human strains.
There is increasing evidence that the
animal reservoir provides new strains of
the influenza virus by recombination
between the influenza viruses of man,
animals and birds.
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SOURCE OF INFECTION
The source of infection usually is a case or
sub–clinical case.
During epidemics, a large number of mild and
asymptomatic infections occur, which play an
important role in the spread of infection.
The secretions of the respiratory tract are
infective.
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PERIOD OF INFECTIVITY
The
present in vir
naso-pharynx us
couple of days
before and a
couple of daysis
after the onsetthe
of
symptoms. a
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HOST FACTORS
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AGE AND SEX
o Influenza affects all ages and people of both
sexes. In general, the attack rate is lower
among adults. Children constitute an
important link in the transmission chain.
o The highest mortality rate during an epidemic
occurs among certain high–risk groups in the
population such as old people (generally over
65 years of age), infants under 18 months,
and persons with diabetes or chronic heart
disease, kidney and respiratory ailments.
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HUMAN MOBILITY
This is an important factor in the spread of the
infection.
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IMMUNITY
Antibodies appear in about seven days
after an attack and reach a maximum level
in about two weeks. After about 8 to 12
months, antibody levels drop to pre–
infection levels.
The antibody to H neutralizes the virus
while the antibody to N modifies the
infection.
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CONTD..
.
Secondary antibodies develop in
the tract
respiratory
after
andpredominantly
consist infection of lgG.
Antibodies must be present in sufficient
concentrations at the superficial cells (the site
of virus invasion) of the respiratory tract.
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ENVIRONMENTAL FACTORS OF INFLUENZA
Season
The seasonal incidence is striking, epidemics usually
occur in the winter months in the northern
hemisphere. In India, however, epidemics have
often occurred in summer
Overcrowding
Overcrowding enhances transmission of the
infection. The attack rates are high in closed
population groups e.g. schools, institutions, ships,
etc.
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INCUBATION PERIOD FOR INFLUENZA
The incubation period is about 18 to 72 hours.
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PATHOGENESIS
The virus enters the respiratory tract and
causes inflammation and necrosis of the
superficial epithelium of the tracheal
and bronchial mucosa, followed by
secondary bacterial invasion.
There is no viraemia.
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SIGNS AND SYMPTOMS
Symptoms begin 1-4 days after infection.
The following symptoms of the flu can vary depending
on the type of virus, a person’s age and overall health:
• Sudden onset of chills and fever (101 – 103 F)
• Sore throat, dry cough
• Fatigue, malaise
• Terrible muscle aches, headaches
• Diarrhea
• Dizziness
Contd.....
Both viruses cause the same symptoms.
Fever lasts from one to five days, averaging
about three days in adults.
The most dreaded complication is
pneumonia, which should be suspected if
fever persists beyond four or five days, or
recurs abruptly after convalescence.
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COMPLICATIONS IN CHILDREN
Studies show a link between the development
of Reye’s syndrome and the use of aspirin for
relieving fevers caused by the influenza virus.
The disease involves the CNS and the liver and
children exhibit symptoms of drowsiness,
persistent vomiting and change in personality.
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DIFFERENCE BETWEEN COLD AND FLU
Symptoms Cold Flu
Fever Rare High
Headaches rare prominent
General aches mild severe
Fatigue mild Can last for 2-3 weeks
Extreme exhaustion absent Early and prominent
Blocked nose common sometimes
sneezing Usual sometimes
Sore throat common sometimes
Chest discomfort Mild present
DIAGNOSIS
OF
INFLUENZ
A
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1. VIRUS ISOLATION
Nasopharyngeal secretions are the best
specimens for obtaining large quantities of
virus–infected cells.
The virus can be detected by the
indirect fluorescent antibody technique.
However, egg inoculation is required for virus
isolation and antigenic analysis.
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2. Paired Sera
A sero diagnosis of influenza A or B can be made by the
examination of two serum specimens from a patient. One
taken as early as possible in the acute phase of the
disease (not later than the fifth day), and another taken
about 10 to 14 days after the onset, i.e. the convalescent
stage of illness.
The titer of influenza antibodies in the human sera is so
variable that only by detecting a rise in Complement Fixing
(CF) antibodies during the course of illness, can a diagnosis
be established. Hence, the need for two specimens.
Fourfold or greater rise in titer are considered diagnostic of
infection.
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RAPID INFLUENZA TESTS
These tests are 70% accurate for determining if the
patient has been infected with the influenza virus
and 90% accurate for determining the type of
influenza pathogen.
Examples of rapid influenza tests: Directigen Flu A,
Directigen Flu A + B, Flu OIA, Quick Vue, and Zstat
flu.
Rapid influenza tests provide results in 24 hours and
can be performed in the physician’s office.
ANTI-VIRAL DRUGS
All anti-viral drugs inhibit viral replication but they act in different
ways to achieve this. Drugs that are effective against influenza A
viruses: amantadine and rimantadine.Drugs that are effective
against influenza A viruses and influenza B viruses: zanamivir and
oseltamivir.
Amantadine Rimantadine Zanamivir Oseltamivir
Influenza A Influenza A
Type of Influenza virus infection Influenza B Influenza B
indicated for use Influenza A Influenza A
Administration oral oral oral inhalation oral
Ages approved for treatment of
flu 1 year 14 year 7 years 18 years
Ages approved for prevention
of flu 1 year 1 year not approved not approved
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SYMPTOMATIC DRUGS
OTC medicines provide relief for 'flu symptoms
Symptom(s) OTC Medicine
fever, ache,
pains, sinus pressure, sore analgesics
throat
nasal congestion, sinus
pressure decongestants
sinus pressure, runny
nose, watery eyes, cough antihistamines
cough cough suppressant
sore throat local anaesthetics
PREVENTION
OF
INFLUENZA
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The only proven method for preventing influenza is a
yearly vaccination approximately 2 weeks before the
“flu season” begins.
Since the influenza virus is subject to genetic
mutations with the HA and NA proteins, new
vaccines that consist of different influenza strains
need to be developed each year.
Vaccine is trivalent, meaning that it provides
resistance to three strains of influenza viruses. The
vaccine consists of 2 influenza A virus pathogens
and 1 influenza B pathogen.
• Since influenza vaccines will not control
epidemics, they are recommended only in certain
select population groups – e.g. in industry, to
reduce absenteeism and in public services, to
prevent disruption of critical public services such
as the police, fire protection, transport and
medical care.
• Moreover, certain groups e.g. the elderly and
individuals in any age group who have a known
underlying chronic or debilitating disease are
selectively immunized because of the high risk of
severe complications including death.
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INFLUENZA
VACCINES
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KILLED VACCINES
Most influenza vaccination programs make
use of inactivated vaccines.
Subcutaneous route. A single inoculation
(0.5ml) is usually given. However, in persons
with no previous immunological experience
two doses of the vaccine, separated by an
interval of three to four weeks are considered
necessary to induce satisfactory antibody
levels
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• The protective value of the vaccine varies between
70 to 90 per cent and immunity lasts for only three
to six months. Re–vaccination on an annual
basis is recommended.
• The killed vaccine can produce fever, local
inflammation at the site of injection, and very
rarely Guillain–Barre syndrome (an ascending
paralysis).
• Since the vaccine strains are grown in eggs,
persons allergic to eggs may develop the
symptoms and signs of hypersensitivity.
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LIVE ATTENUATED VACCINES
Live attenuated vaccines based on
temperature–sensitive (ts) mutants have been
extensively used in the USSR. They may be
administered as “Nose drops” into the
respiratory tract.
They stimulate local as well as systemic
immunity. The frequent antigenic mutations
of the influenza virus present difficulties in
the production of effective vaccines,
particularly live vaccines.
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NEWER VACCINES
Split–virus Vaccine
It is also known as the sub–virion vaccine. It
is a highly purified vaccine, producing
fewer side effects than the “Whole virus”
vaccine. Due to its lower antigenicity, it
requires several injections instead of a
single one. It is recommended for children.
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NEURAMINIDASE–SPECIFIC VACCINE
It is a sub–unit vaccine containing only
the N antigen, which induces antibodies
only to the neuraminidase antigen of
the prevailing influenza virus.
The antibody to neuraminidase reduces
both the amount of virus replicating in
the respiratory tract and the ability to
transmit virus to contacts.
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RECOMBINANT VACCINE
By recombinant
techniques, the
desirable antigenic
properties of a virulent
strain can be transferred
to another strain known
to be of low virulence.
Efforts to improve the
influenza vaccine have
been continuing.
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