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INFLUENZA
8/15/201
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HEMANT
KUMAR
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INTRODUCTION
Influenza, commonly referred to as the flu, is
viruses of the family Ortho-myxoviridae
influenza viruses),
an infectious viral disease caused by RNA
(the
that
affects birds and mammals.
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 .
3
4
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.
5
HISTORY
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 Ÿ 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
American Red Cross nurses keep the flu patients in
temporary wards set up inside the Oakland municipal
Auditorium.
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7
EPIDEMILOGICAL
DETERMINANTS
8
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.
CONTD..
I. Both influenza A and B viruses have two
Hemoglutinin (H) and
9
distinct surface antigens – the
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.
10
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..
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.
11
12
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.
13
‱ 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
been isolated in countries all over the world.
14
‱ 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.
15
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.
STRUCTURE OF VIRION
M1
protein
HA - hemagglutinin
NA - neuraminidase
helical nucleocapsid (RNA
plus NP protein)
lipid bilayer
membrane
polymerase
complex
16
17
18
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.)
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.
19
20
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.
PERIOD OF INFECTIVITY
21
HOST FACTORS
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HEMANT
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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.
HUMAN MOBILITY
This is an important factor in the spread of
the infection.
8/15/201
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HEMANT
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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.
26
CONTD
...
tract after infection
Secondary antibodies develop in the
respiratory and
consist predominantly of lgG.
Antibodies must be present in sufficient
concentrations at the superficial cells (the
site of virus invasion) of the respiratory
tract.
27
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.
INCUBATION PERIOD FOR INFLUENZA
The incubation period is about 18 to 72
hours.
8/15/201
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29
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.
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.
31
32
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.
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
INFLUENZA
34
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.
35
36
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.
37
In India, facilities for isolation
of the influenza virus are
available at:-
1. Government of India Influenza Center, Pasteur
Institute, Coonoor, South India.
2. Haskine Institute, Mumbai.
3. School of Tropical Medicine, Calcutta
4. All India Institute of Medical Sciences, New
Delhi.
5. Vallabhbhai Patel Chest Institute, Delhi,
6. & Armed Forces Medical College, Pune.
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.
39
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
Type of Influenza virus
infection
indicated for use
Influenza A Influenza A
Influenza A
Influenza B
Influenza A
Influenza B
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
8/15/201
6
HEMANT
KUMAR
40
SYMPTOMATIC DRUGS
OTC medicines provide relief for 'flu
symptoms
Symptom(s) OTC Medicine
fever, ache,
pains, sinus pressure,
sore throat
analgesics
nasal congestion,
sinus pressure
decongestants
sinus pressure, runny
nose, watery eyes,
cough
antihistamines
cough cough suppressant
sore throat local anaesthetics
PREVENTION
OF
INFLUENZA
43
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.
44
‱ 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.
45
INFLUENZA
VACCINES
46
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
47
‱ 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.
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.
48
8/15/201
6
HEMANT
KUMAR
49
Influenza

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Influenza

  • 3. INTRODUCTION Influenza, commonly referred to as the flu, is viruses of the family Ortho-myxoviridae influenza viruses), an infectious viral disease caused by RNA (the that affects birds and mammals. 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 . 3
  • 4. 4 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.
  • 5. 5 HISTORY 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 Ÿ 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
  • 6. American Red Cross nurses keep the flu patients in temporary wards set up inside the Oakland municipal Auditorium. 6
  • 8. 8 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.
  • 9. CONTD.. I. Both influenza A and B viruses have two Hemoglutinin (H) and 9 distinct surface antigens – the 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.
  • 10. 10 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..
  • 11. 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. 11
  • 12. 12 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.
  • 13. 13 ‱ 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 been isolated in countries all over the world.
  • 14. 14 ‱ 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.
  • 15. 15 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.
  • 16. STRUCTURE OF VIRION M1 protein HA - hemagglutinin NA - neuraminidase helical nucleocapsid (RNA plus NP protein) lipid bilayer membrane polymerase complex 16
  • 17. 17
  • 18. 18 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.)
  • 19. 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. 19
  • 20. 20 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.
  • 23. 23 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.
  • 24. HUMAN MOBILITY This is an important factor in the spread of the infection. 8/15/201 6 HEMANT KUMAR 24
  • 25. 25 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.
  • 26. 26 CONTD ... tract after infection Secondary antibodies develop in the respiratory and consist predominantly of lgG. Antibodies must be present in sufficient concentrations at the superficial cells (the site of virus invasion) of the respiratory tract.
  • 27. 27 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.
  • 28. INCUBATION PERIOD FOR INFLUENZA The incubation period is about 18 to 72 hours. 8/15/201 6 28
  • 29. 29 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.
  • 30. 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
  • 31. 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. 31
  • 32. 32 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.
  • 33. 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
  • 35. 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. 35
  • 36. 36 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.
  • 37. 37 In India, facilities for isolation of the influenza virus are available at:- 1. Government of India Influenza Center, Pasteur Institute, Coonoor, South India. 2. Haskine Institute, Mumbai. 3. School of Tropical Medicine, Calcutta 4. All India Institute of Medical Sciences, New Delhi. 5. Vallabhbhai Patel Chest Institute, Delhi, 6. & Armed Forces Medical College, Pune.
  • 38. 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.
  • 39. 39 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 Type of Influenza virus infection indicated for use Influenza A Influenza A Influenza A Influenza B Influenza A Influenza B 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
  • 41. SYMPTOMATIC DRUGS OTC medicines provide relief for 'flu symptoms Symptom(s) OTC Medicine fever, ache, pains, sinus pressure, sore throat analgesics nasal congestion, sinus pressure decongestants sinus pressure, runny nose, watery eyes, cough antihistamines cough cough suppressant sore throat local anaesthetics
  • 43. 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.
  • 44. 44 ‱ 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.
  • 46. 46 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
  • 47. 47 ‱ 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.
  • 48. 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. 48