Influenza is caused by RNA viruses of the Orthomyxoviridae family that come in three main types: A, B, and C. Influenza A is the most common cause of epidemics and pandemics as it has multiple subtypes that can reassort. Wild aquatic birds are the natural reservoir for all influenza A subtypes. Seasonal epidemics are caused by antigenic drift while pandemics arise due to antigenic shift involving genetic reassortment between human and avian viruses. The prerequisites for an influenza pandemic are a new virus that humans have little immunity to which can spread efficiently between people. Egypt has reported increased human infections of avian influenza A(H5N1) virus

4. Flu Fears

5. 5

7. Influenza: The Basics

8. ● RNA, enveloped
● Viral family: Orthomyxoviridae
● Size:
80-200nm or .08 – 0.12 μm
(micron) in diameter
● Three types
● A, B, C
● Surface antigens
● H (haemaglutinin)
● N (neuraminidase)
Influenza Virus

9. Influenza Types
● Influenza A Virus
 Wild birds are “natural” reservoir for all
influenza A subtypes
 Epidemics and pandemics
 Animals and humans
 Can infect many animals – ducks, chickens,
pigs, whales, horses and seals.
 Accounts for >80% of influenza infections of
human each year - All ages.

10. Wild birds are “natural” reservoir for all
influenza A subtypes

11. Influenza A viruses of all
subtypes have been detected
in more than 90 species of
apparently healthy wild birds .
Wild water fowl , gulls , shore
birds are the natural reservoir
of all influenza A viruses .

13. Neuraminidase (NA)–9 subtypes
)
M2 protein
(penetration)
Hemagglutinin (HA)–16 subtypes
● Contain 8-segment RNA
strand segments break apart
during replication to mix &
reassort
● The potential for constant
evolution is built in”
Influenza A Virus

14. H1 N1
H2 N2
H3 N3
H4 N4
H5 N5
H6 N6
H7 N7
H8 N8
H9 N9
H10
H11
H12
H13
H14
H15
H16
Haemagglutinin subtype Neuraminidase subtype

15. Species Affected
Genetic Reservoirs
Intermixing
H1, H3
H1, H2, H3
H3, H7
H1-12
H14-15
H1-2, 4-7,
H9-13, 15-16
H10
H1, H3, H4, H7,
H13
Other Aquatic
Birds?
H5N1

16. Avian Influenza
A viruses
H1 - H16
N1 - N9
H1 - H3
N1 –N2
Human Influenza
A Viruses
Natural Reservoir for New Human Influenza A Virus
Subtypes: Waterfowl (Aquatic Ducks, Geese)

17. All subtypes of influenza A are maintained in
aquatic birds
In human
H1, H2, H3 N1, N2
The current subtypes of influenza A viruses found in
people are
A (H1N1) and A (H3N2).

18. ●Influenza A is subtyped by surface proteins .
● The subtypes of influenza A virus demonstrate
species specificity and those, which infect
animals do not usually cause infection in humans .
● Influenza B and C viruses are not divided into
subtypes.
Influenza viruses

19. ● Type B
Milder epidemics
Humans only
Primarily affects children
● Type C
Causes mild disease
humans are natural hosts but isolates also found
in pigs does not cause epidemics
Influenza viruses

20. How influenza virus change?
● Type A viruses undergo changes in their surface
antigens or proteins
● Minor changes Antigenic drift
● Major changes Antigenic shift

22. How do yearly epidemics occur?
 Answer: A process called antigenic DRIFT.
 Imperfect “manufacturing” of virus
– Small changes in H and N
– Partial immunity in population
 Incomplete protection; still get sick
 Need new flu vaccine every year
H3N2 H3N2
Immune
System: “Do I
know you? You
look vaguely
familiar!”

23. 23

24. Antigenic ShiftAntigenic Shift

25. Antigenic Shift

26.  Antigenic shift occurs only in Type A
 Occurs due to genetic exchange or reassortment
 The genetic content of influenza viruses is segmented
into eight genes , this facilitates reassortment , in which
genetic material is exchanged between human & avian
viruses during co-infection of a human or pig (known
as mixing vessel) .
Antigenic shift

28. What drives the occurrence of a pandemic?
Answer:
Instead of antigenic DRIFT occurring,
an antigenic…
…happens.
Immune
System: “Oh my
gosh…I don’t
know you at
all!”
H?N?

29. Reassortment (in human)
Avian virus + Human virus
Migratory
water birds
Pandemic potential

30. New subtype influenza
REASSORTMENT : Pigs

33. Antigenic Shift
Novel HA or NA
Reassortment of the
segment genome
from two different
subtypes
Antigenic Drift
Point mutation in HA
New strains of the
same subtype
Seasonal epidemics
Requirement for a new
vaccine each year
PANADEMIC

34. What is a Pandemic?

35. A new influenza virus emerges to
which the general population has
little/no immunity
The new virus must be able to replicate
in humans and cause disease
The new virus must be efficiently
transmitted from one human to
another
Prerequisites for pandemic influenza

36. Influenza Pandemic
Considerations

37. The origin of pandemic virus
1. Adaptive mutation
 Stepwise changes in the virus, which occur during
sequential infection of humans, where by an avian virus
gradually acquires the changes needed to improve its
transmissibility among human.
 In this condition , the capability of these viruses to bind
to human cells would increase during subsequent
infections of humans.
 In 1918 pandemic evidence to date suggests that the
virus may have evolved through adaptive mutation of
an avian virus .

38. In which genetic material is exchanged between
human & avian viruses during co-infection of a human
or pig and produce a new virus, that had most of the
genes from the human virus, but a HA and/or NA from
the avian virus.
The pandemics of 1957 & 1968 are known to have been
caused by new viruses containing both human & avian
genes, that emerged following a re-assortment event.
2. Reassortment :
The origin of pandemic virus

39. Human
influenza
virus
Avian
influenza
virus
A) Direct genetic mutation (Spanish flu)
OR
B) Genetic “mixing” in animal
(or human) infected with both
human and avian influenza

40. Avian
influenza virus
Human
influenza virus
Pandemic
influenza virus
Ingredients for a pandemic
Or:
ADAPTATION (e.g.1918?)

41. Pandemic influenza in the 20th Century
1920 1940 1960 1980 2000
H1N1 H2N2 H3N2
1918 “Spanish Flu” 1957 “Asian Flu” 1968 “Hong Kong Flu”
20-40 million deaths 1 million deaths 1 million deaths

42.  The influenza pandemic of 1918 killed
more humans than any other disease in a
period of similar duration in the history of
the world.
Alfred W. Crosby, historian & author
America’s Forgotten Pandemic: The Influenza of 1918
The “Forgotten Pandemic”

43. http://www.pbs.org/wgbh/amex/influenza/maps/index.html

44. History of pandemic influenza
History of pandemic influenza

45. MOST FATAL EVENT
IN HUMAN HISTORY
WORLDWIDE FATALITIES:
20-40 MILLION
US FATALITIES:
675,000
U.S. LIFE EXPECTANCY AT BIRTH
35
40
45
50
55
60
65
70
1900 1906 1912 1918 1924 1930 1936 1942 1948 1954 1960
Date
Age

47. Emergency hospital, Camp Funston, Kansas 1918
Courtesy of National Museum of Health and Medicine

48. SCHOOLS FACE TOUGH PANDEMIC QUESTIONS

49. 1918 1957 1968 1977
Influenza A virus in humans since 1918
Spanish
flu
H1N1 H2N2 H3N2
H1N1
Asian
flu
Hong Kong
flu
16 HA
subtypes
9 NA
subtypes
Influenza A reservoir
?

50. Source: Potter, C.W: Textbook of Influenza by Nicholas, Webster, Hay, Blackwell
Science 1998
Recorded Influenza Pandemics
0
1
2
3
1883
30 years
10
10 40 years10 20
2008
H1 H2 H3
H1
1893 1903 1913 1923 1933 1943 1953 1963 1973 1983 1993
*
1918-19
"Spanish Flu"
1957-58
"Asian Flu"
1968
"HK Flu"

51. World facing global A(H1N1)
pandemic 11 June 2009

52. Influenza A(H1N1) 2009

53. Pandemics of influenza
H1N1
H2N2
1889
Russian
influenza
H2N2
H2N2
1957
Asian
influenza
H2N2
H3N2
1968
Hong Kong
influenza
H3N2
H3N8
1900
Old Hong Kong
influenza
H3N8
1918
Spanish
influenza
H1N1
1915 1925 1955 1965 1975 1985 1995 20051895 1905 2010 2015
2009
Novel
influenza
H1N1v
H1N1v
Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus Research,
National Institute of Infectious Diseases (NIID), Japan. Animated slide: Press space bar
H1N1

54. 54

55. N Engl J Med 2005; 353:2210

56. 56

57. 57

58. Situation Report: Avian Influenza

59. 59

60. 60

61.  From February 2003 to 31 March 2015, there
have been 826 cases of human infection
with avian influenza A(H5N1) virus reported
from 16 countries worldwide.
 Of these cases, 440 were fatal, resulting in a
CFR of 53%.
61

62. Year Cases Deaths
2006 18 10
2007 25 9
2008 8 4
2009 39 4
2010 28 13
2011 40 15
2012 11 5
2013 4 3
2014 38 18
2015 (end of 31
March 2015
125 33
Total 336 114
62
Table 1. Cumulative number of laboratory-confirmed human cases of
avian influenza A(H5N1) reported to WHO, 2006-2015 in EGYPT

63.  The most affected countries cumulatively are
Egypt and Indonesia.
 In 2014 and 2015, Egypt reported the most cases
and has become the most affected country with
the highest number of human cases reported by
a country worldwide since the emergence of the
virus.

64.  Since it was first reported in March 2006, a
total of 336 cases of avian influenza
A(H5N1) infections in humans have been
reported, including 114 related deaths
(Case-fatality rate =34%)
64

67. Location of the human cases overlaps
significantly with areas of reported
outbreaks of A(H5N1) in domestic
poultry

68. 68

71.  Although all influenza viruses evolve over time,
preliminary laboratory investigation has not
detected major genetic changes in the limited
number of viruses isolated from the patients and
animals compared to previously circulating
isolates
 The cases reported appear to be sporadic cases
and the virus is known to be circulating
endemically in poultry in Egypt
71

72.  Although Egypt has reported an increased
number of animal-to-human infections over the
past few months, the influenza A(H5) viruses do
not appear to transmit easily among people, no
sustained human-to-human transmission has
been observed.
 As such, the risk of these viruses spreading in the
community remains low.

73. A new influenza virus emerges to
which the general population has
little/no immunity
The new virus must be able to replicate
in humans and cause disease
The new virus must be efficiently
transmitted from one human to
another
NOT TO
DATE
Prerequisites for pandemic influenza

74. Human and avian surveillance of
A(H5N1) in Egypt
 Influenza is a notifiable disease in Egypt, and
the country has well-established sentinel
surveillance systems for influenza-like illnesses
(ILI) and acute respiratory infections (ARI),

75.  Since 2006, all healthcare facilities have been
obliged to notify suspected A(H5N1) cases – ILI/ARI
with bird contact – and confirmed, PCR-positive cases
to the Ministry of Health.
 A hospital-based surveillance system was established
in 2009 to report ILI/severe acute respiratory infection
(SARI)/pneumonia cases, and samples from severe
SARI/pneumonia cases or cases without clear
diagnosis are sent to laboratory to be tested for
influenza viruses and MERS-CoV.

76. 76

77.  Raising poultry in households is common in Egypt,
where community awareness of the risks of avian
influenza seems to remain low
 In December 2014, the Egyptian veterinary
authorities indicated that the capacity of
veterinary services to investigate outbreaks and
carry out surveillance was challenged, mainly by
limited resources (e.g. manpower, vehicles and
equipment).
77

78.  The authorities faced difficulties in controlling the
disease due to the high density of commercial
and household poultry flocks, the intensity of bird
movements and low awareness of the disease in
the rural population.
78

79.  The public health impact of H5 vaccination
programmes in poultry has been limited, as the
vaccination does not prevent shedding and
human exposure to the virus, although it reduces
the severity of clinical signs and mortality of
vaccinated poultry .
 Repeated reports of large numbers of poultry
outbreaks – even among previously vaccinated
poultry has been detected
79

80. Situation of highly pathogenic avian
influenza A(H5N1) in birds in Egypt
 FAO stated that during December 2014 and February
2015, 352 poultry outbreaks were notified in Egypt,
which is a large increase compared to the 44 poultry
outbreaks reported during the same period the year
before , Outbreaks were reported among vaccinated
poultry in commercial farms and households as well
as in unvaccinated backyard poultry ..
 The locations of poultry outbreaks largely overlap
with areas of human cases

81. Conclusions
 Strict implementation of control measures to reduce
and eliminate infection in poultry is essential for
reducing the risk of zoonotic transmission and human
cases.
 Enhanced human infectivity of the circulating virus
and the protection conferred by the poultry vaccines
currently in use should be further investigated.
 Surveillance in poultry as well as in humans needs to
be strengthened , reinforced and ideally,
coordinated.

84. 84

85. 85

86. 86

87. 87

88. 2014

89. 89

90. "The Ebola outbreak in Liberia is over"
Says WHO
May 09, 2015
90

91. 91

92. 92

93. 93

94. 94

95. 95

96. 96

97. 97

98. 98

99. Country
Total Cases
(Suspected,
Probable, and
Confirmed)
Laboratory-
Confirmed
Cases Total Deaths
Guinea 3592 3170 2387
Liberia* 10564 3151 4716
Sierra Leone 12492 8597 3904
Total 26648 14918 11007
99
May 8, 2015: updated case
counts-WHO

100. 10
0
Liberia cautiously
marks end of Ebola
after 4,700 deaths

101. 10
1

102. Work hard in silence
Let success make the noise
10
2

103. “The only thing more difficult than
planning for an emergency is having
to explain why you didn’t.”
Be Proactive NOT Reactive!!!!
Final Messages!

104. 10
4

105. Thank you