Avian Influenza

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Avian Influenza
Prepared by Prof. Ossama Rasslan Professor of
microbiology Infection control Dr.Abdel-Rahman
Elsawy Lecturer of Microbiology
Immunology Al-Azhar Faculty of Medicine
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• Avian influenza, or "bird flu", is an infectious
  disease of animals caused by type A strains of
  influenza virus that normally infect birds only.
• The disease in birds has two forms
• - The first causes mild illness,
• - The second form known as highly pathogenic
  avian influenza,which was first recognized in
  Italy in 1878, is rapidly fatal, with a mortality
  approaching 100.
• Birds can die on the same day that symptoms first
  appear

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• Infected birds shed virus in saliva, nasal
• secretions and feces.
• Avian influenza viruses spread among
• susceptible birds when they have contact with
  contaminated excretions.
• Avian influenza viruses do not usually directly
  infect humans or circulate among humans. It is
  believed that most cases of infection in humans
  have resulted from contact with infected poultry
  or contaminated surfaces.

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Influenza Viruses
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Structure Influenza viruses are spherical or
filamentous enveloped particles 80 to 120 nm in
diameter. The helically symmetric nucleocapsid
consists of a nucleoprotein and a genome of
single-stranded RNA in 7 or 8 segments. Influenza
viruses are divided into types A, B, and C on the
basis of variation in the nucleoprotein antigen.
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• In types A and B the hemagglutinin (H) and
  neuraminidase (N) antigens undergo genetic
  variation, which is the basis for the emergence
  of new strains type C is antigenically stable.
• Influenza A viruses can be divided into
  subtypes on the basis of their surface proteins
  (H) and (N). There are 15 known (H) subtypes 9
  (N) subtypes .
• While all subtypes can be found in birds, only 3
  subtypes of H (H1, H2 and H3) and two subtypes of
  N (N1 and N2) are known to have circulated widely
  from human to human.

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Influenza viruses lack mechanisms for the
proofreading and repair of errors that occur
during replication. These permanent and usually
small changes in the antigenic composition of
influenza A viruses are known as antigenic
drift. Influenza A viruses, including subtypes
from different species, can swap or reassort
genetic materials and merge. This reassortment
process, known as antigenic shift, results in a
novel subtype different from both parent viruses.
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As populations will have no immunity to the new
subtype, and as no existing vaccines can confer
protection, antigenic shift has historically
resulted in highly lethal pandemics. Conditions
favourable for the emergence of antigenic shift
have long been thought to involve humans living
in close proximity to domestic poultry and pigs.
Because pigs are susceptible to infection with
both avian and mammalian viruses, including human
strains, they can serve as a mixing vessel for
the genetic material from human and avian
viruses, resulting in the emergence of a novel
subtype.
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Recent events, however, have identified a second
possible mechanism that humans themselves can
serve as the mixing vessel. If the new virus
contains sufficient human genes, transmission
directly from one person to another (instead of
from birds to humans only) can occur. When this
happens, the conditions for the start of a new
influenza pandemic will have been met.
Person-to-person transmission resulted in
successive generations of severe disease with
high mortality.
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Background on Pandemics in humans
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• There were 3 pandemics of influenza in human in
  the 20th century
• 1918-19, "Spanish flu," A (H1N1),
• caused the highest number of known flu deaths ...
• - 20 million to 50 million people may have died
  worldwide, more than 500,000 people died in the
  United States
• - Many people died within the first few days
  after infection and others died of complications
  soon after.
• - Nearly half of those who died were young,
  healthy adults

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• 1957-58, "Asian flu," A (H2N2),
• First identified in China in late February 1957,
  the Asian flu spread to the United States by June
  , caused about 70,000 deaths in the United
  States.
• 1957.1968-69, "Hong Kong flu," A (H3N2),
• This virus was first detected in Hong Kong in
  early 1968 and spread to the United States later
  that year. caused approximately 34,000 deaths in
  the United States, type A (H3N2) viruses still
  circulate today.

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Background on Pandemics in birds
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• viruses of low pathogenicity can, sometimes after
  circulation for short periods in a poultry
  population, mutate into highly pathogenic
  viruses.
• During a 19831984 epidemic in the USA, the
  AH5N2 virus initially caused low mortality, but
  within 6 months became highly pathogenic, with a
  mortality approaching 90. Control of this
  outbreak required destruction of more than 17
  million birds at a cost of nearly 65 million .

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An outbreak that began in Mexico in 1992 was
not completely controlled until 1995. During a
19992001 epidemic in Italy, the AH7N1 virus,
initially of low pathogenicity, mutated within 9
months to a highly pathogenic form. More than 13
million birds died or were destroyed.
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• Outbreaks in poultry caused by the AH5N1 strain
  have been confirmed in the following countries
• Republic of Korea (12 December 2003 )
• Viet Nam (8 January 2004)
• Japan (12 January 2004)
• Thailand (23 January 2004)
• Cambodia (24 January 2004)
• China (27 January 2004)
• Laos (27 January 2004)
• Indonesia (2 February 2004)

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Confirmed instances of avian influenza viruses
infecting humans
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1997 In Hong Kong, avian influenza A (H5N1) This
was the first time an avian influenza virus had
ever been found to transmit directly from birds
to humans - 18 people were hospitalized, - 6
of them died. - authorities killed about 1.5
million chickens
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1998-99 in China H9N2 Several additional human
infections were reported . 1999 In Hong Kong,
avian influenza A H9N2 - were confirmed in 2
children. - Both patients recovered, and no
additional cases were confirmed. - Poultry was
the source of infection and the main mode of
transmission was from bird to human.
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2003 Two cases of avian influenza A (H5N1) -
Infection occurred among members of a Hong Kong
family that had traveled to China. - One person
recovered, the other died. How or where these 2
family members were infected was not determined.
- Another family member died of a respiratory
illness in China, but no testing was done. No
additional cases were reported.
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2003 Avian influenza A (H7N7) - infections
among poultry workers and their families were
confirmed in the Netherlands . - More than 80
cases were reported - 1 patient died - There
was evidence of some human-to-human transmission.
2003 Avian influenza A( H9N2) - infection was
confirmed in a child in Hong Kong. The child was
hospitalized but recovered.
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• January 2004 The most recent epidemic occurred
  when laboratory tests confirmed the presence of
  H5N1 avian influenza virus in human cases of
  severe respiratory disease in the northern part
  of Viet Nam.
• 10 February 2004, according to WHO reports
• Country Total cases
  Deaths
• Thailand 5
  5
• Viet Nam 18
  13
• Total 23
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How do outbreaks of avian influenza spread
within a country?
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Within a country, the disease spreads easily
from farm to farm. Large amounts of virus are
secreted in bird droppings, contaminating dust
and soil. Airborne particles can spread the
disease from bird to bird, causing infection when
the virus is inhaled. Contaminated equipment,
vehicles, feed, cages or clothing especially
shoes can carry the virus from farm to farm.
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The virus can also be carried on the feet
and bodies of animals, such as rodents, which
act as mechanical vectors for spreading the
disease. Limited evidence suggests that flies can
also act as mechanical vectors.
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How does the disease spread from one country to
another?
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The disease can spread from country to country
through international trade in live poultry.
Migratory birds, can carry the virus for long
distances and have, in the past, been implicated
in the international spread of highly pathogenic
avian influenza.
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Symptoms of Avian Influenza Infection in Humans
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• The reported symptoms of avian influenza in
  humans have ranged from
• - typical influenza-like symptoms (e.g.,
• fever, cough, sore throat and muscle aches) to,
• - eye infections,
• - acute respiratory distress,
• - viral pneumonia, and
• - other severe and life-threatening complications.

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Laboratory
Diagnosis
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• Detection of influenza viruses
• For early diagnosis of acute influenza
• infection , virus detection using rapid
• procedures for virus isolation or antigen
• detection and molecular biology techniques have
  been developed.
• Commercial enzyme immunoassays which allow rapid
  detection of influenza virus type A in clinical
  specimens have been developed several years ago.

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• Serological detection of influenza viruses
• Conventional serological diagnosis is possible by
  means of the complement fixation and
  hemagglutination inhibition tests and allows the
  detection of type and subtype-specific
  antibodies, respectively.
• As part of automated serology, immunofluorescence
  test and ELISA are the most widely available
  methods.

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Treatment
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Two classes of drugs are available. These are
the M2 inhibitors (amantadine and rimantadine)
and the neuraminidase inhibitors (oseltamivir and
zanimivir). These drugs have been licensed for
the prevention and treatment of human influenza
in some countries, and are thought to be
effective regardless of the causative
strain. However, initial analysis of viruses
isolated from the recently fatal cases in Viet
Nam indicates that the viruses are invariably
resistant to the M2 inhibitors.
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Vaccines
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Currently available vaccines will not protect
against disease caused by the H5N1 strain in
humans. An available vaccine prototype virus,
developed using the 2003 strain of H5N1 (which
caused the two human cases in Hong Kong), cannot
be used to vaccine development as initial
analysis of the 2004 virus, conducted by
laboratories in the WHO network, indicates that
the virus has mutated significantly
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As one of several measures for reducing
opportunities for the simultaneous infection of
humans with avian and human influenza viruses,WHO
is recommending the targeted administration of
seasonal influenza vaccine to selected groups at
increased risk of exposure to the H5N1 avian
influenza virus currently circulating in Asia
. Reduced opportunities for dual infections
reduce opportunities for reassortment and for the
eventual emergence of a novel influenza virus
with pandemic potential.
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Selected groups to be immunized All persons who
are expected to be in contact with poultry or
poultry farms suspected or known to be affected
with avian influenza (H5N1), especially (a)
cullers involved in destruction of poultry, and
(b) people living and working on poultry farms
where H5N1 has been reported or is suspected or
where culling takes place.
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Control Measures
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• The virus is killed by heat (56 C for 3 hours or
  60 C for 30 minutes) and common
  disinfectants.The virus can survive, at cool
  temperatures for at least three months.
• In water, the virus can survive for up to 4 days
  at 22 C and more than 30 days at 0 C. For the
  highly pathogenic form, studies have shown that a
  single gram of contaminated manure can contain
  enough virus to infect 1 million birds.

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The most important control measures are I -Rapid
destruction of all infected or exposed birds,
Infected chicken flocks should be destroyed
before having any possibility of entering the
food-chain.
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II - Proper disposal of carcasses
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III - The quarantining and rigorous disinfection
of farms. IV- Restrictions on the movement of
live poultry, both within and between countries,
are another important control measure.
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V. Care should be taken in handling ducks duck
products . Ducks have been reported to be
asymptomatic carriers and duck products could be
contaminated with the virus. A highly pathogenic
strain of avian influenza H5N1 has been isolated
from imported frozen duck meat .
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VI. Care should be taken in handling shell eggs
or raw egg products .Eggs from infected poultry
could also be contaminated with the virus and
therefore care should be taken in handling shell
eggs or raw egg products. VII. Proper cooking of
meat to kill such viruses WHO recommends that
foods should be cooked to reach an internal
temperature of 70C. Freezing and refrigeration
would not substantially reduce the concentration
or virulence of viruses on contaminated meat.
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IIX. Trade restriction have been put in place by
some countries to protect animal health. IX.
WHO continuously emphasizes the importance of
good hygiene practices during handling including
hand washing, prevention of cross-contamination
and thorough cooking of poultry products.
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