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Influenza
History
• “Influenza” epidemics of acute, rapidly spreading
catarrhal fevers of humans. highly lethal, systemic
disease
• Befor 1870s to 1981, Influenza virus was known
by various names including
• fowl plague (most common),
• fowl pest,
• peste aviaire,
• Geflugelpest,
• typhus exudatious gallinarium,
• fowl disease
• fowl or bird grippe
Caustive agent :
• family Orthomyxoviridae,
• genus Influenzavirus
• negative-sense RNA
Economic Significance
Economic losses depending upon :
• strain of virus
• species of bird infected
• number of farms involved
• control methods used
• eradication strategies
• 1990s H9N2 subtype in commercial poultry
• 2003, H5N1 HPAI become endemic in village
poultry (ducks)
History In twentieth century I.V was
reported
• Switzerland
• Russia
• Great Britain
• Egypt,
• China,
• Japan,
• Brazil
• Argentina
In mid-twentieth century, I.V
diagnosed
• Europe
• Russia
• North Africa
• Middle
• East Asia
• South America
• North America
Eradication of I.V in United States.
• Quarantine
• depopulation
• cleaning
• disinfection
Circulating Influenza Strains and
Pandemics 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 1-4 million deaths 1-4 million deaths
History of HPAI in the
Americas in the last 30 years
• HPAI is considered a foreign animal disease
in the Americas
• Five HPAI outbreaks have occurred in the
Americas in the 1990s
– Pennsylvania 1983-84 (17 million birds)
– Mexico 1994-95 (Millions of birds)
– Chile 2002 (2 million birds)
– Canada 2004 (17 million birds)
– Texas 2004-Molecular definition of HPAI only
(5,000 birds)
H5N1 Asian “Bird Flu”
• The HPAI H5N1 Asian lineage was first detected in
China in 1996 with the Goose/Guangdong/1/96 isolate
• This isolate had a unique multi-basic aa cleavage site
and was highly pathogenic for chickens
• 1997 Hong Kong poultry and human H5N1 viruses had
same H5 gene but different internal genes
• 1999 Hong Kong goose viruses were most similar to
Guangdong/96 virus
• 2001 Korean quarantine station isolate (from China) 4
genes like Guangdong/96 including HA and four unique
genes
• 2001 Hong Kong H5N1 viruses with 5 distinct
combinations of genes observed (same HA)
Incubation Period
• Incubation period :is the time period lapses
b/w infection and appearance of its clinical
signs
• Short incubation period (18-72 hour)
• H5N1 HPAI virus from Mongolia producted
clinical signs within 24 hrs.
Morphology
• diameter from 80–120 nm
• Filamentous
• surface covered by two types of glycoprotein
projections (10–14 nm in length and 4–6 nm
in diameter):
• 1) rod-shaped hemagglutinin (HA){H1…..H17}
• 2)mushroom-shaped neuraminidase
(NA){N1……N9}
Chemical Composition
Influenza virius are composed of :
• 0.8–1.0% RNA,
• 5–8% carbohydrate
• 20% lipid (phospholipids, but small amounts
of cholesterol and glycolipid).
• 70% protein
Susceptibility to Chemical and
Physical Agents
• Physical Agents : can inactivate Influenza
viruses.
• Heat
• extremes of pH
• hypertonic conditions
• dryness
Organic Solvents &Disinfectants
• Chemical Agents : influenza virus have lipid
envelopes, it is inactivated by organic solvents
and detergents
• aldehydes
• beta-propiolactone,
• binary ethylenimine.
• sodium desoxycholate
• sodium dodecylsulfate
• Phenolics
• ammonium ions
• oxidizing agents (such as sodium
hypochlorite),
• dilute acids
• hydroxylamine
Transmission and Carriers
Virus transmision
• nares
• mouth
• cloaca
• infected birds
• Virus
• Aerosole :100000-1000000
virions per droplet
Virus replication
• respiratory
• intestinal
• renal
• Reproductive organs.
Viral Re-assortment
Reassortment in pigs
Reassortment in
humans
Pandemic Influenza
Virus
Incidence and Distribution
Most frequent reports of Influenza viruses has
been
• free-flying bird
• aquatic birds (ducks andgeese)
which are considered the biological and genetic
reservoirs of all I.V.
Five distinct man-made ecosystems have been
identified that have impacted AI virus ecology
• 1) integrated indoor commercial poultry
• 2) range-raised commercial Poultry
• 3) live poultry markets
• 4) village, backyard and hobby flocks
• 5) bird collection and trading systems
Isolation Precautions
Methods of Control
• infected flocks destroy them to prevent spread
to other flocks
• Vaccination
• Biosecurity
Laboratory Situation
• The Influenza viruses are relatively stable in
protein-containing solutions,but long-term
storage at –70°C or following lyophilization.
Field Situation
Influenza viruses are protected by :
• organic material…….such as nasal secretions
or feces
• Influenza virus in liquid manure for 105 days in
the winter
• in feces for 30–35 days at 4°C and for 7 days
at 20°C
Antigenic Variation of Strains—Drift
and Shift
• More antigenic variation in HA and NA due to
glycoproteins in nature
• Drift : Minor change HA and NA gene
• Shift : major change HA and NA gene
A H1N1 :new virus
• The 2009 H1N1 virus is a hybrid of swine,
avian and human strains
Influenza A (H1N1)
• H5 N1
• H7 N3
• H9 N2
• H5 N2 & H9 N1 (non-pathogenic)
• H9 N2 & H5 N1 (highly pathogenic )
Clinical Signs
Clinical Signs depend on other factors including:
• host species
• age
• sex
• environmental factors
Signs
• Off feed intake
• Cyanosis
• Swellling of face & Head
• Dirrohea
• Sudden egg drop
Postmortem signs
• Diffused Haemohages in provetriculus
• Tracitis
• Intritis
Pathotype
• pathogenicity : the ability to produce disease
Influenza virus classified into two pathotypes:
• low pathogenic Influenza(LPI)
• Highly pathogenic Influenza(HPI)
Low Pathogenicity Avian Influenza
Viruses
• Respiratory (coughing, sneezing, rales, rattles,
and excessive lacrimation)
• digestive, urinary, and reproductive
• organs.
• egg production
• some cases green diarrhea or “urine
High Pathogenicity Avian Influenza
Viruses
• neurological signs,
• depression,
• anorexia
• tremors of head and neck, inability to stand,
torticollis,
• opisthotonus
• cessation of egg production within six days
Infectious Process
• initial replication in respiratory epithelium
• virions invade in the submucosa
• entering capillaries
• replicates within endothelial cells
• Spreads via the vascular or lymphatic systems
• replicate in visceral organs, brain, and skin
Laboratory Host Systems
• Isolation and propagation Influenza viruses in
9–11-days-old embryonating chicken eggs
• Most inactivated vaccines produced by
cultivation in embryonating eggs.
Mechanism for LPI to HPI
• substitutions of non-basic with basic amino
acids
• insertions of multiple basic amino acid in
hemagglutinin cleavage site
• Insertion of basic and non-basic amino acids
from unknown source
• Non homologous recombination with inserts
that lengthen the proteolytic cleavage site but
which may or may not contain additional basic
amino acids
Diagnosis
A definitive diagnosis of AI :
• 1)Tissues
• swabs
• cell cultures
• embryonating egg
• 2)presumptive diagnosis by detecting
antibodies to AI virus.
Serology
Serologic tests are used to demonstrate the
presence of AI specific antibodies
• agar gel immunodiffusion or AGID
• ELISA
• HI
• HA
Vaccination
• Killed vaccine (inactivate virus & add adjuvent
• reverse genetic generate
• vaccine is given by subcutaneous or wing web
• 1 day post-hatchd AI vaccine
To Vaccinate or Not To Vaccinate
• Vaccines will prevent clinical disease, but not
infection
• Good vaccines, properly administered, can reduce
virus shedding from infected birds and reduce
chance of virus spread
• Vaccines will adversely affect export markets
• Costs of vaccination are not insignificant
• Bad vaccines may contribute to virus spread
Vaccination
• Proper vaccination programs must also
include good surveillance, education,
quarantines and animal movement controls
• Vaccination can be used to reduce the
susceptible population, and when used
with stamping out may be an effective tool
• Vaccination without the proper controls
may reduce disease, but will not eliminate
it
Treatment
• Not specific treatment
• Amantadine : reducing mortality(inhibit
coating of virus)
• antibiotic treatment
• Vit.C
• NSID(Disprine , pain killer )
• The use of human antiinfluenza drugs is
strongly discouraged.
Importance of the Early
Treatment

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Influenza

  • 2. History • “Influenza” epidemics of acute, rapidly spreading catarrhal fevers of humans. highly lethal, systemic disease • Befor 1870s to 1981, Influenza virus was known by various names including • fowl plague (most common), • fowl pest, • peste aviaire, • Geflugelpest, • typhus exudatious gallinarium,
  • 3. • fowl disease • fowl or bird grippe Caustive agent : • family Orthomyxoviridae, • genus Influenzavirus • negative-sense RNA
  • 4.
  • 5. Economic Significance Economic losses depending upon : • strain of virus • species of bird infected • number of farms involved • control methods used • eradication strategies
  • 6. • 1990s H9N2 subtype in commercial poultry • 2003, H5N1 HPAI become endemic in village poultry (ducks)
  • 7. History In twentieth century I.V was reported • Switzerland • Russia • Great Britain • Egypt, • China, • Japan, • Brazil • Argentina
  • 8. In mid-twentieth century, I.V diagnosed • Europe • Russia • North Africa • Middle • East Asia • South America • North America
  • 9. Eradication of I.V in United States. • Quarantine • depopulation • cleaning • disinfection
  • 10. Circulating Influenza Strains and Pandemics 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 1-4 million deaths 1-4 million deaths
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  • 14. History of HPAI in the Americas in the last 30 years • HPAI is considered a foreign animal disease in the Americas • Five HPAI outbreaks have occurred in the Americas in the 1990s – Pennsylvania 1983-84 (17 million birds) – Mexico 1994-95 (Millions of birds) – Chile 2002 (2 million birds) – Canada 2004 (17 million birds) – Texas 2004-Molecular definition of HPAI only (5,000 birds)
  • 15. H5N1 Asian “Bird Flu” • The HPAI H5N1 Asian lineage was first detected in China in 1996 with the Goose/Guangdong/1/96 isolate • This isolate had a unique multi-basic aa cleavage site and was highly pathogenic for chickens • 1997 Hong Kong poultry and human H5N1 viruses had same H5 gene but different internal genes • 1999 Hong Kong goose viruses were most similar to Guangdong/96 virus • 2001 Korean quarantine station isolate (from China) 4 genes like Guangdong/96 including HA and four unique genes • 2001 Hong Kong H5N1 viruses with 5 distinct combinations of genes observed (same HA)
  • 16.
  • 17. Incubation Period • Incubation period :is the time period lapses b/w infection and appearance of its clinical signs • Short incubation period (18-72 hour) • H5N1 HPAI virus from Mongolia producted clinical signs within 24 hrs.
  • 18. Morphology • diameter from 80–120 nm • Filamentous • surface covered by two types of glycoprotein projections (10–14 nm in length and 4–6 nm in diameter): • 1) rod-shaped hemagglutinin (HA){H1…..H17} • 2)mushroom-shaped neuraminidase (NA){N1……N9}
  • 19. Chemical Composition Influenza virius are composed of : • 0.8–1.0% RNA, • 5–8% carbohydrate • 20% lipid (phospholipids, but small amounts of cholesterol and glycolipid). • 70% protein
  • 20. Susceptibility to Chemical and Physical Agents • Physical Agents : can inactivate Influenza viruses. • Heat • extremes of pH • hypertonic conditions • dryness
  • 21. Organic Solvents &Disinfectants • Chemical Agents : influenza virus have lipid envelopes, it is inactivated by organic solvents and detergents • aldehydes • beta-propiolactone, • binary ethylenimine. • sodium desoxycholate • sodium dodecylsulfate
  • 22. • Phenolics • ammonium ions • oxidizing agents (such as sodium hypochlorite), • dilute acids • hydroxylamine
  • 23. Transmission and Carriers Virus transmision • nares • mouth • cloaca • infected birds • Virus • Aerosole :100000-1000000 virions per droplet Virus replication • respiratory • intestinal • renal • Reproductive organs.
  • 24.
  • 25. Viral Re-assortment Reassortment in pigs Reassortment in humans Pandemic Influenza Virus
  • 26.
  • 27. Incidence and Distribution Most frequent reports of Influenza viruses has been • free-flying bird • aquatic birds (ducks andgeese) which are considered the biological and genetic reservoirs of all I.V.
  • 28. Five distinct man-made ecosystems have been identified that have impacted AI virus ecology • 1) integrated indoor commercial poultry • 2) range-raised commercial Poultry • 3) live poultry markets • 4) village, backyard and hobby flocks • 5) bird collection and trading systems
  • 30. Methods of Control • infected flocks destroy them to prevent spread to other flocks • Vaccination • Biosecurity
  • 31. Laboratory Situation • The Influenza viruses are relatively stable in protein-containing solutions,but long-term storage at –70°C or following lyophilization.
  • 32. Field Situation Influenza viruses are protected by : • organic material…….such as nasal secretions or feces • Influenza virus in liquid manure for 105 days in the winter • in feces for 30–35 days at 4°C and for 7 days at 20°C
  • 33. Antigenic Variation of Strains—Drift and Shift • More antigenic variation in HA and NA due to glycoproteins in nature • Drift : Minor change HA and NA gene • Shift : major change HA and NA gene
  • 34. A H1N1 :new virus • The 2009 H1N1 virus is a hybrid of swine, avian and human strains Influenza A (H1N1)
  • 35. • H5 N1 • H7 N3 • H9 N2 • H5 N2 & H9 N1 (non-pathogenic) • H9 N2 & H5 N1 (highly pathogenic )
  • 36. Clinical Signs Clinical Signs depend on other factors including: • host species • age • sex • environmental factors
  • 37. Signs • Off feed intake • Cyanosis • Swellling of face & Head • Dirrohea • Sudden egg drop
  • 38. Postmortem signs • Diffused Haemohages in provetriculus • Tracitis • Intritis
  • 39.
  • 40. Pathotype • pathogenicity : the ability to produce disease Influenza virus classified into two pathotypes: • low pathogenic Influenza(LPI) • Highly pathogenic Influenza(HPI)
  • 41. Low Pathogenicity Avian Influenza Viruses • Respiratory (coughing, sneezing, rales, rattles, and excessive lacrimation) • digestive, urinary, and reproductive • organs. • egg production • some cases green diarrhea or “urine
  • 42. High Pathogenicity Avian Influenza Viruses • neurological signs, • depression, • anorexia • tremors of head and neck, inability to stand, torticollis, • opisthotonus • cessation of egg production within six days
  • 43. Infectious Process • initial replication in respiratory epithelium • virions invade in the submucosa • entering capillaries • replicates within endothelial cells • Spreads via the vascular or lymphatic systems • replicate in visceral organs, brain, and skin
  • 44. Laboratory Host Systems • Isolation and propagation Influenza viruses in 9–11-days-old embryonating chicken eggs • Most inactivated vaccines produced by cultivation in embryonating eggs.
  • 45. Mechanism for LPI to HPI • substitutions of non-basic with basic amino acids • insertions of multiple basic amino acid in hemagglutinin cleavage site • Insertion of basic and non-basic amino acids from unknown source • Non homologous recombination with inserts that lengthen the proteolytic cleavage site but which may or may not contain additional basic amino acids
  • 46. Diagnosis A definitive diagnosis of AI : • 1)Tissues • swabs • cell cultures • embryonating egg • 2)presumptive diagnosis by detecting antibodies to AI virus.
  • 47. Serology Serologic tests are used to demonstrate the presence of AI specific antibodies • agar gel immunodiffusion or AGID • ELISA • HI • HA
  • 48. Vaccination • Killed vaccine (inactivate virus & add adjuvent • reverse genetic generate • vaccine is given by subcutaneous or wing web • 1 day post-hatchd AI vaccine
  • 49. To Vaccinate or Not To Vaccinate • Vaccines will prevent clinical disease, but not infection • Good vaccines, properly administered, can reduce virus shedding from infected birds and reduce chance of virus spread • Vaccines will adversely affect export markets • Costs of vaccination are not insignificant • Bad vaccines may contribute to virus spread
  • 50. Vaccination • Proper vaccination programs must also include good surveillance, education, quarantines and animal movement controls • Vaccination can be used to reduce the susceptible population, and when used with stamping out may be an effective tool • Vaccination without the proper controls may reduce disease, but will not eliminate it
  • 51. Treatment • Not specific treatment • Amantadine : reducing mortality(inhibit coating of virus) • antibiotic treatment • Vit.C • NSID(Disprine , pain killer ) • The use of human antiinfluenza drugs is strongly discouraged.
  • 52. Importance of the Early Treatment