Respiratory viruses

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Respiratory viruses

• Dr. Kevin Forward
• Departments of Pathology, Microbiology and
  Immunology and Medicine
• 473-4109
• kevin.forward_at_cdha.nshealth.ca

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Respiratory viruses

• Influenza A, B
• Respiratory syncytial virus
• Parainfluenza viruses
• Adenovirus
• Rhinovirus Common cold, many serotypes, no
  systemic problems, a nuisance only.

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Viral Lower Respiratory disease
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Why is influenza always in the news?
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Influenza

• A single stranded RNA virus, enveloped and a
  segmented genome.
• There are really three viruses (A, B and C).
  (Forget C it is unimportant)
• Flu A is more important because of the pandemic
  potential and because it it usually more severe.
• Influenza causes epidemics on a yearly basis.
• Spread is usually by respiratory droplets and on
  soiled hands.
• Epidemics occur only during the winter months.

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Epidemiology of influenza

• Two important proteins present on the surface of
  the virus
• hemagglutinin Sticks the virus to cell receptors
• neuraminidase Frees the virus to infect other
  cells
• These proteins serve as the basis for the naming
  of influenza viruses
• eg. Influenza A Beijing H1N1 or Panama H3N2
• And of course the dreaded avian flu
• H5N1!!!!!

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These proteins are always evolving!

• Larger changes are called shifts (A)
• Shifted virus causes pandemics
• Shifts are reassortments of avian and human
  viruses. New viruses emerge with new-to-human
  proteins on their surfaces
• Small changes are called drifts (A and B)
• Drifted virus causes large epidemics and an
  excess number of deaths in the elderly and frail.

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Influenza Pathology
The hemagglutinin of the virus attaches to the
sialic acid covering the surface of the human cell
The virus penetrates the cellular wall
Replication
The virus emerges from the cell covered in sialic
acid
The neuraminidase removes the sialic acid and the
virus is freed from the cell
A.
B.
C.
D.
E.
Hemagglutinin
Viral RNA
Nucleus
Neuraminidase
Sialic acid
10. Laver WG. Bischofberger N, Webster RG.
Disarming flu viruses, Sci Am 1999 January.
Available at http//www.sciam.com/1999/0199issue
/0199/laver.html. Accessed May 6,
1999. 12. Mandell GL, Bennett JE, Dolin R, eds.
Mandell, Douglas and Bennetts Principles and
Practice of Infectious Diseases. 4th edition.
New York, NYChurchill Livingstone19951552-1554
,1556 20. Piedra PA. Influenza virus pneumonia
Pathogenesis, treatment, and prevention. Semin
Respir Infect 199510216-223
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H1N1 H3N2
H1N1 H3N2
High path. Low path.

• All subtypes of influenza A are found in wild
  aquatic birds, it is shed in the faeces
• Achieved evolutionary stasis

• Virus has established lineages in humans, pigs
  and domestic fowl which continue to evolve

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Generation of Pandemic InfluenzaAntigenic Shift
Pandemic
the mixing vessel
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Influenza A PandemicsThere were three important
pandemics in the last century!
Year
Influenza A subtype
Comment
1918
H1N1
Spanish flu
1957
H2N2
Asian flu
1968
H3N2
Hong Kong flu
This one we think spread directly from birds and
then evolved like H5N1 threatens
These we believe occurred when Flu A mixed in
pigs
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H5N1 Influenza The Next Pandemic?

• Ability to infect humans
• Not readily
• Novel strain to which the population lacks
  immunity
• Definitely
• Easily transmitted between hosts
• No conclusive evidence.. Yet!

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Occurrence of Influenza Pandemics and Epidemics
Mandell, Douglas and Bennetts Principles and
Practice of Infectious Diseases, 5th ed. 2000.
Kilbourne ED. Influenza 1987.
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Outbreaks of H5N1 in Birds
WHO 2006.
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Outbreaks of H5N1 in Humans
WHO 2006.
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The spread of pandemic Influenza A
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Influenza-host interaction
inhalation attachment to upper respiratory
mucosa primary replication secondary spread and
cytokines muscles lungs heart
other organs
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Clinical Characteristics of Infection
40
39
o C
Onset Of Illness
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37
0
1
2
3
4
5
6
7
8
Days After Onset
Nasal Congestion
Sore Throat
Muscle Pains
Headache
Cough
Malaise
Infectivity
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Influenza Complications

• Lower respiratory tract (direct viral effect)
• Croup, bronchiolitis (kids)
• Primary influenza pneumonia
• Secondary bacterial infection
• Pneumonia
• Otitis media
• Other complications
• Heart failure

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Occurrence of Influenza Pandemics and Epidemics
Mandell, Douglas and Bennetts Principles and
Practice of Infectious Diseases, 5th ed. 2000.
Kilbourne ED. Influenza 1987.
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Who gets the complications?(and who benefits
most from vaccine?

• Elderly, especially in residential care units
• Patients with
• chronic respiratory disease eg asthma, cystic
  fibrosis
• chronic heart disease
• immunosuppression due to treatment or disease
• haematological disorders
• chronic renal failure
• chronic metabolic disease e.g. diabetes mellitus

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Influenza Vaccination

• Trivalent - 2 type A and 1 type B
• Efficacy
• 60-80 in healthy young adults
• 20-30 in the elderly
• 50-60 in preventing hospitalisation and
  pneumonia
• Protection
• only when good match with circulating viruses
• annual re-vaccination required

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Respiratory syncytial virus

• A paramyxovirus.
• Causes epidemics in winter, and sporadic cases
  throughout the year.
• Virus is transmitted by hand contact and, to a
  lesser extent, by the respiratory route.
• The most common cause of bronchiolitis in
  children produces the common cold in older kids
  and adults

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Respiratory syncytial virus (continued)

• Almost all children are infected by the age of
  four.
• May be fatal in children with heart and lung
  disease, and in the premature.
• One of only a few treatable viral syndromes.
• Ribavirin treatment is expensive, requires
  hospitalization and is reserved for only the most
  severe infections

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Parainfluenza virus

• Second only to RSV as cause of RTI in infants and
  young children.
• Most infections occur late fall and winter.
• Infection is often limited to the nasopharynx.
• Approximately 2 get laryngo-tracheo-bronchitis
  AKA Croup

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Croup
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Adenovirus

• Double stranded, naked DNA virus.
• Virus infects by direct contact or resp droplets
• Produces 5-10 of pediatric respiratory
  infections.

• Clinical syndromes include
• Febrile pharyngitis
• Lower respiratory infections
• Pharyngoconjunctival fever
• Conjunctivitis
• Diarrhea

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Rhinovirus

• A Picornavirus positive strand RNA virus
• There are a large number of antigenic types gt
  reinfections.
• Primarily noted to infect upper airway
• Common cold
• Viral sinusitis
• Children average 3 to 8 colds per year

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Diagnosis of respiratory viral infections

• Clinical syndrome
• Time of year
• Whats in the community?
• Virus isolation
• Virus antigen detection (not rhinovirus)
• Molecular methods eg. PCR
• Serology (not rhinovirus)