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Unit 3 D&D > DD 02-26-14 10am-Noon Influenza - Curtis > Flashcards

DD 02-26-14 10am-Noon Influenza - Curtis Flashcards

1
Q

Influenza : General Principles

A
  • an acute, febrile respiratory disease
  • occurs worldwide, in all ages & ethnicities
  • not a gastrointestinal upset (“stomach flu”) or a mild respiratory illness
  • typically during the winter months
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2
Q

Influenza: Prevalence in US & Impact

A
  • 10-20% of adults
  • 20-50% of children
  • 50 -60 million infections / yr
  • 25 million physician visits & over 250,000 influenza-associated hospitalizations per year
  • influenza & related complications responsible for 51,000 deaths each year in US
  • $3-$5 billion in direct medical costs annually
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3
Q

Influenza burden in children

A

Highest Attack Rates

  • in school-aged children (5-14yo)
  • 2-4 x higher than in adults (including the elderly)
  • may be important in intra-family and community transmission

Hospitalization rates for children <2 years of age similar to rates in over 65 yo group

Highest Mortality/Hospitalization Rates
- In infants

Stress importance of timely vaccination of all children for whom the influenza vaccine is indicated, as well as their household contacts.

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4
Q

Influenza peak

A
  • Winter / Spring months
  • Exact month that influenza activity peaks is not predictable (may be Oct through May)
  • -> Important to receive flu shot as early as possible in the fall, in case of early peak
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5
Q

Influenza virus

A
  • RNA virus with segmented genome
  • Genome made of 8 different pieces of ssRNA, encoding several different viral proteins
  • Lipid envelope surrounds core, with a lining of matrix protein on inner side
  • Two of the best characterized viral proteins are the hemagglutinin (H) and neuraminidase (N) glycoproteins
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6
Q

Hemagglutinin (H) & Neuraminidase (N)

A
  • Two of the best characterized viral proteins
  • Surface proteins

Different types of hemagglutinin & neuraminidase are designated by numbers
= e.g. H1, H2, N1, N2 etc.

Influenza viral subtypes are identified by combination of H & N proteins on viral coat (e.g. H1N1, H3N2 etc)

see pic in notes

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7
Q

3 types of influenza virus

A
  • Type A & Type B strains circulate in population every year.
  • Type C strains cause mild or clinically-insignificant illness
  • Type A strains cause both epidemics & pandemics.
  • Type A strains can infect other animals, for example horses, seals, swine and birds.
  • Repeated influenza epidemics persist b/c type A & B viruses undergo constant rapid change due to antigenic drift
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8
Q

Nomenclature for describing influenza viruses

A 
Example: A/Moscow/21/99 (H3N2)
“A” = strain type (in this case A).  
Next is geographic origin of strain. 
Next is strain number
Then year strain was isolated 
Finally, virus subtype

For non-human strains, animal is listed between virus type & geographic origin.

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9
Q

Antigenic drift

A

= refers to gradual change in virus that occurs through slow series of mutations, substitutions or deletions in amino acids constituting the hemagglutinin or neuraminidase surface antigens

  • only occurring after particular viral strain has become established in humans
  • represents an adaptation to the development of host antibodies
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10
Q

Effects on Influenza of Antigenic drift

A
  • Newly developed antigenic strains of influenza then prevail for a period of 2 to 5 years, only to be replaced by the next emerging strain
  • This new strain can then trigger a new epidemic, since it is now unfamiliar to Ab repertoire of the population
  • Development of yet another set of host Abs eventually protects population–at the same time it puts pressure on the virus to drift yet again
  • Requires ongoing reformulation of influenza vaccines.
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11
Q

Antigenic shift

A

= occurs when type A influenza virus w/ completely novel hemagglutinin or neuraminidase gene segment is introduced into humans

  • The new gene segment is usually acquired from other host species (i.e. birds or swine)
  • Gene reassortment can occur when two or more influenza viruses infect a single human or animal
  • B/c influenza has a segmented genome, some gene segments can be “swapped” between strains to produce a new virus that has gene segments from both viral strains
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12
Q

Pigs & Antigenic Shift

A
  • Pigs are unusual b/c they have can be infected w/influenza strains usually infecting 3 different species: pigs, birds and humans.
  • If pig were to become infected w/ 2 different strains of influenza virus at the same time (ex: a human strain & a bird strain), those strains might both infect the same cell, allowing reassortment of gene segments between human & avian strains
  • -> Might create predominately human strain that now contains a “novel” hemagglutinin or neuraminidase gene from the bird strain.
  • Therefore, pigs can serve as a “mixing vessel” where influenza viruses might exchange genes, producing new & dangerous strains.
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13
Q

Antigenic shift vs. Antigenic drift

A
  • Antigenic shift of type A influenza viruses occurs less frequently than antigenic drift, but with more dramatic impact.
  • The result of global immunologic susceptibility to a new influenza virus is often a pandemic.
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14
Q

Examples of Antigenic Drift

A
  • Influenza pandemics of both 1957 & 1968

- Recent “swine influenza” (2009 H1N1) pandemic - - Pandemic H1N1 strain

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15
Q

“Swine influenza” (2009 H1N1) pandemic

A
  • multiple reassortments between swine, birds, and human strains (antigenic shiift)
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16
Q

Pandemic H1N1 strain

A

has genes from swine influenza viruses that normally circulate in pigs, as well as bird (avian) genes and human genes.

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17
Q

Influenza type B viruses & Antigenic shift

A

Influenza type B viruses are not subject to antigenic shift as they infect only humans.

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18
Q

Spanish Flu of 1918-1919

A
  • Some virologists refer to this as “swine flu.”
  • Esp. affected young healthy adults (1/100 20-39 yo’s died of influenza-related causes)
  • Some historians believe WWI ended in part because of this pandemic.
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19
Q

1st Pandemic of the 21st Century

A

In 2009-2010
caused by an H1N1 strain
“swine influenza”

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20
Q

Transmission of Influenza

A
  • primarily by the respiratory route
  • droplet & small particle aerosols generated by coughing & sneezing are primary mechanisms of spread
  • Virus lives on human hands ~ 5 minutes, on steel or plastic for 24-48 hours, and cloth or paper tissues for 8-12 hours
  • So, touching contaminated object & then mucosal surface (eye, nose, mouth) can transmit virus
  • Incubation period relatively short (1-3 day)
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21
Q

Signs & Symptoms of influenza in adolescents & adults

A
  • dramatic
  • acute onset of fever, chills, myalgias, headache and cough
  • often feel extremely ill & may be confined to bed for several days
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22
Q

Signs & Symptoms of influenza in younger patients

A
  • may differ from those of adult influenza

- even among children, presentation varies with age

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23
Q

Signs & Symptoms of influenza in neonates

A
  • presentation often resembles bacterial sepsis
  • lethargy, decreased eating, mottling
  • high incidence of apnea (cessation of breathing) may also occur
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24
Q

Signs & Symptoms of influenza in infants & toddlers

A

Tend to present w/ …

  • GI symptoms (nausea, vomiting and diarrhea)
  • fever
  • anorexia
  • various respiratory syndromes, including undifferentiated febrile upper respiratory illness, acute laryngotracheobronchitis (croup), bronchiolitis, bronchitis and febrile convulsions
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25
Q

Signs & Symptoms of influenza in older children & adolescents

A
  • more like classic presentation in adults

- rapid onset of illness with high fever; cough; chills; malaise; and other symptoms, such as headache and sore throat

26
Q

Treatment of Influenza

A

Several drugs used:
In general, 2 classes of agents:
1) Matrix protein inhibitors—only subtype A viruses
2) Neuraminidase Inhibitors—for both subtype A & B

27
Q

Matrix Protein Inhibitors

A

1 of 2 classes of antiviral agents used for influenza

Only for susceptible subtype A viruses

  1. Amantadine
  2. Rimantadine
28
Q

Neuraminidase Inhibitors

A

1 of 2 classes of antiviral agents for influenza

For both susceptible subtype A & B viruses

  1. Oseltamivir (Tamiflu)
  2. Zanamivir (Relenza)
29
Q

Resistance of influenza strains to antivirals

A
  • increasingly reported
  • In 2006, ~all influenza A strains resistant to amantidine/rimantidine
  • In 2008, ~all H1N1 strains then circulating (except Pandemic H1N1 “swine influenza” the next year) were resistant to oseltamivir, but susceptible to Zanamivir, amantidine, and rimantidine
  • “Swine influenza” (Pandemic H1N1), H3N2 and B strains remain susceptible to oseltamivir
30
Q

Treating resistant influenza strains

A
  • Most private offices & even many small hospitals do not have on-site technology to be able to distinguish between strains.
  • May be able to distinguish between influenza A or B strains (depending on type of tests they have)
  • Distinguishing between H1 & H3 strains and H1N1 (non-swine) & “swine influenza” (pandemic H1N1) requires more sophisticated testing.

Simply treating everyone w/ zanamivir is problematic

NOTE: All circulating influenza subtypes in the 2013-2014 influenza season are resistant to amantadine/rimantidine and susceptible to oseltamivir and zanamivir.

31
Q

Zanamivir treatment of influenza

A
  • Not approved for treatment of influenza in children under 7 yo
  • Delivered through respiratory route by inhalation
  • A pill placed in holder containing a rotary device.
  • When you put delivery device to mouth & inhale, rotors spin & aerosolize zanamivir
  • Some children & elderly have problems doing this-
  • Should be used with caution w/ asthma or COPD as it can produce bronchospasm (some fatal)
32
Q

Prevention of Influenza – Vaccines

A

Two types of licensed seasonal influenza vaccines:

1) Inactivated influenza vaccine (TIIV)
2) Live attenuated influenza vaccine (LAIV, FluMist)

  • Both contain same 3 strains of influenza
  • Quadrivalent vaccines contain same second B strain

See Table in Notes

33
Q

Inactivated influenza vaccine (TIIV)

A
  • 1 of 2 types of licensed influenza vaccines
  • injectable, killed vaccine
  • licensed for all individuals 6 mo old or older
  • Both trivalent & quadrivalent IIVs available
  • Quadrivalent is relatively new & less widely available (but will likely completely replace all trivalent vaccines)
34
Q

Live attenuated influenza vaccine (LAIV, FluMist)

A
  • delivered intranasally via small needle-free syringe that delivers a fine mist into the nose
  • live, attenuated vaccine
  • licensed for healthy persons 2-49 yo
  • contains same influenza strains as TIV, however, in April 2012 a quadrivalent LAIV was approved by the FDA
  • additional strain is a second B virus
35
Q

Production of yearly flu vaccines

A
  • Both types are reformulated annually to provide best protection possible for strains anticipated to be circulating during next season.
  • Takes several months for vaccine to be produced.
  • Every year after influenza season, decision made as to what 3 or 4 strains are most likely to be circulating the following year.
  • Two “A” strains & one “B” strain are selected for the trivalent, an additional B strain is selected for the quadrivalent.
  • A bit of guess work is involved in this, which may lead to either well-matched years or mismatched years
36
Q

Well-match years for Influenza vaccines

A
  • Years in which predominant circulating strain is contained in the vaccine
  • Hence, vaccinated individuals are protected from influenza.
37
Q

Mismatched years for Influenza vaccines

A
  • Years in which new strains not contained in the vaccine emerge
  • Vaccinated individuals have no protection from these strains & may contract influenza
38
Q

Efficacy of Influenza Vaccines: TIV

A
  • 70-90% effective in preventing influenza

Declines in elderly population

  • only 30-40% efficacy in frail, elderly persons
  • But, reduces hospitalizations by 50-60% & reduces death due to influenza by 80%

Less efficacious than LAIV vaccine in children under 5 yo.

Mixed results in studies of adults as to which vaccine (TIV or LAIV) is more efficacious.

39
Q

Efficacy of Influenza Vaccines: LAIV (FluMist)

A

More efficacious than TIV in children under 5 yo
- particularly in strain mismatched years

Mixed results in studies of adults as to which vaccine (TIV or LAIV) is more efficacious.

40
Q

CDC Recommendations for Use of Influenza Vaccine

A
  • CDC has expanded recommendations for use to include all persons aged 6 mo or older who do not have a contraindication.
  • Everyone >6 months of age should be vaccinated against influenza annually
  • Certain “high-risk” groups are especially targeted for immunization against influenza
  • at high risk of having serious influenza or influenza-related complications or b/c they live w/ or care for people at high risk
  • should have priority in event of vaccine shortage
41
Q

Influenza Vaccination & Infants <6 mo

A
  • Flu vaccines are NOT licensed for use in infants under 6 mo of age
  • However, these infants are at high risk for developing severe disease if get influenza.
  • Therefore, all close contacts of these children should be vaccinated.
  • “Coccooning” babies by vaccinating their contacts & also vaccinating mother during pregnancy is primary way to protect infants < 6 mo
42
Q

High-risk individuals for 2013-2014

A
  1. Children 6 mo through 4 years (59 mo)
  2. Adults 50+ yo
  3. Anyone w/ chronic pulmonary (including asthma), cardiovascular (except HTN), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus)
  4. Anyone who is immunosuppressed (including by medications or by HIV)
  5. Women who are or will be pregnant during flu season;
  6. Children 6 months–18 years receiving long-term aspirin therapy & who therefore might be at risk for Reye syndrome after influenza virus infection
  7. Residents of nursing homes & other chronic-care facilities
  8. American Indians/Alaska Natives;
  9. Anyone morbidly obese (BMI 40+);
  10. Health-care personnel;
  11. Household contacts & caregivers of children younger than 5 years & adults aged 50+ years, esp. contacts of children < 6 mo old
  12. Household contacts & caregivers of persons with medical conditions putting them at higher risk for severe complications from influenza.
43
Q

Prevention of Influenza, besides annual vaccination

A
  • Wash your hands frequently.
  • For health care providers, includes washing hands before & after each patient contact.
  • Sneezing into your arm (rather than covering your mouth with your hand)
44
Q

Swine Influenza (Pandemic H1N1) - sequence of events & spread

A
  • 2009-2010
    • 1st detected in Mexico in 2009, then US & Canada
  • Rapidly became the dominant circulating influenza strain world-wide.
  • On June 11, 2009, WHO raised its pandemic alert level to the highest level, indicating widespread community transmission of Pandemic H1N1 on at least two continents
45
Q

Swine Influenze…why “swine”?

A

referred to as “swine flu” b/c lab testing showed most of virus’ gene segments were similar to influenza viruses known to circulate in pigs (probably result of antigenic shift)

46
Q

Swine Influenza (Pandemic H1N1) - names

A

This virus strain had several names including Swine-origin influenza virus (SOIV), Pandemic H1N1, and is now referred to as 2009 H1N1
- Official designation is: A/California/7/2009 (H1N1)-like virus (1st typed in California in 2009)

47
Q

Swine Influenza (Pandemic H1N1) - Age differences & Immunity

A
  • rate of infection highest among children & young adults ≤24 years of age
  • less common in persons older than 65 years (possibly due to preexisting immunity against antigenically-similar influenza viruses that circulated prior to 1957)
48
Q

Avian Influenza - natural occurance

A

= an infectious disease of birds caused by influenza A subtypes
= virus circulates in wild bird populations but rarely cause mortality
= Wild birds are largely asymptomatic when infected but shed large amounts of virus in their stool – usually into lakes or waterways
= 16 types of hemagglutinin & 9 types of neuraminidase (wild birds can be infected w/all combinations… the only species that can be infected with all influenza strains.)
= So, birds are a reservoir for influenza strains.
= Domesticated poultry can also be infected
= Can have a huge toll on poultry industry, as entire flocks may have to be culled to prevent spread to other farms.

49
Q

H5N1 strain of Avian Influenza

A
  • highly virulent strain circulating in some bird populations
  • can cause severe disease in wild birds, domesticated birds, & can occasionally be transmitted to humans
  • occurs mainly in birds & can be deadly, esp. to domestic poultry
50
Q

H5N1 strain of Avian Influenza - Outbreak

A

Outbreak started when goose farm in China was noted to have an outbreak of illness with a 40% mortality in geese

  • H5N1 was isolated
  • Since then, H5N1 has been responsible for outbreaks in domesticated poultry throughout SE Asia
  • In recent years, outbreaks in Mongolia, Russia, Eastern Europe (Turkey, Romania, Hungary) and Africa (Ghana, Toga).
  • Infected birds have been found in over 20 countries
51
Q

H5N1 strain of Avian Influenza - Names

A

= Highly pathogenic avian influenza A

= often shortened to H5N1

52
Q

Controlling H5N1 Avian Influenza Outbreaks

A
  • To control outbreaks, entire bird populations must be culled (killed).
  • Over 20 million birds have been culled to curb outbreaks
53
Q

Countries endemic for H5N1 Avian Influenza (6)

A

Bangladesh, China, Egypt, India, Indonesia, and Vietnam.

54
Q

Bird to Human Transmission of H5N1 Avian Influenza

A
  • Close contact w/ infected birds is primary risk factor
  • In SE Asia, people live very close to their animals (in some cases, birds are in the house or often backyard animals)
  • To date, attack rate in humans has been relatively low
55
Q

Species specificity of influenza viruses

A

Conferred by the way hemagglutinin binds to the receptor
- Avian viruses bind in an alpha 2, 3 linkage
- Human viruses bind in an alpha 2, 6 linkage
= Explains why many people w/ close contact w/infected birds DO NOT get infected
- However, avian viruses w/avian receptor specificity DO occasionally infect humans, and this has been seen in sporadic cases worldwide

56
Q

Human to Human transmission of avian influenza virus

A
  • Hemagglutinin from an avian virus must preferentially recognize human receptor for efficient human to human transmission
  • A mutation in the hemagglutinin gene might confer such a change in preferred binding
  • EX: Avian virus might mutate such that the preferred receptor binding is in a alpha 2, 6 (human) configuration
  • If this occurred, avian virus would preferentially infect humans

Known to have occurred in the past, such as in the 1918 influenza pandemic (largest pandemic in recorded history)

57
Q

Hemagglutinin mutation and the 1918 influenza pandeminc

A
  • hemagglutinin was from an avian strain & bound human receptors in normal alpha 2, 6 configuration
  • resulted in ability of this “avian strain” to be transmitted efficiently human-to-human
  • Humans had no protection from this novel strain & it rapidly spread around the world killing 50 million people
    = precisely the fear of what could happen w/ current H5N1 avian strain.
58
Q

Reassortment in avian influenza pandemics

A

= another way an avian influenza pandemic could emerge is through reassortment
= as occurred w/ pandemic H1N1 infection, using pigs as mixing vessel for avian & human strains
= If reassortment occurred such that human hemagglutinin gene assorted w/ predominately avian segments, a novel strain would be produced that could bind human receptors
= B/c in SE Asia, people live so closely to their animals & have a lot of animal contact, this scenario is a real concern

59
Q

Risk Factors for Avian Influenza

A
  • Contact w/ poultry in week prior to onset of illness
  • Direct contact w/ sick poultry
  • Direct contact w/ humans w/ avian influenza (limited transmission observed in a few families, where caretakers have developed avian influenza after taking care of sick family member w/ same illness)
  • Travel to areas where avian influenza is known to exist in birds is NOT A RISK FACTOR if person has NO CONTACT with poultry
  • Eating cooked poultry is NOT a risk factor.
60
Q

Pandemic Criteria—How Do You Determine When a Pandemic is Occurring?

A

Three conditions must be met to define when an influenza pandemic is occurring:

  1. Emergence of a new influenza subtype
  2. Virus must infect humans & cause serious illness
  3. Virus must have sustained human-to-human transmission & spread easily (w/out interruption) among humans.
  • all met by swine influenza (Pandemic H1N1)
  • 2/3 met currently by avian influenza (H5N1) – not condition three
61
Q

Distinguishing Viral and Bacterial Infections

A

on verra…

Unit 3 D&D (18 decks)

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