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Part 2 Revision > Influenza > Flashcards

Influenza Flashcards

1
Q

What influenza A subtypes caused the following pandemics:

1957
1968
1977
2009

A

1957 = H2N2 Asian
1968 = H3N2 Hong Kong
1977 = H1N1
2009 = H1N1 (pmd2009)

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2
Q

Are influenza viruses RNA/DNA viruses? What type? And what is unique about their replication cycle?

A

Enveloped, segmented ss-RNA

Unlike most RNA viruses, they replicate in the nucleus rather than the cytoplasm

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3
Q

What are the reservoir hosts of influenza A, B, C and D.

A

A) Main reservoir is waterfowl, but IAV has human and swine reservoir and most other mammals can be infected

B) Humans only (occasion spill over into seals/pigs/ferrets)

C) Humans and pigs

D) Cattle only

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4
Q

What is the function of heamagglutinin and neurominidase in influenza

A

HA - sialic acid receptor binding site (approx 300 per virus)

NA - sialic acid cleavage allowing release of viral particles (approx 40 per virus)

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5
Q

How many HA and NA types are there. Which infect humans?

A

18 HA and 11 NA

HA 17/18 and NA 10/11 are only found in bats and do not infect humans

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6
Q

What is the molecular make up of H1N1pdm09?

A

Quadruple reassortment consisting of two swine origin viruses, one avian and one human origin virus

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7
Q

In relation to influenza infection which sialic acid would you find in the upper and lower respiratory tract?

A

a2,6-linked sialic acid is the main receptor for seasonal influenza. This is expressed by the epithelial cells in the URT

a2,3-liked sialic acid is found in duck gut epithelium and this is the target for AIVs

a2,3-liked sialic acid is also found in the LRT of humans

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8
Q

Risk factors for complicated flu

A

Underlying disease (neurological, hepatic, renal, pulmonary, cardiac)

Severe immunosuppression

Over 65 y

Pregnancy (and 2 weeks post partum)

Under 6 m

Morbid obesity

Asplenia

Learning disability

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9
Q

Complications of influenza

A

Croup, bronchiolitis, otitis media (esp in kids)

Primary viral pneumonia

Secondary bacterial pneumonia

Invasive fungal disease

Exacerbation of underlying illness

Myositis and rhabdomyelitis

Myocarditis

Encephalitis/Meningo-encephalitis

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10
Q

Neurological complications of flu

A

Encephalitis/encephalopathy

Transverse myelitis

Acute disseminated encephalomyelitis

Seizures

Less commonly GBS and Reye’s syndrome (with salicylate exposure)

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11
Q

Diagnostic investigation for flu CNS infection

A

PCR sensitivity in CSF is very low as virus may no longer be present

Intrathecal Ab may be useful

Brian biopsy may be positive

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12
Q

Future possible treatments for influenza

A

MAb to stem region of HA

Epithelial cell targets - interferon lambda and fludase

Immunomodulators - TNFa and IFNab

Etanercept - TNF inhibitors

Umifenovir - used in China and Russia, membrane fusion inhibitor with immunomodulatory effects

Nitazoxanide

Short interfering RNAs

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13
Q

If a patient is on zanamivir and has a poor clinical response, should you switch to oseltamivir?

A

No.

Zanamivir resistance strains will likely also be resistant to oseltamivir, so keep on zanamivir and request resistance testing

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14
Q

In which situations would you continue influenza treatment to >5 days?

A

Severely immunosuppressed patients on oseltamivir require 10 day course

In severe flu can extend treatment to 10+ days, but monitor for resistance

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15
Q

What can result in a poor clinical response to neuraminidase inhibitors?

A

NI resistance

Natural flu progression

Lung damage

Immune mediated damage

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16
Q

In which cases would you consider repeat PCR testing if patients already on neuraminidase inhibitors?

A

Poor clinical response at 5 days and considering extending treatment

Develops ILI whilst on NI prophylaxis

17
Q

Stem cell transplant patient inadvertently given LAIV ?action

A

If an immunocompromised individual receives LAIV then the degree of immunosuppression should be assessed. If the patient is severely immunocompromised, antiviral prophylaxis should be considered, otherwise they should be advised to seek medical advice if they develop flu-like symptoms in the 4 days (the usual incubation period) following administration of the vaccine.

18
Q

Flu reproduction cycle

A

Enters cells through haemaglutinin interaction with sialic acid. Then migrated to a clathrin well on the cell membrane where it is absorbed into an endosome. M2 channels pump protons into the virus envelope which decrease the pH and causes a protein change which migrates the viral envelope to the edge of the endosome. The viral genome is ejected into the nucleus where translation and transcription start following ‘cap snatching’ by the viral RNA polymerase.
Once translation and transcription has completed the viral particle is completed in the cytoplasm. This then buds out of the cell gathering the membrane as the viral envelope. Neuraminidase catalyses sialic acid at this stage and releases the viral particle into the extracellular space.

19
Q

MOA
- Oseltamivir/Zanamivir
- Baloxivir
- Amantadine

A

Neuraminidase inhibitors
- Cap dependent endonuclease inhibitor
- M2 protein channel blocker

20
Q

Treatment dose oseltamivir/zanamivir in adults
- dose
- route
- duration

A

Oseltamivir
- 75mg BD PO for 5 days (10 if severe disease or immunosuppressed)

Zanamivir
- 10mg BD Inh for 5 days (can be IV if inhaler not available and oseltamivir not suitable).

21
Q

What is the make up of H1N1pdm09?

A

Quadruple reassortant

1) Eurasian swine
2) Classic swine H1N1
3) Human H3N2
4) Avian

22
Q

What are the receptors for HA?

A

a2,6-linked sialic acid in URT
a2,3-linked sialic acid in LRT and duck gut epithelium

23
Q

What are the risk factors for complicated flu?

A

Underlying disease - hepatic, cardiac, neurological, renal, pulmonary

Severe immunosuppression

Over 65 years

Under 6 months

Pregnancy

Morbid obesity

Diabetes

Asplenia/splenic dysfunction

Learning disability

24
Q

When do neurological symptoms occur in relation to flu infection, and what neurological disorders can occur?

A

Encephalopathy

Encephalitis

Transverse myelitis

ADEM

Seizures

GBS

Reye’s syndrome (with salicylate exposure)

25
Q

What supportive care is available in flu infection?

A

Hydration

Pain killers

Treating exacerbation of underlying conditions

Oxygen

Antibiotics

26
Q

Options for flu positive mum in labour

A

Treat mum

Baby

1) prophylax with oral oseltamivir suspension
2) separation until after 5 days symptom onset
3) monitor

27
Q

How long post partum are pregnant woman still at risk of severe influenza?

A

2 weeks

28
Q

Treatments of:

  1. Uncomplicated flu in previously healthy patient
  2. Uncomplicated flu in at risk group, not severely immunosuppressed
  3. Complicated flu, not severely immunosuppressed
  4. Uncomplicated flu in severely immunosuppressed
  5. Complicated flu in severely immunosuppressed
A
  1. No treatment (unless at risk of complications)
  2. Oseltamivir 5d
  3. Oseltamivir 5d (second line zanamivir)
  4. Oseltamivir if H3 or IBV. Zanamivir if H1
  5. Oseltamivir if H3 or IBV, second line Zanamivir if poor clinical response, gastro dysfunction. Zanamivir if H1
29
Q

What influenza vaccine and schedule is recommended in the following patients:

1) 18 month old in clinical risk category, never had flu vaccine previously

2) 18 month old in clinical risk category, previously had one flu vaccine

3) 5 y old in clinical risk category, never had flu vaccine previously

4) 5 y old in clinical risk category, previously had one flu vaccine

A

1) 2 doses of QIVc 4 weeks apart (Aged 6-24 m in clinical risk category)

2) 1x doses of QIVc (Aged 6-24 m in clinical risk category having had at least previous flu vaccine dose)

3) 2 doses of LAIV 4 weeks apart (Aged 5-9 in clinical risk category)

4) 1 dose of LAIV (Aged 5-9 in clinical risk category, and in >9 y in clinical risk group)

30
Q

What are the benefits of cell based influenza vaccines over egg based?

A

Overcome issues with lower vaccine effectiveness due to egg adaptions

31
Q

Which groups get influenza vaccine?

A

All at risk patients aged 6 month + in clinical risk groups
All patients aged 65y +
Children aged 2-17
Pregnant women
Carers
Household contacts of the immunosuppressed
Care home residents
Healthcare workers
People working in the avian industry

32
Q

Which type of flu vaccine does JCVI recommend for the following groups:

1)18-59 years eligible groups

2) 60-64 y eligible groups

3) >65 y

A

1) QIVc

2) QIVc or QIV-HD

3) aQIV or QIV-HD

33
Q

Which type of flu vaccine does JCVI recommend for the following groups:

1) At risk 6m-2y

2) 2-18 y

A

1) QIVc

2) LAIV (unless contraindicated then use QIVc)

34
Q

Are the LAIV and inactivated flu vaccines trivalent or quadravalent?

A

LAIV is trivalent

All inactivated vaccines are quadravalent

35
Q

When can you give NIs before/after LAIV?

A

Do not vaccinate until after 48 h after finishing antivirals

If given antivirals within 2 weeks of LAIV then revaccinate

36
Q

Future influenza vaccines

A

Universal flu vaccine is the goal!

Viral like particles
mRNA vaccines
Recombinant HA vaccine using baculovirus expression system
Targeting HA stalk domain

37
Q

PPE for staff and visitors within 2 m of flu patient

A

Plastic apron, gloves, face mask and eye protection

38
Q

PPE for AGP in flu

A

FFP3 face mask, fluid repellent gown, gloves, eye protection

39
Q

How long should patients with flu be isolated for?

A

Until 24 h after resolution of symptoms

Part 2 Revision (48 decks)

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