Influenza

Question 1

How does influenza related to the sun?

Answer 1

More severe epidemics of influenza occur every 11 years; same as increased ‘sunspot activity’

The sun’s radiation may cause mutations leading to “antigenic shifts’ in viral RNA.

Theory that Vitamin D levels help to prevent viral infection

Question 2

what is the structure of influenza?

Answer 2

• RNA virus. 8 segment genome
• Orthomyxoviridae family
• Three main groups:
• A (1933)
• B (1939)
• C (1950)

Question 3

INfluenza A, B and C affect whoa dn what?

Answer 3

IfA infects mammals and birds, IfB & IfC only humans

Question 4

what are the surface proteins of influenza and their function?

Answer 4

18 different H antigens (H1-3 in humans) and 11 different N antigens

Haemagglutinin (H) - facilitates viral attachment and entry to host cell

Neuraminidase (N) - enables new virion to be released from host cell

Question 5

what is antigenic drift?

Answer 5

• Mechanism of genetic variation within the virus
• Occurs continually over time, small on-going point mutations in the genes coding for antibody binding-sites
• May change the antigenic properties and eventually the immune system will not combat the virus as well
• Causes worse than normal epidemics & vaccine mismatch

Question 6

what is antigenic shift?

Answer 6

• Abrupt major change in the virus, resulting in new H/N combinations
• The genetic change that enables a flu strain to jump from one animal species to another
• The process by which two or more different strains of a virus combine to form a new subtype, resulting in new H/N combinations
• Reassortment of the virus’ gene segments
• With new antigenic properties the population at risk is unprotected and this can lead to PANDEMICS

Question 7

What is the difference between antigenic drift and shift?

Answer 7

Antigenic drift - Mutations causing minute changes in the hemagglutinin and neuraminidase antigens on the surface of the Influenza virus is termed as antigenic drift

Antigenic shift - Antigenic shift refers to the gene recombination occurring when influenza viruses re-assort

Question 8

How is pandemic flu different form seasonal flu?

Answer 8

Seasonal flu:

• Occurs every winter
• Affects 10-15 % of the population
• Usually unpleasant but not life-threatening

Pandemic flu:

• Occur sporadically
• Affects 25% + of the population
• More serious, more complications

Question 9

what are the requirements for a pandemic?

Answer 9

Human pathogenicity

‘New’ virus (antigenic shift) - susceptible population

Efficient person-person transmission

Question 10

what age has the greatest mortality?

Answer 10

Question 11

What is avian flu?

Answer 11

• Many types of avian influenza - Few strains affect humans: H5N1 (since 1997), H7N9 (since 2013)
• Spreads through direct contact with infected birds, dead or alive
• Occasional transmission via close human to human contact (staff, caregivers)
• No known transmission by eating properly cooked food/eggs etc
• High case fatality rate: 60% (H5N1), 36% (H7N9)
• Current outbreaks in China (H7N9) and Egypt (H5N1)

Question 12

what are the clinical features of influenza?

Answer 12

• Incubation period 2-4 days (range 1-7 days)
• Abrupt fever up to 41°C (commonly 38-40°C) which lasts 3 days (range 1-5 days)
• Plus 2 or more of: Cough, [sore throat, rhinorrhoea], myalgia, headache, malaise.
• Predominance of systemic symptoms
• Less common symptoms: Nausea, vomiting, diarrhoea

Question 13

Influenza like illness (ILI)

WHO definition (2011); for epidemiological purpose is what?

Answer 13

• Fever (>38°C) and
• Cough
• Onset within the last 10 days

(if requires hospitalization defined as severe acute respiratory infection (SARI))

Question 14

what are the symptoms of swine flu?

Answer 14

Question 15

how is it transmitted?

Answer 15

• Airborne - person = person by large droplets >5 microns
• Contact – direct (person = person)

– indirect (person = fomite = person)

Question 16

what is virus shedding?

Answer 16

viral shedding occurs when a virus replicates inside your body and is released into the environment. at that point, it may be contagious

Question 17

what is the virus shedding of this infection?

Answer 17

• First 4 days of illness (range 1-7 days)

Longer in young children & immunocompromised

Question 18

what is the virus survival?

Answer 18

• 24-48 hours on non-porous surfaces
• 8-12 hours on porous surface e.g. tissue

Question 19

high risk groups:

What are some risk factors for complicated influenza?

Answer 19

a. Neurological, hepatic, renal, pulmonary and chronic cardiac disease
b. Diabetes mellitus
c. Severe immunosuppression
d. Age over 65 years
e. Pregnancy (including up to two weeks post partum)
f. Children under 6 months of age
g. Morbid obesity (BMI ≥40)

Question 20

what are some common respiratory complications?

Answer 20

• Acute Bronchitis
• Secondary Bacterial Pneumonia (~20%) - Appears 4-5 days after start of ‘flu

Question 21

What are some Less Common respiratory Complications?

Answer 21

• Primary viral pneumonia

• appears common in human cases of avian influenza (H5N1)
• rapid respiratory failure; within 48 hours
• mortality >40%; within 7 days

Question 22

what are some less common cardiac complications?

Answer 22

Myocarditis/pericarditis

Question 23

What are some less common CNS complications?

Answer 23

• Transverse myelitis/Guillain-Barre
• Myositis & Myoglobinuria

Question 24

influenza is a ____________ disorder

Answer 24

multi-system

Question 25

what is the diagnosis and investigations required?

Answer 25

* Viral nose and throat swabs/VTS (Molecular detection /PCR; using flocked swabs) * Chest X-ray – pneumonitis/pneumonia/ARDS * Blood culture * Pulse oximetry – SpO2 \<92% need ABG and oxygen * Respiratory rate ! * U & E’s, FBC, CRP (CRP monitoring recovery of pneumonia - should halve in 4 days)

Question 26

what is secondary bacterial pneumonia and what needs to be done?

Answer 26

* Patients with ‘flu symptoms and a fever for \> 4days – should have an urgent CXR * Severity assessment – use C(U)RB-65 score - Confusion - Urea \>7mmol/l - Respiratory rate \>30mm - Blood Pressure (diastolic \<60 or systolic \<90) - \>65 years of age • C(U)RB score: Risk of death in the next 30 days (0=0.6%, 1=3.2%, 2=13%, 3=17%, 4=41.5%, 5=57%)

Question 27

should you use antiviral therapy?

Answer 27

Use ASAP and within 48hours of symptom onset!

Question 28

what antiviral treatments are there avalible?

Answer 28

OSELTAMIVIR (TAMIFLU) - Oral Dose : Over 13 years – 75mg every 12 hours for 5 days Adverse Effects: Common – Nausea, vomiting, abdominal pain, diarrhoea Less Common – Headache, hallucinations, insomnia and rash Cautions: Renal dosing needed ZANAMIVIR (RELENZA) – Inhaled & or I.V. Available only as a dry powder inhaler Dose: Over 12 years – 10mg inhaled daily for up to 10 days Adverse Effects: Rare – occasional bronchospasm

Question 29

what are some other antiviral therapies?

Answer 29

•Peramivir (Alpivab®) –Neuroaminidase inhibitor –Licensed in USA and approved by European Medicines Agency (EMA) 1st May 2018 ! –Intravenous infusion, for uncomplicated influenza • Favipiravir (Avigan®, Toyama Chemicals Ltd) –Viral RNA polymerase inhibitor –Licenced in Japan for ‘re-emerging influenza viruses’ –Oral medication • Baloxavir Marboxil (Xofluza®, Roche) –Endonuclease inhibitor –One single dose •(Amantadine & Rimantadine not used due to resistance)

Question 30

what are the current guidelines for antiviral therapy in pregnancy?

Answer 30

Antivirals have been recommended…due to the adverse outcomes …in this group Oseltamivir remains first line option… Recent studies (2014) suggests there is no evidence of harm of either oseltamivir or zanamivir FDA pregnancy category C: No malformation, maternal toxicity or embryotoxcity were observed in animal studies. No data available in humans.

Question 31

Antiviral therapy and breastfeeding

Answer 31

* Only tiny amounts of Oseltamivir in milk * Current guidance is – Oral Oseltamivir

Question 32

When does an individual become non-infectious?

Answer 32

IMMUNOCOMPETENT ADULTS * 24hrs after last flu symptoms (fever & cough) * Or when anti-viral therapy completed, Which ever is longer IMMUNOCOMPROMISED ADULTS & YOUNG CHILDREN •Consider each case separately

Question 33

what protection is required for healthcare staff?

Answer 33

* Surgical face mask * Plastic apron * Gloves Wash hands after any examination

Question 34

what is the vaccine prepared and given? (seasonal flu vaccine)

Answer 34

* Prepared each year using viruses considered most likely to be circulating in the forthcoming winter * Grown in chick embryos (therefore C.I. in those with egg allergy) * Chemically inactivated and purified, trivalent vaccines - Containing 2 type A & 1 type B subtype viruses * Single 0.5 ml intramuscular injection * Only adverse effect in large placebo controlled trials is sore arm

Question 35

why should healthcare workers have the vaccine?

Answer 35

* To protect themselves and their families * To reduce the risk to ‘at risk’ patients * To reduce absence from work during influenza ‘surge’ activity