Influenza

Question 1

What are the features of influenza?

Answer 1

Highly infectious acute respiratory disease

Causes regular epidemics

Significant morbidity, mortality and economic loss

Influenza A has cross species transmission and pandemic potential

Question 2

What are the different types of Influenza?

Answer 2

Influenza A
Influenza B
Influenza C

Question 3

What are the features of Influenza B?

Answer 3

Mostly human strains
Common in school outbreaks
Less severe than A
Epidemics occur less often than A

Question 4

What are the features of Influenza C?

Answer 4

Infects Humans and swine (zoonotic)
Different pattern of surface proteins
Mild to no symptoms
By age 15, most have antibodies

Question 5

What are the different strains of Influenza A?

Answer 5

Human
Avian Influenza
Swine flu

Question 6

How is influenza classified?

Answer 6

Classification by surface antigens into subtypes

• Haemagglutinin (H or HA)
• Neuraminidase (N or NA)

16 HA and 9 NA for influenza A
- All in aquatic birds

Question 7

What is the function of Haemagglutinin (HA)?

Answer 7

Attachment to infect host cells

Question 8

What is the function of Neuraminidase (NA)?

Answer 8

Removes neuraminic acid from mucin and release from cell

Question 9

What are the clinical symptoms of Influenza?

Answer 9

Coryza 
Pharyngitis 
Cough
Fever 38 – 40 C
Headache
Anorexia
Malaise, aches & pains

Question 10

What complications can occur with influenza?

Answer 10

Primary Influenza Pneumonia
Secondary bacterial pneumonia
Cardiac failure
Reyes syndrome
CNS disorders e.g. encephalopathy

Question 11

Describe the replication cycle of influenza viruses

Answer 11

(1) The viral HA binds to sialic acid residues on glycoproteins or glycolipids on the cell surface.
(2) Engulfment of the virus by the cell plasma membrane and formation of an endocytic vesicle.
(3) Delivery of the virus to the endosomal cell compartment.
(4) Fusion of the viral membrane with the membrane of the endosome, induced by the mildly acidic pH in the endosomal lumen.
(5) Delivery of viral RNA to the nucleus, synthesis of messenger RNA (mRNA) and viral RNA replication.
(6) Synthesis of viral protein components in the cell cytosol (internal proteins) and endoplasmic reticulum (ER) (membrane proteins).
(7) Assembly and budding of progeny viruses

Question 12

Describe the pathogenesis of Influenza A

Answer 12

Replicates in URT and LRT
Peak shedding 2 days, self-limiting 4-7 day

Leads to complex cytopathic effects due to downregulation of host cell protein synthesis and apoptosis, predominantly in the airways epithelial cells

Apoptosis occurs also in lymphocytes explaining the lymphopenia observed during acute infection

IgA and IgG produced

Cell Mediated Immunity important for clearance

Question 13

How is influenza transmitted?

Answer 13

Transmission by aerosol and droplet, lesser extent direct contact

Question 14

Describe Influenza A epidemiology

Answer 14

Maintained in humans throughout the year
- Peak prevalence in winter

Young children major vectors in transmission

Seasonal Influenza - Epidemics every 2 -3 years, often follow school autumn term

• Indicator – ‘herald wave’ (late spring)
• Summer outbreaks occasionally seen
• Annually 3-5 million cases of severe illness
• Up to 500,000 deaths worldwide

Question 15

What types of influenza undergo antigenic drift?

Answer 15

A and B

Question 16

What types of influenza undergo antigenic shift?

Answer 16

Type A only

Question 17

Describe the host range of influenza

Answer 17

HA 1 -16 NA 1 –9
Wild waterfowl natural hosts to all known influenza A subtypes

H1N1, H1N2, H3N2 currently circulating in humans

H5, H7, H9 & N7 also infect humans, but on/limited human-human transmission

Question 18

What are the important determinants for host range and tissue tropism?

Answer 18

Epithelial cell surface receptors

Question 19

What 3 conditions are necessary for influenza A pandemic?

Answer 19

1. Emergence of novel Influenza A virus
2. Ability to cause disease in humans
3. Human – human transmission

Question 20

By what 2 mechanisms can pandemic influenza originate?

Answer 20

The avian influenza virus can replicate and by chance change its receptor to human type, when you can get direct transfer to humans.

A non-human and human virus can get into another host, making reassortant virus.

Question 21

What are the features of Avian Influenza?

Answer 21

Most AI do not infect humans
Some cause severe infections in humans
Outbreaks of AI in poultry raise global public health concerns:
~ severe disease in poultry populations
~ potential to cause severe disease in people
~ pandemic potential

Question 22

Describe the pathogenicity

Answer 22

All AI is divided into 2 subtypes based on genetic features and/or disease severity in poultry:
Low pathogenic AI (LPAI)
H1 to H16 subtypes
Not generally associated with severe disease in poultry
Highly pathogenic AI (HPAI)
Some H5 or H7 subtypes
High death rates in poultry (up to 100% in 48 hrs)
LPAI H5 or H7 subtypes can mutate into HPAI

Question 23

Describe the features of AI H5N1

Answer 23

H5N1 in humans first described Hong Kong 1997 (18 infected, 6 deaths)
Widespread re-emergence in 2003 and 2004
> 600 human HPAI H5N1 reported since November 2003.
Case fatality 60%

Question 24

Describe the features of AI H7N9

Answer 24

H7N9 in humans first described China, spring 2013 (132 infected , 44 deaths)
First case outside China reported February 2014 in Malaysia.
Case fatality 33%

No evidence sustained person-to-person spread
Evidence limited person-to-person spread
Slight mutation could convert to a strain transmissible from human to human

Question 25

What is the primary risk factor of AI H5N1 and H7N9?

Answer 25

Primary risk factor for humans infection with H5N1 or H7N9 is direct or indirect exposure to infected live or dead poultry or contaminated environments

Question 26

Describe the features of Swine Flu H1N1

Answer 26

Novel Influenza strain Generally mild respiratory illness (severe disease or death in vulnerable individuals) H1 N1 Reassortment of human and swine influenza viruses. 6 genes from American swine flu (mix of swine, bird & human flu) HA gene similar to swine flu viruses present in U.S. pigs since 1999 NA and matrix protein genes from European swine flu

Question 27

How does swine flu H1N1 differ from seasonal flu?

Answer 27

Unlike seasonal flu, pandemic H1N1 can replicate efficiently in cells deeper in the lung, similar to the more pathogenic H5N1 'bird flu'

Question 28

What are the symptoms of swine influenza?

Answer 28

``` Coughing Sore throat Lethargy Lack of appetite Diarrhea Sneezing Watery eyes Runny nose Fever Weight loss Poor growth ```

Question 29

Describe the outbreak history of swine flu H1N1

Answer 29

April 2009 outbreaks in Mexico and the USA June 2009 WHO declared an H1N1 pandemic January 2010 - transmission in 208 countries,13,554 deaths Highest incidence in school age children > hospitalised cases children &young adults (highest 0-4 yrs) Few cases in older adults but highest case-fatality ratio 70% of hospitalised cases have underlying medical condition From September 2010 Antigenically unchanged virus circulating > hospital cases in 40-50 year olds with no underlying medical conditions

Question 30

What are the WHO guidelines for global surveillance of Influenza A?

Answer 30

Monitor global occurrence Identify and characterize emergent influenza strains Monitor changes in transmission patterns Monitor unusual morbidity / mortality due to acute respiratory illness Monitor global activity of influenza viruses in animal/avian populations

Question 31

What are the vaccination types against influenza?

Answer 31

Inactivated vaccine Propagated in eggs or human diploid fibroblast Purified HA & NA harvested & lipids extracted - Trivalent vaccines Protect against 3 strains A/H3N2, A/H1N1, and influenza B - Quadivalent vaccines Protect against 4 strains of the flu, A/H3N2, A/H1N1, and 2 strains of influenza B ``` Live attenuated vaccine - Only in Russia, not licenced in UK Serial passage at 33oC intranasal trivalent duration of immunity at least 1 year ```

Question 32

What antiviral therapies are available to treat influenza?

Answer 32

Amantadine hydrochloride Inhibits viral uncoating Rimantadine hydrochloride Inhibits viral uncoating Zanamivir (Relenza) Neuraminidase inhibitor ``` Osteltamivir phosphate (Tamiflu) Neurominidase inhibitor ``` (1st 2 no longer given, immediate resistance. 2nd 2 must be given within 24 hours)