Pandemic flu

Question 1

Rank these pandemics in order of number of deaths:

            ○ 1968 - Hong Kong Flu 
	○ 1918 - Spanish Flu 
            ○ 2009 - Swine Flu 
	○ 1957 - Asian Flu

Answer 1

○ 1918 - Spanish Flu (50 million deaths)
○ 1957 - Asian Flu (2 million deaths)
○ 1968 - Hong Kong Flu (1 million deaths)
○ 2009 - Swine Flu (200,000 deaths)

Question 2

influenza viruses are acquired in humans how?

Answer 2

zoonotic transmission initially - so reservoirs are animals

usually from Avian influenza viruses

Question 3

The natural reservoir for influenza A viruses is __?

Answer 3

ducks (migratory waterfowl - eg geese and swans )

Question 4

why does influenza cause respiratory disease?

Answer 4

because the virus requires activation by host cell proteases that are only expressed in the respiratory tract

Question 5

what is the enzyme specific to the lungs that is responsible for cleaving influenza haemaglutinin?

Answer 5

Human airway tryptase: HAT

Question 6

what is the mutation that is associated with bird flu being able to cross into humans?

Answer 6

polymerase protein - PB2 627K

Question 7

which bird flu’s have a high mortality rate and why?

Answer 7

H7N9 - biggest pandemic threat
H5N1

cause massive cytokine response

Question 8

two steps required for influenza viruses to infect humans ?

Answer 8

○ Acquire the ability to infect human cells (either by PB2 627K or by reassortment)

○ Develop the ability to transmit between humans : reassortment of genes and antigenic shift

Question 9

uman influenza viruses are transmitted via __?

Answer 9

respiratory droplets

Question 10

3 requirements necessary for a virus to cause a pandemic?

Answer 10

A pandemic virus will have novel antigenicity.

A pandemic virus will replicate efficiently in human airway.

A pandemic virus will transmit efficiently between people.

Question 11

list some Features of HA and NA that affect influenza transmission - conferring ability to infect?

Answer 11

NA stalk length - longer stalk

Virion stability - HA should be stable at low pH to prevent dissolution in endoscopes

Receptor binding - HA adapted to bind a2, 6, SA

Question 12

which influenza circulates in pigs?

Answer 12

H1, H3

Question 13

Loss of which protein is linked with severe influenza?

Answer 13

IFITM3

Interferon Induced Transmembrane Protein 3

Question 14

list 3 antivirals used in flu and their mode of transmission ?

Answer 14

Neuraminidase inhibitors and mode of administration:
Tamiflu (oseltamivir) oral
Relenza (zanamivir) inhaled or iv formulation

Amantadine:
Targets M2 ion channelDoes not work against influenza B or pH1N1 or seasonal H3N2

Polymerase inhibitors - Japan only

Question 15

how has Emergence of multidrug resistant pH1N1 been reduced?

Answer 15

use of triple therapy

Question 16

The seasonal influenza vaccine given to HIGH RISK GROUPS (e.g. > 65 years) in the UK is?

Answer 16

a purified fraction containing HA and NA of an inactivated virus

usually require an adjuvant to stimulate the immune response

Question 17

every school-aged child in the UK of a certain age are given which vaccine ?

Answer 17

a live-attenuated vaccine

Question 18

difference between the inactivated virus vaccine and live attenuated vaccines?

Answer 18

live vaccines provides a broader, more cross-reactive immunity than the inactivated vaccines

live: from cold adapted virus

Question 19

characteristics of inactivated vaccine?

Answer 19

Split or subunit- HA rich

Question 20

Novel oil-in-water adjuvants used in monovalent vaccines AS03 Pandemrix had which side effect?

Answer 20

Narcolepsy

Question 21

narcolepsy involves which symptoms?

Answer 21

excessive daytime sleepiness

disturbed night time sleep

Question 22

MOA linking vaccines to narcolpesy?

Answer 22

Vaccine generates cross reactive antibodies

These traverse into the CNS and bind to hypocretin receptor 2

Hypocretin production down regulated

sleep symptoms

Question 23

where do antibodies bind on the influenza?

Answer 23

the stem on the spike protein (HA)