Influenza Flashcards
Influenza family & genome
Orthomyxovirus
4 types - A to D
A to C cause human infection
A & B - 8 pieces segmented (-) SS RNA
Haemagglutin & Neuraminidase function
H - facilitate attachment to host cell
N - facilitate release of new virus particles from host cell
Antigenic shift and drift
D - mutations in H&N leading to new variants
S - reassortment between 2 distinct flu viruses in same host
Classes of drugs for influenza
- Adamantanes - blocks M2 ion channels of ONLY flu A. Eg - Amantidine. No longer preferred due to high resistance
- Neuraminidase inhibitors - competitive inhibitors of Neuraminidase of both A&B. Eg - Oseltamavir, Zanamavir.
Neuraminidase inhibitors
- Oseltamavir
- Zanamavir - not licensed for <5y
- Peramavir - single dose infusion
- Laninamivir - Japan
Oseltamavir resistance
H275Y mutation in Neuraminidase
Also affects Peramivir but NOT Zanamivir
R292K mutation - Both Oseltamavir & Zanamivir reduced susceptibility
Neuraminidase resistance testing
- Pyrosequencing
- Digital PCR
Newer agents in Flu
- Baloxavir - inhibits cap-dependent endonuclease (mRNA synthesis)
- Favipiravir - inhibits RNA dependent RNA polymerase ( NOT licenced)
- Peramivir - Neuraminidase inhibitor - 600mg IV single dose
- Laninamivir. NOT licenced
R0 for Flu & SRS-CoV-2
- Influenza - 1.8
- COVID - 2.6
Influenza H & N types
H 1 to 18
N 1 to 11
Avian influenza HPAIs & Swine Flu
Avian - H7N9 & H5N1
Swine - H1N1 & H1N2 & H3N2
Avian flu PEP
Oseltamavir 75mg OD x 10 days started up to 7 days post exposure
Followed up for 10 days from last exposure
Signs of bird flu in BIRDS
- Sudden death
- Swollen head
- Runny eyes
- Lethargy
- Unresponsive
- Lack of coordination
- Loss of appetite
- Wing droop
- Dragging legs
- Haemorrhage
- Breathing difficulties
- Fever
- Loose stools
- Drop in egg production
Flu treatment
Uncomplicated: healthy - no prophylaxis
At risk: Oseltamavir 75 BD for 5 days/ 10 if immunocompromised
Complicated: Oseltamavir as above/ inhaled Zanamivir 10mg BD for 5 days
Severely immunosuppressed: depends on circulating strain - if strain has higher chances of Oseltamavir resistance, then start Zanamivir for 5 to 10 days
Flu vaccine patient groups
- > 65
- Pregnancy
- BMI > 40
- Children 2 to 17
Flu vaccine types, strains & doses
Quadrivalent/Trivalent - 2 subtypes of A + 1 or 2 of B - B/Victoria +/- B/Yamagata
LAIV for children - 1 dose intranasal if previously immunised - CAN BE GIVEN WITH OTHER LIVE VACCINES
Inactivated chicken embryo - IM
Flu vaccine in children
6mo to 2 years - only for RISK group. Quadrivalent 2 doses 4 weeks apart
2 to 9 - LAIV
9 to 18 - LAIV
Highly pathogenic avian influenza (HPAI)
H5N1
Dairy cattle in the USA & persists in raw milk
4 human cases as of 7th July 2024- all mild
Found in wild birds in the UK
Vaccine: AFLUNOV
Surface antigens (H&N) of inactivated of strain - Turkey/2005 H5N1 like strain Clade 2.2.1
Propagated in fertilised hen egg
HAIRS risk - Very low
2 doses recommended in poultry workers and other farm workers >18 years
Conjunctival swab testing recommended by CDC for all suspected cases
Influenza protein & receptor
Matrix 1 - viral assembly and nuclear transport PCR target
Matrix 2 - Channel protein with uncoating (Adamantines site of action)
Receptor - Sialic acid - Alpha 2-6 in humans, Alpha 2-3 in Birds, Pigs have both.
Thogotovirus Genus
Tick borne Orthomyxos - 6 segmented (-)ssRNA
Thogoto
Dhori
Bourbon
Flu plan 24/25
> 65: Adjuvanted quadrivalent influenza vaccine (aQIV)
High-dose quadrivalent influenza vaccine (QIV-HD)
18 to 59 years: Cell-based quadrivalent influenza vaccine (QIVc)
60 to 64 years: Cell-based quadrivalent influenza vaccine (QIVc)
High-dose quadrivalent influenza vaccine (QIV-HD)