Influenza Flashcards
What are the features of influenza?
Highly infectious acute respiratory disease
Causes regular epidemics
Significant morbidity, mortality and economic loss
Influenza A has cross species transmission and pandemic potential
What are the different types of Influenza?
Influenza A
Influenza B
Influenza C
What are the features of Influenza B?
Mostly human strains
Common in school outbreaks
Less severe than A
Epidemics occur less often than A
What are the features of Influenza C?
Infects Humans and swine (zoonotic)
Different pattern of surface proteins
Mild to no symptoms
By age 15, most have antibodies
What are the different strains of Influenza A?
Human
Avian Influenza
Swine flu
How is influenza classified?
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
What is the function of Haemagglutinin (HA)?
Attachment to infect host cells
What is the function of Neuraminidase (NA)?
Removes neuraminic acid from mucin and release from cell
What are the clinical symptoms of Influenza?
Coryza Pharyngitis Cough Fever 38 – 40 C Headache Anorexia Malaise, aches & pains
What complications can occur with influenza?
Primary Influenza Pneumonia Secondary bacterial pneumonia Cardiac failure Reyes syndrome CNS disorders e.g. encephalopathy
Describe the replication cycle of influenza viruses
(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
Describe the pathogenesis of Influenza A
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
How is influenza transmitted?
Transmission by aerosol and droplet, lesser extent direct contact
Describe Influenza A epidemiology
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
What types of influenza undergo antigenic drift?
A and B
What types of influenza undergo antigenic shift?
Type A only
Describe the host range of influenza
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
What are the important determinants for host range and tissue tropism?
Epithelial cell surface receptors
What 3 conditions are necessary for influenza A pandemic?
- Emergence of novel Influenza A virus
- Ability to cause disease in humans
- Human – human transmission
By what 2 mechanisms can pandemic influenza originate?
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.
What are the features of Avian Influenza?
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
Describe the pathogenicity
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
Describe the features of AI H5N1
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%
Describe the features of AI H7N9
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
What is the primary risk factor of AI H5N1 and H7N9?
Primary risk factor for humans infection with H5N1 or H7N9 is direct or indirect exposure to infected live or dead poultry or contaminated environments
Describe the features of Swine Flu H1N1
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
How does swine flu H1N1 differ from seasonal flu?
Unlike seasonal flu, pandemic H1N1 can replicate efficiently in cells deeper in the lung, similar to the more pathogenic H5N1 ‘bird flu’
What are the symptoms of swine influenza?
Coughing Sore throat Lethargy Lack of appetite Diarrhea Sneezing Watery eyes Runny nose Fever Weight loss Poor growth
Describe the outbreak history of swine flu H1N1
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
What are the WHO guidelines for global surveillance of Influenza A?
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
What are the vaccination types against influenza?
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
What antiviral therapies are available to treat influenza?
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)
