Influenza
last updated 6th March 2020 - Tom Heaton
Influenza is a serious viral infection.
This is an excellent overview video from the Osmosis team: https://www.youtube.com/watch?v=85R-6O6rrgw
This is an excellent overview video from the Osmosis team: https://www.youtube.com/watch?v=85R-6O6rrgw
The influenza viruses are categorised as A, B, and C.
They are negative single-stranded RNA orthomyxoviridae with a helical nucleocapsid.
They are enveloped, with 2 different types of glycoprotein on the envelope:
The NA glycoproteins are thought to relate to facilitating the release of newly produced viral particles from the cell.
Such receptors are also found on RBCs, and can lead to agglutination of these, hence the nomenclature.
They are pleomorphic (demonstrating a potential variety of shapes) and are about 80-120 nm in diameter.
The types of flu (A,B,C) have numerous different subtypes characterised by the variation on HA and NA receptors (e.g. H1N1).
The different types have differing nuclear and antigenic material.
Type A is the common form of worldwide pandemics, and can transmit across species e.g. birds, mammals.
Types B and C are human only, and more responsible for localised outbreaks (and often milder).
Type C is generally a much rarer and milder form, more akin to the common cold.
Changes in these glycoproteins through gradual mutation over time results in the changing strains, and the subsequent new outbreaks (termed antigenic drift).
Type A can occasionally under major changes in protein structure, resulting in pandemics (called antigenic shift).
This can result from genetic code that has arisen in an animal reservoir, perhaps from the ‘shuffling’ of the genetic material from different strains within that host.
The type of flu will come and go in epidemic patterns.
17/18 - H3N2 and flu B
18/19 - H1N1
2009 - ‘Swine flu’ H1N1
They are named through a specific classification system:
Type/geographic origin/strain number/year of isolation/(HA & NA subtypes)
Type A may also include any animal of origin.
They are negative single-stranded RNA orthomyxoviridae with a helical nucleocapsid.
They are enveloped, with 2 different types of glycoprotein on the envelope:
- HA - Hemagglutinin activity
- NA - Neuraminidase activity
The NA glycoproteins are thought to relate to facilitating the release of newly produced viral particles from the cell.
Such receptors are also found on RBCs, and can lead to agglutination of these, hence the nomenclature.
They are pleomorphic (demonstrating a potential variety of shapes) and are about 80-120 nm in diameter.
The types of flu (A,B,C) have numerous different subtypes characterised by the variation on HA and NA receptors (e.g. H1N1).
The different types have differing nuclear and antigenic material.
Type A is the common form of worldwide pandemics, and can transmit across species e.g. birds, mammals.
Types B and C are human only, and more responsible for localised outbreaks (and often milder).
Type C is generally a much rarer and milder form, more akin to the common cold.
Changes in these glycoproteins through gradual mutation over time results in the changing strains, and the subsequent new outbreaks (termed antigenic drift).
Type A can occasionally under major changes in protein structure, resulting in pandemics (called antigenic shift).
This can result from genetic code that has arisen in an animal reservoir, perhaps from the ‘shuffling’ of the genetic material from different strains within that host.
The type of flu will come and go in epidemic patterns.
17/18 - H3N2 and flu B
18/19 - H1N1
2009 - ‘Swine flu’ H1N1
They are named through a specific classification system:
Type/geographic origin/strain number/year of isolation/(HA & NA subtypes)
Type A may also include any animal of origin.
Pathophysiology
Transmission is through droplets/aerosols from an infected patient's respiratory tract.
These can be under 10 micrometers in size and be small enough to reach the alveoli.
These can be transmitted directly or indirectly through surfaces.
Viral levels remain high for the first 24-48 hours after symptoms start.
The virus invades the epithelial cells of the upper airway.
This viral processes and subsequent immune response (effects of interferon, cytotoxic T cells) result in cell death and desquamation.
Damage to the normal barrier defensive mechanisms of the respiratory tract (including mucus clearance) can result in increased susceptibility to secondary infections.
The initial innate immune response is followed by a humoral response as well as developing cellular immunity.
These can be under 10 micrometers in size and be small enough to reach the alveoli.
These can be transmitted directly or indirectly through surfaces.
Viral levels remain high for the first 24-48 hours after symptoms start.
The virus invades the epithelial cells of the upper airway.
This viral processes and subsequent immune response (effects of interferon, cytotoxic T cells) result in cell death and desquamation.
Damage to the normal barrier defensive mechanisms of the respiratory tract (including mucus clearance) can result in increased susceptibility to secondary infections.
The initial innate immune response is followed by a humoral response as well as developing cellular immunity.
Presentation
This is usually non-specific:
Risk factors for severe disease include:
In temperate areas, cases tend to occur through the winter months (December to March in the UK).
Pandemics may occur with new viral strains.
Transmission rates are high, at ratios of 3:1 to 9:1.
- Malaise
- Fever
- Myalgia/arthralgia
- Cough
- Headache
- Sore throat
- Sneezing/nasal discharge
- GI upset (in children)
Risk factors for severe disease include:
- Chronic disease
- Respiratory
- Renal
- CVS
- Respiratory
- Extremes of age
- High BMI
- Immunosuppression
- Pregnancy
- DM
- Transplant
- Cancer
- Pregnancy
In temperate areas, cases tend to occur through the winter months (December to March in the UK).
Pandemics may occur with new viral strains.
Transmission rates are high, at ratios of 3:1 to 9:1.
Investigation
Investigations will be detected towards the investigation of the presenting complaint.
Specific identification is through RT-PCR of airway samples (upper and lower).
Sensitivity is best when samples are taken early (quoted as within the first 3 days), but can remain high with ongoing URTI symptoms.
In cases of high suspicion, negative tests should be repeated because of the risk of false negative results.
In the critically ill (e.g. intubated) lower respiratory tract samples may be needed because throat samples may be negative.
Specific testing setups at different sites will clearly vary, but are increasingly being able to provide rapid on-site testing, with an expansion of point-of-care testing availability.
Specific identification is through RT-PCR of airway samples (upper and lower).
Sensitivity is best when samples are taken early (quoted as within the first 3 days), but can remain high with ongoing URTI symptoms.
In cases of high suspicion, negative tests should be repeated because of the risk of false negative results.
In the critically ill (e.g. intubated) lower respiratory tract samples may be needed because throat samples may be negative.
Specific testing setups at different sites will clearly vary, but are increasingly being able to provide rapid on-site testing, with an expansion of point-of-care testing availability.
Management
Investigations will be detected towards the investigation of the presenting complaint.
Specific identification is through RT-PCR of airway samples (upper and lower).
Sensitivity is best when samples are taken early (quoted as within the first 3 days), but can remain high with ongoing URTI symptoms.
In cases of high suspicion, negative tests should be repeated because of the risk of false negative results.
In the critically ill (e.g. intubated) lower respiratory tract samples may be needed because throat samples may be negative.
Specific testing setups at different sites will clearly vary, but are increasingly being able to provide rapid on-site testing, with an expansion of point-of-care testing availability.
Management
This can be broken down to:
Specific therapy relates to antiviral therapy, and is usually indicated for high risk patients.
Agents used include the neuraminidase inhibitors:
Any effect from treatment beyond this is dubious, and indeed there is some controversy about actual efficacy.
The quoted benefits are primarily reduction of complications and reduced duration of symptoms.
Resistance to oseltamivir is a potential problem (appears more common with H1N1).
Testing for this usually takes a more prolonged time than simple viral identification.
Specific identification is through RT-PCR of airway samples (upper and lower).
Sensitivity is best when samples are taken early (quoted as within the first 3 days), but can remain high with ongoing URTI symptoms.
In cases of high suspicion, negative tests should be repeated because of the risk of false negative results.
In the critically ill (e.g. intubated) lower respiratory tract samples may be needed because throat samples may be negative.
Specific testing setups at different sites will clearly vary, but are increasingly being able to provide rapid on-site testing, with an expansion of point-of-care testing availability.
Management
This can be broken down to:
- Supportive
- Specific
Specific therapy relates to antiviral therapy, and is usually indicated for high risk patients.
Agents used include the neuraminidase inhibitors:
- Oseltamivir - 75mg BD for 5 days (generally immunocompetent patients)
- Zanamivir - 10mg BD (inhaled) (generally immunocompromised)
Any effect from treatment beyond this is dubious, and indeed there is some controversy about actual efficacy.
The quoted benefits are primarily reduction of complications and reduced duration of symptoms.
Resistance to oseltamivir is a potential problem (appears more common with H1N1).
Testing for this usually takes a more prolonged time than simple viral identification.
Complications
These can include:
- Secondary bacterial infection
- Staph aureus
- Strep pneumoniae
- Staph aureus
- Primary viral pneumonia
- Acute bronchitis
- Exacerbation of existing airways disease
- Guillain-Barre syndrome
- Encephalitis
- Toxic shock syndrome
- Myocarditis
- Otitis media
Infection Control
Droplet spread up to 2 m (although really mainly 1m)
Survives for hours on surfaces.
Transmision to hands from fomites, and then to face
Precautions therefore include:
Guidance suggests continuing precautions for 24 hours after resolution of symptoms.
This can be difficult as symptoms can be prolonged.
PCR testing as a guide may be helpful, but unlikely to become negative as not a measure of ‘live’ viruses.
Infectivity is described as usually lasting for about 5 days after onset, but may be longer in children or the immunocompromised.
Survives for hours on surfaces.
Transmision to hands from fomites, and then to face
Precautions therefore include:
- Single room - negative pressure
- Mask - FFP3 - needs fit testing
- Eye protection
- Apron
- Glove
Guidance suggests continuing precautions for 24 hours after resolution of symptoms.
This can be difficult as symptoms can be prolonged.
PCR testing as a guide may be helpful, but unlikely to become negative as not a measure of ‘live’ viruses.
Infectivity is described as usually lasting for about 5 days after onset, but may be longer in children or the immunocompromised.
Annual vaccination for common flu strains is provided to high risk groups.
Post-exposure prophylaxis of oseltamivir may be provided in some cases of exposure to an identified infected patient.
Post-exposure prophylaxis of oseltamivir may be provided in some cases of exposure to an identified infected patient.
Links & References
- Johnstone, C. et al. Common viral illnesses in intensive care: presentation, diagnosis and management. CEACCP. 2015. 14(5): 213-219. https://academic.oup.com/bjaed/article/14/5/213/286737
- Nickson, C. Influenza. LITFL. 2019. https://litfl.com/influenza/
- Nelson C. Wigan FICM teaching. 2019.
- Kean, J. Respiratory tract infection part 1. e-LFH. 2016. https://portal.e-lfh.org.uk/Component/Details/433735
- Tidy, C. Influenza. Patient.info. 2015. https://patient.info/doctor/influenza
- Osmosis. Influenza. 2019. Youtube. https://www.youtube.com/watch?v=85R-6O6rrgw
