Influenza

Overview

Also known as the flu, influenza is an acute viral infection of the respiratory tract causing inflammation of the nasal mucosa, pharynx, and conjunctiva due to influenza viruses, RNA viruses of which there are three types:

• Influenza A – most common and virulent, responsible for outbreaks, epidemics, and pandemics
• Influenza B – generally causes less severe illness than A and does not tend to cause pandemics
• Influenza C – usually mild/asymptomatic and similar to the common cold

Uncomplicated influenza describes an acute infection by influenza A or B that is usually self-limiting.

Complicated influenza is more severe and associated with influenza A and is associated with requiring hospital admission, antiviral treatment, and involvement of the lower respiratory tract, nervous system, or exacerbation of an underlying condition (e.g. COPD).

Pathophysiology

Influenza enters respiratory epithelial cells, replicates, and releases new copies and the affected cell dies. This can lead to inflammation of the trachea and bronchi. If severe enough, this can lead to primary viral pneumonia, however, this is uncommon. Bacterial superinfection may occur due to damage causing impaired mucociliary clearance and white cell function. Antigenic variation allows the virus to cause infection repeatedly and reduces herd immunity.

Epidemiology

• Influenza usually occurs in the UK during the winter months, typically between December and March.

Risk Factors

Risk factors for infection and more serious diseases include:

• Older (>65 years old) or younger age (<5 years old)
• Cardiovascular/respiratory comorbidities such as COPD or heart failure
• Diabetes mellitus
• Chronic kidney disease
• Pregnancy
• Immunocompromised states (e.g. HIV, chemotherapy, immunosuppressants)
• Haemoglobinopathy (e.g. sickle cell disease)
• Contact with infected individuals (e.g. household contacts, healthcare workers etc.)

Presentation

Uncomplicated influenza

Uncomplicated influenza has an incubation period of up to 2 days followed by abrupt symptoms which can include:

• General features – fever, chills, malaise, myalgia, headache, anorexia
• Respiratory features – cough, nasal discharge, sore throat
• Eye pain and conjunctivitis may occur – red eye, lacrimation, photophobia, pain with eye movement 

Infants and children may have different features:

• Cervical lymphadenopathy
• Diarrhoea and vomiting – gastrointestinal symptoms are more common in children
• High fever (typically 38–40°C) – they may also present with febrile convulsions
• Respiratory tract inflammation – croup, bronchiolitis, bronchitis
• Myalgia or myositis – often the calf muscles and more common in children
• Tachypnoea

From day 3 onwards, fever and general features tend to settle, and respiratory features predominate.

Complicated influenza

Features of complicated influenza include:

• Features warranting hospital admission – such as deranged vital signs
• Lower respiratory tract features – hypoxia, dyspnoea, rapidly worsening cough, crackles
• Central nervous system involvement – such as features suggesting encephalitis
• Significant exacerbation of an underlying condition – such as COPD, cystic fibrosis, and diabetic ketoacidosis in people with type 1 diabetes mellitus

Investigations

Overview

Influenza is generally clinically diagnosed if it is known to be circulating in the fever. People with complicated influenza are offered rapid testing for influenza.

In some cases, testing may be needed to confirm or refute influenza to identify potential antiviral resistance, such as in people who develop symptoms despite antiviral treatment/prophylaxis.

Differential Diagnoses

Bacterial pneumonia

• Although both can present with cough and fever, bacterial pneumonia is associated with dyspnoea and sputum production and may have pleuritic chest pain
• Crackles may be heard on auscultation
• Bacterial pneumonia may develop following influenza

Common cold (coryza)

• The common cold tends to predominantly cause nasal problems such as running, congestion, and sneezing. Fever, fatigue, and myalgia are less commonly seen and/or less severe.

Respiratory syncytial virus (RSV) infection

• RSV is the most common lower respiratory tract infection in children aged <1 year
• Upper and lower respiratory tract symptoms are seen and resolve within 7-10 days

Parainfluenza virus infection

• Parainfluenza virus is one of the most common causes of croup
• In adults, it tends to cause mild upper respiratory tract infection but can be severe in immunocompromised people

Infectious mononucleosis (glandular fever)

• Infectious mononucleosis is more common in adolescents/young adults
• It is associated with prolonged fever, severe sore throat, lymphadenopathy, and fatigue 

Pertussis (whooping couth)

• Pertussis can have a prodrome with similar features to influenza, however, an intractable cough develops that makes a characteristic inspiratory ‘whoop’ sound. Coughing bouts may be severe enough to cause vomiting

Management

Overview

In most cases of uncomplicated pneumonia, management is supportive with adequate fluids, simple analgesia, and rest.

In some people who are ‘at risk’ and national surveillance shows that influenza is circulating, oral oseltamivir or inhaled zanamivir may be prescribed. Criteria can be found on the NICE CKS site.

Vaccines

Overview

Since seasonal influenza can cause significant complications and morality in the UK, vaccination is offered to children, adults, and at-risk groups.

Children

In children, the vaccination is given intranasally at 2-3 years, then annually after. The intranasal vaccine is a live vaccine, however, if this is not appropriate (e.g. immunosuppression), then the injectable vaccine may be given.

Contraindications to the live nasal vaccine in children include:

• <2 years old
• Current fever or coryzal features
• Egg allergy
• Pregnancy or breastfeeding 
• Current wheeze (e.g. viral-induced wheeze, asthma) or severe asthma
• Immunocompromise
• If the child is taking aspirin for Kawasaki disease due to the risk of Reye’s syndrome

Adverse effects can include fever, nasal congestion, anorexia, headaches, and tenderness at the injection site.

Adults and at-risk groups

The injectable influenza vaccine is an inactivated vaccine. Its contraindications include egg allergy and its adverse effects can include fever, anorexia, headaches, and myalgia. 

Annual influenza vaccination should be offered to all people >65 years old and all people >6 months with:

• Chronic respiratory diseases – such as COPD and asthma requiring steroid inhalers
• Cardiovascular disease – such as ischaemic heart disease, heart failure, and complicated hypertension
• Chronic kidney disease
• Diabetes mellitus – including if diet-controlled
• Chronic liver disease – such as chronic hepatitis, cirrhosis, biliary atresia
• Chronic neurological disease – such as stroke, transient ischaemic attack 
• Pregnancy
• BMI >40 kg/m²
• Immunosuppression – such as HIV or immunosuppressive drugs
• Hyposplenism – such as asplenia or splenic dysfunction

Other at-risk people include healthcare workers, living in residential care homes, and carers of elderly/disabled people.

Complications

• Exacerbation of respiratory diseases – such as asthma, COPD, and cystic fibrosis
• Secondary bacterial infection – seen after an initial period of improvement, a common cause includes Staphylococcus aureus. More common in at-risk individuals. 
• Other upper respiratory tract infections – otitis media (more common in children) and sinusitis
• Cardiac complications – exacerbation of cardiac disease (e.g. heart failure) and myocarditis
• Pregnancy complications – preterm labour, low birth weight, increased morbidity and mortality rates, especially in the third trimester

Prognosis

• In most cases of uncomplicated influenza, symptoms resolve after around 1 week