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Influenza

Essentials

In the Northern Hemisphere, seasonal influenza epidemics usually occur during the winter (”the flu season”) with the peak typically around January and February.
At-risk groups should be vaccinated annually well in advance (October-November) before the start of the expected influenza epidemic. Find out about locally relevant timing.
National public health organizations issue recommendations of groups to whom annual influenza vaccination should be offered (possibly free of charge), i.e. of individuals whose health would be essentially threatened by influenza or who would gain significant health benefit from influenza vaccination.
Influenza can be diagnosed on the basis of the clinical presentation combined with a confirmed epidemic circulating in the community, or on the basis of virological (rapid) diagnostic test results.
The treatment of influenza in a healthy adult patient is generally symptomatic.
Antiviral agents should be considered for children, pregnant women, patients with exceptionally severe symptoms and those belonging to at-risk groups.
The sooner the drug therapy is started, the better the effect. Treatment should be started within 48 hours of symptom onset.
Since the COVID-19 pandemia started in spring 2020, the number of influenza infections has decreased considerably (see e.g. http://www.ecdc.europa.eu/en/publications-data/influenza-virus-characterisation-summary-europe-september-2021). The clinical picture of both infections can be similar. Symptoms originating from other organs than the respiratory system, such as bowel symptoms, as well as disturbed sense of smell or taste, are, however, more typical for the coronavirus.

Virus types

Influenza viruses are classified into three types: A, B and C. Influenza A and B viruses are clinically the most significant.
Influenza A viruses are subtyped according to the type of haemagglutinin (H, 1-16) and neuraminidase (N, 1-9) they contain. Types H1N1, H2N2, H3N2 and H3N8 are known to have caused epidemics in humans. In addition, virus types H5N1, H7N7 and H7N9, and possibly others, have caused human infection. Typical features of the most important influenza viruses: see table T1.

Typical features of the most important influenza viruses

Virus type	Type of outbreak	Epidemiology	Susceptible individuals
A (H1N1)	Seasonal influenza	During the winter months, not every winter	The virus mainly infects children and adolescents
A (H3N2)	Seasonal influenza	Encountered most winters	All age groups, causes excess mortality in the age group of 65 and over
A (H1N1) 2009	”Swine influenza” Seasonal influenza	Pandemic 6/2009-2/2010 The virus has thereafter continued to circulate worldwide as a seasonal influenza virus with very few changes	Children, adolescents, pregnant women. Rare in individuals aged 65 and over
A (H5N1) A (H7N9)	Avian influenza (”bird flu”)	Has caused small clusters of infection in Egypt and the Far East in the 2000s. The cumulative number of confirmed human cases is approximately 600. A notifiable communicable disease.	Has pandemic potential, but at present the transmission to humans, and from human to human, appears to be non-sustained. Mortality rate has been over 60%.Since spring 2013 there have been reports from China concerning cases of illness caused by a new type H7N9 virus. About in one third of the cases the patient has eventually died.
B	Seasonal influenza	Irregular outbreaks during the winter months, epidemics usually later in the spring than with influenza A	Everyone. Clinical picture usually milder than that of influenza A.

Epidemiology

In tropical areas, influenza occurs throughout the year. In the Northern hemisphere, the influenza season typically occurs during winter.
The severity of influenza epidemics varies significantly from year to year depending on the antigenic variation of the circulating virus type and the population's susceptibility to the infection (disease history, protection provided by vaccination).
The latest influenza updates are available through national public health services and the WHO Internet pageshttp://www.who.int/influenza/surveillance_monitoring/en/.

Infectiousness and clinical picture

The transmission of influenza viruses occurs via aerosols exhaled by an infectious person and by direct contact.
The incubation period ranges between 1 and 7 days but is most commonly 2-3 days.
Viral shedding can start 1-2 days before the onset of clinical symptoms.
The duration of major symptoms is usually 3-8 days.
Influenza starts suddenly in adults and the symptoms are severe, including high fever, chills, headache, myalgia, malaise and dry cough. Rhinitis is not a common first symptom of influenza (it is more common in a coronavirus infection). During an epidemic, the diagnosis can be made based on this difference Diagnosis of Influenza on the Basis of History and Physical Examination.
In children, it is more difficult to distinguish influenza from other viral respiratory infections only on the basis of clinical picture since several other viruses capable of producing a similar clinical picture frequently circulate also during an influenza epidemic. Almost all affected children have fever, but the majority will also present with rhinitis at the start of the illness. Febrile convulsions may also be an early feature.
The most common complications in adults are pneumonia and maxillary sinusitis as well as the worsening of asthma, COPD and chronic bronchitis. Pneumonia is usually caused by bacteria (pneumococci, Staphylococcus aureus), but influenza viruses may also cause primary viral pneumonia, the clinical picture of which may be severe. Rarely, complications affecting the central nervous system (meningitis, encephalitis) and the heart (myocarditis, pericarditis) may develop.
Influenza may also worsen the patient's primary diseases and trigger, for example, a myocardial infarction in a patient with coronary artery disease.
The most common complication in children is acute otitis media which occurs in about 40% of children aged less than 3 years.

Diagnosis

Rapid point-of-care (POC) influenza antigen tests are available. The sample is taken from the nasopharyngeal mucus, and the result is available even within just 10-30 minutes. The specificity of the tests is good, but their sensitivity is only about 60%, so a negative test result cannot be considered to exclude influenza http://www.dynamed.com/lab-monograph/rapid-influenza-test.
A POC test based on the polymerase chain reaction (PCR) is available, with 90-98% sensitivity. In addition to influenza A and B viruses, it can also detect RSV and the COVID-19 virus. The result is usually ready in 3-4 hours after the sample has arrived at the laboratory.
Even if rapid diagnostic tests were available, there is no requirement to perform a test for the diagnosis of influenza in a primary care setting if more than 48 hours have elapsed from the start of symptoms since it will not be possible to greatly influence the duration of the infection with drug therapy. Patients who are severely symptomatic or susceptible to complications are an exception, as are close contacts.
At discretion CRP, basic blood count with platelet count and chest x-ray, especially when suspecting a complicating bacterial infection.
- CRP may be moderately elevated also in influenza.
- A clearly increased CRP concentration, especially when combined with a radiographic finding of lobar pneumonia, strongly suggests a complicating bacterial pneumonia in a patient with a positive influenza test result.
- Mild leucopenia in blood picture is typical for influenza, as it is for other viral infections. In influenza, also monocytosis associated with lymphocytopenia has been reported.

Treatment Chinese Medicinal Herbs for Influenza

Treatment is mainly symptomatic: rest and an anti-inflammatory drug or paracetamol.
- Aspirin should not be used in influenza, particularly not in children and adolescents due to the risk of Reye's syndrome.

Antiviral treatment Use of Neuraminidase Inhibitors in Patients with 2009 Pandemic Influenza (H1n1), Amantadine and Rimantadine in the Prevention and Treatment of Influenza, Neuraminidase Inhibitors for Treating and Preventing Influenza in Healthy Adults and Children

Neuraminidase inhibitors are antiviral drugs indicated for the treatment of influenza http://www.dynamed.com/management/treatment-of-influenza#NIEFFICACY:
- oseltamivir for oral use; the dose for adults is 75 mg twice daily for 5 days http://www.dynamed.com/management/treatment-of-influenza#OSELTAMIVIR_DOSING; for children, an oral suspension is also available with dosage based on weight
- zanamivir for inhalation; the dose for adults and children over 5 years is 2 inhalations (2 × 5 mg) twice daily for 5 days http://www.dynamed.com/management/treatment-of-influenza#ZANAMIVIR_DOSING. Zanamivir is also available as a preparation for intravenous administration.
Indications for antiviral drug therapy: see table T2.
All drugs reduce the length of illness by less than 1 day Neuraminidase Inhibitors for Treating and Preventing Influenza in Healthy Adults and Children when the treatment is initiated within 48 hours of the symptom onset.
The sooner the treatment is started, the better the effect http://www.dynamed.com/management/treatment-of-influenza#GUID-ED39BAA6-4012-47C0-84E9-CC03CC89EB5B.
In children with influenza diagnosed with a rapid point-of-care test, oseltamivir treatment shortens the duration of influenza by about 1.5 days Neuraminidase Inhibitors for Preventing and Treating Influenza in Children. If the treatment is started very quickly, i.e. within 12 to 24 hours, it may shorten the duration of the illness by up to 3 to 4 days. In practice, however, testing and initiation of treatment only seldom take place this quickly.
The drugs are effective for the treatment of influenza A or B. Oseltamivir-resistance is rare and occurs mainly in immunosuppressed individuals.
The use of zanamivir is limited as it is administered via an inhalation device the use of which may be difficult to master, particularly by elderly patients.
The use of amantadine is not recommended for the treatment of influenza http://www.dynamed.com/management/treatment-of-influenza#ADAMANTES. Practically all the currently circulating influenza A(H1N1) and A(H3N2) viruses are resistant to amantadine.

Indications for antiviral drug therapy in influenza

Always start an antiviral drug regardless of the symptom duration	Consider starting an antiviral drug*	Treat symptomatically without antiviral drugs
Patients with severe symptoms http://www.dynamed.com/management/treatment-of-influenza#GUID-65BBB6E6-BE4C-4C99-8249-DC1071E5AE4D Obvious lower respiratory tract symptoms Deteriorated general condition	At-risk http://www.dynamed.com/management/treatment-of-influenza#EFFICACY_IN_HIGH_RISK_PATIENTS and pregnant patients, particularly if < 48 hours from symptom onset http://www.dynamed.com/management/treatment-of-influenza#GUID-65BBB6E6-BE4C-4C99-8249-DC1071E5AE4D Paediatric patients if symptom onset < 48 hours and diagnosis considered sufficiently certain In special cases **, patients not in at-risk groups when < 48 hours from symptom onset, prophylaxis of patient's family members	Uncomplicated influenza, symptom duration > 48 hours

* Unrestricted use of medication is curbed by, for example, the development of resistance, possible difficulties obtaining medication during an epidemic etc.

** A special case could, for example, consist of an unusually heavy burden caused by illness from influenza (need to look after an ill family member etc.)

Other specific treatment

The possibility of influenza being complicated by bacterial infections should be considered if the illness is prolonged or the clinical picture exceptionally severe.
- Pneumonia (either bacterial pneumonia or viral pneumonia caused by the influenza virus, the clinical picture of which is often severe)
- Otitis, sinusitis

Prevention

Proper hand hygiene and cough/sneeze etiquette are pivotal. Once symptoms develop the person should stay at home.
There are 2 types of vaccines http://www.dynamed.com/prevention/seasonal-influenza-vaccination#TOPIC_ZWM_RCL_CNB available for the prevention of influenza, i.e. an inactivated vaccine administered intramuscularly and a live attenuated vaccine administered as a nasal spray. The nasal spray is indicated for influenza prevention in individuals of 2 to 17 years of age.

Seasonal influenza

National public health organizations issue recommendations of groups to whom annual influenza vaccination should be offered (possibly free of charge), i.e. of individuals whose health would be essentially threatened by influenza or who would gain significant health benefit from influenza vaccination.
National advice must be followed as regards routine influenza vaccination programmes. In many countries, influenza vaccination is offered (possibly free of charge) to individuals whose health would be essentially threatened by influenza or who would gain significant health benefit from influenza vaccination http://www.dynamed.com/prevention/seasonal-influenza-vaccination#TOPIC_NT3_F3V_BNB. E.g. in Finland these include
- social and health care professionals as well as professionals in pharmaceutical services, who are in contact with patients/customers
- pregnant women
- all persons aged over 65 years
- all children aged 6 months to 6 years
- persons living in close contact with individuals prone to severe influenza infections
- persons entering military service.
- Patients belonging to a risk group due to their primary disease or treatment, including, for example, the following conditions (the list is indicative only, and the treating physician makes the final decision whether vaccination is indicated):
  - cardiovascular disease, e.g. coronary heart disease Influenza Vaccines for Preventing Cardiovascular Disease or heart failure
  - lung disease, e.g. asthma or COPD
  - diabetes
  - renal insufficiency
  - a weakened immune system either due to an illness or its treatment
  - chronic neurological or neuromuscular disease.
Find out about local regulation concerning the potentially mandatory role of influenza vaccination for health care staff, considering for example persons who care for immunocompromized individuals, pregnant women, children below 12 months of age or over 65-year-old patients.
The vaccine should be given annually due to the variation in the viral strains and the composition of the vaccine Protection Against Influenza after Annually Repeated Vaccination.
Children receiving an influenza vaccination for the first time need two vaccine doses at about a one-month interval. The strongest evidence on the effectiveness of vaccination in preventing influenza concerns children over 2 years of age Vaccines for Preventing Influenza in Healthy Children.
At its best, the vaccination prevents in children and healthy adults of working age 5-8 out of 10 influenza infections and in the elderly every second influenza infection.
The level of influenza vaccination coverage has been in children about 35% and in persons over 65 years of age about 50%. This means that many individuals in the at-risk groups contract influenza annually.

Pandemic influenza

Pandemrix^® vaccine was used for the pandemic influenza vaccination campaign in 2009-2010. There have been reports of a possible relationship between the vaccine and an increased incidence of narcolepsy among children and adolescents. Later on, an increased risk was recognized among adults as well: for persons aged 20 to 64 years who had received Pandemrix^® vaccine, the risk of developing narcolepsy was 3-to-5-fold compared to age-matched unvaccinated persons. The increased vaccination-associated risk in adults was one case of narcolepsy per 100 000 vaccinated persons while in children and adolescents the risk was 6 cases per 100 000 vaccinated persons. The mechanism behind the relationship is thought to have an autoimmune basis, but the exact mechanism still remains unclear.
The seasonal vaccine contains no adjuvants or preservatives, and it is not suspected to have caused any cases of narcolepsy even if (H1N1)2009 virus was included in it.

References

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Dobson J, Whitley RJ, Pocock S et al. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet 2015;385(9979):1729-1737. [PubMed]
Alves Galvão MG, Rocha Crispino Santos MA, Alves da Cunha AJ. Amantadine and rimantadine for influenza A in children and the elderly. Cochrane Database Syst Rev 2014;(11):CD002745. [PubMed]
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