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Prévention de l’InfluenzaPublished by: Groupe de travail Développement de recommandations de première ligneLast published: 2018Preventie van influenzaPublished by: Werkgroep Ontwikkeling Richtlijnen Eerste Lijn (Worel)Last published: 2018The main goals of treatment at the patient level are reduction in severity and duration of symptoms and prevention of complications. At a public health level, the aim is to prevent or control outbreaks of influenza to avoid an epidemic or pandemic situation. CDC: influenza (flu) Opens in new window
When antiviral treatment is indicated, it should ideally be given within the first 48 hours of suspected or laboratory-confirmed influenza.
Treatment is recommended for people at high risk of developing complications of influenza, and therapy can be started within 48 hours of onset of symptoms. Treatment can be considered for people diagnosed with influenza 48 hours after onset of symptoms, who have continued symptoms.
All patients hospitalised for influenza require antiviral treatment.
People not at high risk of complications may be given antiviral treatment if influenza is highly suspected or confirmed, it is within 48 hours of symptom onset, and they wish to shorten the duration of their illness.
Complications may occur in any patient and it is not always possible to estimate the risk of complications, which makes treatment decisions more difficult; however, a variety of high-risk subgroups are more susceptible. At-risk groups include:[2]
Patients with chronic pulmonary (including asthma) or cardiac conditions
Patients with diabetes mellitus, renal disease, liver disease, chronic neurological conditions, or immunosuppression
Patients in nursing homes or long-term care facilities
Children aged <2 years
Adults aged ≥65 years
Pregnant women.
Antiviral prophylaxis after exposure to an infected individual is reserved for at-risk populations.[2][109][110]
In the US, the Centers for Disease Control and Prevention (CDC) has provided guidance on testing and treatment of influenza when influenza and SARS-CoV-2 viruses are co-circulating.[84] Recommendations may vary in different locations and you should consult your local guidance.
Uncomplicated influenza infection
Uncomplicated influenza infection is an acute respiratory infection caused by influenza A or B viruses that is usually self-limiting in the general population.[2] The symptoms typically resolve in approximately 1 week; however, cough and fatigue may persist for longer.[111] Treatment is aimed at supportive care of the symptoms associated with the respiratory tract infection. These treatments usually include antipyretics/analgesics for fever, and increased fluid intake to counter dehydration. One Cochrane review found that there is currently no evidence for or against the recommendation to increase fluids in acute respiratory infections. Observational data (in hospitalised patients) suggest that increasing fluid intake in acute respiratory infections of the lower respiratory tract may increase risk of symptomatic hyponatraemia; randomised controlled trials are needed.[112]
Complicated influenza infection
A more severe, complicated illness can occur in influenza infection and is associated more often with influenza A infection rather than influenza B infection.
Complications of upper respiratory tract infection include otitis media and bacterial sinusitis. Complications of lower respiratory tract infection include primary viral pneumonia and secondary bacterial pneumonia.
Treatment of these complications may require more aggressive supportive care, often necessitating hospitalisation, accompanied by antibiotics and/or antiviral treatment.
The highest rates of hospitalisation are in infants, patients aged >65 years, and patients with chronic medical conditions. Over 90% of influenza-related deaths have been in patients aged >65 years.[14]
Antiviral treatment of early influenza infection
The US Centers for Disease Control and Prevention (CDC) recommends antiviral treatment is given as soon as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness, or who require hospitalisation, as well as for patients who are at higher risk for complications.[2][110] While antivirals are approved by the US Food and Drug Administration (FDA) for uncomplicated acute illness, guidelines tend to recommend these drugs for complicated illness as well as for those at risk of complications. Local guidelines may vary and should be consulted.[113]
The neuraminidase inhibitors (zanamivir, oseltamivir, and peramivir) are active against both influenza A and B.[110][114][115][116][117] Oseltamivir and zanamivir have modest effectiveness against the symptoms of influenza in otherwise healthy adults.[118]
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They have also been widely used in the treatment of 2009 influenza A/H1N1.[114][119][120][121] However, there has been extensive debate over the use of oseltamivir and whether it does reduce complications in otherwise healthy adults and children.[114][122][123][124] Findings from meta-analyses show that oseltamivir modestly reduces time to clinical symptom alleviation in adults with influenza, but increases the incidence of nausea and vomiting.[121][125] The effect on mortality and complication rates is uncertain.[121][126] Observational studies suggest oseltamivir may reduce mortality in hospitalised patients with seasonal influenza.[127]
It has been reported that oral oseltamivir and inhaled zanamivir reduce the duration of influenza illness when started within 48 hours of symptom onset, both in children up to age 12 years and in adults.[110][116][128] The benefits of treatment are greatest when medicines are initiated in the first 24-30 hours of symptom onset.[129][130] Analysis of data from a large surveillance network found that early antiviral treatment with oseltamivir was associated with shorter length of stay in children hospitalised with influenza.[131]
The CDC recommendations for antiviral treatment are:[110]
Hospitalised patients with suspected or confirmed influenza start treatment with oral or enterically administered oseltamivir as soon as possible.
Outpatients with complications or progressive disease and suspected or confirmed influenza (e.g., pneumonia, or exacerbation of underlying chronic medical conditions) start treatment with oral oseltamivir as soon as possible.
Outpatients with suspected or confirmed uncomplicated influenza may receive oral oseltamivir, inhaled zanamivir, intravenous peramivir, or oral baloxavir marboxil, depending upon approved age groups and contraindications.
If being prescribed, oseltamivir and zanamivir should be given to patients presenting within 2 days of onset of symptoms and given for 5 days. Peramivir is given in a single infusion, and should also be given within 2 days of symptom onset.[2][110] Peramivir may be recommended for those who are unable to take oral or inhaled neuraminidase inhibitors.
Oseltamivir is generally well tolerated in adults but may cause vomiting in children. There is less evidence for zanamivir than with oseltamivir that it reduces respiratory complications in adults.
A drug safety alert relating to oseltamivir was issued in November 2006 following reports of self-injury and delirium associated with its use. The alert states that people with influenza, particularly children, may be at an increased risk of self-injury and confusion shortly after taking oseltamivir and should be closely monitored for signs of unusual behaviour.
An intravenous formulation of zanamivir is approved in Europe for the treatment of complicated and potentially life-threatening influenza in children ≥6 months of age and adults. The indication is for patients in whom other treatments for influenza, including the inhaled formulation of zanamivir, are unsuitable, and/or the patient's influenza virus is known or suspected to be resistant to other treatments. Local availability may vary. It is not available in the US.
Pregnant women presenting with uncomplicated illness due to influenza, and who have no evidence of systemic disease, can be offered oseltamivir.[2][33][110] Children aged <1 year who have symptoms of seasonal influenza should be treated with oseltamivir.[110]
Baloxavir marboxil, a polymerase acidic endonuclease inhibitor, is active against both influenza A and B. The US FDA has approved baloxavir marboxil for the treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours, and who are otherwise healthy but at high risk of developing influenza-related complications. In Europe, baloxavir marboxil is approved for patients 1 year of age and older. In adult and adolescent outpatients at high risk of developing complications, baloxavir marboxil has demonstrated superior efficacy to placebo and similar efficacy to oseltamivir in reducing risk.[132] Use of baloxavir is not recommended in people who are severely immunosuppressed.[110]
The M2 inhibitors amantadine and rimantadine are only active against influenza A.
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Due to high levels of resistance, they are not recommended for antiviral treatment or chemoprophylaxis.
Due to an increase in resistant isolates, physicians should seek advice from local authorities regarding antivirals based on seasonal resistance patterns.[110]
Post-exposure antiviral chemoprophylaxis
Should be considered for:[2][109][110]
People at high risk of developing complications of influenza if illness develops shortly after influenza vaccination, before an adequate immune response develops.
People in whom the vaccine is contraindicated. This may include anaphylaxis to egg or allergy to other components of the vaccine, febrile illness, or history of Guillain-Barre syndrome within 6 weeks of previously administered influenza vaccine.
People who have not received the vaccine but present with acute respiratory symptoms during a known influenza outbreak.
Unvaccinated people in close contact with those at high risk of developing complications of influenza during an influenza outbreak.
All residents of long-term facilities or nursing homes, including those already vaccinated, if an outbreak of influenza occurs in the community where they are living. [
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People who have highest risk of complications, including death. This may include immunocompromised people.
People who were unable to receive vaccine due to shortage, if they are at high risk of developing complications of influenza.
Both oseltamivir and zanamivir have been shown to be effective as prophylaxis against infection when given early after exposure to an infected individual.
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One meta-analysis has shown that oseltamivir used prophylactically may reduce the spread of symptomatic influenza within households.[121] Baloxavir marboxil is approved in the US for post-exposure prophylaxis in those aged 5 years and older and in Europe for those aged 1 year and older. In phase 3 trials, single-dose baloxavir was effective in preventing influenza in household contacts (both adults and children) of patients with influenza.[133][134]
Antibiotic therapy
Antibiotic therapy may be required for certain complications of acute influenza, such as bacterial pneumonia, sinusitis, or otitis media.
Secondary bacterial pneumonia is an important complication of seasonal influenza and contributes to 25% of all seasonal influenza deaths.[98] The most common bacteria associated with pneumonia in the context of influenza co-infection are Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. Antibiotics should target these organisms.[2]
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