Influenza is a highly contagious airborne viral disease characterized by abrupt onset of symptoms. Vaccination remains the key effort in preventing development of this illness and possible influenza-related complications. Still, a history of influenza vaccination does not rule out the possibility of influenza virus infection in an ill patient with clinical signs and symptoms compatible with influenza.
Thus treatment should not be delayed until the results of diagnostic tests are available. Recommendations from The Centers for Disease Control and Prevention (CDC) state that treatment should be initiated as soon as possible after the onset of symptoms in patients meeting certain criteria. The CDC also recommends antiviral prophylaxis for all individuals in close contact with an infected person during the infectious period. Treatment of patients with severe influenza (those who require hospitalization) presents multiple challenges.
Clinical trials and observational data show that early antiviral treatment can shorten the duration of fever and other symptoms of influenza, as well as reduce the risk of complications. The benefit is greatest when treatment is initiated early, preferably within 48 hours of illness onset. Two classes of antiviral drugs used against influenza are neuraminidase inhibitors and M2 ion channel inhibitors (adamantanes).
Neuraminidase inhibitors block the viral neuraminidase function, critical in releasing virions from the infected host's cells, and thus effectively stop spread and reinfection of influenza A and B. Although four neuraminidase inhibitors have been approved for use in humans (oseltamivir, zanamivir, laninamivir and peramivir), only the first two are broadly used in most countries.
Oseltamivir (trade name Tamiflu) is an oral agent approved for the treatment of uncomplicated acute influenza in patients one year and older who have been symptomatic for no more than two days, as well as for influenza prophylaxis in patients one year and older. Influenza virus mutants with resistance genes have been characterized from cell culture and particularly well-studied for this drug.
Zanamivir (trade name Relenza) is an oral inhalation agent approved for influenza prophylaxis in patients five years and older, and for the treatment of influenza in patients seven years and older with symptomatic disease not longer than two days. Since inhaled zanamivir can worsen pulmonary status in patients with underlying pulmonary pathology, it should not be administered in these individuals.
Adamantanes (amantadine and rimantadine) are M2 ion channel blockers characterized by three condensed cyclohexane rings fused in the chair conformation. They interfere with hydrogen ion channel activity of the influenza virus, blocking its entry into a host’s cell. Although they were widely used against influenza, they are now largely discontinued and replaced by neuraminidase inhibitors.
The efficacy of adamantanes is limited to influenza A only, as influenza B viruses lack M2. Furthermore, basically all influenza strains have now developed significant resistance against both amantadine and rimantadine. This has primarily been attributed to their over-the-counter availability in densely populated nations such as Russia and China, and their large-scale use in the poultry.
Ribavirin and arbidol have long been acknowledged as broad-spectrum antiviral agents against viruses from diverse families. The clinical effectiveness of ribavirin on influenza is inferior to that of adamantanes or NA inhibitors and more reliant on the delivery manner. WHO guidelines recommend that ribavirin should be used to treat influenza only in an approved research protocol.
Symptomatic relief and approach during pregnancy
Symptomatic measures can also help patients with influenza. Over-the-counter antipyretic drugs and anti-inflammatory agents are most often used for that purpose. However, medications containing acetylsalicylic acid should be avoided in children because of the risk of Reye syndrome – an extremely rare but serious illness that can affect the liver and the brain. The development of complications or bacterial coinfection may require the use of antimicrobial drugs in patients with influenza.
Pregnant and postpartum women (including those with pregnancy loss) are at significant risk of severe influenza-related complications, mostly due to the changes in respiratory, cardiovascular and immune systems that occur during pregnancy. In past influenza outbreaks, pregnant women who were otherwise healthy were more likely to become very sick or even die, when compared to non-pregnant women. In addition, pregnant women who develop high fever or pneumonia are at higher risk for early labor and other complications.
Thus the official CDC recommendations are that neuraminidase inhibitors should be prescribed for pregnant women and for those up to two weeks postpartum with suspected or confirmed influenza disease. Women can continue to breastfeed while being treated with antivirals. As pregnancy is a particularly vulnerable period for influenza, vaccination should be an integral element of preconception, prenatal and postpartum care.
- Nicholson KG, Webster RG, Hay AJ. Textbook of Influenza. Blackwell Science, Oxford, 1998.
- Lamb RA, Krug RM. Orthomyxoviridae: The viruses and their Replication. In: Fields Virology fourth edition, Knipe DM, Howley PM eds, Lippincott, Philadelphia 2001, pp 1487-1531.