Influenza update 2018–2019: 100 years after the great pandemic
ABSTRACT
Four influenza pandemics, starting with the historic 1918 pandemic, have killed thousands of people around the world. Vaccination, still the most important means of preventing influenza, is currently recommended yearly for all people age 6 months and older, with a goal of vaccinating 80% of all Americans and 90% of at-risk populations. Neuraminidase inhibitors are underused, and a new drug with a different mechanism of action, baloxavir marboxil, is expected to be approved soon in the United States.
KEY POINTS
- Influenza A(H7N9) is a prime candidate to cause the next influenza pandemic.
- Influenza vaccine prevents 300 to 4,000 deaths in the United States every year.
- The 2018–2019 quadrivalent influenza vaccine contains updated A(H3N2) and B/Victoria lineage components different from those in the 2017–2018 Northern Hemisphere vaccine.
- The live-attenuated influenza vaccine, which was not recommended during the 2016–2017 and 2017–2018 influenza seasons, is recommended for the 2018–2019 influenza season.
- Influenza vaccine is recommended any time during pregnancy and is associated with lower infant mortality rates.
- Overall influenza vaccination rates remain below the 80% target for all Americans and 90% for at-risk populations.
TREATMENT
Numerous studies have found anti-influenza medications to be effective. Nevertheless, in an analysis of the 2011–2016 influenza seasons, only 15% of high-risk patients were prescribed anti-influenza medications within 2 days of symptom onset, including 37% in those with laboratory-confirmed influenza.55 Fever was associated with an increased rate of antiviral treatment, but 25% of high-risk outpatients were afebrile. Empiric treatment of 4 high-risk outpatients with acute respiratory illness was needed to treat 1 patient with influenza.55
Treatment with a neuraminidase inhibitor within 2 days of illness has recently been shown to improve survival and shorten duration of viral shedding in patients with avian influenza A(H7N9) infection.56 Antiviral treatment within 2 days of illness is associated with improved outcomes in transplant recipients57 and with a lower risk of otitis media in children.58
Appropriate anti-influenza treatment is as important as avoiding unnecessary antibiotics. Regrettably, as many as one-third of patients with laboratory-confirmed influenza are prescribed antibiotics.59
,The US Food and Drug Administration warns against fraudulent unapproved over-the-counter influenza products.60
Baloxavir marboxil
Baloxavir marboxil is a new anti-influenza medication approved in Japan in February 2018 and anticipated to be available in the United States sometime in 2019.
This prodrug is hydrolyzed in vivo to the active metabolite, which selectively inhibits cap-dependent endonuclease enzyme, a key enzyme in initiation of messenger ribonucleic acid synthesis required for influenza viral replication.61
In a double-blind phase 3 trial, the median time to alleviation of influenza symptoms is 26.5 hours shorter with baloxavir marboxil than with placebo. One tablet was as effective as 5 days of the neuraminidase inhibitor oseltamivir and was associated with greater reduction in viral load 1 day after initiation, and similar side effects.62 Of concern is the emergence of nucleic acid substitutions conferring resistance to baloxavir; this occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 and 3 trials, respectively.
CLOSING THE GAPS
Several gaps in the management of influenza persist since the 1918 pandemic.1 These include gaps in epidemiology, prevention, diagnosis, treatment, and prognosis.
- Global networks wider than current ones are needed to address this global disease and to prioritize coordination efforts.
- Establishing and strengthening clinical capacity is needed in limited resource settings. New technologies are needed to expedite vaccine development and to achieve progress toward a universal vaccine.
- Current diagnostic tests do not distinguish between seasonal and novel influenza A viruses of zoonotic origin, which are expected to cause the next pandemic.
- Current antivirals have been shown to shorten duration of illness in outpatients with uncomplicated influenza, but the benefit in hospitalized patients has been less well established.
- In 2007, resistance of seasonal influenza A(H1N1) to oseltamivir became widespread. In 2009, pandemic influenza A(H1N1), which is highly susceptible to oseltamivir, replaced the seasonal virus and remains the predominantly circulating A(H1N1) strain.
- A small-molecule fragment, N-cyclohexyaltaurine, binds to the conserved hemagglutinin receptor-binding site in a manner that mimics the binding mode of the natural receptor sialic acid. This can serve as a template to guide the development of novel broad-spectrum small-molecule anti-influenza drugs.63
- Biomarkers that can accurately predict development of severe disease in patients with influenza are needed.
