Have you enjoyed the lovely summer and fall? I hope so because as some people say, “winter is coming,” and with winter comes the return of influenza.

The 2014–2015 Flu Season

By the first week of September 2014, the yearly cycle of influenza had dropped to its nadir. Only 1 percent of all influenza tests were positive at participating laboratories surveyed by the Centers for Disease Control and Prevention (CDC). After peaking at 5,000 positive tests per biweekly period last Christmas, now there were fewer than 20. Since September, we’ve been witnessing a gradual increase in both positive tests and percentage of tests positive.¹

The last two influenza seasons reached epidemic thresholds in the United States. The winters of both 2013 and 2014 experienced significant spikes in mortality associated with pneumonia and influenza, several standard deviations above the seasonal norm. Last season, at its peak, the vast majority of infections were influenza A viruses, and the predominant strain was the H1N1 subtype, the so-called “swine flu,” initially detected in 2009. This strain of influenza has been associated with increased case-fatality rates, particularly at the age-range extremes of greater than 65 years and less than 5. This strain is also associated with an excess incidence of the acute respiratory distress syndrome secondary to cytokine and chemokine release in otherwise healthy individuals outside the typical risk groups.

While the particular strains of circulating influenza are challenging to predict, this year’s influenza vaccines in the Northern Hemisphere consist of the following:

• Influenza A/California/7/2009 (H1N1)pdm09–like virus
• Influenza A/Texas/50/2012 (H3N2)–like virus
• Influenza B/Massachusetts/2/2012–like virus.

Approximately half of the doses manufactured for the 2014–2015 season will be tetravalent and include an additional B virus:

• Influenza B/Brisbane/60/2008–like virus

The only change from last year’s vaccine is an updated version of the H3N2 variant, replacing an influenza A/Victoria/361/2011–like virus. Vaccination group recommendations are unchanged from previous years, and health care workers are again universally encouraged to protect themselves and their patients through vaccination.

As with each influenza season, the CDC tracks the emergence of novel influenza A variants. The prevailing worrisome variant has been a highly pathogenic H5N1 strain known as “avian influenza.” At this time, only sporadic cases have been reported to the World Health Organization from the Middle East and Southeast Asia, and they have followed close contact with poultry. Another relatively lethal avian strain, H7N9, has been reported in sporadic cases throughout China and Malaysia. Lastly, a novel variant H3N2v avian strain containing genetic material from the H1N1 swine strain is being tracked. However, after peaking at 309 reported cases in 2012, only two cases of this crossover strain have been reported as of this writing. While it is too late to change the 2014–2015 vaccine components, emergence of any new pathogenic strains may change CDC recommendations for antiviral use.

Updates on Antiviral Use

The CDC has not altered its current recommendations for treatment of seasonal influenza.² As is familiar to most clinicians, this includes the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza), with recommendations to initiate therapy in high-risk groups within 48 hours of symptom onset. Patients hospitalized for respiratory illness and suspected or confirmed influenza should also be considered for antiviral therapy beyond 48 hours.

However, what is new since the last influenza season is incremental progress in opening the data on oseltamivir. As has been detailed extensively on the BMJ Tamiflu campaign, substantial doubts remain regarding the effectiveness and utility of broad use of oseltamivir for seasonal influenza.³ Independent investigators from The Cochrane Collaboration have persistently campaigned for Roche, manufacturer of oseltamivir, to provide access to full trial reports, including several early trials for which no data have been released. The overwhelming concern from this group of investigators is the data currently available for review incompletely describe the adverse effects of neuraminidase inhibitors and the quality of reporting of complications is low. Extensive meetings between the Cochrane group, Roche, and another Roche-funded reanalysis group have resulted in additional data available for analysis.

The first such updated publication provides a mixed picture regarding the utility of oseltamivir. The authors report that oseltamivir use in symptomatic adults reduced average symptom duration from 7 to 6.3 days and that use of oseltamivir as influenza prophylaxis reduced risk of influenza transmission at a rate of one case prevented for every 33 treated. However, the use of oseltamivir did not exhibit a significant effect reducing subsequent influenza complications or hospitalizations while resulting in an excess of nausea, diarrhea, cardiac adverse events, and neuropsychiatric effects. The Cochrane group concludes the use of oseltamivir for treatment of influenza must consider potential benefits and harms of treatment on an individual patient basis.⁴

The CDC, however, prefers to justify its recommendations mostly on observational data reflecting decreased mortality following treatment with neuraminidase inhibitors.⁵ CDC representatives acknowledge the trials may demonstrate little benefit to use in healthy individuals, but they note high-risk patients are underrepresented and the observational reports from pragmatic use may be more informative for such populations. Unfortunately, many of these observational reports are from investigators funded by Roche, have hotly debated statistical methodology, and are subject to the many biases inherent to such retrospective investigations.⁶

What’s the bottom line? We still don’t have good evidence describing the efficacy of oseltamivir. An otherwise healthy patient with influenza-like symptoms may receive a trivial half-day reduction in symptoms associated with a weeklong illness at the expense of the cost of medication and risk of adverse medication effects. If this season again is primarily H1N1 or a new highly pathogenic strain, it is probably reasonable to offer the drug to high-risk individuals while communicating that the benefits are suspected but unproven. Finally, for hospitalized patients with severe illness, the potential benefits almost certainly outweigh the small incremental costs of oseltamivir relative to those of hospitalization, and observational evidence, flawed as it may be, supports its use.

Dr. Radecki is assistant professor of emergency medicine at The University of Texas Medical School at Houston. He blogs at Emergency Medicine Literature of Note (emlitofnote.com) and can be found on Twitter @emlitofnote.

References

1. Centers for Disease Control and Prevention. FluView. Available at: http://www.cdc.gov/flu/weekly. Accessed October 23, 2014.
2. Centers for Disease Control and Prevention. Influenza antiviral medications: summary for clinicians. Updated September 4, 2014. Available at: http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm. Accessed October 23, 2014.
3. The BMJ. Tamiflu campaign. Available at: http:// www.bmj.com/tamiflu. Accessed October 23, 2014.
4. Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014;4:CD008965.
5. 3Centers for Disease Control and Prevention. CDC recommendations for influenza antiviral medications remain unchanged. Have You Heard? Available at: http://www.cdc.gov/media/haveyouheard/stories/Influenza_antiviral2.html. Accessed October 23, 2014.
6. Muthuri SG, Venkatesan S, Myles PR, et al. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014;2:395-404.