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Early flu treatment associated with 30% lower mortality from H3N2

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February 15, 2019

Theodore Lytras, MD, PhD
Theodore Lytras

Early treatment with oseltamivir was associated with a 30% lower mortality rate compared with later treatment in patients with influenza A(H3N2) during eight recent influenza seasons in Greece, according to study results.

By contrast, the timing of treatment had no observable impact on mortality in patients with influenza A(H1N1) or influenza B, according to Theodore Lytras, MD, PhD, epidemiologist at the Hellenic Centre for Disease Control and Prevention, and colleagues.

“The take home message, in our opinion, is that oseltamivir may have different clinical effectiveness against different influenza types,” Lytras told Infectious Disease News. “This is important, because nearly all past studies of oseltamivir have focused on influenza A(H1N1)pdm09. Our study illustrates that those findings cannot be assumed applicable to influenza A(H3N2) or B, and more research is needed on that front.”

Lytras and colleagues stressed that oseltamivir should be administered early when treating severely ill patients with suspected influenza, especially when H3N2 is circulating, as it was last season.

In December, the Infectious Diseases Society of America released new influenza guidelines that emphasized the prompt testing and treatment of high-risk populations. However, even if an individual has been sick for more than 48 hours, the guidelines still recommend prescribing antivirals for patients at high risk for influenza-related complications.

For their study, Lytras and colleagues compared early (within 48 hours of symptom onset) and late (after 48 hours) oseltamivir treatment in a nationwide cohort of ICU patients with laboratory-confirmed influenza from 2010-2011 to 2017-2018.

Overall, 1,330 adult patients aged 18 years or older were included in the analysis. Of these, 46.8% died in the ICU.

The researchers observed significantly lower mortality associated with early treatment among patients with H3N2 (RR = 0.69; 95% credible intervals [CrI], 0.49-0.94; subdistribution HR = 0.58; 95% CrI, 0.37-0.88). Among patients who survived, the median ICU stay was 1.8 days shorter with early treatment (95% CrI, 0.5-3.5).

Although early oseltamivir treatment was not demonstrated to have an effect on the instantaneous risk for a patient dying at any time, or “hazard of death,” it did significantly increase the “hazard” of live discharge, translating into “substantially lower mortality among influenza A(H3N2) patients, as fewer remain at risk in the ICU,” Lytras and colleagues wrote.

They noted that the efficacy of oseltamivir “should not be assumed to be equal against all types of influenza” and suggested further research into the antiviral’s impact on the different influenza types.

“From a clinical standpoint, our finding of 30% lower mortality with early oseltamivir treatment in critically ill influenza A(H3N2) patients is immensely significant, as subtype A(H3N2) accounts for a lot of disease, especially in the elderly, and is often poorly covered by the seasonal influenza vaccine,” Lytras said. “Even though we would still like to see this finding replicated in other similar studies, we believe it vindicates the current recommendations to promptly treat with oseltamivir severely ill patients with suspected influenza.” – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.

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Perspective

This study highlights the utility of early antiviral treatment for severe influenza. It is worth noting that this study is looking at early vs. late antiviral treatment; it is not comparing antiviral treatment vs. no treatment. Further study may be merited to look at whether antiviral treatment effects vary by influenza strain.

Although this study indicates the importance of early antiviral treatment, influenza virus shedding can be prolonged in severe influenza disease, so antiviral treatment can be of use even when begun later in illness.

Matthew Zahn, MD

Chair, Infectious Diseases Society of America’s Public Health Committee
Medical director, Orange County (California) Health Care Agency

Disclosure: Zahn reports no relevant financial disclosures.