ECDC experts confirm support for neuraminidase inhibitors

An expert panel from the European Center for Disease Prevention and Control (ECDC) yesterday reaffirmed that there is clear evidence to support using neuraminidase inhibitors to treat and prevent flu.

In other antiviral drug developments, a research team based at the National Institute for Allergy and Infectious Diseases (NIAID) today reported on a potential new broad-spectrum antiviral, based on unexpected findings during experiments with herpes simplex virus (HSV).

Study focuses on three large reviews

In its 34-page review posted on the ECDC's Web site, the ECDC experts also said more studies are needed on severe outcomes and in high-risk groups and that new, more powerful antivirals are urgently needed.

The new review of neuraminidase inhibitors—considered the gold standard for treating flu—comes in the wake of two controversies around their use, one in which BMJ pressed Roche, the maker of oseltamivir (Tamiflu) to release full data on efficacy trials, and the other involving questions that arose in Europe about the cost of antiviral stockpiling during the 2009 H1N1 pandemic.

The ECDC expert group began its review in 2015, then opened it for public feedback in the spring of 2016.

For their analysis, the experts focused on three large systematic reviews and meta-analyses from 2014 and 2015, including one from the Cochrane Collaboration. They also looked at other views and studies.

Findings support current guidance

For adults, the three main reviews found that oseltamivir shortens flulike illness symptoms by about 17 to 18 hours, and by about a day for those with lab-confirmed flu. Two of the large reviews found statistically significant decreases in patient-reported pneumonia, lower respiratory-tract infections, and hospital admissions.

All three reviews emphasized the importance of starting treatment early—within 48 hours for oseltamivir, and for children treated with the inhaled drug zanamivir (Relenza), within 36 hours.

Regarding prophylaxis, the experts report that several randomized controlled trials found reduced risk of flu after treatment with oseltamivir or zanamivir.

The most commonly reported adverse effects of the drugs were nausea and vomiting.

The review process revealed that more studies are needed to shore up the research base, especially to flesh out any benefits on severe clinical outcomes and for risk groups, such as people with asthma, chronic obstructive pulmonary disease, cardiovascular disease, or diabetes.

Experts didn't find any new evidence to support any changes to already-approved neuraminidase inhibitor recommendations in European Union member states, and they said their assessment is consistent with that of the World Health Organization and public health groups in many parts of the world.

Use of neuraminidase inhibitors is a reasonable public health measure during seasonal, pandemic, and susceptible zoonotic flu outbreaks, the group wrote, adding that the findings also support stockpiling the drugs as part of country preparedness planning.

Early experiments find antiviral activity for cancer research drug

The potential new broad-spectrum antiviral identified by NIAID researchers came from experiments on how EZH2/1 inhibitors, epigenetic drugs that are under study for cancer treatment, regulate HSV infection. Unexpectedly, they found that inhibiting EZH2/1 suppressed viral infection. They detailed their findings today in the latest edition of mBio.

They also found that the drugs enhanced cellular antiviral response in cell culture and in mice and that, based on human cell cultures, they also suppressed human cytomegalovirus, adenovirus, and Zika virus.

In a press release from the American Society for Microbiology (ASM), the published of mBio, lead author Thomas Kristie, PhD, principal investigator at NIAID's laboratory of viral diseases, suggested that EZH2/1 inhibitors might be useful for boosting an individual's innate immunity of emerging or drug-resistant viruses.

"This could also be a novel way of treating infections by enhancing the infected cell’s own ability to fight the virus," he said. "Many viruses, such as herpesviruses, have mechanisms to circumvent cellular immune responses. What was striking was that these viruses were not able to escape the suppression mediated by these inhibitors."

See also:

Aug 14 ECDC press release

Aug 14 ECDC expert panel review

Aug 15 mBio study

Aug 15 ASM press release

Aug 15 NIH press release

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