A recent study by University of Michigan researchers on the efficacy of an antiviral drug, baloxavir, in preventing transmission of influenza found that a single-dose treatment with the drug led to a significantly reduced transmission of influenza to close contacts. Published April 23 in the New England Journal of Medicine, the study analyzed the effect of baloxavir use specifically within households.
Using a double-blind, randomized controlled trial, the study included 1,457 influenza-positive patients and 2,681 household contacts across 15 countries and ranging in age from five to 64 years old. By day 5, transmission of influenza was reduced using baloxavir by approximately 30% compared with a placebo.
In an interview with The Michigan Daily, Arnold Monto, professor emeritus of public health and lead author of the study, said baloxavir is unique compared to older classes of antivirals used to treat influenza. One such antiviral, Oseltamivir, also known by its brand name Tamiflu, inhibits the neuraminidase enzyme used by the influenza virus to spread throughout the body after it has replicated. Baloxavir, in contrast, inhibits the cap-dependent endonuclease, which stops the virus from replicating itself to begin with. Baloxavir also requires only one dose whereas Tamiflu requires twice-daily dosage for five days.
Monto said studies on Tamiflu did not clearly show the treatment reduced influenza transmission, whereas baloxavir showed faster reduction in virus shedding, or the virus spreading to others from an infected person.
“We always wondered whether the older neuraminidase inhibitors (such as) Tamiflu, which is all over the place, inhibit transmission, or is it only useful within (a patient’s) family, for example, in treating influenza, and does it reduce the spread at all,” Monto said. “Most of the studies have been equivocal or negative. And we wondered, was it the study design or was it the fact that it really wasn’t reducing transmission? Along comes baloxavir, and in comparative studies with influenza, we could see that the shedding of the virus from infected individuals dropped much quicker than when an individual was treated with Tamiflu.”
In an interview with The Daily, Public Health student Joshua Foster-Tucker, who is studying under Monto, said he thinks baloxavir has the potential to change how flu outbreaks and pandemics are handled by public health systems, describing an ideal outcome where an entire household is tested for influenza and treated with baloxavir after one member tests positive.
“I could see this drug being brought to market as part of a cascade testing paradigm wherein the index patient who tests positive for influenza, in a perfect world, triggers a perfect cascade of all other household members being tested for flu within a week,” Foster-Tucker said. “Then we are able to, with baloxavir, catch transmission at its base and prevent household transmission, but also prevent transmission outside of that household.”
Foster-Tucker said one unintended consequence of his scenario is family members being prescribed baloxavir even without testing positive for influenza, which may make the virus more resistant to baloxavir for those patients in the future.
“I could also see it maybe not necessarily going as perfectly as we would intend,” Foster-Tucker siad. “Sure, an index case in a household is prescribed the drug after a positive test, but everybody else in the household, at least if they were to seek it out, would also be prescribed baloxavir, even without a positive test. You could see how that could be good, but it could also have unintended consequences of furthering resistance, if resistance is clinically meaningful in this context.”
Monto said his study notes that baloxavir has minimal side effects and works against all influenza viruses, though the specific case of avian influenza requires further clinical exploration.
“The problem there is that the cases in humans are sporadic and often aren’t diagnosed until after the fact,” Monto said. “But there is a discussion about trying to use it, at least in various models, to confirm that it works against avian influenza. It has been done in the laboratory, but it would be interesting to be able to use it in treatment.”
President Donald Trump’s administration has made cuts to public health infrastructure. Foster-Tucker said these changes have separated him and Monto from their colleagues, which creates an additional barrier to researching and developing baloxavir.
“It’s also so incredibly hard to say anything about the public health establishment or lack thereof now, because it’s been absolutely decimated,” Foster-Tucker said. “Colleagues of mine, and especially colleagues of Dr. Monto, people who we knew, were reassigned to Alaska (to work on) flu. There is no easy answer, and there’s no consistency coming out of the government with regard to public health interventions.”
JoLynn Montgomery, lead epidemiologist of the University Health Service, oversees its Research & Applied Analytics data team, monitoring gastrointestinal and respiratory illnesses on campus. In an interview with The Daily, Montgomery said it is important to research new tools to fight influenza, such as baloxavir, to help control pandemics.
“In general, anything we can do to prevent influenza will help us during a pandemic or outbreak,” Montgomery said. “Having additional tools and knowing more about these tools is always beneficial. (For) this particular thing, I think none of the medications or vaccines, in and of themselves, will stop a pandemic, but combined, they are great resources and can have a big impact.”
Daily Staff Reporter Savannah Halpern can be reached at savhal@umich.edu.
