Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission

• DOI: 10.1371/journal.ppat.1008395
• Publication Date: 2020-04-15T17:23:31Z
• Authors: Leo Yi Yang Lee; Jie Zhou; Rebecca Frise; Daniel H. Goldhill; Paulina Koszalka; Edin J. Mifsud; Kaoru Baba; Takahiro Noda; Yoshinori Ando; Kenji Sato; Aoe-Ishikawa Yuki; Takao Shishido; Takeki Uehara; Steffen Wildum; Elke Zwanziger; Neil Collinson; Klaus Kuhlbusch; Barry Clinch; Aeron C. Hurt; Wendy S. Barclay
• Keywords: Viral Shedding; Neuraminidase inhibitor; Oseltamivir; Pandemic; Antiviral drug

Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season vaccine novel virus manufactured using current technology will not be fast enough to mitigate the effect of first wave. Antivirals can effective against many different but have thus far been used extensively outbreak control. Baloxavir, recently licensed antiviral drug that targets endonuclease, has shown reduce shedding more effectively than oseltamivir, widely neuraminidase inhibitor drug. Thus it is possible treatment with baloxavir might also interrupt onward transmission. To test this, we utilized ferret model, which most commonly animal model study We established subcutaneous administration method in ferrets achieved similar pharmacokinetics approved human oral dose. Transmission studies were then conducted two locations experimental setups compare transmission A(H1N1)pdm09 from infected treated baloxavir, oseltamivir or placebo naïve sentinel exposed either indirectly adjacent cages directly by co-housing. found reduced infectious viral upper respiratory tract compared placebo, frequency amongst sentinels both setups, even when was delayed until 2 days post-infection. In contrast, did substantially affect placebo. detect emergence baloxavir-resistant variants animals untreated sentinels. Our results support concept antivirals decrease could community.