Baloxavir marboxil, a polymerase acidic protein endonuclease inhibitor, has been shown to be effective in the treatment of uncomplicated influenza. Yet, it isn't known whether it can also prevent infection among household contacts of index patients. In a multicenter, randomized, double-blind, placebo-controlled trial, researchers evaluated the efficacy of single-dose baloxavir for the prevention of influenza in household contacts of index patients and assessed the risks of emergence and transmission of virus variants that have reduced susceptibility to baloxavir.

Index patients were identified after a positive result on a rapid influenza diagnostic test at primary care clinics in Japan and received antiviral treatment-either baloxavir or a neuraminidase inhibitor. Eligible participants in the trial were defined as household contacts who had no influenza symptoms and an axillary temperature of less than 37[degrees]C. Participants were randomly assigned to receive a single oral dose of baloxavir or placebo. Of the 545 index patients, 73.6% were younger than age 12, as were 19% of the 752 study participants.

Laboratory-confirmed clinical influenza, the primary end point, occurred significantly less often in participants who received baloxavir than in those who received placebo (1.9% versus 13.6%). Baloxavir prophylaxis was effective in high-risk participants, unvaccinated participants, and children younger than age 12. The risk of infection was lower in the group that received baloxavir compared with the group that received placebo. The incidence of adverse effects was similar in the two groups.

Among participants who received baloxavir, the viral polymerase acidic protein substitutions 138T/M and E23K emerged in 10 and five participants, respectively, during or after prophylaxis. Transmission of these variants from baloxavir-treated index patients or contacts outside the household couldn't be ruled out.

The researchers note an important limitation of the study: the frequency of the emergence of resistant variants in index patients couldn't be determined because follow-up samples hadn't been obtained.