Clinical Pearls & Morning Reports
Households and other close-contact settings such as dormitories and schools are important sites for seasonal and pandemic transmission of influenza virus. Ikematsu et al. assessed the efficacy of postexposure prophylaxis with a single dose of baloxavir for the prevention of influenza in household contacts. Read the NEJM Original Article here.
Q: What is baloxavir marboxil?
A: Baloxavir marboxil (baloxavir), a prodrug of the cap-dependent endonuclease inhibitor baloxavir acid (“cap” refers to a 7-methyl guanosine that is added to the 5′ end of the host messenger RNA strand), was approved as a single-dose treatment for uncomplicated influenza A and B in Japan and the United States in 2018 and was recently approved in the United States for the treatment of influenza in patients who were at risk for complications. Baloxavir treatment within 2 days after the onset of illness shortened the duration of illness by approximately 1 day as compared with placebo and showed superior antiviral efficacy to both placebo and oseltamivir.
Q: Has baloxavir treatment been associated with the emergence of variant viruses that confer reduced in vitro susceptibility?
A: Variant viruses with amino acid substitutions in the polymerase acidic protein (PA) have emerged after baloxavir treatment. Position PA I38 substitutions (T, M, S, or F) are most common, and a virus with such a substitution is 10 to more than 420 times less susceptible to baloxavir in vitro than is wild-type virus; a virus with a substitution at other positions, such as PA E23, PA A37, or PA E199, is 3 to 10 times less susceptible. PA I38X–substituted viruses have emerged in 2.2 to 9.8% of baloxavir-treated adolescents and adults and in 19.3 to 23.4% of baloxavir-treated children. The detection of PA I38X variant viruses has been associated with prolongation of infectious virus replication and potential transmissibility, including one instance of household transmission.
A: This randomized, placebo-controlled clinical trial showed that rapid administration of single-dose baloxavir as postexposure prophylaxis was highly effective in preventing influenza in the household setting and was associated with an incidence of adverse events similar to that with placebo. Baloxavir prophylaxis was effective in high-risk participants, in children younger than 12 years of age, and in unvaccinated participants. Baloxavir not only showed prophylactic efficacy in participants who had not been infected at baseline but also reduced the risk of symptom development among those who were already infected. Baloxavir prophylaxis resulted in a significantly lower risk of clinical influenza in pediatric participants than placebo, but as previously observed with oseltamivir, its protective efficacy was lower than that in teenagers and adults.
A: The authors could not assess the prophylactic efficacy for influenza B virus because circulation of this virus was limited in their single-season trial. The therapeutic efficacy of baloxavir has been shown in high-risk outpatients with influenza B virus infection, in whom baloxavir treatment was associated with greater antiviral and clinical effects than placebo or oseltamivir. These findings suggest that baloxavir could be effective for prophylaxis against influenza B, but additional studies are required.