Effectiveness of baloxavir marboxil in reducing household influenza transmission: a systematic review

Background Influenza causes substantial global morbidity and mortality. Baloxavir marboxil, approved in 2018, has strong antiviral activity. However, its effectiveness in reducing household influenza transmission remains unclear. Methods We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 1 January 2018 to 25 June 2025 for randomized and observational studies assessing two baloxavir-based strategies for reducing household influenza transmission: index-patient treatment, in which baloxavir is administered to infected individuals to reduce infectiousness and onward household transmission, and post-exposure prophylaxis (PEP), in which baloxavir is administered to exposed household contacts to prevent infection establishment, reporting laboratory-confirmed or symptomatic influenza among contacts, with comparators including placebo or neuraminidase inhibitors. Results This systematic review included 4 studies involving 5,784 participants, comprising 1,991 index patients and 3,793 household contacts from three Japan-based studies and one 15-country multinational CENTERSTONE trial. Baloxavir PEP for household contacts was associated with relative risk reductions of 57–86% in household influenza outcomes compared with control regimens. In contrast, index-patient treatment was associated with more modest relative risk reductions of 24–29%, including a 24% reduction in symptomatic transmission at 5 days that was not statistically significant ( P = 0.16). These findings suggest a larger estimated protective effect for PEP than for index-patient treatment. Conclusions Baloxavir-based strategies may reduce household influenza transmission, but the magnitude and strength of evidence differ by intervention mechanism. Current evidence suggests larger reductions with PEP for exposed household contacts, whereas treatment of index patients alone was associated with more modest indirect reductions, including a non-significant reduction in symptomatic transmission at 5 days. Future studies should define optimal timing, identify populations most likely to benefit, and clarify the role of targeted PEP in household influenza control.