Evaluation of influenza antiviral prophylaxis for long-term care residents: a systematic review and meta-analysis

Background Influenza is a pervasive respiratory infection which disproportionately burdens long-term care residents. To limit outbreaks, guidelines recommend antiviral prophylaxis, particularly oseltamivir or zanamivir, despite acknowledging the inadequate supporting evidence. Therefore, we aimed to review the literature on the efficacy of oseltamivir, zanamivir, and baloxavir prophylaxis for influenza in long-term care. Methods Medline, Embase, PubMed, and several other databases were searched from inception to August 16, 2023. For inclusion, observational studies or randomized controlled trials (RCTs) had to report influenza-like illness (ILI) or infection rates amongst adult long-term care populations receiving prophylaxis. Outcome values were meta-analyzed as intervention-specific pooled proportions (PPs) and risk ratios (RRs) when applicable. Risk of bias was assessed via the Cochrane risk of bias tool 2.0 and Joanna Briggs Institute checklist. Results In total, 14 studies were included, comprising 12,672 residents. Individuals given oseltamivir or zanamivir experienced the fewest symptomatic, test-confirmed infections (oseltamivir PP: 0.7%, 95%CI: 0.1-4.7%, zanamivir PP: 3.0%, 95%CI: 0.9-9.4%) and ILIs (oseltamivir PP: 2.8%, 95%CI: 1.8-4.3%, zanamivir PP: 3.4%, 95%CI: 1.3-7.2%). However, no significant statistical differences were detected versus most other interventions (ILI PP range: 4.5-6.4%, infection PP range: 4.6-7.9%). Similarly, in studies directly comparing either antiviral to placebo, there were no associated benefits despite every RR being below 1 (0.51-0.75) due to expansive 95%CIs. Conclusions Oseltamivir or zanamivir could provide some benefit but low statistical power behind most estimates precluded definitive conclusions. Therefore, additional studies (RCTs) are needed to expand the evidence base and validate whether prophylaxis is beneficial in this setting.