Effect of Oseltamivir, Zanamivir or Oseltamivir– Zanamivir Combination Treatments on Transmission of Influenza in Households

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Abstract
Background: The effectiveness of neuraminidase inhibitors to reduce transmission when used as treatment in influenza-infected patients remains debated. Methods: In a prespecified analysis of a blinded randomized controlled trial on the efficacy of oseltamivir– zanamivir combination therapy versus oseltamivir and zanamivir monotherapy conducted during the 2008– 2009 seasonal influenza epidemic, we compared the rate of secondary illness in household contacts of influenza-positive index patients between arms. Secondary illness was defined as occurrence in contacts of fever plus cough within 7 days from randomization of index patients. Analyses were conducted according to the delay between patients’ onset of symptoms and intervention. Results: A total of 543 household contacts of 267 index patients were included, of which 466 had follow-up assessment. A secondary illness was reported in 58 (12.5%) contacts with no significant difference between arms overall ( P=0.07). When the analysis was limited to the 232 contacts of 136 index patients with first treatment intake within 24 h of onset of symptoms, a lower rate of secondary illness was reported in the combination therapy arm (2 of 56 [4%]) than in the oseltamivir arm (14 of 81 [17%]; P=0.014) and the zanamivir arm (14 of 95 [15%]; P=0.031). Multivariate analysis accounting for intra-household correlation confirmed these findings. Conclusions: Our analysis suggests a greater effectiveness of the combination therapy to reduce transmissibility when given to the index patient within 24 h of onset of symptoms. As the finding was obtained from a subgroup analysis, it should be interpreted with caution.

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