Prophylaxis Strategies to Prevent Influenza | CDC EID

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Volume 15, Number 10–October 2009
Research
A Model-based Assessment of Oseltamivir Prophylaxis Strategies to Prevent Influenza in Nursing Homes
Carline van den Dool, Eelko Hak, Marc J.M. Bonten,1 and Jacco Wallinga1
Author affiliations: University Medical Center, Utrecht, the Netherlands (C. van den Dool, E. Hak, M.J.M. Bonten, J. Wallinga); University Medical Center, Groningen, the Netherlands (E. Hak); and National Institute for Public Health and the Environment, Bilthoven, the Netherlands (J. Wallinga)

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Abstract
Prophylaxis with neuraminidase inhibitors is important for controlling seasonal influenza outbreaks in long-term care settings. We used a stochastic individual-based model that simulates influenza virus transmission in a long-term care nursing home department to study the protection offered to patients by different strategies of prophylaxis with oseltamivir and determined the effect of emerging resistance. Without resistance, postexposure and continuous prophylaxis reduced the patient infection attack rate from 0.19 to 0.13 (relative risk [RR] 0.67) and 0.05 (RR 0.23), respectively. Postexposure prophylaxis prevented more infections per dose (118 and 323 daily doses needed to prevent 1 infection, respectively) and required fewer doses per season than continuous prophylaxis. If resistance to oseltamivir was increased, both prophylaxis strategies became less efficacious and efficient, but postexposure prophylaxis posed a lower selection pressure for resistant virus strains. Extension of prophylaxis to healthcare workers offered little additional protection to patients.

The prophylactic use of neuraminidase inhibitors is a key component of influenza outbreak control in healthcare institutions (1,2). Based on its proven efficacy in reducing susceptibility, duration of illness, and infectiousness in household studies (3–6), oseltamivir is now the antiviral agent recommended for prophylactic use in nursing homes. Although the efficacy of oseltamivir has not been extensively assessed in the elderly, some observational and experimental studies suggest beneficial effects of both continuous and postexposure prophylaxis in containing outbreaks and reducing the number of severe complications among nursing home residents (2,7–10).

During the 2007–08 and 2008–09 influenza seasons, the number of isolated influenza A (H1N1) viruses with resistance to the neuraminidase inhibitor oseltamivir increased considerably (11,12). Following the emerging resistance against the M2-inhibitors amantadine and rimantadine, the efficacy of this class of neuraminidase inhibitors may also be threatened (13). Given the speed at which resistant strains have spread and the large variability of influenza activity, it has been impossible to obtain evidence on how resistance has affected influenza control strategies from randomized controlled trials. This effect can, however, be derived using modeling studies (14,15). Therefore, we developed a mathematical model of influenza transmission in long-term care facilities to study different scenarios and to perform multiple simulations that minimize the probability of chance outcomes. We primarily determined the effect and efficiency of postexposure and continuous exposure prophylaxis strategies with oseltamivir, as compared with no prophylaxis, on infection attack rates among patients in a long-term care nursing home department. We also determined the influence of increased introduction of resistant virus strains on both strategies and assessed the potential benefits of extending prophylaxis to healthcare workers (HCWs).

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