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Open Access Open Badges Research article

Combination strategies for pandemic influenza response - a systematic review of mathematical modeling studies

Vernon J Lee1234*, David C Lye5 and Annelies Wilder-Smith6

Author Affiliations

1 Center for Health Services Research, National University of Singapore, Singapore

2 Biodefence Center, Ministry of Defence, Singapore

3 Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore

4 National Center for Epidemiology and Population Health, Australian National University, Australia

5 Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore

6 Department of Epidemiology and Public Health, National University of Singapore, Singapore

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BMC Medicine 2009, 7:76  doi:10.1186/1741-7015-7-76

Published: 10 December 2009



Individual strategies in pandemic preparedness plans may not reduce the impact of an influenza pandemic.


We searched modeling publications through PubMed and associated references from 1990 to 30 September 2009. Inclusion criteria were modeling papers quantifying the effectiveness of combination strategies, both pharmaceutical and non-pharmaceutical.


Nineteen modeling papers on combination strategies were selected. Four studies examined combination strategies on a global scale, 14 on single countries, and one on a small community. Stochastic individual-based modeling was used in nine studies, stochastic meta-population modeling in five, and deterministic compartmental modeling in another five. As part of combination strategies, vaccination was explored in eight studies, antiviral prophylaxis and/or treatment in 16, area or household quarantine in eight, case isolation in six, social distancing measures in 10 and air travel restriction in six studies. Two studies suggested a high probability of successful influenza epicenter containment with combination strategies under favorable conditions. During a pandemic, combination strategies delayed spread, reduced overall number of cases, and delayed and reduced peak attack rate more than individual strategies. Combination strategies remained effective at high reproductive numbers compared with single strategy. Global cooperative strategies, including redistribution of antiviral drugs, were effective in reducing the global impact and attack rates of pandemic influenza.


Combination strategies increase the effectiveness of individual strategies. They include pharmaceutical (antiviral agents, antibiotics and vaccines) and non-pharmaceutical interventions (case isolation, quarantine, personal hygiene measures, social distancing and travel restriction). Local epidemiological and modeling studies are needed to validate efficacy and feasibility.