Antiviral resistance during pandemic influenza: implications for stockpiling and drug use

被引:31
作者
Arino, Julien [1 ,2 ]
Bowman, Christopher S. [1 ,3 ]
Moghadas, Seyed M. [1 ,4 ,5 ]
机构
[1] Natl Res Council Canada, Inst Biodiagnost, Winnipeg, MB R3B 1Y6, Canada
[2] Univ Manitoba, Dept Math, Winnipeg, MB R3T 2N2, Canada
[3] Univ Manitoba, Dept Elect & Comp Engn, Winnipeg, MB R3T 5V6, Canada
[4] Univ Winnipeg, Dept Math & Stat, Winnipeg, MB R3B 2E9, Canada
[5] Univ Manitoba, Dept Stat, Winnipeg, MB R3T 2N2, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
OSELTAMIVIR RESISTANCE; EMERGENCE; NEURAMINIDASE; POPULATION; EPIDEMIC; IMPACT; VIRUS; TRANSMISSIBILITY; H5N1;
D O I
10.1186/1471-2334-9-8
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background: The anticipated extent of antiviral use during an influenza pandemic can have adverse consequences for the development of drug resistance and rationing of limited stockpiles. The strategic use of drugs is therefore a major public health concern in planning for effective pandemic responses. Methods: We employed a mathematical model that includes both sensitive and resistant strains of a virus with pandemic potential, and applies antiviral drugs for treatment of clinical infections. Using estimated parameters in the published literature, the model was simulated for various sizes of stockpiles to evaluate the outcome of different antiviral strategies. Results: We demonstrated that the emergence of highly transmissible resistant strains has no significant impact on the use of available stockpiles if treatment is maintained at low levels or the reproduction number of the sensitive strain is sufficiently high. However, moderate to high treatment levels can result in a more rapid depletion of stockpiles, leading to run-out, by promoting wide-spread drug resistance. We applied an antiviral strategy that delays the onset of aggressive treatment for a certain amount of time after the onset of the outbreak. Our results show that if high treatment levels are enforced too early during the outbreak, a second wave of infections can potentially occur with a substantially larger magnitude. However, a timely implementation of wide-scale treatment can prevent resistance spread in the population, and minimize the final size of the pandemic. Conclusion: Our results reveal that conservative treatment levels during the early stages of the outbreak, followed by a timely increase in the scale of drug-use, will offer an effective strategy to manage drug resistance in the population and avoid run-out. For a 1918-like strain, the findings suggest that pandemic plans should consider stockpiling antiviral drugs to cover at least 20% of the population.
引用
收藏
页数:12
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