Alexander Murray E, Bowman Christopher S, Feng Zhilan, Gardam Michael, Moghadas Seyed M, Röst Gergely, Wu Jianhong, Yan Ping
Institute for Biodiagnostics, National Research Council Canada, Winnipeg, Manitoba, Canada.
Proc Biol Sci. 2007 Jul 22;274(1619):1675-84. doi: 10.1098/rspb.2007.0422.
Given the danger of an unprecedented spread of the highly pathogenic avian influenza strain H5N1 in humans, and great challenges to the development of an effective influenza vaccine, antiviral drugs will probably play a pivotal role in combating a novel pandemic strain. A critical limitation to the use of these drugs is the evolution of highly transmissible drug-resistant viral mutants. Here, we develop a mathematical model to evaluate the potential impact of an antiviral treatment strategy on the emergence of drug resistance and containment of a pandemic. The results show that elimination of the wild-type strain depends crucially on both the early onset of treatment in indexed cases and population-level treatment. Given the probable delay of 0.5-1 day in seeking healthcare and therefore initiating therapy, the findings indicate that a single strategy of antiviral treatment will be unsuccessful at controlling the spread of disease if the reproduction number of the wild-type strain (R0s) exceeds 1.4. We demonstrate the possible occurrence of a self-sustaining epidemic of resistant strain, in terms of its transmission fitness relative to the wild-type, and the reproduction number R0s. Considering reproduction numbers estimated for the past three pandemics, the findings suggest that an uncontrollable pandemic is likely to occur if resistant viruses with relative transmission fitness above 0.4 emerge. While an antiviral strategy is crucial for containing a pandemic, its effectiveness depends critically on timely and strategic use of drugs.
鉴于高致病性禽流感病毒H5N1在人类中前所未有的传播风险，以及开发有效流感疫苗面临的巨大挑战，抗病毒药物可能在对抗新型大流行毒株中发挥关键作用。使用这些药物的一个关键限制是高传播性耐药病毒突变体的出现。在此，我们建立了一个数学模型，以评估抗病毒治疗策略对耐药性出现和大流行控制的潜在影响。结果表明，野生型毒株的消除关键取决于索引病例治疗的早期开始以及人群水平的治疗。鉴于寻求医疗保健并因此开始治疗可能会延迟0.5 - 1天，研究结果表明，如果野生型毒株的繁殖数（R0s）超过1.4，单一的抗病毒治疗策略将无法成功控制疾病传播。我们根据耐药毒株相对于野生型的传播适应性以及繁殖数R0s，证明了耐药毒株自我维持流行的可能发生。考虑到过去三次大流行估计的繁殖数，研究结果表明，如果出现相对传播适应性高于0.4的耐药病毒，可能会发生无法控制的大流行。虽然抗病毒策略对于控制大流行至关重要，但其有效性关键取决于药物的及时和策略性使用。
