Wagner Bradley G, Earn David J D
Department of Mathematics and Statistics, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Bull Math Biol. 2008 Jan;70(1):253-80. doi: 10.1007/s11538-007-9255-4. Epub 2007 Oct 13.
Poliomyelitis vaccination via live Oral Polio Vaccine (OPV) suffers from the inherent problem of reversion: the vaccine may, upon replication in the human gut, mutate back to virulence and transmissibility resulting in circulating vaccine derived polio viruses (cVDPVs). We formulate a general mathematical model to assess the impact of cVDPVs on prospects for polio eradication. We find that for OPV coverage levels below a certain threshold, cVDPVs have a small impact in comparison to the expected endemic level of the disease in the absence of reversion. Above this threshold, the model predicts a small but significant endemic level of the disease, even where standard models predict eradication. In light of this, we consider and analyze three alternative eradication strategies involving a transition from continuous OPV vaccination to either continuous Inactivated Polio Vaccine (IPV), pulsed OPV vaccination, or a one-time IPV pulse vaccination. Stochastic modeling shows continuous IPV vaccination is effective at achieving eradication for moderate coverage levels, while pulsed OPV is effective if higher coverage levels are maintained. The one-time pulse IPV method may also be a viable strategy, especially in terms of the number of vaccinations required and time to eradication, provided that a sufficiently large pulse is practically feasible. More investigation is needed regarding the frequency of revertant virus infection resulting directly from vaccination, the ability of IPV to induce gut immunity, and the potential role of spatial transmission dynamics in eradication efforts.
通过口服脊髓灰质炎减毒活疫苗(OPV)进行脊髓灰质炎疫苗接种存在一个内在的返祖问题:该疫苗在人体肠道内复制时,可能会突变为具有毒力和传播性,从而产生循环疫苗衍生脊髓灰质炎病毒(cVDPV)。我们构建了一个通用的数学模型,以评估cVDPV对脊髓灰质炎根除前景的影响。我们发现,对于低于某个阈值的OPV覆盖率水平,与不存在返祖现象时疾病的预期流行水平相比,cVDPV的影响较小。高于此阈值时,即使在标准模型预测可实现根除的情况下,该模型也预测疾病会出现一个虽小但显著的流行水平。鉴于此,我们考虑并分析了三种替代根除策略,包括从持续口服脊髓灰质炎减毒活疫苗接种过渡到持续接种脊髓灰质炎灭活疫苗(IPV)、脉冲式口服脊髓灰质炎减毒活疫苗接种或一次性脊髓灰质炎灭活疫苗脉冲接种。随机模型表明,对于中等覆盖率水平,持续接种脊髓灰质炎灭活疫苗在实现根除方面是有效的,而如果维持较高的覆盖率水平,脉冲式口服脊髓灰质炎减毒活疫苗接种则是有效的。一次性脉冲接种脊髓灰质炎灭活疫苗方法也可能是一种可行的策略,特别是在所需接种次数和根除时间方面,前提是实际可行地进行足够大剂量的脉冲接种。对于直接由疫苗接种导致还原病毒感染的频率、脊髓灰质炎灭活疫苗诱导肠道免疫的能力以及空间传播动态在根除工作中的潜在作用,还需要进行更多的研究。