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Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

ABSTRACT: Smallpox was eradicated in the 1970s, but new outbreaks could be seeded by bioterrorism or accidental release. Substantial vaccine-induced morbidity and mortality make pre-emptive mass vaccination controversial, and if vaccination is voluntary, then there is a conflict between self- and group interests. This conflict can be framed as a tragedy of the commons, in which herd immunity plays the role of the commons, and free-riding (i.e. not vaccinating pre-emptively) is analogous to exploiting the commons. This game has been analysed previously for a particular post-outbreak vaccination scenario. We consider several post-outbreak vaccination scenarios and compare the expected increase in mortality that results from voluntary versus imposed vaccination. Below a threshold level of post-outbreak vaccination effort, expected mortality is independent of the level of response effort. A lag between an outbreak starting and a response being initiated increases the post-outbreak vaccination effort necessary to reduce mortality. For some post-outbreak vaccination scenarios, even modest response lags make it impractical to reduce mortality by increasing post-outbreak vaccination effort. In such situations, if decreasing the response lag is impossible, the only practical way to reduce mortality is to make the vaccine safer (greater post-outbreak vaccination effort leads only to fewer people vaccinating pre-emptively).

SUBMITTER: Molina C

PROVIDER: S-EPMC4590493 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

Molina Chai C Earn David J D DJ

Journal of the Royal Society, Interface 20150601 107

Smallpox was eradicated in the 1970s, but new outbreaks could be seeded by bioterrorism or accidental release. Substantial vaccine-induced morbidity and mortality make pre-emptive mass vaccination controversial, and if vaccination is voluntary, then there is a conflict between self- and group interests. This conflict can be framed as a tragedy of the commons, in which herd immunity plays the role of the commons, and free-riding (i.e. not vaccinating pre-emptively) is analogous to exploiting the ...[more]

PMID: 25926701

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Project description:BackgroundHepatitis E Virus (HEV) is the leading cause of acute viral hepatitis globally. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women and it is estimated to account for ~10,000 annual pregnancy-related deaths in southern Asia alone. Recently, large and well-documented outbreaks with high mortality have occurred in displaced population camps in Sudan, Uganda and South Sudan. However, the epidemiology of HEV is poorly defined, and the value of different immunisation strategies in outbreak settings uncertain. We aimed to estimate the critical epidemiological parameters for HEV and to evaluate the potential impact of both reactive vaccination (initiated in response to an epidemic) and pre-emptive vaccination.MethodsWe analysed data from one of the world's largest recorded HEV epidemics, which occurred in internally-displaced persons camps in Uganda (2007-2009), using transmission dynamic models to estimate epidemiological parameters and assess the potential impact of reactive and pre-emptive vaccination strategies.ResultsUnder baseline assumptions we estimated the basic reproduction number of HEV in three separate camps to range from 3.7 (95% Credible Interval [CrI] 2.8, 5.1) to 8.5 (5.3, 11.4). Mean latent and infectious periods were estimated to be 34 (95% CrI 28, 39) and 40 (95% CrI 23, 71) days respectively. Assuming 90% vaccine coverage, reactive two-dose vaccination of those aged 16-65 years excluding pregnant women (for whom vaccine is not licensed), if initiated after 50 reported cases, led to mean camp-specific reductions in mortality of 10 to 29%. Pre-emptive vaccination with two doses reduced mortality by 35 to 65%. Both strategies were more effective if coverage was extended to groups for whom the vaccine is not currently licensed. For example, two dose pre-emptive vaccination, if extended to include pregnant women, led to mean reductions in mortality of 66 to 82%.ConclusionsHEV has a high transmission potential in displaced population settings. Substantial reductions in mortality through vaccination are expected, even if used reactively. There is potential for greater impact if vaccine safety and effectiveness can be established in pregnant women.

Project description:The propagation of epileptic seizure activity in the brain is a widespread pathophysiology that, in principle, should yield to intervention techniques guided by mathematical models of neuronal ensemble dynamics. During a seizure, neural activity will deviate from its current dynamical regime to one in which there are significant signal fluctuations. In silico treatments of neural activity are an important tool for the understanding of how the healthy brain can maintain stability, as well as of how pathology can lead to seizures. The hope is that, contained within the mathematical foundations of such treatments, there lie potential strategies for mitigating instabilities, e.g. via external stimulation. Here, we demonstrate that the dynamic causal modelling neuronal state equation generalises to a Fokker-Planck formalism if one extends the framework to model the ways in which activity propagates along the structural connections of neural systems. Using the Jacobian of this generalised state equation, we show that an initially unstable system can be rendered stable via a reduction in diffusivity-i.e., by lowering the rate at which neuronal fluctuations disperse to neighbouring regions. We show, for neural systems prone to epileptic seizures, that such a reduction in diffusivity can be achieved via external stimulation. Specifically, we show that this stimulation should be applied in such a way as to temporarily mirror the activity profile of a pathological region in its functionally connected areas. This counter-intuitive method is intended to be used pre-emptively-i.e., in order to mitigate the effects of the seizure, or ideally even prevent it from occurring in the first place. We offer proof of principle using simulations based on functional neuroimaging data collected from patients with idiopathic generalised epilepsy, in which we successfully suppress pathological activity in a distinct sub-network prior to seizure onset. Our hope is that this technique can form the basis for future real-time monitoring and intervention devices that are capable of treating epilepsy in a non-invasive manner.

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Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

Publications

Game theory of pre-emptive vaccination before bioterrorism or accidental release of smallpox.

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