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发表于 2006-8-3 01:02:40
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malariacontrolnet
ok, 用了零碎的时间终于完成了，不过有些专业名词还是不行,各位给个意见？
How does MalariaControl.net work?MalariaControl.net 如何运作？
Mathematical models are important decision-making tools for the control of infectious diseases and malaria was one of the first infections to which this was applied. In the 19th century, a pioneer of malaria modeling, Ronald Ross, saw the value of mathematical analyses in planning malaria control, and developed the first mathematical model for malaria.对传染病控制来说，数学模型是重要且具有决定性作用的工具。疟疾就是第一个在控制疾病传播中运用数学模型的传染病。在19世纪，一位开发疟疾模型的先驱Ronald Ross，看到了数学分析这一方法在进行疟疾控制中的价值，并开发了第一个疟疾的数学模型。
The likely impact of malaria control interventions has generally been inferred from clinical trial results, even though only short-term effects are assessed in trials. Few comparative analyses of the potential impact of different malaria control strategies have aimed to quantify the inevitable longer term impacts.虽然临床试验只评估疟疾控制的短期的效果，但从试验的结果中却能初步推断出这种方法可能带来的影响。然而，在比较性地分析不同疟疾控制方法的潜在影响时，我们发现，这些方法中几乎没有以确定更长期必然影响的程度为目标的。
The inherent uncertainties make it difficult to optimize malaria control strategies or to prioritize areas of research.内在的不确定性使得最优化疟疾控制方法或者为这方面的研究领域划分优先次序变得相当困难。
Requirements of a predictive model for the effects of malaria interventions.疟疾控制效果的预测性模型的要求：
Characteristics of individual P. falciparum infections. A model for use in predicting the population impact of a malaria intervention strategy must embed within it a relevant description of the course of individual infections.P.falciparum个体感染的特性。用于预测疟疾控制所造成的人口影响的模型必须包括对个体感染过程的相关描述。
Short-term effects on individuals. Drug treatments and vaccines may have effects on outcomes that are more complex than the effects on primary infections in the non-immune host.对个体的短期影响。药物治疗及疫苗可能对结果产生影响，而这种影响比非免疫宿主的初始感染影响要复杂得多。
If the effect of a vaccine is simply to reduce the force of infection, the short-term consequences in terms of morbidity and mortality risks are not simply proportional to the reduction in infection rate.如果疫苗的作用只是要降低感染率，那么按照发病和死亡的风险来说，这种短期的结果和感染率的降低并不是简单成比例的。
Long-term effects individual impact. The introduction of insecticide-treated nets (ITNs) for malaria control has been accompanied by extensive debate about possible long-term effects. Related issues arise with regard to vaccines.个体效果的长期影响。在疟疾控制中使用经杀虫剂处理过的蚊帐这一做法引发了关于其可能的长期影响的广泛争议。与疫苗有关的争论同样地出现了。
Long term effects of vaccination programs are even more difficult to predict, since field trials of malaria vaccines carried out thus far consider only impacts that can be measured during the 6-18 months follow-up periods. Unfortunately, the longer term consequences of a vaccination program cannot simply be extrapolated from the results of such trials. For example, some benefits of vaccination may take an extended period to become evident. This will be particularly the case if there is natural boosting or if there are effects on transmission dynamics. Conversely, vaccination may result merely in delay of morbidity and mortality in some individuals, in which case field trials may suggest a greater benefit than will be observed during implementation and scaling up of malaria vaccine programs.疫苗计划的长期影响甚至更难以预测，因为疟疾疫苗的实地试验只考虑在追踪期6-18个月里能被估量出的结果。然而，疫苗计划更长期的结果无法从这样的试验中简单地推算出来。比如，一些疫苗的益处需要更长的时间才能显现。如果有自然因素或者传播方面的影响，这种对长期影响的预测难度就更为明显了。相反的，接种疫苗有可能只是使发病或死亡在某些个体上被推迟。在这种情况下，相比较于执行期的观测值或者按比例扩大疟疾疫苗计划，实地试验也许会呈现出更为有利的结果。
Interdependence of hosts. An epidemiologic model for the effects of an intervention program must consider the dependence between events in different individuals. Field trials of interventions are generally designed with the objective of directly protecting individuals either from infection or from consequent morbidity and mortality, and do not consider broader effects on transmission.宿主的相互依赖。一个衡量疾病控制的影响的流行病学模型必须考虑不同个体事件间的相互依赖性。疟疾控制的实地试验是以直接保护个体免受感染及随之而来的发病和死亡作为设计目的的，并不考虑传输中更为广泛的影响。
Interdependence of hosts has been the core of most subsequent malaria modeling exercises.宿主的相互依赖已成为后来大多数建立疟疾模型的核心所在。
Structure of the malaria models used by MalariaControl.net MalariaControl.net 使用的疟疾模型的结构
Swiss Tropical Institute has developed new models to make quantitative predictions of the potential impact of vaccination against P. falciparum malaria.瑞士热带研究所已开发出新模型，用来进行抗P.falciparum疟疾疫苗潜在影响的量化预测。
The main component of these models is a stochastic simulation of the epidemiology of P. falciparum that incorporates insights from the within-host models, but is implemented independently of them. We have used this epidemiologic model to simulate the results from the recently completed trials of the malaria vaccine RTS,S/AS02 carried out in adult men in the Gambia and in children aged 1-5 years in Mozambique.这些模型的主要构成是对P.falciparum的流行病学方面的随机模拟，这种模拟还要和从宿主内模型中得到的结果结合在一起，但是又独立于此结果执行。我们已经运用这种流行病学模型来模拟近期完成的疟疾疫苗RTS,S/AS02在冈比亚成人男性及在莫桑比克1-5岁的孩子里完成的试验结果。
The model has also been employed to predict the potential epidemiologic impact of such a vaccine, and the cost-effectiveness. To make these predictions we incorporated costing data and a model for the health system currently in place in a low-income country context, based largely on data from Tanzania.此模型也被运用于预测某种疫苗的潜在流行病学影响以及使用这种疫苗是否划算。为了完成这些预测，我们结合了成本费用数据和一个健康系统的模型，这个健康系统现今是以低收入国家作为背景的，它很大程度上基于来自坦桑尼亚的数据。
In addition Swiss Tropical Institute has also made progress on developing within-host dynamics of malaria. This work is intended to complement earlier within-host models, specifically with a view to providing insights relevant to modeling vaccination, useful for informing the epidemiologic models. The within-host models have been fitted to data from malariatherapy patients and lead to conclusions that are particularly relevant to the modeling of asexual blood-stage vaccination.另外，瑞士热带研究所也已在开发宿主体内疟疾动力方面有了进展。此项工作意欲补充早前的宿主体内模型，尤其是以提供疟疾建模相关成果为目的，这些成果对建立流行病学模型是有帮助的。宿主体内模型业已和疟疾治愈患者的数据吻合，其导致的结果还明显和无性血液层疫苗建模有关。
An important strength is that the epidemiologic model ties together an ensemble of interconnected sub-models validated against actual field data from various settings across AFRICA. In view of the complex malaria life cycle and gaps in our current knowledge there are inherent limitations attached to some of these components, which in turn influence the overall model outcomes.我们项目一个重要的力量来自于整体结合了流行病学模型和相互连接的子模型，这些子模型已经由从许多遍及非洲的试验中所获取的真实的实地数据证实了可靠性。由于复杂的疟疾周期以及我们在这方面知识的缺陷，模型的某些组成部分有着内在的局限性，也因此影响了整个模型的预测结果。
To the best STI team's knowledge this is the most comprehensive population-based simulation of malaria yet developed. It represents an important new tool for rational planning of malaria control and vaccine development, and can readily be adapted to assess efficacy and cost-effectiveness of other malaria control interventions employed singly or in combination. This makes it possible to integrate epidemiologic and economic considerations in rational formulation of policy to reduce the intolerable burden of malaria.就最好的STI小组所知，我们使用的模型是迄今为止开发的最复杂的基于人口的疟疾模拟。它是在进行疟疾控制和疫苗开发的合理计划中所使用的全新的重要工具，它还能立即用于评估其他独立使用或结合使用的疟疾控制的功效和成本效率。这样就使得我们在合理表述那些减轻疟疾沉重负担的政策时，有可能可以将流行病学和经济效益同时纳入考虑。
The current burden of malaria morbidity and mortality, particularly in sub-Saharan Africa, is so large that even an intervention that modifies the course of infection in only a proportion of recipients without any effects on transmission may be worth pursuing. Transmission effects should not be ignored, but need to be just one part of a model that includes also the independent effects.现今疟疾发病和死亡的所造成的压力十分巨大，这在非洲下撒哈拉地区尤其明显。在这种情况下，即使某种控制方法只在一部分接受者中变更感染的过程，同时不影响任何传播，那么这种控制方法就值得一试。疾病传播的影响不应被忽视，而应成为包含这种独立影响的模型中的一部分。
Strategy of epidemiologic modeling流行病学模型的策略
The models need to simulate the processes that may be affected by vaccination, and also to capture the relationships between these processes and outcomes of public health importance. For our model we use as input the seasonal pattern of transmission, and make predictions of the consequent infection rate of humans. We then consider how this relationship may be modified by naturally acquired immunity, or by vaccination.模型需要模拟可能受接种疫苗影响的过程，并体现出在公共卫生重要性的成果和这些过程之间的关系。就我们的模型而言，我们输入并使用了疾病传播的季节性模式，就随后的人类感染率做出了预测。然后我们思索这种关系是如何被自然获得的免疫力——或被接种的疫苗——所修正。
Swiss Tropical Institute embed an empirical description of within-host asexual parasite densities in the model for the infection process to give stochastic predictions of parasite densities as a function of the age of a malaria infection, and model the effect of immunity to asexual blood stages by considering how the distribution of parasite densities is modified in the semi-immune host. This model for immunity provides a straightforward basis for analyzing possible effects of asexual blood-stage vaccines, which can be simulated by a function that reduces parasite densities.瑞士热带研究所在传染过程模型里嵌入了关于宿主体内无性生殖寄生虫密度的经验描述，以此根据疟疾感染的年数给出寄生虫密度的随机预测，并通过考虑寄生虫密度分布是如何在半免疫宿主体内得到修正的，进一步取得在无性血液层面模拟免疫的效果。这样一种免疫的模拟能为分析无性血液层疫苗的可能影响建立直接的基础，而这种疫苗的可能影响可以使用降低寄生虫密度的函数来模拟。
Swiss Tropical Institute analyze the relationship between asexual parasite densities and infectivity to the vector in malariatherapy patients in order to derive a model for the transmission to the mosquito vector. This relationship is used to simulate the transmission-blocking effects of vaccines. This makes use of the simulated population distribution of parasite densities to predict the human infectious reservoir for P. falciparum.瑞士热带研究所分析了无性寄生虫密度、疟疾传染性和疟疾病人中的带菌者之间的关系，由此推出蚊子带菌传播的模型。这种关系被用来模拟疫苗的传输阻塞现象。研究所还进而使用寄生虫密度分布模拟来预测P.falciparum在人类中的易感染区域。
An important simplification in the strategy is to avoid predicting those intermediate variables whose quantitative relationships with epidemiologic outcomes are very uncertain.此项策略中的一个很重要的简化就是避免预测那些和流行病学结果之间的关系非常不确定的中间变量。
Stochastic simulation. Swiss Tropical Institute use individual-based simulations with 5-day time steps to implement our models of P. falciparum epidemiology. This approach makes it possible to model populations of hosts and infections, each characterized by a set of continuous and static variables (parasite densities, infection durations, and immune status variables for individual hosts). This approach can allow more realistic consideration of the stochastic interactions between individual hosts and pathogens than the use of compartment models. A disadvantage is that it is computationally more intensive than the deterministic alternatives. All modules were implemented using the FORTRAN programming language.随机模拟。瑞士热带研究所使用为期5天的进行定时步骤的个体模拟来建立我们针对P.falciparum的流行病学模型。这种方式使得建立宿主和感染人数的模型成为可能，每个模型都有一系列连续且静态的变量，如寄生虫密度、感染持续期，以及个体宿主免疫状态变量。这种方法，能使研究人员更多地现实地考虑个体宿主和病原体之间的随机交互作用，而不是考虑使用间接模型。但这种方法的缺陷在于它在计算上比已确定的替代方式要有更高的要求。它所有的模块都是使用FORTRAN语言来完成的。
Fitting to real data. The uncertainty inherent in complex models needs to be minimized by ensuring that all elements of the model conform as much as possible to reality.在实际数据中调试。需要通过确保模型的所有元素尽可能适应现实环境来使复杂模型内在的不确定性最小化。
Swiss Tropical Institute has fitted different components of the model to a wealth of datasets from many different ecologic and epidemiologic settings. Our approach leads to implicit statistical models requiring many repeated simulations in order to make approximate parameter estimates. Swiss Tropical Institute was able to fit these using a simulated annealing algorithm, distributing simulations across our local computer network.瑞士热带研究所已经将模型中的不同部分试用到很多具有不同生态学和流行病学设置的数据集里。为了能得到近似的参数估计，我们要使用要求重复模拟的固有统计模型。瑞士热带研究所已经能够通过使用一种模拟的annealing algorithm，并将此模拟分布到本地网络里，来实现模型的调试。
Modular structure. The computational demands and complexity of the fitting process meant that it was not feasible to fit our overall model to all the relevant data simultaneously, so different sub-models were fitted separately.模块结构。调试过程的计算要求和复杂性意味着同时将我们所有模型试用于相关的数据中是不太可能实现的，所以不同的亚模型是分开调试的。
These sub-models were fitted to field data quantifying the relationship between malaria transmission and the outcome of interest. Each sub-model was thus fitted conditionally on the parameter estimates made at earlier stages in the fitting process. This approach made it possible for us to allow for the dynamic effects of the treatment of clinical episodes, an important consideration when STI use the model to predict the impact of interventions.这些亚模型在实地数据中进行调试，试图确定疟疾传播和影响结果之间的关系。因此每个亚模型都是有条件地在早期参数估计结果中进行调试。
Equations. In view of the modular structure of the project, the underlying equations of the epidemiologic model are grouped around six main components: (i) infection of the human host; (ii) characteristics of the simulated infections; (iii) infectivity to mosquitoes; (iv) acute morbidity; (v) mortality; (vi) anemia.影响因素。就项目的模块结构来说，我们所使用的流行病学模型潜在的影响因素能被分为六大部分：1.人体宿主的感染；2.模拟感染的特征；3.蚊子的易感染性；4.急性发病率；5.死亡率；6.贫血症。
[ Last edited by Nye on 2006-8-12 at 17:53 ] |
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