Epidemiological modelling to address burden of hepatitis B in resource poor settings: Impact & cost-effectiveness of intervention strategies

乙肝是一种病毒，如果不进行治疗，可能会导致肝脏损伤和肝癌。在发展中国家，特别是在撒哈拉以南非洲，尽管估计有高达15%的人口长期感染该病毒，但免费治疗并不普遍。替诺福韦是一种安全有效的药物，在发达国家用于治疗乙肝病毒，现在也经常用于发展中国家的艾滋病毒治疗方案。最近在西非建立了一个由欧盟资助的名为PROLIFICA(预防非洲肝纤维化和癌症)的5年研究平台，以筛查人群中的乙肝携带者(通常没有症状)，并在需要时提供治疗，主要目的是减少西非的肝癌和因乙肝病毒造成的死亡。它还在研究涉及西非人口肝癌发展的各种流行病学、生物学和遗传因素。由于乙肝病毒通常是一种进展缓慢的慢性病，通过跟踪临床观察队列，可能需要数十年的时间来评估降低乙肝病毒发病率和死亡率的干预措施的实际影响。因此，流行病学模型是公共卫生中一种有用的工具，可以利用疾病如何发展的现有知识，预测干预措施对控制疾病及其相关死亡率的可能影响。将干预措施推迟到完全结果可用时，可能会错失帮助那些已经受该疾病困扰的人的重要机会。虽然存在乙肝病毒的流行病学模型，但它们大多适用于高/中等收入国家，即乙肝病毒流行率较低的国家，模型结构过于简单，不评估基于社区的筛查效果。因此，它们在预测SSA疾病控制战略方面的应用是有限的。我的目标是开发一个专门适用于资源贫乏国家的乙肝模型，并使用该模型来预测包括筛查和治疗计划在内的各种干预措施的影响。假说是，早期干预应能减少原发性肝癌和因乙肝病毒引起的死亡。最初的方法包括回顾已发表的关于乙肝病毒自然病史和疾病不同阶段发生概率的文献。将采用基于计算机的编程技术来生成疾病传播模型。关于乙肝病毒在非洲人群中的行为，已发表的数据有限。因此，作为Prolifica计划的一部分，可以输入数据，使这一模式适用于西非人口。在预算有限的国家，仅证明临床干预措施对疾病有效是不够的，而且它们也代表着金钱的价值。因此，我建议探讨这一战略是否具有成本效益。同样，分析也是存在的，但主要是在高收入国家，而且使用的药物各不相同。利用当地适用的医疗保健提供者和家庭成本数据，这些经济分析将为卫生政策制定者提供关键信息。在西非，由于乙肝病毒导致的肝癌通常发生在30-40岁的男性中，传统的CE分析可能低估了经济损失。这项研究的结果将为卫生政策制定者(如世卫组织)和资助机构(如全球基金)提供重要的信息，使他们认识到为发展中国家的乙肝患者提供免费治疗(如Proifica提供的治疗)对公共卫生的巨大重要性，以防止过早死亡和因乙肝而遭受的痛苦。虽然最初的重点是西非的乙肝病毒，但这项研究将开发一个模型，该模型可以进行调整，以适用于其他乙肝流行率和成本不同的国家。

Hepatitis B (HBV) is a virus which can cause liver damage and liver cancer if left untreated. In the developing world, in particular in sub-Saharan Africa (SSA), although up to 15% of the population are estimated to be chronically infected with the virus, free treatment is not universally available. Tenofovir is a safe & effective drug which is used to treat HBV in the developed world and is now is also routinely available for use in HIV treatment programmes in developing countries. A recent 5 year research platform called PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa), funded by the EU, has been set up in West Africa to screen the population for hepatitis B carriers (who often have no symptoms), and offer treatment if needed, with the main aim of reducing liver cancer and death due to HBV, in West Africa. It is also looking at various epidemiological, biological and genetic factors involved in the development of liver cancer in the West African population.Since HBV, is often, a slowly progressing chronic disease, the actual impact of interventions to reduce HBV morbidity and mortality can takes decades to assess by following clinical observation cohorts. Epidemiological models are therefore, a useful tool in public health to use current knowledge of how a disease progresses, to project the likely impact of interventions on controlling the disease and its related mortality. Delaying interventions until full outcomes are available can miss a vital opportunity to help those already afflicted by the disease. Although epidemiological models for HBV exist, they mostly apply to high/middle income countries, countries with lower prevalence of HBV, have too simplistic model structures and don't evaluate the effect of community based screening. Therefore, their use in projecting disease control strategies in SSA, is limited.I aim to develop a model for HBV, specifically applicable to resource-poor countries and use this model, to predict the impact of various interventions including screening & treatment programmes. The hypothesis is that early intervention should reduce primary liver cancer and death due to HBV. Initial methods include reviewing published literature on the natural history of HBV and the probabilities of developing different stages of the disease. Computer based programming techniques will be employed to generate disease transmission models. Limited published data exists on how the Hepatitis B virus behaves in the African population. Therefore, data derived as part of the PROLIFICA programme, can be inputted to make this model applicable to the West African population.In countries, where budgets are limited, it is not sufficient to just demonstrate that clinical interventions are effective against a disease, but that they also represent value for money. I therefore propose to explore whether this strategy is cost effective. Again, analyses exist, but mainly in high-income countries, and vary in medications used. Using locally applicable data on costs, both to the health care provider and to the households, these economic analyses will provide key information for health policy makers. As liver cancer due to HBV, in West Africa, often occurs in males in their 30s-40s, loss to the economy is potentially underestimated by traditional CE analyses, which are routinely used in the western world.Results from this research, will be important in informing health policy makers, like WHO, and funding agencies, like the Global Fund, into the immense public health importance of providing treatment (like that offered in PROLIFICA) free for patients suffering from HBV, in the developing world, to prevent premature death and suffering due to HBV. While initially focusing on HBV in West Africa, the research will develop a model that can be adjusted to be applicable in other countries with varying prevalence of hepatitis B and costs.