L. Zuhlke, University of Cape Town: Etiological, intervention and outcome studies in African children, adolescents and young adults with heart disease

我们计划致力于治疗三种心脏病，这些心脏病会给非洲和其他发展中国家的数百万儿童和年轻人带来重大健康问题。风湿性心脏病(RHD)风湿性心脏病是指人体自身的免疫系统对一种常见的、通常是自限性的健康问题--喉咙痛--做出异常且可能是灾难性的反应。大约三分之一的喉咙痛是由一种名为A组链球菌(GAS)的细菌感染引起的。特别是在贫穷、过度拥挤和反复感染的条件下，人体可以通过产生免疫反应来对气体感染做出反应，这种免疫反应攻击患者自己的一些器官--这被称为急性风湿热(ARF)。ARF的反复发作，甚至一次严重的发作，都可能通过心脏瓣膜的异常免疫反应而导致损害。这反过来会导致心力衰竭，需要心脏瓣膜手术，如果不治疗，就会死亡。大多数受风湿性心脏病影响的人是儿童和年轻人，因此，这种被忽视的贫困疾病损失的生产寿命年数非常高。如果气性咽喉痛得到及时诊断和抗生素治疗，风湿性心脏病就不太可能发生。尽管这在西方国家被证明是可行的，因为风湿性心脏病现在很少见，但风湿性心脏病在非洲仍然是一个祸害。我们迫切需要探索促进气体感染诊断和治疗的障碍，并制定克服这些障碍的策略。我们还需要更好地了解急性疾病所涉及的分子过程，这样我们才能帮助那些在生命早期发展为严重风湿性心脏病的患者。我们将在拟议的研究中解决这些问题。先天性心脏病(CHD)先天性心脏病包括一组在婴儿在子宫中发育过程中心脏形成不正常的情况。先天性心脏病影响了近1%的新生儿，是导致儿童死亡和终身残疾的主要原因。在发达国家，由于护理的进步，冠心病患者的存活率有了显著的改善。在非洲，绝大多数人口现在无法获得类似水平的医疗服务，今后也很可能继续如此。因此，照顾非洲冠心病患者的医疗团队需要制定和采取在严格资源限制的情况下提供最佳结果的战略。在冠心病中，绝对缺乏非洲特有的证据基础来告知这一过程。在过去的一年里，我们的团队已经开始改变这一点，在开普敦建立了一项针对冠心病患者的研究，在六个月内招募了500多名患者。我们现在计划进一步发展这项研究，在另外五个非洲国家建立它，在这些中心评估一组严重冠心病患者的结果，并探索和评估一种在非洲中心推广实践改进的方法。这项研究还将通过采集适合研究遗传和其他因素的患者样本，试图从分子水平更好地理解CHD发生的原因。儿童和青少年中与艾滋病毒有关的心脏病南非是世界上艾滋病毒流行最严重的国家；目前约有700万人感染艾滋病毒。婴儿可能会在出生时被母亲感染艾滋病毒。尽管由于对艾滋病毒阳性母亲的治疗，母婴传播率大幅下降，但就在最近的2010年，大约20%的艾滋病毒阳性母亲将艾滋病毒传染给了她们的婴儿。因此，有相当数量的艾滋病毒阳性儿童需要长期接受抗逆转录病毒疗法(ART)治疗以遏制病毒。艾滋病毒可影响心血管健康的许多不同方面，包括导致心脏肌肉无力和心力衰竭。我们将在一组长期服用抗逆转录病毒药物的艾滋病毒感染青少年中进行调查，使用先进的成像技术来显示病毒及其治疗的效果。

We plan to work in three heart diseases causing major health problems in millions of children and young adults in Africa and other parts of the developing world.1. Rheumatic heart disease (RHD)RHD is a condition in which the body's own immune system mounts an abnormal and potentially catastrophic response to a common and usually self-limiting health problem, a sore throat. Around a third of sore throats are caused by a bacterial infection with an organism called Group A Streptococcus (GAS). Particularly in conditions of poverty, overcrowding and repeated infection, the body can react to the GAS infection by producing an immune response which attacks a number of the patient's own organs - this is called acute rheumatic fever (ARF). Repeated attacks of ARF, or even one serious attack, can result in damage by the abnormal immune response to the valves of the heart. This can in turn result in heart failure, the need for heart valve surgery, and if untreated, death. Most people affected by RHD are children and young adults, and so the number of productive life years lost from this neglected disease of poverty is very high. If GAS sore throat is promptly diagnosed and treated with antibiotics, RHD is unlikely to develop. Although this has proved feasible in Western countries, where RHD is now rare, RHD remains a scourge in Africa. We urgently need to explore the blocks to prompt diagnosis and treatment of GAS infection and develop strategies to overcome these. We also need to develop a better understanding of the molecular processes involved in acute disease, so we can help that subset of patients who develop severe RHD early in life. We will address these questions in the proposed research.2. Congenital heart disease (CHD)CHD comprises a group of conditions in which the heart is not formed properly during the baby's development in the womb. CHD affects nearly 1% of births and is a major cause of childhood death and lifelong disability. In developed countries, there has been a dramatic improvement in survival of patients with CHD thanks to advances in care. Access to similar levels of care in Africa is, and will likely remain, unavailable for the vast majority of the population. So, healthcare teams caring for African CHD patients need to formulate and adopt strategies which will deliver the best outcomes in a setting of severe resource restriction. There is an absolute lack of an African-specific evidence base in CHD to inform such a process. Over the last year, our team has begun to change this, establishing a study of CHD patients in Cape Town which has enrolled over 500 patients in six months. We now plan to develop this study further, by establishing it in five further African countries, evaluating the outcomes in a group of patients with severe CHD in these centres, and exploring and evaluating a way to roll out practice improvements across African centres. The study will also attempt to better understand why CHD occurs at the molecular level, by taking patient samples suitable to study inherited and other factors.3. Heart disease associated with HIV in children and young adultsSouth Africa has the world's largest HIV epidemic; some 7 million people are currently living with HIV infection. Babies can be infected with HIV by their mothers around the time of birth. Although rates of mother to child transmission have dropped considerably due to treatment of HIV positive mothers, as recently as 2010, around 20% of HIV positive mothers passed on HIV to their baby. Therefore, there is a substantial number of HIV positive children who need longterm treatment with Anti Retroviral Therapy (ART) to contain the virus. HIV can affect many different aspects of cardiovascular health including causing weakness of the heart muscle and heart failure. We will investigate this in a group of HIV infected adolescents taking long-term ART, using advanced imaging technologies to show the effect of the virus and its treatment.