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

L. Zuhlke，开普敦大学：非洲儿童、青少年和年轻人心脏病的病因、干预和结果研究

• 批准号: MR/S005242/1
• 负责人: Bernard Keavney
• 金额: $ 97.23万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS005242%2F1
• 关键词: L.; Zuhlke; University; Cape; Town

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.

我们计划在三种心脏病方面开展工作，这些心脏病导致非洲和其他发展中国家数百万儿童和年轻人的主要健康问题。风湿性心脏病（RHD）RHD是一种身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--产生异常和潜在的灾难性反应的疾病。大约三分之一的喉咙痛是由一种叫做A组链球菌（GAS）的细菌感染引起的。特别是在贫困、过度拥挤和反复感染的情况下，身体可以通过产生攻击患者自身器官的免疫反应来对GAS感染做出反应-这被称为急性风湿热（ARF）。ARF的反复发作，甚至一次严重发作，都可能导致心脏瓣膜的异常免疫反应损害。这反过来会导致心力衰竭，需要心脏瓣膜手术，如果不治疗，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造成的生产生命年数损失非常高。如果及时诊断GAS喉咙痛并使用抗生素治疗，RHD不太可能发展。虽然这在西方国家证明是可行的，但在非洲，风湿性心脏病仍然是一个祸害。我们迫切需要探索促进GAS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的分子过程，这样我们就可以帮助那些在生命早期发展为严重RHD的患者。我们将在拟议的研究中解决这些问题。2.先天性心脏病（CHD）CHD包括一组在婴儿在子宫内发育期间心脏不能正常形成的疾病。CHD影响近1%的新生儿，是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，冠心病患者的生存率有了显著改善。在非洲，绝大多数人口现在无法获得类似水平的护理，而且很可能仍然无法获得。因此，照顾非洲冠心病患者的医疗保健团队需要制定和采取战略，在严重资源限制的情况下提供最佳结果。在冠心病方面，绝对缺乏非洲特有的证据基础来为这一进程提供信息。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开展这项研究，评估这些中心一组严重冠心病患者的结局，并探索和评估在非洲中心推广实践改进的方法。该研究还将通过采集适合研究遗传和其他因素的患者样本，试图更好地了解CHD在分子水平上发生的原因。儿童和青少年与艾滋病毒有关的心脏病南非是世界上艾滋病毒流行最多的国家，目前约有700万人感染艾滋病毒。婴儿可能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2010年，约有20%的艾滋病毒阳性母亲将艾滋病毒传给了婴儿。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治疗（ART）以遏制病毒。艾滋病毒可以影响心血管健康的许多不同方面，包括导致心肌无力和心力衰竭。我们将在一组接受长期ART的HIV感染青少年中调查这一点，使用先进的成像技术来显示病毒及其治疗的效果。

项目成果

PROTEA, A Southern African Multicenter Congenital Heart Disease Registry and Biorepository: Rationale, Design, and Initial Results.

• DOI: 10.3389/fped.2021.763060
• 发表时间: 2021
• 期刊: Frontiers in pediatrics
• 影响因子: 2.6
• 作者: Aldersley T;Lawrenson J;Human P;Shaboodien G;Cupido B;Comitis G;De Decker R;Fourie B;Swanson L;Joachim A;Magadla P;Ngoepe M;Swanson L;Revell A;Ramesar R;Brooks A;Saacks N;De Koning B;Sliwa K;Anthony J;Osman A;Keavney B;Zühlke L
• 通讯作者: Zühlke L

Integrating the Prevention and Control of Rheumatic Heart Disease into Country Health Systems: A Systematic Review and Meta-Analysis.

• DOI: 10.5334/gh.874
• 发表时间: 2020-09-14
• 期刊: Global heart
• 影响因子: 3.7
• 作者: Abrams J;Watkins DA;Abdullahi LH;Zühlke LJ;Engel ME
• 通讯作者: Engel ME

Health trends, inequalities and opportunities in South Africa's provinces, 1990-2019: findings from the Global Burden of Disease 2019 Study.

• DOI: 10.1136/jech-2021-217480
• 发表时间: 2022-01-19
• 期刊: Journal of epidemiology and community health
• 影响因子: 6.3
• 作者: Achoki T;Sartorius B;Watkins D;Glenn SD;Kengne AP;Oni T;Wiysonge CS;Walker A;Adetokunboh OO;Babalola TK;Bolarinwa OA;Claassens MM;Cowden RG;Day CT;Ezekannagha O;Ginindza TG;Iwu CCD;Iwu CJ;Karangwa I;Katoto PD;Kugbey N;Kuupiel D;Mahasha PW;Mashamba-Thompson TP;Mensah GA;Ndwandwe DE;Nnaji CA;Ntsekhe M;Nyirenda TE;Odhiambo JN;Oppong Asante K;Parry CDH;Pillay JD;Schutte AE;Seedat S;Sliwa K;Stein DJ;Tanser FC;Useh U;Zar HJ;Zühlke LJ;Mayosi BM;Hay SI;Murray CJL;Naghavi M
• 通讯作者: Naghavi M

The RHD Action Small Grants Programme: Small Investment, Big Return!

• DOI: 10.5334/gh.996
• 发表时间: 2021-04-27
• 期刊: Global heart
• 影响因子: 3.7
• 作者: Abdullahi L;Albertus C;Perkins S;Ralston K;White A;Mwangi J;Zühlke LJ
• 通讯作者: Zühlke LJ

Task Sharing in the Diagnosis, Prevention, and Management of Rheumatic Heart Disease: A Systematic Review.

风湿性心脏病的诊断、预防和管理中的任务共享：系统评价。

• DOI: 10.1016/j.gheart.2019.04.002
• 发表时间: 2019
• 期刊: Global heart
• 影响因子: 3.7
• 作者: Abdullahi LH