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

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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.