15 years after its first democratic election, South Africa is in the midst of a profound health transition that is characterised by a quadruple burden of communicable, non-communicable, perinatal and maternal, and injury-related disorders. Non-communicable diseases are emerging in both rural and urban areas, most prominently in poor people living in urban settings, and are resulting in increasing pressure on acute and chronic health-care services. Major factors include demographic change leading to a rise in the proportion of people older than 60 years, despite the negative effect of HIV/AIDS on life expectancy. The burden of these diseases will probably increase as the roll-out of antiretroviral therapy takes effect and reduces mortality from HIV/AIDS. The scale of the challenge posed by the combined and growing burden of HIV/AIDS and non-communicable diseases demands an extraordinary response that South Africa is well able to provide. Concerted action is needed to strengthen the district-based primary health-care system, to integrate the care of chronic diseases and management of risk factors, to develop a national surveillance system, and to apply interventions of proven cost-effectiveness in the primary and secondary prevention of such diseases within populations and health services. We urge the launching of a national initiative to establish sites of service excellence in urban and rural settings throughout South Africa to trial, assess, and implement integrated care interventions for chronic infectious and non-communicable diseases.

Violence and injuries are the second leading cause of death and lost disability-adjusted life years in South Africa. The overall injury death rate of 157.8 per 100,000 population is nearly twice the global average, and the rate of homicide of women by intimate partners is six times the global average. With a focus on homicide, and violence against women and children, we review the magnitude, contexts of occurrence, and patterns of violence, and refer to traffic-related and other unintentional injuries. The social dynamics that support violence are widespread poverty, unemployment, and income inequality; patriarchal notions of masculinity that valourise toughness, risk-taking, and defence of honour; exposure to abuse in childhood and weak parenting; access to firearms; widespread alcohol misuse; and weaknesses in the mechanisms of law enforcement. Although there have been advances in development of services for victims of violence, innovation from non-governmental organisations, and evidence from research, there has been a conspicuous absence of government stewardship and leadership. Successful prevention of violence and injury is contingent on identification by the government of violence as a strategic priority and development of an intersectoral plan based on empirically driven programmes and policies.

One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0.7% of the world's population, had 17% of the global burden of HIV infection, and one of the world's worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Government's response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART). Care for acutely ill AIDS patients and long-term provision of ART are two issues that dominate medical practice and the health-care system. Decisive action is needed to implement evidence-based priorities for the control of the HIV and tuberculosis epidemics. By use of the framework of the Strategic Plans for South Africa for tuberculosis and HIV/AIDS, we provide prioritised four-step approaches for tuberculosis control, HIV prevention, and HIV treatment. Strong leadership, political will, social mobilisation, adequate human and financial resources, and sustainable development of health-care services are needed for successful implementation of these approaches.

South Africa is one of only 12 countries in which mortality rates for children have increased since the baseline for the Millennium Development Goals (MDGs) in 1990. Continuing poverty and the HIV/AIDS epidemic are important factors. Additionally, suboptimum implementation of high-impact interventions limits programme effectiveness; between a quarter and half of maternal, neonatal, and child deaths in national audits have an avoidable health-system factor contributing to the death. Using the LiST model, we estimate that 11,500 infants' lives could be saved by effective implementation of basic neonatal care at 95% coverage. Similar coverage of dual-therapy prevention of mother-to-child transmission with appropriate feeding choices could save 37,200 children's lives in South Africa per year in 2015 compared with 2008. These interventions would also avert many maternal deaths and stillbirths. The total cost of such a target package is US$1.5 billion per year, 24% of the public-sector health expenditure; the incremental cost is $220 million per year. Such progress would put South Africa squarely on track to meet MDG 4 and probably also MDG 5. The costs are affordable and the key gap is leadership and effective implementation at every level of the health system, including national and local accountability for service provision.

The roots of a dysfunctional health system and the collision of the epidemics of communicable and non-communicable diseases in South Africa can be found in policies from periods of the country's history, from colonial subjugation, apartheid dispossession, to the post-apartheid period. Racial and gender discrimination, the migrant labour system, the destruction of family life, vast income inequalities, and extreme violence have all formed part of South Africa's troubled past, and all have inexorably affected health and health services. In 1994, when apartheid ended, the health system faced massive challenges, many of which still persist. Macroeconomic policies, fostering growth rather than redistribution, contributed to the persistence of economic disparities between races despite a large expansion in social grants. The public health system has been transformed into an integrated, comprehensive national service, but failures in leadership and stewardship and weak management have led to inadequate implementation of what are often good policies. Pivotal facets of primary health care are not in place and there is a substantial human resources crisis facing the health sector. The HIV epidemic has contributed to and accelerated these challenges. All of these factors need to be addressed by the new government if health is to be improved and the Millennium Development Goals achieved in South Africa.

People with severe mental disorders are a neglected and vulnerable group in complex emergencies. Here, we describe field experiences in establishing mental health services in five humanitarian settings. We show data to quantify the issue, and suggest reasons for this neglect. We then outline the actions needed to establish services in these settings, including the provision of practical training, medication, psychosocial supports, and, when appropriate, work with traditional healers. We have identified some persisting problems locally, nationally, and internationally, and suggest some solutions. Protection and care of people with severe mental disorders in complex emergencies is a humanitarian responsibility.

Schizophrenia is still one of the most mysterious and costliest mental disorders in terms of human suffering and societal expenditure. Here, we focus on the key developments in biology, epidemiology, and pharmacology of schizophrenia and provide a syndromal framework in which these aspects can be understood together. Symptoms typically emerge in adolescence and early adulthood. The incidence of the disorder varies greatly across places and migrant groups, as do symptoms, course, and treatment response across individuals. Genetic vulnerability is shared in part with bipolar disorder and recent molecular genetic findings also indicate an overlap with developmental disorders such as autism. The diagnosis of schizophrenia is associated with demonstrable alterations in brain structure and changes in dopamine neurotransmission, the latter being directly related to hallucinations and delusions. Pharmacological treatments, which block the dopamine system, are effective for delusions and hallucinations but less so for disabling cognitive and motivational impairments. Specific vocational and psychological interventions, in combination with antipsychotic medication in a context of community-case management, can improve functional outcome but are not widely available. 100 years after being so named, research is beginning to understand the biological mechanisms underlying the symptoms of schizophrenia and the psychosocial factors that moderate their expression. Although current treatments provide control rather than cure, long-term hospitalisation is not required and prognosis is better than traditionally assumed.

Gout is a common arthritis caused by deposition of monosodium urate crystals within joints after chronic hyperuricaemia. It affects 1-2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in prevalence of gout. Diet and genetic polymorphisms of renal transporters of urate seem to be the main causal factors of primary gout. Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases. Non-steroidal anti-inflammatory drugs and colchicine remain the most widely recommended drugs to treat acute attacks. Oral corticosteroids could be an alternative to these drugs. Interleukin 1beta is a pivotal mediator of acute gout and could become a therapeutic target. When serum uric acid concentrations are lowered below monosodium urate saturation point, the crystals dissolve and gout can be cured. Patient education, appropriate lifestyle advice, and treatment of comorbidities are an important part of management of patients with gout.

Tetralogy of Fallot is the most common form of cyanotic congenital heart disease, and one of the first to be successfully repaired by congenital heart surgeons. Since the first procedures in the 1950s, advances in the diagnosis, perioperative and surgical treatment, and postoperative care have been such that almost all those born with tetralogy of Fallot can now expect to survive to adulthood. The startling improvement in outcomes for babies born with congenital heart disease in general-and for those with tetralogy of Fallot in particular-is one of the success stories of modern medicine. Indeed, in many countries adults with tetralogy of Fallot outnumber children. Consequently, new issues have emerged, ranging from hitherto unpredicted medical complications to issues with training for caregivers and resource allocation for this population of survivors. Therefore, evolution of treatment, recognition of late complications, research on disease mechanisms and therapies-with feedback to changes in care of affected children born nowadays-are templates on which the timely discussion of organisation of care of those affected by congenital heart diseases from the fetus to the elderly can be based. Here, we focus on new developments in the understanding of the causes, diagnosis, early treatment, and late outcomes of tetralogy of Fallot, emphasising the continuum of multidisciplinary care that is necessary for best possible lifelong treatment of the 1% of the population born with congenital heart diseases.

The initial association between the development of valvular heart disease and drugs stems from observations made during the use of methysergide and ergotamine for migraine prophylaxis in the 1960s. Since then, the appetite suppressants fenfluramine and dexfenfluramine, the dopamine agonists pergolide and cabergoline, and more recently, the recreational drug ecstasy (3,4 methylenedioxymethamphetamine; MDMA) have been implicated. Results from clinical trials show that drug dose and treatment duration affect both the risk of developing the disease and its severity. The natural history of the disease remains unclear, although regression of valvular lesions after the end of treatment has been reported. Interference with serotonin metabolism and its associated receptors and transporter gene seems a likely mechanism for development of the drug-induced valvular heart disease. Physicians need to balance the benefits of continued therapy with these drugs against possible risks. Further investigation is needed to assist with treatment decisions. Continued vigilance is necessary because several commonly prescribed treatments interact with serotonergic pathways.

Over 4 million people worldwide have received a prosthetic heart valve, and an estimated 300,000 valves are being implanted every year. Prosthetic heart valves improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thrombotic complications in valve recipients poses challenges for clinicians and patients. Here, we review antithrombotic therapies for patients with prosthetic heart valves and management of thromboembolic complications. Advances in antithrombotic therapy and valve technologies are likely to improve the management of patients with prosthetic heart valves in developed countries, but the most important unmet need and potential for benefit from these new therapies is in developing countries where a massive and rapidly increasing burden of valvular heart disease exists.

Hypoplastic left heart syndrome is a rare congenital heart defect in which the left side of the heart is underdeveloped. Surgical management of hypoplastic left heart syndrome has changed the prognosis of the condition that was previously regarded as fatal. We discuss surgical strategies based on staged procedures, with the right ventricle supporting both systemic and pulmonary circulation. We also discuss other management options, such as neonatal transplantation and the recent innovation of hybrid techniques. Surgical techniques and the understanding of the pathophysiology of this condition have been at the forefront of neonatal cardiac surgery and intensive care. The management of the syndrome remains a challenge because affected children grow into adolescence and adulthood posing various new problems and demands.

Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its incidence. Two important developments are associated with the decrease in rates of peptic ulcer disease: the discovery of effective and potent acid suppressants, and of Helicobacter pylori. With the discovery of H pylori infection, the causes, pathogenesis, and treatment of peptic ulcer disease have been rewritten. We focus on this revolution of understanding and management of peptic ulcer disease over the past 25 years. Despite substantial advances, this disease remains an important clinical problem, largely because of the increasingly widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. We discuss the role of these agents in the causes of ulcer disease and therapeutic and preventive strategies for drug-induced ulcers. The rare but increasingly problematic H pylori-negative NSAID-negative ulcer is also examined.