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Twenty years after the fall of apartheid, social and economic disparities persist in South Africa and have a profound effect on the health of the population. HIV infection and tuberculosis remain major health problems, and there are not enough health care workers. In the 20 years since South Africa underwent a peaceful transition from apartheid to a constitutional democracy, considerable social progress has been made toward reversing the discriminatory practices that pervaded all aspects of life before 1994. 1 – 5 Yet the health and well-being of most South Africans remain plagued by a relentless burden of infectious and noncommunicable diseases, persisting social disparities, and inadequate human resources to provide care for a growing population with a rising tide of refugees and economic migrants. 4 , 6 Appropriate responses to South African health care challenges would be to address the social determinants of health (which lie . . .

Africa is currently host to a number of international genomics research and biobanking consortia, each with a mandate to advance genomics research and biobanking in Africa. Whilst most of these consortia promise to transform the way international health research is done in Africa, few have articulated exactly how they propose to go about this. In this paper, we report on a qualitative interviewing study in which we involved 17 genomics researchers in Africa. We describe their perceptions and expectations of international genomics research and biobanking initiatives in Africa. All interviewees were of the view that externally funded genomics research and biobanking initiatives in Africa, have played a critical role in building capacity for genomics research and biobanking in Africa and in providing an opportunity for researchers in Africa to collaborate and network with other researchers. Whilst the opportunity to collaborate was seen as a benefit, some interviewees stressed the importance of recognizing that these collaborations carry mutual benefits for all partners, including their collaborators in HICs. They also voiced two major concerns of being part of these collaborative initiatives: the possibility of exploitation of African researchers and the non-sustainability of research capacity building efforts. As a way of minimising exploitation, researchers in Africa recommended that genuine efforts be made to create transparent and equitable international health research partnerships. They suggested that this could be achieved through,: having rules of engagement, enabling African researchers to contribute to the design and conduct of international health projects in Africa, and mutual and respectful exchange of experience and capacity between research collaborators. These were identified as hallmarks to equitable international health research collaborations in Africa. Genomics research and biobanking initiatives in Africa such as H3Africa have gone some way in defining aspects of fair and equitable research collaborations in Africa. However, they will need to strive at achieving equitable health research collaborations if they truly aim at setting a gold standard for how international health research should be conducted in Africa.

Data from the Global Burden of Disease study indicate that there were 319,400 deaths due to rheumatic heart disease and 33.4 million cases of rheumatic heart disease in 2015. The highest death and prevalence rates were found in Oceania, South Asia, and central sub-Saharan Africa.

Key Points Death rates from ischaemic heart disease (IHD), stroke, and other cardiovascular diseases (CVDs) are decreasing in high-income and many Latin American countries, and this trend shows no signs of slowing Declines in some behavioural risk factors, including smoking, and physiological risk factors, such as blood pressure and serum cholesterol, are likely to have helped to reduce CVDs By contrast, the nearly universal increase in adiposity seems not to have modified the long-term declining trend in CVD mortality, although it might have had some slowing effect Improved medical care, including effective treatment of physiological risk factors, diagnosis, treatment of acute CVDs, and post-hospital care, has also contributed to declining CVD events and mortality Measured risk factor and treatment variables, while important, explain neither why the decline began when it did nor many of the similarities and differences between countries or between men and women Substantial fluctuations in CVDs, and in alcohol intake, in former communist countries of Europe have followed times of massive political and social changes since the early 1990s Cardiovascular disease (CVD) remains a leading cause of death worldwide, but age-standardized CVD death rates are decreasing steadily. In this Review, Ezzati and colleagues use the available epidemiological data to examine regional and global changes in CVD mortality, as well as trends in smoking, alcohol consumption, diet, physiological risk factors, and improvements in medical care that might underlie these changes. Ischaemic heart disease, stroke, and other cardiovascular diseases (CVDs) lead to 17.5 million deaths worldwide per year. Taking into account population ageing, CVD death rates are decreasing steadily both in regions with reliable trend data and globally. The declines in high-income countries and some Latin American countries have been ongoing for decades without slowing. These positive trends have broadly coincided with, and benefited from, declines in smoking and physiological risk factors, such as blood pressure and serum cholesterol levels. These declines have also coincided with, and benefited from, improvements in medical care, including primary prevention, diagnosis, and treatment of acute CVDs, as well as post-hospital care, especially in the past 40 years. These variables, however, explain neither why the decline began when it did, nor the similarities and differences in the start time and rate of the decline between countries and sexes. In Russia and some other former Soviet countries, changes in volume and patterns of alcohol consumption have caused sharp rises in CVD mortality since the early 1990s. An important challenge in reaching firm conclusions about the drivers of these remarkable international trends is the paucity of time-trend data on CVD incidence, risk factors throughout the life-course, and clinical care.

Heart failure in sub-Saharan Africans is mainly due to non-ischaemic causes, such as hypertension, rheumatic heart disease, cardiomyopathy and pericarditis. The two endemic diseases that are major contributors to the clinical syndrome of heart failure in Africa are cardiomyopathy and pericarditis. The major forms of endemic cardiomyopathy are idiopathic dilated cardiomyopathy, peripartum cardiomyopathy and endomyocardial fibrosis. Endomyocardial fibrosis, which affects children, has the worst prognosis. Other cardiomyopathies have similar epidemiological characteristics to those of other populations in the world. HIV infection is associated with occurrence of HIV-associated cardiomyopathy in patients with advanced immunosuppression, and the rise in the incidence of tuberculous pericarditis. HIV-associated tuberculous pericarditis is characterised by larger pericardial effusion, a greater frequency of myopericarditis, and a higher mortality than in people without AIDS. Population-based studies on the epidemiology of heart failure, cardiomyopathy and pericarditis in Africans, and studies of new interventions to reduce mortality, particularly in endomyocardial fibrosis and tuberculous pericarditis, are needed.

Since the 2009 Lancet Health in South Africa Series, important changes have occurred in the country, resulting in an increase in life expectancy to 60 years. Historical injustices together with the disastrous health policies of the previous administration are being transformed. The change in leadership of the Ministry of Health has been key, but new momentum is inhibited by stasis within the health management bureaucracy. Specific policy and programme changes are evident for all four of the so-called colliding epidemics: HIV and tuberculosis; chronic illness and mental health; injury and violence; and maternal, neonatal, and child health. South Africa now has the world's largest programme of antiretroviral therapy, and some advances have been made in implementation of new tuberculosis diagnostics and treatment scale-up and integration. HIV prevention has received increased attention. Child mortality has benefited from progress in addressing HIV. However, more attention to postnatal feeding support is needed. Many risk factors for non-communicable diseases have increased substantially during the past two decades, but an ambitious government policy to address lifestyle risks such as consumption of salt and alcohol provide real potential for change. Although mortality due to injuries seems to be decreasing, high levels of interpersonal violence and accidents persist. An integrated strategic framework for prevention of injury and violence is in progress but its successful implementation will need high-level commitment, support for evidence-led prevention interventions, investment in surveillance systems and research, and improved human-resources and management capacities. A radical system of national health insurance and re-engineering of primary health care will be phased in for 14 years to enable universal, equitable, and affordable health-care coverage. Finally, national consensus has been reached about seven priorities for health research with a commitment to increase the health research budget to 2·0% of national health spending. However, large racial differentials exist in social determinants of health, especially housing and sanitation for the poor and inequity between the sexes, although progress has been made in access to basic education, electricity, piped water, and social protection. Integration of the private and public sectors and of services for HIV, tuberculosis, and non-communicable diseases needs to improve, as do surveillance and information systems. Additionally, successful interventions need to be delivered widely. Transformation of the health system into a national institution that is based on equity and merit and is built on an effective human-resources system could still place South Africa on track to achieve Millennium Development Goals 4, 5, and 6 and would enhance the lives of its citizens.

Single nucleotide polymorphisms (SNPs) on chromosome 9p21 are associated with coronary artery disease, diabetes, and multiple cancers. Risk SNPs are mainly non-coding, suggesting that they influence expression and may act in cis. We examined the association between 56 SNPs in this region and peripheral blood expression of the three nearest genes CDKN2A, CDKN2B, and ANRIL using total and allelic expression in two populations of healthy volunteers: 177 British Caucasians and 310 mixed-ancestry South Africans. Total expression of the three genes was correlated (P<0.05), suggesting that they are co-regulated. SNP associations mapped by allelic and total expression were similar (r = 0.97, P = 4.8x10(-99)), but the power to detect effects was greater for allelic expression. The proportion of expression variance attributable to cis-acting effects was 8% for CDKN2A, 5% for CDKN2B, and 20% for ANRIL. SNP associations were similar in the two populations (r = 0.94, P = 10(-72)). Multiple SNPs were independently associated with expression of each gene (P<0.05 after correction for multiple testing), suggesting that several sites may modulate disease susceptibility. Individual SNPs correlated with changes in expression up to 1.4-fold for CDKN2A, 1.3-fold for CDKN2B, and 2-fold for ANRIL. Risk SNPs for coronary disease, stroke, diabetes, melanoma, and glioma were all associated with allelic expression of ANRIL (all P<0.05 after correction for multiple testing), while association with the other two genes was only detectable for some risk SNPs. SNPs had an inverse effect on ANRIL and CDKN2B expression, supporting a role of antisense transcription in CDKN2B regulation. Our study suggests that modulation of ANRIL expression mediates susceptibility to several important human diseases.

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.

There is controversy regarding the inclusion of patients with hypertension among cases of peripartum cardiomyopathy (PPCM), as the practice has contributed significantly to the discrepancy in reported characteristics of PPCM. We sought to determine whether hypertensive heart failure of pregnancy (HHFP) (i.e., peripartum cardiac failure associated with any form of hypertension) and PPCM have similar or different clinical features and outcome. We compared the time of onset of symptoms, clinical profile (including electrocardiographic [ECG] and echocardiographic features) and outcome of patients with HHFP (n = 53; age 29.6 ± 6.6 years) and PPCM (n = 30; age 31.5 ± 7.5 years). The onset of symptoms was postpartum in all PPCM patients, whereas it was antepartum in 85% of HHFP cases (p<0.001). PPCM was more significantly associated with the following features than HHFP (p<0.05): twin pregnancy, smoking, cardiomegaly with lower left ventricular ejection fraction on echocardiography, and longer QRS duration, QRS abnormalities, left atrial hypertrophy, left bundle branch block, T wave inversion and atrial fibrillation on ECG. By contrast, HHFP patients were significantly more likely (p<0.05) to have a family history of hypertension, hypertension and pre-eclampsia in a previous pregnancy, tachycardia at presentation on ECG, and left ventricular hypertrophy on echocardiography. Chronic heart failure, intra-cardiac thrombus and pulmonary hypertension were found significantly more commonly in PPCM than in HHFP (p<0.05). There were 5 deaths in the PPCM group compared to none among HHFP cases (p = 0.005) during follow-up. There are significant differences in the time of onset of heart failure, clinical, ECG and echocardiographic features, and outcome of HHFP compared to PPCM, indicating that the presence of hypertension in pregnancy-associated heart failure may not fit the case definition of idiopathic PPCM.

Acute rheumatic fever is considered to be a heritable condition, but the magnitude of the genetic effect is unknown. The objective of this study was to conduct a systematic review and meta-analysis of twin studies of concordance of acute rheumatic fever in order to derive quantitative estimates of the size of the genetic effect. We searched PubMed/MEDLINE, ISI Web of Science, EMBASE, and Google Scholar from their inception to 31 January 2011, and bibliographies of retrieved articles, for twin studies of the concordance for acute rheumatic fever or rheumatic heart disease in monozygotic versus dizygotic twins that used accepted diagnostic criteria for acute rheumatic fever and zygosity without age, gender or language restrictions. Twin similarity was measured by probandwise concordance rate and odds ratio (OR), and aggregate probandwise concordance risk was calculated by combining raw data from each study. ORs from separate studies were combined by random-effects meta-analysis to evaluate association between zygosity status and concordance. Heritability was estimated by fitting a variance components model to the data. 435 twin pairs from six independent studies met the inclusion criteria. The pooled probandwise concordance risk for acute rheumatic fever was 44% in monozygotic twins and 12% in dizygotic twins, and the association between zygosity and concordance was strong (OR 6.39; 95% confidence interval, 3.39 to 12.06; P<0.001), with no significant study heterogeneity (P = 0.768). The estimated heritability across all the studies was 60%. Acute rheumatic fever is an autoimmune disorder with a high heritability. The discovery of all genetic susceptibility loci through whole genome scanning may provide a clinically useful genetic risk prediction tool for acute rheumatic fever and its sequel, rheumatic heart disease.