Bongani M. Mayosi

The burden of non-communicable diseases in South Africa

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.

Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression.

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 = 4.8×10−99), 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.

Health in South Africa: changes and challenges since 2009

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 worlds 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.All the authorsKarim QA, Karim SS, Barron P, Bradshaw D, Chopra M, Churchyard GJ, Coovadia HM, Jewkes R, Lalloo UG, Lawn JE, Lawn SD, Mayosi BM, Pattinson R, Seedat M, Sitas F, Suffla S, Tollman SM, Van Niekerk A.

Achieving the health Millennium Development Goals for South Africa: challenges and priorities

15 years after liberation from apartheid, South Africans are facing new challenges for which the highest calibre of leadership, vision, and commitment is needed. The effect of the unprecedented HIV/AIDS epidemic has been immense. Substantial increases in mortality and morbidity are threatening to overwhelm the health system and undermine the potential of South Africa to attain the Millennium Development Goals (MDGs). However The Lancets Series on South Africa has identified several examples of leadership and innovation that point towards a different future scenario. We discuss the type of vision, leadership, and priority actions needed to achieve such a change. We still have time to change the health trajectory of the country, and even meet the MDGs. The South African Government, installed in April, 2009, has the mandate and potential to address the public health emergencies facing the country--will they do so or will another opportunity and many more lives be lost?

Epidemiology and etiology of cardiomyopathy in Africa.

Background— Cardiomyopathy, an often irreversible form of heart muscle disease that is associated with a dismal outcome, is endemic in Africa. The primary objective of this review was to summarize the current state of knowledge on the epidemiology and etiology of cardiomyopathy in people living in Africa and to identify new avenues for research. Methods and Results— We searched MEDLINE (January 1, 1966, through February 12, 2005) and reference lists of articles for relevant references. Unlike other parts of the world in which cardiomyopathy is rare, dilated cardiomyopathy is a major cause of heart failure throughout Africa. Similarly, peripartum cardiomyopathy is ubiquitous on the continent, with an incidence ranging from 1 in 100 to 1 in 1000 deliveries. There is an apparent marked regional variation in the pathogenesis of dilated cardiomyopathy and peripartum cardiomyopathy, underlining the heterogeneity of causative factors in these conditions. By contrast, endomyocardial fibrosis is restricted to the tropical regions of East, Central, and West Africa. Although the pathogenesis of endomyocardial fibrosis is not fully understood, it seems that the conditioning factors are geography and diet, the triggering factor may be an as yet unidentified infective agent, and the perpetuating factor is eosinophilia. Although epidemiological studies are lacking, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy seem to have characteristics similar to those of other populations elsewhere in the world. Conclusions— There is a need for large-scale epidemiological studies of the incidence, prevalence, determinants, and outcome of cardiomyopathy in Africa to inform strategies for the treatment and prevention of heart muscle disease on the continent.

Tracking Myocardial Motion From Cine DENSE Images Using Spatiotemporal Phase Unwrapping and Temporal Fitting

Displacement encoding with stimulated echoes (DENSE) encodes myocardial tissue displacement into the phase of the MR image. Cine DENSE allows for rapid quantification of myocardial displacement at multiple cardiac phases through the majority of the cardiac cycle. For practical sensitivities to motion, relatively high displacement encoding frequencies are used and phase wrapping typically occurs. In order to obtain absolute measures of displacement, a two-dimensional (2-D) quality-guided phase unwrapping algorithm was adapted to unwrap both spatially and temporally. Both a fully automated algorithm and a faster semi-automated algorithm are proposed. A method for computing the 2-D trajectories of discrete points in the myocardium as they move through the cardiac cycle is introduced. The error in individual displacement measurements is reduced by fitting a time series to sequential displacement measurements along each trajectory. This improvement is in turn reflected in strain maps, which are derived directly from the trajectories. These methods were validated both in vivo and on a rotating phantom. Further measurements were made to optimize the displacement encoding frequency and to estimate the baseline strain noise both on the phantom and in vivo. The fully automated phase unwrapping algorithm was successful for 767 out of 800 images (95.9%), and the semi-automated algorithm was successful for 786 out of 800 images (98.3%). The accuracy of the tracking algorithm for typical cardiac displacements on a rotating phantom is 0.24plusmn0.15mm. The optimal displacement encoding frequency is in the region of 0.1 cycles/mm, and, for 2 scans of 17-s duration, the strain noise after temporal fitting was estimated to be 2.5plusmn3.0% at end-diastole, 3.1plusmn3.1% at end-systole, and 5.3plusmn5.0% in mid-diastole. The improvement in intra-myocardial strain measurements due to temporal fitting is apparent in strain histograms, and also in identifying regions of dysfunctional myocardium in studies of patients with infarcts

Contemporary trends in the epidemiology and management of cardiomyopathy and pericarditis in sub-Saharan Africa

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.

How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis.

Objective To quantify the effect of first-line antihypertensive treatment with beta-blockers on mortality, morbidity and withdrawal rates, compared with the other main classes of antihypertensive agents. Methods We identified eligible trials by searching the Cochrane Controlled Trials Register, Medline, Embase, reference lists of previous reviews, and contacting researchers. We extracted data independently in duplicate and conducted meta-analysis by analysing trial participants in groups to which they were randomized, regardless of subsequent treatment actually received. Results Thirteen trials with 91 561 participants, meeting inclusion criteria, compared beta-blockers to placebo (four trials; n = 23 613), diuretics (five trials; n = 18 241), calcium-channel blockers (CCBs) (four trials; n = 44 825), and renin–angiotensin system (RAS) inhibitors, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (three trials; n = 10 828). Compared to placebo, beta-blockers reduced the risk of stroke (relative risk 0.80; 95% confidence interval 0.66–0.96) with a marginal fall in total cardiovascular events (0.88, 0.79–0.97), but did not affect all-cause mortality (0.99, 0.88–1.11), coronary heart disease (0.93, 0.81–1.07) or cardiovascular mortality (0.93, 0.80–1.09). The effect on stroke was less than that of CCBs (1.24, 1.11–1.40) and RAS inhibitors (1.30, 1.11–1.53), and that on total cardiovascular events less than that of CCBs (1.18, 1.08–1.29). In addition, patients on beta-blockers were more likely to discontinue treatment than those on diuretics (1.80; 1.33–2.42) or RAS inhibitors (1.41; 1.29–1.54). Conclusion Beta-blockers are inferior to CCBs and to RAS inhibitors for reducing several important hard end points. Compared with diuretics, they had similar outcomes, but were less well tolerated. Hence beta-blockers are generally suboptimal first-line antihypertensive drugs.

Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis

BackgroundRheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever.MethodsTrials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966–2003), EMBASE (1966–2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever.ResultsTen trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21–0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11–0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately US

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study)

46 in South Africa.ConclusionAntibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered.