Research Outputs (Clinical Medicine)

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A brief history of South Africa's response to Aids
(2014) Simelela, N.P.; Venter, W.D.F.
The story of the AIDS response in South Africa over the past 4 years is one of great progress after almost a decade of complex and tragic denialism that united the world and civil society in a way not seen since the opposition to apartheid. Today the country can boast >2 million people on antiretroviral therapy, far and away the largest number in the world. Prevention efforts appear to be yielding results. The estimated number of annual new HIV infections declined by 79 000 between 2011 and 2012. New HIV infections among adults aged 15 - 49 years are projected to decline by 48% by 2016, from 414 000 (2010) to ~215 000 (2016). The national incidence rate has reached its lowest level since the disease was first declared an epidemic in 1992, translating into reductions in both infant and under-5 mortality and an increase in life expectancy from 56 to 60 years over the period 2009 - 2011 alone. This is largely thanks to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial, and to brave health officials, politicians and clinicians working in a hostile system to bring about change.
Factors associated with mortality in HIV-infected people in rural and urban South Africa
(2014) Otwombe, KN; Petzold, M; Modisenyane, T
Background: Factors associated with mortality in HIV-infected people in sub-Saharan Africa are widely reported. However rural urban disparities and their association with all-cause mortality remain unclear. Furthermore, commonly used classical Cox regression ignores unmeasured variables and frailty. Objective: To incorporate frailty in assessing factors associated with mortality in HIV-infected people in rural and urban South Africa. Design: Using data from a prospective cohort following 6,690 HIV-infected participants from Soweto (urban) and Mpumalanga (rural) enrolled from 2003 to 2010; covariates of mortality were assessed by the integrated nested Laplace approximation method. Results: We enrolled 2,221 (33%) rural and 4,469 (67%) urban participants of whom 1,555 (70%) and 3,480 (78%) were females respectively. Median age (IQR) was 36.4 (31.0 44.1) in rural and 32.7 (28.2 38.1) in the urban participants. The mortality rate per 100 person-years was 11 (9.7 12.5) and 4 (3.6 4.5) in the rural and urban participants, respectively. Compared to those not on HAART, rural participants had a reduced risk of mortality if on HAART for 6 12 (HR: 0.20, 95% CI: 0.10 0.39) and 12 months (HR: 0.10, 95% CI: 0.05 0.18). Relative to those not on HAART, urban participants had a lower risk if on HAART 12 months (HR: 0.35, 95% CI: 0.27 0.46). The frailty variance was significant and 1 in rural participants indicating more heterogeneity. Similarly it was significant but B1 in the urban participants indicating less heterogeneity. Conclusion: The frailty model findings suggest an elevated risk of mortality in rural participants relative to the urban participants potentially due to unmeasured variables that could be biological, socio economic, or healthcare related. Use of robust methods that optimise data and account for unmeasured variables could be helpful in assessing the effect of unknown risk factors thus improving patient management and care in South Africa and elsewhere.
Parents' perceptions of HIV counselling and testing in schools : Ethical, legal and social implications
(2014-01) Gwandure, R; Ross, E; Dhai, A; et al
In view of the high prevalence of HIV and AIDS in South Africa, particularly among adolescents, the Departments of Health and Education have proposed a school-based HIV counselling and testing (HCT) campaign to reduce HIV infections and sexual risk behaviour. Through the use of semi-structured interviews, our qualitative study explored perceptions of parents regarding the ethico-legal and social implications of the proposed campaign. Despite some concerns, parents were generally in favour of the HCT campaign. However, they were not aware of their parental limitations in terms of the Children’s Act. Their views suggest that the HCT campaign has the potential to make a positive contribution to the fight against HIV and AIDS, but needs to be well planned. To ensure the campaign’s success, there is a need to enhance awareness of the programme. All stakeholders, including parents, need to engage in the programme as equal partners.
Charting the path along the continuum of PMCT or HIV-1 to elimination and finally to eradication
(2014-01) Ramkissoon, A; Coovadia, H
In this editorial we traverse the continuum of transmission of HIV-1 from mothers to children to highlight the biomedical history of this problem. Treatment has progressed from prevention with antiretrovirals (ARVs) through to a broader set of interventions, including various breastfeeding options and other health system improvements, that have increased the possibility of eliminating mother-to-child-transmission (MTCT) of HIV.
Extrapulmonary tuberculosis among adults : Experience at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
(2014-01) Karstaedt, A.S.
Prevalence and incidence of symmetrical symptomatic peripheral neuropathy in patients with multidrug - resistant TB
(2014-01) Conradie, F; Mabiletsa, T; Sefoka, M; et al
Background: Symptomatic symmetrical peripheral neuropathy (SSPN) is common in patients with HIV infection. It is also a common adverse event associated with both tuberculosis (TB) treatment and antiretroviral therapy (ART), particularly stavudine. While tenofovir is the one of recommended first-line nucleotide reverse transcriptase inhibitors (NRTIs), there is a risk of nephrotoxicity when using tenofovir together with the aminoglycosides needed to treat multidrug-resistant (MDR) TB. Thus, stavudine is often chosen as a treatment option for the HIV-infected MDR TB patient. Objective: To assess whether use of stavudine both before and during treatment for MDR TB increased the prevalence and incidence of SSPN. Method: MDR TB patients at Sizwe Tropical Disease Hospital were examined for signs of prevalent SSPN. Age, gender, HIV status, alcohol use, TB and HIV treatment regimens both prior to admission and current, and concomitant medications were recorded. Results: In this cohort of 246 patients, we found that 24.4% of patients with MDR TB had SSPN at time of admission for treatment of MDR TB. They were more likely to be HIV-infected (odds ratio (OR) 3.21; 95% CI 1.25 - 8.21) and tended to have longer (>7 months) exposure to stavudine (OR 1.81; 95% CI 0.90 - 3.63). Incident SSPN occurred in 17% of patients and was associated with older age (hazard ratio (HR) 3.00; 95% CI 1.30 - 6.89) and exposure to terizidone (HR 2.98; 95% CI 0.94 to 4.61) or, to a lesser extent, with stavudine (crude HR 1.62; 95% CI 0.65 - 4.01) in the first 6 months of MDR TB treatment. This common adverse event emphasises the need for the development of less toxic drugs for the treatment of MDR TB.
Traditional male circumcision : Balancing cultural rights and the prevention of serious, avoidable harm.
(2014-01) Behrens, K G
The right to participate in cultural practices should be protected. However, it is a limited right, and does not entail a right to activities that cause serious and avoidable harms. I argue that the harms currently resulting from traditional circumcision are very serious, and that we have an obligation to ensure that the practice is effectively regulated so as to minimise them
The cost of harmful alcohol use in South Africa
(2014-02) Matzopoulos, R G; Truen, S; Bowman, B; et al.
Background. The economic, social and health costs associated with alcohol-related harms are important measures with which to inform alcohol management policies and laws. This analysis builds on previous cost estimates for South Africa. Methods. We reviewed existing international best-practice costing frameworks to provide the costing definitions and dimensions. We sourced data from South African costing literature or, if unavailable, estimated costs using socio-economic and health data from secondary sources. Care was taken to avoid possible causes of cost overestimation, in particular double counting and, as far as possible, second-round effects of alcohol abuse. Results. The combined total tangible and intangible costs of alcohol harm to the economy were estimated at 10 - 12% of the 2009 gross domestic product (GDP). The tangible financial cost of harmful alcohol use alone was estimated at R37.9 billion, or 1.6% of the 2009 GDP. Discussion. The costs of alcohol-related harms provide a substantial counterbalance to the economic benefits highlighted by the alcohol industry to counter stricter regulation. Curtailing these costs by regulatory and policy interventions contributes directly and indirectly to social well-being and the economy. Conclusions. Existing frameworks that guide the regulation and distribution of alcohol frequently focus on maximising the contribution of the alcohol sector to the economy, but should also take into account the associated economic, social and health costs. Current interventions do not systematically address the most important causes of harm from alcohol, and need to be informed by reliable evidence of the ongoing costs of alcohol-related harms.
The research ethics evolution : From Nuremberg to Helsinki
(2014-03) Dhai, A
Health research sets out to acquire not only theoretical knowledge but also benefits for many people and often society as a whole, and is therefore justified. The quandary, though, is how such an important, shared purpose can be pursued with full protection of individuals and communities, in particular those with vulnerabilities. Abuses in the field surfaced in the early 1800s, and by the 1890s, anti-vivisectionists were calling for laws to protect children because of the increasing numbers of institutionalised children being subjected to unethical research. When read together, the Nuremberg Code and the Universal Declaration of Human Rights can be interpreted as establishing a basis for underpinning the principles of free and informed consent and avoiding harms and exploitation in scientific experiments involving human participants. The Declaration of Helsinki has been recognised as one of the most authoritative statements on ethical standards for human research in the world.
New imaging approaches for improving diagnosis of childhood tuberculosis
(2014-03) Bélard, S; Andronikou, S; Pillay, T; et al
Successfully controlling malaria in South Africa
(2014-03) Blumberg, I; Frean, J; Moonasar, D
Following major successes in malaria control over the past 75 years, South Africa is now embarking on a malaria elimination campaign with the goal of zero local transmission by the year 2018. The key control elements have been intensive vector control, primarily through indoor residual spraying, case management based on parasitological diagnosis using evidence-based drug policies with artemisinin-based combination therapy since 2001, active health promotion in partnership with communities living in the malaria transmission areas, and cross-border collaborations. Political commitment and long-term funding for the malaria control programme have been a critical component of the programme’s success. Breaking the cycle of transmission through strengthening of active surveillance using sensitive molecular tests and field treatment of asymptomatic persons, monitoring for antimalarial drug resistance and insecticide resistance, strengthening cross-border initiatives, and ongoing programme advocacy in the face of a significant decrease in disease burden are key priorities for achieving the elimination goal.
Clinical access to Bedaquiline Programme for the treatment of drug-resistant tuberculosis
(2014-03) Conradie, F; Meintjies, G; Hughes, J; et al
While clinical disease caused by drug-sensitive Mycobacterium tuberculosis (MTB) can usually be treated successfully, clinical disease caused by drug-insensitive MTB is associated with a poorer prognosis. In December 2012, a new drug, bedaquiline, was approved by the US Food and Drug Administration. This article documents the process whereby the National Department of Health, Right to Care and Médecins Sans Frontières obtained access to this medication for South Africans who might benefit from subsequent implementation of the Clinical Access to Bedaquiline Programme.
Self- induction of abortion among women accessing second- trimester abortion services in the public sector, Western Cape Province, South Africa : An exploratory study
(2014-04) Constant, D; Grossman, D; Lince, N; et al
Background: Despite South Africa's liberal abortion law permitting abortion on request in the first trimester and under restricted conditions for second-trimester pregnancies, the practice of unsafe self-induced abortion persists. However, the prevalence of this practice, the methods used and the reasons behind it are relatively under-researched. As part of a larger study seeking to improve abortion services in the Western Cape Province, we explored reports of prior attempts to self-induce abortion among women undergoing legal second-trimester abortion. Objectives: To describe the prevalence and methods of and factors related to unsuccessful attempts at self-induction of abortion by women presenting without complications and seeking second-trimester abortion at public health facilities in the Western Cape. Methods: In a cross-sectional study from April to August 2010, 194 consenting women undergoing second-trimester abortion were interviewed by trained fieldworkers using structured questionnaires at four public sector facilities near Cape Town. Results: Thirty-four women (17.5%; 95% confidence interval 12.7 - 23.4) reported an unsuccessful attempt to self-induce abortion during the current pregnancy before going to a facility for second-trimester abortion. No factors were significantly associated with self-induction, but a relatively high proportion of this small sample were unemployed and spoke an indigenous African language at home. A readily available herbal product called Stametta was most commonly used; other methods included taking tablets bought from unlicensed providers and using other herbal remedies. No use of physical methods was reported. Conclusions: The prevalence of unsafe self-induction of abortion is relatively high in the Western Cape. Efforts to inform women in the community about the availability of free services in the public sector and to educate them about the dangers of self-induction and unsafe providers should be strengthened to help address this public health issue.
Perceptions of mental illness among Muslim general practitioners in South Africa
(2014-05) Mohamed- Kaloo, Z; Laher, S
Background: Mental health literacy on the part of medical practitioners is an important component of mental healthcare. General practitioners (GPs) are typically the first doctors consulted by a person who is ill. Exploration of their perceptions regarding mental illness, aetiological issues and treatment is important. Objective: To investigate perceptions of mental illness in a sample of ten South African Muslim GPs (five male, five female) in the Lenasia area (Johannesburg, South Africa). Methods: Using a qualitative approach, semi-structured interviews were conducted with each GP. The questionnaire encompassed 37 questions relating to the context in which the GPs practised, perceptions of mental illness, understanding of religion and culture, and treatment of mental illness (including aspects of spiritual illness). Thematic content analysis was used to analyse the data. Results: Six dominant themes were identified, namely GPs' understanding of mental illness and its causation; stigma, secrecy and somatisation; the beneficial effects of religion in mental illnesses; perceptions of spiritual illnesses; collaboration with traditional healers; and collaboration with psychiatrists and psychologists. Conclusion: Greater awareness regarding the stigmatisation of mental illness is needed. Furthermore, it is important that healthcare professionals have an understanding of religious and cultural taxonomies of illness as well as the use of traditional healing as a mode of treatment. Participants identified a need for increased collaboration between healthcare professionals, including traditional healers.
The challenges of managing breast cancer in the developing world- a perspective from sub- Saharan Africa
(2014-05) Edge, J; Buccimazza, I; Cubasch, H; et al.
Communicable diseases are the major cause of mortality in lower-income countries. Consequently, local and international resources are channelled mainly into addressing the impact of these conditions. HIV, however, is being successfully treated, people are living longer, and disease patterns are changing. As populations age, the incidence of cancer inevitably increases. The World Health Organization has predicted a dramatic increase in global cancer cases during the next 15 years, the majority of which will occur in low- and middle-income countries. Cancer treatment is expensive and complex and in the developing world 5% of global cancer funds are spent on 70% of cancer cases. This paper reviews the challenges of managing breast cancer in the developing world, using sub-Saharan Africa as a model.
Setting ART initiation targets in response to changing guidelines : The importance of addressing both steady-state and backlog
(2014-06) Martin, C; Naidoo, N P; Venter, W D F; et al.
Background: Target setting is useful in planning, assessing and improving antiretroviral treatment (ART) programmes. In the past 4 years, the ART initiation environment has been transformed due to the change in eligibility criteria (starting ART at a CD4+ count <350 cells/μl v. <200 cells/μl) and the roll-out of nurse-initiated management of ART. Objective: To describe and illustrate the use of a target-setting model for estimating district-based targets in the era of an expanding ART programme and changing CD4+ count thresholds for ART initiation. Method: Using previously described models and data for annual new HIV infections, we estimated both steady-state need for ART initiation and backlog in a North West Province district, accounting for the shift in eligibility. Comparison of actual v. targeted ART initiations was undertaken. The change in CD4+ count threshold adds a once-off group of newly eligible patients to the pool requiring ART – the backlog. The steady-state remains unchanged as it is determined by the annual rate of new HIV infections in previous years. Results: The steady-state need for the district was 639 initiations/month, and the backlog was ~15 388 patients. After the shift in eligibility in September 2011, the steady-state target was exceeded over several months with some backlog addressed. Of the total backlog for this district, 72% remains to be cleared. Conclusion: South Africa has two pools of patients who need ART: the steady-state of HIV-infected patients entering the programme each year, determined by historical infection rates; and the backlog created by the shift in eligibility. The healthcare system needs to build longterm capacity to meet the steady-state need for ART and additional capacity to address the backlog.
National expenditure on health research in South Africa : What is the benchmark ?
(2014-07) Paruk, F.; Blackburn, J.M.; Friedman, I.B.; et al.
The Mexico (2004), Bamako (2008) and Algiers (2008) declarations committed the South African (SA) Ministry of Health to allocate 2% of the national health budget to research, while the National Health Research Policy (2001) proposed that the country budget for health research should be 2% of total public sector health expenditure. The National Health Research Committee has performed an audit to determine whether these goals have been met, judged by: (i) health research expenditure as proportions of gross expenditure on research and development (GERD) and the gross domestic product (GDP); and (ii) the proportion of the national health and Department of Health budgets apportioned to research. We found that total expenditure on health research in SA, aggregated across the public and private sectors,was R3.5 billion in 2009/10, equating to 16.7% of GERD. However, the total government plus science council spend on health research that year was only R729 million, equating to 3.5% of GERD (0.03% of the GDP) or 0.80% of the R91.4 billion consolidated government expenditure on health. We further found that R418 million was spent through the 2009/2010 Health Vote on health research, equating to 0.46% of the consolidated government expenditure on health or 0.9% of the R45.2 billion Health Vote. Data from other recent years were similar. Current SA public sector health research allocations therefore remain well below the aspirational goal of 2% of the national health budget. We recommend that new, realistic, clearly defined targets be adopted and an efficient monitoring mechanism be developed to track future health research expenditure.
South African Menopause Society revised consensus position statement on menopausal hormone therapy, 2014
(2014-08) Guidozzi, F; Alperstein, A; Bagratee, J S; et al.
The South African Menopause Society (SAMS) consensus position statement on menopausal hormone therapy (HT) 2014 is a revision of the SAMS Council consensus statement on menopausal HT published in the SAMJ in May 2007. Information presented in the previous statement has been re-evaluated and new evidence has been incorporated. While the recommendations pertaining to HT remain similar to those in the previous statement, the 2014 revision includes a wider range of clinical benefits for HT, the inclusion of non-hormonal alternatives such as selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors for the management of vasomotor symptoms, and an appraisal of bioidentical hormones and complementary medicines used for treatment of menopausal symptoms. New preparations that are likely to be more commonly used in the future are also mentioned. The revised statement emphasises that commencing HT during the ‘therapeutic window of opportunity’ maximises the benefit-to-risk profile of therapy in symptomatic menopausal women.
Should HIV be a notifiable disease? Old questions with some new arguments
(2014-09) Venter, W D F; Black, A; Allais, L; et al
HIV notification enters national debate regularly, often introduced by politicians and supported by many individual healthcare workers. We argue that its proponents advance confused or poorly informed rationales for making HIV notifiable. We present reasons why making HIV notifiable would be inappropriate in South Africa, why the public health benefits of a notification programme are not even likely, and why there are risks of public health and human rights harms.
Pregnancy and cardiac disease
(2014-09) Elliot, C; Sliwa, K; Burton, R
Medical disorders in pregnancy are one of the top five causes of maternal mortality in South Africa (SA), cardiac disease (CD) being the main contributor to this group. In developed countries, surgically corrected congenital heart disease (CHD) comprises the greater proportion of maternal deaths from CD. In SA and other developing countries, acquired heart disease such as rheumatic heart disease and cardiomyopathies are the major causes, although CHD remains significantly represented. Both congenital and acquired cardiac lesions may present for the first time during pregnancy. CD may also occur for the first time during or after pregnancy, e.g. peripartum cardiomyopathy. The risk to both the mother and the fetus increases exponentially with the complexity of the underlying disease. Generally, the ability to tolerate a pregnancy is related to: (i) the haemodynamic significance of any lesion; (ii) the functional class – New York Heart Association classes III and IV have poorer outcomes; (iii) the presence of cyanosis; and (iv) the presence of pulmonary hypertension. While the ideal time to assess these factors is before conception, women frequently present when already pregnant. This review discusses risk assessment and management of CD in pregnant women and the role of a combined cardiology and obstetric clinic.

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