The state and future of research at the University of Cape Town’s Faculty of Health Sciences

The nature of research has continued to change considerably over the last century. Our Faculty’s challenge has been to keep abreast of those changes to remain at the cutting edge, while contributing meaningfully to the scientific literature which informs clinical and public health practice in South Africa and beyond. The Faculty must possess an agreed-on research strategy that is dynamic and responsive. Over the years our Faculty has ‘grown’ such a strategy document. This article, summarising its main thrusts, is offered because we feel that while it applies specifically to UCT, the issues raised surely apply to all similar faculties in our country and on the continent, to varying degrees

Development of the health system in the Western Cape: experiences since 1994

Provincial governments in South Africa have a critical responsibility in terms of population health, yet few provincial-level analyses of health-system development have been undertaken. This chapter reports on research being conducted in the Western Cape to understand the province’s particular experience of health-system transformation since 1994, set against wider national experience. The research is being undertaken collaboratively by the authors of this chapter, a team of Western Cape provincial health managers and researchers. The chapter is structured to reflect the Western Cape’s 22-year experience. The situation that faced the province in 1994 is outlined briefly, followed by a description of key features of the three health strategies that have driven provincial health-system development over time. An assessment is then presented of the overall nature and patterns of Western Cape health-system change, and the achievements and limitations of this transformation are considered. The chapter concludes with some early lessons from this experience, and relevant, international experience is considered.DHE

Advances in childhood tuberculosis – contributions from the University of Cape Town

Childhood tuberculosis (TB) is common in high TB burden countries, contributing a substantial proportion to the TB caseload. The HIV epidemic has had a large impact on the incidence, diagnosis and management of childhood TB. Aim. To review the contributions from researchers at the University of Cape Town to the field of childhood TB over the past decades. Methods. Review of published literature on studies of childhood TB done by investigators from the University of Cape Town. Results. Important advances have been made, especially in the areas of epidemiology, diagnosis and prevention of childhood TB. Epidemiological research has led to improved understanding of the large burden of childhood TB in Cape Town. Advances in diagnosis include use of improved specimens, particularly induced sputum and better diagnostic tests. The efficacy of GeneXpert, a rapid polymerase chain reaction (PCR)-based diagnostic test, on induced sputum specimens, has potential to enable a confirmed diagnosis in children of all ages at a range of healthcare facilities, and represents an important advance in management of children presenting with suspected TB. Advances in prevention include the establishment of a vaccine study site and several studies on immunisation, and on the use of primary isoniazid prophylaxis as an effective preventive strategy in symptomatic HIV-infected children. Conclusion. Research in childhood TB has led to important advances in diagnosis and management, enabling better care for HIV-infected and uninfected children

Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis in South African infants: randomised trial

Objective To compare the incidence of tuberculosis over two years in infants vaccinated at birth with intradermal BCG or with percutaneous BCG

SATVI - after 10 years closing in on a new and better vaccine to prevent tuberculosis

The vision of the South African Tuberculosis Vaccine Initiative (SATVI) (www.satvi.uct.ac.za) is ‘A World Without TB’ and our mission is ‘Innovative and high-quality TB vaccine research in Africa, to impact the global epidemic’. Over the last 10 years, our focus has been twofold: first, clinical trials of BCG and of new candidate vaccines, and second, complementary research that addresses critical questions in TB vaccine development. SATVI is now widely regarded as the leading TB vaccine clinical research site in the world

Advances in childhood immunisation in South Africa: where to now? Programme managers’ views and evidence from systematic reviews.

Background: The Expanded Programme on Immunisation (EPI) is one of the most powerful and cost-effective public health programmes to improve child survival. We assessed challenges and enablers for the programme in South Africa, as we approach the 2015 deadline for the Millennium Development Goals. Methods: Between September 2009 and September 2010 we requested national and provincial EPI managers in South Africa to identify key challenges facing EPI, and to propose appropriate solutions. We collated their responses and searched for systematic reviews on the effectiveness of the proposed solutions; in the Health Systems Evidence, Cochrane Library, and PubMed electronic databases. We screened the search outputs, selected systematic reviews, extracted data, and assessed the quality of included reviews (using AMSTAR) and the quality of the evidence (using GRADE) in duplicate; resolving disagreements by discussion and consensus. Results: Challenges identified by EPI managers were linked to healthcare workers (insufficient knowledge of vaccines and immunisation), the public (anti-immunisation rumours and reluctance from parents), and health system (insufficient financial and human resources). Strategies proposed by managers to overcome the challenges include training, supervision, and audit and feedback; strengthening advocacy and social mobilisation; and sustainable EPI funding schemes, respectively. The findings from reliable systematic reviews indicate that interactive educational meetings, audit and feedback, and supportive supervision improve healthcare worker performance. Structured and interactive communication tools probably increase parents’ understanding of immunisation; and reminders and recall, use of community health workers, conditional cash transfers, and mass media interventions probably increase immunisation coverage. Finally, a national social health insurance scheme is a potential EPI financing mechanism; however, given the absence of high-quality evidence of effects, its implementation should be pilot-tested and the impacts and costs rigorously monitored. Conclusion: In line with the Millennium Development Goals, we have to ensure that our children’s right to health, development and survival is respected, protected and promoted. EPI is central to this vision. We found numerous promising strategies for improving EPI performance in South Africa. However, their implementation would need to be tailored to local circumstances and accompanied by high-quality monitoring and evaluation. The strength of our approach comes from having a strong framework for interventions before looking for systematic reviews. Without a framework, we would have been driven by what reviews have been done and what is easily researchable; rather than the values and preferences of key immunisation stakeholders

Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants

The development of effective immunoprophylaxis against tuberculosis (TB) remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG) vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR) variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S) was associated with increased BCG-induced IFN-γ in both discovery (n = 240) and validation (n = 240) cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S) and TLR6_G1083C (synonymous) were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2). After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes) secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the development of adaptive immune responses after in vivo vaccination against a bacterial pathogen in humans. These findings could potentially guide novel adjuvant vaccine strategies as well as have implications for IFN-γ-based diagnostic testing for TB

Utilisation of private general practitioners to provide caesarean deliveries in five rural district public hospitals in South Africa: a mixed-methods study

Objective Researching how public–private engagements may promote universal access to safe obstetric care including caesarean delivery is essential. The aim of this research was to document the utilisation of private general practitioners (GPs) contracted to provide caesarean delivery services in five rural district hospitals in the Western Cape, the profile and outcomes of caesarean deliveries. We also describe stakeholder experiences of these arrangements in order to inform potential models of public–private contracting for obstetric services.Design We used a mixed-methods study design to describe rural district hospitals’ utilisation of private GP contracting for caesarean deliveries. Between April 2021 and March 2022, we collated routine data from delivery and theatre registers to capture the profile of deliveries and maternal outcomes. We conducted 23 semistructured qualitative interviews with district managers, hospital-employed doctors and private GPs to explore their experiences of the contracting arrangements.Setting The study was conducted in five rural district hospitals in the Western Cape province, South Africa.Results The use of private GPs as surgeon or anaesthetist for caesarean deliveries differed widely across the hospitals. Overall, the utilisation of private GPs for anaesthetics was similar (29% of all caesarean deliveries) to the utilisation of private GPs as surgeons (33% of all caesarean deliveries). The proportion of caesarean deliveries undertaken by private GPs as the primary surgeon was inversely related to size of hospital and mean monthly deliveries. Adverse outcomes following a caesarean delivery were rare. Qualitative data provided insights into contributions made by private GPs and the contracting models, which did not incentivise overservicing.Conclusion The findings of this study suggest that private GPs can play an important role in filling gaps and expanding quality care in rural public facilities that have insufficient obstetric skills and expertise. Different approaches to enable access to safe caesarean delivery are needed for different contexts, and contracting with experienced private GP’s is one resource for rural district hospitals to consider