The University of Stellenbosch

Core Research Competencies

Clinical trials

The Desmond Tutu TB Centre (DTTC) has extensive experience in conducting individual-level randomized control trials (RCTs) and community randomized trials. The majority of these trials are conducted from well-established community research sites in the Western Cape Province. Focus areas for RCTs include; Therapeutics for drug-susceptible and drug-resistant TB in children; Preventive trials for TB in children, Diagnostics, biomarkers and lung health in children with TB, and HIV prevention interventions in adults. The DTTC has successfully completed two unique large-scale community based trials evaluating community-based interventions for TB and HIV prevention: ZAMSTAR (The Zambia South Africa TB and HIV Reduction study) and HPTN 071- Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART).

Socio-behavioural Sciences

The socio-behavioural science team are disciplinarily diverse – with training in psychology, sociology, anthropology, health and development studies, and political science. The SBS team is built around postgraduate students implementing nested, sub-, or ancillary studies to existing DTTC protocols to supplement clinical/epidemiological understanding. To achieve this, socio-behavioural science team priorities are organised to mirror the DTTC’s strategy house and provide core input across the DTTC scientific agenda. The SBS group focuses on method innovation and rigour – including the development of an innovated ‘qualitative cohort’ design to understand patient experiences holistically – and on theory-generative research on health in social context. In addition, the socio-behavioural science team are leading research at the DTTC on health behaviour theory, child-patient and caregiver acceptability of TB care, and inclusivity in health service access.

Community Engagement and Advocacy

The DTTC strongly believes in the underlying principle of research, “with communities, for communities”. Their partnership with communities is underpinned by the institutional community advisory board (CAB), established in 2015 to manage an expanding research agenda and the community-level footprint at the DTTC. Prior to this, community engagement had included study-specific CABs and activities nested in the Clinical Trials Unit structures. The CAB members are passionate, highly-skilled volunteers who guide the DTTC’s research staff through the many complexities of studies with vulnerable people affected by TB and HIV. The community of health services are a key collaborator with the DTTC in implementing a strategic agenda with and for communities. To continue this collaboration, the DTTC hosts a monthly TB clinical forum convened by the Department of Health and manages an operational research assistance programme for health services staff learning to conduct research. Community engagement between communities affected by TB/HIV and health service stakeholders is the solid foundation that the DTTC mobilises to advocate at local, national, and international platforms – using highest quality science interpreted with complexity.

Policy Transfer

The DTTC is committed to ensuring that research findings are effectively disseminated throughout South Africa and globally, through active participation in conferences, workshops and publication of research in peer reviewed journals. DTTC researchers also maximize opportunities to conduct high impact research through close collaborate with provincial and national departments of health, a multitude of implementing partners (non-governmental organizations, advocacy groups and other civil society organizations) and more than 15 international research organisations. The DTTC is also well represented on national and international HIV and TB committees, such as the South African National TB Think Tank, the National TB Consortium and the World Health Organisation; assisting to guide national and global policy.

Health Systems strengthening

Health systems research recognises the complex path of policy implementation and seeks to understand how a health system functions. At the DTTC, we develop and implement projects that take into account the context of the existing health system. We work with health care providers, patients and communities to understand the impact of these interventions from varied perspectives. We seek to develop projects that utilise a variety of research methodologies and work with local, provincial, national and international collaborators. We aim to develop and test ideas within the existing health system and measure the resultant impact of these changes on the broader health system.

Management and analysis of large data sets

The data centre directs all data-related aspects at the DTTC. The team provides support to multiple structures, including the HIV Prevention Trials Network (HPTN), the International Maternal, Paediatric, Adolescent AIDS Clinical Trials (IMPAACT) group, and to the various paediatric, operational and HIV-prevention studies conducted at the Centre. The team has extensive experience in the full lifecycle of research data; from the initiation of research projects through to the final stages of analysis. The data centre manages a number of systems to support studies and the team specialises in the management, storage and restructuring large datasets, including the National Department of Health Electronic Tuberculosis Register (ETR) and the Electronic Drug-Resistant Tuberculosis Register (EDR). We are skilled in various statistical methods and we have expertise in knowledge extraction from both structured and unstructured data through data restructuring and analysis. We also have experience in Geographic Information Systems (GIS), used to expand the knowledgebase of studies and to effectively manage community based research.

Epidemiological analysis and mathematical modelling

At the DTTC, we specialise in the mathematical modelling of tuberculosis (TB) and HIV in populations and the population-level impact of specific control interventions. Established in 2018, the DTTC Working Group for Data Analysis and Modelling (WGDAM) aims at building and strengthening capacity for mathematical modelling of TB and HIV at Stellenbosch University in collaboration with other research groups and public health specialists in South Africa. The working group members have backgrounds in medicine, epidemiology and public health, mathematics, data management and statistics. A strategic TB modelling partnership and research programme between the DTTC and the Department of Science and Technology – National Research Foundation (DST-NRF) South African Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA) is in preparation. This novel initiative is intended to provide a platform for mathematical modelling and intervention research to inform decision making towards effective and cost-effective TB control interventions in South Africa, the African continent, and globally.

Biostatistics

Biostatistics at the DTTC comprises of a combination of epidemiological and statistical data analyses. In particular, the team provides epidemiological, statistical and methodological support to various studies at DTTC and collaborates in joint research projects with external researchers. The research areas where the team is involved include, among others, the evaluation of community-based HIV and TB Testing Services, TB transmission within households, and socioeconomic drivers of the HIV/TB epidemic in South Africa.

Pharmacokinetics

The pharmacokinetics (PK) at the DTTC platform focuses on the study of antituberculosis medications in children for prevention and treatment of drug-susceptible and drug-resistant TB. The PK team is leading the design of multiple observational PK studies as well as phase I and II trials in children, and contributes an in-depth knowledge of trial design, pharmacokinetics, acceptability/palatability assessments, and clinical management of paediatric TB. The team has extensive experience with implementing these specialised studies at the state-of-the-art paediatric TB PK unit at the Brooklyn Hospital for Chest Diseases (BHCD), adjacent to the routine paediatric wards at BHCD. This unique six-bed research facility is a satellite site of the DTTC with a staff complement of 25 research personnel. It is specifically designed, equipped and staffed to be able to perform highly technical PK studies, and is uniquely positioned to engage and serve children with TB and multidrug-resistant TB. The PK team is committed to improving the treatment of TB in children with local, national and international collaborators, through high quality clinical research, translation of research findings into policy, and advocacy.

TB Diagnostics and Biomarkers

As part of its diagnostic and biomarker research, the DTTC aims to evaluate different approaches to improve the diagnosis of tuberculosis in children; novel diagnostic biomarkers of active TB and; predictive biomarkers of active TB following infection, response to treatment and recurrent TB. These novel strategies are evaluated both within diagnostic cohort studies and as nested questions in treatment trials. DTTC has a well-developed biorepository of clinical specimens which will be used to evaluate both diagnostic and predictive biomarkers. Recent work has focused on the evaluation of stool as an alternative and more feasible specimen for TB testing in young children, which has shown promising results. Work is ongoing to assess the diagnostic and predictive potential of different serum and urine biomarker signatures in children, using different study designs. This work is supported by both local and international collaborations and grants.

Lung Health

At the DTTC, we evaluate the impact of TB and other respiratory diseases on lung health by looking at the co-infections, lung function measurements and quality of life. We are investigating the role of co-infections on the pathogenesis, clinical presentation and morbidity of TB. This includes viral, bacterial and fungal pathogens in both respiratory and blood compartments. In addition, there is ongoing research on the respiratory and gastro-intestinal microbiome. Lung function and lung function tracking is investigated in children with TB and other respiratory diseases to evaluate functional outcomes in these children. In collaboration with the sociobehavioural science team, we are investigating the impact of respiratory diseases on quality of life in our setting. This work is supported by both local and international collaborations and grants.