A historical and ethnographic study of efforts to preserve the efficacy of antitubercular and other antibiotics in South Africa

Antimicrobial Resistance (AMR) is a critical threat to global health. Infections that rely on antimicrobials for treatment are becoming increasingly challenging to cure due to the (mis)use of antibiotics and increased primary transmission of AMR. Given AMR's pervasiveness, academics, public health officials, and governments have established specific programmes and attendant discourses to 'steward' medications. Whilst stewardship remains a recent addition to public health vocabulary, efforts to preserve the efficacy of drugs can be found in the discourses, practices, and histories of numerous global health efforts. Tuberculosis (TB), making up one-third of AMR statistics, is an example of this. This thesis, through a multidisciplinary lens that merges perspectives from anthropology and history, aims to provide insights that can enhance future interventions' effectiveness in combating TB and AMR. To do so, it explores the tensions between AMR efforts and TB programming within the context of South Africa, examining how efforts to preserve the efficacy of antituberculosis drugs have been managed. This is done through four objectives, which are presented in paper style. The first manuscript reviews the literature on the management of TB and resistance within South African TB programme over a 70-year period, beginning with the advent of effective antitubercular chemotherapy in the 1950s. Focusing on treatment evolution and implementation practices, my findings show how South Africa is caught in a cycle of decision-making around antibiotics that is driven by emergent resistance, and led to a deepening reliance on pharmaceuticals. The second manuscript builds upon these findings and further explores the socio-historical factors that led to South Africa entering into this recurrent pattern. Using archival materials to examine apartheid’s legacy on TB strategies, the findings of this paper demonstrate how segregationist policies and the neglect of social determinants of health exacerbated the spread of TB and 3 entrenched the disease within vulnerable communities that still contend with the consequences today. The third manuscript examines a more recent history and highlights the tensions between AMR stewardship imperatives and the immediate demands of DR-TB treatment. Through ethnographic and semi-structured interviews, TB control and containment experts describe the exciting yet controversial period when Bedaquiline (BDQ) became accessible. BDQ, the first novel class of antitubercular treatments to arrive in over 40 years, sparked debates over the safety, efficacy, and ethical considerations of making the drug widely accessible. The final manuscript situates TB and stewardship debates within the broader context of AMR policy in South Africa. It examines how global health frameworks influence the implementation of these policies within LMICS and shows, ultimately, that there is a disconnect between global AMR directives and the local realities in which they are implemented. In turn, I argue that these implementation gaps are a product of more than just “on-the-ground challenges” in LMICs, as they are so often framed. Ultimately, this research concludes that a more nuanced approach to AMR stewardship is required – one that not only considers the immediate demands of treating drug-resistant TB but also addresses the long-term sustainability of antibiotic efficacy. It presents novel perspectives on pharmaceutical-reliant interventions and considers the broader implications for vulnerable populations, 'vulnerable' drugs, and the future of disease management.