Cycles of antibiotic use and emergent antimicrobial resistance in the South African tuberculosis programme (1950-2021): A scoping review and critical reflections on stewardship.

The emergent threat of antimicrobial resistance (AMR) has resulted in debates around the use and preservation of effective antimicrobials. Concerns around AMR reflect a history of increasing dependence on antibiotics to address disease epidemics rooted in profound structural and systemic challenges. In the context of global health, this process, often referred to as pharmaceuticalisation, has commonly occurred within disease programmes, of which lessons are vital for adding nuance to conversations around antimicrobial stewardship. Tuberculosis (TB) is a notable example. A disease which accounts for one-third of AMR globally and remains the leading cause of death from a single infectious agent in many low - and middle-income countries, including South Africa. In this scoping review, we chart TB science in South Africa over 70 years of programming. We reviewed published manuscripts about the programme and critically reflected on the implications of our findings for stewardship. We identified cycles of programmatic responses to new drug availability and the emergence of drug resistance, which intersected with cycles of pharmaceuticalisation. These cycles reflect the political, economic, and social factors influencing programmatic decision-making. Our analysis offers a starting point for research exploring these cycles and drawing out implications for stewardship across the TB and AMR communities.

Beyond tuberculosis: a person-centred and rights-based approach to screening for household contacts.

Households affected by tuberculosis have syndemic vulnerability, reflecting a concentration of and interactions between multiple biomedical, psychosocial, and structural determinants of health. Traditional approaches to tuberculosis screening do not address pre-existing risks, such as undernutrition and other chronic conditions, or the indirect effects of tuberculosis, such as loss of livelihood. These pre-existing risks and consequences not only perpetuate the global tuberculosis epidemic but, for those affected, lead to poor health and deepen poverty. We propose reimagining tuberculosis screening as an opportunity to deliver a contextually relevant package of services that address the needs of households affected by tuberculosis. This approach puts people and their rights at the centre of efforts to end tuberculosis, and has equity at the core. This approach could support progress towards universal health coverage, benefiting communities and health systems. Leadership, flexibility in funding allocation, and innovative care models will be required to realise this approach at scale.

Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study.

With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centres for Diseases Prevention and Control proposed the '100-100-70%' strategy which aims to vaccinate all healthcare workers, all vulnerable groups, and 70% of the general population. Understanding whether healthcare workers were reached during previous vaccination campaigns and what can be done to address concerns, anxieties, and other influences on vaccine uptake, will be important to optimally plan how to achieve these ambitious targets. In this mixed-methods study, between June 2021 and July 2022 a quantitative survey was conducted with healthcare workers accessing a comprehensive health check in Zimbabwe to determine whether and, if so, when they had received a COVID-19 vaccine. Healthcare workers were categorized as those who had received the vaccine 'early' (before 30.06.2021) and those who had received it 'late' (after 30.06.2021). In addition, 17 in-depth interviews were conducted to understand perceptions and beliefs about COVID-19 vaccines. Of the 3,086 healthcare workers employed at 43 facilities who participated in the study, 2,986 (97%, 95% CI [92%-100%]) reported that they had received at least one vaccine dose. Geographical location, older age, higher educational attainment and having a chronic condition was associated with receiving the vaccine early. Qualitatively, (mis)information, infection risk perception, quasi-mandatory vaccination requirements, and legitimate concerns such as safety and efficacy influenced vaccine uptake. Meeting the proposed 100-100-70 target entails continued emphasis on strong communication while engaging meaningfully with healthcare workers' concerns. Mandatory vaccination may undermine trust and should not be a substitute for sustained engagement.

Household antibiotic use in Malawi: A cross-sectional survey from urban and peri-urban Blantyre.

Antimicrobial resistance (AMR) is a significant threat to public health. Use of antibiotics, particularly in contexts where weaker regulatory frameworks make informal access easier, has been identified as an important driver of AMR. However, knowledge is limited about the ways antibiotics are used in communities in Malawi and sub-Saharan Africa. Between April and July 2021, we undertook a cross-sectional survey of community antibiotic use practices in Blantyre, Malawi. We selected two densely-populated neighbourhoods (Chilomoni and Ndirande) and one peri-urban neighbourhood (Chileka) and undertook detailed interviews to assess current and recent antibiotic use, supported by the innovative "drug bag" methodology. Regression modelling investigated associations with patterns of antibiotic recognition. We interviewed 217 households with a total of 1051 household members. The number of antibiotics recognised was significantly lower among people with poorer formal health care access (people with unknown HIV status vs. HIV-negative, adjusted odds ratio [aOR]: 0.76, 95% CI: 0.77-.099) and amongst men (aOR: 0.83, 95% CI: 0.69-0.99), who are less likely to support healthcare-seeking for family members. Reported antibiotic use was mostly limited to a small number of antibiotics (amoxicillin, erythromycin and cotrimoxazole), with current antibiotic use reported by 67/1051 (6.4%) and recent use (last 6 months) by 440/1051 (41.9%). Our findings support the need for improved access to quality healthcare in urban and peri-urban African settings to promote appropriate antibiotic use and limit the development and spread of AMR.

The effect of a comprehensive typhoid conjugate vaccine campaign on antimicrobial prescribing in children in Harare, Zimbabwe: a mixed methods study.

BACKGROUND: Vaccines prevent infections and could subsequently reduce antimicrobial use. A 1-week mass vaccination campaign was done with Typbar-TCV (Bharat Biotech, Hyderabad, India) between Feb 25 and March 4, 2019. We investigated whether this typhoid conjugate vaccine campaign could affect antimicrobial prescribing in children presenting to primary care in Harare, Zimbabwe. METHODS: In this mixed methods study, data for acute paediatric outpatient consultations between Jan 1, 2018, and March 31, 2020, were collected from five clinics in Harare. Interrupted time series analysis was done to compare prescription data before and after the campaign. To contextualise findings, qualitative data were collected between April 20, 2021, and July 20, 2022, comprising ethnographic research (ie, workshops, surveys, observations, and interviews) in 14 clinics. Ethnographic data were used for thematic analysis. The primary outcome was monthly antimicrobial prescriptions in children aged 6 months to 15 years, normalised by the number of trauma events in all age groups. FINDINGS: In the data collection period, 27 107 paediatric consultations were recorded. 17 951 (66·2%) of 27 107 children were prescribed antimicrobials. Despite the perceived reduction in typhoid cases and a decreasing trend in the prescription of antimicrobials commonly used to treat typhoid (ie, ciprofloxacin and azithromycin), mass vaccination with Typbar-TCV did not affect the total rate of antimicrobials (adjusted rate ratio, 1·20, 95% CI 0·70-2·05, p=0·51) or the rate of typhoid antimicrobials prescribed (0·93, 0·44-1·96, p=0·85). Unsafe water sources and insufficient diagnostic services were reported to contribute to the continued disease burden and antimicrobial prescription. INTERPRETATION: Non-specific febrile illness caused by confirmed or suspected typhoid is a common cause of antimicrobial use in endemic areas. Although effective in preventing typhoid fever, we were unable to identify any effect of Typbar-TCV on antimicrobial prescribing. Ethnographic research showed the effect of contextual factors on antimicrobial prescribing, including concerns regarding safe water access, appropriate sewage disposal, health-care and diagnostic availability. To realise effects beyond disease burden reduction, holistic approaches addressing these concerns are needed so that the value of vaccines mitigating the effects of antimicrobial use as a driver of antimicrobial resistance is fully achieved. FUNDING: Wellcome Trust. TRANSLATION: For the Shona translation of the abstract see Supplementary Materials section.

Exploring COVID-19 vaccine uptake among healthcare workers in Zimbabwe: A mixed methods study.

With COVID-19 no longer categorized as a public health emergency of international concern, vaccination strategies and priority groups for vaccination have evolved. Africa Centers for Diseases Prevention and Control proposed the '100-100-70%' strategy which aims to vaccinate all healthcare workers, all vulnerable groups, and 70% of the general population. Understanding whether healthcare workers were reached during previous vaccination campaigns and what can be done to address concerns, anxieties, and other influences on vaccine uptake, will be important to optimally plan how to achieve these ambitious targets. In this mixed-methods study, between June 2021 and July 2022 a quantitative survey was conducted with healthcare workers accessing a comprehensive health check in Zimbabwe to determine whether and, if so, when they had received a COVID-19 vaccine. Healthcare workers were categorized as those who had received the vaccine 'early' (before 30.06.2021) and those who had received it 'late' (after 30.06.2021). In addition, 17 in-depth interviews were conducted to understand perceptions and beliefs about COVID-19 vaccines. Of the 2905 healthcare workers employed at 37 facilities who participated in the study, 2818 (97%, 95% CI [92%-102%]) reported that they had received at least one vaccine dose. Geographical location, older age, higher educational attainment and having a chronic condition was associated with receiving the vaccine early. Qualitatively, (mis)information, infection risk perception, quasi-mandatory vaccination requirements, and legitimate concerns such as safety and efficacy influenced vaccine uptake. Meeting the proposed 100-100-70 target entails continued emphasis on strong communication while engaging meaningfully with healthcare workers' concerns. Mandatory vaccination may undermine trust and should not be a substitute for sustained engagement.

Making morbidity multiple: History, legacies, and possibilities for global health.

Multimorbidity has been framed as a pressing global health challenge that exposes the limits of systems organised around single diseases. This article seeks to expand and strengthen current thinking around multimorbidity by analysing its construction within the field of global health. We suggest that the significance of multimorbidity lies not only in challenging divisions between disease categories but also in what it reveals about the culture and history of transnational biomedicine. Drawing on social research from sub-Saharan Africa to ground our arguments, we begin by describing the historical processes through which morbidity was made divisible in biomedicine and how the single disease became integral not only to disease control but to the extension of biopolitical power. Multimorbidity, we observe, is hoped to challenge single disease approaches but is assembled from the same problematic, historically-loaded categories that it exposes as breaking down. Next, we highlight the consequences of such classificatory legacies in everyday lives and suggest why frameworks and interventions to integrate care have tended to have limited traction in practice. Finally, we argue that efforts to align priorities and disciplines around a standardised biomedical definition of multimorbidity risks retracing the same steps. We call for transdisciplinary work across the field of global health around a more holistic, reflexive understanding of multimorbidity that foregrounds the culture and history of translocated biomedicine, the intractability of single disease thinking, and its often-adverse consequences in local worlds. We outline key domains within the architecture of global health where transformation is needed, including care delivery, medical training, the organisation of knowledge and expertise, global governance, and financing.

Antibiotics and the Biopolitics of Sex Work in Zimbabwe.

The advent of antibiotics transformed the global public health landscape, dramatically improving health outcomes. Drawing on historical and ethnographic research on sex work in Zimbabwe, we examine the role of antibiotics in the management of sexually transmitted infections among sex workers, from punitive colonial approaches to "empowerment"-based discourses. We illustrate how programs for sex workers, while valued by these women, are narrow, exclusionary, and enact a pharmaceuticalized form of governance that hangs on the efficacy of antibiotics. With antibiotics' efficacy under threat, we consider how latent colonial logics are in danger of being reactivated to control both infections and women.

Understanding antimicrobial resistance through the lens of antibiotic vulnerabilities in primary health care in rural Malawi.

The diminishing effectiveness of antimicrobials raises serious concerns for human health. While policy makers grapple to reduce the overuse of antimicrobial medicines to stem the rise of antimicrobial resistance, insufficient attention has been paid to how this applies to low-resource contexts. We provide an in-depth portrayal of antimicrobial prescribing at primary health care level in rural Chikwawa District, Malawi. Ethnographic fieldwork took place over 18 months (2018-2020). We surveyed 22 health facilities in the district, observed 1348 health worker-patient consultations, and carried out 49 in-depth interviews with staff and patients. Care was centred around provision of an antimicrobial. Amid chronic lack of essential medicines and other resources, clinic interactions were tightly scripted, providing patients little time to question or negotiate their treatment. We develop the concept of 'antibiotic vulnerabilities' to reveal multiple ways in which provision of antimicrobials in rural Malawi impacts care in conditions of extreme scarcity. Antibiotics are central and essential to primary care. As targets for optimal antimicrobial prescribing take a more central role in global policy, close attention is required of the ramifications for the delivery of care to ensure that efforts to stem resistance do not undermine the goal of improved health for all.

Understanding antimicrobial use in subsistence farmers in Chikwawa District Malawi, implications for public awareness campaigns.

Drug resistant infections are increasing across the world and urgent action is required to preserve current classes of antibiotics. Antibiotic use practices in low-and-middle-income countries have gained international attention, especially as antibiotics are often accessed beyond the formal health system. Public awareness campaigns have gained popularity, often conceptualising antimicrobial resistance (AMR) as a problem of excess, precipitated by irrational behaviour. Insufficient attention has been paid to people's lived experiences of accessing medicines in low-income contexts. In Chikwawa District, Malawi, a place of extreme scarcity, our study aimed to understand the care and medicine use practices of households dependent on subsistence farming. Adopting an anthropological approach, we undertook medicine interviews (100), ethnographic fieldwork (six-month period) and key informant interviews (33) with a range of participants in two villages in rural Chikwawa. The most frequently used drugs were cotrimoxazole and amoxicillin, not considered to be of critical importance to human health. Participants recognised that keeping, sharing, and buying medicines informally was not the "right thing." However, they described using antibiotics and other medicines in these ways due to conditions of extreme precarity, the costs and limitations of seeking formal care in the public sector, and the inevitability of future illness. Our findings emphasise the need in contexts of extreme scarcity to equip policy actors with interventions to address AMR through strengthening health systems, rather than public awareness campaigns that foreground overuse and the dangers of using antibiotics beyond the formal sector.

Antibiotic stories: a mixed-methods, multi-country analysis of household antibiotic use in Malawi, Uganda and Zimbabwe.

BACKGROUND: As concerns about the prevalence of infections that are resistant to available antibiotics increase, attention has turned toward the use of these medicines both within and outside of formal healthcare settings. Much of what is known about use beyond formal settings is informed by survey-based research. Few studies to date have used comparative, mixed-methods approaches to render visible patterns of use within and between settings as well as wider points of context shaping these patterns. DESIGN: This article analyses findings from mixed-methods anthropological studies of antibiotic use in a range of rural and urban settings in Zimbabwe, Malawi and Uganda between 2018 and 2020. All used a 'drug bag' survey tool to capture the frequency and types of antibiotics used among 1811 households. We then undertook observations and interviews in residential settings, with health providers and key stakeholders to better understand the stories behind the most-used antibiotics. RESULTS: The most self-reported 'frequently used' antibiotics across settings were amoxicillin, cotrimoxazole and metronidazole. The stories behind their use varied between settings, reflecting differences in the configuration of health systems and antibiotic supplies. At the same time, these stories reveal cross-cutting features and omissions of contemporary global health programming that shape the contours of antibiotic (over)use at national and local levels. CONCLUSIONS: Our findings challenge the predominant focus of stewardship frameworks on the practices of antibiotic end users. We suggest future interventions could consider systems-rather than individuals-as stewards of antibiotics, reducing the need to rely on these medicines to fix other issues of inequity, productivity and security.

Antibiotics, rational drug use and the architecture of global health in Zimbabwe.

Rising concerns around antimicrobial resistance (AMR) have led to a renewed push to rationalise antibiotic prescribing in low- and middle-income countries (LMICs). There is increasing unease in conceptualising antibiotic use as individuals behaving '(ir)rationally' and recognition that rising use is emergent of and contributing to wider economic and political challenges. But in between these individual and societal 'drivers' of antibiotic use is an everyday articulation of care through these substances, written-in to the scripts, delivery chains and pedagogics of global healthcare. This article focuses on this everyday 'architecture' that over time and across spaces has knitted-in antibiotics and rhetorics of control that inform current responses to AMR. Based on historically informed ethnographic research in Zimbabwe, we examine points of continuity and change between 20th Century rational drug use (RDU) discourses and contemporary socio-political formations around AMR and antimicrobial stewardship (AMS), paying particular attention to their co-evolution with the process of pharmaceuticalisation. We illustrate how the framework and techniques of RDU were embedded within programmes to increase access to essential medicines and as such complemented the building of one of Africa's strongest postcolonial health systems in Zimbabwe. Whilst 20th Century RDU was focused on securing the health and safety of patients and affordability for systems, AMS programmes aim to secure medicines. Continuous through both RDU and AMS programmes is the persistent rhetoric of 'irrational use'. Health workers in Harare, attuned to the values and language of these programmes, enact in their everyday practice an architecture in which antibiotics have been designed-in. This research illustrates the struggle to optimise antibiotic use within current framings for action. We propose a reconfiguring of the architecture of global health such that frontline prescribers are able to provide 'good' care without necessarily turning to antibiotics. To design-out antibiotic reliance would require attention beyond '(ir)rationality', to the redrafting of blueprints that inscribe practice.

Knowledge, attitudes and practices relating to antibiotic use and resistance among prescribers from public primary healthcare facilities in Harare, Zimbabwe.

Background Overuse of antibiotics is one of the main drivers for antimicrobial resistance (AMR). Globally, most antibiotics are prescribed in the outpatient setting. This survey aimed to explore attitudes and practices with regards to microbiology tests, AMR and antibiotic prescribing among healthcare providers at public primary health clinics in Harare, Zimbabwe. Methods This cross-sectional survey was conducted in nine primary health clinics located in low-income suburbs of Harare between October and December 2020. In Zimbabwe, primary health clinics provide nurse-led outpatient care for acute and chronic illnesses. Healthcare providers who independently prescribe antibiotics and order diagnostic tests were invited to participate. The survey used self-administered questionnaires. A five-point Likert scale was used to determine attitudes and beliefs. Results A total of 91 healthcare providers agreed to participate in the survey. The majority of participants (62/91, 68%) had more than 10 years of work experience. Most participants reported that they consider AMR as a global (75/91, 82%) and/or national (81/91, 89%) problem, while 52/91 (57%) considered AMR to be a problem in their healthcare facilities. A fifth of participants (20/91, 22%) were unsure if AMR was a problem in their clinics. Participants felt that availability of national guidelines (89/89, 100%), training sessions on antibiotic prescribing (89/89, 100%) and regular audit and feedback on prescribing (82/88, 93%) were helpful interventions to improve prescribing. Conclusions These findings support the need for increased availability of data on AMR and antibiotic use in primary care. Educational interventions, regular audit and feedback, and access to practice guidelines may be useful to limit overuse of antibiotics.

The 'Drug Bag' method: lessons from anthropological studies of antibiotic use in Africa and South-East Asia.

Understanding the prevalence and types of antibiotics used in a given human and/or animal population is important for informing stewardship strategies. Methods used to capture such data often rely on verbal elicitation of reported use that tend to assume shared medical terminology. Studies have shown the category 'antibiotic' does not translate well linguistically or conceptually, which limits the accuracy of these reports. This article presents a 'Drug Bag' method to study antibiotic use (ABU) in households and on farms, which involves using physical samples of all the antibiotics available within a given study site. We present the conceptual underpinnings of the method, and our experiences of using this method to produce data about antibiotic recognition, use and accessibility in the context of anthropological research in Africa and South-East Asia. We illustrate the kinds of qualitative and quantitative data the method can produce, comparing and contrasting our experiences in different settings. The Drug Bag method produce accurate antibiotic use data as well as provide a talking point for participants to discuss antibiotic experiences. We propose it can help improve our understanding of antibiotic use in peoples' everyday lives across different contexts, and our reflections add to a growing conversation around methods to study ABU beyond prescriber settings, where data gaps are currently substantial.

Clean Blood, Religion, and Moral Triage in Tuberculosis Vaccine Trials.

During ethnographic research at a tuberculosis vaccine trial site in South Africa, trial participants often evoked the idiom of "clean blood." In this article, we illustrate how the trials enacted a form of moral triage in which "objective" bioscientific knowledge and moral subjectivity were coproduced. Participation created possibilities to demonstrate healthiness, respectability, and godliness in a context where positive self-imaginings were hard won, but could also lead to dejection and shame. We suggest that struggles to be recognized as virtuous are often overlooked in anthropological critiques of clinical trials and bioethics, but are important for understanding how trials meld with local moral worlds.

Witnesses in action: the effect of physical exertion on recall and recognition.

Understanding memory performance under different operational conditions is critical in many occupational settings. To examine the effect of physical exertion on memory for a witnessed event, we placed two groups of law-enforcement officers in a live, occupationally relevant scenario. One group had previously completed a high-intensity physical-assault exercise, and the other had not. Participants who completed the assault exercise showed impaired recall and recognition performance compared with the control group. Specifically, they provided significantly less accurate information concerning critical and incidental target individuals encountered during the scenario, recalled less briefing information, and provided fewer briefing updates than control participants did. Exertion was also associated with reduced accuracy in identifying the critical target from a lineup. These results support arousal-based competition accounts proposing differential allocation of resources under physiological arousal. These novel findings relating to eyewitness memory performance have important implications for victims, ordinary citizens who become witnesses, and witnesses in policing, military, and related operational contexts.

Differentiation associated changes in gene expression profiles of interstitial cystitis and control urothelial cells.

PURPOSE: We evaluated gene expression profiles after inducing differentiation in cultured interstitial cystitis and control urothelial cells. MATERIALS AND METHODS: Bladder biopsies were taken from patients with interstitial cystitis and controls, that is women undergoing surgery for stress incontinence. Primary cultures were grown in keratinocyte growth medium with supplements. To induce differentiation in some plates the medium was changed to Dulbecco's modified Eagle's minimal essential medium-F12 (Media Tech, Herndon, Virginia) with supplements. RNA was analyzed with Affymetrix(R) chips. Three patients with nonulcerative interstitial cystitis were compared with 3 controls. RESULTS: After inducing differentiation 302 genes with a described function were altered at least 3-fold in interstitial cystitis and control cells (p <0.01). Functions of the 162 up-regulated genes included cell adhesion (eg claudins, occludin and cingulin), urothelial differentiation, the retinoic acid pathway and keratinocyte differentiation (eg skin cornified envelope components). The 140 down-regulated transcripts included genes associated with basal urothelium (eg p63, integrins beta4, alpha5 and alpha6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins, and members of the Wnt and Notch pathways. When comparing interstitial cystitis control cells after differentiation, only 7 genes with a described function were altered at least 3-fold (p <0.01). PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased, and AKR1C2 and MKNK1 were increased in interstitial cystitis cases. CONCLUSIONS: Differentiation associated changes occurred in interstitial cystitis and control cells. Comparing interstitial cystitis vs control cases revealed few differences. This study may have included patients with interstitial cystitis and minimal urothelial deficiency, and/or we may have selected cells that were most robust in culture. Also, the abnormal urothelium in interstitial cystitis cases may be due to post-translational changes and/or to the bladder environment.