Burden of bacterial antimicrobial resistance in low-income and middle-income countries avertible by existing interventions: an evidence review and modelling analysis.

National action plans enumerate many interventions as potential strategies to reduce the burden of bacterial antimicrobial resistance (AMR). However, knowledge of the benefits achievable by specific approaches is needed to inform policy making, especially in low-income and middle-income countries (LMICs) with substantial AMR burden and low health-care system capacity. In a modelling analysis, we estimated that improving infection prevention and control programmes in LMIC health-care settings could prevent at least 337 000 (95% CI 250 200-465 200) AMR-associated deaths annually. Ensuring universal access to high-quality water, sanitation, and hygiene services would prevent 247 800 (160 000-337 800) AMR-associated deaths and paediatric vaccines 181 500 (153 400-206 800) AMR-associated deaths, from both direct prevention of resistant infections and reductions in antibiotic consumption. These estimates translate to prevention of 7·8% (5·6-11·0) of all AMR-associated mortality in LMICs by infection prevention and control, 5·7% (3·7-8·0) by water, sanitation, and hygiene, and 4·2% (3·4-5·1) by vaccination interventions. Despite the continuing need for research and innovation to overcome limitations of existing approaches, our findings indicate that reducing global AMR burden by 10% by the year 2030 is achievable with existing interventions. Our results should guide investments in public health interventions with the greatest potential to reduce AMR burden.

"Arming half-baked people with weapons!" Information enclaving among professionals and the need for a care-centred model for antibiotic use information in Uganda, Tanzania and Malawi.

BACKGROUND: The overuse of antimicrobial medicines is a global health concern, including as a major driver of antimicrobial resistance. In many low- and middle-income countries, a substantial proportion of antibiotics are purchased over-the-counter without a prescription. But while antibiotics are widely available, information on when and how to use them is not. OBJECTIVE: We aimed to understand the acceptability among experts and professionals of sharing information on antibiotic use with end users - patients, carers and farmers - in Uganda, Tanzania and Malawi. METHODS: Building on extended periods of fieldwork amongst end-users and antibiotic providers in the three countries, we conducted two workshops in each, with a total of 44 medical and veterinary professionals, policy makers and drug regulators, in December 2021. We carried out extensive documentary and literature reviews to characterise antibiotic information systems in each setting. RESULTS: Participants reported that the general public had been provided information on medicine use in all three countries by national drug authorities, health care providers and in package inserts. Participants expressed concern over the danger of sharing detailed information on antibiotic use, particularly that end-users are not equipped to determine appropriate use of medicines. Sharing of general instructions to encourage professionally-prescribed practices was preferred. CONCLUSIONS: Without good access to prescribers, the tension between enclaving and sharing of knowledge presents an equity issue. Transitioning to a client care-centred model that begins with the needs of the patient, carer or farmer will require sharing unbiased antibiotic information at the point of care.

Biosecurity and water, sanitation, and hygiene (WASH) interventions in animal agricultural settings for reducing infection burden, antibiotic use, and antibiotic resistance: a One Health systematic review.

Prevention and control of infections across the One Health spectrum is essential for improving antibiotic use and addressing the emergence and spread of antibiotic resistance. Evidence for how best to manage these risks in agricultural communities-45% of households globally-has not been systematically assembled. This systematic review identifies and summarises evidence from on-farm biosecurity and water, sanitation, and hygiene (WASH) interventions with the potential to directly or indirectly reduce infections and antibiotic resistance in animal agricultural settings. We searched 17 scientific databases (including Web of Science, PubMed, and regional databases) and grey literature from database inception to Dec 31, 2019 for articles that assessed biosecurity or WASH interventions measuring our outcomes of interest; namely, infection burden, microbial loads, antibiotic use, and antibiotic resistance in animals, humans, or the environment. Risk of bias was assessed with the Systematic Review Centre for Laboratory Animal Experimentation tool, Risk of Bias in Non-Randomized Studies of Interventions, and the Appraisal tool for Cross-Sectional Studies, although no studies were excluded as a result. Due to the heterogeneity of interventions found, we conducted a narrative synthesis. The protocol was pre-registered with PROSPERO (CRD42020162345). Of the 20 672 publications screened, 104 were included in this systematic review. 64 studies were conducted in high-income countries, 24 studies in upper-middle-income countries, 13 studies in lower-middle-income countries, two in low-income countries, and one included both upper-middle-income countries and lower-middle-income countries. 48 interventions focused on livestock (mainly pigs), 43 poultry (mainly chickens), one on livestock and poultry, and 12 on aquaculture farms. 68 of 104 interventions took place on intensive farms, 22 in experimental settings, and ten in smallholder or subsistence farms. Positive outcomes were reported for ten of 23 water studies, 17 of 35 hygiene studies, 15 of 24 sanitation studies, all three air-quality studies, and 11 of 17 other biosecurity-related interventions. In total, 18 of 26 studies reported reduced infection or diseases, 37 of 71 studies reported reduced microbial loads, four of five studies reported reduced antibiotic use, and seven of 20 studies reported reduced antibiotic resistance. Overall, risk of bias was high in 28 of 57 studies with positive interventions and 17 of 30 studies with negative or neutral interventions. Farm-management interventions successfully reduced antibiotic use by up to 57%. Manure-oriented interventions reduced antibiotic resistance genes or antibiotic-resistant bacteria in animal waste by up to 99%. This systematic review highlights the challenges of preventing and controlling infections and antimicrobial resistance, even in well resourced agricultural settings. Most of the evidence emerges from studies that focus on the farm itself, rather than targeting agricultural communities or the broader social, economic, and policy environment that could affect their outcomes. WASH and biosecurity interventions could complement each other when addressing antimicrobial resistance in the human, animal, and environmental interface.

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.

Awareness of antibiotic resistance: a tool for measurement among human and animal health care professionals in LMICs and UMICs.

BACKGROUND: Raising awareness of antimicrobial resistance is a cornerstone of action plans to tackle this global One Health challenge. Tools that can reliably assess levels of awareness of antibiotic resistance (ABR) among human or animal healthcare professionals (HCPs) are required to guide and evaluate interventions. METHODS: We designed and tested an ABR awareness scale, a self-administered questionnaire completed by human and animal HCPs trained to prescribe and dispense antibiotics in six countries-Ghana, Nigeria, Tanzania, Vietnam, Thailand and Peru. Questionnaires also elicited demographic, practice, and contextual information. Psychometric analysis for the scale followed Rasch Measurement Theory. Bivariate analysis was carried out to identify factors associated with awareness scores. RESULTS: Overall, 941 HCPs (625 human and 316 animal) from Ghana, Nigeria, Tanzania, Vietnam, Thailand and Peru were included in the study. The 23-item ABR awareness scale had high-reliability coefficients (0.88 for human and 0.90 for animal HCPs) but performed better within countries than across countries. Median ABR awareness scores were 54.6-63.5 for human HCPs and 55.2-63.8 for animal HCPs (scale of 0-100). Physicians and veterinarians scored higher than other HCPs in every country tested. HCPs in this study reported working in contexts with limited laboratory infrastructures. More than 95% of HCPs were interested in receiving information or training on ABR and antimicrobial stewardship. CONCLUSION: HCPs' awareness of ABR can be reliably assessed with this validated 23-item scale within the countries tested. Using the scale alongside context questions and objective measurement of practices is recommended to inform interventions to improve antibiotic use.

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.

Mystifying medicines and maximising profit: Antibiotic distribution in community pharmacies in Thailand.

Thailand's antimicrobial stewardship strategy has focussed on promoting 'rational drug use' in the public sector, to reduce the threat of drug resistance and control healthcare expenditure. The strategy's next ambition is to attend to the private sector, where antibiotics are widely available over the counter without prescription. Using ethnographic and survey data, this paper follows antibiotics through community pharmacies, to explore drug distribution and access, and identify potential challenges for stewardship. We extend the analytical frame beyond 'irrational' dispenser-customer transactions, to explore the logics of practice of a multiplicity of actors in the context of a highly competitive pharmaceutical market. Highlighting the role of the pharmaceutical industry in mystifying medicines, we show how antibiotics are collapsed into a category of 'strong medicines' and requested by customers using 'prescriptions by proxy'. We further examine how Thailand's drug regulation and classificatory systems, historically orientated around access to medicines, enable the proliferation of antibiotics in the context of contemporary efforts to control distribution. Recognising the negotiations involved in dispensing antibiotics in a pluralistic health system, we attempt to reconfigure allocations of responsibility, advocating for stewardship approaches that take into account local ecologies of care, as well as implications for access, equity, and accountability.

Reconciling imperatives: Clinical guidelines, antibiotic prescribing and the enactment of good care in lower-level health facilities in Tororo, Uganda.

Faced with the threat of antimicrobial resistance, health workers are urged to reduce unnecessary prescription of antimicrobials. Clinical guidelines are expected to form the basis of prescribing decisions in practice. Emerging through evaluations of best practice - bundling clinical, technological and economic dimensions - guidelines also create benchmarks through which practice can be assessed with metrics. To understand the relationships between guidelines and practice in the prescribing and dispensing of antibiotics, ethnographic fieldwork was undertaken in lower-level health care facilities in rural Eastern Uganda for 10 months between January and October 2020, involving direct observations during and outside of clinics and interviews with staff. In a context of scarcity, where 'care' is characterised by delivery of medicines, and is constituted beyond algorithmic outputs, we observed that clinical practice was shaped by availability of resources, and professional and patient expectations, as much as by the clinical guidelines. For stewardship to care for patients as well as for medicines, a better understanding of clinical practice and expectations of care is required in relation to and beyond clinical guidelines.

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.

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.

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.

Understanding Antibiotic Use in Companion Animals: A Literature Review Identifying Avenues for Future Efforts.

Addressing antibiotic use is essential to tackle antimicrobial resistance, a major human and animal health challenge. This review seeks to inform stewardship efforts in companion animals by collating research insights regarding antibiotic use in this group and identifying overlooked avenues for future research and stewardship efforts. The development of population-based methods has established that antibiotics are frequently used in companion animal care. Research insights are also contributing toward an in-depth comprehension of the contexts to antibiotic use. Qualitative approaches, for example, have enabled a nuanced understanding in four key areas: interactions with owners, clinical and financial risk management, time pressures, and clinic dynamics. This review identifies that much of the existing research frames antibiotic use as the result of choices made by the individuals at the interface of their use. Future research and policy endeavours could look beyond the moment of prescribing to consider the societal structures and networks in which companion animal antibiotic use is entangled. A diversification in research approaches and frameworks through which antibiotic use is understood will facilitate the identification of additional targets for stewardship initiatives beyond providing information and awareness campaigns.

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.

What drives antimicrobial prescribing for companion animals? A mixed-methods study of UK veterinary clinics.

Antimicrobial use in companion animals is a largely overlooked contributor to the complex problem of antimicrobial resistance. Humans and companion animals share living spaces and some classes of antimicrobials, including those categorised as Highest Priority Critically Important Antimicrobials (HPCIAs). Veterinary guidelines recommend that these agents are not used as routine first line treatment and their frequent deployment could offer a surrogate measure of 'inappropriate' antimicrobial use. Anthropological methods provide a complementary means to understand how medicines use makes sense 'on-the-ground' and situated in the broader social context. This mixed-methods study sought to investigate antimicrobial use in companion animals whilst considering the organisational context in which increasing numbers of veterinarians work. Its aims were to i) to epidemiologically analyse the variation in the percentage of antimicrobial events comprising of HPCIAs in companion animal dogs attending UK clinics belonging to large veterinary groups and, ii) to analyse how the organisational structure of companion animal practice influences antimicrobial use, based on insight gained from anthropological fieldwork. A VetCompassTM dataset composed of 468,665 antimicrobial dispensing events in 240,998 dogs from June 2012 to June 2014 was analysed. A hierarchical model for HPCIA usage was built using a backwards elimination approach with clinic and dog identity numbers included as random effects, whilst veterinary group, age quartile, breed and clinic region were included as fixed effects. The largest odds ratio of an antimicrobial event comprising of a HPCIA by veterinary group was 7.34 (95% confidence interval 5.14 - 10.49), compared to the lowest group (p < 0.001). Intraclass correlation was more strongly clustered at dog (0.710, 95% confidence interval 0.701 - 0.719) than clinic level (0.089, 95% confidence interval 0.076 -0.104). This suggests that veterinarians working in the same clinic do not automatically share ways of working with antimicrobials. Fieldwork revealed how the structure of the companion animal veterinary sector was more fluid than that depicted in the statistical model, and identified opportunities and challenges regarding altering antimicrobial use. These findings were organised into the following themes: "Highest priority what?"; "He's just not himself"; "Oh no - here comes the antibiotics police"; "We're like ships that pass in the night"; and "There's not enough hours in the day". This rigorous mixed-methods study demonstrates the importance of working across disciplinary silos when tackling the complex problem of antimicrobial resistance. The findings can help inform the design of sustainable stewardship schemes for the companion animal veterinary sector.

Setting the standard: multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy.

There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an 'implementation gap'. At a policy level, the design of internationally salient solutions that are able to address AMR's interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise 'good' antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scales.