Exploring Models for an International Legal Agreement on the Global Antimicrobial Commons: Lessons from Climate Agreements.

An international legal agreement governing the global antimicrobial commons would represent the strongest commitment mechanism for achieving collective action on antimicrobial resistance (AMR). Since AMR has important similarities to climate change-both are common pool resource challenges that require massive, long-term political commitments-the first article in this special issue draws lessons from various climate agreements that could be applicable for developing a grand bargain on AMR. We consider the similarities and differences between the Paris Climate Agreement and current governance structures for AMR, and identify the merits and challenges associated with different international forums for developing a long-term international agreement on AMR. To be effective, fair, and feasible, an enduring legal agreement on AMR will require a combination of universal, differentiated, and individualized requirements, nationally determined contributions that are regularly reviewed and ratcheted up in level of ambition, a regular independent scientific stocktake to support evidence informed policymaking, and a concrete global goal to rally support.

Governing the Global Antimicrobial Commons: Introduction to Special Issue.

Antimicrobial resistance is one of the greatest public health crises of our time. The natural biological process that causes microbes to become resistant to antimicrobial drugs presents a complex social challenge requiring more effective and sustainable management of the global antimicrobial commons-the common pool of effective antimicrobials. This special issue of Health Care Analysis explores the potential of two legal approaches-one long-term and one short-term-for managing the antimicrobial commons. The first article explores the lessons for antimicrobial resistance that can be learned from recent climate change agreements, and the second article explores how existing international laws can be adapted to better support global action in the short-term.

Making Use of Existing International Legal Mechanisms to Manage the Global Antimicrobial Commons: Identifying Legal Hooks and Institutional Mandates.

Antimicrobial resistance (AMR) is an urgent threat to global public health and development. Mitigating this threat requires substantial short-term action on key AMR priorities. While international legal agreements are the strongest mechanism for ensuring collaboration among countries, negotiating new international agreements can be a slow process. In the second article in this special issue, we consider whether harnessing existing international legal agreements offers an opportunity to increase collective action on AMR goals in the short-term. We highlight ten AMR priorities and several strategies for achieving these goals using existing "legal hooks" that draw on elements of international environmental, trade and health laws governing related matters that could be used as they exist or revised to include AMR. We also consider the institutional mandates of international authorities to highlight areas where additional steps could be taken on AMR without constitutional changes. Overall, we identify 37 possible mechanisms to strengthen AMR governance using the International Health Regulations, the Agreement on the Application of Sanitary and Phytosanitary Measures, the Agreement on Trade-Related Aspects of Intellectual Property Rights, the Agreement on Technical Barriers to Trade, the International Convention on the Harmonized Commodity Description and Coding System, and the Basel, Rotterdam, and Stockholm conventions. Although we identify many shorter-term opportunities for addressing AMR using existing legal hooks, none of these options are capable of comprehensively addressing all global governance challenges related to AMR, such that they should be pursued simultaneously with longer-term approaches including a dedicated international legal agreement on AMR.

Typhoid-From Past to Future.

Making a Difference? brings together medical humanities and sciences experts to analyze how historical and new data on typhoid control can be brought to bear on the current context of typhoid conjugate vaccine rollouts and extensively drug-resistant typhoid.

A Biohistorical Perspective of Typhoid and Antimicrobial Resistance.

We combine methodology from history and genetics to reconstruct the biosocial history of antimicrobial resistance (AMR) in the bacterium Salmonella enterica serovar Typhi (S. Typhi). We show how evolutionary divergence in S. Typhi was driven by rising global antibiotic use and by the neglect of typhoid outside of high-income countries. Although high-income countries pioneered 1960s precautionary antibiotic regulations to prevent selection for multidrug resistance, new antibiotic classes, typhoid's cultural status as a supposedly ancient disease of "undeveloped" countries, limited international funding, and narrow biosecurity agendas helped fragment effective global collective action for typhoid control. Antibiotic-intensive compensation for weak water and healthcare systems subsequently fueled AMR selection in low- and middle-income countries but often remained invisible due to lacking surveillance capabilities. The recent rise of extensively drug-resistant typhoid bears the biosocial footprint of more than half a century of antibiotic-intensive international neglect.

Water and Filth: Reevaluating the First Era of Sanitary Typhoid Intervention (1840-1940).

While typhoid fever remains an important cause of illness in many low- and middle-income countries, important insights can be learned by exploring the historical experience with typhoid fever in industrialized countries. We used archival research to examine British and American attempts to control typhoid via sanitary interventions from the 1840s to 1940s. First, we assess how varying perceptions of typhoid and conflicts of interest led to a nonlinear evolution of control attempts in Oxford, United Kingdom. Our qualitative analysis shows how professional rivalries and tensions between Oxford's university and citizens ("gown and town"), as well as competing theories of typhoid proliferation stalled sanitary reform until the provision of cheap external credit created cross-party alliances at the municipal level. Second, we use historical mortality data to evaluate and quantify the impact of individual sanitary measures on typhoid transmission in major US cities. Together a historiographic and epidemiological study of past interventions provides insights for the planning of future sanitary programs.

Swann Song: Antibiotic Regulation in British Livestock Production (1953-2006).

Antibiotics have played a significant yet ambivalent role in Western livestock husbandry. Mass introduced to agriculture to boost animal production and reduce feed consumption in the early 1950s, agricultural antibiotics were soon accused of selecting for bacterial resistance, causing residues and enabling bad animal welfare. The dilemma posed by agricultural antibiotic regulation persists to this day. This essay traces the history of British antibiotic regulation from 1953 to the influential 1969 Swann report. It highlights the role that individual experts using bacteriophage typing played in warning about the mass selection for bacterial resistance on farms and the response of a corporatist system, whose traditional laissez-faire arrangements struggled to cope with the risk posed by bacterial resistance. In addition to contextualizing the Swann report's origins, the essay also discusses the report's fate and implications for current antibiotic regulation.

Shifting targets: typhoid's transformation from an environmental to a vaccine-preventable disease, 1940-2019.

160 years after the discovery of its waterborne transmission and 120 years after the development of the first-generation of vaccines, typhoid fever remains a major health threat globally. In this Historical Review, we use WHO's Institutional Repository for Information Sharing to examine changes in typhoid control policy from January, 1940, to December, 2019. We used a mixed-methods approach in the analysis of infection control priorities, combining semi-inductive thematic coding with historical analysis to show major thematic shifts in typhoid control policy, away from water, sanitation, and hygiene (WASH)-based control towards vaccine-based interventions concurrent with declining attention to the disease. Documentary analysis shows that, although international planners never officially disavowed WASH and low-income countries persistently lobbied for WASH, vaccines emerged as a permanent stopgap while meaningful support of sustained WASH strengthening lost momentum-with serious, long-term ramifications for typhoid control.

Giants on Clay Feet-COVID-19, infection control and public health laboratory networks in England, the USA and (West-)Germany (1945-2020).

In early 2020, COVID-19 exposed differences in public health laboratory systems' testing abilities. Focusing on Germany, the USA and the UK between 1900 and 2020, this article argues that studying the distinct evolution of laboratory infrastructures is critical to understanding the history of infection control and the limits of template-based reforms in global health. While each analysed laboratory infrastructure was shaped by a unique national context, neoliberal visions of lean public services and declining resources led to significant reform pressure from the 1970s. The US Center of Disease Control's model of epidemic intelligence provided an attractive template to integrate resources and focus planning on preparedness scenarios. It also helped justify cuts to local laboratory infrastructures. Effects were uneven: in the USA and the UK, improved integration failed to compensate for local laboratory cuts and loss of autonomy. By contrast, Germany's subsidiary principle allowed for limited federal integration while leaving local services mostly intact.

Hardwiring antimicrobial resistance mitigation into global policy.

In the wake of COVID-19, antimicrobial resistance (AMR) has become termed the 'silent pandemic', with a growing number of editorials warning that international momentum for AMR mitigation is being lost amidst the global turmoil of COVID-19, economic crises and the climate emergency. Yet, is it sufficient to now simply turn the volume of the pre-existing AMR policy discourse back up? Although existing AMR initiatives have previously achieved high levels of international attention, their impact remains limited. We believe it is time to critically reflect on the achievements of the past 7 years and adapt our AMR policies based on the substantial literature and evidence base that exists on the socioecological drivers of AMR. We argue that developing a more sustainable and impactful response requires a shift away from framing AMR as a unique threat in competition with other global challenges. Instead, we need to move towards an approach that emphasizes AMR as inherently interlinked and consciously hardwires upstream interventions into broader global developmental agendas.

An Awkward Fit: Antimicrobial Resistance and the Evolution of International Health Politics (1945-2022).

Despite being acknowledged as a major global health challenge, growing levels of antimicrobial resistance (AMR) in pathogenic and commensal organisms have proven an awkward fit for international health frameworks. This article surveys the history of attempts to coordinate international responses to AMR alongside the origins and evolution of the current international health regulations (IHR). It argues that AMR, which encompasses a vast range of microbial properties and ecological reservoirs, is an awkward fit for the 'organismal' philosophies that centre on the rapid control of individual pathogens that have characterised international policy-making since the 19th century.

Between paternalism and illegality: a longitudinal analysis of the role and condition of manual scavengers in India.

Manual scavengers, or 'Safai Karamcharis', as they are known in India, are sanitation workers who manually clean human waste for a living and face considerable occupational health risks. They are subject to deep-seated, caste-based stigma associated with their perceived 'caste impurity' and lack of cleanliness, which result both in consistently dangerous substandard working conditions and lack of social mobility, with women facing greater hardships. The COVID-19 pandemic has further exacerbated their plight. Despite the considerable efforts of social advocates, organised movements and government institutions, reforms and criminalisation have produced mixed results and campaigners remain divided on whether banning manual scavenging is an effective solution. This article reviews the history of attempts to address scavenging in India. Starting in the colonial period and ending with the current government's Swachh Bharat Mission, it highlights how attempts to deal with scavenging via quick-fix solutions like legal bans criminalising their employment, infrastructure upgrades or paternalistic interventions have either failed to resolve issues or exacerbated scavengers' situation by pushing long-standing problems out of view. It argues that meaningful progress depends on abandoning top-down modes of decision-making, addressing the underlying sociocultural and infrastructural factors that perpetuate the ill health and social conditions of manual scavengers, collecting data on the true extent of scavenging, and investing in and providing political agency to communities themselves.

Reconstructing the history of helminth prevalence in the UK.

Intestinal helminth parasites (worms) have afflicted humans throughout history and their eggs are readily detected in archaeological deposits including at locations where intestinal parasites are no longer considered endemic (e.g. the UK). Parasites provide valuable archaeological insights into historical health, sanitation, hygiene, dietary and culinary practices, as well as other factors. Differences in the prevalence of helminths over time may help us understand factors that affected the rate of infection of these parasites in past populations. While communal deposits often contain relatively high numbers of parasite eggs, these cannot be used to calculate prevalence rates, which are a key epidemiological measure of infection. The prevalence of intestinal helminths was investigated through time in England, based on analysis of 464 human burials from 17 sites, dating from the Prehistoric to Industrial periods. Eggs from two faecal-oral transmitted nematodes (Ascaris sp. and Trichuris sp.) and the food-derived cestodes (Taenia spp. and Diphyllobothrium latum syn Dibothriocephalus latus) were identified, although only Ascaris was detected at a high frequency. The changing prevalence of nematode infections can be attributed to changes in effective sanitation or other factors that affect these faecal-oral transmitted parasites and the presence of cestode infections reflect dietary and culinary preferences. These results indicate that the impact of helminth infections on past populations varied over time, and that some locations witnessed a dramatic reduction in parasite prevalence during the industrial era (18th-19th century), whereas other locations continued to experience high prevalence levels. The factors underlying these reductions and the variation in prevalence provide a key historical context for modern anthelmintic programs.

NIMble innovation-a networked model for public antibiotic trials.

Antibiotic research and development is at an inflection point. Faced with ongoing problems with commercial innovation, we argue for a networked public approach to support and coordinate existing research and development initiatives by sustainably moving promising compounds through clinical trials. We propose a global public infrastructure of institutes tasked with (1) conducting all trial stages up to market authorisation, including small-scale compound production; (2) negotiating licensing agreements for global production and distribution by industry partners; and (3) using public purchasing agreements or subscription models to ensure commercially viable drug production at equitable prices. We invite stakeholders to consider our Networked Institute Model's benefits for unblocking the public and private antibiotic pipeline.

There is no market for new antibiotics: this allows an open approach to research and development.

There is an increasingly urgent need for new antibiotics, yet there is a significant and persistent economic problem when it comes to developing such medicines. The problem stems from the perceived need for a "market" to drive commercial antibiotic development. In this article, we explore abandoning the market as a prerequisite for successful antibiotic research and development. Once one stops trying to fix a market model that has stopped functioning, one is free to carry out research and development (R&D) in ways that are more openly collaborative, a mechanism that has been demonstrably effective for the R&D underpinning the response to the COVID pandemic. New "open source" research models have great potential for the development of medicines for areas of public health where the traditional profit-driven model struggles to deliver. New financial initiatives, including major push/pull incentives, aimed at fixing the broken antibiotics market provide one possible means for funding an openly collaborative approach to drug development. We argue that now is therefore the time to evaluate, at scale, whether such methods can deliver new medicines through to patients, in a timely manner.

Waves of attention: patterns and themes of international antimicrobial resistance reports, 1945-2020.

This article uses quantitative and qualitative approaches to review 75 years of international policy reports on antimicrobial resistance (AMR). Our review of 248 policy reports and expert consultation revealed waves of political attention and repeated reframings of AMR as a policy object. AMR emerged as an object of international policy-making during the 1990s. Until then, AMR was primarily defined as a challenge of human and agricultural domains within the Global North that could be overcome via 'rational' drug use and selective restrictions. While a growing number of reports jointly addressed human and agricultural AMR selection, international organisations (IOs) initially focused on whistleblowing and reviewing data. Since 2000, there has been a marked shift in the ecological and geographic focus of AMR risk scenarios. The Global South and One Health (OH) emerged as foci of AMR reports. Using the deterritorialised language of OH to frame AMR as a Southern risk made global stewardship meaningful to donors and legitimised pressure on low-income and middle-income countries to adopt Northern stewardship and surveillance frameworks. It also enabled IOs to move from whistleblowing to managing governance frameworks for antibiotic stewardship. Although the environmental OH domain remains neglected, realisation of the complexity of necessary interventions has increased the range of topics targeted by international action plans. Investment nonetheless continues to focus on biomedical innovation and tends to leave aside broader socioeconomic issues. Better knowledge of how AMR framings have evolved is key to broadening participation in international stewardship going forward.

(Inter)nationalising the antibiotic research and development pipeline.

In this Personal View, we critically examine the wider context of international efforts to stimulate commercial antibiotic research and development via public-private initiatives. Despite these efforts, antibiotics remain a global resource without an international support structure that is commensurate to the risks from antibiotic-resistant infections and the long-term nature of required solutions. To protect this resource, we propose a two-pronged antibiotic research and development strategy based on a short-term strengthening of incentives (such as market entry rewards) to maximise the delivery of existing opportunities in the pipeline, and on a concurrent medium-term to long-term establishment of a global, publicly funded antibiotic research and development institute. Designed sustainably to deliver novel and first-in-class antibiotics targeting key human health gaps, the institute and its staff would become a global resource that, unlike the private pharmaceutical sector, would be managed as an open science platform. Our model of internationalised public research and development would maximise scientific synergy and cross-fertilisation, minimise replication of effort, acquire and preserve existing know-how, and ensure equitable and sustainable access to novel and effective antibiotics. Its genuinely global focus would also help counteract tendencies to equate donor with global health priorities. Our proposal is not radical. Historical precedent and developments in other research areas show that sustained international funding of publicly owned research can hasten the delivery of critically needed drugs and lower barriers to access.