"Iraqibacter": Exploring the Links Between War and Antimicrobial Resistance

WHO and the G20 have identified the growing threats of Anti-Microbial resistance (AMR) as a major concern that will define the future of global health. Despite these urgent calls, the emergence of AMR in settings of war and distress migration has not been systematically explored. Case reports from Syria, Iraq, Libya, Yemen, and Afghanistan have shown the proliferation of AMR in combatants and civilians injured in these protracted conflicts. With regional conflicts spreading across state borders as well as one of the largest global refugee crises in decades, AMR in the context of conflict has come to pose a serious threat both regionally and internationally. So began penicillin in the Second World War: antibiotics arose in war. Today, in the context of long-running military conflicts we see harbingers of the end of antibiotics.
The core question underpinning this proposal is how war, particularly weapons and the industrialised, urbanised context of contemporary conflicts, drives antibiotic resistance by contaminating the environment and the human and non-human organisms that live there. So far, there has been no systematic or holistic consideration of the environmental health impacts of contemporary conflicts conducted in cities.
Our program draws together scholars working in the fields of medicine, anthropology, history of science, ethics, epidemiology, microbiology, molecular biology, and environmental sciences to examine the specific intersection of antibiotic resistance and war. Rather than focus on antibiotic resistance as a universal problem afflicting modern societies in general, we focus first on the impact of global conflict on antibiotic resistance more holistically, and second on the case of multi-drug resistant Acinetobacer baumanii (MDRAB), initially reported by American military surgeons under the moniker Iraqibacter, and that has been identified recently by the WHO as a "critical pathogen" for research and the development of new antibiotics. We will focus on a number of specific countries - Iraq, Syria, Palestine, Yemen, and Lebanon-places with history of protracted conflicts and with different, yet overlapping, ecologies of war.
The potential global health significance of conflict-related heavy metal mediated antimicrobial resistance is enormous and warrants further study. It will contribute to the field of environmental pathways for antimicrobial resistance more broadly as well as informing the specific intersection of war and antibiotic resistance.

Our working hypothesis is that heavy metal exposure is driving antimicrobial resistance in the setting of contemporary Middle East conflicts. This would represent a previously unknown epidemiological pathway for AMR of enormous public health significance in the Middle East and a game changer for understanding and addressing AMR globally. The drivers of AMRs in war settings are outlined by several factors that would impact the selection, survival and spread of AMR, such as poor hygiene, improper infrastructure, lack of proper antibiotic stewardship, in addition to cross border transmission of resistance through travelling organisms and populations. However, little attention has been paid to the role of heavy metals, because it is not widely known that these metal toxicants can co-select for antibiotic resistance-as demonstrated in emerging literature in industrial and agricultural settings. In the current conflicts, high levels of heavy metals have been demonstrated in conflict zones in the Middle East, and have been linked to a number of health-related outcomes among war-afflicted populations. Destruction of the built environment, a new feature of contemporary conflicts, also releases heavy metals contained in building and civic infrastructures, and can lead to leakage of antibiotics otherwise contained by waste treatment systems. These observations and reports raise many questions about the links between environmental contamination with heavy metals and the proliferation of AMR among the war wounded. Our goal in this project is to develop an interdisciplinary research program focused on the emerging problem of multi-drug resistant infections in war setting, with a focus on MDRAB. The overall research question investigates the development of MDRAB and the impact of war practices and use of heavy metal weapons on its emergence. Developing this program will help in understanding the drivers of AMR and develop regional strategies to limit it.

- Establish an interdisciplinary research network to investigate the drivers of AMR in war settings, bringing together research expertise of different partners and collaborators to devise innovative methodological streams and a holistic approach to investigate the links between war and AMR. This network consolidates through workshops, expansion of partnerships, and the work of the different clusters to strengthen connections between international, regional and local researchers and actors. While our main focus is to explore the links between heavy metals and AMR, one of our broader aims is to generate a better understanding of the intersections of different drivers of AMR in war settings. This includes the impact of movement of populations, antibiotic prescription practices, infrastructure breakdown, environmental pollutions, and clinical management.

- Strengthen links between academic institutions in the UK and beneficiaries in LMIC. With the pre-existing research connections between KCL and MENA academic institutions, this project will contribute to the consolidation of these connections and devise long-term relationships. These connections will be essential for research, practice, and capacity building, and devising training programs based on concrete research projects.

- Build a regional research hub in conflict medicine at the AUB with connections to regional and international institutions. Through the core KCL-AUB leadership, the project will contribute to strengthening the research and practice roles of the conflict medicine program at AUB, and other university units involved in the research. The project builds on the strategic location and history of AUB and its leading role in responding to global health challenges of regional conflicts, facilitated by the pool of renowned investigators from the institution.

- Develop a base-line state of knowledge on the subject in preparation for the larger research project. With the lack of evidence and knowledge about the situation of AMR in war settings, the scoping phase will consolidate the present evidence, filling the wide gap of knowledge on the topic. Through working on publishing scoping reviews, conducting informants' and stakeholders' interviews, and retrospective analysis of available data, the work of the consortium will generate invaluable knowledge, which will advance our understanding of the drivers and burdens of AMR in war settings, and translating that knowledge to local, regional and international beneficiaries and policy makers.

- Strengthen the inter-sectorial collaboration between academic and humanitarian organizations. Building on the critical partnership with ICRC and MSF in this project, the work of the research network will buttress the connections between researchers and practitioners in the field of war medicine and AMR. The input of these organizations will be essential in shaping the direction of the research questions, pertinent to those working on the ground, dealing with the immediate fallouts of war and AMR. This will potentially devise a revision of present clinical, public health, and ethical guidelines for the management of patients and populations in war settings.

- Exposure and training of researchers in LMIC in interdisciplinary methodologies to investigate AMR, and improving practice skills of practitioners and medical institutions in the detection of AMR and the management of wound infections, as well as capacity building of laboratory infrastructure in conflict settings. While might prove difficult to access such sites, we believe that our pre-existing regional connections with AUB, ICRC, and MSF, will prove to be fruitful in facilitating such connections and access to the various conflict settings. This will also present an important platform to generating comparative understanding about the manifestations of AMR in different settings of war.