The need for One Health systems-thinking approaches to understand multiscale dissemination of antimicrobial resistance.

Although the effects of antimicrobial resistance (AMR) are most obvious at clinical treatment failure, AMR evolution, transmission, and dispersal happen largely in environmental settings, for example within farms, waterways, livestock, and wildlife. We argue that systems-thinking, One Health approaches are crucial for tackling AMR, by understanding and predicting how anthropogenic activities interact within environmental subsystems, to drive AMR emergence and transmission. Innovative computational methods integrating big data streams (eg, from clinical, agricultural, and environmental monitoring) will accelerate our understanding of AMR, supporting decision making. There are challenges to accessing, integrating, synthesising, and interpreting such complex, multidimensional, heterogeneous datasets, including the lack of specific metrics to quantify anthropogenic AMR. Moreover, data confidentiality, geopolitical and cultural variation, surveillance gaps, and science funding cause biases, uncertainty, and gaps in AMR data and metadata. Combining systems-thinking with modelling will allow exploration, scaling-up, and extrapolation of existing data. This combination will provide vital understanding of the dynamic movement and transmission of AMR within and among environmental subsystems, and its effects across the greater system. Consequently, strategies for slowing down AMR dissemination can be modelled and compared for efficacy and cost-effectiveness.

Strategies to reduce antimicrobials in livestock and aquaculture, and their impact under field conditions: a structured scoping literature review.

Antimicrobial resistance is a pandemic problem, causing substantial health and economic burdens. Antimicrobials are extensively used in livestock and aquaculture, exacerbating this global threat. Fostering the prudent use of antimicrobials will safeguard animal and human health. A lack of knowledge about alternatives to replace antimicrobials, and their effectiveness under field conditions, hampers changes in farming practices. This work aimed to understand the impact of strategies to reduce antimicrobial usage (AMU) in livestock and aquaculture, under field conditions, using a structured scoping literature review. The Extension for Scoping Reviews of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA-ScR) were followed and the Patient, Intervention, Comparison, Outcome, Time and Setting (PICOTS) framework used. Articles were identified from CAB Abstracts, MEDLINE and Scopus. A total of 7505 unique research articles were identified, 926 of which were eligible for full-text assessment; 203 articles were included in data extraction. Given heterogeneity across articles in the way alternatives to antimicrobials or interventions against their usage were described, there was a need to standardize these by grouping them in categories. There were differences in the impacts of the strategies between and within species; this highlights the absence of a 'one-size-fits-all' solution. Nevertheless, some options seem more promising than others, as their impacts were consistently equivalent or positive when compared with animal performance using antimicrobials. This was particularly the case for bioactive protein and peptides, and feed/water management. The outcomes of this work provide data to inform cost-effectiveness assessments of strategies to reduce AMU.

Moving health to the heart of agri-food policies; mitigating risk from our food systems.

Our food systems are progressively more industrialized and consolidated with many modern food value chains involving multiple countries and continents, and as such being associated with changes in risk profile and impacts of emerging and re-emerging diseases. Disease outbreaks that sweep through a single region can have massive impacts on food supply, while severe outbreaks of human pathogens can disrupt agricultural labor supply or demand for products perceived as 'unsafe'. Market pressures have generally rewarded production of cash crops for fuel and energy dense, low nutrient processed foods over production of fruits and vegetables for local consumption. Climbing rates of food-related NCDs and pre-existing conditions leave the population increasingly susceptible to infectious diseases that are often driven by or arise from the food system. Therefore disease and diet from our food systems cause impacts on human health, and human health issues can impact on the functioning of the food system. The COVID-19 outbreak is the most recent example of food system driven disease emergence and of massive supply and demand shocks in the food system, experienced as a direct and indirect result of this disease. The effects of the food system on disease spread (and vice versa) must be addressed in future plans to prevent and mitigate large scale outbreaks. Health policies must acknowledge the food system as the base of our health system, as must agri-food policy recognize the pre-eminence of human health (directly and indirectly) in decision making.

Providing information about triclabendazole resistance status influences farmers to change liver fluke control practices.

BACKGROUND: Reports of disease and production losses associated with Fasciola hepatica, the common liver fluke, have increased in recent years. Resistance to triclabendazole, one of the principal veterinary medicines used to prevent losses, has been reported and is now considered widespread in fluke endemic regions of the UK. METHODS: Thirteen farmers participated in a trial in 2013 and the triclabendazole resistance status was obtained for each farm. Based on these results, a knowledge exchange programme on fluke control was delivered to nearly 100 farmers in the region. In this follow-up study, 11 farmers involved in the original trial, participated in semistructured in-depth qualitative interviews in July 2017. RESULTS: Overall, participants identified benefits from participating in the 2013 trial, gaining information about triclabendazole resistance on their farms and knowledge about fluke control. The information on their farm's resistance status was a driver for changing their liver fluke control programmes. Factors such as habitual and repetitive behaviours, grazing restrictions due to agri-environmental schemes, economic pressures and climate change were identified that could impede or prevent the adoption of new control strategies. CONCLUSIONS: The study highlights the significance of resistance to triclabendazole and the impact of knowledge exchange programmes in changing liver fluke control practices.

Exploring the Socioeconomic Importance of Antimicrobial Use in the Small-Scale Pig Sector in Vietnam.

Antimicrobial resistance (AMR) is influenced by antimicrobial use in human and animal health. This use exerts selection pressure on pathogen populations with the development of resistance and the exchange of resistance genes. While the exact scale of AMR in Vietnam remains uncertain, recent studies suggest that it is a major issue in both human and animal health. This study explored antimicrobial use behaviors in 36 pig farms in the Nam Dinh Province (North) and the Dong Nai Province (South) of Vietnam (with a median of 5.5 breeding sows and 41 fattening pigs). It also estimated the economic costs and benefits of use for the producer. Data were collected through a structured face-to-face interview with additional productivity data collected by farmers during a six-week period following the initial interview. Overall, antimicrobial use was high across the farms; however, in-feed antimicrobial use is likely to be under-reported due to misleading and imprecise labelling on premixed commercial feeds. An economic analysis found that the cost of antimicrobials was low relative to other farm inputs (~2% of total costs), and that farm profitability was precariously balanced, with high disease and poor prices leading to negative and low profits. Future policies for smallholder farms need to consider farm-level economics and livestock food supply issues when developing further antimicrobial use interventions in the region.

The Costs, Benefits and Human Behaviours for Antimicrobial Use in Small Commercial Broiler Chicken Systems in Indonesia.

There are growing concerns over the threat to human health from the unregulated use of antimicrobials in livestock. Broiler production is of great economic and social importance in Indonesia. This study used a structured questionnaire approach to explore the human behaviours and economic drivers associated with antimicrobial use in small commercial broiler systems in Indonesia (n = 509). The study showed that antimicrobial use was high with farmers easily able to access antimicrobials through local animal medicine, however, it was difficult for farmers to access veterinary advice on responsible antimicrobial use. The most significant finding was that the relative cost of antimicrobials was low, and farmers observed improvements in productivity rates from routine antimicrobial administration. However, farmers seldom kept detailed records on farm productivity or economic costs; this is a hurdle to undertaking a more detailed economic analysis of antimicrobial use. There is a need for further research on the cost-effectiveness of alternative methods of preventing disease and ensuring that feasible alternatives are easily available. Farm-level economics and securing the food supply chain need to be central to any future policy interventions to reduce antimicrobial use in broiler systems in Indonesia and this observation is relevant at a regional and global level.

Exploring Perspectives on Antimicrobial Use in Livestock: A Mixed-Methods Study of UK Pig Farmers.

Increasing levels of antimicrobial resistance in human and veterinary medicine have raised concerns over the irresponsible use of antimicrobials. The role of administering antimicrobials in food producing animals most frequently falls to the farmer, therefore it is essential that their use of antimicrobials is both optimal and responsible. This study sought in-depth information on the drivers behind antimicrobial use behaviors and farmer attitudes to responsible use using a mixed-methodological approach. Initially, in-depth semi-structured interviews were conducted with a purposively selected sample of farmers (n = 22). A thematic analysis approach was taken to identify key themes from these qualitative data. The generalizability and variation of these themes was then tested on a larger randomly selected sample of pig farmers through a questionnaire study (n = 261). The influences behind antimicrobial use were complex with multiple drivers motivating decisions. There was no consensual opinion on what farming systems resulted in either a low or high antimicrobial requirement however, farmers reported that good management practices, low stocking densities, and a high health status were associated with low antimicrobial use. Farmers expressed desire to avoid the long-term use of in-feed antimicrobials, but identified barriers to discontinuing such behaviors, such as pig morbidity, mortality, and economic losses. The high cost of antimicrobials was described as a motivation toward seeking alternative methods of controlling disease to prophylactic use; however, this expense was balanced against the losses from an increased burden of disease. The high financial costs involved in pig production alongside the economic uncertainty of production and pressure from retailers, were identified as limiting the scope for improvements in pig accommodation and facilities which could reduce the antimicrobial requirements on farm. Long-term, sustainable and economically stable relationships between retailers and farmers may allow farmers to make necessary investments in improving management and housing in order to reduce antimicrobial use. Greater use and more widespread deployment of effective vaccinations were highlighted by farmers as being a feasible alternative to antimicrobial use in preventing disease.

Characterizing Antimicrobial Use in the Livestock Sector in Three South East Asian Countries (Indonesia, Thailand, and Vietnam).

A framework was developed to characterize the antimicrobial use/antimicrobial resistance complex in livestock systems in Indonesia, Vietnam, and Thailand. Farm profitability, disease prevention, and mortality rate reduction were identified as drivers toward antimicrobial use in livestock systems. It revealed that antimicrobial use was high in all sectors studied, and that routine preventative use was of particular importance to broiler production systems. Misleading feed labeling was identified as a hurdle to the collection of accurate antimicrobial use data, with farmers being unaware of the antimicrobials contained in some commercial feed. Economic analysis found that the cost of antimicrobials was low relative to other farm inputs, and that farm profitability was precariously balanced. High disease and poor prices were identified as potential drivers toward economic loss. The research indicates that antimicrobial use in small-scale poultry production systems improves feed conversion ratios and overall productivity. However, data were limited to quantify adequately these potential gains and their impacts on the food supply. During the study, all countries embraced and implemented policies on better management of antimicrobial use in livestock and surveillance of antimicrobial resistance. Future policies need to consider farm-level economics and livestock food supply issues when developing further antimicrobial use interventions in the region.

The dynamic changes in the number of uterine natural killer cells are specific to the eutopic but not to the ectopic endometrium in women and in a baboon model of endometriosis.

BACKGROUND: Endometriosis is a common condition associated with growth of endometrial-like tissue beyond the uterine cavity. Previous reports have suggested a role for uNK cells in the pathogenesis of endometriosis postulating that survival and accumulation of menstrual endometrial tissue in the peritoneal cavity may relate to a reduction in the cytotoxic activity of peripheral blood NK cells. We aimed to assess the differences in percentage of uNK cells and their phenotypical characterization in eutopic and ectopic endometrial samples from women with and without endometriosis and baboons with induced endometriosis. METHODS: Eutopic and ectopic endometrial samples from 82 women across the menstrual cycle with/without endometriosis and from 8 baboons before and after induction of endometriosis were examined for CD56 and NKp30 expression with immunohistochemistry, quantified using computer assisted image analysis. Curated secretory phase endometrial microarray datasets were interrogated for NK cell receptors and their ligands. In silico data was validated by examining the secretory phase eutopic endometrium of women with and without endometriosis (n = 8/group) for the immuno-expression of BAG6 protein. RESULTS: The percentage of uNK cells increased progressively from the proliferative phase with the highest levels in the late secretory phase in the eutopic endometrium of women with and without endometriosis. The percentage of uNK cells in ectopic lesions remained significantly low throughout the cycle. In baboons, induction of endometriosis increased the percentage of uNK in the ectopic lesions but not NKp30. Published eutopic endometrial microarray datasets demonstrated significant upregulation of NKp30 and its ligand BAG6 in women with endometriosis compared with controls. Immunohistochemical staining scores for BAG6 was also significantly higher in secretory phase eutopic endometrium from women with endometriosis compared with the endometrium of healthy women (n = 8/group). CONCLUSIONS: The dynamic increase in the percentage of uNK cells in the secretory phase is preserved in the endometrium of women with endometriosis. The low number of uNK cells in human and baboon ectopic lesions may be due to their exaggerated reduction in hormonal responsiveness (progesterone resistance).

Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study.

OBJECTIVE: To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta. DESIGN: A case-control study, with operators performing the image analysis blinded. SETTING: Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom. PARTICIPANTS: A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy. METHODS: Each fetus was scanned with MRI at 22-27 weeks and 33-38 weeks gestational age (GA). MAIN OUTCOME MEASURES: Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes. RESULTS: Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume. CONCLUSION: Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.

Antibodies to Chlamydia trachomatis in serum and peritoneal fluid of women with endometriosis.

The specifics of inflammation created by infection with Chlamydia trachomatis could be favourable to the genesis of endometriosis. To investigate this hypothesis, we studied the association between Chlamydia trachomatis specific IgG and IgA antibodies in serum and the peritoneal fluid of 51 women undergoing laparoscopic surgery. There was no significant difference between women with and without endometriosis with respect to the incidence of IgG and IgA in serum or the peritoneal fluid. The results of our preliminary study did not show any significant link between past infection with Chlamydia trachomatis and the presence of endometriosis.

3D ultrasound in gynecology and reproductive medicine.

With advances occurring in medicine on a daily basis, it was only a matter of time before essential gynecological investigations, such as ultrasound, were modified. Many clinicians remain unconvinced by its reputed advantages and 3D ultrasound is not without disadvantages. These mainly relate to the cost implications and training requirements. 3D ultrasound imaging is still at a relatively early stage in terms of its role as a day-to-day imaging modality in gynecology and reproductive medicine. 3D imaging has several obvious benefits that relate to an improved spatial orientation and the demonstration of multiplanar views, of which the coronal plane is particularly useful. It offers a more objective and reproducible measurement of volume and vascularity of the region of interest, and an improved assessment of normal and pathological pelvic organs through further postprocessing modalities, including tomographic ultrasound imaging and various rendering modalities. It also has the benefit of offering reduced scanning time, the option of teleconsultation and storage of images for re-evaluation. However, other than its application in the assessment and differentiation of uterine anomalies, there is very little evidence demonstrating that 3D ultrasound results in a clinically relevant benefit or negates the need for further investigation. Future work should ensure that 3D ultrasound is compared with conventional imaging in randomized trials where the observer is blind to the outcome, only after which will we truly be able to evaluate its role in an evidence-based manner.