Protocol: WASH and biosecurity interventions for reducing burdens of infection, antibiotic use and antimicrobial resistance: a One Health mixed methods systematic review

Antimicrobial resistance (AMR) is a growing global problem. Like many other public health issues, research points to the important role of structural factors in shaping the emergence, transmission and burden of AMR. However, mirroring other areas of public health, the evidence-base of interventions that address these structural issues is slim and infrequently synthesised. Structural interventions (SIs) seek to alter the context that produces or co-produces ill-health4. AMR has been configured as a One Health problem to be understood in terms of human-animal-environment interconnections. Infection control and prevention is recognised as essential to addressing AMR, but how best to achieve this through a One Health perspective remains a challenge. This review addresses this gap by identifying and synthesising evidence of interventions that operate on a structural level to Improve water, hygiene, sanitation and biosecurity in communities that live and/or work with animals In Low- and Middle-Income Countries (LMICs). The premise of this review is that interventions to improve water, sanitation, hygiene (WASH), and biosecurity intend to reduce burdens of infection and have the potential to reduce reliance on antibiotics for humans and animals. Therefore, such interventions have the ability to reduce both transmission and emergence of AMR. Two further observations inform the focus of this review: growing evidence of the insufficiency of purely technical or behavioural WASH/biosecurity Interventions to reduce disease burdens across LMICs, accompanied by calls for structural Interventions; and that most reviews retain classificatory silos of either human WASH or animal biosecurity which belies the realities of many rural and urban populations whose lives are interconnected with animals across LMIC settings. This review, therefore, addresses the potential for structural interventions on WASH/biosecurity to have an impact on Infections, antibiotic use and AMR in LMICs. Methodologically, this review is influenced by impact assessments in development studies, where interventions are often complex in design and implementation and their effects multifaceted. The kinds of intervention that operate at a structural level are similarly challenging to identify and to characterise neatly, and are unlikely to be restricted to a randomised controlled trial design. Therefore, our search criteria and strategy are wide and our methods mixed, in order to capture potential interventions that could have an impact on our set of outcomes. In addition, in this review we recognise that interventions have impacts beyond a particular pre-defined outcome, and to be able to recommend a particular intervention strategy requires consideration of not only what that intervention comprised and required, but also what unintended consequences or co-benefits the intervention may have produced. Finally, a key consideration for this review is that many studies undertaken in Spanish, Portuguese and French speaking countries, where different interventions may have been developed and piloted, can be excluded due to language criteria, and in this case, we deliberately include studies in these languages in addition to English in the search and review. This systematic review will summarise evidence on how WASH and biosecurity interventions could have the potential to reduce the burden of infections, antimicrobial use and/or AMR in animal agriculture and in people in contact with animals in different country settings, with a focus on LMICs. WASH and biosecurity interventions for reducing burdens of infection, antibiotic use and antimicrobial resistance: a One Health mixed methods systematic review Included studies have to examine the impact of WASH and biosecurity interventions on reducing burden of infections and therefore promote healthier production systems where the use of antibiotics is reduced or limited. Our review will categorise these interventions according to the context where they were performed (e.g., LMICs country, region, urban or rural, type of productions systems, livelihoods systems, agroecological situation, beneficiaries, climate conditions). The aim of this study is to identify points for WASH and biosecurity interventions at structural and system levels that will enable reduction in reliance on antibiotics in the everyday lives of people living with animals in urbanised and rural landscapes

Antimicrobial Use/Consumption Surveillance in Zimbabwe: Desk Review Report

Antimicrobial Resistance (AMR) now poses a significant global threat to animal and human health, and over the years, inappropriate antimicrobial use (AMU), both in animals and humans, has been identified as the most significant driver of AMR. Recognizing the urgent need to tackle AMR, in 2015, the WHO, WOAH and FAO endorsed a Global Action Plan (GAP) on AMR, which includes five strategic objectives targeted at curbing AMR development. Amongst these objectives is the need to “strengthen knowledge through surveillance and research”. Zimbabwe, one of many African countries experiencing challenges arising from AMR in both the animal and human health sectors, needs to map a way forward to address this critical challenge. The objectives of this report were firstly to determine the current status of antimicrobial use or consumption (AMU/C) surveillance in Zimbabwe in the animal sector and identify gaps in knowledge. Secondly, to explore AMU/C surveillance strategies in food-producing animals in other countries, including data collection methods, data entry platforms, data analysis and reporting. Finally, to provide a situational analysis of existing systems, plans, software platforms and human and physical resources in relevant institutions in Zimbabwe to identify potential strategies for implementing AMU/C surveillance in the country. Methods The objectives were addressed through various methods, including key informant interviews of personnel in key government institutions such as the Department of Veterinary Services (DVS) and the Medicines Control Authority of Zimbabwe (MCAZ), among others. Information was also derived from relevant publications searched from scientific databases, including PubMed and PLOS. Key findings The first part of the report describes the situation analysis of Zimbabwe, which details the country’s animal production sector and the Department of Veterinary Services (DVS), and AMR & AMU/C surveillance initiatives in the country, including the reporting of AMU/C data to the WOAH. The second part of the report reviews global standards and methods for AMU/C in animals, including the WOAH standards for AMC data collection. Also included in this section are the AMU/C surveillance strategies in food-producing animals in Low-and Middle-Income Countries (LMICs) and high-income countries (HICs). The report also includes a brief on the different types of antimicrobial use metrics and indicators used in AMU/C surveillance in food-producing animals, as well as their advantages and disadvantages. The last section of the report includes proposals for implementing AMU/C surveillance in Zimbabwe and a feasibility assessment for each proposal. Conclusion and recommendations Zimbabwe generally has adequate human resource capacity to implement AMU/C surveillance in food-producing animals. The key personnel to perform these activities will need to be identified and adequately capacitated through training and provision of other key resources. To coordinate the AMU/C surveillance activities, the relevant institutions, the DVS and MCAZ, will need to collaborate closely to conduct the process activities efficiently. Of paramount importance is that the two government institutions will also need to establish funding mechanisms for AMU/C surveillance in food-producing animals in order to make it sustainable

Measurement of antibiotic use on poultry farms in Zimbabwe: Evaluation of a tool and procedures

Introduction The emergence of antimicrobial resistance (AMR) as a major global threat to human and animal health and development cannot be overemphasised. Since the misuse and overuse of antimicrobials have been identified as the main drivers of AMR globally, Zimbabwe, through a collaboration between the Department of Veterinary Services (DVS) and the Food and Agriculture Organization (FAO), developed and piloted an antimicrobial use (AMU) tool in the poultry production sector, to quantify antimicrobial use. The purpose of this study was to evaluate the tool and procedures used in the pilot survey and its ability to collect quality AMU data. We identified areas of improvement and developed recommendations for implementation in future AMU surveys in the poultry sector in Zimbabwe. Methods This research used mixed methods, involving quantitative and qualitative approaches. This involved initially piloting a predesigned antibiotic use (ABU) data collection tool in practice, then assessing the tool's ability to collect quality data, and finally evaluating the procedures that enabled and limited the collection of ABU data. The tool was assessed by evaluating the completeness of data collected in the pilot survey and its consistency, appraising the items included in the tool, and determining the analysability of data collected. The procedures used were evaluated by observing the tool's administration in the field and through a focus group discussion involving all data collectors of the pilot survey. Findings AMU data was collected from 191 farms, about 50% of the initially targeted 384 broiler farms. There were missing data on various questions in the tool, including farm georeferences, bird populations, and information about the treatment, including the identification of the antibiotic active ingredient and their concentrations, routes of administration, treatment dosage and duration, as well as the age and weight of birds at the time of treatment. Inconsistencies were also noted in the data collected, particularly in the way antibiotics were recorded. The analysability of data collected was negatively affected by the missing data and question phrasing, in particular, those to do with the treatment of birds with antibiotics, which were found to have excluded the majority of survey respondents from further analyses. Broiler farms in communal areas were over-represented in the pilot survey due to most data collectors working in these areas. Various challenges were encountered during the recruitment of participants, including farmers not keeping birds at the time of the survey, farmers declining to participate in the study due to lack of incentives, some farms being in remote locations, and political interference. Most data collectors in the pilot survey, who were recruited from the Agricultural Extension Services (AGRITEX) department within the Ministry of Agriculture, indicated that the timing of the survey (January to May of the calendar year) was not conducive for them since it coincided with the cropping season in Zimbabwe, which induced high workloads, leaving less time to participate in data collection activities. Conclusions and recommendations The pilot AMU survey in broiler production serves as an important milestone in establishing a monitoring system for the use of antimicrobials in food producing animals in Zimbabwe. To a moderate extent, the pilot tool and procedures used in broilers enabled the collection of AMU data, but some key challenges also arose, mainly related to questionnaire design (i.e., question formulation), data collection procedures, participant recruitment, timing of the survey and inadequate training of data collectors, among other issues. Key recommendations made included using the ‘Drug Bag’ method in monitoring the use of antibiotics in poultry, carefully selecting enumerators to ensure representation of different farming scales, adequately training data collectors prior to surveys, and giving them standard operating procedures to use in data collection to ensure consistency. More research needs to be done in this area of monitoring the use of antimicrobials in food producing animals in Zimbabwe and beyond, to strengthen capacities to collect quality AMU data, thereby contributing to antimicrobial stewardship efforts, and in turn with the global fight against AMR

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

Secular evolution versus hierarchical merging: galaxy evolution along the Hubble sequence, in the field and rich environments

In the current galaxy formation scenarios, two physical phenomena are invoked to build disk galaxies: hierarchical mergers and more quiescent external gas accretion, coming from intergalactic filaments. Although both are thought to play a role, their relative importance is not known precisely. Here we consider the constraints on these scenarios brought by the observation-deduced star formation history on the one hand, and observed dynamics of galaxies on the other hand: the high frequency of bars and spirals, the high frequency of perturbations such as lopsidedness, warps, or polar rings. All these observations are not easily reproduced in simulations without important gas accretion. N-body simulations taking into account the mass exchange between stars and gas through star formation and feedback, can reproduce the data, only if galaxies double their mass in about 10 Gyr through gas accretion. Warped and polar ring systems are good tracers of this accretion, which occurs from cold gas which has not been virialised in the system's potential. The relative importance of these phenomena are compared between the field and rich clusters. The respective role of mergers and gas accretion vary considerably with environment.Comment: 18 pages, 8 figures, review paper to "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", Pilanesberg, ed. D. Block et al., Kluwe

A possible new syndrome with growth-hormone secreting pituitary adenoma, colonic polyposis, lipomatosis, lentigines and renal carcinoma in association with familial testicular germ cell malignancy: A case report

BACKGROUND: Germ-cell testicular cancer has not been definitively linked to any known hereditary cancer susceptibility disorder. Familial testicular cancer in the presence of other findings in affected and unaffected family members might indicate a previously-unidentified hereditary cancer syndrome. CASE PRESENTATION: The patient was diagnosed with a left testicular seminoma at age 28, and treated with left orchiectomy followed by adjuvant cobalt radiation. His family history is significant for testicular seminoma in his son, bladder cancer in his sister, and lipomatosis in his father. His evaluation as part of an etiologic study of familial testicular cancer revealed multiple colon polyps (adenomatous, hyperplastic, and hamartomatous) first found in his 50 s, multiple lipomas, multiple hyperpigmented skin lesions, left kidney cancer diagnosed at age 64, and a growth-hormone producing pituitary adenoma with associated acromegaly diagnosed at age 64. The patient underwent genetic testing for Cowden syndrome (PTEN gene), Carney complex (PRKAR1A gene), and multiple endocrine neoplasia syndrome type 1 (MEN1 gene); no deleterious mutations were identified. DISCUSSION: The constellation of benign and malignant neoplasms in the context of this patient's familial testicular cancer raised the possibility that these might be manifestations of a known hereditary susceptibility cancer syndrome; however, genetic testing for the three syndromes that were most likely to explain these findings did not show any mutation. Alternatively, this family's phenotype might represent a novel neoplasm susceptibility disorder. This possibility cannot be evaluated definitively on the basis of a single case report; additional observations and studies are necessary to investigate this hypothesis further

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

Steroid-refractory ulcerative colitis treated with corticosteroids, metronidazole and vancomycin: a case report

BACKGROUND: Increasing evidence elucidating the pathogenic mechanisms of ulcerative colitis (UC) has accumulated and the disease is widely assumed to be the consequence of genetic susceptibility and an abnormal immune response to commensal bacteria. However evidence regarding an infectious etiology in UC remains elusive. CASE PRESENTATION: We report a provocative case of UC with profound rheumatologic involvement directly preceded by Clostridium difficile infection and accompanying fever, vomiting, bloody diarrhea, and arthritis. Colonic biopsy revealed a histopathology suggestive of UC. Antibiotic treatment eliminated detectable levels of enteric pathogens but did not abate symptoms. Resolution of symptoms was procurable with oral prednisone, but tapering of corticosteroids was only achievable in combination therapy with vancomycin and metronidazole. CONCLUSIONS: An infectious pathogen may have both precipitated and exacerbated autoimmune disease attributes in UC, symptoms of which could be resolved only with a combination of corticosteroids, vancomycin and metronidazole. This may warrant the need for more perceptive scrutiny of C. difficile and the like in patients with UC

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT