Users' perception of the OH-EpiCap evaluation tool based on its application to nine national antimicrobial resistance surveillance systems.

Introduction: Antimicrobial resistance (AMR) is a One Health (OH) challenge. To achieve or maintain an effective and efficient AMR surveillance system, it is crucial to evaluate its performance in meeting the proposed objectives, while complying with resource restrictions. The OH-EpiCap tool was created to evaluate the degree of compliance of hazard surveillance activities with essential OH concepts across the following dimensions: organization, operational activities, and impact of the surveillance system. We present feedback on the application of the OH-EpiCap tool from a user's perspective, based on the use of the tool to evaluate nine national AMR surveillance systems, each with different contexts and objectives. Methods: The OH-EpiCap was assessed using the updated CoEvalAMR methodology. This methodology allows the evaluation of the content themes and functional aspects of the tool and captures the user's subjective experiences via a strengths, weaknesses, opportunities, and threats (SWOT) approach. Results and Discussion: The results of the evaluation of the OH-EpiCap are presented and discussed. The OH-EpiCap is an easy-to-use tool, which can facilitate a fast macro-overview of the application of the OH concept to AMR surveillance. When used by specialists in the matter, an evaluation using OH-EpiCap can serve as a basis for the discussion of possible adaptations of AMR surveillance activities or targeting areas that may be further investigated using other evaluation tools.

Capturing systematically users' experience of evaluation tools for integrated AMU and AMR surveillance.

Tackling antimicrobial resistance (AMR) is a goal for many countries. Integrated surveillance of antimicrobial use (AMU) and resistance is a prerequisite for effective risk mitigation. Regular evaluation of any surveillance is needed to ensure its effectiveness and efficiency. The question is how to evaluate specifically integrated surveillance for AMU and AMR. In an international network called CoEvalAMR, we have developed guidelines for selection of the most appropriate tools for such an evaluation. Moreover, we have assessed different evaluation tools as examples using a country case format and a methodology with a focus on the user's experience. This paper describes the updated methodology, which consists of a brief introduction to the case and to the tool separately. Moreover, there are 12 functional aspects and nine content themes which should be scored using a 4-tiered scale. Additionally, four Strengths, Weaknesses, Opportunities, Threats (SWOT) questions should be addressed. Results are illustrated using radar diagrams. An example of application of the updated methodology is given using the ECoSur evaluation tool. No tool can cover all evaluation aspects comprehensively in a user-friendly manner, so the choice of tool must be based upon the specific evaluation purpose. Moreover, adequate resources, time and training are needed to obtain useful outputs from the evaluation. Our updated methodology can be used by tool users to share their experience with available tools, and hereby assist other users in identifying the most suited tool for their evaluation purpose. Additionally, tool developers can get valuable information for further improvements of their tool.

Population Genetic Structure of Phlebotomus sergenti (Diptera: Psychodidae) Collected in Four Regions of Morocco Based on the Analysis of Cyt b and EF-1α Genes.

Phlebotomus (Ph.) sergenti is the main vector of Leishmania (L.) tropica (Trypanosomatida: Trypanosomatidae), the causative agent of anthroponotic cutaneous leishmaniasis in Morocco. This species has an extended geographical distribution, wider than that of the parasite. The main objective of our study was to analyze the genetic diversity of Ph. sergenti collected in four foci in Morocco: Taza, Foum Jemâa, El Hanchane, and Ouarzazate. We studied a set of diversity and population structure indices by sequencing two markers; nuclear EF-1α and mitochondrial Cyt b from 175 individual sand flies. Our results showed a considerable degree of intraspecific polymorphism with a high number of haplotypes identified in both genes. Many polymorphic sites detected in the Cyt b sequences (SCyt b = 45) indicate that it is the most polymorphic marker showing a distinct distribution of haplotypes according to their geographical origin, whereas the EF-1α marker showed no geographical isolation. Analysis by Tajima's D and Fu's Fs tests revealed a possible recent expansion of the populations, especially with the EF-1α marker, showing significant values in Taza and Ouarzazate sequences. The present study revealed significant genetic diversity within Ph. sergenti populations in Morocco. The results warrant further research using a combination of more than two markers including mitochondrial and non-mitochondrial markers, which may provide more information to clarify the genetic status of Ph. sergenti.

Evaluating Integrated Surveillance for Antimicrobial Use and Resistance in England: A Qualitative Study.

Integrated surveillance systems for antimicrobial use (AMU) and antimicrobial resistance (AMR) require regular evaluation to ensure the effectiveness and efficiency of the system. An important step in the evaluation is to choose an appropriate tool for the purpose of the evaluation. The "Integrated Surveillance System Evaluation" (ISSE) framework is a conceptual framework that was developed to evaluate One Health (OH) integration in surveillance system for AMU/AMR. This study aimed to evaluate the performance and value of integrated surveillance system for AMU/AMR in England by applying the ISSE framework, which was used to develop data collection protocols and define the study design. A qualitative study using semi-structured interviews was conducted to collect the data and analyse it thematically. Eighteen stakeholders from human, animal, food and environment sectors that are involved in AMU/AMR surveillance were interviewed. Four main themes emerged from the analysis: (1) Cross-sectoral integration in the surveillance system for AMU/AMR; (2) Production of OH outputs and outcomes; (3) Drivers and barriers to cross-sectoral collaboration; and 4) Need for more cross-sectoral collaboration. The findings showed that there were links between integrated surveillance information, decision making and interventions. However, there were only few OH examples, such as the UK AMR contingency plan, where the potential of cross-sectoral collaboration was fully exploited. A lot of the benefits described were related to the generation of information and increase in knowledge and understanding without links to how the information generated was used. While these intangible benefits have a value on their own, being able to link surveillance information and mitigation measures would help to enhance the value of integrated surveillance. In terms of improvement, the main areas identified were the development of more harmonised methods for data collection and analysis, provision of resources dedicated to cross-sectoral collaboration, improved coordination, and collection of surveillance data from the environment and from companion animals. By identifying links between OH surveillance information produced and various outputs and outcomes; this study helped to understand the wider benefits of integrated surveillance for AMU/AMR in England and provided insights on how the system could be improved and efficiency increased.

Computational Analysis of Missense Variants in the Human Transmembrane Protease Serine 2 (TMPRSS2) and SARS-CoV-2.

The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the TMPRSS2 stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of TMPRSS2 native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2.

Assessment of Evaluation Tools for Integrated Surveillance of Antimicrobial Use and Resistance Based on Selected Case Studies.

Regular evaluation of integrated surveillance for antimicrobial use (AMU) and resistance (AMR) in animals, humans, and the environment is needed to ensure system effectiveness, but the question is how. In this study, six different evaluation tools were assessed after being applied to AMU and AMR surveillance in eight countries: (1) ATLASS: the Assessment Tool for Laboratories and AMR Surveillance Systems developed by the Food and Agriculture Organization (FAO) of the United Nations, (2) ECoSur: Evaluation of Collaboration for Surveillance tool, (3) ISSEP: Integrated Surveillance System Evaluation Project, (4) NEOH: developed by the EU COST Action "Network for Evaluation of One Health," (5) PMP-AMR: The Progressive Management Pathway tool on AMR developed by the FAO, and (6) SURVTOOLS: developed in the FP7-EU project "RISKSUR." Each tool was scored using (i) 11 pre-defined functional aspects (e.g., workability concerning the need for data, time, and people); (ii) a strengths, weaknesses, opportunities, and threats (SWOT)-like approach of user experiences (e.g., things that I liked or that the tool covered well); and (iii) eight predefined content themes related to scope (e.g., development purpose and collaboration). PMP-AMR, ATLASS, ECoSur, and NEOH are evaluation tools that provide a scoring system to obtain semi-quantitative results, whereas ISSEP and SURVTOOLS will result in a plan for how to conduct evaluation(s). ISSEP, ECoSur, NEOH, and SURVTOOLS allow for in-depth analyses and therefore require more complex data, information, and specific training of evaluator(s). PMP-AMR, ATLASS, and ISSEP were developed specifically for AMR-related activities-only ISSEP included production of a direct measure for "integration" and "impact on decision making." NEOH and ISSEP were perceived as the best tools for evaluation of One Health (OH) aspects, and ECoSur as best for evaluation of the quality of collaboration. PMP-AMR and ATLASS seemed to be the most user-friendly tools, particularly designed for risk managers. ATLASS was the only tool focusing specifically on laboratory activities. Our experience is that adequate resources are needed to perform evaluation(s). In most cases, evaluation would require involvement of several assessors and/or stakeholders, taking from weeks to months to complete. This study can help direct future evaluators of integrated AMU and AMR surveillance toward the most adequate tool for their specific evaluation purpose.

Multilocus sequence analysis provides new insight into population structure and genetic diversity of Leishmania tropica in Morocco.

Cutaneous leishmaniasis (CL) is one of the most neglected tropical diseases, caused by different Leishmania species. Despite its high incidence in Morocco, CL due to Leishmania tropica is poorly understood in terms of its epidemiological status and population structure. In this study, we used multilocus sequence typing (MLST) in order to explore the genetic heterogeneity of L. tropica strains. Samples (N = 48) were collected from CL patients in two localities in Morocco (Foum Jamaa in the Azilal province and Imintanoute in Chichaoua province). PCR-sequencing of 18 strains was carried out for six housekeeping genes (cytb, me, fh, g6pd, pgd and gpi), Genetic diversity indices showed a high population genetic differentiation between and among populations. There was no shared haplotypes between the two localities studied. Our results reveal a considerable degree of differentiation through the relatively high FST value (> 0.4) and remarkable intraspecific polymorphism (S = 29). Imintanoute strains have more polymorphisms (S = 22) than the Foum Jamaa strains despite their small sample size. These results provide crucial background information of epidemiology in Imintanoute which raises questions about animal involvement in L. tropica transmission cycle.

Evaluating the Integration of One Health in Surveillance Systems for Antimicrobial Use and Resistance: A Conceptual Framework.

It is now widely acknowledged that surveillance of antimicrobial resistance (AMR) must adopt a "One Health" (OH) approach to successfully address the significant threats this global public health issue poses to humans, animals, and the environment. While many protocols exist for the evaluation of surveillance, the specific aspect of the integration of a OH approach into surveillance systems for AMR and antimicrobial Use (AMU), suffers from a lack of common and accepted guidelines and metrics for its monitoring and evaluation functions. This article presents a conceptual framework to evaluate the integration of OH in surveillance systems for AMR and AMU, named the Integrated Surveillance System Evaluation framework (ISSE framework). The ISSE framework aims to assist stakeholders and researchers who design an overall evaluation plan to select the relevant evaluation questions and tools. The framework was developed in partnership with the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). It consists of five evaluation components, which consider the capacity of the system to: [1] integrate a OH approach, [2] produce OH information and expertise, [3] generate actionable knowledge, [4] influence decision-making, and [5] positively impact outcomes. For each component, a set of evaluation questions is defined, and links to other available evaluation tools are shown. The ISSE framework helps evaluators to systematically assess the different OH aspects of a surveillance system, to gain comprehensive information on the performance and value of these integrated efforts, and to use the evaluation results to refine and improve the surveillance of AMR and AMU globally.

Characterisation and mapping of the surveillance system for antimicrobial resistance and antimicrobial use in the United Kingdom.

BACKGROUND: Surveillance of antimicrobial resistance (AMR) is an essential component of any strategy to mitigate AMR and needs regular evaluation to ensure its effectiveness. A first step for any evaluation is to describe the system and context. In this study, we aimed to characterise and map the surveillance system for AMR and antimicrobial use (AMU) in the United Kingdom (UK) using a One Health (OH) approach and to identify integration points in the system. METHODS: To describe the surveillance system for AMR/AMU, international guidelines for establishing surveillance systems for AMR and AMU were used. A review of the literature was conducted to collect information on the different parameters identified. RESULTS: Multiple data collection systems exist for AMU and AMR in humans, animals and food. Each sector is responsible for the planning, implementation, analysis and reporting of its own surveillance for AMR and AMU. Some cross-sectoral collaborative activities exist such as the UK AMR contingency plan and the publication of UK OH reports; there are opportunities for further integration such as the harmonisation of data analyses methods and interpretation across sectors and the publication of joint surveillance reports. CONCLUSION: This overview of key stakeholders, data collection streams, reporting, linkages within and across sectors and international monitoring forms an important basis for future evaluation of the UK AMR/AMU surveillance system from a OH perspective.

Overview of Evidence of Antimicrobial Use and Antimicrobial Resistance in the Food Chain.

Antimicrobial resistance (AMR) is a global health problem. Bacteria carrying resistance genes can be transmitted between humans, animals and the environment. There are concerns that the widespread use of antimicrobials in the food chain constitutes an important source of AMR in humans, but the extent of this transmission is not well understood. The aim of this review is to examine published evidence on the links between antimicrobial use (AMU) in the food chain and AMR in people and animals. The evidence showed a link between AMU in animals and the occurrence of resistance in these animals. However, evidence of the benefits of a reduction in AMU in animals on the prevalence of resistant bacteria in humans is scarce. The presence of resistant bacteria is documented in the human food supply chain, which presents a potential exposure route and risk to public health. Microbial genome sequencing has enabled the establishment of some links between the presence of resistant bacteria in humans and animals but, for some antimicrobials, no link could be established. Research and monitoring of AMU and AMR in an integrated manner is essential for a better understanding of the biology and the dynamics of antimicrobial resistance.

A one health framework for the evaluation of rabies control programmes: a case study from Colombo City, Sri Lanka.

BACKGROUND: One Health addresses complex challenges to promote the health of all species and the environment by integrating relevant sciences at systems level. Its application to zoonotic diseases is recommended, but few coherent frameworks exist that combine approaches from multiple disciplines. Rabies requires an interdisciplinary approach for effective and efficient management. METHODOLOGY/PRINCIPAL FINDINGS: A framework is proposed to assess the value of rabies interventions holistically. The economic assessment compares additional monetary and non-monetary costs and benefits of an intervention taking into account epidemiological, animal welfare, societal impact and cost data. It is complemented by an ethical assessment. The framework is applied to Colombo City, Sri Lanka, where modified dog rabies intervention measures were implemented in 2007. The two options included for analysis were the control measures in place until 2006 ("baseline scenario") and the new comprehensive intervention measures ("intervention") for a four-year duration. Differences in control cost; monetary human health costs after exposure; Disability-Adjusted Life Years (DALYs) lost due to human rabies deaths and the psychological burden following a bite; negative impact on animal welfare; epidemiological indicators; social acceptance of dogs; and ethical considerations were estimated using a mixed method approach including primary and secondary data. Over the four years analysed, the intervention cost US $1.03 million more than the baseline scenario in 2011 prices (adjusted for inflation) and caused a reduction in dog rabies cases; 738 DALYs averted; an increase in acceptability among non-dog owners; a perception of positive changes in society including a decrease in the number of roaming dogs; and a net reduction in the impact on animal welfare from intermediate-high to low-intermediate. CONCLUSIONS: The findings illustrate the multiple outcomes relevant to stakeholders and allow greater understanding of the value of the implemented rabies control measures, thereby providing a solid foundation for informed decision-making and sustainable control.