Evolutionary Aspects of Emerging Lyme Disease in Canada

In North America, Lyme disease (LD) is a tick-borne zoonosis caused by the spirochete bacterium Borrelia burgdorferi sensu stricto, which is maintained by wildlife. Tick vectors and bacteria are currently spreading into Canada and causing increasing numbers of cases of LD in humans and raising a pressing need for public health responses. There is no vaccine, and LD prevention depends on knowing who is at risk and informing them how to protect themselves from infection. Recently, it was found in the United States that some strains of B. burgdorferi sensu stricto cause severe disease, whereas others cause mild, self-limiting disease. While many strains occurring in the United States also occur in Canada, strains in some parts of Canada are different from those in the United States. We therefore recognize a need to identify which strains specific to Canada can cause severe disease and to characterize their geographic distribution to determine which Canadians are particularly at risk. In this review, we summarize the history of emergence of LD in North America, our current knowledge of B. burgdorferi sensu stricto diversity, its intriguing origins in the ecology and evolution of the bacterium, and its importance for the epidemiology and clinical and laboratory diagnosis of LD. We propose methods for investigating associations between B. burgdorferi sensu stricto diversity, ecology, and pathogenicity and for developing predictive tools to guide public health interventions. We also highlight the emergence of B. burgdorferi sensu stricto in Canada as a unique opportunity for exploring the evolutionary aspects of tick-borne pathogen emergence.     

Conspicuous impacts of inconspicuous hosts on the Lyme disease epidemic

Emerging zoonotic pathogens are a constant threat to human health throughout the world. Control strategies to protect public health regularly fail, due in part to the tendency to focus on a single host species assumed to be the primary reservoir for a pathogen. Here, we present evidence that a diverse set of species can play an important role in determining disease risk to humans using Lyme disease as a model. Host-targeted public health strategies to control the Lyme disease epidemic in North America have focused on interrupting Borrelia burgdorferi sensu stricto (ss) transmission between blacklegged ticks and the putative dominant reservoir species, white-footed mice. However, B. burgdorferi ss infects more than a dozen vertebrate species, any of which could transmit the pathogen to feeding ticks and increase the density of infected ticks and Lyme disease risk. Using genetic and ecological data, we demonstrate that mice are neither the primary host for ticks nor the primary reservoir for B. burgdorferi ss, feeding 10% of all ticks and 25% of B. burgdorferi-infected ticks. Inconspicuous shrews feed 35% of all ticks and 55% of infected ticks. Because several important host species influence Lyme disease risk, interventions directed at a multiple host species will be required to control this epidemic.     

Assisted Suicide in Switzerland: Clarifying Liberties and Claims

Assisting suicide is legal in Switzerland if it is offered without selfish motive to a person with decision‐making capacity. Although the ‘Swiss model’ for suicide assistance has been extensively described in the literature, the formally and informally protected liberties and claims of assistors and recipients of suicide assistance in Switzerland are incompletely captured in the literature. In this article, we describe the package of rights involved in the ‘Swiss model’ using the framework of Hohfeldian rights as modified by Wenar. After outlining this framework, we dissect the rights involved in suicide assistance in Switzerland, and compare it with the situation in England and Germany. Based on this approach, we conclude that in Switzerland, claim rights exist for those requesting suicide assistance, and for those who are considering providing such assistance, even though no entitlements exist toward suicide assistance. We then describe the implementation of the ‘Swiss model’ and difficulties arising within it. Clarifying these issues is important to understand the Swiss situation, to evaluate what features of it may or may not be worth correcting or emulating, and to understand how it can impact requests for suicide assistance in other countries due to ‘suicide tourism’. It is also important to understand exactly what sets Switzerland apart from other countries with different legislations regarding suicide assistance.     

Inter-Model Comparison of the Landscape Determinants of Vector-Borne Disease: Implications for Epidemiological and Entomological Risk Modeling

Extrapolating landscape regression models for use in assessing vector-borne disease risk and other applications requires thoughtful evaluation of fundamental model choice issues. To examine implications of such choices, an analysis was conducted to explore the extent to which disparate landscape models agree in their epidemiological and entomological risk predictions when extrapolated to new regions. Agreement between six literature-drawn landscape models was examined by comparing predicted county-level distributions of either Lyme disease or Ixodes scapularis vector using Spearman ranked correlation. AUC analyses and multinomial logistic regression were used to assess the ability of these extrapolated landscape models to predict observed national data. Three models based on measures of vegetation, habitat patch characteristics, and herbaceous landcover emerged as effective predictors of observed disease and vector distribution. An ensemble model containing these three models improved precision and predictive ability over individual models. A priori assessment of qualitative model characteristics effectively identified models that subsequently emerged as better predictors in quantitative analysis. Both a methodology for quantitative model comparison and a checklist for qualitative assessment of candidate models for extrapolation are provided; both tools aim to improve collaboration between those producing models and those interested in applying them to new areas and research questions.     

Multi-criteria decision analysis approach for strategy scale-up with application to Chagas disease management in Bolivia

ObjectiveDesign and build a strategy construction and evaluation software system to help stakeholders to develop viable strategies to expand (and adapt) the Chagas Platform healthcare model through the primary healthcare system in Bolivia.MethodsThe software was built based on a ranking of medical Interventions and Actions (needed to support Interventions’ implementation) needed for comprehensive management of Chagas Disease in Bolivia. The ranking was performed using a Multi Criteria Decision Analysis (MCDA) methodology adapted to the WHO’s building blocks framework. Data regarding the criteria and the rankings was obtained through surveys and interviews with health care professionals working on Chagas disease. The Analytical Hierarchy Process was used to construct the decision criteria weights. Data Envelopment Analysis was used to identify the Interventions that lay on the efficiency frontier of outcomes and the complexity of associated Actions. These techniques were combined with integer programing tools using the open-source software R to build a decision-making tool to assess the outcomes and complexity of any combination of Interventions and Actions. This model and tool were applied to data concerning the care of Chagas disease in Bolivia collected through surveys of experts. The tool works by loading the data from each specific context.ResultsThe initial set of Interventions and Actions recommended after analysis of the survey data was further refined through face-to-face interviews with field experts in Bolivia, resulting in a strategy of 18 Interventions and 15 Actions. Within the WHO model the Leadership and Governance building block came up as the one needing more support with Actions such as the inclusion of Chagas into Annual Municipal Operational Plans by appointing local and provincial coordinators.ConclusionThis project established the suitability of the model for constructing healthcare strategies. The model could be developed further resulting in a decision-making tool for program managers in a wide range of healthcare related issues, including neglected and/ or prevalent diseases. The tool has the potential to be used at different stages of decision making by diverse stakeholders in order to coordinate activities needed to address a health problem.     

A simple way to unify multicriteria decision analysis (MCDA) and stochastic multicriteria acceptability analysis (SMAA) using a Dirichlet distribution in benefit–risk assessment

Quantitative methodologies have been proposed to support decision making in drug development and monitoring. In particular, multicriteria decision analysis (MCDA) and stochastic multicriteria acceptability analysis (SMAA) are useful tools to assess the benefit–risk ratio of medicines according to the performances of the treatments on several criteria, accounting for the preferences of the decision makers regarding the relative importance of these criteria. However, even in its probabilistic form, MCDA requires the exact elicitations of the weights of the criteria by the decision makers, which may be difficult to achieve in practice. SMAA allows for more flexibility and can be used with unknown or partially known preferences, but it is less popular due to its increased complexity and the high degree of uncertainty in its results. In this paper, we propose a simple model as a generalization of MCDA and SMAA, by applying a Dirichlet distribution to the weights of the criteria and by making its parameters vary. This unique model permits to fit both MCDA and SMAA, and allows for a more extended exploration of the benefit–risk assessment of treatments. The precision of its results depends on the precision parameter of the Dirichlet distribution, which could be naturally interpreted as the strength of confidence of the decision makers in their elicitation of preferences.     

Weighting of Criteria for Disease Prioritization Using Conjoint Analysis and Based on Health Professional and Student Opinion

Disease prioritization exercises have been used by several organizations to inform surveillance and control measures. Though most methodologies for disease prioritization are based on expert opinion, it is becoming more common to include different stakeholders in the prioritization exercise. This study was performed to compare the weighting of disease criteria, and the consequent prioritization of zoonoses, by both health professionals and students in Switzerland using a Conjoint Analysis questionnaire. The health professionals comprised public health and food safety experts, cantonal physicians and cantonal veterinarians, while the student group comprised first-year veterinary and agronomy students. Eight criteria were selected for this prioritization based on expert elicitation and literature review. These criteria, described on a 3-tiered scale, were evaluated through a choice-based Conjoint Analysis questionnaire with 25 choice tasks. Questionnaire results were analyzed to obtain importance scores (for each criterion) and mean utility values (for each criterion level), and the latter were then used to rank 16 zoonoses. While the most important criterion for both groups was “Severity of the disease in humans”, the second ranked criteria by the health professionals and students were “Economy” and “Treatment in humans”, respectively. Regarding the criterion “Control and Prevention”, health professionals tended to prioritize a disease when the control and preventive measures were described to be 95% effective, while students prioritized a disease if there were almost no control and preventive measures available. Bovine Spongiform Encephalopathy was the top-ranked disease by both groups. Health professionals and students agreed on the weighting of certain criteria such as “Severity” and “Treatment of disease in humans”, but disagreed on others such as “Economy” or “Control and Prevention”. Nonetheless, the overall disease ranking lists were similar, and these may be taken into consideration when making future decisions regarding resource allocation for disease control and prevention in Switzerland.     

Support for Sustainable Development Policy Decisions A Case Study from Highway Maintenance

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http://dx.doi.org/10.1065/lca2006.04.009

Goal, Scope and Method

logy. This paper describes a case study carried out as part of a wider programme to provide support for environmental decision-making in the highway maintenance programme of a local government body: Surrey County Council (SCC). UK local authorities are required to demonstrate that sustainable development principles are addressed in service provision, by improving environmental, economic or social wellbeing and improving public consultation. A methodological approach was developed to meet these requirements by using life cycle assessment (LCA) and multi-criteria decision analysis (MCDA) through the process of decision conferencing.

Results

In projects requiring strategic decisions, difficulties arise in identifying relevant sustainable development criteria and in evaluating maintenance options against these criteria where the context for decision-making is complex and characterised by uncertainty, where multiple public policy objectives compete and a number of decision-makers and key players are affected by the outcome. Clearly, a structured process is needed to engage such stakeholders in the decision process, utilising quantitative and qualitative information. The approach described proved to be capable of fulfilling these requirements.

Conclusions

and Recommendations. The approach of combining LCA with MCDA through decision conferencing is capable of further development to support other strategic decision-making activities. However, this illustrative case study has revealed a need for methodological developments in LCA for local, project-level decisions.

     

Multi-criteria decision analysis to select metrics for design and monitoring of sustainable ecosystem restorations

The selection of metrics for ecosystem restoration programs is critical for improving the quality and utility of design and monitoring programs, informing adaptive management actions, and characterizing project success. The metrics selection process, that in practice is left to the subjective judgment of stakeholders, is often complex and should simultaneously take into account monitoring data, environmental models, socio-economic considerations, and stakeholder interests. With limited funding, it is often very difficult to balance the importance of multiple metrics, often competing, intended to measure different environmental, social, and economic aspects of the system. To help restoration planners and practitioners develop the most useful and informative design and monitoring programs, we propose the use of multi-criteria decision analysis (MCDA) methods, broadly defined, to select optimal ecosystem restoration metric sets. In this paper, we apply and compare two MCDA methods, multi-attribute utility theory (MAUT), and probabilistic multi-criteria acceptability analysis (ProMAA), for a hypothetical river restoration case study involving multiple stakeholders with competing interests. Overall, the MCDA results in a systematic, quantitative, and transparent evaluation and comparison of potential metrics that provides planners and practitioners with a clear basis for selecting the optimal set of metrics to evaluate restoration alternatives and to inform restoration design and monitoring. In our case study, the two MCDA methods provide comparable results in terms of selected metrics. However, because ProMAA can consider probability distributions for weights and utility values of metrics for each criterion, it is most likely the best option for projects with highly uncertain data and significant stakeholder involvement. Despite the increase in complexity in the metrics selection process, MCDA improves upon the current, commonly-used ad-hoc decision practice based on consultations with stakeholders by applying and presenting quantitative aggregation of data and judgment, thereby increasing the effectiveness of environmental design and monitoring and the transparency of decision making in restoration projects.     

Application of fuzzy VIKOR for evaluation of green supply chain management practices

Environmentally sustainable activities have received an increasing interest among the firms to improve their practices in the supply chain. Although environmental regulations force firms consider these issues, but, green issues are new, evolving every day, and requires a continuous study in the field to gain a complete understanding of the problems. In this study, we illustrate the case of a laptop manufacturer in Malaysia that pursues to evaluate green supply chain management (GSCM) indicators among its practitioners. This paper develops a quantitative evaluation model to measure the uncertainty of GSCM activities and applies an approach based on Vlsekriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method which is an extension of intuitionistic fuzzy environment aiming to solve the green multi-criteria decision making (GMCDM) problem. The triangular fuzzy numbers (TFNs) were used to handle imprecise numerical quantities. Then, a hierarchical multiple criteria decision making (MCDM) model was proposed based on fuzzy sets theory and VIKOR method to deal with the problem. The results show the alternative ranks of the four evaluated companies which was based on their performance in GSCM initiatives. The results also indicated that the main criteria of the research ranked as follows respectively: eco-design, green production, green purchasing, green recycling, green transportation and green warehousing. Finally, a comparative analysis of results by fuzzy VIKOR is presented. Additionally the scope for future studies is provided at the end of the paper.     

Prevalence and prediction of Lyme disease in Hainan province

Lyme disease (LD) is one of the most important vector-borne diseases worldwide. However, there is limited information on the prevalence and risk analysis using correlated factors in the tropical areas. A total of 1583 serum samples, collected from five hospitals of Hainan Province, were tested by immunofluorescence assay (IFA) and western blot (WB) analyses using anti-Borrelia burgdorferi antibodies. Then, we mapped the distribution of positive rate (by IFA) and the spread of confirmed Lyme patients (by WB). Using ArcGIS, we compiled host-vector-human interactions and correlated data as risk factor layers to predict LD risk in Hainan Province. There are three LD hotspots, designated hotspot I, which is located in central Hainan, hotspot II, which contains Sanya district, and hotspot III, which lies in the Haikou-Qiongshan area. The positive rate (16.67% by IFA) of LD in Qiongzhong, located in hotspot I, was higher than that in four other areas. Of confirmed cases of LD, 80.77% of patients (42/52) whose results had been confirmed by WB were in hotspots I and III. Hotspot II, with unknowed prevalence of LD, need to be paid more attention considering human-vector interaction. Wuzhi and Limu mountains might be the most important areas for the prevalence of LD, as the severe host-vector and human-vector interactions lead to a potential origin site for LD. Qiongzhong is the riskiest area and is located to the east of Wuzhi Mountain. In the Sanya and Haikou-Qiongshan area, intervening in the human-vector interaction would help control the prevalence of LD.     

Protective immunity in lyme borreliosis

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne illness in the USA. Although early infection can be treated with antibiotics, the initial diagnosis is difficult and late disease may be recalcitrant to therapy. A vaccine against Lyme disease is therefore needed, and murine models of Lyme borreliosis have facilitated its development. In this review, Erol Fikrig, Fred Kantor, Stephen Barthold and Richard Flavell focus on the use of Borrelia surface antigens as vaccine candidates for Lyme disease.     

Sex-biased genetic structure in the vector of Lyme disease,Ixodes ricinus

Abstract.— We analyzed 725 Ixodes ricinus ticks (the principal vector of Lyme disease in Europe) collected in Switzerland in 1995 and 1996 (three and eight samples, respectively) and in Tunisia in 1996 (one sample) with five microsatellite markers. We found highly significant genetic differentiation between Swiss and Tunisian samples but detected almost no differentiation within Switzerland, even between those samples separated by the Alps. Interestingly, we found that I. ricinus females were more genetically related to one another than were males at a local scale, which would indicate a higher dispersal rate of immature males. Possible explanations for these findings in terms of sex-specific association of ticks with certain hosts (e.g., birds) and their epidemiological consequences are discussed.     

Bovine virus diarrhea and the vector-borne diseases Anaplasmosis and Bluetongue: a sero-surveillance in free-ranging red deer (<Emphasis Type="Italic">Cervus elaphus</Emphasis>) in selected areas of Switzerland

Due to climate changes, diseases emerging from southerly adjacent areas (Mediterranean countries) are likely to spread northward. Expanded migration of red deer harbors the risk of introducing new pathogens into a naive population of either wild or domestic animals. Little is known about the importance of red deer as a potential reservoir for diseases of domestic ruminants in Switzerland. Deer is susceptible for all three agents that were selected in this study: bovine virus diarrhea virus (BVDV), Anaplasma marginale (AM), and Bluetongue virus (BTV). The goal of this project was to establish the serological status of red deer in Switzerland concerning BVDV, AM, and BTV, and to assess the possible impact of disease dynamics with a focus on potential transmission of these diseases from red deer to cattle or vice versa. Sampling areas were selected according the following criteria: abundance of red deer, potential insect vector distribution due to climatic conditions, and traditional alpine pasture husbandry along with known migration routes of red deer. Blood samples were collected during the regular hunting season 2004 and 2005 by hunters and gamekeepers. There was no serological evidence for the presence of the vector-borne diseases AM and BT in red deer in Switzerland. Four out of 234 sera showed a positive result for BVD, corresponding to a sero-prevalence of 1.7% (95% CI 0.46–4.38). Facing the fact of the high sero-prevalence for BVD in Swiss cattle (60–80%) disease transmission from red deer to cattle in these areas under investigation is rather unlikely.     

Borrelia burgdorferi genes selectively expressed in ticks and mammals

Lyme disease is a tick-borne infection caused by the spirochete Borrelia burgdorferi. Recent studies have focused on how the Lyme disease bacterium overcomes the challenges faced by an organism that depends on a vector-borne life style. These studies indicate that the spirochete expresses different surface proteins at different stages of its life. Here, Aravinda de Silva and Erol Fikrig review the evidence for differential gene expression and discuss the implications of these findings for the Lyme disease vaccine that is currently being tested in human trials.     

Alpha fucosidase and beta galactosidase in serum of a Lyme disease patients as a possible marker of accelerated senescence - a preliminary study

Lyme disease (LD) is the most prevalent tick-borne disease in Europe. LD is caused by the spirochete Borrelia burgdorferi. LD is a chronic disease which can attack a number of organs: skin, heart, brain, joints. Chronic, low-grade inflammation involves general production of pro-inflammatory cytokines and inflammatory markers and is a typical feature of aging. So far, the best method of diagnosing LD is a time-consuming and expensive two-stage serological method. The aim of our study was to evaluate the activity of two lysosomal exoglycosidases: α-fucosidase (FUC) and β-galactosidase (GAL) in the serum of patients with Lyme disease, as potential markers of LD. Due to the increasing number of patients with Lyme disease and a number of false results, new ways to diagnose this disease are still being sought. As elevated level of β-galactosidase is a manifestation of residual lysosomal activity in senescent cells, the increase in its activity in serum during chronic Lyme disease might be a marker of a potentially accelerated senescence process. The study was performed on serum taken from cubital veins of 15 patients with Lyme disease and eight healthy subjects (control group). FUC and GAL activity was measured by the method of Chatterjee et al. as modified by Zwierz et al. In the serum of patients with Lyme disease, GAL activity significantly increased (p = 0.029), and the activity of FUC had a tendency to increase (p = 0.153), compared to the control group. A significant increase in GAL activity in the serum of patients with Lyme disease indicates an increased catabolism of glycoconjugates (glycoproteins, glycolipids, proteoglycans) and could be helpful in the diagnosis of Lyme disease, although this requires confirmation in a larger group of patients. As GAL is the most widely used assay for detection of senescent cells, an elevated level of β-galactosidase might be a manifestation of accelerated senescence process in the course of Lyme disease.     

TACKLING SOCIALLY DETERMINED DENTAL INEQUALITIES: ETHICAL ASPECTS OF CHILDSMILE, THE NATIONAL CHILD ORAL HEALTH DEMONSTRATION PROGRAMME IN SCOTLAND

Many ethical issues are posed by public health interventions. Although abstract theorizing about these issues can be useful, it is the application of ethical theory to real cases which will ultimately be of benefit in decision-making. To this end, this paper will analyse the ethical issues involved in Childsmile, a national oral health demonstration programme in Scotland that aims to improve the oral health of the nation's children and reduce dental inequalities through a combination of targeted and universal interventions. With Scotland's level of dental caries among the worst in Europe, Childsmile represents one of the largest programmes of work aimed at combating oral health inequalities in the UK. The areas of ethical interest include several contrasting themes: reducing health inequalities and improving health; universal and targeted interventions; political values and evidence base; prevention and treatment; and underlying all of these, justice and utility.     

Dynamic Epidemiological Models for Dengue Transmission: A Systematic Review of Structural Approaches

Dengue is a vector-borne disease recognized as the major arbovirose with four immunologically distant dengue serotypes coexisting in many endemic areas. Several mathematical models have been developed to understand the transmission dynamics of dengue, including the role of cross-reactive antibodies for the four different dengue serotypes. We aimed to review deterministic models of dengue transmission, in order to summarize the evolution of insights for, and provided by, such models, and to identify important characteristics for future model development. We identified relevant publications using PubMed and ISI Web of Knowledge, focusing on mathematical deterministic models of dengue transmission. Model assumptions were systematically extracted from each reviewed model structure, and were linked with their underlying epidemiological concepts. After defining common terms in vector-borne disease modelling, we generally categorised fourty-two published models of interest into single serotype and multiserotype models. The multi-serotype models assumed either vector-host or direct host-to-host transmission (ignoring the vector component). For each approach, we discussed the underlying structural and parameter assumptions, threshold behaviour and the projected impact of interventions. In view of the expected availability of dengue vaccines, modelling approaches will increasingly focus on the effectiveness and cost-effectiveness of vaccination options. For this purpose, the level of representation of the vector and host populations seems pivotal. Since vector-host transmission models would be required for projections of combined vaccination and vector control interventions, we advocate their use as most relevant to advice health policy in the future. The limited understanding of the factors which influence dengue transmission as well as limited data availability remain important concerns when applying dengue models to real-world decision problems.     

Climate Change,Vector-borne Disease and Interdisciplinary Research: Social Science Perspectives on an Environment and Health Controversy

Over the last two decades, the science of climate change’s theoretical impacts on vector-borne disease has generated controversy related to its methodological validity and relevance to disease control policy. Critical social science analysis, drawing on science and technology studies and the sociology of social movements, demonstrates consistency between this controversy and the theory that climate change is serving as a collective action frame for some health researchers. Within this frame, vector-borne disease data are interpreted as a symptom of climate change, with the need for further interdisiplinary research put forth as the logical and necessary next step. Reaction to this tendency on the part of a handful of vector-borne disease specialists exhibits characteristics of academic boundary work aimed at preserving the integrity of existing disciplinary boundaries. Possible reasons for this conflict include the leadership role for health professionals and disciplines in the envisioned interdiscipline, and disagreements over the appropriate scale of interventions to control vector-borne diseases. Analysis of the competing frames in this controversy also allows identification of excluded voices and themes, such as international political economic explanations for the health problems in question. A logical conclusion of this analysis, therefore, is the need for critical reflection on environment and health research and policy to achieve integration with considerations of global health equity.