Disease Risk Analysis Research Articles

Biosecurity for Translocations: Cirl Bunting (Emberiza cirlus), Fisher's Estuarine Moth (Gortyna borelii lunata), Short-Haired Bumblebee (Bombus subterraneus) and Pool Frog (Pelophylax lessonae) Translocations as Case Studies.

Exposure to parasites in conservation translocations increases the risks to recipient and translocated populations from disease, and therefore there has been interest in implementing biosecurity methods. Using four case examples we described how biosecurity was applied in practical translocation scenarios prior to and during a translocation and also post-release. We implemented biosecurity, including quarantine barriers, at specific points in the translocation pathway where hazards, identified by the disease risk analysis, had the potential to induce disease. Evidence that biosecurity protected translocated and recipient populations, included an absence of mortality associated with high-risk non-native parasites, a reduction in mortality associated with endemic parasites, the absence of high-risk pathogenic parasites, or associated diseases, at the destination; and the apparent absence of diseases in closely related species at the destination site. The biosecurity protocols did not alter the level or duration of translocated species confinement and therefore probably did not act as a stressor. There is a monetary cost involved in biosecurity but the epidemiological evidence suggests that conservation translocation managers should carefully consider its use. Breakdowns in quarantine have occurred in human hospitals despite considerable investment and training for health professionals, and we therefore judge that there is a need for training in the objectives and maintenance of quarantine barriers in conservation translocations. Biosecurity protocols for conservation translocations should be continually updated in response to findings from disease risk analysis and post-release disease surveillance and we recommend further studies to evaluate their effectiveness.

Disease Risk Analysis and Post-Release Health Surveillance for a Reintroduction Programme: the Pool Frog Pelophylax lessonae.

There are risks from disease in undertaking wild animal reintroduction programmes. Methods of disease risk analysis have been advocated to assess and mitigate these risks, and post-release health and disease surveillance can be used to assess the effectiveness of the disease risk analysis, but results for a reintroduction programme have not to date been recorded. We carried out a disease risk analysis for the reintroduction of pool frogs (Pelophylax lessonae) to England, using information gained from the literature and from diagnostic testing of Swedish pool frogs and native amphibians. Ranavirus and Batrachochytrium dendrobatidis were considered high-risk disease threats for pool frogs at the destination site. Quarantine was used to manage risks from disease due to these two agents at the reintroduction site: the quarantine barrier surrounded the reintroduced pool frogs. Post-release health surveillance was carried out through regular health examinations of amphibians in the field at the reintroduction site and collection and examination of dead amphibians. No significant health or disease problems were detected, but the detection rate of dead amphibians was very low. Methods to detect a higher proportion of dead reintroduced animals and closely related species are required to better assess the effects of reintroduction on health and disease.

Methods of Disease Risk Analysis in Wildlife Translocations for Conservation Purposes

Wildlife is intentionally and unintentionally translocated regularly carrying with it a range of parasites and pathogens. There are numerous examples of disease outbreaks originating from translocated animals. Managers of conservation projects, which involve translocating wildlife have a responsibility to protect humans, domestic animals, other wildlife and the ecosystem from negative effects of disease carried by the focus species. There is a significant lack of data available on the susceptibility, epidemiology and impacts of pathogens in wildlife populations making preventative actions challenging. Risk analysis has been developed to provide an objective, repeatable, transparent and documented assessment of the risks posed by a course of action. Standardised techniques have been developed and are utilised routinely to aid decision making. It is a tool used to guide policy making and disease control planning by governments and international organisations such as the OIE (World Organisation for Animal Health). Qualitative risk analysis is particularly useful in fields when quantitative data is lacking. Risk analysis has been developed for use in animal health risk management and subsequently adapted for wildlife disease management scenarios, cumulating in publication of the OIE/IUCN Manual of Procedures for Wildlife Disease Risk Analysis (2014). This paper considers further modification of risk analysis methods for wildlife translocations undertaken for conservation purposes. The challenges of these specific scenarios including hazard identification, multiple epidemiological pathways and data gaps are addressed and tools which could improve the usefulness of the technique, such as developing scenario trees and rating uncertainty are proposed.

Carrier Screening is a Deficient Strategy for Determining Sperm Donor Eligibility and Reducing Risk of Disease in Recipient Children.

Aims: DNA-based carrier screening is a standard component of donor eligibility protocols practiced by U.S. sperm banks. Applicants who test positive for carrying a recessive disease mutation are typically disqualified. The aim of our study was to examine the utility of a range of screening panels adopted by the industry and the effectiveness of the screening paradigm in reducing a future child's risk of inheriting disease. Methods: A cohort of 27 donor applicants, who tested negative on an initial cystic fibrosis carrier test, was further screened with three expanded commercial carrier testing panels. These results were then compared to a systematic analysis of the applicants' DNA using next-generation sequencing (NGS) data. Results: The carrier panels detected serious pediatric disease mutations in one, four, or six donor applicants. Because each panel screens distinct regions of the genome, no single donor was uniformly identified as carrier positive by all three panels. In contrast, systematic NGS analysis identified all donors as carriers of one or more mutations associated with severe monogenic pediatric disease. These included 30 variants classified as “pathogenic” based on clinical observation and 66 with a high likelihood of causing gene dysfunction. Conclusion: Despite tremendous advances in variant identification, understanding, and analysis, the vast majority of disease-causing mutation combinations remain undetected by commercial carrier screening panels, which cover a narrow, and often distinct, subset of genes and mutations. The biological reality is that all donors and recipients carry serious recessive disease mutations. This challenges the utility of any screening protocol that anchors donor eligibility to carrier status. A more effective approach to reducing recessive disease risk would consider joint comprehensive analysis of both donor and recipient disease mutations. This type of high-resolution recessive disease risk analysis is now available and affordable, but industry practice must be modified to incorporate its use.

LESSONS FROM A RETROSPECTIVE ANALYSIS OF A 5-YR PERIOD OF QUARANTINE AT SAN DIEGO ZOO: A RISK-BASED APPROACH TO QUARANTINE ISOLATION AND TESTING MAY BENEFIT ANIMAL WELFARE.

Quarantine is designed primarily to prevent the introduction of transmissible diseases to zoological collections. Improvements in preventive medicine, disease eradication, and comprehensive pathology programs call into question current industry quarantine standards. Disease risk analysis was used at the San Diego Zoo (SDZ) and the SDZ Safari Park to eliminate quarantine isolation and transmissible disease testing for animals transferred between the two institutions. To determine if a risk-based approach might be valid between other institutions and SDZ, we reviewed quarantine data for animals arriving at SDZ from 81 Association of Zoos and Aquariums (AZA)-accredited and 124 other sources (e.g., non-AZA-accredited institutions, private breeders, private dealers, governmental bodies) over a 5-yr period (2009-2013). No mammal or herptile failed quarantine due to transmissible diseases of concern. Approximately 2.5% of incoming birds failed quarantine due to transmissible disease; however, all 14 failed individuals were obtained from three nonaccredited sources (private breeders, confiscation). The results of our study suggest that a risk-based approach could be used to minimize or eliminate quarantine for the transfer of animals from institutions with comprehensive disease surveillance programs and/or preshipment testing practices. Quarantine isolation with testing remains an essential defense against introducing transmissible diseases of concern when there is a lack of health knowledge about the animals being received.

Bringing Back a Healthy Buzz? Invertebrate Parasites and Reintroductions: A Case Study in Bumblebees.

Reintroductions can play a key role in the conservation of endangered species. Parasites may impact reintroductions, both positively and negatively, but few case studies of how to manage parasites during reintroductions exist. Bumblebees are in decline at regional and global scales, and reintroductions can be used to re-establish extinct local populations. Here we report on how the risks associated with parasites are being managed in an ongoing reintroduction of the short-haired bumblebee, Bombus subterraneus, to the UK. Disease risk analysis was conducted and disease risk management plans constructed to design a capture-quarantine-release system that minimised the impacts on both the bumblebees and on their natural parasites. Given that bumblebee parasites are (i) generalists, (ii) geographically ubiquitous, and (iii) show evidence of local adaptation, the disease risk management plan was designed to limit the co-introduction of parasites from the source population in Sweden to the destination site in the UK. Results suggest that this process at best eliminated, or at least severely curtailed the co-introduction of parasites, and ongoing updates of the plan enabled minimization of impacts on natural host-parasite dynamics in the Swedish source population. This study suggests that methods designed for reintroductions of vertebrate species can be successfully applied to invertebrates. Future reintroductions of invertebrates where the parasite fauna is less well known should take advantage of next-generation barcoding and multiple survey years prior to the start of reintroductions, to develop comprehensive disease risk management plans.

Using Qualitative Disease Risk Analysis for Herpetofauna Conservation Translocations Transgressing Ecological and Geographical Barriers

Through the exploration of disease risk analysis methods employed for four different UK herpetofauna translocations, we illustrate how disease hazards can be identified, and how the risk of disease can be analysed. Where ecological or geographical barriers between source and destination sites exist, parasite populations are likely to differ in identity or strain between the two sites, elevating the risk from disease and increasing the number and category of hazards requiring analysis. Simplification of the translocation pathway through the avoidance of these barriers reduces the risk from disease. The disease risk analysis tool is intended to aid conservation practitioners in decision making relating to disease hazards prior to implementation of a translocation.

Plasma metabolomic profiles enhance precision medicine for volunteers of normal health

Precision medicine, taking account of human individuality in genes, environment, and lifestyle for early disease diagnosis and individualized therapy, has shown great promise to transform medical care. Nontargeted metabolomics, with the ability to detect broad classes of biochemicals, can provide a comprehensive functional phenotype integrating clinical phenotypes with genetic and nongenetic factors. To test the application of metabolomics in individual diagnosis, we conducted a metabolomics analysis on plasma samples collected from 80 volunteers of normal health with complete medical records and three-generation pedigrees. Using a broad-spectrum metabolomics platform consisting of liquid chromatography and GC coupled with MS, we profiled nearly 600 metabolites covering 72 biochemical pathways in all major branches of biosynthesis, catabolism, gut microbiome activities, and xenobiotics. Statistical analysis revealed a considerable range of variation and potential metabolic abnormalities across the individuals in this cohort. Examination of the convergence of metabolomics profiles with whole-exon sequences (WESs) provided an effective approach to assess and interpret clinical significance of genetic mutations, as shown in a number of cases, including fructose intolerance, xanthinuria, and carnitine deficiency. Metabolic abnormalities consistent with early indications of diabetes, liver dysfunction, and disruption of gut microbiome homeostasis were identified in several volunteers. Additionally, diverse metabolic responses to medications among the volunteers may assist to identify therapeutic effects and sensitivity to toxicity. The results of this study demonstrate that metabolomics could be an effective approach to complement next generation sequencing (NGS) for disease risk analysis, disease monitoring, and drug management in our goal toward precision care.

Single-nucleotide polymorphism of the UMOD promoter is associated with the outcome of chronic kidney disease patients.

Uromodulin (UMOD) is the most abundant protein secreted in urine and the mutated form of the UMOD gene is associated with UMOD-associated kidney disease (UAKD). Although UMOD accumulates in the kidney of UAKD patients, it is unclear whether this also occurred in the chronic kidney disease (CKD) patients. Therefore, the association of single-nucleotide polymorphisms (SNPs) in the promoter region of UMOD gene with the kidney survival time of CKD was investigated. The promoter region of the UMOD gene was sequenced for 111 CKD patients. The Kaplan-Meier method was used to identify the disease outcome associated with SNPs in the promoter region of the UMOD gene in CKD patients. The Cox proportional hazard model was used to identify risk factors for the kidney survival time of CKD. SNPs in reference to GenBank accession NG-000016 were detected at 23 sites of the 481-bp in the UMOD promoter region from the CKD patients and the healthy controls. The 6 SNPs with minor allele frequency >5% in the CKD patients or controls were used for disease risk and outcome analysis. The frequent allele rs13333226AA was associated with a shorter period of kidney survival time in CKD patients (P=0.005). The length of kidney survival time in CKD patients with the rs13333226AA genotype was significantly shorter than that of patients with the frequent allele rs13333226AG+GG (relative risk, 0.361; 95% confidence interval, 0.171-0.761; P=0.007). In conclusion, analysis of genetic polymorphisms in UMOD may help to identify the CKD patient subgroups at a high risk for a disease outcome, thereby helping to refine therapeutic decisions in CKD patients.

Whole Genome Sequencing in Cancer Clinics

Whole Genome Sequencing in Cancer Clinics

Redevelopment of the Rapid Inquiry Facility Software for Assessment of Environmental Health Risks

Background: The Rapid Inquiry Facility (RIF), an embedded application to a Geographical Information System (GIS), has been successfully used worldwide to support disease mappings and risk analysis ...

개인 식품섭취 선호도에 따른 만성질환 발생 위험도 분석 시스템 설계 및 구현

IT 기술의 발달로 인터넷에 다양한 콘텐츠가 늘고, 다양한 정보에서 개인의 적합한 정보를 제공받고자 하는 요구가 급증하면서 다양한 개인화 서비스를 제공 방법에 관한 연구가 활발히 진행되고 있다. 본 논문에서는 구매 선호도에 따른 상품 추천 시스템의 분석방법을 개인 식품섭취 선호도에 따른 고혈압 및 당뇨 발생위험도를 분석하는 시스템에 적용하는 방법을 제안하고자 한다. 개인의 식품섭취 선호도 분석을 위해, 피어슨 상관계수를 이용하여 참조데이터와 샘플데이터의 유사도 가중치를 계산하고, 개인과의 유사도에 따른 집단을 구성하여 고혈압과 당뇨의 발생 위험도를 산출한다. 시스템의 유의성 검정을 위해 1,021명의 샘플을 시스템에 적용하였다. 고혈압과 당뇨병의 유병군에서 정상인군에 비해 더 높은 발생 위험도가 산출되는 통계적으로 유의한 경향을 확인할 수 있어 식품섭취 선호도와 고혈압/ 당뇨의 발생 위험도의 관련성이 있음을 확인하였다. 본 연구에서는 개인의 식품섭취 선호도에 따른 고혈압 및 당뇨 발생 위험도 분석 시스템의 유효성을 검증하였다.

Feeding behaviour of Culicoides spp. (Diptera: Ceratopogonidae) on cattle and sheep in northeast Germany

BackgroundCulicoides spp. play an important role in the transmission of several vector-borne pathogens such as Bluetongue and Schmallenberg virus in Europe. To better understand the biology of local Culicoides species, a study divided into three parts was performed in northeast Germany to elucidate the feeding activity patterns (study A), preferential landing and feeding sites (study B) and host feeding preferences (study C) of Culicoides spp. using cattle and sheep as baits.MethodsIn study A, the activity of Culicoides spp. was monitored over a 72 h period by collecting insects at regular intervals from the interior of drop traps with cattle or sheep standing inside. In study B, Culicoides spp. were directly aspirated from the coat and fleece of cattle and sheep during the peak activity period of Culicoides. In study C, Culicoides spp. were collected using drop traps with either cattle or sheep standing inside and located 10 m apart.ResultsIn study A, 3,545 Culicoides midges belonging to 13 species were collected, peak activity was observed at sunset. In study B, 2,024 Culicoides midges were collected. A significantly higher number of midges was collected from the belly and flank of cattle in comparison to their head region. In study C, 3,710 Culicoides midges were collected; 3,077 (83%) originated from cattle and 633 (17%) from sheep. Nearly half (46.7%) of the midges collected from cattle were engorged, significantly more than the number of engorged midges collected from sheep (7.5%). Culicoides from the Obsoletus complex (C. obsoletus and C. scoticus) were the most common Culicoides species encountered, followed by C. punctatus. Other species identified were C. dewulfi, C. chiopterus, C. pulicaris, C. lupicaris, C. pallidicornis, C. subfascipennis, C. achrayi, C. stigma, C. griseidorsum and C. subfagineus, the last two species are reported for the first time in Germany. Engorged C. chiopterus were collected in relatively high numbers from sheep, suggesting that this species may have a preference for sheep.ConclusionsAn insight into the feeding behaviour of local Culicoides species under field conditions in northeast Germany was obtained, with implications for the implementation of control measures and midge-borne disease risk analysis.

Spatial risk mapping for rare disease with hidden Markov fields and variational EM

Current risk mapping models for pooled data focus on the estimated risk for each geographical unit. A risk classification, that is, grouping of geographical units with similar risk, is then necessary to easily draw interpretable maps, with clearly delimited zones in which protection measures can be applied. As an illustration, we focus on the Bovine Spongiform Encephalopathy (BSE) disease that threatened the bovine production in Europe and generated drastic cow culling. This example features typical animal disease risk analysis issues with very low risk values, small numbers of observed cases and population sizes that increase the difficulty of an automatic classification. We propose to handle this task in a spatial clustering framework using a nonstandard discrete hidden Markov model prior designed to favor a smooth risk variation. The model parameters are estimated using an EM algorithm and a mean field approximation for which we develop a new initialization strategy appropriate for spatial Poisson mixtures. Using both simulated and our BSE data, we show that our strategy performs well in dealing with low population sizes and accurately determines high risk regions, both in terms of localization and risk level estimation.

Bovine TB and badger culling

WE are dismayed that this Government is issuing licences to cull badgers. Defra's own Independent Scientific Group (Defra 2007) concludes its £50 million research project by stating ‘careful evaluation of our own and others’ data indicates that badger culling can make no meaningful contribution to cattle TB control in Britain'. This massacre would cause untold suffering to badgers, and the ‘perturbation effect’ could cause TB outbreaks in surrounding areas (Defra 2007). Perturbation of other TB carrying species such as foxes, deer, rats, voles, mice and birds (Chambers 2009, Hardstaff and others 2012) could also further its spread. Has a thorough disease risk analysis …

Identification of Single Nucleotide Polymorphism Interactions Associated with Survival and Risk In Multiple Myeloma Using Novel Data Mining Methods

AbstractAbstract 2973Disease risk and therapeutic outcomes are impacted by both tumor heterogeneity as well as germline variations found in the population. Multiple myeloma (MM) shows significant heterogeneity in genetic aberrations in tumor cells, that together with inherited polymorphisms, affects disease risk and therapeutic response. In order to identify the impact of genetic variations (SNPs) on MM we have developed a Bank On A Cure platform for examining 3404 SNPs, selected in 983 genes associated with pathways affecting cellular functions important in cancer. Using SNP data sets we sought to identify genetic interactions, beyond single univariate association analysis. The challenge was to use data mining methods that take into account relatively small cohorts of patients, in which false discovery rates typically exceed the power of the study. We report results from using novel computational approaches that efficiently identify higher order SNP interactions associated with disease risk as well as survival outcomes, while minimizing the false discovery rate. The BOAC SNP panel was used to develop a data base on 143 patients selected for short (<1yr) versus long (>3yr) survival in ECOG 9486 and SWOG 9321; as well as 247 newly diagnosed patients and equal number of controls for disease risk analysis. One algorithm developed employs a discriminative pattern mining approach in which defined pathway sets of SNPs are used in combination testing. A second algorithm used identified SNPs that had some association with outcome (survival or disease status); but demonstrated a significant increase in associations when examined in combinations – we refer to this as a p-value jump association. Variations in genes associated with cell cycle, apoptosis, drug metabolism, stress response and immunity reached very low p-values, and survived multiple comparison testing when analyzed in combinations associated with both survival (PFS) predictions as well as analysis of case-control disease risk. Some of the key genetic variations identified in various combinations, included: PTRB, PTEN, CDK5, XRCC4, GSTA4, GPX, DYPD, PCNA, CYP4F2, VEGF, PON1, ALK, and BAG3. The data mining methods and algorithms used, and specific combinations associated with risk and survival, will be presented. These results are being further validated in new cohorts, and functional implications of identified genetic variants are being investigated in HapMap cell lines. Disclosures:No relevant conflicts of interest to declare.

Basic anthropometry and health status of elderly: findings of the Maracaibo Aging Study.

Determine basic anthropometry for elderly participants in a Venezuelan community and compare results for subgroups with different health status. Standardized anthropometric, nutritional, neurological, neuropsychiatric, and cardiovascular assessments generated data on weight, height, and body mass index (BMI) by sex and age for the total sample, for normative groups without health problems that might impact anthropometry, and for reference groups with no major health problems. Centile curves of anthropometric measurements versus age are determined for women and men in the normative group. Mean weight and height are significantly different between sexes, but not BMI. All three parameters show gradual declines with age. The mean 90% central interval for BMI in the normative and reference groups is 20-29 kg/m(2). The anthropometric data for healthy elderly Venezuelans can be used in monitoring anthropometric changes and disease risk analysis for this population and possibly for other Latin American populations.

Effective Spatial Smoothing of Disease: A Tool for Epidemiologists

ISEE-0776 Background and Objective: The availability of routinely collected geocoded data on health, population distribution and environmental pollutants, in conjunction with improved statistical and geographical information science methods, offers an opportunity to assess environmental health risks quickly, at relatively low cost to rapidly address public concerns about perceived environmental health risks. Visualising mortality or morbidity rates and spatial patterns of health outcomes can highlight areas of good or poor health event ascertainment and possibly identify important public health problems. Methods: An application for disease mapping and risk analysis, the Rapid Inquiry Facility (RIF) has been developed by the Small Area Health Statistics Unit (SAHSU) at Imperial College London, in collaboration with the US CDC Environmental Public Health Tracking Program and the EUROHEIS project. Disease mapping is a valuable method for exploring spatial patterns of health outcomes, however, when dealing with low population numbers and/or rare diseases such methods can be problematic. Both rates and SMRs become numerically unstable and typically the less populated areas will show the highest risks. One way of addressing these problems is using Bayesian smoothing methods. Results: The RIF allows users to carry out Empirical Bayes smoothing and to automatically link to WinBUGs to run a number of other smoothing models. We will outline four different smoothing models that can be used with the RIF for: Empirical Bayes, heterogeneity, conditional autoregressive modelling (CAR) and the Besag, York and Mollie (BYM) model and discuss, with examples, advantages of each approach. Conclusion: We will demonstrate that a number of different models should always be run for more accurate interpretation. Furthermore, when adopting the Bayesian approach we will outline the key issues that should be included for the choice of prior distributions of the parameters, in particular for variance parameters and the checking of the convergence.

Public Survey and Survival Data Do Not Support Recommendations to Discontinue Prostate-specific Antigen Screening in Men at Age 75

To evaluate the US Preventative Services Task Force (USPSTF) recommendation to discontinue prostate-specific antigen (PSA) screening at age 75. Public survey: A cohort of 340 patients was surveyed at our PSA screening clinic and stratified by awareness of the recommendation and education level. Age (< 75, >or= 75), race, health insurance status, knowledge of prostate cancer, and opinion on screening discontinuation at age 75 was evaluated between groups. Disease risk and survival analysis: A cohort of 4196 men who underwent radical prostatectomy between 1988 and 2008 was stratified into age groups: < 65, 65-74, and >or= 75. Associations between clinicopathologic variables, disease risk, and survival were compared between age groups using univariate and multivariate analysis. Approximately 78% of men surveyed disagreed with the USPSTF recommendation. The number of men who disagreed was not significantly different between awareness groups (P = .962). Awareness of new screening guidelines showed a significant difference (P = .006) between education groups. Age >or= 75 years was predictive of high-risk disease based on D'Amico's criteria (odds ratio = 2.72, P = .003). Kaplan-Meier and Cox regression analyses showed an association of men aged >or= 75 years with higher rate of PSA recurrence, distant metastasis, and disease specific death compared with the age groups of < 65 and 65-74 (P <.05). Men presenting to our PSA screening clinic disagreed with discontinuation of screening at age 75. Men aged >or= 75 years had higher risk disease and poorer survival. The USPSTF recommendation was supported neither by public opinion nor disease risk and survival results.

Comparison of the efficiency of five suction light traps under field conditions in South Africa for the collection of Culicoides species

Culicoides biting midges (Diptera: Ceratopogonidae) are involved in the transmission of a variety of pathogens, the economically most important being the orbiviruses that cause bluetongue and African horse sickness; both of which have been shown to be multi-vector diseases. The identification of all potential vectors will be crucial for the implementation of integrated control measures and disease risk analysis. The primary monitoring tools used for the collection of Culicoides midges are various models of suction light traps. In order to facilitate comparison of data between laboratories the efficiency of five traps (Onderstepoort, Rieb, mini-CDC, Pirbright, BG-sentinel), used at present and in the past in Europe, was compared in the field in South Africa. Comparisons were done either in three replicates of a 4 × 4 or two replicates of a 5 × 5 randomized Latin square design. The Onderstepoort trap collected significantly more Culicoides midges than the other traps. Relatively small but statistically significant differences were found in the species composition, parous rates, sex ratios as well as the ratio of Culicoides midges to other insects, as determined by the different traps. It will be important to determine the significance and underlying causes for these differences.