Advancing One human-animal-environment Health for global health security: what does the evidence say?

In this Series paper, we review the contributions of One Health approaches (ie, at the human-animal-environment interface) to improve global health security across a range of health hazards and we summarise contemporary evidence of incremental benefits of a One Health approach. We assessed how One Health approaches were reported to the Food and Agricultural Organization of the UN, the World Organisation for Animal Health (WOAH, formerly OIE), and WHO, within the monitoring and assessment frameworks, including WHO International Health Regulations (2005) and WOAH Performance of Veterinary Services. We reviewed One Health theoretical foundations, methods, and case studies. Examples from joint health services and infrastructure, surveillance-response systems, surveillance of antimicrobial resistance, food safety and security, environmental hazards, water and sanitation, and zoonoses control clearly show incremental benefits of One Health approaches. One Health approaches appear to be most effective and sustainable in the prevention, preparedness, and early detection and investigation of evolving risks and hazards; the evidence base for their application is strongest in the control of endemic and neglected tropical diseases. For benefits to be maximised and extended, improved One Health operationalisation is needed by strengthening multisectoral coordination mechanisms at national, regional, and global levels.

Sensitivity of contact-tracing for COVID-19 in Thailand: a capture-recapture application.

BACKGROUND: We investigate the completeness of contact tracing for COVID-19 during the first wave of the COVID-19 pandemic in Thailand, from early January 2020 to 30 June 2020. METHODS: Uni-list capture-recapture models were applied to the frequency distributions of index cases to inform two questions: (1) the unobserved number of index cases with contacts, and (2) the unobserved number of index cases with secondary cases among their contacts. RESULTS: Generalized linear models (using Poisson and logistic families) did not return any significant predictor (age, sex, nationality, number of contacts per case) on the risk of transmission and hence capture-recapture models did not adjust for observed heterogeneity. Best fitting models, a zero truncated negative binomial for question 1 and zero-truncated Poisson for question 2, returned sensitivity estimates for contact tracing performance of 77.6% (95% CI = 73.75-81.54%) and 67.6% (95% CI = 53.84-81.38%), respectively. A zero-inflated negative binomial model on the distribution of index cases with secondary cases allowed the estimation of the effective reproduction number at 0.14 (95% CI = 0.09-0.22), and the overdispersion parameter at 0.1. CONCLUSION: Completeness of COVID-19 contact tracing in Thailand during the first wave appeared moderate, with around 67% of infectious transmission chains detected. Overdispersion was present suggesting that most of the index cases did not result in infectious transmission chains and the majority of transmission events stemmed from a small proportion of index cases.

Public health research priorities for WHO on COVID-19 in the South-East Asia Region: results of a prioritization survey.

BACKGROUND: Effectively addressing the coronavirus disease 2019 (COVID-19) pandemic caused by the new pathogen requires continuous generation of evidence to inform decision-making. Despite an unprecedented amount of research occurring globally, the need to identify gaps in knowledge and prioritize a research agenda that is linked to public health action is indisputable. The WHO South-East Asia Region (SEAR) is likely to have region-specific research needs. METHODS: We aimed to identify a priority research agenda for guiding the regional and national response to the COVID-19 pandemic in SEAR countries. An online, anonymous research prioritization exercise using recent WHO guidance was conducted among the technical staff of WHO's country and regional offices engaged with the national COVID-19 response during October 2020. They were each asked to contribute up to five priority research ideas across seven thematic areas. These research ideas were reviewed, consolidated and scored by a core group on six parameters: regional specificity, relevance to the COVID-19 response, feasibility within regional research capacity, time to availability for decision-making, likely impact on practice, and promoting equity and gender responsiveness. The total scores for individual suggestions were organized in descending order, and ideas in the upper tertile were considered to be of high priority. RESULTS: A total of 203 priority research ideas were received from 48 respondents, who were primarily research and emergency response focal points in country and regional offices. These were consolidated into 78 research ideas and scored. The final priority research agenda of 27 items covered all thematic areas-health system (n=10), public health interventions (n=6), disease epidemiology (n=5), socioeconomic and equity (n=3), basic sciences (n=1), clinical sciences (n=1) and pandemic preparedness (n=1). CONCLUSIONS: This exercise, a part of WHO's mandate to "shape the research agenda", can help build a research roadmap ensuring efficient use of limited resources. This prioritized research agenda can act as a catalyst for Member States to accelerate research that could impact the COVID-19 response in SEAR.

Towards rabies elimination in the Asia-Pacific region: From theory to practice.

Rabies is a major neglected zoonotic disease and causes a substantial burden in the Asian region. Currently, Pacific Oceania is free of rabies but enzootic areas throughout southeast Asia represent a major risk of disease introduction to this region. On September 25-26, 2019, researchers, government officials and related stakeholders met at an IABS conference in Bangkok, Thailand to engage on the topic of human rabies mediated by dogs. The objective of the meeting was focused upon snowballing efforts towards achieving substantial progress in rabies prevention, control and elimination within Asia by 2030, and thereby to safeguard the Pacific region. Individual sessions focused upon domestic animal, wildlife and human vaccination; the production and evaluation of quality, safety and efficacy of existing rabies biologics; and the future development of new products. Participants reviewed the progress to date in eliminating canine rabies by mass vaccination, described supportive methods to parenteral administration by oral vaccine application, considered updated global and local approaches at human prophylaxis and discussed the considerable challenges ahead. Such opportunities provide continuous engagement on disease management among professionals at a trans-disciplinary level and promote new applied research collaborations in a modern One Health context.

Revisiting area risk classification of visceral leishmaniasis in Brazil.

BACKGROUND: Visceral leishmaniasis (VL) is a neglected tropical disease of public health relevance in Brazil. To prioritize disease control measures, the Secretaria de Vigilância em Saúde of Brazil's Ministry of Health (SVS/MH) uses retrospective human case counts from VL surveillance data to inform a municipality-based risk classification. In this study, we compared the underlying VL risk, using a spatiotemporal explicit Bayesian hierarchical model (BHM), with the risk classification currently in use by the Brazil's Ministry of Health. We aim to assess how well the current risk classes capture the underlying VL risk as modelled by the BHM. METHODS: Annual counts of human VL cases and the population at risk for all Brazil's 5564 municipalities between 2004 and 2014 were used to fit a relative risk BHM. We then computed the predicted counts and exceedence risk for each municipality and classified them into four categories to allow comparison with the four risk categories by the SVS/MH. RESULTS: Municipalities identified as high-risk by the model partially agreed with the current risk classification by the SVS/MH. Our results suggest that counts of VL cases may suffice as general indicators of the underlying risk, but can underestimate risks, especially in areas with intense transmission. CONCLUSION: According to our BHM the SVS/MH risk classification underestimated the risk in several municipalities with moderate to intense VL transmission. Newly identified high-risk areas should be further evaluated to identify potential risk factors and assess the needs for additional surveillance and mitigation efforts.

First inter-laboratory comparison of Echinococcus granulosus sensu lato diagnosis in Latin America.

OBJECTIVE: To compare the performance of polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) tests for diagnosing Echinococcus granulosus in dog feces among national reference laboratories in Argentina, Chile, Peru, and Uruguay. METHODS: National laboratories affiliated with the Ministry of Health/Agriculture of each country exchanged panels of 10 positive/negative samples obtained from their regular national surveillance programs in November 2015 - November 2016. All laboratories applied PCR; two also applied ELISA techniques. Sensitivity and specificity were determined for each laboratory and concordance of results among the laboratories was evaluated by Cohen Kappa coefficient. RESULTS: Poor concordance (3 of 10 paired comparisons had values of Kappa > 0.4), low sensitivity and specificity across all laboratories, and poor performance of both techniques in detecting E. granulosus in canine feces was demonstrated in this study. An ex-post comparison of the laboratories' test protocols showed substantial heterogeneity that could partially explain poor concordance of results. CONCLUSION: The results underscore the heterogeneity of canine echinococcosis diagnosis across the region and indicate possible sources of variability. Efforts to standardize canine echinococcosis testing must be included in the plan of action for the Regional Initiative for the Control of Cystic Echinococcosis. Future comparisons with fecal samples of known parasite load are needed.

Assessment of geographical accessibility to COVID-19 testing facilities in Nepal (2021).

Background: Ensuring equitable physical access to SARS-CoV-2 testing has proven to be crucial for controlling the COVID-19 epidemic, especially in countries like Nepal with its challenging terrain. During the second wave of the pandemic in May 2021, there was immense pressure to expand the laboratory network in Nepal to ensure calibration of epidemic response. The expansion led to an increase in the number of testing facilities from 69 laboratories in May 2021 to 89 laboratories by November 2021. We assessed the equity of physical access to COVID-19 testing facilities in Nepal during 2021. Furthermore, we investigated the potential of mathematical optimisation in improving accessibility to COVID-19 testing facilities. Methods: Based on up-to-date publicly available data sets and on the COVID-19-related daily reports published by Nepal's Ministry of Health and Population from May 1 to November 15, 2021, we measured the disparities in geographical accessibility to COVID-19 testing across Nepal at a resolution of 1 km2. In addition, we proposed an optimisation model to prescribe the best possible locations to set up testing laboratories maximizing access, and tested its potential impact in Nepal. Findings: The analysis identified vulnerable districts where, despite ramping up efforts, physical accessibility to testing facilities remains low under two modes of travel-walking and motorized driving. Both geographical accessibility and its equality were better under the motorised mode compared with the walking mode. If motorised transportation were available to everyone, the population coverage within 60 min of any testing facility (public and private) would be close to threefold the coverage for pedestrians within the same hour: 61.4% motorised against 22.2% pedestrian access within the hour, considering the whole population of Nepal. Very low accessibility was found in most areas except those with private test centres concentrated in the capital city of Kathmandu. The hypothetical use of mathematical optimisation to select 20 laboratories to add to the original 69 could have improved access from the observed 61.4% offered by the laboratories operating in November to 71.4%, if those 20 could be chosen optimally from all existing healthcare facilities in Nepal. In mountainous terrain, accessibility is very low and could not be improved, even considering all existing healthcare facilities as potential testing locations. Interpretation: The findings related to geographical accessibility to COVID-19 testing facilities should provide valuable information for health-related planning in Nepal, especially in emergencies where data might be limited and decisions time-sensitive. The potential use of publicly available data and mathematical optimisation could be considered in the future. Funding: WHO Special Programme for Research and Training in Tropical Diseases (TDR).

Cost-Effectiveness Analysis of Integrated Bite Case Management and Sustained Dog Vaccination for Rabies Control.

The successful prevention, control, and elimination of dog-mediated rabies is challenging due to insufficient resource availability and inadequate placement. An integrated dog bite case management (IBCM) system plus dog vaccination can help address these challenges. Based on data from the IBCM system in Haiti, we conducted a cost-effectiveness evaluation of a newly established IBCM system plus sustained vaccination and compared it with 1) a no bite-case management (NBCM) and 2) a non-risk-based (NRB) program, where bite victims presenting at a health clinic would receive post-exposure prophylaxis regardless of risk assessment. We also provide cost-effectiveness guidance for an ongoing IBCM system and for sub-optimal dog vaccination coverages, considering that not all cost-effective interventions are affordable. Cost-effectiveness outcomes included average cost per human death averted (USD/death averted) and per life-year gained (LYG). The analysis used a governmental perspective. Considering a sustained 5-year implementation with 70% dog vaccination coverage, IBCM had a lower average cost per death averted (IBCM: $7,528, NBCM: $7,797, NRB: $15,244) and cost per LYG (IBCM: $152, NBCM: $158, NRB: $308) than NBCM and NRB programs. As sensitivity analysis, we estimated cost-effectiveness for alternative scenarios with lower dog-vaccination coverages (30%, 55%) and lower implementation costs. Our results suggest that better health and cost-effectiveness outcomes are achieved with the continued implementation of an IBCM program ($118 per life-year saved) compared with a newly established IBCM program ($152 per life-year saved). Our results suggest that IBCM is more cost-effective than non-integrated programs to eliminate dog-mediated human rabies.

Bayesian shared spatial-component models to combine and borrow strength across sparse disease surveillance sources.

When analyzing the geographical variations of disease risk, one common problem is data sparseness. In such a setting, we investigate the possibility of using Bayesian shared spatial component models to strengthen inference and correct for any spatially structured sources of bias, when distinct data sources on one or more related diseases are available. Specifically, we apply our models to analyze the spatial variation of risk of two forms of scrapie infection affecting sheep in Wales (UK) using three surveillance sources on each disease. We first model each disease separately from the combined data sources and then extend our approach to jointly analyze diseases and data sources. We assess the predictive performances of several nested joint models through pseudo cross-validatory predictive model checks.

The Relative Importance of Vulnerability and Efficiency in COVID-19 Contact Tracing Programmes: A Discrete Choice Experiment.

Objectives: This study aims to assess the trade-offs between vulnerability and efficiency attributes of contact tracing programmes based on preferences of COVID-19 contact tracing practitioners, researchers and other relevant stakeholders at the global level. Methods: We conducted an online discrete choice experiment (DCE). Respondents were recruited globally to explore preferences according to country income level and the prevailing epidemiology of COVID-19 in the local setting. The DCE attributes represented efficiency (timeliness, completeness, number of contacts), vulnerability (vulnerable population), cooperation and privacy. A mixed-logit model and latent class analysis were used. Results: The number of respondents was 181. Timeliness was the most important attribute regardless of country income level and COVID-19 epidemiological condition. Vulnerability of contacts was the second most important attribute for low-to-lower-middle-income countries and third for upper-middle-to-high income countries. When normalised against conditional relative importance of timeliness, conditional relative importance of vulnerability ranged from 0.38 to 0.42. Conclusion: Vulnerability and efficiency criteria were both considered to be important attributes of contact tracing programmes. However, the relative values placed on these criteria varied significantly between epidemiological and economic context.

Participation in One Health Networks and Involvement in the COVID-19 Pandemic Response: A Global Study.

The COVID-19 pandemic exemplifies a One Health issue at the intersection of human, animal, and environmental health that requires collaboration across sectors to manage it successfully. The global One Health community includes professionals working in many different fields including human medicine, veterinary medicine, public health, ecosystem health, and, increasingly, social sciences. The aims of this cross-sectional study were to describe the involvement of the global One Health community in COVID-19 pandemic response activities. One Health networks (OHNs) have formed globally to serve professionals with common interests in collaborative approaches. We assessed the potential association between being part of an OHN and involvement in COVID-19 response activities. Data were collected in July-August 2020 using an online questionnaire that addressed work characteristics, perceived connection to OHNs, involvement in COVID-19 pandemic response activities, and barriers and facilitators to the involvement. The sample included 1,050 respondents from 94 countries across a range of organizations and work sectors including, but not restricted to, those typically associated with a One Health approach. Sixty-four percent of survey respondents indicated involvement in pandemic response activities. Being part of an OHN was positively associated with being involved in the COVID-19 response (odds ratio: 1.8, 95% confidence interval: 1.3-2.4). Lack of opportunities was a commonly reported barrier to involvement globally, with lack of funding the largest barrier in the WHO African region. This insight into diverse workforce involvement in the pandemic helps fill a gap in the global health workforce and public health education literature. An expanded understanding of the perceived roles and value of OHNs can inform targeted interventions to improve public health education and workforce capacity to prepare for and respond to public health emergencies.

Records of Human Deaths from Echinococcosis in Brazil, 1995-2016.

Echinococcosis is a zoonotic disease relevant to public health in many countries, on all continents except Antarctica. The objective of the study is to describe the registered cases and mortality from echinococcosis in Brazil, from 1995 to 2016. The records of two national databases, the Hospital Information System (HIS) and the Mortality Information System (MIS), were accessed during the period of 1995-2016. Demographic, epidemiological, and health care data related to the occurrence of disease and deaths attributed to echinococcosis in Brazil are described. The results showed that 7955 records of hospitalizations were documented in the HIS, during the study period, with 185 deaths from echinococcosis, and 113 records of deaths were documented in the MIS Deaths in every state of Brazil in the period. When comparing between states, the HIS showed great variability in mortality rates, possibly indicating heterogeneity in diagnosis and in the quality of health care received by patients. Less severe cases that do not require specialized care are not recorded by the information systems, thus the true burden of the disease could be underrepresented in the country. A change in the coding of disease records in the HIS in the late 1990s, (the integration of echinococcosis cases with other pathologies), led to the loss of specificity of the records. The records showed a wide geographic distribution of deaths from echinococcosis, reinforcing the need to expand the notification of the disease in Brazil. Currently, notification of cases is compulsory in the state of Rio Grande do Sul.

Contact tracing indicators for COVID-19: Rapid scoping review and conceptual framework.

BACKGROUND: Contact tracing is one of the key interventions in response to the COVID-19 pandemic but its implementation varies widely across countries. There is little guidance on how to monitor contact tracing performance, and no systematic overview of indicators to assess contact tracing systems or conceptual framework for such indicators exists to date. METHODS: We conducted a rapid scoping review using a systematic literature search strategy in the peer-reviewed and grey literature as well as open source online documents. We developed a conceptual framework to map indicators by type (input, process, output, outcome, impact) and thematic area (human resources, financial resources, case investigation, contact identification, contact testing, contact follow up, case isolation, contact quarantine, transmission chain interruption, incidence reduction). RESULTS: We identified a total of 153 contact tracing indicators from 1,555 peer-reviewed studies, 894 studies from grey literature sources, and 15 sources from internet searches. Two-thirds of indicators were process indicators (102; 67%), while 48 (31%) indicators were output indicators. Only three (2%) indicators were input indicators. Indicators covered seven out of ten conceptualized thematic areas, with more than half being related to either case investigation (37; 24%) or contact identification (44; 29%). There were no indicators for the input area "financial resources", the outcome area "transmission chain interruption", and the impact area "incidence reduction". CONCLUSIONS: Almost all identified indicators were either process or output indicators focusing on case investigation, contact identification, case isolation or contact quarantine. We identified important gaps in input, outcome and impact indicators, which constrains evidence-based assessment of contact tracing systems. A universally agreed set of indicators is needed to allow for cross-system comparisons and to improve the performance of contact tracing systems.

Antimicrobial resistance control efforts in Africa: a survey of the role of Civil Society Organisations.

Background: Antimicrobial resistance (AMR) is a growing public health threat in Africa. AMR prevention and control requires coordination across multiple sectors of government and civil society partners. Objectives: To assess the current role, needs, and capacities of CSOs working in AMR in Africa. Methods: We conducted an online survey of 35 CSOs working in 37 countries across Africa. The survey asked about priorities for AMR, current AMR-specific activities, monitoring practices, training needs, and preferences for sharing information on AMR. Further data were gathered on the main roles of the organisations, the length of time engaged in and budget spent on AMR-related activities, and their involvement in the development and implementation of National Action Plans (NAPs). Results were assessed against The Africa Centres for Disease Control and Prevention (Africa CDC) Framework for Antimicrobial Resistance (2018-2023). Results: CSOs with AMR-related activities are working in all four areas of Africa CDC's Framework: improving surveillance, delaying emergence, limiting transmission, and mitigating harm from infections caused by AMR microorganisms. Engagement with the four objectives is mainly through advocacy, followed by accountability and service delivery. There were limited monitoring activities reported by CSOs, with only seven (20%) providing an example metric used to monitor their activities related to AMR, and 27 (80%) CSOs reporting having no AMR-related strategy. Half the CSOs reported engaging with the development and implementation of NAPs; however, only three CSOs are aligning their work with these national strategies. Conclusion: CSOs across Africa are supporting AMR prevention and control, however, there is potential for more engagement. Africa CDC and other government agencies should support the training of CSOs in strategies to control AMR. Tailored training programmes can build knowledge of AMR, capacity for monitoring processes, and facilitate further identification of CSOs' contribution to the AMR Framework and alignment with NAPs and regional strategies.

Rabies in the Middle East, Eastern Europe, Central Asia and North Africa: Building evidence and delivering a regional approach to rabies elimination.

The Middle East, Eastern Europe, Central Asia and North Africa Rabies Control Network (MERACON), is built upon the achievements of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB). MERACON aims to foster collaboration among Member States (MS) and develop shared regional objectives, building momentum towards dog-mediated rabies control and elimination. Here we assess the epidemiology of rabies and preparedness in twelve participating MS, using case and rabies capacity data for 2017, and compare our findings with previous published reports and a predictive burden model. Across MS, the number of reported cases of dog rabies per 100,000 dog population and the number of reported human deaths per 100,000 population as a result of dog-mediated rabies appeared weakly associated. Compared to 2014 there has been a decrease in the number of reported human cases in five of the twelve MS, three MS reported an increase, two MS continued to report zero cases, and the remaining two MS were not listed in the 2014 study and therefore no comparison could be drawn. Vaccination coverage in dogs has increased since 2014 in half (4/8) of the MS where data are available. Most importantly, it is evident that there is a need for improved data collection, sharing and reporting at both the national and international levels. With the formation of the MERACON network, MS will be able to align with international best practices, while also fostering international support with other MS and international organisations.

Antimicrobial practices among small animal veterinarians in Greece: a survey.

BACKGROUND: The inappropriate use of antibiotics is a major issue in clinical practice in Greece with serious implications for public health and animal health. The purpose of the present study was to provide a first insight into the use of antibiotics by small animal practitioners in Greece and assess their compliance with general rules for the rational use of antibiotics. This is the first survey of its kind in Greece. METHODS: A questionnaire was designed to collect basic information on the use of antibiotics by pet veterinarians. The questionnaire was sent to a total of 70 veterinarians mainly operating in the region of Attica, a region that comprises almost 50% of the Greek population and where veterinarians are engaged solely in small animal practice. The questionnaire consisted of 37 closed questions dealing with various aspects on the use of antibiotics. RESULTS: The majority of practitioners report cases where the pet owner initiated antibiotic treatment without veterinary prescription. Almost every clinician reported owner-compliance challenges. Regarding microbiological analysis, 73% of respondents initiate empirical treatment while waiting for laboratory results or use antibiogram only when the treatment is unsuccessful. Eighty-eight per cent declared to use antimicrobials postoperatively in clean surgical procedures. Different types of antimicrobials and treatment durations than the ones proposed by guidelines on rational use of antibiotics are preferred for various organ systems e.g. in urinary and gastrointestinal infections. CONCLUSIONS: Our findings suggest the need for guidelines on antibiotic use in small animal practice in Greece, and the deployment of systematic surveillance on antimicrobials use and resistance to inform the initial choice of antibiotics upon local antimicrobial resistance profiles. Targeting the other end of the problem, pet owners, our findings indicate the need to educate them on the rational use of antibiotics and, critically, stop antibiotic availability without prescription.

Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to echinococcosis in Rio Negro, Argentina.

The analysis of zoonotic disease risk requires the consideration of both human and animal geo-referenced disease incidence data. Here we show an application of joint Bayesian analyses to the study of echinococcosis granulosus (EG) in the province of Rio Negro, Argentina. We focus on merging passive and active surveillance data sources of animal and human EG cases using joint Bayesian spatial and spatio-temporal models. While similar spatial clustering and temporal trending was apparent, there appears to be limited lagged dependence between animal and human outcomes. Beyond the data quality issues relating to missingness at different times, we were able to identify relations between dog and human data and the highest 'at risk' areas for echinococcosis within the province.

Quantifying and mapping the burden of human and animal rabies in Iraq.

Rabies was first reported in ancient Iraqi civilizations, yet it remains a poorly quantified and important public health threat in the region. Efforts to control rabies in Iraq including dog population control, and vaccination of livestock and dogs, have increased since 2010. Officially reported data on human rabies, dog bites, and animal rabies cases between 2012 and 2017 are analysed here to assess the effect of existing control efforts, to inform future strategies, and to highlight gaps in surveillance and reporting. The results of molecular characterization of 32 viruses from animal cases from throughout Iraq are presented, to improve the understanding of rabies dynamics in the animal reservoir. Although annual numbers of reported human cases were lower in the period between 2012 and 2017 than prior to 2010, human cases continue. There was a distinct gender and age bias among human cases with nine cases in males for every one female and twice as many cases in children than adults. Spatial clustering analysis and phylogenetic evidence suggests rabies is endemic throughout the country, with no regional variation in risk, but better surveillance and reporting is required to underpin control strategies.

On the question of proportionality of the count of observed scrapie cases and the size of holding.

BACKGROUND: The present paper investigates the question of a suitable basic model for the number of scrapie cases in a holding and applications of this knowledge to the estimation of scrapie-affected holding population sizes and adequacy of control measures within holding. Is the number of scrapie cases proportional to the size of the holding in which case it should be incorporated into the parameter of the error distribution for the scrapie counts? Or, is there a different - potentially more complex - relationship between case count and holding size in which case the information about the size of the holding should be better incorporated as a covariate in the modeling? METHODS: We show that this question can be appropriately addressed via a simple zero-truncated Poisson model in which the hypothesis of proportionality enters as a special offset-model. Model comparisons can be achieved by means of likelihood ratio testing. The procedure is illustrated by means of surveillance data on classical scrapie in Great Britain. Furthermore, the model with the best fit is used to estimate the size of the scrapie-affected holding population in Great Britain by means of two capture-recapture estimators: the Poisson estimator and the generalized Zelterman estimator. RESULTS: No evidence could be found for the hypothesis of proportionality. In fact, there is some evidence that this relationship follows a curved line which increases for small holdings up to a maximum after which it declines again. Furthermore, it is pointed out how crucial the correct model choice is when applied to capture-recapture estimation on the basis of zero-truncated Poisson models as well as on the basis of the generalized Zelterman estimator. Estimators based on the proportionality model return very different and unreasonable estimates for the population sizes. CONCLUSION: Our results stress the importance of an adequate modelling approach to the association between holding size and the number of cases of classical scrapie within holding. Reporting artefacts and speculative biological effects are hypothesized as the underlying causes of the observed curved relationship. The lack of adjustment for these artefacts might well render ineffective the current strategies for the control of the disease.

Classical sheep scrapie in Great Britain: spatial analysis and identification of environmental and farm-related risk factors.

BACKGROUND: Previous studies suggest that the spatial distribution of classical sheep scrapie in Great Britain is uneven and that certain flock characteristics may be associated with occurrence of the disease. However, the existence of areas of high and low disease-risk may also result from differences in the spatial distribution of environmental characteristics. In this study we explored the spatial pattern of classical scrapie in Great Britain between 2002 and 2005 and investigated the association between disease occurrence and various environmental and farm-related risk factors. RESULTS: Exploratory spatial analysis: South Wales was found to have a higher density of scrapie-positive farms than the rest of Great Britain. In addition, a small cluster of high-risk farms was identified in the center of this region in which clustering of scrapie-positive farms occurred up to a distance of approximately 40 km. SPATIAL MODELLING: A mixed-effects regression model identified flock-size and soil drainage to be significantly associated with the occurrence of scrapie in England and Wales (area under the curve (AUC) 0.71 +/- 0.01, 95% CI 0.68 - 0.74). The predictive risk map based on the estimated association between these factors and disease occurrence showed most of Wales to be at risk of being confirmed positive for scrapie with areas of highest risk in central and south Wales. In England, areas with the highest risk occurred mainly in the north and the midlands. CONCLUSION: The observed distribution of scrapie in Great Britain exhibited a definite spatial pattern with south Wales identified as an area of high occurrence. In addition both flock (flock size) and environmental variables (soil drainage) were found to be significantly associated with the occurrence of the disease. However, the model's AUC indicated unexplained variation remaining in the model and the source of this variation may lie in farm-level characteristics rather than spatially-varying ones such as environmental factors.