Reshaping surveillance for infectious diseases: less chasing of pathogens and more monitoring of drivers.

Animal health surveillance, despite its name, tends to focus on looking for disease. Often this involves searching for cases of infection with known pathogens (â€Ëœpathogen chasing'). Such an approach is both resource intensive and limited by the requirement for prior knowledge of disease likelihood. In this paper, the authors propose the gradual reshaping of surveillance towards the systems level, focusing on the processes (â€Ëœdrivers') that promote disease or health, rather than on the presence or absence of specific pathogens. Examples of relevant drivers include land-use change, increasing global interconnectedness, and finance and capital flows. Importantly, the authors suggest that surveillance should focus on detecting changes in patterns or quantities associated with such drivers. This would generate systems-level, risk-based surveillance information to identify areas where additional attention may be needed, and, over time, inform the implementation of prevention efforts. The collection, integration and analysis of data on drivers is likely to require investment in improving data infrastructures. A period of overlap would allow the two systems (traditional surveillance and driver monitoring) to be compared and calibrated. This would also lead to a better understanding of the drivers and their linkages, and thereby generate new knowledge that can improve surveillance and inform mitigation efforts. Since surveillance of drivers may give signals when changes are occurring, which could act as alerts and enable targeted mitigation, this might even enable disease to be prevented before it happens by directly intervening in the drivers themselves. Such surveillance focused on the drivers could be expected to bring additional benefits, since the same drivers promote multiple diseases. Further, focusing on drivers rather than pathogens should enable control of currently unknown diseases, making this approach particularly timely, given the increasing risk of emergence of new diseases.

La surveillance de la santé animale a tendance, malgré son nom, à se focaliser sur la recherche des maladies. Elle implique souvent de chercher les cas d'infection par des agents pathogènes connus (" chasse aux agents pathogènes "). Ce type d'approche exige non seulement beaucoup de ressources, mais elle est aussi limitée par la nécessité d'avoir une connaissance préalable de la probabilité de survenue de la maladie en question. Dans cet article, les auteurs proposent une refonte progressive de la surveillance pour la déplacer au niveau systémique, en se concentrant sur les processus (" facteurs ") influençant la maladie ou la santé plutôt que sur la présence ou non d'agents pathogènes spécifiques. Parmi les facteurs pertinents, on peut citer les changements dans l'utilisation des sols, l'interconnexion accrue au niveau mondial et les flux financiers et de capitaux. Les auteurs soulignent cet élément important : la surveillance devrait se focaliser sur la détection de changements au niveau des schémas ou des quantités associés à ces facteurs. Cela permettrait d'obtenir des informations de surveillance au niveau systémique et basées sur les risques, afin d'identifier les domaines auxquels il pourrait être nécessaire de porter une attention particulière - ce qui informerait, à terme, la mise en oeuvre des efforts de prévention. Il est probable qu'une amélioration des infrastructures de données soit nécessaire pour assurer la collecte, l'intégration et l'analyse des données sur les facteurs. Une période de chevauchement permettrait de comparer et de calibrer les deux systèmes (surveillance traditionnelle et surveillance des facteurs). Les facteurs et les liens entre eux seraient également mieux compris, ce qui générerait de nouvelles connaissances pouvant améliorer la surveillance et informer les efforts d'atténuation. Grâce à la surveillance des facteurs, des signaux pourraient être identifiés lorsque des changements se produisent, ce qui constituerait une alerte pour que des efforts d'atténuation ciblés soient mis en place afin d'intervenir directement sur les facteurs eux-mêmes et donc prévenir une maladie avant même qu'elle ne survienne. On peut s'attendre à ce que ce type de surveillance centrée sur les facteurs apporte des bénéfices supplémentaires, puisque les mêmes facteurs peuvent favoriser de multiples maladies. De surcroît, cette orientation axée sur les facteurs plutôt que sur les agents pathogènes devrait permettre de contrôler des maladies aujourd'hui inconnues, ce qui rend cette approche d'autant plus opportune, compte tenu du risque croissant d'émergence de nouvelles maladies.

La vigilancia zoosanitaria, pese a lo que su nombre indica, tiende a centrarse en la búsqueda de enfermedades, lo que a menudo pasa por tratar de localizar casos de infección por un patógeno conocido ("persecución de patógenos"). Semejante método no solo exige cuantiosos recursos, sino que además presenta la limitación de que obliga a conocer de antemano la probabilidad de aparición de una enfermedad. Los autores proponen una remodelación gradual de la vigilancia tendente a dotarla de carácter sistémico y a centrarla no tanto en la presencia o ausencia de determinados patógenos, sino en los procesos ("inductores" o "factores de inducción", drivers) que favorecen la enfermedad o la salud. Son ejemplo de tales procesos la evolución de los usos del suelo, el creciente nivel de interconexión mundial o los flujos financieros y de capitales. Un aspecto importante que apuntan los autores es que la vigilancia debería tener por objetivo la detección de cambios en las características o cantidades de esos factores de inducción. Ello generaría información de vigilancia basada en el riesgo de carácter sistémico, que serviría para determinar aquellas zonas a las que convendría prestar más atención y, con el tiempo, fundamentar la realización de actividades de prevención. Es probable que la obtención, integración y análisis de datos sobre los factores de inducción exijan inversiones para mejorar las infraestructuras de datos. Si hubiera una fase de solapamiento, sería posible comparar y valorar los resultados de ambos sistemas (vigilancia tradicional y seguimiento de los factores de inducción). Ello serviría para entender mejor los inductores y su vinculación recíproca, lo que generaría nuevos conocimientos con los que perfeccionar la vigilancia y en los que cimentar las actividades de mitigación. Dado que la vigilancia de los inductores puede generar una señal cuando se estén produciendo cambios, señal que a su vez activaría una alerta y propiciaría medidas selectivas de mitigación, podría ser que ello sirviera incluso para prevenir una enfermedad antes de que surgiera, actuando directamente sobre los propios factores de inducción. Cabría pensar que semejante tipo de vigilancia, centrarse en los inductores, puede tener otros efectos beneficiosos, en la medida en que un mismo inductor alimenta la aparición de varias enfermedades. Además, el hecho de centrarse en los factores de inducción, y no tanto en los patógenos, debería servir para controlar enfermedades actualmente desconocidas, por lo que este planteamiento, ante el creciente riesgo de aparición de nuevas enfermedades, resulta especialmente oportuno.

Surveillance and risk assessment for early detection of emerging infectious diseases in livestock.

Those who work in the area of surveillance and prevention of emerging infectious diseases (EIDs) face a challenge in accurately predicting where infection will occur and who (or what) it will affect. Establishing surveillance and control programmes for EIDs requires substantial and long-term commitment of resources that are limited in nature. This contrasts with the unquantifiable number of possible zoonotic and non-zoonotic infectious diseases that may emerge, even when the focus is restricted to diseases involving livestock. Such diseases may emerge from many combinations of, and changes in, host species, production systems, environments/habitats and pathogen types. Given these multiple elements, risk prioritisation frameworks should be used more widely to support decision-making and resource allocation for surveillance. In this paper, the authors use recent examples of EID events in livestock to review surveillance approaches for the early detection of EIDs, and highlight the need for surveillance programmes to be informed and prioritised by regularly updated risk assessment frameworks. They conclude by discussing some unmet needs in risk assessment practices for EIDs, and the need for improved coordination in global infectious disease surveillance.

Les personnes travaillant dans le domaine de la surveillance et de la prévention des maladies infectieuses émergentes (MIE) sont confrontées à la difficulté de prédire avec exactitude le lieu d'émergence d'une maladie, ainsi que l'espèce, le système ou le site affectés. La mise en place de programmes de surveillance et de lutte contre les MIE exige une mobilisation conséquente et durable de ressources nécessairement limitées. Par contraste, le nombre des maladies infectieuses zoonotiques et non zoonotiques pouvant se déclarer est impossible à quantifier, même si l'on s'en tient aux seules maladies affectant les animaux d'élevage. Ces maladies surviennent à la faveur des nombreuses et diverses configurations, associations ou modifications qui peuvent se produire parmi les espèces hôtes, les systèmes de production, les environnements ou habitats et les types d'agents pathogènes. Compte tenu de la multiplicité de ces éléments, il devrait être fait plus largement appel à des cadres de priorisation du risque afin de soutenir les processus de prise de décision et d'allocation des ressources en matière de surveillance. Les auteurs s'appuient sur des exemples récents d'événements liés à des MIE pour faire le point sur les méthodes de surveillance appliquées pour la détection précoce de ces maladies et soulignent l'importance de documenter et de prioriser les programmes de surveillance en procédant à des mises à jour régulières des cadres utilisés pour l'évaluation du risque. Ils concluent en évoquant certains aspects importants que les pratiques actuelles d'évaluation du risque ne permettent pas de couvrir lorsqu'il s'agit de MIE, ainsi que l'importance d'améliorer la coordination de la surveillance des maladies infectieuses au niveau mondial.

Cuantos trabajan en el ámbito de la vigilancia y la prevención de enfermedades infecciosas emergentes (EIE) tienen dificultades para predecir con precisión dónde va a surgir y a quién (o qué) afectará una infección. La instauración de programas de vigilancia y control de EIE exige una inversión sustancial y duradera de recursos que por definición son escasos, sobre todo teniendo en cuenta el número incalculable de enfermedades infecciosas zoonóticas y no zoonóticas que pueden aparecer, aun considerando solo aquellas que afectan al ganado. Este tipo de enfermedades pueden surgir como resultado de muchas combinaciones distintas de especie hospedadora, sistema productivo, medio/hábitat y tipo de patógeno o por efecto de cambios que se den en cualquiera de estos elementos. En vista de la multiplicidad de factores que concurren, convendría emplear de modo más generalizado un sistema de jerarquización de los riesgos en el cual fundamentar las decisiones de vigilancia y la distribución de los recursos destinados a ella. Los autores, valiéndose de ejemplos recientes de episodios infecciosos emergentes que afectaron al ganado, pasan revista a distintos métodos de vigilancia para la detección temprana de EIE y recalcan que los programas de vigilancia deben reposar en procedimientos de determinación del riesgo periódicamente actualizados y en las prioridades fijadas a partir de estos procedimientos. Por último, los autores se detienen en algunas necesidades desatendidas en la praxis de la determinación del riesgo de EIE y en la necesidad de una mejor coordinación de la vigilancia mundial de las enfermedades infecciosas.

Regulation of bone mineral density in the grey squirrel, Sciurus carolinensis: Bioavailability of calcium oxalate, and implications for bark stripping.

The damage caused when grey squirrels strip the outer bark off trees and ingest the underlying phloem can result in reduced timber quality or tree death. This is extremely costly to the UK forestry industry and can alter woodland composition, hampering conservation efforts. The calcium hypothesis proposes that grey squirrels ingest phloem to ameliorate a seasonal calcium deficiency. Calcium in the phloem predominantly takes the form of calcium oxalate (CaOx), however not all mammals can utilise CaOx as a source of calcium. Here, we present the results of a small-scale study to determine the extent to which grey squirrels can utilise CaOx. One of three custom-made diets containing calcium in varying forms and quantities (CaOx diet, Low-calcium carbonate (CaCO3 ) diet and Control diet) were fed to three treatment groups of six squirrels for 8 weeks. Bone densitometric properties were measured at the end of this time using peripheral quantitative computed tomography and micro-computed tomography. Pyridinoline-a serum marker of bone resorption-was measured regularly throughout the study. Bone mineral density and cortical mineralisation were lower in squirrels fed the CaOx diet compared to the Control group but similar to that of those on the Low-calcium diet, suggesting that calcium from calcium oxalate was not effectively utilised to maintain bone mineralisation. Whilst no differences were observed in serum pyridinoline levels between individuals on different diets, females had on average higher levels than males throughout the study. Future work should seek to determine if this apparent lack of ability to utilise CaOx is common to a large sample of grey squirrels and if so, whether it is consistent across all areas and seasons.

Quantitative interferon-gamma responses predict future disease progression in badgers naturally infected with Mycobacterium bovis.

The diagnosis and control of Mycobacterium bovis infection (bovine tuberculosis: TB) continues to present huge challenges to the British cattle industry. A clearer understanding of the magnitude and duration of immune response to M. bovis infection in the European badger (Meles meles) - a wildlife maintenance host - may assist with the future development of diagnostic tests, and vaccination and disease management strategies. Here, we analyse 5280 diagnostic test results from 550 live wild badgers from a naturally-infected population to investigate whether one diagnostic test (a gamma interferon release [IFNγ] assay, n = 550 tests) could be used to predict future positive results on two other tests for the same disease (a serological test [n = 2342 tests] and mycobacterial culture [n = 2388 tests]) and hence act as an indicator of likely bacterial excretion or disease progression. Badgers with the highest IFNγ optical density (OD) values were most likely to subsequently test positive on both serological and culture tests, and this effect was detectable for up to 24 months after the IFNγ test. Furthermore, the higher the original IFNγ OD value, the greater the chance that a badger would subsequently test positive using serology. Relationships between IFNγ titres and mycobacterial culture results from different types of clinical sample suggest that the route of infection may affect the magnitude of immune response in badgers. These findings identify further value in the IFNγ test as a useful research tool, as it may help us to target studies at animals and groups that are most likely to succumb to more progressive disease.

Active animal health surveillance in European Union Member States: gaps and opportunities.

Animal health surveillance enables the detection and control of animal diseases including zoonoses. Under the EU-FP7 project RISKSUR, a survey was conducted in 11 EU Member States and Switzerland to describe active surveillance components in 2011 managed by the public or private sector and identify gaps and opportunities. Information was collected about hazard, target population, geographical focus, legal obligation, management, surveillance design, risk-based sampling, and multi-hazard surveillance. Two countries were excluded due to incompleteness of data. Most of the 664 components targeted cattle (26·7%), pigs (17·5%) or poultry (16·0%). The most common surveillance objectives were demonstrating freedom from disease (43·8%) and case detection (26·8%). Over half of components applied risk-based sampling (57·1%), but mainly focused on a single population stratum (targeted risk-based) rather than differentiating between risk levels of different strata (stratified risk-based). About a third of components were multi-hazard (37·3%). Both risk-based sampling and multi-hazard surveillance were used more frequently in privately funded components. The study identified several gaps (e.g. lack of systematic documentation, inconsistent application of terminology) and opportunities (e.g. stratified risk-based sampling). The greater flexibility provided by the new EU Animal Health Law means that systematic evaluation of surveillance alternatives will be required to optimize cost-effectiveness.

Diagnosis of tuberculosis in groups of badgers: an exploration of the impact of trapping efficiency, infection prevalence and the use of multiple tests.

Accurate detection of infection with Mycobacterium bovis in live badgers would enable targeted tuberculosis control. Practical challenges in sampling wild badger populations mean that diagnosis of infection at the group (rather than the individual) level is attractive. We modelled data spanning 7 years containing over 2000 sampling events from a population of wild badgers in southwest England to quantify the ability to correctly identify the infection status of badgers at the group level. We explored the effects of variations in: (1) trapping efficiency; (2) prevalence of M. bovis; (3) using three diagnostic tests singly and in combination with one another; and (4) the number of badgers required to test positive in order to classify groups as infected. No single test was able to reliably identify infected badger groups if 80% sensitive, at least 94% specific, and able to be performed rapidly in the field.

Evaluation of the usefulness at national level of the dairy cattle health and production recording systems in Great Britain.

The aim of this study was to formally evaluate, qualitatively, the ability of existing recording systems to generate accurate and reliable estimates of the frequency of selected health conditions in the dairy herd of Great Britain. Fifty-nine recording systems were identified, of which 36 had their key characteristics defined through a web-based questionnaire. Nineteen of them were further assessed following the SERVAL, a SuRveillance EVALuation framework against a set of 12 attributes: benefit, bias, communication, coverage, data collection, data management, data analysis, data completeness, flexibility, multiple utility, representativeness and stability/sustainability. The evaluated systems showed considerable differences in their coverage, implementation and objectives. There were overlaps in recorded conditions, with Johne's disease, bovine viral diarrhoea, mastitis and lameness being recorded by most of the systems. Selection bias, data ownership and lack of integration of data from different systems appeared to be a key limitation on the future use of existing systems for nationwide monitoring. The results showed that even though the individual systems can provide reliable estimates of dairy health for individual farmers, none of the systems alone could provide accurate and reliable estimates for any of the conditions of interest at national level.

Risk factors for visible lesions or positive laboratory tests in bovine tuberculosis reactor cattle in Northern Ireland.

An observational case-control study was conducted to investigate risk factors for confirmed bovine tuberculosis (bTB) infection in cattle reacting positively to the single intradermal comparative cervical test (SICCT) in Northern Ireland in the years 1998, 2002 and 2006. Macroscopic lesions were detected at slaughter (positive visible lesion (VL) status) in 43.0% of reactor cattle, whilst 45.3% of those sampled were confirmed as bTB positive due to the presence of lesions or positive histopathology/mycobacterial culture (positive bTB status). In 97.5% of the reactors, the VL status and bTB status were either both negative or both positive. Generalized linear mixed model analyses were conducted on data of 24,923 reactor cattle with the variables herd identifier, local veterinary office (DVO) and abattoir being used as random effects within all the models generated at univariable and multivariable level. The other variables within the dataset were used as fixed effects. Significant risk factors associated with VL status and bTB status at multivariable level (p<0.05) included age at death, breed, sex, test year, net increase in skin thickness at bovine tuberculin injection site, epidemiological status of skin test, total number of reactors at the disclosure test, mean herd size and prior response to the skin test. These risk factors are likely related to the time since infection, the strength of the challenge of infection and the susceptibility of the animal. These findings are important as the detection of visible lesions and the confirmation of bTB are an integral part of the overall bTB control programme in Northern Ireland and the veterinary meat inspection and hygiene programme. The visible lesion status and bTB status of an animal can affect the way in which bTB breakdowns are managed, since failure to detect visible lesions and recovery of Mycobacterium bovis can lead to a less stringent follow-up after other risk factors have been taken into account.

SERVAL: a new framework for the evaluation of animal health surveillance.

Animal health surveillance programmes may change in response to altering requirements or perceived weaknesses but are seldom subjected to any formal evaluation to ensure that they provide valuable information in an efficient manner. The literature on the evaluation of animal health surveillance systems is sparse, and those that are published may be unstructured and therefore incomplete. To address this gap, we have developed SERVAL, a SuRveillance EVALuation framework, which is novel and aims to be generic and therefore suitable for the evaluation of any animal health surveillance system. The inclusion of socio-economic criteria ensures that economic evaluation is an integral part of this framework. SERVAL was developed with input from a technical workshop of international experts followed by a consultation process involving providers and users of surveillance and evaluation data. It has been applied to a range of case studies encompassing different surveillance and evaluation objectives. Here, we describe the development, structure and application of the SERVAL framework. We discuss users' experiences in applying SERVAL to evaluate animal health surveillance systems in Great Britain.

Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice.

INTRODUCTION: It was the aim of the present experiments to examine potential antidiabetic effects of the Cimicifuga racemosa extract Ze 450. METHODS: Ze 450 and some of its components (23-epi-26-deoxyactein, protopine and cimiracemoside C) were investigated in vitro for their effects on AMP-activated protein kinase (AMPK) compared to metformin in HepaRG cells. Ze 450 (given orally (PO) and intraperitonally (IP)), metformin (PO) and controls were given over 7 days to 68 male ob/ob mice. Glucose and insulin concentrations were measured at baseline and during an oral glucose tolerance test (OGTT). RESULTS: Ze 450 and its components activated AMPK to the same extent as metformin. In mice, Ze 450 (PO/IP) decreased significantly average daily and cumulative weight gain, average daily food and water intake, while metformin had no effect. In contrast to metformin, PO Ze 450 virtually did not change maximum glucose levels during OGTT, however, prolonged elimination. Ze 450 administered PO and IP decreased significantly post-stimulated insulin, whereas metformin did not. HOMA-IR index of insulin resistance improved significantly after IP and PO Ze 450 and slightly after metformin. In summary, the results demonstrate that Ze 450 reduced significantly body weight, plasma glucose, improved glucose metabolism and insulin sensitivity in diabetic ob/ob mice. In vitro experiments suggest that part of the effects may be related to AMPK activation. CONCLUSIONS: Ze 450 may have utility in the treatment of type 2 diabetes. However, longer term studies in additional animal models or patients with disturbed glucose tolerance or diabetes may be of use to investigate this further.

Assessing the expenditure distribution of animal health surveillance: the case of Great Britain.

Animal health surveillance in Great Britain (GB) is conducted through public and private initiatives, yet there is no consolidated information on these activities and their outcomes. We developed an inventory of livestock health surveillance programmes in GB to identify gaps in resource use and potential synergies that could be exploited. The inventory contained details of 36 livestock surveillance activities active in 2011. Data were collected by questionnaire and interviews. Livestock health surveillance funding was found to be unevenly distributed between species: the vast majority (approximately 94 per cent) was spent on cattle diseases (tuberculosis surveillance accounted for most of this expenditure), with 2 per cent on pigs, 2 per cent on sheep/goats, 1 per cent on poultry, and 1 per cent on antimicrobial resistance surveillance across all species. Consequently, surveillance efforts in GB appears heavily skewed towards regions with high cattle densities, particularly high-prevalence tuberculosis areas such as the southwest. The contribution of private schemes to surveillance funding was hard to quantify due to limited access to data, but was estimated to be about 10 per cent. There is scope to better understand the benefits of surveillance, enhance data sharing, clarify costs and identify who pays and who gains. Health surveillance should be considered within the sharing of responsibilities for disease control.

Spatial and temporal interactions between livestock and wildlife in South Central Spain assessed by camera traps.

The diversification of livestock farms into hunting estates in South Central Spain (SCS) may impede the success of Mycobacterium bovis eradication programmes by facilitating transmission between wildlife and livestock. In this observational study we aimed to provide information of relevance about the nature and frequency of interactions (observed visits to study points) between livestock (cattle and domestic pigs) and wildlife (wild boar and red deer). The study was conducted in an extensive cattle farm in SCS where the land is also used for game hunting. During a period of one year, camera traps (n=16) were placed at a priori risk points for interspecies interactions: water (natural and artificial troughs), food placed on the ground for baiting wildlife, and pasture. To define indirect interspecies interactions, a critical time window for M. bovis to survive in the environment was selected based on the literature. Results suggest that wildlife frequented food and pasture points more often than water points, and that the number of visits increased through the dry season, peaking during the acorn season (October-January) and the deer breeding season (June-July). Direct interactions were rare (n=10), as opposed to indirect interactions (n=8992). Wildlife-followed-by-livestock interactions (n=7714) occurred much more often than livestock-followed-by-wildlife (n=1278) and were frequent at water points (66% water points, 17% food, 17% pasture). Results also suggest that water points are a hotspot for indirect interactions and might therefore be a source of infection at the wildlife-livestock interface in the territory covered, particularly for M. bovis, as it is around water where the bacteria seem to survive the longest. Preventing aggregation and therefore reducing contact rates between domestic and wild animals especially at water points may be valuable for disease control in South Central Spain.

Proposed terms and concepts for describing and evaluating animal-health surveillance systems.

The information provided by animal-health surveillance helps to reduce the impact of animal diseases. The widespread movement of animals and their products around the world results in an increasing risk that disease will spread. There is, therefore, a need for exchange between countries of comparable information about disease incidence; the exchange must be based on a common understanding of surveillance approaches and how surveillance systems are designed and implemented. Establishing agreed-upon definitions of surveillance terms would be a first step in achieving this standardisation, and will enhance transparency and confidence. To this end, a workshop was held with the aim of agreeing upon key terms and concepts for animal-health surveillance. In this paper, we describe the methods used at the workshop and summarise the discussions. A complete list of all the proposed definitions including lists of characteristics that can be used to describe surveillance activities and attributes for evaluation of surveillance is available in the workshop report (available at http://www.defra.gov.uk/ahvla-en/disease-control/surveillance/icahs-workshop/). Some important issues were highlighted during these discussions; of particular note was the importance of economic efficiency as an evaluation attribute. Some remaining inconsistencies in the proposed use of terms are highlighted (including the definition of 'risk-based surveillance' and the use of the term 'event-based surveillance').

Patterns of direct and indirect contact between cattle and badgers naturally infected with tuberculosis.

Tuberculosis (TB) due to infection with Mycobacterium bovis is transmitted between cattle and badgers (Meles meles) in the UK and Ireland but it is unclear where or when transmission occurs. We investigated direct and indirect interactions between badgers and cattle using automated proximity loggers on animals and at badger latrines located on pasture, in an area of south-west England with a high-density badger population. Direct contacts (interactions within 1.4 m) between badgers and cattle at pasture were very rare (four out of >500000 recorded animal-to-animal contacts) despite ample opportunity for interactions to occur. Indirect interactions (visits to badger latrines by badgers and cattle) were two orders of magnitude more frequent than direct contacts: 400 visits by badgers and 1700 visits by cattle were recorded. This suggests that indirect contacts might be more important than direct contacts in terms of disease transmission at pasture. The TB infection status of individual badgers (ascribed with 93% accuracy using three diagnostic tests) did not affect the frequency or duration of their visits to latrines located on pasture grazed by cattle. Nevertheless, there was wide variation in contact behaviour between individuals, which highlights the importance of understanding heterogeneity in contact patterns when developing strategies to control disease spread in wildlife and livestock.

Neural effects of green tea extract on dorsolateral prefrontal cortex.

BACKGROUND/OBJECTIVES: Green tea is being recognized as a beverage with potential benefits for human health and cognitive functions. In vivo studies provide preliminary evidence that green tea intake may have a positive role in improving effects on cognitive functions. We aimed to examine the neural effects of green tea extract on brain activation in humans. SUBJECTS/METHODS: Functional magnetic resonance imaging was recorded while 12 healthy volunteers performed a working memory task following administration of 250 or 500 ml of a milk whey based green tea containing soft drink or milk whey based soft drink without green tea as control in a double-blind, controlled repeated measures within-subject design with counterbalanced order of substance administration. A whole-brain analysis with a cluster-level threshold of P<0.001 (unadjusted) was followed by an a priori-defined region of interest (ROI) analysis of the dorsolateral prefrontal cortex (DLPFC) including a cluster-level threshold of P<0.05 and family-wise error (FWE) adjustment for multiple comparisons. RESULTS: Whole-brain analyses revealed no significant effects after correction for multiple comparisons (FWE P<0.05). Using a ROI approach, green tea extract increased activation in the DLPFC relative to a control condition (FWE P<0.001). This neural effect was related to green tea dosage. Green tea extract was not associated with any significant attenuation in regional activation relative to control condition. CONCLUSIONS: These data suggest that green tea extract may modulate brain activity in the DLPFC, a key area that mediates working memory processing in the human brain. Moreover, this is the first neuroimaging study implicating that functional neuroimaging methods provide a means of examining how green tea extract acts on the brain.

Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers.

The pharmacokinetics and pharmacodynamics of a highly concentrated cyclodextrin-based intranasal (i.n.) midazolam formulation containing the absorption-enhancer chitosan were studied in 12 healthy volunteers and compared with intravenous (i.v.) midazolam. The pharmacodynamic (PD) effects were assessed using quantitative electroencephalography (EEG). Maximal plasma concentrations of 63 and 110 ng/ml were reached at 8.4 and 7.6 min after 3 and 6 mg i.n. midazolam, respectively. After 5 mg i.v. and 6 and 3 mg i.n. midazolam, the times to onset of significant EEG effects in the ß2 band (18-25 Hz) were 1.2, 5.5, and 6.9 min, respectively, and the times to loss of response to auditory stimuli were 3.0, 8.0, and 15.0 min, respectively. A sigmoid maximum-effect (E(max)) model indicated disequilibrium between plasma and effect-site concentrations, with equilibration half-lives of 2.1-4.8 min. The observed pharmacokinetic-PD (PK-PD) properties suggest that i.n. midazolam deserves to be evaluated as an easy and noninvasive method of administering a first benzodiazepine dose, e.g., in out-of-hospital emergency settings with no immediate i.v. access.

Evaluation of animal and public health surveillance systems: a systematic review.

Disease surveillance programmes ought to be evaluated regularly to ensure they provide valuable information in an efficient manner. Evaluation of human and animal health surveillance programmes around the world is currently not standardized and therefore inconsistent. The aim of this systematic review was to review surveillance system attributes and the methods used for their assessment, together with the strengths and weaknesses of existing frameworks for evaluating surveillance in animal health, public health and allied disciplines. Information from 99 articles describing the evaluation of 101 surveillance systems was examined. A wide range of approaches for assessing 23 different system attributes was identified although most evaluations addressed only one or two attributes and comprehensive evaluations were uncommon. Surveillance objectives were often not stated in the articles reviewed and so the reasons for choosing certain attributes for assessment were not always apparent. This has the potential to introduce misleading results in surveillance evaluation. Due to the wide range of system attributes that may be assessed, methods should be explored which collapse these down into a small number of grouped characteristics by focusing on the relationships between attributes and their links to the objectives of the surveillance system and the evaluation. A generic and comprehensive evaluation framework could then be developed consisting of a limited number of common attributes together with several sets of secondary attributes which could be selected depending on the disease or range of diseases under surveillance and the purpose of the surveillance. Economic evaluation should be an integral part of the surveillance evaluation process. This would provide a significant benefit to decision-makers who often need to make choices based on limited or diminishing resources.

The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).

BACKGROUND & AIMS: Enteroendocrine cells are thought to directly sense nutrients via α-gustducin coupled taste receptors (originally identified in the oral epithelium) to modulate the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). METHODS: We measured mRNA expression of α-gustducin and T1R3 along the human gut; immunohistochemistry was used to confirm co-localization with GLP-1. Functional implication of sweet taste receptors in glucose-stimulated secretion of GLP-1 and PYY was determined by intragastric infusion of glucose with or without lactisole (a sweet taste receptor antagonist) in 16 healthy subjects. RESULTS: α-gustducin was expressed in a region-specific manner (predominantly in the proximal gut and less in ileum and colon, P < 0.05). Both, T1R3 and α-gustducin were co-localized with GLP-1. Glucose-stimulated secretions of GLP-1 (P = 0.026) and PYY (P = 0.034) were reduced by blocking sweet receptors with lactisole. CONCLUSION: Key proteins implicated in taste signaling are present in the human gut and co-localized with GLP-1 suggesting that these proteins are functionally linked to peptide secretion from enteroendocrine cells. Glucose-stimulated secretion of GLP-1 and PYY is reduced by a sweet taste antagonist, suggesting the functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of both peptides in humans.

Safety, tolerability and pharmacokinetics of intravaginal pentamycin.

BACKGROUND/AIMS: Intravaginal pentamycin is a polyene macrolide with a broad spectrum of antimicrobial activity and is effective in various forms of infectious vaginitis. We evaluated the safety, tolerability and pharmacokinetics of escalating doses of this product. METHODS: Nineteen healthy volunteers were randomized to receive double blind one of five doses of intravaginal pentamycin (3, 10, 30, 60 or 100 mg) or the corresponding dose of pentamycin vehicle daily for 6 days. Patients with symptomatic vaginitis received a single dose of 60 (n = 6) or 100 mg (n = 6) of intravaginal pentamycin. Safety and tolerability parameters were monitored throughout the study. Plasma concentrations of pentamycin were measured daily in the healthy volunteers and on the day of drug application in the patients. RESULTS: The most frequently reported adverse events were mild or moderate vaginal discharge and mild symptoms of vaginal irritation (mainly pruritus or burning sensation), which also occurred in women who applied the vehicle. No patient with symptomatic vaginitis reported treatment-related adverse events. The plasma levels of pentamycin were below the quantification limit in all samples. CONCLUSION: Intravaginal pentamycin does not cause adverse reactions compared with vehicle and is not absorbed through the intact or the inflamed vagina.