Capturing free-roaming dogs for sterilisation: A multi-site study in Goa, India.

Sterilisation and rabies vaccination programs seek to manage free-roaming domestic dog (Canis familiaris) populations with the aim to reduce inter-species disease transmission and conflicts. As effective, permanent, remotely-administered options are not yet available for sterilisation, and oral vaccination is not yet commonly used; free-roaming dogs are typically captured for these interventions. There is a paucity of information describing how dog capture rates change over time within defined areas following repeated capture efforts. This data is needed to allow efficient dog capture programmes to be developed. Using spatial co-ordinates of dog capture, we characterise where dogs are more likely to be captured in six catch-sterilise-release campaigns, in Goa state, India. Combining capture numbers with population survey data collected in five sites, we document the increasing difficulty of catching entire (non-sterilised) dogs as sterilisation coverage increases and demonstrate how this leads to increased unit costs. Accounting for the extra resources required to capture dogs when sterilisation coverage is high will improve estimation of the resources required to manage free-roaming dog populations and assist in planning the most efficient intervention strategies.

Modelling bodyweight to avoid anthelmintic underdosing of goats in resources-limited settings.

Improved management of livestock in resource-limited settings can provide a means towards improved human nutrition and livelihoods. However, gastrointestinal nematodes (GIN) are a significant production-limiting factor. Anthelmintics play a role in GIN management; however, few anthelmintic classes are available in many low-middle-income countries. Utilising a limited range of classes may increase selection for anthelmintic resistance; therefore, strategies to reduce other selective pressures are of heightened importance. Avoiding anthelmintic underdosing is one such strategy, but it can be challenging without access to accurate bodyweight measurement. Many previous studies have used thoracic girth as a practical proxy for bodyweight in goats; however, they have rarely considered the potential impact of natural variation on therapeutic doses. Here, the relationship between bodyweight and thoracic girth was modelled using data from 820 goats from three Malawian biomes in two seasons, with the specific aim of avoiding underestimation of bodyweight. The internally cross-validated linear regression (∛Weight ~ 0.053 + 0.040*Girth, R2 = 0.92, rounded up to the nearest 5 kg) was validated against data from an additional 352 Malawian goats (1.4% of goats allocated an underdose and 10.2% allocated a dose > 200% of bodyweight). The equation was further externally validated using an historical dataset of 150 goats from Assam, India (2.7% of goats were allocated to an underdose and 24.8% allocated to a > 200% of bodyweight). These results suggest that a more globally generalisable approach may be feasible, provided the accuracy of the estimate is considered alongside the therapeutic index of the pharmaceutical.

Community attitudes and perceptions towards free-roaming dogs in Goa, India.

Free-roaming dogs (FRD) represent a large proportion of the canine population in India and are often implicated as a source of conflict with humans. However, objective data on the attitudes and perceptions of local communities toward FRD are lacking. This study collected baseline data from 1141 households in Goa, India, on FRD feeding practices and assessed people's attitudes toward FRD in urban and rural communities. Additionally, respondents identified problems caused by FRD and proposed potential solutions.The study reported that 37% of respondents fed FRD with dog owners and Hindus being the most likely to feed. The majority of respondents agreed FRD were a menace (57%), a nuisance (58%) and scary (60%). Most respondents also agreed FRD were a vulnerable population (59%), that belong in communities (66%) and have a right to live on the streets (53%). Barking was the most commonly reported problem associated with FRD and the preferred solution was to impound FRD in shelters. This study reveals the complex and often misunderstood relationship between local communities and FRD and highlights potential strategies to reduce human-dog conflict.

Elimination of human rabies in Goa, India through an integrated One Health approach.

Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.

Free-roaming dog population dynamics in Ranchi, India.

Rabies causes approximately 20,000 human deaths in India each year. Nearly all of these occur following dog bites. Large-scale, high-coverage dog rabies vaccination campaigns are the cornerstone of rabies elimination strategies in both human and dog populations, although this is particularly challenging to achieve in India as a large proportion of the dog population are free-roaming and unowned. Further, little is known about free-roaming dog ecology in India which makes defining optimum vaccination strategies difficult. In this study, data collected using a mobile phone application during three annual mass vaccination and neutering (surgical sterilisation of both males and females) campaigns of free-roaming dogs in Ranchi, India (during which a total of 43,847 vaccinations, 26,213 neuter surgeries and 28,172 re-sight observations were made) were interrogated, using two novel approaches to estimate the proportion of neutered dogs that were lost from the city (assumed due to mortality or migration) between campaign years. Analysis revealed high losses of neutered dogs each year, ranging from 25.3% (28.2-22.8) to 55.8% (57.0-54.6). We also estimated that the total population declined by 12.58% (9.89-15.03) over the three-year period. This demonstrates that there is a high turnover of free-roaming dogs and that despite neutering a large number of dogs in an annual sterilisation campaign, the decline in population size was modest over a three-year time period. These findings have significant implications for the planning of rabies vaccination campaigns and population management programmes as well as highlighting the need for further research into the demographics of free-roaming, unowned dogs in India.

Timing of reproduction and association with environmental factors in female free-roaming dogs in southern India.

Annual peaks in reproductive activity have been identified in multiple domestic dog populations. However, there is little evidence to describe how these peaks may be associated with environmental factors such as daylength, which plays a well-established role in breeding patterns of seasonally-reproductive species. Data were collected 2016-2020 during 7,743 and 4,681 neuter surgeries on adult female unowned free-roaming dogs in veterinary clinics in Goa and Tamil Nadu respectively. Temperature, precipitation, relative humidity, and daylength data were gathered for time periods preceding the neuter surgery that may have influenced the likelihood of pregnancy (potential influence periods). A multivariable generalised additive model was used to assess the relationship between these factors and pregnancy. The prevalence of pregnancy varied by month in both locations indicating seasonality of reproduction in these groups. The annual pattern was more distinct in Goa with a peak in pregnancies between September and December. In Goa, decreasing daylength was associated with a higher probability of pregnancy (p = 0.040). Decreasing temperature was associated with decreasing probability of pregnancy in the Nilgiris (p = 0.034). Bitches had a median of 6 foetuses, with no evidence of seasonal variation. Environmental factors were associated with patterns of pregnancy in free-roaming dogs, however statistically-significant factors varied by geographical location. Establishing local seasonal patterns of breeding in free-roaming dogs and assessing their relationship with environmental influences is recommended to facilitate effective and efficient population management strategies, which aim to reduce conflict between human and free-roaming dog populations.

Conjunctival mucous membrane colour as an indicator for the targeted selective treatment of haemonchosis and of the general health status of peri-urban smallholder goats in southern Malawi.

The world's growing population is becoming increasingly centred around large cities, affording opportunities for peri-urban food production. Goats are well-suited to conversion of resources that are available in peri-urban settings into meat and occasionally milk. Haemonchus contortus has been described as "the nemesis of small ruminant production systems in tropical and subtropical regions"; hence control of haemonchosis through planned animal health management affords a pragmatic first step in improving the production efficiency of peri-urban goats. This study of peri-urban goat production investigated the potential value of targeted selective treatment of haemonchosis. 452 peri-urban goat keepers in southern Malawi were visited during three seasonal periods with relevance to the epidemiology of haemonchosis. 622, 599 and 455 individually identified goats were clinically examined during the dry season, the rainy season, and shortly after the end of the rainy season, respectively. Data were recorded for sex, age, weight, conjunctival mucous membrane colour score (FAMACHA©), body condition score (BCS) and faecal worm egg count (FEC); and where possible for pregnancy and lactation status. Animals with pale ocular mucous membranes were treated with 10 mg/kg albendazole, then re-examined 14 days later. Animals with pink mucous membranes, but FECs ≥250 eggs per gram were also re-examined and treated 14 days later. The results show high variability in growth rates deduced from the ages and bodyweights of each of 999 goats at the time of their enrolment. FAMACHA© scores alone were a poor index for the targeted selective treatment of haemonchosis, because they failed to identify too many animals that would have required treatment at different times of year and using different FAMACHA© and FEC cut-offs. Combining the indices of FAMACHA© scores ≥4, body condition scores ≥2, and age >18 months was more reliable in identifying those animals requiring treatment when different epidemiologically-relevant FEC thresholds for different seasons were taken into account. Inclusion of late pregnancy or early lactation status would have resulted in very few animals requiring treatment being missed. The use of conjunctival mucous membrane colour scoring in this way provided a valuable insight of the general health status of the peri-urban goats, to create opportunities for planned animal health management to improve productivity. The efficacy of albendazole treatment was poor, putatively due to drug resistance, or poor drug bioavailability in goats. In summary, our study shows opportunities for better production efficiency in peri-urban goats, and demonstrates the value of simple clinical diagnostic indices as decision support tools in planned animal health management.

Oral bait handout as a method to access roaming dogs for rabies vaccination in Goa, India: A proof of principle study.

Rabies has profound public health, social and economic impacts on developing countries, with an estimated 59,000 annual human rabies deaths globally. Mass dog vaccination is effective at eliminating the disease but remains challenging to achieve in India due to the high proportion of roaming dogs that cannot be readily handled for parenteral vaccination. Two methods for the vaccination of dogs that could not be handled for injection were compared in Goa, India; the oral bait handout (OBH) method, where teams of two travelled by scooter offering dogs an empty oral bait construct, and the catch-vaccinate-release (CVR) method, where teams of seven travel by supply vehicle and use nets to catch dogs for parenteral vaccination. Both groups parenterally vaccinated any dogs that could be held for vaccination. The OBH method was more efficient on human resources, accessing 35 dogs per person per day, compared to 9 dogs per person per day through CVR. OBH accessed 80% of sighted dogs, compared to 63% by CVR teams, with OBH accessing a significantly higher proportion of inaccessible dogs in all land types. All staff reported that they believed OBH would be more successful in accessing dogs for vaccination. Fixed operational team cost of CVR was four times higher than OBH, at 127 USD per day, compared to 34 USD per day. Mean per dog vaccination cost of CVR was 2.53 USD, whilst OBH was 2.29 USD. Extrapolation to a two week India national campaign estimated that 1.1 million staff would be required using CVR, but 293,000 staff would be needed for OBH. OBH was operationally feasible, economical and effective at accessing the free roaming dog population. This study provides evidence for the continued expansion of research into the use of OBH as a supplementary activity to parenteral mass dog vaccination activities in India.

Estimating the effectiveness of vaccine programs in dog populations.

Dogs harbor numerous zoonotic pathogens, many of which are controlled through vaccination programs. The delivery of these programs can be difficult where resources are limited. We developed a dynamic model to estimate vaccination coverage and cost-per-dog vaccinated. The model considers the main factors that affect vaccination programs: dog demographics, effectiveness of strategies, efficacy of interventions and cost. The model was evaluated on data from 18 vaccination programs representing eight countries. Sensitivity analysis was performed for dog confinement and vaccination strategies. The average difference between modelled vaccination coverage and field data was 3.8% (2.3%-5.3%). Central point vaccination was the most cost-effective vaccination strategy when >88% of the dog population was confined. More active methods of vaccination, such as door-to-door or capture-vaccinate-release, achieved higher vaccination coverage in free-roaming dog populations but were more costly. This open-access tool can aid in planning more efficient vaccination campaigns in countries with limited resources.

Implementation of high coverage mass rabies vaccination in rural Uganda using predominantly static point methodology.

Despite successful eradication programmes in many regions, rabies remains responsible for approximately 60,000 human deaths annually, and no country in Africa is rabies-free. Dogs are the principal reservoir of the virus in Africa and the World Health Organisation recommends that at least 70% of the dog population be vaccinated in order to break the transmission cycle. Most attempts at mass rabies vaccinations in Africa have failed to vaccinate high numbers of dogs at a high coverage. Successful studies have often used a door-to-door (DTD) approach, which is logistically challenging and expensive compared to a static point (SP) approach. Mission Rabies has successfully implemented a combined SP and DTD method in cities in India and Malawi. This campaign used a combined methodology in rural Uganda, starting with a SP campaign, followed by a DTD campaign, and then subsequent transect surveys to assess vaccination coverage. This was facilitated by the use of a smartphone application which recorded all vaccinations and survey responses along with their Global Positioning System location. A total of 4172 dogs were vaccinated in 7 days, attaining an estimated 88.4% coverage. This campaign is of particular note as 95.9% of the vaccinations were performed at SPs. The human-to-dog ratio was 4.9 with a mean dogs per house of 1.2. Most dogs were owned (93.7%). This demonstrates that high-number, high-coverage vaccination is achievable in rural Uganda and provides data that may refine future campaign approaches.

A comparison of population estimation techniques for individually unidentifiable free-roaming dogs.

BACKGROUND: Measuring the size of free roaming dog populations quickly and accurately is critical in the implementation of numerous preventive health and population control interventions. However, few studies have investigated the relative performance of population size assessment tools when applied to dogs. The aim of this study was to compare the commonly used mark-resight methodology with distance sampling methods, which are less resource intensive, to estimate free-roaming dog abundance in Goa, India. Twenty-six working zones were surveyed along all roads twice by the same surveyor at the same time of day, following a vaccination campaign which included marking of vaccinated dogs with a coloured paint. The Chapman estimate was then used to evaluate the mark-resight abundance. Additionally, the number of dogs and perpendicular distance from the road for all dogs sighted was recorded. This was used to estimate dog density and abundance using distance sampling methods. The detection function was fitted based on goodness-of-fit and AIC. RESULTS: The Chapman abundance estimate for the entire study area was 5202 dogs (95%CI 4733.8-5671.0), and the distance sampling method abundance estimate was 5067 dogs (95%CI 4454.3-5764.2). For individual working zones, after taking other factors into account in a mixed effects model, the average distance sampling estimate was 35% higher (95%CI 20-53%) than the Chapman estimate. There was also evidence of a difference in estimates between surveyors of 21% (95%CI 7-37%) and between days (22% lower on day 2, 95%CI 8-38%) for individual working zones. CONCLUSION: Our study demonstrated that the distance sampling estimates were comparable overall to the Chapman method of abundance estimation of free roaming dogs across the entire study region but there was noticeable variation between the two methods when individual zones were compared. Consequently, distance sampling methods may be suitable to enumerate dogs over large areas in a more time efficient manner than the widely used mark-resight approach.

Development of non-governmental organisation-academic partnership to tackle rabies in Africa and Asia.

Rabies kills approximately 60,000 people each year, mainly in sub-Saharan Africa and Asia, of which 40% of victims are less than 15 years old. Once clinical signs develop, the disease is almost invariably fatal. Globally, rabies has been estimated to cause 3∙7 million disability-adjusted life years and $8∙6B in economic losses annually. The vast majority of human rabies cases are caused by bites from rabies-infected dogs. Despite this loss of human life and resultant economic and societal costs, rabies can be prevented in both humans and dogs by vaccination. This has been demonstrated in many countries, notably in Central and South America, where large-scale, high coverage mass dog vaccination programmes have dramatically reduced the incidence of rabies. Even in parts of Africa and Asia, projects have shown that rabies can be eliminated locally. Nevertheless, rabies remains an important cause of mortality in many sub-Saharan and Asian countries. The reasons why some countries have been able to effectively eliminate rabies whereas others have not are complex and often impossible to definitively identify; commonly cited explanations include political, economic, logistical and societal barriers.

Investigation of short-term surgical complications in a low-resource, high-volume dog sterilisation clinic in India.

BACKGROUND: Surgical sterilisation is currently the method of choice for controlling free-roaming dog populations. However, there are significant logistical challenges to neutering large numbers of dogs in low-resource clinics. The aim of this study was to investigate the incidence of short-term surgical complications in a low-resource sterilisation clinic which did not routinely administer post-operative antibiotics. The medical records of all sterilisation surgeries performed in 2015 at the Worldwide Veterinary Service International Training Centre in Tamil Nadu, India were reviewed (group A) to assess immediate surgical complications. All animals in this group were monitored for at least 24 h post-surgery but were not released until assessed by a veterinarian as having uncomplicated wound healing. In the second part of this study from August to December 2015, 200 free-roaming dogs undergoing sterilisation surgery, were monitored for a minimum of 4-days post-surgery to further assess postoperative complications (group B). RESULTS: Surgery related complications were seen in 5.4% (95%CI, 4.5-6.5%) of the 1998 group A dogs monitored for at least 24 h, and in 7.0% (3.9-11.5%) of the 200 group B dogs monitored for 4 days. Major complications were classed as those requiring an intervention and resulted in increased morbidity or mortality. Major complications were seen in 2.8% (2.1-3.6%) and 1.5% (3.1-4.3%) of group A and B, respectively. Minor complications requiring little or no intervention were recorded for 2.6% (1.9-3.4%) for group A and 5.5% (2.8-9.6%) for group B. There was no evidence for a difference in complication rates between the two groups in a multivariate regression model. CONCLUSION: This study demonstrated that high volume, low-resource sterilisation of dogs can be performed with a low incidence of surgical complications and low mortality.

Historical, current and expected future occurrence of rabies in enzootic regions.

Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii. Australia is the only inhabited continent with enzootic rabies, without the presence of rabies virus. Europe and North America have broken the cycle of dog-mediated rabies, with a few remaining focal points in Latin America and the Caribbean, but wildlife rabies predominates. The greatest burden resides in the 'Old World'. The elimination of human rabies mediated via dogs by 2030 in Africa, Asia and the Middle East will not be simple, rapid or inexpensive, but it may be achievable through the use of widely available tools and the application of lessons learned during the course of the 20th century.

La rage est l'une des plus anciennes maladies infectieuses enregistrées et la zoonose virale la plus largement représentée dans le monde. On présume que l'Antarctique est indemne de tout lyssavirus mais cette hypothèse n'est étayée par aucune surveillance basée sur des analyses de laboratoire. Il existe une menace de réintroduction de la maladie en Océanie, comme l'ont révélé le foyer historique survenu à Guam ainsi que l'arrivée de chauves-souris enragées à Hawaï. L'Australie est le seul continent habité où la rage ne sévit pas à l'état enzootique, le virus de la rage y étant absent. L'Europe et l'Amérique du Nord ont mis fin au cycle de la rage transmise par les chiens, dont il ne subsiste que quelques rares foyers de propagation en Amérique latine ; en revanche, la rage sylvatique reste prépondérante dans ces régions. Le fardeau le plus lourd est supporté par l'Ancien Monde. L'élimination de la rage humaine transmise par les chiens à l'horizon 2030 en Afrique, en Asie et au Moyen-Orient ne sera pas une tâche facile, rapide ni exempte de coûts mais elle peut réussir grâce aux outils disponibles partout dans le monde et aux enseignements tirés de l'expérience acquise tout au long du xxe siècle.

La rabia, causada por uno de los patógenos más antiguos de los que hay constancia, presenta la distribución más amplia de cuantas zoonosis víricas se conocen. Se piensa que la Antártida está libre de todo tipo de lisavirus, pero no ha habido labores de vigilancia en laboratorio que prueben tal suposición. Oceanía está bajo la amenaza de reintroducción de la enfermedad, como demuestran el histórico brote registrado en Guam o el desplazamiento de murciélagos rabiosos a Hawái. Australia es el único continente habitado en el que no hay rabia enzoótica, esto es, en que el virus rábico no está presente. Europa y América del Norte han interrumpido el ciclo de la rabia transmitida por perros, de la que aún quedan contados focos en América Latina y el Caribe, aunque sigue prevaleciendo la rabia de la fauna silvestre. La carga más importante recae en el «Viejo Mundo¼. La eliminación de la rabia humana transmitida por perros para 2030 en África, Asia y el Oriente Medio no será sencilla, rápida ni barata, pero es factible si se emplean herramientas que ya están extendidas y se aplican las lecciones que hemos aprendido a lo largo del siglo XX.

Global rabies management: perspectives on regional strategies for prevention and control.

Rabies is a major neglected zoonotic disease, despite the availability of highly sensitive diagnostic tests and efficacious human and animal vaccines. Perpetuation of rabies among multiple species of bats and wild carnivores, together with the presence of diverse lyssaviruses, remains a challenge for the prevention and control of this disease. However, most of the global burden may be reduced by mass vaccination of dogs, the major reservoir. Elimination of human rabies mediated by dogs may be feasible, based upon the elicitation of herd immunity, the application of sound health economic principles for appropriate disease management and technology transfer to those developing countries where rabies is hyper-endemic. Global canine rabies elimination has clear benefits for public health, veterinary medicine and conservation biology, so these sectors must collaborate using a transdisciplinary 'One Health' approach that allows the creation of long-term regional strategies for enhanced surveillance and practical intervention.

La rage est une maladie zoonotique majeure, qui demeure négligée malgré l'existence de tests de diagnostic hautement sensibles et de vaccins efficaces chez l'homme comme chez l'animal. La persistance de la rage chez de nombreuses espèces de carnivores sauvages et de chauves-souris et la diversité des espèces de Lyssavirus continuent de poser des difficultés en termes de prévention et de lutte contre la maladie. Néanmoins, le fardeau mondial de la rage peut être considérablement réduit en pratiquant la vaccination massive des chiens, ces derniers constituant le principal réservoir. L'élimination de la rage transmise par les chiens est un objectif atteignable si l'on s'appuie sur des concepts solides en matière d'immunité à l'échelle des troupeaux, d'économie de la santé et de transfert technologique, tout en apportant des bénéfices mutuels accrus pour la santé publique, la médecine vétérinaire et la biologie de la conservation grâce à la mise en oeuvre d'une approche régionale pour la surveillance, les interventions, la certification et la collaboration pluridisciplinaire dans un contexte Une seule santé.

La rabia es una importante enfermedad zoonótica desatendida, y ello pese a que existen pruebas de diagnóstico de gran sensibilidad y vacunas de contrastada eficacia en personas y animales. La perpetuación de la rabia en múltiples especies de carnívoros silvestres y murciélagos y la presencia de diversos lisavirus siguen dificultando el trabajo de prevención y control de la enfermedad. Con todo, cabe reducir buena parte de la carga mundial que impone la rabia mediante la vacunación masiva de perros, que son su principal reservorio. Si se aplican conceptos sólidos en materia de inmunidad de rebaño, economía de la salud y transferencia de tecnología, abordando las labores de vigilancia, intervención, certificación y colaboración multidisciplinar desde una lógica regional y desde los postulados de «Una sola salud¼, la eliminación de la rabia humana transmitida por perros puede ser un objetivo factible y muy beneficioso para la salud pública, la medicina veterinaria y la biología de la conservación.

The problem of stray dogs.

The effective management of stray dogs is critically important in any rabies vaccination programme. In many rabies-endemic countries, stray dogs represent a significant proportion of both the free-roaming and total dog populations, and to ensure that rabies elimination programmes are successful, it is essential that this portion of the dog population (stray dogs) is vaccinated at high coverage. However, there are a number of challenges to managing and delivering rabies vaccinations to stray dogs. This paper will review the most pertinent issues relating to the problem of stray dogs and rabies elimination, focusing on the challenges relating to the estimation of population size, vaccination administration and vaccine coverage assessment in stray dog populations. The authors will highlight how these challenges can be overcome, notably by reviewing the census techniques that have been employed to assess stray dog populations, which then facilitate the planning and design of vaccination programmes. In addition, they discuss the range of vaccination strategies that are available and that have been used to vaccinate stray dogs and review how vaccination coverage can be assessed in this population. Finally, the benefits of population management in stray dogs through neutering programmes are reviewed. In short, this paper highlights the importance of ensuring that stray dogs, as well as owned dogs, are included in vaccination programmes and emphasises that many of the challenges related to protecting stray dogs from rabies can be overcome.

L'efficacité de la gestion des populations de chiens errants est un aspect essentiel de tout programme de vaccination contre la rage. Dans de nombreux pays où la rage est endémique, les chiens errants constituent un segment important des populations de chiens laissés en liberté et plus généralement de la population canine totale, de sorte que le succès des programmes d'élimination de la rage repose sur l'impératif d'assurer une forte couverture vaccinale au sein de cette partie de la population canine. Toutefois, s'agissant des chiens errants la gestion de la vaccination et l'administration des vaccins antirabiques présentent des difficultés particulières. Les auteurs font le point sur les principales questions posées par la problématique des chiens errants dans une perspective d'élimination de la rage, qui concernent notamment la difficulté d'évaluer la taille des populations concernées, d'administrer les vaccins dans ce cadre et d'évaluer la couverture vaccinale obtenue. Les auteurs soulignent les réponses qui peuvent être apportées à ces problèmes, en particulier en revoyant les techniques de recensement appliquées jusqu'à présent pour évaluer les populations de chiens errants, ce qui permettra ensuite de faciliter la planification et la conception des programmes de vaccination. En outre, ils examinent les différentes stratégies de vaccination mises en oeuvre en la matière et font le point sur les moyens d'évaluer la couverture vaccinale de ces populations. Enfin, ils analysent les avantages apportés par les programmes de stérilisation pour maîtriser les populations de chiens errants. En résumé, cet article met l'accent sur l'importance d'inclure les chiens errants au même titre que les chiens ayant un maître dans les programmes de vaccination et souligne que la plupart des difficultés liées à la protection des chiens errants contre la rage peuvent être résolues.

Uno de los aspectos capitales de todo programa de vacunación antirrábica es la gestión eficaz de las poblaciones de perros vagabundos. En muchos países con rabia endémica, estos perros representan un porcentaje sustancial tanto de la población canina total como de los perros en libertad. El éxito de todo programa de eliminación de la rabia pasa necesariamente por lograr una elevada cobertura de vacunación en este segmento de la población canina (los perros vagabundos). Sin embargo, la gestión y la vacunación antirrábica de los perros vagabundos presentan una serie de dificultades. Los autores pasan revista a los aspectos que más inciden en el problema de los perros vagabundos y la eliminación de la rabia, prestando especial atención a las dificultades que presentan la estimación del tamaño de la población, la administración de vacunas y el cálculo de la cobertura de vacunación de las poblaciones de perros vagabundos. Después explican la manera de superar estas dificultades, en particular describiendo las técnicas de censo empleadas para calcular el tamaño de las poblaciones, lo que a su vez facilita la concepción y planificación de programas de vacunación. Además, describen el arsenal existente de procedimientos de vacunación que se han utilizado para vacunar a los perros vagabundos y explican cómo estimar en estas poblaciones la cobertura de vacunación. Por último exponen los beneficios de gestionar las poblaciones de perros vagabundos con programas de esterilización. En resumidas cuentas, los autores recalcan aquí la importancia de que los programas de vacunación canina lleguen a los perros vagabundos, y no solo a los animales con dueño, e insisten en que muchos de los problemas que se plantean para proteger de la rabia a los perros vagabundos tienen solución.

MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63.

MYCN amplification is a major biomarker of poor prognosis, occurring in 25-30% of neuroblastomas. MYCN has contradictory roles in promoting cell growth and sensitizing cells to apoptosis. We have recently shown that p53 is a direct transcriptional target of MYCN in neuroblastoma and that p53-mediated apoptosis may be an important mechanism of MYCN-induced apoptosis. Although p53 mutations are rare in neuroblastoma at diagnosis, the p53/MDM2/p14(ARF) pathway is often inactivated through MDM2 amplification or p14(ARF) inactivation. We hypothesized that reactivation of p53 by inhibition of its negative regulator MDM2, using the MDM2-p53 antagonists Nutlin-3 and MI-63, will result in p53-mediated growth arrest and apoptosis especially in MYCN-amplified cells. Using the SHEP Tet21N MYCN-regulatable system, MYCN(-) cells were more resistant to both Nutlin-3 and MI-63 mediated growth inhibition and apoptosis compared with MYCN(+) cells and siRNA-mediated knockdown of MYCN in four MYCN-amplified cell lines resulted in decreased p53 expression and activation, as well as decreased levels of apoptosis following treatment with MDM2-p53 antagonists. In a panel of 18 neuroblastoma cell lines treated with Nutlin-3 and MI-63, the subset amplified for MYCN had a significantly lower mean GI(50) value (50% growth inhibition) and increased caspase 3/7 activity compared with the non-MYCN-amplified group of cell lines, but p53 mutant cell lines were resistant to the antagonists regardless of MYCN status. We conclude that amplification or overexpression of MYCN sensitizes neuroblastoma cell lines with wild-type p53 to MDM2-p53 antagonists and that these compounds may therefore be particularly effective in treating high-risk MYCN-amplified disease.

Bioactive polymer grafting onto titanium alloy surfaces.

Bioactive polymers bearing sulfonate (styrene sodium sulfonate, NaSS) and carboxylate (methylacrylic acid, MA) groups were grafted onto Ti6Al4V alloy surfaces by a two-step procedure. The Ti alloy surfaces were first chemically oxidized in a piranha solution and then directly subjected to radical polymerization at 70 degrees C in the absence of oxygen. The grafted surfaces were characterized by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS) and the toluidine blue colorimetric method. Toluidine blue results showed 1-5microgcm(-2) of polymer was grafted onto the oxidized Ti surfaces. Grafting resulted in a decrease in the XPS Ti and O signals from the underlying Ti substrate and a corresponding increase in the XPS C and S signals from the polymer layer. The ToF-SIMS intensities of the S(-) and SO(-) ions correlated linearly with the XPS atomic percent S concentrations and the ToF-SIMS intensity of the TiO(3)H(2)(-) ion correlated linearly with the XPS atomic per cent Ti concentration. Thus, the ToF-SIMS S(-), SO(-) and TiO(3)H(2)(-) intensities can be used to quantify the composition and amount of grafted polymer. ToF-SIMS also detected ions that were more characteristic of the polymer molecular structure (C(6)H(4)SO(3)(-) and C(8)H(7)SO(3)(-) from NaSS, C(4)H(5)O(2)(-) from MA), but the intensity of these peaks depended on the polymer thickness and composition. An in vitro cell culture test was carried out with human osteoblast-like cells to assess the influence of the grafted polymers on cell response. Cell adhesion after 30min of incubation showed significant differences between the grafted and ungrafted surfaces. The NaSS grafted surfaces showed the highest degree of cell adhesion while the MA-NaSS grafted surfaces showed the lowest degree of cell adhesion. After 4 weeks in vivo in rabbit femoral bones, bone was observed to be in direct contact with all implants. The percentage of mineralized tissue around the implants was similar for NaSS grafted and non-grafted implants (59% and 57%). The MA-NaSS grafted implant exhibited a lower amount of mineralized tissue (47%).

Modulus-dependent macrophage adhesion and behavior.

Macrophage attachment and activation to implanted materials is crucial in determining the extent of acute and chronic inflammation, and biomaterials degradation. In an effort to improve implant performance, considerable attention has centered on altering material surface chemistry to modulate macrophage behavior. In this work, the influence of the modulus of a material on the behavior of model macrophages (i.e., human promonocytic THP-1 cells) was investigated. We synthesized interpenetrating polymer network (IPN) coatings with varying moduli to test the hypothesis that lower moduli surfaces attenuate THP-1 cell attachment and activation. The surface chemistry and moduli of the IPN coatings were characterized using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), respectively. THP-1 cells preferentially attached to stiffer coatings of identical surface chemistry, confirming that fewer macrophages attach to lower moduli surfaces. The secretion of human TNF-alpha, IL-10, IL-8 and IL-1beta from THP-1 cells attached to the IPNs was measured to assess the concentration of both pro- and anti-inflammatory cytokines. The global amount of TNF-alpha released did not vary for IPN surfaces of different moduli; however, the amount of the pro-inflammatory cytokine IL-8 released demonstrated a biphasic response, where lower (approx. 1.4 kPa) and very high (approx. 348 kPa) moduli IPN surfaces attenuated IL-8 secretion. The different trends for TNF-alpha and IL-8 secretion highlight the complexity of the wound healing response, suggesting that there may not be a unique surface chemistry and substratum modulus combination that minimizes the pro-inflammatory cytokines produced by activated macrophages.

Bioactive poly(ethylene terephthalate) fibers and fabrics: grafting, chemical characterization, and biological assessment.

The grafting of poly(sodium styrene sulfonate) (pNaSS) onto ozone-treated poly(ethylene terephthalate) (PET) fabric surfaces was characterized by X-ray photoelectron spectroscopy and toluidine blue colorimetry. Significant amounts of pNaSS were grafted over the range of experimental conditions examined in this study (30-120 min of ozonation, reaction at 65 or 70 degrees C, and reaction times up to 240 min). Within these ranges the amount of grafted pNaSS increased with both ozonation time and reaction temperature. The amount of grafted pNaSS increased over the first 60 min of reaction, then remained relatively constant from 60 to 240 min. For the biological experiments pNaSS-grafted samples were prepared with 30 min of ozonation and 60 min of reaction at a grafting temperature of 70 degrees C. The ozonation time was limited to 30 min to minimize any possible degradation of the PET fabrics by the ozonation treatment. The pNaSS-grafted PET surface adsorbed a factor of 4 more compared to the nongrafted surfaces. The strength of fibroblast adhesion was an order of magnitude higher on pNaSS-grafted PET fabrics compared to that on nongrafted PET fabrics. This difference in the cell attachment was correlated to the cell spreading, which was better and more homogeneous on the grafted fibers compared to the nongrafted fibers. Fibroblasts adhered more strongly on surfaces precoated with normal human plasma compared to surfaces precoated with 10% fetal calf serum in Dulbecco's modified Eagle's medium.