Lessons for rabies control and elimination programmes: a decade of One Health experience from Bali, Indonesia.

Since the emergence of rabies on Bali, Indonesia, in 2008, the Indonesian Government and other stakeholders have implemented disease control and prevention activities with the aim of re-securing Bali's freedom from dog-mediated rabies. The authors report on the lessons learned during these efforts, and their applicability to other regions where canine rabies is endemic, as well as to rabies-free populations that are at risk from incursions. To eliminate rabies from Bali will require time and commitment, as well as a combination of approaches employing the principle of One Health. Efforts should be directed towards well-coordinated, highcoverage, annual dog vaccination campaigns using high-quality vaccines, and enhanced surveillance focused on investigations of biting animals. Bali, an island, is an ideal target for achieving freedom from rabies, but the logistics of vaccinating its very large, free-roaming dog population are challenging. Lessons can be drawn from Bali for other large and dense dog populations, where dog management and rabies control appear difficult. Well-trained teams with nets can rapidly catch and vaccinate large numbers of dogs where central-point vaccination is insufficient, and post vaccination surveys of collared dogs can be used to evaluate coverage and target supplementary vaccination. However, careful planning is required to ensure that all communities are reached during such campaigns and that sufficient vaccine is available over the following years. Effective communication strategies are needed to coordinate intersectoral activities, and to keep communities engaged, particularly during the 'end game', when the risk of rabies appears only minimal. An effective One Health approach to eliminate rabies requires long-term planning, multisectoral communication and coordination, and sustained effort, using tried and tested methods.

Suite à l'émergence de la rage à Bali (Indonésie) en 2008, le gouvernement indonésien et d'autre parties prenantes ont introduit des mesures de contrôle et de prévention de la maladie afin de sécuriser le statut précédemment indemne de Bali au regard de la rage transmise par les chiens. Les auteurs font le point sur les enseignements tirés de cette expérience et évaluent sa pertinence pour d'autres régions, par exemple celles où la rage canine est endémique ou qui possèdent des populations indemnes de rage mais exposées au risque d'une incursion du virus. L'élimination de la rage à Bali est une entreprise qui prendra du temps et exigera une grande détermination ainsi que le recours combiné à diverses méthodes suivant les principes Une seule santé. Les efforts devront s'orienter vers des campagnes annuelles de vaccination des chiens, qu'il faudra coordonner avec soin en assurant une couverture élevée et en faisant appel à des vaccins de haute qualité, et vers une surveillance accrue avec notamment l'investigation de tout chien responsable de morsure. De par son insularité, Bali constitue un territoire idéal pour réussir l'élimination totale de la rage, mais la logistique requise pour la vaccination est lourde, en plus du défi majeur que posent les effectifs importants de chiens errants. Les leçons tirées de l'expérience de Bali peuvent se révéler fructueuses dans d'autres régions dotées de populations canines denses et nombreuses et où les opérations de gestion de ces populations et de lutte contre la rage se présentent sous un jour peu favorable. Dans les contextes où il n'y a pas suffisamment de centres de vaccination, les chiens peuvent être capturés et vaccinés en grand nombre par des équipes bien entraînées et disposant de filets, tandis que le suivi post-vaccinal des chiens enregistrés offre un bon moyen d'évaluer la couverture vaccinale et de cibler les besoins supplémentaires. Il est essentiel de bien planifier ces campagnes afin de s'assurer qu'elles ont touché toutes les communautés et que les stocks de vaccins sont suffisants pour les années à venir. Des stratégies efficaces de communication sont nécessaires pour coordonner les activités intersectorielles et pour maintenir le niveau de motivation des communautés, en particulier en fin de campagne car les risques de rage sont alors perçus comme étant minimes. Pour être efficace, une approche Une seule santé d'élimination de la rage requiert une planification sur le long terme, une communication multisectorielle et des efforts de longue haleine recourant à des méthodes éprouvées.

Desde que en 2008 la rabia hizo su aparición en Bali (Indonesia), el Gobierno del país y otras partes interesadas han llevado a cabo una serie de actividades de control y prevención de la enfermedad con el objetivo de devolver a la isla la condición de «libre de la rabia transmitida por perros¼. Los autores dan cuenta de las enseñanzas extraídas de esta labor y examinan la viabilidad de aplicarlas a otras regiones donde la rabia canina es endémica, así como a poblaciones libres de rabia que corren peligro de sufrir incursiones de la enfermedad. Para eliminar la rabia de Bali hará falta tiempo y dedicación, así como una combinación de métodos regida por los principios de Una sola salud. Convendría centrar el trabajo en campañas anuales de vacunación de perros bien coordinadas, de amplia cobertura y realizadas con vacunas de gran calidad, que se acompañen de una vigilancia más intensa centrada en la investigación de los casos de animales mordedores. Por su condición insular, Bali ofrece condiciones idóneas para lograr la eliminación de la rabia, pero la logística de las vacunaciones es muy aparatosa y las poblaciones de perros vagabundos plantean grandes problemas. De la experiencia balinesa cabe extraer enseñanzas útiles para otras zonas que albergan poblaciones de perros amplias y densas, donde la gestión de estas poblaciones y la lucha antirrábica parecen resultar dificultosas. Allí donde la vacunación centralizada no baste, cabe desplegar equipos bien formados y provistos de redes que puedan capturar y vacunar rápidamente a un gran número de perros, empleando después, eventualmente, estudios posvacunales de los perros con collar identificativo para evaluar la cobertura y seleccionar objetivos de vacunación complementaria. Sin embargo, para llegar a todas las comunidades en el curso de tales campañas y tener la seguridad de disponer de un suministro suficiente de vacunas en los años subsiguientes hace falta una minuciosa planificación. Se necesitan asimismo dispositivos eficaces de comunicación para coordinar las actividades intersectoriales, y también hay que mantener movilizadas a las comunidades, especialmente en la fase final, cuando el riesgo de rabia parece ser mínimo. Todo método eficaz de eliminación de la rabia que parta de los postulados de Una sola salud exige planificación a largo plazo, comunicación y coordinación multisectoriales y una labor sostenida, con empleo de métodos de probada y contrastada eficacia.

On the path to rabies elimination: The need for risk assessments to improve administration of post-exposure prophylaxis.

BACKGROUND: Costs of rabies post-exposure prophylaxis (PEP) often remain high in regions where rabies has been controlled in dogs, presenting a challenge for sustaining rabies elimination programmes. We investigated the potential for bite patient risk assessments to improve PEP provision and surveillance in settings approaching elimination of dog-mediated rabies. METHODS: We conducted a longitudinal study of patients presenting to animal bite treatment centres (ABTCs) on the island province of Bohol in the Philippines to investigate the health status of biting dogs and to quantify current expenditure on PEP. RESULTS: Incidence of bite patients presenting to ABTCs was high (>300/100,000 persons/year) and increasing, resulting in substantial health provider costs. Over $142,000 was spent on PEP in 2013 for a population of 1.3 million. From follow up of 3820 bite patients we found that  >92% were bitten by healthy dogs (alive 14 days after the bite) and just 1.4% were bitten by probable or confirmed rabid dogs. The status of dogs that bit 6% of patients could not be determined. During the course of investigations of bites by suspect dogs, we were able to obtain samples for case confirmation, identify exposed persons who had not sought PEP as well as in-contact dogs at risk of developing rabies. We calculate that expenditure on PEP could at least be halved through more judicious approaches to provision of PEP, based on the histories of biting animals determined through risk assessments with bite patients. CONCLUSIONS: We conclude that a One Health approach to surveillance based on Integrated Bite Case Management could improve the sustainability and effectiveness of rabies elimination programmes while also improving patient care by identifying those genuinely in need of lifesaving PEP.

The risk of rabies spread in Japan: a mathematical modelling assessment.

Rabies was eliminated from Japan in 1957. In the 60 years since elimination, vaccination coverage has declined and dog ownership habits have changed. The purpose of this study was to assess the current risk of rabies spread in Japan. A spatially explicit transmission model was developed at the 1 km2 grid scale for Hokkaido and Ibaraki Prefectures. Parameters associated with dog movement and bite injuries were estimated using historical records from Japan, and were used with previously published epidemiological parameters. The final epidemic size, efficacy of rabies contingency plans and the influence of dog owner responses to incursions were assessed by the model. Average outbreak sizes for dog rabies were 3.1 and 4.7 dogs in Hokkaido and Ibaraki Prefectures, respectively. Average number of bite injury cases were 4.4 and 6.7 persons in Hokkaido and Ibaraki Prefectures, respectively. Discontinuation of mandatory vaccination increased outbreak sizes in these prefectures. Sensitivity analyses showed that higher chance of unintentional release of rabid dogs by their owners (from 0.5 to 0.9 probability) increased outbreak size twofolds. Our model outputs suggested that at present, incursions of rabies into Japan are very unlikely to cause large outbreaks. Critically, the reaction of dog owners to their dogs developing rabies considerably impacts the course of outbreaks. Contingency measures should therefore include sensitisation of dog owners.

Proof of concept of mass dog vaccination for thecontrol and elimination of canine rabies.

For more than 100 years, canine rabies vaccination has been available as a tool for rabies control and elimination. However, domestic dogs still remain a major reservoir for rabies, and although canine rabies has been eliminated through mass dog vaccination in some parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. This review focuses on the situation on those two continents, presenting evidence to show that canine rabies elimination is both epidemiologically and operationally feasible, and could be achieved across a wide range of settings in Africa and Asia. The challenges of achieving the large-scale, comprehensive dog vaccination coverage that is required are discussed, and opportunities for developing new strategies that generate multiple benefits for human and animal health and welfare are highlighted. Finally, the substantial progress that has been made in developing the tools, partnerships and frameworks needed to move towards global canine rabies elimination is outlined.

La vaccination antirabique des chiens est pratiquée depuis plus d'un siècle en tant qu'outil de contrôle et d'élimination de la rage. Néanmoins, les chiens domestiques constituent encore aujourd'hui un réservoir majeur du virus de la rage et si la rage canine a pu être éliminée dans certaines régions du monde grâce à la vaccination massive des chiens, la maladie continue de faire des dizaines de milliers de victimes humaines chaque année en Afrique et en Asie. Les auteurs font le point sur la situation dans ces deux continents en montrant que l'élimination de la rage canine est un objectif réaliste, tant au plan épidémiologique qu'opérationnel, et atteignable dans de très diverses configurations d'Afrique et d'Asie. Ils décrivent les difficultés d'obtenir le niveau requis de couverture vaccinale des populations canines en termes d'effectifs vaccinés et de territoires couverts, et soulignent les perspectives de développement de nouvelles stratégies pouvant générer de multiples bénéfices pour la santé et le bien-être des hommes et des animaux. Enfin, ils évoquent les progrès considérables accomplis dans la mise en place des outils, des partenariats et des cadres nécessaires pour avancer vers l'objectif de l'élimination mondiale de la rage canine.

La vacunación contra la rabia canina es una herramienta utilizada desde hace más de 100 años con fines de control y eliminación de la enfermedad. No obstante, los perros domésticos aún constituyen un importante reservorio de rabia, y pese que en algunas partes del mundo se ha logrado eliminar la rabia canina gracias a la vacunación masiva de perros, esta afección sigue matando a decenas de miles de personas al año en África y Asia. Los autores, centrándose en la situación reinante en estos dos continentes, presentan datos demostrativos de que la eliminación de la rabia canina es un objetivo factible tanto epidemiológica como operativamente, hacedero en muy diversos lugares de África y Asia. También exponen los problemas existentes para lograr la amplia cobertura de vacunación canina a gran escala que se requiere para cumplir tal objetivo y destacan las oportunidades existentes para elaborar nuevas estrategias que deparen múltiples beneficios para la salud y el bienestar de personas y animales. Por último, repasan a grandes líneas los sustanciales progresos registrados en la creación de las herramientas, las alianzas y los marcos de referencia que se necesitan para avanzar hacia la eliminación de la rabia canina en todo el mundo.

One Health contributions towards more effective and equitable approaches to health in low- and middle-income countries.

Emerging zoonoses with pandemic potential are a stated priority for the global health security agenda, but endemic zoonoses also have a major societal impact in low-resource settings. Although many endemic zoonoses can be treated, timely diagnosis and appropriate clinical management of human cases is often challenging. Preventive 'One Health' interventions, e.g. interventions in animal populations that generate human health benefits, may provide a useful approach to overcoming some of these challenges. Effective strategies, such as animal vaccination, already exist for the prevention, control and elimination of many endemic zoonoses, including rabies, and several livestock zoonoses (e.g. brucellosis, leptospirosis, Q fever) that are important causes of human febrile illness and livestock productivity losses in low- and middle-income countries. We make the case that, for these diseases, One Health interventions have the potential to be more effective and generate more equitable benefits for human health and livelihoods, particularly in rural areas, than approaches that rely exclusively on treatment of human cases. We hypothesize that applying One Health interventions to tackle these health challenges will help to build trust, community engagement and cross-sectoral collaboration, which will in turn strengthen the capacity of fragile health systems to respond to the threat of emerging zoonoses and other future health challenges. One Health interventions thus have the potential to align the ongoing needs of disadvantaged communities with the concerns of the broader global community, providing a pragmatic and equitable approach to meeting the global goals for sustainable development and supporting the global health security agenda.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'.

Bovine rabies in Turkey: patterns of infection and implications for costs and control.

The incidence of rabies in livestock is an important factor for estimating the economic impact of the disease, but obtaining reliable data is hindered by inadequate surveillance. In order to understand the contribution of livestock rabies to the overall burden of disease, the rabies incidence in cattle was investigated in detail for Turkey between 2008 and 2011. Data were compiled on cattle numbers, samples submitted for rabies diagnosis, vaccinated animals and positive rabies cases in animals for seven regions in Turkey. Rabies incidence in cattle fluctuated annually and differed between regions from 0·10 to 3·87 cases/100 000 animals. The positive influence of compensation schemes was observed. Livestock losses were conservatively estimated at around $250 000 international dollars per annum, although in areas where compensation schemes are not operating this could be an underestimate of the economic burden. Vaccination of cattle remains an option for disease prevention, although oral rabies vaccination through aerially distributed baits should be implemented to prevent the further spread of fox-mediated rabies, which could result in much greater economic costs.

Integrating the landscape epidemiology and genetics of RNA viruses: rabies in domestic dogs as a model.

Landscape epidemiology and landscape genetics combine advances in molecular techniques, spatial analyses and epidemiological models to generate a more real-world understanding of infectious disease dynamics and provide powerful new tools for the study of RNA viruses. Using dog rabies as a model we have identified how key questions regarding viral spread and persistence can be addressed using a combination of these techniques. In contrast to wildlife rabies, investigations into the landscape epidemiology of domestic dog rabies requires more detailed assessment of the role of humans in disease spread, including the incorporation of anthropogenic landscape features, human movements and socio-cultural factors into spatial models. In particular, identifying and quantifying the influence of anthropogenic features on pathogen spread and measuring the permeability of dispersal barriers are important considerations for planning control strategies, and may differ according to cultural, social and geographical variation across countries or continents. Challenges for dog rabies research include the development of metapopulation models and transmission networks using genetic information to uncover potential source/sink dynamics and identify the main routes of viral dissemination. Information generated from a landscape genetics approach will facilitate spatially strategic control programmes that accommodate for heterogeneities in the landscape and therefore utilise resources in the most cost-effective way. This can include the efficient placement of vaccine barriers, surveillance points and adaptive management for large-scale control programmes.

Bioreactors for connective tissue engineering: design and monitoring innovations.

The challenges for the tissue engineering of connective tissue lie in creating off-the-shelf tissue constructs which are capable of providing organs for transplantation. These strategies aim to grow a complex tissue with the appropriate mechanical integrity necessary for functional load bearing. Monolayer culture systems lack correlation with the in vivo environment and the naturally occur ring cell phenotypes. Part of the development of more recent models is to create growth environments or bioreactors which enable three-dimensional culture. Evidence suggests that in order to grow functional load-bearing tissues in a bioreactor, the cells must experience mechanical loading stimuli similar to that experienced in vivo which sets out the requirements for mechanical loading bioreactors. An essential part of developing new bioreactors for tissue growth is identifying ways of routinely and continuously measuring neo-tissue formation and in order to fully identify the successful generation of a tissue implant, the appropriate on-line monitoring must be developed. New technologies are being developed to advance our efforts to grow tissue ex vivo. The bioreactor is a critical part of these developments in supporting growth of biological implants and combining this with new advances in the detection of tissue formation allows us to refine our protocols and move nearer to off-the-shelf implants for clinical applications.

Rabies control in rural Africa: evaluating strategies for effective domestic dog vaccination.

Effective vaccination campaigns need to reach a sufficient percentage of the population to eliminate disease and prevent future outbreaks, which for rabies is predicted to be 70%, at a cost that is economically and logistically sustainable. Domestic dog rabies has been increasing across most of sub-Saharan Africa indicating that dog vaccination programmes to date have been inadequate. We compare the effectiveness of a variety of dog vaccination strategies in terms of their cost and coverage in different community settings in rural Tanzania. Central-point (CP) vaccination was extremely effective in agro-pastoralist communities achieving a high coverage (>80%) at a low cost (US$5/dog) and inadequate (<20% coverage); combined approaches using CP and either house-to-house vaccination or trained community-based animal health workers were most effective with coverage exceeding 70%, although costs were still high (>US$6 and >US$4/dog, respectively). No single vaccination strategy is likely to be effective in all populations and therefore alternative approaches must be deployed under different settings. CP vaccination is cost-effective and efficient for the majority of dog populations in rural Tanzania and potentially elsewhere in sub-Saharan Africa, whereas a combination strategy is necessary in remote pastoralist communities. These results suggest that rabies control is logistically feasible across most of the developing world and that the annual costs of effective vaccination campaigns in Tanzania are likely to be affordable.

Binocular correlation of ocular aberration dynamics.

Fluctuations in accommodation have been shown to be correlated in the two eyes of the same subject. However, the dynamic correlation of higher-order aberrations in the frequency domain has not been studied previously. A binocular Shack-Hartmann wavefront sensor is used to measure the ocular wavefront aberrations concurrently in both eyes of six subjects at a sampling rate of 20.5 Hz. Coherence function analysis shows that the inter-ocular correlation between aberrations depends on subject, Zernike mode and frequency. For each subject, the coherence values are generally low across the resolvable frequency range (mean 0.11), indicating poor dynamic correlation between the aberrations of the two eyes. Further analysis showed that phase consistency dominates the coherence values. Monocular and binocular viewing conditions showed similar power spectral density functions.

Isolation of strains of Thermus aquaticus from the Australian Artesian Basin and a simple and rapid procedure for the preparation of their plasmids.

Thirty four Thermus aquaticus strains have been isolated from the non-volcanically naturally heated waters of the Australian Artesian Basin which extends the known ecological habitat of this group of organisms. A simple and rapid method developed for isolation of plasmids indicated that considerable variation in numbers and molecular sizes existed within the 23 strains that were investigated. Dissimilar plasmid profiles were obtained from the strains that been isolated from the source waters and those that had been isolated from the runoff channels formed by these source waters.