Comparing the genetic typing methods for effective surveillance and rabies control in Georgia.

A full nucleoprotein gene sequencing of 68 isolates collected from passive rabies surveillance system in Georgia between 2015 and 2016 identified two distinct dog rabies phylogroups, GEO_V1 and GEO_V2, which both belonged to the cosmopolitan dog clade. GEO_V1 was found throughout the country and was further divided into four sub-phylogroups that overlapped geographically; GEO_V2 was found in the southeast region and was closely related to dog rabies in Azerbaijan. A sequence analysis of the full N gene, partial nucleoprotein gene of N-terminal and C-terminal, and the amplicon sequences of pan-lyssavirus RT-qPCR LN34 showed that all four sequencing approaches provided clear genetic typing results of canine rabies and could further differentiate GEO_V1 and GEO_V2. The phylogenetic analysis results vary and were affected by the length of the sequences used. Amplicon sequencing of the LN34 assay positive samples provided a rapid and cost-effective method for rabies genetic typing, which is important for improving rabies surveillance and canine rabies eradication globally.

Evaluation of an iELISA for detection and quantification of rabies antibodies in domestic dog sera.

Many rabies endemic-countries have recognized rabies as a public health problem that can be eliminated. As a result, some countries have started implementing small-scale vaccination programs with the aim of scaling them up. Post-vaccination serological monitoring is crucial to assess the efficacy of these programs. The recommended serological tests, the rapid fluorescent focus inhibition test, and the fluorescent antibody virus neutralization (FAVN) are accurate; however, the procedures require considerable expertise and must be carried out in high containment facilities, which are often not available in rabies endemic countries. Given these constraints, enzyme linked immunosorbent assays (ELISAs) have been considered as alternative methods to neutralization tests. This is the first study to evaluate, under field conditions, the performance of the commercial rabies indirect-ELISA (iELISA), the PlateliaTM Rabies II kit ad usum Veterinarium kit, using sera from domestic dogs. Serum samples were collected from two groups of community dogs in northern Tanzania: i) dogs with no history of vaccination against rabies (n = 100) and ii) dogs vaccinated with the Nobivac Canine Rabies® vaccine (n = 101) four weeks previously. When compared to the gold standard FAVN test, the iELISA was found to be 99% specific and 98% sensitive and there was a significant correlation between the two tests (p < 0.001, r = 0.92). Given these findings, we conclude that the PlateliaTM Rabies II kit ad usum Veterinarium can be considered a valuable tool for the rapid assessment of vaccination status of animals in vaccination programs.

Emerging Genomic Trends on Rabies Virus in Davao Region, Philippines, 2018-2021.

Rabies, caused by the rabies virus (RABV), remains a significant public health issue in the Philippines despite efforts to control it. To eliminate rabies by 2030, effective surveillance strategies are crucial. In this study, we examined RABV evolution and phylodynamics in the Davao Region using genome sequences from Davao City and nearby provinces. We adapted the RABV ARTIC Protocol for Oxford Nanopore High-Throughput Sequencing to optimize workflow efficiency under limited resources. Comparing new virus samples collected from June 2019 to June 2021 (n = 38) with baseline samples from June 2018 to May 2019 (n = 49), new sub-clades were observed in the phylogenetic tree, suggesting divergence from older variants that were previously undetected. Most of the new viruses belonged to the Asian SEA4_A1.1.1 lineage, but new (SEA4_B1 and SEA4_B1.1) and emerging (SEA4_B1.1_E1) lineages that have never been reported in the Philippines were also identified. The baseline study reported phylogeographic clustering of RABV isolates from the same areas. However, this pattern was disrupted in the current biosurveillance, with variants detected in areas outside the original cluster. Furthermore, our findings revealed significant transmission routes between Davao City and neighboring provinces, contrasting with the predominantly intra-city transmission observed in the baseline study. These results underscore the need for ongoing and timely genomic surveillance to monitor genetic diversity changes and the emergence of novel strains, as well as to track alterations in transmission pathways. Implementing cost-effective next-generation sequencing workflows will facilitate the integration of genomic surveillance into rabies control programs, particularly in resource-limited settings. Collaborations between different sectors can empower local laboratories and experts in genomic technologies and analysis.

The New Face of Human Rabies in Mexico, What's Next After Eradicating Rabies in Dogs.

In pre-Hispanic Mexico, dogs were not identified as an important source of rabies. We know from codexes and chronicles of the conquerors that at that time, rabies cases in humans and domestic animals were caused by local wildlife species such as bats. Canine-rabies virus variant seems to have arrived with Europeans. The first documented case of canine rabies in the Americas is found in Mexico in the Annals of the Holy Inquisition (16th century). During Mexico's independence, cases were frequently reported. In the 19th century the first attempts to control human rabies were made through sanitary measures such as elimination of rabid dogs and applying postexposure vaccination. During the first half of the 20th century, the efficacy of canine vaccination to prevent human rabies was established. However, in Mexico, despite reports of numerous human cases (>70/year), canine vaccination did not have enough coverage. It was only during the 1990s that Mexico made a serious commitment to eliminate dog-transmitted human rabies. Since the beginning, vaccination campaigns have been free and massive. Coverage increased from 7,100,000 doses in 1990 to more than 18,000,000 since 2017. This culminated in the elimination of dog-mediated human rabies cases since 2006. Subsequently, the epidemiology of rabies had changed. Nowadays, it is wildlife species (mainly bats and skunks) that are the source of human rabies. As a mega-biodiverse country Mexico has numerous wildlife species with potential to transmit rabies virus. Thus it is paramount to remain vigilant with respect to canine vaccination campaigns and to promote rabies research in wildlife.

Review of Oral Rabies Vaccination of Dogs and Its Application in India.

Oral rabies vaccines (ORVs) have been in use to successfully control rabies in wildlife since 1978 across Europe and the USA. This review focuses on the potential and need for the use of ORVs in free-roaming dogs to control dog-transmitted rabies in India. Iterative work to improve ORVs over the past four decades has resulted in vaccines that have high safety profiles whilst generating a consistent protective immune response to the rabies virus. The available evidence for safety and efficacy of modern ORVs in dogs and the broad and outspoken support from prominent global public health institutions for their use provides confidence to national authorities considering their use in rabies-endemic regions. India is estimated to have the largest rabies burden of any country and, whilst considerable progress has been made to increase access to human rabies prophylaxis, examples of high-output mass dog vaccination campaigns to eliminate the virus at the source remain limited. Efficiently accessing a large proportion of the dog population through parenteral methods is a considerable challenge due to the large, evasive stray dog population in many settings. Existing parenteral approaches require large skilled dog-catching teams to reach these dogs, which present financial, operational and logistical limitations to achieve 70% dog vaccination coverage in urban settings in a short duration. ORV presents the potential to accelerate the development of approaches to eliminate rabies across large areas of the South Asia region. Here we review the use of ORVs in wildlife and dogs, with specific consideration of the India setting. We also present the results of a risk analysis for a hypothetical campaign using ORV for the vaccination of dogs in an Indian state.

Sharing the Load by One Health: Integrating Canine Rabies Vaccination With Bovine Foot-and-Mouth Vaccination Program and Community Public Health Services in Rural Nilgiris District, Tamil Nadu, India.

Background: India carries the largest national burden for rabies globally. Coordinating large-scale canine rabies elimination programs is challenging, particularly in rural areas, where the majority of human rabies deaths occur. This study evaluated the feasibility of combining canine rabies vaccination with pre-existing animal-health interventions or public health programs in a rural area of India. Materials and Methods: Canine rabies vaccination teams collaborated with a bi-annual bovine foot-and-mouth vaccination program coordinated by the Animal Husbandry Department (AH-collaboration) and with a village health program by the Public Health Department (PH-collaboration) in Nilgiris, Tamil Nadu, to vaccinate dogs during the implementation of these government-led health initiatives. Results: A total of 251 dogs were vaccinated over 7 days during the AH-collaboration, and 1083 dogs were vaccinated over 15 days during the PH-collaboration. The AH-collaboration achieved a vaccination coverage of 76% based on same-time sighting survey, and 58% based on post-vaccination survey. The PH-collaboration achieved vaccination coverage of 79% based on the same-time survey and 83% based on the post-vaccination survey. Conclusions: The integration of mass dog vaccination into existing government sector initiatives may facilitate the scaling up of canine rabies vaccination campaigns.

Lessons Learned and Paths Forward for Rabies Dog Vaccination in Madagascar: A Case Study of Pilot Vaccination Campaigns in Moramanga District.

Canine rabies causes an estimated 60,000 human deaths per year, but these deaths are preventable through post-exposure prophylaxis of people and vaccination of domestic dogs. Dog vaccination campaigns targeting 70% of the population are effective at interrupting transmission. Here, we report on lessons learned during pilot dog vaccination campaigns in the Moramanga District of Madagascar. We compare two different vaccination strategies: a volunteer-driven effort to vaccinate dogs in two communes using static point vaccination and continuous vaccination as part of routine veterinary services. We used dog age data from the campaigns to estimate key demographic parameters and to simulate different vaccination strategies. Overall, we found that dog vaccination was feasible and that most dogs were accessible to vaccination. The static-point campaign achieved higher coverage but required more resources and had a limited geographic scope compared to the continuous delivery campaign. Our modeling results suggest that targeting puppies through community-based vaccination efforts could improve coverage. We found that mass dog vaccination is feasible and can achieve high coverage in Madagascar; however, context-specific strategies and an investment in dog vaccination as a public good will be required to move the country towards elimination.

Barriers and opportunities for canine rabies vaccination campaigns in Addis Ababa, Ethiopia.

BACKGROUND: Canine rabies is endemic in Ethiopia and presents a significant burden for both animal and human health. We investigate barriers to dog vaccination in Addis Ababa, Ethiopia. These results can be utilized to improve and target future rabies control efforts. METHODOLOGY/PRINCIPLE FINDINGS: During May of 2017, dog owners were surveyed during a free canine rabies vaccination programs that utilized both door-to-door (DtD) and central point (CP) vaccination methods. Surveys collected information on preferences for rabies vaccine delivery and were administered in Amharic. A total of 1057 surveys were completed. Of those surveyed, 62.4 % indicated that their dogs had been vaccinated against rabies within the last year. Commonly reported barriers to vaccination were a lack of awareness that dogs required rabies vaccines (18.1 %) and lack of knowledge about where to find vaccine (15.0 %). The median price owners were willing to pay for vaccination was 25 birr ($0.91 USD) and the median distance willing to travel was 1.0 km; however, 48.9 % of those surveyed during DtD were unwilling to travel at all. We identified 3 classes of respondents who were grouped due to their responses by latent class analysis: 'the Unaware', 'the Vaccinators', and 'the Multiple Barriers'. CONCLUSIONS/SIGNIFICANCE: Although many respondents were willing to pay for rabies vaccine (94.0 %); the preferred cost (median) was less than the actual cost of providing the vaccine. This supports the need for reduced-cost or free vaccine to achieve and sustain the 70 % vaccine coverage target threshold for canine rabies elimination. Additionally, a significant portion (41.5 %) of those surveyed indicated that they were unwilling to travel in order to have their dog vaccinated. The latent class analysis provides useful guidance on how to reach target vaccination. Owners from 'the Unaware' group made up 18.1 % of respondents and their high rate of allowing their dogs to roam identifies them as a prime target for canine health and behavior education. 'The Multiple Barriers' owners reported lower degrees of dog roaming and were substantially more likely to be found by DtD campaigns, possibly because they have limited ability/interest in handling their dogs. These results demonstrate the importance of incorporating DtD vaccination as well as subsidies to maximize vaccine coverage in Addis Ababa.

Portable Rabies Virus Sequencing in Canine Rabies Endemic Countries Using the Oxford Nanopore MinION.

As countries with endemic canine rabies progress towards elimination by 2030, it will become necessary to employ techniques to help plan, monitor, and confirm canine rabies elimination. Sequencing can provide critical information to inform control and vaccination strategies by identifying genetically distinct virus variants that may have different host reservoir species or geographic distributions. However, many rabies testing laboratories lack the resources or expertise for sequencing, especially in remote or rural areas where human rabies deaths are highest. We developed a low-cost, high throughput rabies virus sequencing method using the Oxford Nanopore MinION portable sequencer. A total of 259 sequences were generated from diverse rabies virus isolates in public health laboratories lacking rabies virus sequencing capacity in Guatemala, India, Kenya, and Vietnam. Phylogenetic analysis provided valuable insight into rabies virus diversity and distribution in these countries and identified a new rabies virus lineage in Kenya, the first published canine rabies virus sequence from Guatemala, evidence of rabies spread across an international border in Vietnam, and importation of a rabid dog into a state working to become rabies-free in India. Taken together, our evaluation highlights the MinION's potential for low-cost, high volume sequencing of pathogens in locations with limited resources.

Spatio-temporal evolution of canine rabies in Tunisia, 2011-2016.

Tunisia is an endemic country for dog mediated rabies. An increase in canine rabies cases during the last decade has been suspected. Since no studies have been conducted on rabies spatial distribution, the present work was focused on spatiotemporal evolution of rabies in Tunisia during the 2011-2016 period with a special focus on the reservoir species. Data collected concerned suspected dogs that originate from the whole country. Surveillance indicators such as positive fractions and number of suspected dogs received at the laboratory have been calculated. Spatiotemporal hotspots were then mapped, spatial and spatio-temporal analysis were carried out using discrete Poisson spatial model and space-time permutation models available in SaTScan9 software. The study revealed that an actual increase in canine rabies incidence occurred in Tunisia since 2012. Spatial and spatio-temporal analysis identified clusters centered in the North and in the Center East of the country. Spatio-temporal clusters were non overlapping, indicating that this spatial distribution is not fixed through time. A large heterogeneity in surveillance indicators such as number of suspected dogs was associated to the distance to the laboratory or to insufficient coordination between governorates.

Towards the elimination of dog-mediated rabies: development and application of an evidence-based management tool.

BACKGROUND: International organizations advocate for the elimination of dog-mediated rabies, but there is only limited guidance on interpreting surveillance data for managing elimination programmes. With the regional programme in Latin America approaching elimination of dog-mediated rabies, we aimed to develop a tool to evaluate the programme's performance and generate locally-tailored rabies control programme management guidance to overcome remaining obstacles. METHODS: We developed and validated a robust algorithm to classify progress towards rabies elimination within sub-national administrative units, which we applied to surveillance data from Brazil and Mexico. The method combines criteria that are easy to understand, including logistic regression analysis of case detection time series, assessment of rabies virus variants, and of incursion risk. Subjecting the algorithm to robustness testing, we further employed simulated data sub-sampled at differing levels of case detection to assess the algorithm's performance and sensitivity to surveillance quality. RESULTS: Our tool demonstrated clear epidemiological transitions in Mexico and Brazil: most states progressed rapidly towards elimination, but a few regressed due to incursions and control lapses. In 2015, dog-mediated rabies continued to circulate in the poorest states, with foci remaining in only 1 of 32 states in Mexico, and 2 of 27 in Brazil, posing incursion risks to the wider region. The classification tool was robust in determining epidemiological status irrespective of most levels of surveillance quality. In endemic settings, surveillance would need to detect less than 2.5% of all circulating cases to result in misclassification, whereas in settings where incursions become the main source of cases the threshold detection level for correct classification should not be less than 5%. CONCLUSION: Our tool provides guidance on how to progress effectively towards elimination targets and tailor strategies to local epidemiological situations, while revealing insights into rabies dynamics. Post-campaign assessments of dog vaccination coverage in endemic states, and enhanced surveillance to verify and maintain freedom in states threatened by incursions were identified as priorities to catalyze progress towards elimination. Our finding suggests genomic surveillance should become increasingly valuable during the endgame for discriminating circulating variants and pinpointing sources of incursions.

Movement patterns of free-roaming dogs on heterogeneous urban landscapes: Implications for rabies control.

In 2015, a case of canine rabies in Arequipa, Peru indicated the re-emergence of rabies virus in the city. Despite mass dog vaccination campaigns across the city and reactive ring vaccination and other control activities around positive cases (e.g. elimination of unowned dogs), the outbreak has spread. Here we explore how the urban landscape of Arequipa affects the movement patterns of free-roaming dogs, the main reservoirs of the rabies virus in the area. We tracked 23 free-roaming dogs using Global Positioning System (GPS) collars. We analyzed the spatio-temporal GPS data using the time- local convex hull method. Dog movement patterns varied across local environments. We found that water channels, an urban feature of Arequipa that are dry most of the year, promote movement. Dogs that used the water channels extensively move on average 7 times further (p = 0.002) and 1.2 times more directionally (p = 0.027) than dogs that do not use the water channels at all. They were also 1.3 times faster on average, but this difference was not statistically significant (p = 0.197). Our findings suggest that water channels can be used by dogs as 'highways' to transverse the city and have the potential to spread disease far beyond the radius of control practices. Control efforts should focus on a robust vaccination campaign attuned to the geography of the city, and not limited to small-scale rings surrounding cases.

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.

Progress towards rabies control and elimination in Vietnam.

Rabies is a fatal viral disease that causes an estimated 59,000 human deaths each year. The majority of these deaths occur in developing countries in Asia. Canine rabies is endemic to Vietnam, which is, however, moving towards the disease's elimination. Many countries, such as Vietnam, have invested tremendous resources in controlling rabies, highlighting the goal of regional and global elimination of this neglected disease. In Vietnam, rabies is recognised as one of five high-priority, zoonotic diseases by the Ministry of Health and the Ministry of Agriculture and Rural Development. Investment by the government and by international partners for rabies prevention and control has played a substantial role in reducing human rabies deaths from 404 cases in 1992 to 74 cases in 2017. The catalyst for this effort was the Prime Minister's creation of the National Rabies Program in 1996, which led to increased support and resources for rabies prevention and control. Interventions carried out since then include the expansion of post-exposure prophylaxis centres throughout the country, the introduction or revision of key legislation and guidelines, and improved multisectoral One Health collaboration. In addition, support from international partners, such as the World Organisation for Animal Health (OIE), the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and the Centers for Disease Control and Prevention (CDC), has helped to increase awareness, manage dog populations more effectively, and improve Vietnam's surveillance and diagnostic capabilities. To pursue the goal of eliminating dog-mediated rabies in Vietnam, political commitment is crucial. Resources must be made available to enforce the regulations and guidelines that will enable Vietnam to achieve greater canine rabies vaccination coverage. In this paper, the authors provide an overview of the animal and human health systems in Vietnam, as well as past, current and future directions of rabies prevention and control.

La rage est une maladie virale à l'issue mortelle faisant chaque année un nombre estimé de 59 000 victimes humaines. La plupart de ces décès surviennent dans les pays en développement d'Asie. Au Vietnam, la rage canine est endémique mais le pays poursuit activement l'objectif d'éliminer la rage de son territoire. À l'instar du Vietnam, plusieurs pays ont investi des ressources colossales pour contrôler la rage, renforçant ainsi la dimension régionale et mondiale de l'objectif d'élimination de cette maladie négligée. Au Vietnam, la rage figure parmi les cinq zoonoses hautement prioritaires prises en compte par le ministère de la Santé et le ministère de l'Agriculture et du développement rural. Les investissements consacrés à la prévention et au contrôle de la rage par le gouvernement et ses partenaires internationaux ont joué un rôle déterminant dans la réduction du nombre de décès humains dus à la rage, qui est passé de 404 cas en 1992 à 74 cas en 2017. L'élément catalyseur de cet effort a été la création en 1996 du Programme national de lutte contre la rage par le premier ministre de l'époque, ce qui a permis de renforcer les ressources et le soutien dédiés à la prévention et à la lutte contre la rage. Depuis lors, les interventions ont porté sur la création de centres de prophylaxie post-exposition sur tout le territoire, l'introduction ou la révision de la législation et des lignes directrices applicables et l'amélioration de la collaboration Une seule santé. En outre, le soutien de partenaires internationaux tels que l'Organisation mondiale de la santé animale (OIE), l'Organisation mondiale de la santé (OMS), l'Organisation des Nations Unies pour l'alimentation et l'agriculture (FAO) et les Centres pour le contrôle et la prévention des maladies (CDC, États-Unis d'Amérique) a abouti à une meilleure sensibilisation, à une gestion plus efficace des populations de chiens et à un renforcement des capacités de surveillance et de diagnostic au Vietnam. Un engagement politique fort est indispensable pour réussir à éliminer totalement la rage transmise par les chiens au Vietnam. Des ressources doivent être rendues disponibles afin de mettre en oeuvre la réglementation et les lignes directrices pertinentes et d'augmenter ainsi la couverture vaccinale de la population canine du pays. Les auteurs décrivent les systèmes de santé animale et publique du Vietnam ainsi que les orientations passées, actuelles et futures de la prévention et du contrôle de la rage dans le pays.

La rabia es una enfermedad vírica fatal, que según las estimaciones mata a 59 000 personas al año, mayoritariamente en países en desarrollo asiáticos. La rabia canina es endémica en el Vietnam, país que no obstante avanza ahora hacia la eliminación de la enfermedad. Como el Vietnam, muchos países han invertido cantidades colosales de recursos en la lucha antirrábica, subrayando con ello su compromiso con el objetivo de eliminar esta enfermedad desatendida a escala regional y mundial. El Ministerio de Salud y el Ministerio de Agricultura y Desarrollo Rural del Vietnam tienen catalogada la rabia como una de las cinco enfermedades zoonóticas que revisten máxima prioridad. Las inversiones en prevención y control de la rabia realizadas por el gobierno y por asociados internacionales han ayudado sensiblemente a reducir el número de personas muertas por la rabia, que ha pasado de 404 casos en 1992 a 74 en 2017. El catalizador de este esfuerzo fue la creación en 1996, por iniciativa del Primer Ministro, del Programa Nacional contra la Rabia, que se tradujo en un aumento del apoyo y los recursos destinados a prevenir y combatir la enfermedad. Entre otras intervenciones, desde entonces se ha multiplicado en todo el país el número de centros donde se dispensa profilaxis tras la exposición, se han promulgado o revisado leyes, decretos y directrices fundamentales y se ha mejorado la colaboración multisectorial en clave de Una sola salud. Además, el respaldo de asociados internacionales como la Organización Mundial de Sanidad Animal (OIE), la Organización Mundial de la Salud (OMS), la Organización de las Naciones Unidas para la Alimentación y la Agricultura (FAO) o los Centros para el Control y la Prevención de Enfermedades (CDC) de los Estados Unidos ha ayudado a generar una mayor conciencia del problema, a gestionar más eficazmente las poblaciones de perros y a dotar al país de mejores medios de vigilancia y diagnóstico. Para hacer realidad el objetivo de eliminar del Vietnam la rabia transmitida por perros, la voluntad política es un factor clave, pues hay que poner sobre la mesa los recursos necesarios para aplicar los reglamentos y normas que permitirán al país ampliar la cobertura de vacunación canina antirrábica. Tras trazar una panorámica de los sistemas sanitario y zoosanitario del Vietnam, los autores describen el rumbo pasado, presente y futuro de las labores de prevención y control de la rabia en el país.

Targeted pre-emptive rabies vaccination strategies in a susceptible domestic dog population with heterogeneous roaming patterns.

Australia is free of canine rabies, however northern regions - such as the Northern Peninsula Area (NPA), Queensland - are at risk of an incursion from nearby rabies-infected Indonesian islands. Early detection and reactive vaccination is the current Australian policy to eradicate an incursion. Early detection in this region is challenging, so pre-emptive vaccination might be an effective strategy. The NPA dog population also has a heterogenous contact structure, with three roaming categories previously characterised, which could be exploited in targeted pre-emptive vaccination strategies for more efficient use of limited resources. To evaluate the effectiveness of a pre-emptive vaccination program, an agent-based rabies spread simulation model was used to simulate outbreaks with a range of pre-emptive vaccination coverages. Increasing proportions (10% increments) of the dog population randomly vaccinated were modelled, and at the most efficient random vaccination coverage we then explored 10 pre-emptive vaccination strategies targeting different dog roaming categories (whilst maintaining the same overall population level vaccination coverage). All pre-emptive vaccination strategies were simulated 2000 times without and with a 70% random reactive vaccination strategy, following rabies detection. All random pre-emptive vaccination coverages reduced outbreak size and duration compared to no pre-emptive vaccination. A 40% random coverage was most efficient. Targeted strategies that pre-emptively vaccinated proportionally more roaming dogs were more effective than a random 40% vaccination coverage and strategies that targeted non-roaming dogs. The pre-emptive vaccination strategies that targeted non-roaming dogs produced significantly larger and longer outbreaks. These results suggest that pre-emptive vaccination can reduce potential rabies outbreaks in this region and that such a strategy should not just focus on easily accessible dogs that do not roam often or at all. A cost-benefit analysis is required to determine whether the implementation of such pre-emptive vaccination strategies is also cost-effective, which is essential in the resource-poor communities of this region.

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.

Impact of Integrating Rabies Education Into the Curriculum of Public Elementary Schools in Ilocos Norte, Philippines on Rabies Knowledge, and Animal Bite Incidence.

As part of a province wide rabies elimination program, rabies specific information was integrated into the curriculum of all public elementary schools in Ilocos Norte, Philippines using a specifically developed teachers' manual. The rabies educational messages included rabies, animal bite prevention, bite management and responsible pet ownership and were integrated into lessons in several subjects. Four elementary schools were randomly selected and an assessment of the change in student's rabies knowledge and animal bite incidence were conducted. The study tested all students in grades 1-5 before the curriculum integration was implemented and retested these cohorts 1 year later, after implementation. Awareness of rabies was high before the implementation, likely due to the province-wide elimination campaign. However, awareness still increased significantly across all schools, and detailed knowledge of rabies increased significantly in all but one school and age cohort. Bite incidence in the 6 months prior to each survey was also recorded and the percentage of students suffering animal bites fell significantly between the two tests. The data suggested that knowledge increase correlated with decreased bite incidence in some groups but not all, suggesting a more complex relationship between knowledge acquisition and behavioral change which warrants further investigation.

Evaluation of immune responses in dogs to oral rabies vaccine under field conditions.

During the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. However, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. Alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was supplemented with ORV to improve vaccination coverage and to evaluate the use of ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were placed in intestine bait and distributed to dogs by hand. Serum was collected from 107 dogs, aged 3-12 months with no reported prior rabies vaccination, pre-vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid florescent focus inhibition test (RFFIT) was used to detect neutralizing antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination, 38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody (RFFIT >0.05 IU/mL), compared to 16/27 (59.3%, p < 0.01) dogs that received ORV or 21/27 (77.8%) as measured by ELISA (>40% blocking, p < 0.05). The fate of 291 oral vaccines was recorded; 283 dogs (97.2%) consumed the bait; 272 dogs (93.4%) were observed to puncture the blister, and only 14 blisters (4.8%) could not be retrieved by vaccinators and were potentially left in the environment. Pre-vaccination antibodies (RFFIT >0.05 IU/mL) were detected in 10/107 reportedly vaccine-naïve dogs (9.3%). Parenteral vaccination remains the most reliable method for ensuring adequate immune response in dogs, however ORV represents a viable strategy to supplement existing parental vaccination campaigns in hard-to-reach dog populations. The hand-out model reduces the risk of unintended contact with ORV through minimizing vaccine blisters left in the community.

Zero human deaths from dog-mediated rabies by 2030: perspectives from quantitative and mathematical modelling.

Dog-mediated rabies continues to kill tens of thousands of people every year in low- and middle-income countries despite being an entirely vaccine-preventable disease. WHO and partners have launched a global campaign to reach zero human deaths from dog-mediated rabies by 2030. The primary tools for reaching this target are mass dog vaccination to control and interrupt transmission in domestic dog populations that maintain infection, and appropriate post-exposure prophylaxis (PEP) for rabies-exposed persons to prevent the fatal onset of disease. Models have been developed to assess the feasibility, impact and cost-effectiveness of these measures. From these models, we argue that the 2030 target of zero human rabies deaths is achievable, but will require concerted effort, engagement and investment. A proposed Gavi investment in human rabies vaccines has potential to drive progress towards the 2030 target; however, concomitant investment is needed to scale up mass dog vaccination or this target will be missed. Predicted economic benefits of mass dog vaccination vary according to national PEP provisioning and access to care. Integrated Bite Case Management can enhance surveillance and rationalize PEP use, but needs adapting to and integrating within local health systems and international reporting systems to improve PEP accountability, monitor impacts and support verification of disease freedom. Modelling is required for projecting more realistic and geographically specific timelines for achieving targets, in line with the implementation of interventions. The greatest risk to the 'Zero by 30' strategy is the limited long-term cross-sectoral or targeted financing to support countries to deliver and sustain mass dog vaccination.

Healthcare utilization, provisioning of post-exposure prophylaxis, and estimation of human rabies burden in Madagascar.

In Madagascar, dog-mediated rabies has been endemic for over a century, however there is little data on its incidence or impact. We collected data over a 16-month period on provisioning of post-exposure prophylaxis (PEP) at a focal clinic in the Moramanga District and determined the rabies status of biting animals using clinical and laboratory diagnosis. We find that animal rabies cases are widespread, and clinic-based triage and investigation are effective ways to increase detection of rabies exposures and to rule out non-cases. A high proportion of rabies-exposed persons from Moramanga sought (84%) and completed PEP (90% of those that initiated PEP), likely reflecting the access and free provisioning of PEP in the district. Current clinic vial sharing practices demonstrate the potential for intradermal administration of PEP in endemic African settings, reducing vaccine use by 50% in comparison to intramuscular administration. A high proportion of PEP demand was attributed to rabies cases, with approximately 20% of PEP administered to probable rabies exposures and an additional 20% to low-to-no risk contacts with confirmed/probable animal or human cases. Using a simplified decision tree and our data on rabies exposure status and health-seeking behavior, we estimated an annual incidence of 42-110 rabies exposures and 1-3 deaths per 100,000 persons annually. Extrapolating to Madagascar, we estimate an annual burden of 282-745 human rabies deaths with current PEP provisioning averting 1499-3958 deaths each year. Data from other clinics and districts are needed to improve these estimates, particularly given that PEP availability is currently limited to only 31 clinics in the country. A combined strategy of mass dog vaccination, enhanced surveillance, and expanded access to PEP along with more judicious guidelines for administration could effectively reduce and eventually eliminate the burden of rabies in Madagascar.