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1.  Implementation of an Intersectoral Program to Eliminate Human and Canine Rabies: The Bohol Rabies Prevention and Elimination Project 
Background
The province of Bohol, located in the Visayas islands region in the Philippines has a human population of 1.13 million and was the 4th highest region for human rabies deaths in the country, averaging 10 per year, prior to the initiation of the Bohol Rabies Prevention and Elimination Project (BRPEP).
Aims
The BRPEP was initiated in 2007 with the goal of building a sustainable program that would prevent human rabies by eliminating rabies at its source, in dogs, by 2010. This goal was in line with the Philippine National Rabies Program whose objective is to eliminate rabies by 2020.
Methods
The intersectoral BRPEP was launched in 2007 and integrated the expertise and resources from the sectors of agriculture, public health and safety, education, environment, legal affairs, interior and local government. The program included: increasing local community involvement; implementing dog population control; conducting mass dog vaccination; improving dog bite management; instituting veterinary quarantine; and improving diagnostic capability, surveillance and monitoring. Funding was secured from the national government, provincial, municipal and village units, dog owners, NGOs, the regional office of the WHO, the UBS Optimus Foundation, and the Global Alliance for Rabies Control. The BRPEP was managed by the Bohol Rabies Prevention and Eradication Council (BRPEC) under the jurisdiction of the Governor of Bohol. Parallel organizations were created at the municipal level and village level. Community volunteers facilitated the institution of the program. Dog population surveys were conducted to plan for sufficient resources to vaccinate the required 70% of the dogs living in the province. Two island-wide mass vaccination campaigns were conducted followed by “catch up” vaccination campaigns. Registration of dogs was implemented including a small fee that was rolled back into the program to maintain sustainability. Children were educated by introducing rabies prevention modules into all elementary schools in Bohol. Existing public health legislation at the national, provincial, and municipal level strengthened the enforcement of activities. A Knowledge, Attitude and Practices (KAP) survey was conducted in 2009 to evaluate the educational knowledge of the population. Increased surveillance was instituted to ensure that dogs traveling into and out of the province were vaccinated against rabies. Human and animal cases of rabies were reported to provincial and national authorities.
Key Results
Within the first 18 months of the BRPEP, human rabies deaths had decreased annually from 0.77 to 0.37 to zero per 100,000 population from 2007–2009. Between October 2008 and November 2010 no human and animal cases were detected. Increased surveillance on the island detected one suspected human rabies case in November 2010 and one confirmed case of canine rabies in April 2011. Two mass vaccination campaigns conducted in 2007 and 2008 successfully registered and vaccinated 44% and 70% of the dogs on the island. The additional surveillance activities enabled a mobilization of mop up vaccination activities in the region where the human and canine case was located. Due to the increased effective and continuous surveillance activities, rabies was stopped before it could spread to other areas on the island. The program costs totaled USD 450,000. Registration fees collected to maintain the program amounted to USD 105,740 and were re-allocated back into the community to sustain the program.
Author Summary
The Province of Bohol, Philippines has eliminated dog and human rabies in less than three years by empowering the community and implementing an intersectoral strategy. In 2006, Bohol ranked 4th highest in the Philippines for human rabies, averaging 10 deaths per year. Launched in 2007, the program utilized a social awareness campaign, dog population control, mass dog vaccination campaigns, improved dog bite management and veterinary quarantine, a new diagnostic laboratory, expanded surveillance, and the inclusion of education modules into the school curriculum. Improving community compliance to existing national and provincial rabies laws and engaging volunteers to help conduct the project was a key to success. The program, led by the Governor of Bohol, was administered through a group of departments working together at a provincial and local level, and supervised through the Office of the Provincial Veterinarian. Financial support came through the Governor and several NGOs including the Global Alliance for Rabies Control. The program is self-sustaining, through a small dog registration fee fed back into the program, through the continuing education of children in their classrooms, and through the dedicated efforts of over 15,000 staff and volunteers throughout the island.
doi:10.1371/journal.pntd.0001891
PMCID: PMC3516573  PMID: 23236525
2.  Intracerebral Administration of Recombinant Rabies Virus Expressing GM-CSF Prevents the Development of Rabies after Infection with Street Virus 
PLoS ONE  2011;6(9):e25414.
Recently it was found that prior immunization with recombinant rabies virus (RABV) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) (LBNSE-GM-CSF) resulted in high innate/adaptive immune responses and protection against challenge with virulent RABV (Wen et al., JVI, 2011). In this study, the ability of LBNSE-GM-CSF to prevent animals from developing rabies was investigated in mice after infection with lethal doses of street RABV. It was found that intracerebral administration of LBNSE-GM-CSF protected more mice from developing rabies than sham-treated mice as late as day 5 after infection with street RABV. Intracerebral administration of LBNSE-GM-CSF resulted in significantly higher levels of chemokine/cytokine expression and more infiltration of inflammatory and immune cells into the central nervous system (CNS) than sham-administration or administration with UV-inactivated LBNSE-GM-CSF. Enhancement of blood-brain barrier (BBB) permeability and increases in virus neutralizing antibodies (VNA) were also observed in mice treated with LBNSE-GM-CSF. On the other hand, intracerebral administration with UV-inactivated LBNSE-GM-CSF did not increase protection despite the fact that VNA were induced in the periphery. However, intracerebral administration with chemoattractant protein-1 (MCP-1, also termed CCL2) increased significantly the protective efficacy of UV-inactivated LBNSE-GM-CSF. Together these studies confirm that direct administration of LBNSE-GM-CSF can enhance the innate and adaptive immunity as well as the BBB permeability, thus allowing infiltration of inflammatory cells and other immune effectors enter into the CNS to clear the virus and prevent the development of rabies.
doi:10.1371/journal.pone.0025414
PMCID: PMC3182207  PMID: 21980450
3.  Factors Associated with Dog Rabies Vaccination in Bohol, Philippines: Results of a Cross-Sectional Cluster Survey Conducted Following the Island-Wide Rabies Elimination Campaign 
Zoonoses and public health  2012;60(7):494-503.
Summary
The Philippines has a long history of rabies control efforts in their dog populations; however, long-term success of such programmes and the goal of rabies elimination have not yet been realized. The Bohol Rabies Prevention and Elimination Program was developed as an innovative approach to canine rabies control in 2007. The objective of this study was to assess canine rabies vaccination coverage in the owned-dog population in Bohol and to describe factors associated with rabies vaccination two years after implementation of the programme. We utilized a cross-sectional cluster survey based on the World Health Organization’s Expanded Programme on Immunization coverage survey technique. We sampled 460 households and collected data on 539 dogs residing within these households. Seventy-seven percent of surveyed households reported owning at least one dog. The human to dog ratio was approximately 4 : 1, and the mean number of dogs owned per household was 1.6. Based on this ratio, we calculated an owned-dog population of almost 300 000. Overall, 71% of dogs were reported as having been vaccinated for rabies at some time in their lives; however, only 64% of dogs were reported as having been recently vaccinated. Dogs in our study were young (median age = 24 months). The odds of vaccination increased with increasing age. Dogs aged 12 – 23 months had 4.6 times the odds of vaccination compared to dogs aged 3 – 11 months (95% CI 1.8 – 12.0; P = 0.002). Confinement of the dog both day and night was also associated with increased odds of vaccination (OR = 2.1; 95% CI 0.9 – 4.9; P = 0.07), and this result approached statistical significance. While the programme is on track to meet its goal of 80% vaccination coverage, educational efforts should focus on the need to confine dogs and vaccinate young dogs.
doi:10.1111/zph.12026
PMCID: PMC3805987  PMID: 23280122
rabies; dog; cross-sectional; Philippines; cluster survey
4.  Human rabies postexposure prophylaxis during a raccoon rabies epizootic in New York, 1993 and 1994. 
Emerging Infectious Diseases  1999;5(3):415-423.
We describe the epidemiology of human rabies postexposure prophylaxis (PEP) in four upstate New York counties during the 1st and 2nd year of a raccoon rabies epizootic. We obtained data from records of 1,173 persons whose rabies PEP was reported to local health departments in 1993 and 1994. Mean annual PEP incidence rates were highest in rural counties, in summer, and in patients 10 to 14 and 35 to 44 years of age. PEP given after bites was primarily associated with unvaccinated dogs and cats, but most (70%) was not attributable to bites. Although pet vaccination and stray animal control, which target direct exposure, remain the cornerstones of human rabies prevention, the risk for rabies by the nonbite route (e. g., raccoon saliva on pet dogs' and cats' fur) should also be considered.
PMCID: PMC2640781  PMID: 10341178
5.  Experimental rabies vaccines for humans 
Expert review of vaccines  2010;9(10):1177-1186.
Rabies remains a global public health threat that kills more than 55,000 people per year. Rabies disproportionately affects children and, therefore, is ranked the seventh most important infectious disease due to years lost. Prevention of human rabies is accomplished by controlling rabies in domestic and wild animals, including the use of vaccination programs. The usefulness of human rabies vaccines is hampered by high cost, complicated vaccination regimens and lack of compliance, especially in areas of Africa and Asia where human rabies infections are endemic. A single-dose vaccine would greatly benefit efforts to combat this global health threat. However, a single-dose vaccine based on current inactivated vaccines does not appear feasible and other approaches are needed. Technology has advanced since modern human rabies vaccines were developed over 40 years ago. In addition, our understanding of immunological principles that influence the outcome of vaccination has increased. This article describes the current status of inactivated rabies virus vaccines and recent developments arising from the use of reverse genetics technologies designed to develop replication-deficient or single-cycle live rabies virus-based vectors for use as a single-dose rabies vaccine for humans.
doi:10.1586/erv.10.105
PMCID: PMC3072237  PMID: 20923268
attenuated rabies vaccines; post-exposure vaccines; pre-exposure vaccines; rabies vaccines; replication-deficient vectors; reverse genetics; single-cycle vectors
6.  Laboratory Diagnosis of Human Rabies: Recent Advances 
The Scientific World Journal  2013;2013:569712.
Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre- or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future.
doi:10.1155/2013/569712
PMCID: PMC3848253  PMID: 24348170
7.  Epidemiological investigations of human rabies in China 
Background
The epidemic of rabies showed a rising trend in China in recent years. To identify the potential factors involved in the emergence, we investigated and analyzed the status and characteristics of human rabies between 1996 and 2008. Moreover, the status of rabies infection and vaccination in dogs, and prophylaxis of humans after rabies exposure were analyzed.
Methods
Human rabies data in China between 1996 and 2008 collected from the annual reports of Chinese Center for Disease Control and Prevention (China CDC) were analyzed. To investigate the status of dogs and postexposure prophylaxis (PEP) of humans, brain specimens of domestic dogs were collected and detected, and the demographic details, exposure status and PEP of rabies patients were obtained in 2005 and 2006 in Guangxi, Hunan and Guizhou provinces.
Results
The results showed 19,806 human rabies cases were reported in China from 1996 to 2008, with an average of 1,524 cases each year, and the incidence almost was rising rapidly, with the peak in 2007 (3,300 cases). It was notable that nearly 50% of the total rabies cases nationwide were reported in Guangxi, Hunan and Guizhou provinces. In these three provinces, the rabies infection rate in dogs was 2.3%, and 60% investigated cities had a dog vaccination rate of below 70%; among the 315 recorded human cases, 66.3% did not receive any PEP at all, 27.6% received inadequate PEP, and only 6.0% received a full regime of PEP.
Conclusions
In recent years, rabies is reemerging and becoming a major public-health problem in China. Our analysis showed that unsuccessful control of dog rabies and inadequate PEP of patients were the main factors leading to the high incidence of human rabies in China, then there are following suggestions: (1) Strict control of free-ranging dogs and mandatory rabies vaccination should be enforced. (2)Establishing national animal rabies surveillance network is imperative. (3) PEP should be decided to initiate or withhold according to postmortem diagnosis of the biting animal. (4) The cost of PEP should be decreased or free, especially in rural areas. (5)Education of the public and health care staff should be enhanced.
doi:10.1186/1471-2334-9-210
PMCID: PMC2803182  PMID: 20025742
8.  Bats, emerging infectious diseases, and the rabies paradigm revisited 
Emerging Health Threats Journal  2011;4:10.3402/ehtj.v4i0.7159.
The significance of bats as sources of emerging infectious diseases has been increasingly appreciated, and new data have been accumulated rapidly during recent years. For some emerging pathogens the bat origin has been confirmed (such as lyssaviruses, henipaviruses, coronaviruses), for other it has been suggested (filoviruses). Several recently identified viruses remain to be ‘orphan’ but have a potential for further emergence (such as Tioman, Menangle, and Pulau viruses). In the present review we summarize information on major bat-associated emerging infections and discuss specific characteristics of bats as carriers of pathogens (from evolutionary, ecological, and immunological positions). We also discuss drivers and forces of an infectious disease emergence and describe various existing and potential approaches for control and prevention of such infections at individual, populational, and societal levels.
doi:10.3402/ehtj.v4i0.7159
PMCID: PMC3168224  PMID: 24149032
bats; Chiroptera; emerging infectious disease; rabies; lyssavirus; coronavirus; filovirus; henipavirus; prevention; control
9.  Human Rabies in the WHO Southeast Asia Region: Forward Steps for Elimination 
There are eleven Member States in the WHO southeast Asia region (Bangladesh, Bhutan, Democratic People's Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, Timor-Leste) of which eight are endemic for rabies. More than 1.4 billion people in the Region are at risk of rabies infection, and approximately 45% of worldwide rabies deaths occur in Asia. Dog bites account for 96% of human rabies cases. Progress in preventing human rabies through control of the disease in dogs has been slow due to various factors. Innovative control tools and techniques have been developed and standardized in recent years. The introduction of cost-effective intradermal rabies vaccination regimens in Asian countries has increased the availability and affordability of postexposure prophylaxis. Elimination of rabies is not possible without regional and intersectoral cooperation. Considering the importance of consolidating achievements in rabies control in Member countries, the WHO Regional Office for southeast Asia has developed a regional strategy for elimination of human rabies transmitted by dogs in the Region. They have committed to provide technical leadership, to advocate national health authorities to develop major stakeholder consensus for a comprehensive rabies elimination programme, and to implement national strategies for elimination of human rabies.
doi:10.4061/2011/383870
PMCID: PMC3178116  PMID: 21991437
10.  Strategic model of national rabies control in Korea 
Rabies is an important zoonosis in the public and veterinary healthy arenas. This article provides information on the situation of current rabies outbreak, analyzes the current national rabies control system, reviews the weaknesses of the national rabies control strategy, and identifies an appropriate solution to manage the current situation. Current rabies outbreak was shown to be present from rural areas to urban regions. Moreover, the situation worldwide demonstrates that each nation struggles to prevent or control rabies. Proper application and execution of the rabies control program require the overcoming of existing weaknesses. Bait vaccines and other complex programs are suggested to prevent rabies transmission or infection. Acceleration of the rabies control strategy also requires supplementation of current policy and of public information. In addition, these prevention strategies should be executed over a mid- to long-term period to control rabies.
doi:10.7774/cevr.2014.3.1.78
PMCID: PMC3890453  PMID: 24427765
Rabies; Raccoon dogs; Oral vaccine; Prevention and Control
11.  Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control 
Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this “incurable wound” persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector. Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect. Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs. Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination.
doi:10.4061/2011/923149
PMCID: PMC3135331  PMID: 21776359
12.  A quantitative risk assessment model to evaluate effective border control measures for rabies prevention 
Veterinary Research  2009;41(1):11.
Border control is the primary method to prevent rabies emergence. This study developed a quantitative risk model incorporating stochastic processes to evaluate whether border control measures could efficiently prevent rabies introduction through importation of cats and dogs using Taiwan as an example. Both legal importation and illegal smuggling were investigated. The impacts of reduced quarantine and/or waiting period on the risk of rabies introduction were also evaluated. The results showed that Taiwan’s current animal importation policy could effectively prevent rabies introduction through legal importation of cats and dogs. The median risk of a rabid animal to penetrate current border control measures and enter Taiwan was 5.33 × 10−8 (95th percentile: 3.20 × 10−7). However, illegal smuggling may pose Taiwan to the great risk of rabies emergence. Reduction of quarantine and/or waiting period would affect the risk differently, depending on the applied assumptions, such as increased vaccination coverage, enforced custom checking, and/or change in number of legal importations. Although the changes in the estimated risk under the assumed alternatives were not substantial except for completely abolishing quarantine, the consequences of rabies introduction may yet be considered to be significant in a rabies-free area. Therefore, a comprehensive benefit-cost analysis needs to be conducted before recommending these alternative measures.
doi:10.1051/vetres/2009059
PMCID: PMC2775170  PMID: 19822125
rabies; importation; risk assessment; quarantine; animal
13.  Regulatory Systems for Prevention and Control of Rabies, Japan 
Emerging Infectious Diseases  2008;14(9):1368-1374.
Japan’s systems provide an effective model for elimination of rabies worldwide.
Japan is one of the few rabies-free countries. Although 3 imported cases of human rabies were seen in 1970 and 2006, no other cases have been reported for ≈50 years. The elimination of rabies in Japan is attributed to not only its geographic isolation but also to effective prevention and control measures, such as registration and vaccination of domestic dogs, required quarantine of susceptible imported animals, and national plans of action based on scientific research. Countermeasures against rabies have been upgraded; an improved management system for domestic dogs under the amended Enforcement Regulations of the Rabies Prevention Law has been in effect since April 2007. The latest regulatory systems for preventing and controlling rabies provide an effective model for elimination of the disease worldwide.
doi:10.3201/eid1409.070845
PMCID: PMC2603086  PMID: 18760002
rabies; laws; government regulations; synopsis
14.  The present and future of rabies vaccine in animals 
An effective strategy for preventing rabies consists of controlling rabies in the host reservoir with vaccination. Rabies vaccine has proven to be the most effective weapon for coping with this fatal viral zoonotic disease of warm-blooded animals, including human. Natural rabies infection of an individual is always associated with exposure to rabid animals, and the duration of clinical signs can vary from days to months. The incubation period for the disease depends on the site of the bite, severity of injury, and the amount of infecting virus at the time of exposure. The mortality of untreated cases in humans is 100%. Over the last 100 years, various rabies vaccines have been developed and used to prevent or control rabies in animals, such as modified live vaccine, inactivated rabies vaccine, and oral modified live vaccine. These have proved safe and efficacious worldwide. New-generation rabies vaccines, including recombinant rabies virus-based vaccines, vectored vaccines, DNA-based vaccines, and plant vaccines, have been explored to overcome the limitations of conventional rabies vaccines. This article discusses current and next-generation rabies vaccines in animals.
doi:10.7774/cevr.2013.2.1.19
PMCID: PMC3623496  PMID: 23596586
Rabies vaccines; Bait vaccine; Vectored vaccine; Plant vaccine
15.  Epidemiologic Features of Animal Bite Cases Occurring in Rabies-Endemic Areas of Korea, 2005 to 2009 
Objectives
Human rabies is a reemerging infectious disease in Korea. There was no human rabies case for 14 years until the disease had reoccurred in 1999. To prevent occurrence of human rabies, surveillance for animal bite patients in rabies endemic areas in Korea was conducted since 2005 as a part of a human rabies control program. The animal bite cases were analyzed to determine whether patients were treated according to the post-exposure prophylaxis (PEP) guideline of the Korea Centers for Disease Control and Prevention.
Methods
Information of animal bite cases that occurred from 2005 to 2009 in rabies high-risk regions were collected by cooperation with Regional Public Health Centers in 18 cities/districts of rabies endemic areas.
Results
A total of 2458 animal bite cases were reported. Dogs accounted for 86% of animal bites and 67% of the animals were not vaccinated against rabies virus. For PEP, among rabies-vaccinated animals, 92.7% were observed for clinical signs and 1.4% underwent necropsy. Among unvaccinated animals, 72.7% were observed for clinical signs and 4.1% underwent necropsy. The remaining animals were not available for examination. Of the animal bite patients, 32.5% received PEP and 51.6% were treated by first aid or by washing the wound.
Conclusions
Given that no human rabies cases were reported since 2005 and animal rabies was continuously reported in endemic areas of Korea, the human rabies control program implemented in 2005 appears to have a significant role in the prevention and control of human rabies.
doi:10.1016/j.phrp.2012.01.002
PMCID: PMC3738676  PMID: 24159481
animal bite; post-exposure prophylaxis; rabies; wild animal
16.  Spatial Control of Rabies on Heterogeneous Landscapes 
PLoS ONE  2006;1(1):e27.
Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier) to best exploit the barrier for rabies control has not been addressed using mathematical models. Given an advancing epidemic wave, should the vaccine be distributed on both sides of barrier, behind the barrier, or in front of it? Here, we introduce a new mathematical model for the dynamics of raccoon rabies on a spatially heterogeneous landscape that is both simple and realistic. We demonstrate that the vaccine should always be deployed behind a barrier to minimize the recurrence of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce herd immunity inside the vaccinated area, it simultaneously creates a demographic refuge. When that refuge is in front of a natural barrier, seasonal dispersal from the vaccine corridor into an endemic region sustains epidemic oscillations of raccoon rabies. When the vaccine barrier creates a refuge behind the river, the low permeability of the barrier to host movement limits dispersal of the host population from the protected populations into the rabies endemic area and limits subsequent rabies epidemics.
doi:10.1371/journal.pone.0000027
PMCID: PMC1762310  PMID: 17183654
17.  THE NEGRI BODIES IN RABIES 
1. The Negri bodies, as the etiological agent in rabies, present two general types or phases in morphology, in growth, and in reproduction. 2. These two phases are constantly cyclic in their development and correspond (1) to a multiplicative, or schizogonous, and (2) to a reproductive, or sporogonous, life cycle. 3. By the detailed study of these forms and their succeeding stages we are inclined to believe that the Negri bodies are definite protozoan parasites, and from a study of their life history we are led to place them in the suborder of Cryptocysts, or Microsporidia, of the Sporozoa, and more definitely among the Oligosporogenea of the Glugeidae family, which forms produce but one pansporoblast. With the recent advances in the growth of tissues outside the body, particularly the work of Carrel, Burrows, Harrison, Lewis and Lewis, and Rous upon the infectiousness of tumor extracts, with the results of Noguchi in cultivating pathogenic Treponema pallidum, important discoveries concerning the Negri bodies will undoubtedly be made in the near future.
PMCID: PMC2125011  PMID: 19867623
18.  Oral Rabies Vaccination in North America: Opportunities, Complexities, and Challenges 
Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV). Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus) rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus) rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans) through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor) rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US. Progress continues toward the development and testing of new bait-vaccine combinations that increase the chance for improved delivery and performance in the diverse meso-carnivore rabies reservoir complex in the US.
doi:10.1371/journal.pntd.0000549
PMCID: PMC2791170  PMID: 20027214
19.  Advancements in web-database applications for rabies surveillance 
Background
Protection of public health from rabies is informed by the analysis of surveillance data from human and animal populations. In Canada, public health, agricultural and wildlife agencies at the provincial and federal level are responsible for rabies disease control, and this has led to multiple agency-specific data repositories. Aggregation of agency-specific data into one database application would enable more comprehensive data analyses and effective communication among participating agencies. In Québec, RageDB was developed to house surveillance data for the raccoon rabies variant, representing the next generation in web-based database applications that provide a key resource for the protection of public health.
Results
RageDB incorporates data from, and grants access to, all agencies responsible for the surveillance of raccoon rabies in Québec. Technological advancements of RageDB to rabies surveillance databases include 1) automatic integration of multi-agency data and diagnostic results on a daily basis; 2) a web-based data editing interface that enables authorized users to add, edit and extract data; and 3) an interactive dashboard to help visualize data simply and efficiently, in table, chart, and cartographic formats. Furthermore, RageDB stores data from citizens who voluntarily report sightings of rabies suspect animals. We also discuss how sightings data can indicate public perception to the risk of racoon rabies and thus aid in directing the allocation of disease control resources for protecting public health.
Conclusions
RageDB provides an example in the evolution of spatio-temporal database applications for the storage, analysis and communication of disease surveillance data. The database was fast and inexpensive to develop by using open-source technologies, simple and efficient design strategies, and shared web hosting. The database increases communication among agencies collaborating to protect human health from raccoon rabies. Furthermore, health agencies have real-time access to a wide assortment of data documenting new developments in the raccoon rabies epidemic and this enables a more timely and appropriate response.
doi:10.1186/1476-072X-10-48
PMCID: PMC3163173  PMID: 21810215
20.  Integrating the landscape epidemiology and genetics of RNA viruses: rabies in domestic dogs as a model 
Parasitology  2012;139(14):1899-1913.
SUMMARY
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.
doi:10.1017/S003118201200090X
PMCID: PMC3526958  PMID: 22814380
Canis familiaris; landscape genetics; phylogeography; spatial heterogeneity; transmission dynamics; vaccination; zoonosis
21.  Knowledge, attitudes, and practices survey of rabies in a community in Sri Lanka 
Objectives
The primary objective of this study was to determine the level of knowledge, attitudes and practices (KAP) of rabies management and control of a sample population. The secondary objective was to compare the KAP with respect to rabies management and control between urban and rural areas and between pet and non-pet owners.
Methods
This cross-sectional study was carried out by conducting face-to-face interviews using structured questionnaires among 1570 respondents from selected households in the Kandy District, Sri Landa.
Results
Approximately 58% of the sample population was pet owners. Among all the respondents, there was a high level of awareness (90%) that dogs are the most common rabies reservoir, that the disease is fatal (79%), and that rabies can be prevented by vaccination (88%). Most of the subjects (96%) would seek treatment from a doctor or a hospital after being bitten by a dog. Although 76% of the respondents said that their pet dogs were vaccinated, only one-half were able to present a vaccination certificate upon request. The subjects from the urban areas would submit the head of an animal for rabies evaluation (69%) compared with those from the rural areas (57%). Pet owners (93%) are more aware that dog rabies vaccines are available from authorized offices than non-pet owners (87%).
Conclusions
The level of awareness of rabies and the level of receptiveness to rabies control measures are high. There is a difference in the attitudes and pet care practices relevant to rabies control between urban and rural areas. Pet owners tend to be more cooperative to rabies control activities. The attitudes and practices of the respondents may reflect the inaccessibility of facilities and the lack of services that would enable community participation in rabies control.
doi:10.1007/BF02898154
PMCID: PMC2723644  PMID: 21431824
knowledge; attitude; practice; rabies; Sri Lanka
22.  Analysis of Rabies in China: Transmission Dynamics and Control 
PLoS ONE  2011;6(7):e20891.
Human rabies is one of the major public-health problems in China. The number of human rabies cases has increased dramatically in the last 15 years, partially due to the poor understanding of the transmission dynamics of rabies and the lack of effective control measures of the disease. In this article, in order to explore effective control and prevention measures we propose a deterministic model to study the transmission dynamics of rabies in China. The model consists of susceptible, exposed, infectious, and recovered subpopulations of both dogs and humans and describes the spread of rabies among dogs and from infectious dogs to humans. The model simulations agree with the human rabies data reported by the Chinese Ministry of Health. We estimate that the basic reproduction number for the rabies transmission in China and predict that the number of the human rabies is decreasing but may reach another peak around 2030. We also perform some sensitivity analysis of in terms of the model parameters and compare the effects of culling and immunization of dogs. Our study demonstrates that (i) reducing dog birth rate and increasing dog immunization coverage rate are the most effective methods for controlling rabies in China; and (ii) large scale culling of susceptible dogs can be replaced by immunization of them.
doi:10.1371/journal.pone.0020891
PMCID: PMC3137549  PMID: 21789166
23.  Report of the First Meeting of the Middle East and Eastern Europe Rabies Expert Bureau, Istanbul, Turkey (June 8-9, 2010) 
Rabies is a threat in all parts of the world where animal reservoirs persists, including Eastern Europe and the Middle East. Rabies experts from seven Middle East and Eastern European countries (Croatia, Egypt, Georgia, Iran, Serbia, Turkey, and Ukraine) met for two days in Istanbul, Turkey (June 8-9, 2010), to exchange information on the epidemiological situation concerning human and animal rabies in their respective countries and to discuss strategies for rabies elimination and control. They decided to establish a regional network, the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB), a regional network of experts, to increase collaboration in rabies prevention and control at the local, regional, and global levels.
doi:10.4061/2011/812515
PMCID: PMC3173715  PMID: 21991443
24.  Reemergence of Rabies in Chhukha District, Bhutan, 2008 
Emerging Infectious Diseases  2010;16(12):1925-1930.
TOC summary: A major outbreak affected dogs, domestic livestock, and humans.
From January through July 2008, rabies reemerged in the Chhukha district of southwestern Bhutan. To clarify the distribution and direction of spread of this outbreak, we mapped reported cases and conducted directional tests (mean center and standard deviational ellipse). The outbreak resulted in the death of 97 animals (42 cattle, 52 dogs, and 3 horses). Antirabies vaccine was given free of charge to ≈674 persons suspected to have been exposed. The outbreak spread south to north and appeared to follow road networks, towns, and areas of high human density associated with a large, free-roaming, dog population. The outbreak was controlled by culling free-roaming dogs. To prevent spread into the interior of Bhutan, a well-coordinated national rabies control program should be implemented in disease-endemic areas.
doi:10.3201/eid1612.100958
PMCID: PMC3294548  PMID: 21122223
Rabies; epidemic; Bhutan; epidemiology; geographic information systems; spatial distribution; viruses; zoonoses; research
25.  Estimating the Public Health Impact of Rabies 
Emerging Infectious Diseases  2004;10(1):140-142.
Rabies is a fatal, preventable zoonosis, but it is not effectively controlled throughout much of the developing world. The impetus for control is hampered by a lack of awareness of its true impact. We estimate a disability-adjusted life year (DALY) score for rabies to quantify the disease impact relative to other diseases to set priorities for public health interventions.
doi:10.3201/eid1001.020744
PMCID: PMC3322764  PMID: 15078611
Rabies; DALY; public health

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