Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination.

The mass vaccination of dogs is a proven tool for rabies prevention. Besides parenteral delivery of inactivated vaccines, over the past several decades, several self-replicating biologics, including modified-live, attenuated and recombinant viruses, have been evaluated for the oral vaccination of dogs against rabies. Vaccines are included within an attractive bait for oral consumption by free-ranging dogs. Due to the high affinity between dogs and humans, such biologics intended for oral vaccination of dogs (OVD) need to be efficacious as well as safe. Baits should be preferentially attractive to dogs and not to non-target species. Although many different types have been evaluated successfully, no universal bait has been identified to date. Moreover, high bait acceptance does not necessarily mean that vaccine efficacy and programmatic success is predictable. The use of OVD in the laboratory and field has demonstrated the safety and utility of this technology. Within a One Health context, OVD should be considered as part of a holistic plan for the global elimination of canine rabies.

Correction to: Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination.

The original article [1] contained an error in the Author details paragraph. "5Neglected Zoonotic Diseases, World Health Organization, Geneva, Switzerland" should be replaced by "5Le Grand-Saconnex, Switzerland".

Customized online and onsite training for rabies-control officers.

PROBLEM: It is difficult to deliver adequate training for people working in rabies control in low and middle-income countries. Popular e-learning systems for low-income settings are not well suited to developing and testing practical skills, including laboratory methods. APPROACH: We customized training in rabies control methods for African professionals and students from different disciplines. Trainees participated in preparatory online sessions, evaluations and exercises before and after a 12-day workshop. Trainees and mentors continued to interact through an online forum up to one year after the workshop. LOCAL SETTING: In Africa, 15,000 deaths from rabies occur each year due to a lack of awareness, inaccessibility of post-exposure prophylaxis, inadequate or absent canine rabies-control programmes and lack of governmental financial support. RELEVANT CHANGES: Thirty two trainees - working in health departments, hospitals, veterinary stations and research institutes - were selected to participate; 28 completed the course and passed the final evaluation. Pilot rabies investigation programmes were developed, and two manuscripts submitted for publication. An online forum facilitated further progress for a year after the workshop. LESSONS LEARNT: A combination of customized online and onsite training is suitable for teaching disease-control personnel in low-income countries. Participation in this course enabled trainees to advocate for the development of national disease-control strategies. Mentoring is needed to develop a strong network of experts in similar settings.

Priorities in applied research to ensure programmatic success in the global elimination of canine rabies.

The elimination of human rabies mediated by dogs is attainable in concept, based upon current sensitive and specific diagnostic methods, existing safe and effective human and veterinary vaccines and a sound virological, pathological and epidemiological understanding of the disease. Globally, all developed countries achieved this goal. Regionally, major progress occurred throughout the Americas. However, less advancement is evident in Africa and Asia. Our objective was to concentrate upon those salient improvements to extant tools and methods over the next five years which could assist and simplify the task for both those developing countries that have already begun the process, as well as other localities in the earlier stages of consideration. We considered several categories of applied research which could be accomplished in the short term, based upon the available scientific evidence and recent recommendations from subject matter experts and key opinion leaders, focused upon perceived major limitations to prior program success. Areas of concentration included: laboratory-based surveillance, pathogen detection and characterization; human rabies prophylaxis; veterinary biologics; implementation of canine vaccination; and oral vaccination of free-ranging community dogs. Further real-time application in these core areas with proven techniques and technology would simplify attaining not only the global goal focused subtly upon human mortality, but the actual elimination of canine rabies as well.

Toward Elimination of Dog-Mediated Human Rabies: Experiences from Implementing a Large-scale Demonstration Project in Southern Tanzania.

A Rabies Elimination Demonstration Project was implemented in Tanzania from 2010 through to 2015, bringing together government ministries from the health and veterinary sectors, the World Health Organization, and national and international research institutions. Detailed data on mass dog vaccination campaigns, bite exposures, use of post-exposure prophylaxis (PEP), and human rabies deaths were collected throughout the project duration and project areas. Despite no previous experience in dog vaccination within the project areas, district veterinary officers were able to implement district-wide vaccination campaigns that, for most part, progressively increased the numbers of dogs vaccinated with each phase of the project. Bite exposures declined, particularly in the southernmost districts with the smallest dog populations, and health workers successfully transitioned from primarily intramuscular administration of PEP to intradermal administration, resulting in major cost savings. However, even with improved PEP provision, vaccine shortages still occurred in some districts. In laboratory diagnosis, there were several logistical challenges in sample handling and submission but compared to the situation before the project started, there was a moderate increase in the number of laboratory samples submitted and tested for rabies in the project areas with a decrease in the proportion of rabies-positive samples over time. The project had a major impact on public health policy and practice with the formation of a One Health Coordination Unit at the Prime Minister's Office and development of the Tanzania National Rabies Control Strategy, which lays a roadmap for elimination of rabies in Tanzania by 2030 by following the Stepwise Approach towards Rabies Elimination (SARE). Overall, the project generated many important lessons relevant to rabies prevention and control in particular and disease surveillance in general. Lessons include the need for (1) a specific unit in the government for managing disease surveillance; (2) application of innovative data collection and management approaches such as the use of mobile phones; (3) close cooperation and effective communication among all key sectors and stakeholders; and (4) flexible and adaptive programs that can incorporate new information to improve their delivery, and overcome challenges of logistics and procurement.

Rabies as a traveler's risk, especially in high-endemicity areas.

Rabies is a viral zoonosis, an animal disease transmissible to humans, caused by rhabdoviruses of the genus Lyssavirus. It is almost invariably fatal in humans. Rabies is widely distributed throughout the world and present in all continents. More than 99.,9 % of human deaths from rabies reported worldwide result from the bite of a rabid dog. Prompt and thorough cleansing of the wound, together with administration of immunoglobulin in cases of severe exposure, and immunization with modern vaccines starting immediately after exposure, virtually guarantee complete protection. When assessing the risk of contracting the disease for a traveller visiting a rabies- affected area, to contract the disease one should consider the probability of: rabies exposure that which is directly related to the incidence of rabies in the area and the probability of contact with an infected rabies- susceptible animals, be it either wild or and domestic animals, especially dogs and cats; being provided with the best possible treatment, which depends upon the availability of modern safe and efficacious rabies vaccines and rabies immunoglobulin, and the rabies awareness of the health care providers in charge of rabies prophylaxis in the area where the exposure occurs. This article,paper using a number of examples and recent data on dog bite incidence and vaccine availability in various parts of the world, provides guidance on how to assess the risk and proposes means to avoid or mitigate this risk.

Estimating the global burden of endemic canine rabies.

BACKGROUND: Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). CONCLUSIONS/SIGNIFICANCE: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.

Rabies update for travel medicine advisors.

Rabies is a neglected disease in many developing countries. It is preventable, and the tools to prevent it are known. There is urgent need for more funding, for study of innovative dog population-control measures, and for sustainable canine immunization. Safe and effective tissue-culture rabies vaccines and human and equine rabies immunoglobulins (HRIG and ERIG) are not readily available in many regions where rabies is endemic. This and the continuing presence and spread of rabies have increased the risk for travelers, who cannot rely on being able to receive optimal postexposure treatment in many parts of the world. Alternatives to HRIG or ERIG are not available. Travelers who leave the safe environments of tourist hotels and buses in regions of Asia, Russia, Africa, and Latin America where canine rabies is endemic may be at risk of life-threatening exposure to rabies.

The changing landscape of rabies epidemiology and control.

Over the past 20 years, major progress has been made in our understanding of critical aspects of rabies epidemiology and control. This paper presents results of recent research, highlighting methodological advances that have been applied to burden of disease studies, rabies epidemiological modelling and rabies surveillance. These results contribute new insights and understanding with regard to the epidemiology of rabies and help to counteract misperceptions that currently hamper rabies control efforts in Africa. The conclusion of these analyses is that the elimination of canine rabies in Africa is feasible, even in wildlife-rich areas, through mass vaccination of domestic dogs and without the need for indiscriminate culling to reduce dog population density. Furthermore, the research provides valuable practical insights that support the operational planning and design of dog vaccination campaigns and rabies surveillance measures.

Animal health in the 21st century-a global challenge.

On the occasion of the centenary of the Friedrich-Loeffler-Institut, a conference entitled 'Animal Health in the 21st Century' was held in Greifswald, Germany, on 11-13 October 2010 to discuss current and future challenges regarding the global situation regarding infectious animal diseases and zoonoses, animal breeding, animal nutrition and animal welfare. Particular attention was paid to the impact of recent developments and anticipated future trends on livestock production.

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.

Zoonoses and marginalised infectious diseases of poverty: where do we stand?

Despite growing awareness of the importance of controlling neglected tropical diseases as a contribution to poverty alleviation and achieving the Millennium Development Goals, there is a need to up-scale programmes to achieve wider public health benefits. This implementation deficit is attributable to several factors but one often overlooked is the specific difficulty in tackling diseases that involve both people and animals - the zoonoses. A Disease Reference Group on Zoonoses and Marginalised Infectious Diseases (DRG6) was convened by the Special Programme for Research and Training in Tropical Diseases (TDR), a programme executed by the World Health Organization and co-sponsored by UNICEF, UNDP, the World Bank and WHO. The key considerations included: (a) the general lack of reliable quantitative data on their public health burden; (b) the need to evaluate livestock production losses and their additional impacts on health and poverty; (c) the relevance of cross-sectoral issues essential to designing and implementing public health interventions for zoonotic diseases; and (d) identifying priority areas for research and interventions to harness resources most effectively. Beyond disease specific research issues, a set of common macro-priorities and interventions were identified which, if implemented through a more integrated approach by countries, would have a significant impact on human health of the most marginalised populations characteristically dependent on livestock.

Public health impact of zoonoses and international approaches for their detection and containment.

Many new, emerging and re-emerging diseases of humans are caused by pathogens that originate from animals or products of animal origin. A wide variety of both domestic and wild animal species act as reservoirs for these pathogens, which may be viruses, bacteria or parasites. Given the extensive distribution of the animal species affected, the effective surveillance, prevention and control of zoonotic diseases pose a significant challenge. There are direct and indirect implications for public health of emerging zoonoses. Direct implications are defined as the consequences for human health in terms of morbidity and mortality. Indirect implications are defined as the effect of the influence of emerging zoonotic disease on health professionals and the general public. The tremendous indirect impact of emerging zoonotic diseases on public health policy and structures and on public perception of health risks is acknowledged. A biphasic approach for handling emerging zoonoses is proposed, i.e. a short- to intermediate-term response to an outbreak or emergency and a long-term comprehensive study of the ecology of the zoonotic pathogen. Resource-rich countries should invest in the establishment and strengthening of surveillance systems in resource-limited countries considering the international significance of emerging zoonoses. Based on the new international health regulations, emphasis should be placed on building the appropriate preparedness and response capacity in countries and on promoting intersectoral collaboration and coordination.

A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.

BACKGROUND: The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. METHODS: Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. FINDINGS: All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. CONCLUSIONS: This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN 30087513.

Wildlife, exotic pets, and emerging zoonoses.

Most emerging infectious diseases are zoonotic; wildlife constitutes a large and often unknown reservoir. Wildlife can also be a source for reemergence of previously controlled zoonoses. Although the discovery of such zoonoses is often related to better diagnostic tools, the leading causes of their emergence are human behavior and modifications to natural habitats (expansion of human populations and their encroachment on wildlife habitat), changes in agricultural practices, and globalization of trade. However, other factors include wildlife trade and translocation, live animal and bushmeat markets, consumption of exotic foods, development of ecotourism, access to petting zoos, and ownership of exotic pets. To reduce risk for emerging zoonoses, the public should be educated about the risks associated with wildlife, bushmeat, and exotic pet trades; and proper surveillance systems should be implemented.

Emerging or re-emerging bacterial zoonoses: factors of emergence, surveillance and control.

Surveillance and control of emerging bacterial zoonoses is essential in order to prevent both human and animal deaths and to avoid potential economic disorders created by trade barriers or a ban on free circulation of human or animal populations. An increased risk of exposition to zoonotic agents, the breakdown of the host's defenses, the emergence of bacterial strains resistant to antibiotics and their widespread distribution as well as conjunctural causes associated with the action or inaction of man have been identified as the main factors leading to the emergence or re-emergence of bacterial zoonoses. After an in-depth review of these various factors, the present manuscript reviews the main components of detection and surveillance of emerging or re-emerging bacterial zoonoses. A description of the systems of control and the main obstacles to their success is also presented. Detection and surveillance of emerging zoonoses have greatly benefited from technical progress in diagnostics. The success of detection and control of emerging bacterial zoonoses is largely based on international solidarity and cooperation between countries.

Re-evaluating the burden of rabies in Africa and Asia.

OBJECTIVE: To quantify the public health and economic burden of endemic canine rabies in Africa and Asia. METHODS: Data from these regions were applied to a set of linked epidemiological and economic models. The human population at risk from endemic canine rabies was predicted using data on dog density, and human rabies deaths were estimated using a series of probability steps to determine the likelihood of clinical rabies developing in a person after being bitten by a dog suspected of having rabies. Model outputs on mortality and morbidity associated with rabies were used to calculate an improved disability-adjusted life year (DALY) score for the disease. The total societal cost incurred by the disease is presented. FINDINGS: Human mortality from endemic canine rabies was estimated to be 55 000 deaths per year (90% confidence interval (CI) = 24 000-93 000). Deaths due to rabies are responsible for 1.74 million DALYs lost each year (90% CI = 0.75-2.93). An additional 0.04 million DALYs are lost through morbidity and mortality following side-effects of nerve-tissue vaccines. The estimated annual cost of rabies is USD 583.5 million (90% CI = USD 540.1-626.3 million). Patient-borne costs for post-exposure treatment form the bulk of expenditure, accounting for nearly half the total costs of rabies. CONCLUSION: Rabies remains an important yet neglected disease in Africa and Asia. Disparities in the affordability and accessibility of post-exposure treatment and risks of exposure to rabid dogs result in a skewed distribution of the disease burden across society, with the major impact falling on those living in poor rural communities, in particular children.