F. X. Meslin

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.

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.

Dogs, zoonoses and public health.

Zoonotic diseases constitute a public health problem throughout the world. Addressing a little studied area of veterinary and medical science, this book covers the viruses, bacteria and protozoan and helminth parasites that are transmitted between man and dogs, discussing population management, control disease agents and human-dog relationships. Fully updated throughout, this new edition also includes two new chapters on benefits of the human-dog relationship and non-infectious disease issues with dogs. It is a valuable resource for researchers and students of veterinary and human medicine, microbiology, parasitology and public health.

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.

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.

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.

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

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.

More Accurate Insight into the Incidence of Human Rabies in Developing Countries through Validated Laboratory Techniques

The authors have declared that no competing interests exist. Major funding for the project in Institut Pasteur was provided by the Institut Pasteur International Network with Actions Concertees InterPasteuriennes 2003/687 and 2006/562. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Correction: Estimating the global burden of endemic canine rabies.

There are a number of errors in Table 3. The table legend should read: Breakdown of economic costs of rabies by cluster in millions of USD. The headings for columns six, seven, and eight are incorrect. They should be in the following order: Dog vaccination, Dog population management, Livestock losses. Please see the correct Table 3 below. Table 3 Breakdown of economic costs of rabies by cluster in millions of USD.