Marco Vigilato

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.

Progress towards eliminating canine rabies: policies and perspectives from Latin America and the Caribbean

Human rabies transmitted by dogs is considered a neglected disease that can be eliminated in Latin America and the Caribbean (LAC) by 2015. The aim of this paper is to discuss canine rabies policies and projections for LAC regarding current strategies for achieving this target and to critically review the political, economic and geographical factors related to the successful elimination of this deadly disease in the context of the difficulties and challenges of the region. The strong political and technical commitment to control rabies in LAC in the 1980s, started with the regional programme coordinated by the Pan American Health Organization. National and subnational programmes involve a range of strategies including mass canine vaccination with more than 51 million doses of canine vaccine produced annually, pre- and post-exposure prophylaxis, improvements in disease diagnosis and intensive surveillance. Rabies incidence in LAC has dramatically declined over the last few decades, with laboratory confirmed dog rabies cases decreasing from approximately 25 000 in 1980 to less than 300 in 2010. Dog-transmitted human rabies cases also decreased from 350 to less than 10 during the same period. Several countries have been declared free of human cases of dog-transmitted rabies, and from the 35 countries in the Americas, there is now only notification of human rabies transmitted by dogs in seven countries (Bolivia, Peru, Honduras, Haiti, Dominican Republic, Guatemala and some states in north and northeast Brazil). Here, we emphasize the importance of the political commitment in the final progression towards disease elimination. The availability of strategies for rabies control, the experience of most countries in the region and the historical ties of solidarity between countries with the support of the scientific community are evidence to affirm that the elimination of dog-transmitted rabies can be achieved in the short term. The final efforts to confront the remaining obstacles, like achieving and sustaining high vaccination coverage in communities that are most impoverished or in remote locations, are faced by countries that struggle to allocate sufficient financial and human resources for rabies control. Continent-wide cooperation is therefore required in the final efforts to secure the free status of remaining countries in the Americas, which is key to the regional elimination of human rabies transmitted by dogs.

Rabies update for Latin America and the Caribbean.

To the Editor: Rabies incidence in Latin America and the Caribbean has decreased and several countries (Uruguay, Chile, Costa Rica, Mexico, and Panama) and areas of Peru, Brazil, and Argentina are free of human rabies transmitted by dogs, although there are certain areas to which this disease is still endemic (1). Coordinated actions for regional elimination of human rabies transmitted by dogs began in 1983 in Latin America and the Caribbean with the assistance of the Pan American Health Organization (PAHO). This effort has led to an ≈90% reduction of human and canine rabies (2). In this region, rabies is associated with poverty and considered a neglected disease (3). Resolution 19 of the 49th Directing Council of PAHO in 2009 regarding neglected diseases and other infections related to poverty set a target for eliminating human rabies transmitted by dogs by 2015. PAHO is currently developing strategies to assist countries during this period (4). Since 2010, a total of 111 human rabies cases transmitted by bats, dogs, and other animal species were reported from Latin America and the Caribbean: 40 transmitted by dogs and 63 by bats (Table). Although a major reduction in human rabies transmitted by dogs was observed in 2010 (only 6 cases), the total number of cases increased to 24 in 2011; most were confirmed by laboratory testing. Table Cases of human rabies in 10 countries in Latin America and the Caribbean, 2010–2012* The higher risk areas for human rabies transmitted by dogs, for which more collaboration and financial support are urgently needed, are Haiti, Bolivia, Guatemala, Dominican Republic, and parts of Brazil (Maranhao State) and Peru (Puno Region). Unfavorable conditions in which persons in these areas are living limit control strategies and maintain rabies transmission (3). According to the PAHO Epidemiologic Surveillance System for Rabies, during 2010–2012, Bolivia and Haiti had the highest incidence of human rabies transmitted by dogs in the Western Hemisphere: 15% (6/40) and 40% (16/40) of all cases, respectively (5). Many factors, including national disasters and social, cultural, and economic factors, have interfered with canine rabies control programs in these countries. Bolivia has a population of 10 million, and 60.0% of the population is considered below the national poverty line. This country has poor suburbs on the outskirts of large cities, with large populations of unowned dogs and limited resources to implement dog mass vaccination campaigns and animal birth control programs. Haiti has a population of >10 million, and 77% of the population is considered below the national poverty line. In 2010, Haiti was devastated by a major earthquake that affected all sectors, including laboratory diagnosis for rabies (6). After the earthquake, the country was struck by a cholera epidemic. Financial resources have been diverted to control such priorities and to provide humanitarian aid. Haiti and Bolivia heavily depend on technical cooperation and donations from other governments or institutions, and are a high priority for elimination of human rabies transmitted by dogs (7). Another challenge for Latin America and the Caribbean is development of a common strategy for preventing human rabies transmitted by bats, especially in remote areas in the Amazon region (Peru, Ecuador, and Brazil) and Mexico (7), from which 97% of human rabies cases were reported during this period. Since 2000, vampire bats have been the leading cause of human rabies in Latin America and the Caribbean (8). Comparison of data for 2010–2012 with data for the previous 3 years shows a 5.2% increase in bat-transmitted human rabies, especially during 2011, which accounted for ≈53% of reports during the past 3 years (5). Bats have been identified as a reservoir for many Lyssavirus spp. genotypes, and the geographic distribution of variants has been associated with climate changes and ecologic imbalances. Spread of bats has been facilitated by human-made shelters near human dwellings (9). Although rabies control in Latin America and the Caribbean has been successful, certain approaches currently used, such as mass vaccination campaigns for dogs, postexposure prophylaxis, and epidemiologic surveillance, require improvement in some countries. In addition, allocation of resources is needed to enhance national programs to eliminate human rabies transmitted by dogs. PAHO is responsible for coordination and technical cooperation of the Rabies Elimination Program and Operation of the Epidemiologic Surveillance System for Rabies. For the past 60 years, the Pan American Center for Foot-and-Mouth Disease/PAHO has accumulated capabilities to develop national programs for zoonoses prevention and control, particularly for rabies elimination in Latin America and the Caribbean. Strengthening regional, national, and subnational rabies control programs must be a priority. The decision in Latin America and the Caribbean to eliminate dog-transmitted rabies began in 1983 and involved strong political commitment with multinational efforts, as well as support and coordination of other international organizations, nongovernmental organizations, and the private sector. This interinstitutional collaboration is needed to promote prevention and control activities to achieve the elimination of human rabies transmitted by dogs in the Western Hemisphere by 2015.

Pre-exposure rabies prophylaxis: a systematic review

Abstract Objective To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost–effectiveness and recommendations for use, particularly in high-risk settings. Methods We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Findings Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Conclusion Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.

Gains and Future Road Map for the Elimination of Dog-Transmitted Rabies in the Americas

In 1983 the countries of the Americas, with the technical cooperation of the Pan American Health Organization (PAHO), pledged to eliminate human rabies transmitted by dogs.1 Since then, countries have made great efforts to eliminate this disease, with notable success, within the framework of the Regional Program of Elimination of Human Rabies. The success achieved during the last 30 years and the historical solidarity between countries in the region support the goal of elimination of dog-transmitted rabies in the American continent by 2015. As this date approaches, there is a need to reflect and reassess the current plan of rabies elimination. This work briefly describes the achievements of the Regional Program and the proposed new Regional Action Plan for the elimination of dog-transmitted rabies.

Prioritization of capacities for the elimination of dog-mediated human rabies in the Americas: building the framework

Abstract The region of the Americas pledged to eliminate dog-transmitted human rabies by 2015. After 30 years of sustained efforts, regional elimination appears possible as dog-mediated human rabies cases are at an all-time low, and a number of countries and territories have already eliminated the disease. In this setting, there is an opportunity to generate a framework to support countries strategies in the achievement and maintenance of rabies-free status (RFS). To this end, we describe the development of a multi-criteria decision analysis (MCDA) model to help the evaluation of rabies programmes and the identification of the best investment strategy for countries and territories to improve and efficiently maintain their rabies status. The model contemplates human and animal related capacities, six in each area, to comprehensively assess the wide scope of rabies programmes. An initial elicitation of expert opinion of values and weights for the MCDA model was performed via a web-based questionnaire. Even at this pilot stage, the model produces comparable capacity-scores, and overall (combined for public and animal health areas) as well as area-specific investment strategies. The model is being developed by the Pan American Health Organization (PAHO) as part of the regional efforts towards dog-mediated human rabies elimination and will be presented to the countries for review, refinement, contextualization, and testing. The aspiration is that countries use the model to identify the best allocation of resources towards the elimination of dog-mediated human rabies.

Rabies in the Americas: 1998-2014

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998–2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence.

Tribulations of the Last Mile: Sides from a Regional Program

In Latin American and Caribbean (LAC) countries, the number of cases of dog-mediated human rabies is at its lowest since the onset of the Regional Program for Rabies Elimination in 1983, a commitment from LAC countries to eliminate dog-mediated rabies coordinated by the Pan American Health Organization. Despite minor setbacks, the decline in the number of human cases has been constant since 1983. While many LAC countries have significantly reduced rabies to a level where it is no longer significant public health concern, elimination has proven elusive and pockets of the disease remain across the region. In the 33-year period since 1983, the region has set and committed to four dates for elimination (1990, 2000, 2012, and 2015). In this paper, we ponder on the multiple causes behind the elusive goal of rabies elimination, such as blanket regional goals oblivious to the large heterogeneity in national rabies capacities. Looking ahead to the elimination of dog-mediated rabies in the region, now established for 2022, we also review the many challenges and questions that the region faces in the last mile of the epidemic. Given the advanced position of the Americas in the race toward elimination, our considerations could provide valuable knowledge to other regions pursuing elimination goals.

An inter- laboratory proficiency testing exercise for rabies diagnosis in Latin America and the Caribbean

The direct fluorescent antibody test (DFA), is performed in all rabies reference laboratories across Latin America and the Caribbean (LAC). Despite DFA being a critical capacity in the control of rabies, there is not a standardized protocol in the region. We describe the results of the first inter-laboratory proficiency exercise of national rabies laboratories in LAC countries as part of the regional efforts towards dog-maintained rabies elimination in the American region. Twenty three laboratories affiliated to the Ministries of Health and Ministries of Agriculture participated in this exercise. In addition, the laboratories completed an online questionnaire to assess laboratory practices. Answers to the online questionnaire indicated large variability in the laboratories throughput, equipment used, protocols availability, quality control standards and biosafety requirements. Our results will inform actions to improve and harmonize laboratory rabies capacities across LAC in support for the regional efforts towards elimination of dog-maintained rabies.

The health impact of rabies in Haiti and recent developments on the path toward elimination, 2010–2015

Abstract. Haiti, a Caribbean country of 10.5 million people, is estimated to have the highest burden of canine-mediated human rabies deaths in the Western Hemisphere, and one of the highest rates of human rabies deaths in the world. Haiti is also the poorest country in the Western Hemisphere and has numerous economic and health priorities that compete for rabies-control resources. As a result, primary rabies-control actions, including canine vaccination programs, surveillance systems for human and animal rabies, and appropriate postbite treatment, have not been fully implemented at a national scale. After the 2010 earthquake that further hindered the development of public health program infrastructure and services, the U.S. Centers for Disease Control and Prevention worked with the Ministry of Public Health and Population and key health development partners (including the Pan-American Health Organization) to provide technical expertise and funding for general disease surveillance systems, laboratory capacity, and selected disease control programs; including rabies. In 2011, a cross-ministerial rabies consortium was convened with participation from multiple international rabies experts to develop a strategy for successful rabies control in Haiti. The consortium focused on seven pillars: 1) enhancement of laboratory diagnostic capacity, 2) development of comprehensive animal surveillance system, 3) development of comprehensive human rabies surveillance system, 4) educational outreach, 5) sustainable human rabies biologics supply, 6) achievement of sustained canine vaccination rates of ≥ 70%, and 7) finalization of a national rabies control strategy. From 2010 until 2015, Haiti has seen improvements in the program infrastructure for canine rabies control. The greatest improvements were seen in the area of animal rabies surveillance, in support of which an internationally recognized rabies laboratory was developed thereby leading to an 18-fold increase in the detection of rabid animals. Canine rabies vaccination practices also improved, from a 2010 level of approximately 12% to a 2015 dog population coverage level estimated to be 45%. Rabies vaccine coverage is still below the goal of 70%, however, the positive trend is encouraging. Gaps exist in the capacity to conduct national surveillance for human rabies cases and access to human rabies vaccine is lacking in many parts of the country. However, control has improved over the past 5 years as a result of the efforts of Haiti’s health and agriculture sectors with assistance from multiple international organizations. Haiti is well situated to eliminate canine-mediated human rabies deaths in the near future and should serve as a great example to many developing countries struggling with similar barriers and limitations.