Burden Of Rabies Research Articles

Taking the Bite Out of Rabies, Putting Teeth Into “One Health”

In this issue, Fitzpatrick and colleagues discuss the dramatic reduction in the health burden of rabies in 2 rural areas of Africa through vaccination of domestic dogs. The editorialist discusses t...

Cost-Effectiveness of Canine Vaccination to Prevent Human Rabies in Rural Tanzania

The annual mortality rate of human rabies in rural Africa is 3.6 deaths per 100 000 persons. Rabies can be prevented with prompt postexposure prophylaxis, but this is costly and often inaccessible in rural Africa. Because 99% of human exposures occur through rabid dogs, canine vaccination also prevents transmission of rabies to humans. To evaluate the cost-effectiveness of rabies control through annual canine vaccination campaigns in rural sub-Saharan Africa. We model transmission dynamics in dogs and wildlife and assess empirical uncertainty in the biological variables to make probability-based evaluations of cost-effectiveness. Epidemiologic variables from a contact-tracing study and literature and cost data from ongoing vaccination campaigns. Two districts of rural Tanzania: Ngorongoro and Serengeti. 10 years. Health policymaker. Vaccination coverage ranging from 0% to 95% in increments of 5%. Life-years for health outcomes and 2010 U.S. dollars for economic outcomes. Annual canine vaccination campaigns were very cost-effective in both districts compared with no canine vaccination. In Serengeti, annual campaigns with as much as 70% coverage were cost-saving. Across a wide range of variable assumptions and levels of societal willingness to pay for life-years, the optimal vaccination coverage for Serengeti was 70%. In Ngorongoro, although optimal coverage depended on willingness to pay, vaccination campaigns were always cost-effective and lifesaving and therefore preferred. Canine vaccination was very cost-effective in both districts, but there was greater uncertainty about the optimal coverage in Ngorongoro. Annual canine rabies vaccination campaigns conferred extraordinary value and dramatically reduced the health burden of rabies. National Institutes of Health.

The burden of rabies in Tanzania and its impact on local communities.

BackgroundRabies remains a major public health threat in many parts of the world and is responsible for an estimated 55,000 human deaths annually. The burden of rabies is estimated to be around US$20 million in Africa, with the highest financial expenditure being the cost of post-exposure prophylaxis (PEP). However, these calculations may be substantial underestimates because the costs to households of coping with endemic rabies have not been investigated. We therefore aimed to estimate the household costs, health-seeking behaviour, coping strategies, and outcomes of exposure to rabies in rural and urban communities in Tanzania.Methods and FindingsExtensive investigative interviews were used to estimate the incidence of human deaths and bite exposures. Questionnaires with bite victims and their families were used to investigate health-seeking behaviour and costs (medical and non-medical costs) associated with exposure to rabies. We calculated that an average patient in rural Tanzania, where most people live on less than US$1 per day, would need to spend over US$100 to complete WHO recommended PEP schedules. High costs and frequent shortages of PEP led to poor compliance with PEP regimens, delays in presentation to health facilities, and increased risk of death.ConclusionThe true costs of obtaining PEP were twice as high as those previously reported from Africa and should be considered in re-evaluations of the burden of rabies.

Controlling rabies through a multidisciplinary, public health system in Trujillo, La Libertad, Peru

Rabies remains endemic in Peru. In 1983, Latin America and the Caribbean promised to eliminate canine-transmitted rabies from the continent. This led to Peru introducing a multidisciplinary public health system for controlling and managing rabies across the country. The system consists of mass canine vaccination campaigns, post exposure prophylaxis and monitoring aggressor animals for signs of rabies. The Peruvian city of Trujillo, La Libertad, is an urban area where dogs are the principal reservoir for rabies. The disease burden of rabies in Trujillo, La Libertad is currently minimal, with no rabies cases in humans for over 10 years, and only three canine cases. No human deaths due to rabies have occurred for several decades. From this it can be inferred that antirabies systems such as this do have real effects in reducing cases of human rabies at a grass roots level.

The Cost of Canine Rabies on Four Continents

We estimated the economic impacts of canine rabies in Latin America, Africa and Asia. Direct and indirect costs of rabies post-exposure prophylaxis, dog vaccination and control, rabies diagnostic testing and cattle mortality-related costs were accounted for. The number of human deaths was updated from previous estimates based on population growth, and the costs associated with the risk of human mortality were incorporated. We accounted for uncertainty associated with the parameter estimates using a Monte Carlo simulation and estimated that the global burden of canine rabies is approximately $124 billion annually. This result illustrates the potential benefits that could be realized if canine rabies was eliminated and provides an important benchmark against which the cost of any potential elimination campaign can be compared.

Incidence of Rabies in Humans and Domestic Animals and People's Awareness in North Gondar Zone, Ethiopia

BackgroundRabies is a zoonotic disease that has been prevalent in humans and animals for centuries in Ethiopia and it is often dealt with using traditional practices. There is lack of accurate quantitative information on rabies both in humans and animals in Ethiopia and little is known about the awareness of the people about the disease. In this study, we estimated the incidence of rabies in humans and domestic animals, and assessed the people's awareness about the disease in North Gondar zone, Ethiopia.Methodology/Principal FindingsThe incidence of rabies in humans and domestic animals was prospectively followed up for one year period based on clinical observation. A questionnaire was also administered to 120 randomly selected dog owners and 5 traditional healers to assess the knowledge and practices about the disease. We found an annual estimated rabies incidence of 2.33 cases per 100,000 in humans, 412.83 cases per 100,000 in dogs, 19.89 cases per 100,000 in cattle, 67.68 cases per 100,000 in equines, and 14.45 cases per 100,000 in goats. Dog bite was the source of infection for all fatal rabies cases. Ninety eight percent of the questionnaire respondents were familiar with rabies and mentioned dog bite as a means of transmission. But discordant with current scientific knowledge, 84% and 32% of the respondents respectively mentioned any type of contact (irrespective of skin condition) with saliva, and inhalation as a means of transmission of rabies. Eighty four percent of the respondents relied on traditional healers for management of rabies.ConclusionsThe study shows high canine rabies burden, and lack of sufficient awareness about the disease and high reliance on traditional treatment that interfere with timely post exposure management. Vaccination of dogs, proper post exposure management, and increasing the awareness of the community are suggested to reduce the disease burden.

One in a million, or one in thousand: What is the morbidity of rabies in India?

One in a million, or one in thousand: What is the morbidity of rabies in India?

Detection of rabies viral RNA by TaqMan real-time RT-PCR using non-neural specimens from dogs infected with rabies virus

To determine the burden of rabies in developing countries, a reliable and accurate diagnostic test for the examination of the brains of animals is needed. Recently, the number of samples and carcasses submitted to rabies diagnostic units has been declining. Methods for obtaining tissues from different regions of the brain are even more difficult, and direct florescent antibody examination may fail if the samples decomposed. The spread of rabies virus to peripheral non-nervous tissues starts early during the pre-clinical phase. It has been shown that saliva and skin biopsies taken at the neck and containing hair follicles can be used in the ante-mortem diagnosis of rabies in humans. Obtaining oral swab samples, whisker or hair follicles from the heads of canines is easy and practical and can be performed without special equipment. The objective of this study was to determine whether these non-neural specimens can be used for the detection of rabies viral RNA. The RNAs extracted from these specimens were tested using a real-time reverse transcriptase polymerase chain reaction (RT-PCR). The sensitivity of the TaqMan real-time RT-PCR analysis using samples from dogs confirmed to be infected with rabies virus was 84.6% (55/65), 81.8% (54/66) and 66.7% (44/66) when using oral swab samples, extracted whisker follicles and extracted hair follicles; the specificity of all specimen types was 100%. The negative predictive values were 77.8%, 74.4% and 61.4%, respectively. Although the rate of positivity when combining the three non-neural specimen types was increased to 86.4%, this level of sensitivity was not sufficient to help physicians whether to administer post exposure prophylaxis. However, these oral swab and whisker specimens may serve to enhance epidemiological surveillance; such data will contribute in the planning of rabies control programs.

Evaluation of cost-effective strategies for rabies post-exposure vaccination in low-income countries.

BackgroundPrompt post-exposure prophylaxis (PEP) is essential in preventing the fatal onset of disease in persons exposed to rabies. Unfortunately, life-saving rabies vaccines and biologicals are often neither accessible nor affordable, particularly to the poorest sectors of society who are most at risk and upon whom the largest burden of rabies falls. Increasing accessibility, reducing costs and preventing delays in delivery of PEP should therefore be prioritized.Methodology/Principal FindingsWe analyzed different PEP vaccination regimens and evaluated their relative costs and benefits to bite victims and healthcare providers. We found PEP vaccination to be an extremely cost-effective intervention (from $200 to less than $60/death averted). Switching from intramuscular (IM) administration of PEP to equally efficacious intradermal (ID) regimens was shown to result in significant savings in the volume of vaccine required to treat the same number of patients, which could mitigate vaccine shortages, and would dramatically reduce the costs of implementing PEP. We present financing mechanisms that would make PEP more affordable and accessible, could help subsidize the cost for those most in need, and could even support new and existing rabies control and prevention programs.Conclusions/SignificanceWe conclude that a universal switch to ID delivery would improve the affordability and accessibility of PEP for bite victims, leading to a likely reduction in human rabies deaths, as well as being economical for healthcare providers.

Recent Advances in Prevention and Control of Rabies

Recent Advances in Prevention and Control of Rabies

Epidemiology of human rabies in South Africa, 1983–2007

Rabies remains a global public health problem but increasingly so in the developing world. Given a lack of awareness, priority and diagnostic capability, very few developing countries, especially in Africa, report on laboratory confirmed human rabies cases. Here we present a retrospective study on the epidemiology of human rabies in Republic of South Africa for a 25-year period, 1983–2007, based on laboratory confirmed cases. The study highlights the role of the domestic dog as a reservoir and vector of rabies and contrasts this to the almost negligible contribution of wildlife vectors to the overall burden of human rabies in dog rabies endemic areas. From the collective data set, epidemiological aspects that include various features of these human rabies cases as well as failures in or towards the treatment of exposures are reported. Molecular analysis of virus isolates did not identify any additional cases of rabies attributed to infection with the Duvenhage, Lagos bat or Mokola or any other rabies-related viruses.

Reducing the global burden of rabies

Reducing the global burden of rabies

The Feasibility of Canine Rabies Elimination in Africa: Dispelling Doubts with Data

BackgroundCanine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent.Methodology/Principal FindingsThis paper identifies four common reasons given for the lack of effective canine rabies control in Africa: (a) a low priority given for disease control as a result of lack of awareness of the rabies burden; (b) epidemiological constraints such as uncertainties about the required levels of vaccination coverage and the possibility of sustained cycles of infection in wildlife; (c) operational constraints including accessibility of dogs for vaccination and insufficient knowledge of dog population sizes for planning of vaccination campaigns; and (d) limited resources for implementation of rabies surveillance and control. We address each of these issues in turn, presenting data from field studies and modelling approaches used in Tanzania, including burden of disease evaluations, detailed epidemiological studies, operational data from vaccination campaigns in different demographic and ecological settings, and economic analyses of the cost-effectiveness of dog vaccination for human rabies prevention.Conclusions/SignificanceWe conclude that there are no insurmountable problems to canine rabies control in most of Africa; that elimination of canine rabies is epidemiologically and practically feasible through mass vaccination of domestic dogs; and that domestic dog vaccination provides a cost-effective approach to the prevention and elimination of human rabies deaths.

Rabies Control in Finland: A 12‐Year Experience of Human and Veterinary Surveillance

Little is known about the public health burden of rabies in rabies-free countries. In these countries, the surveillance of suspected and treated cases serves as a substitute for estimating the risk and burden of human rabies because deaths due to rabies are extremely rare. Suspected rabies exposures among Finnish inhabitants were characterized using data from the National Infectious Disease Registry as well as animal surveillance data from the Finnish Food Safety Authority Evira, 1995-2006. In total, 195 suspected rabies exposures were reported (incidence 3/million inhabitants/year). Exposures were equally common among both genders and the median age was 35 years. Exposures were more common among 20- to 49-year olds than among other age groups. Less than one-third of the exposures occurred in Finland (incidence of indigenous exposures 0.9/million inhabitants/year). Indigenous rabies exposures were most frequently reported in southeastern Finland, with cats and dogs as the main sources. The high prevalence in the Baltic countries and Russia poses a risk for rabies reintroduction. The present control of wildlife rabies appears successful and important. The import of animals from endemic areas, however, remains a risk, which can be reduced by increasing public awareness of the disease, vaccination of imported animals and better rabies control in endemic countries.

Rabies epidemiology and control in Turkey: past and present

SUMMARYTurkey is the only country in Europe where urban dog-mediated rabies persists. Control measures in recent decades have reduced the burden of rabies to relatively low levels but foci of disease still persist, particularly in urban areas. Occasional human cases result from this persistence although the source of these appears to be both dog and wildlife reservoirs. This review considers the current state of rabies in Turkey including current control measures, the varying epidemiology of the disease throughout this country and the prospects for rabies elimination.

Phylogenetic analysis of nucleoprotein gene of dog rabies virus isolates from Southern India

India like several other South East Asian and African countries continues to face the public health and economic problems associated with the disease. Our objective was to perform a limited sequence analysis of a portion of nucleoprotein gene of 22 rabies virus isolates obtained from domestic animals in Southern India during 2004–2005. These isolates were compared with rabies virus isolates originating from Asia, Europe, Africa and North America. The phylogenetic analysis showed that RV isolates in Southern India belong to genotype 1. They were similar to one another forming a single major genetic cluster not ordered by geography or species of origin. However, they were dissimilar to RV isolates in Northern India and in other parts of the world. The data indicated that dog rabies virus variants are the major circulating viruses and control of dog rabies would result in overall reduction in the burden and incidence of rabies in India.

Evolutionary history and dynamics of dog rabies virus in western and central Africa

The burden of rabies in Africa is estimated at 24,000 human deaths year(-1), almost all of which result from infection with dog rabies viruses (RABV). To investigate the evolutionary dynamics of RABV in western and central Africa, 92 isolates sampled from 27 African countries over 29 years were collected and sequenced. This revealed that RABV currently circulating in dogs in this region fell into a single lineage designated 'Africa 2'. A detailed analysis of the phylogeographical structure of this Africa 2 lineage revealed strong population subdivision at the country level, with only limited movement of virus among localities, including a possible east-to-west spread across Africa. In addition, Bayesian coalescent analysis suggested that the Africa 2 lineage was introduced into this region of Africa only recently (probably <200 years ago), in accordance with the timescale of expanding European colonial influence and urbanization, and then spread relatively slowly, perhaps occupying the entire region in a 100 year period.

Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey

Human rabies has been endemic in India since time immemorial, and the true incidence of the disease and nationwide epidemiological factors have never been studied. The main objectives of the present study were to estimate the annual incidence of human rabies in India based on a community survey and to describe its salient epidemiological features. The Association for Prevention and Control of Rabies in India (APCRI) conducted a national multi-center survey with the help of 21 medical schools during the period February-August 2003. This community-based survey covered a representative population of 10.8 million in mainland India. Hospital-based data were also obtained from the 22 infectious diseases hospitals. A separate survey of the islands of Andaman, Nicobar, and Lakshadweep, reported to be free from rabies, was also undertaken. The annual incidence of human rabies was estimated to be 17,137 (95% CI 14,109-20,165). Based on expert group advice, an additional 20% was added to this to include paralytic/atypical forms of rabies, providing an estimate of 20,565 or about 2 per 100000 population. The majority of the victims were male, adult, from rural areas, and unvaccinated. The main animals responsible for bites were dogs (96.2%), most of which were stray. The most common bite sites were the extremities. The disease incubation period ranged from two weeks to six months. Hydrophobia was the predominant clinical feature. Many of the victims had resorted to indigenous forms of treatment following animal bite, and only about half of them had sought hospital attention. Approximately 10% of these patients had taken a partial course of either Semple or a cell culture vaccine. The islands of Andaman, Nicobar, and Lakshadweep were found to be free of rabies. Human rabies continues to be endemic in India except for the islands of Andaman, Nicobar, and Lakshadweep. Dogs continue to be the principal reservoir. The disease is taking its toll on adult men and children, the majority from rural areas, due to lack of awareness about proper post-exposure immunization. The keys to success in the further reduction of rabies in India lies in improved coverage with modern rabies vaccines, canine rabies control, and intensifying public education about the disease.

Ecoepidemiological and social factors related to rabies incidence in Venezuela during 2002-2004

Rabies in Venezuela has been important in last years, affecting dogs, cats, and human, among other animals, being a reportable disease. In Zulia state, it is considered a major public health concern. Recently, a considerable increase in the incidence of rabies has been occurring, involving many epidemiological but also ecoepidemiological and social factors. These factors are analyzed in this report. During 2002-2004, 416 rabies cases were recorded. Incidence has been increasingly significantly, affecting mainly dogs (88.94%). Given this epidemiology we associated ecoepidemiological and social factors with rabies incidence in the most affected state, Zulia. In this period 411 rabies cases were recorded. Zulia has varied environmental conditions. It is composed mostly of lowlands bordered in the west by mountain system and in the south by the Andes. The mean is temperature 27.8C, and mean yearly rainfall is 750mm. Climatologically, 2002 corresponded with El Nino (drought), middle 2003 evolved to a Neutral period, and 2004 corresponded to La Nina (rainy); this change may have affected many diseases, including rabies. Ecological analysis showed that most cases occurred in lowland area of the state and during rainy season (p&lt;0.05). Additionally, there is an important social problem due to educational deficiencies in the native population. Many ethnic groups live un Zulia, many myths about rabies are in circulation, and the importance of the disease is not widely realized. The full scale of the rabies burden is unknown, owing to inadequate disease surveillance. Although there have been important advances in our knowledge and ability to diagnose and prevent it, enormous challenges remain in animal rabies control and provision of accessible-appropriate human prophylaxis worldwide. Human and animal surveillance including ecological and social factors is needed.

The epidemiology of animal bite injuries in Uganda and projections of the burden of rabies

Rabies is a global problem, although it is often under-reported in developing countries. We aimed at describing the profile of patients presenting to health centres with animal bite injuries in Uganda, and use a predictive model to estimate the mortality of rabies at a national level. We conducted a passive surveillance study in Uganda based in a random sample of health centres supplied with rabies vaccine to determine the characteristics of bite injury patients and establish the age and sex profiles of patients, the site of bites and their severity, wound management techniques and details of the vaccination course given. We also applied a decision tree model to the data to estimate the rabies mortality from the bite injury data using an established protocol. We found that most patients are bitten by dogs, and that a considerable proportion of these are young children, who are at greater risk of developing rabies in the absence of treatment due to the location of the bites they receive. From conservative parameter estimates, we estimate that in the absence of post-exposure prophylaxis (PET), 592 (95% CI 345-920) deaths would occur, and that if one dose of PET is sufficient for protection following a rabid animal bite, 20 (95% CI 5-50) deaths would occur annually. If a complete course of PET is required for protection following a rabid animal bite, up to 210 (95% CI 115-359) deaths would occur, as 41% of patients did not complete their course of PET. Active animal bite surveillance studies are required to improve our mortality estimates and determine the true burden of rabies in the Ugandan population. We emphasize the need for small-scale active case detection studies and improved data on the recognition of rabies in dogs as inputs for improving national-level estimates of rabies mortality.