Sarah Cleaveland

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.

Identifying reservoirs of infection: a conceptual and practical challenge.

Many infectious agents, especially those that cause emerging diseases, infect more than one host species. Managing reservoirs of multihost pathogens often plays a crucial role in effective disease control. However, reservoirs remain variously and loosely defined. We propose that reservoirs can only be understood with reference to defined target populations. Therefore, we define a reservoir as one or more epidemiologically connected populations or environments in which the pathogen can be permanently maintained and from which infection is transmitted to the defined target population. Existence of a reservoir is confirmed when infection within the target population cannot be sustained after all transmission between target and nontarget populations has been eliminated. When disease can be controlled solely by interventions within target populations, little knowledge of potentially complex reservoir infection dynamics is necessary for effective control. We discuss the practical value of different approaches that may be used to identify reservoirs in the field.

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.

Transmission Dynamics and Prospects for the Elimination of Canine Rabies

Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R0, is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal.

Animal movements and the spread of infectious diseases

Domestic and wild animal population movements are important in the spread of disease. There are many recent examples of disease spread that have occurred as a result of intentional movements of livestock or wildlife. Understanding the volume of these movements and the risks associated with them is fundamental in elucidating the epidemiology of these diseases, some of which might entail zoonotic risks. The importance of the worldwide animal trade is reviewed and the role of the unregulated trade in animals is highlighted. A range of key examples are discussed in which animal movements have resulted in the introduction of pathogens to previously disease-free areas. Measures based on heightened surveillance are proposed that mitigate the risks of new pathogen introductions.

Estimating human rabies mortality in the United Republic of Tanzania from dog bite injuries

OBJECTIVE To make quantitative predictions about the magnitude of underreporting of human rabies deaths in the United Republic of Tanzania. METHODS Human rabies deaths were estimated by using a series of probability steps to calculate the likelihood of rabies developing after the bite of a suspected rabid dog, incorporating field data on the incidence of animal bite injuries, the accuracy of rabies recognition, the distribution of bite wounds, and post-exposure treatment. FINDINGS Predicted human rabies mortality was estimated to be (a) 1499 deaths per year (95% confidence interval 891-2238), equivalent to an annual incidence of 4.9 (2.9-7.2) deaths/100,000, when active surveillance data on bite incidence were used, and (b) 193 deaths per year (32-409), corresponding to an annual incidence of 0.62 (0.1-1.32) deaths/100,000, when national bite statistics were used. The annual mean number of rabies deaths officially recorded for the same period was 10.8 (7.7-14.0). CONCLUSION In the United Republic of Tanzania, cases of rabies in humans have been greatly underreported. Dog bite injuries are an accessible source of epidemiological data that may be used to estimate the public health burden of rabies and to monitor epidemiological trends in developing countries.

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

Background Canine rabies causes many thousands of human deaths every year in Africa, and continues to increase throughout much of the continent. Methodology/Principal Findings This 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/Significance We 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.

A dog rabies vaccination campaign in rural Africa: impact on the incidence of dog rabies and human dog-bite injuries

Despite the availability of safe and effective rabies vaccines, the incidence of dog rabies has been increasing throughout much of sub-Saharan Africa. Here we describe a vaccination strategy that has resulted in successful control of rabies in a rural dog population of Northwestern Tanzania. From October 1996 to February 2001, four central-point dog vaccination campaigns were conducted in villages within Serengeti District with a mean interval between campaigns of 338, 319 and 456 days. Vaccination coverage of the dog population was estimated from household questionnaires as 64.5, 61.1, 70.6 and 73.7% following each of the four campaigns, respectively. The incidence of dog rabies declined significantly in Serengeti District falling by 70% after the first campaign and by 97% after the second campaign. Over the same period, the incidence of dog rabies did not differ significantly in unvaccinated control villages of Musoma District. The incidence of human bite injuries from suspected rabid dogs declined significantly in Serengeti District after dog vaccination but not in adjacent unvaccinated districts. Vaccination of 60-70% of dogs has been sufficient to control dog rabies in this area and to significantly reduce demand for human post-exposure rabies treatment. Dog-bite injuries can provide a valuable and accessible source of data for surveillance in countries where case incidence data are difficult to obtain.

Serological and demographic evidence for domestic dogs as a source of canine distemper virus infection for Serengeti wildlife.

Following an epidemic of canine distemper virus (CDV) in Serengeti lions in 1994, the role of domestic dogs in the epidemiology of the disease was investigated by serological and demographic analyses. From 1992 to 1994, data were collected from two domestic dog populations bordering the Serengeti National Park. Several lines of evidence indicated that patterns of CDV infection differed significantly between higher-density dog populations of Serengeti District to the west of the park and lower-density populations of Ngorongoro District to the south-east: (a) CDV age-seroprevalence patterns differed significantly between years in Ngorongoro District populations but not in Serengeti District populations; (b) CDV seropositive pups (<12 months of age) were detected in Ngorongoro District only in 1994, whereas a proportion of pups in Serengeti District were seropositive in each year of the study; (c) in Ngorongoro District, the proportion of deaths attributed to disease was significantly higher in 1994 than in 1993, whereas in Serengeti District, there was no significant difference in disease-related mortality between years; (d) in Ngorongoro District, significantly more CDV seronegative dogs than seropositive dogs died in 1994, whereas there was no difference in survival of CDV seropositives and seronegatives between years in Serengeti District. We concluded that, between 1992 and 1994, CDV persisted in higher-density dog populations of Serengeti District, but occurred only sporadically in lower-density Ngorongoro District populations. Data from Ngorongoro District are consistent with exposure of dogs to CDV in 1991 and 1994, but not in 1992 and 1993. These findings suggest that higher-density domestic dog populations to the west of the Serengeti National Park were a more likely source of CDV infection for wildlife during 1994 than lower-density pastoralist dogs to the south and east of the park.

Evaluation of a direct, rapid immunohistochemical test for rabies diagnosis.

A direct rapid immunohistochemical test (dRIT) was evaluated under field and laboratory conditions to detect rabies virus antigen in frozen and glycerol-preserved field brain samples from northwestern Tanzania. Compared to the direct fluorescent antibody test, the traditional standard in rabies diagnosis, the dRIT was 100% sensitive and specific.