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Showing papers by "Charles E. Rupprecht published in 2007"


Journal ArticleDOI
TL;DR: This study demonstrates the combined evolutionary and population dynamic processes characterizing the spread of pathogen after its introduction into a fully susceptible host population and validate the use of coalescent approaches for uncovering even relatively complex population histories.
Abstract: Emerging pathogens potentially undergo rapid evolution while expanding in population size and geographic range during the course of invasion, yet it is generally difficult to demonstrate how these processes interact. Our analysis of a 30-yr data set covering a large-scale rabies virus outbreak among North American raccoons reveals the long lasting effect of the initial infection wave in determining how viral populations are genetically structured in space. We further find that coalescent-based estimates derived from the genetic data yielded an amazingly accurate reconstruction of the known spatial and demographic dynamics of the virus over time. Our study demonstrates the combined evolutionary and population dynamic processes characterizing the spread of pathogen after its introduction into a fully susceptible host population. Furthermore, the results provide important insights regarding the spatial scale of rabies persistence and validate the use of coalescent approaches for uncovering even relatively complex population histories. Such approaches will be of increasing relevance for understanding the epidemiology of emerging zoonotic diseases in a landscape context.

219 citations


Journal ArticleDOI
TL;DR: Findings from surveillance data support the contention that the canine rabies virus variant is no longer in circulation in the United States.
Abstract: Summary—During 2006, 49 states and Puerto Rico reported 6,940 cases of rabies in animals and 3 cases in humans to the CDC, representing an 8.2% increase from the 6,417 cases in animals and 1 case in a human reported in 2005. Approximately 92% of the cases were in wildlife, and 8% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,615 raccoons (37.7%), 1,692 bats (24.4%), 1,494 skunks (21.5%), 427 foxes (6.2%), 318 cats (4.6%), 82 cattle (1.2%), and 79 dogs (1.1%). Compared with numbers of reported cases in 2005, cases in 2006 increased among all groups except cattle. Increases in numbers of rabid raccoons during 2006 were reported by 11 of the 20 eastern states where raccoon rabies was enzootic, and reported cases increased by 3.2% overall, compared with 2005. On a national level, the number of rabies cases in skunks during 2006 increased by 6.1% from the number reported in 2005. Once again, Texas reported the greatest number (n = 351) of rabid skunks and the gr...

209 citations


Book ChapterDOI
01 Jan 2007
TL;DR: With highly effective methods for the prevention of human rabies, including effective tools for the elimination of rabies in dogs, there is a successful extinction of many unique rabies virus variants through oral vaccination.
Abstract: Publisher Summary Rabies is the most important viral zoonosis and an occupational hazard to all of those exposed to particular animals, intentionally or accidentally. Preventive public health practices of vaccination, leash restraint, confinement, observation, quarantine relate directly to animals. Pure, potent, safe, and effective rabies vaccines are developed through evaluation in experimental trials in animals. Elimination of the source of rabies in animals is a desirable goal. However, elimination of animal populations as a means to control rabies, because a particular species is a reservoir, is neither achievable nor desirable. In the 21st century, with highly effective methods for the prevention of human rabies, including effective tools for the elimination of rabies in dogs, there is a successful extinction of many unique rabies virus variants. In particular, significant advances are made in the past 25 years in the control and elimination of rabies in major wildlife sources through oral vaccination.

77 citations


Journal ArticleDOI
12 Apr 2007-Vaccine
TL;DR: HuMAb 17C7 was the most promising antibody identified because it neutralized all rabies virus isolates tested and protected hamsters from a lethal dose of rabiesirus in a well-established in vivo model of post-exposure prophylaxis.

75 citations


Book ChapterDOI
TL;DR: Both Duvenhage and Lagos bat viruses are adapted to bats, but their epidemiology, together with Mokola virus, is poorly understood, which is a major cause for concern among these emerging viral agents.
Abstract: Rabies has a long history of occurrence throughout Africa, spanning hundreds of years. At least four distinct Lyssavirus species persist throughout the continent, among carnivores, bats and other mammals. Rabies virus is the most cosmopolitan member, with primary reservoirs within dogs and mongoose, but other wildlife vectors are important in viral maintenance, such as jackals. Besides a prominent toll on humans and domestic animals, the disease has an underappreciated role in conservation biology, especially for such highly endangered fauna as African wild dogs and Ethiopian wolves. Both Duvenhage and Lagos bat viruses are adapted to bats, but their epidemiology, together with Mokola virus, is poorly understood. Significantly, less than ideal cross-reactivity with modern biologicals used for veterinary and public health interventions is a major cause for concern among these emerging viral agents.

75 citations


Journal ArticleDOI
TL;DR: The criteria used to guide development of a cocktail of human monoclonal antibodies as a replacement for RIG are set out and the general requirements for development of safe and efficacious monOClonal antibody alternatives to currently used polyclonal serum products are discussed.
Abstract: The currently recommended treatment for individuals exposed to rabies virus is the combined administration of rabies vaccine and rabies immune globulin (RIG). This review sets out the criteria used to guide development of a cocktail of human monoclonal antibodies as a replacement for RIG. Using this process as a model, the general requirements for development of safe and efficacious monoclonal antibody alternatives to currently used polyclonal serum products are discussed.

73 citations


Journal ArticleDOI
TL;DR: The application of a molecular clock indicates the emergence of current canine RABV diversity to have occurred at about the same time (approx. 1870) in the Middle East and Europe, following divergence from established lineages in Africa and Asia.
Abstract: Four novel phylogenetic clades of canine rabies virus (RABV) variants have been identified in the Middle East and North Africa. The three novel Middle Eastern clades comprise RABV isolates from the borders between Israel and neighbouring countries. The North African clade (Africa 4) comprises four RABV isolates from Egypt and one from Israel. We characterized various RABV lineages antigenically by using a panel of monoclonal antibodies to the nucleoprotein (N) and phylogenetically by analysis of entire N gene sequences. The estimated mean substitution rate for the N gene alignment (2.7×10−4 substitutions per site per year) is comparable with previous estimates for RABV. The application of a molecular clock indicates the emergence of current canine RABV diversity to have occurred at about the same time (approx. 1870) in the Middle East and Europe, following divergence from established lineages in Africa and Asia.

66 citations


Journal ArticleDOI
22 May 2007-Vaccine
TL;DR: Most reported AEs are non-serious and consistent with pre-licensure safety data, and the rabies risk must be carefully considered before vaccine discontinuation.

55 citations


Journal ArticleDOI
TL;DR: The direct and indirect costs of suspected human rabies exposure were estimated for San Luis Obispo and Santa Barbara counties, California, USA with a mean total cost of $3,688, the direct costs per case were $2,564, and the indirect costs were $1,124.
Abstract: The direct and indirect costs of suspected human rabies exposure were estimated for San Luis Obispo and Santa Barbara counties, California, USA. Clinic, hospital, and county public health records (1998-2002) were examined to determine direct costs for postexposure prophylaxis (PEP), and 55 (41%) former patients were contacted to voluntarily provide estimates of their indirect costs associated with receiving PEP. Additional costs due to public health and animal control personnel responses to rabid animals were collected, including diagnostic testing and wages. The mean total cost of a suspected human rabies exposure was $3,688, the direct costs per case were $2,564, and the indirect costs were $1,124 of that total. About one third of the total cost for suspected human rabies exposure was attributed to indirect costs (e.g., lost wages, transportation, and day-care fees), most of which were not reimbursable to the patient.

54 citations


Journal ArticleDOI
TL;DR: Molecular phylogenetics is used to test whether distinct virus–host associations occur in this species-rich carnivore community in the Serengeti ecosystem, and identifies a single major variant belonging to the group of southern Africa canid-associated viruses to be circulating within this ecosystem.
Abstract: Understanding the transmission dynamics of generalist pathogens that infect multiple host species is essential for their effective control. Only by identifying those host populations that are critical to the permanent maintenance of the pathogen, as opposed to populations in which outbreaks are the result of ‘spillover’ infections, can control measures be appropriately directed. Rabies virus is capable of infecting a wide range of host species, but in many ecosystems, particular variants circulate among only a limited range of potential host populations. The Serengeti ecosystem (in northwestern Tanzania) supports a complex community of wild carnivores that are threatened by generalist pathogens that also circulate in domestic dog populations surrounding the park boundaries. While the combined assemblage of host species appears capable of permanently maintaining rabies in the ecosystem, little is known about the patterns of circulation within and between these host populations. Here we use molecular phylogenetics to test whether distinct virus–host associations occur in this species-rich carnivore community. Our analysis identifies a single major variant belonging to the group of southern Africa canid-associated viruses (Africa 1b) to be circulating within this ecosystem, and no evidence for species-specific grouping. A statistical parsimony analysis of nucleoprotein and glycoprotein gene sequence data is consistent with both within- and between-species transmission events. While likely differential sampling effort between host species precludes a definitive inference, the results are most consistent with dogs comprising the reservoir of rabies and emphasize the importance of applying control efforts in dog populations.

45 citations


Journal ArticleDOI
22 May 2007-Vaccine
TL;DR: The generation and immunological testing of a recombinant MVA expressing a rabies virus glycoprotein gene is described, which boosted humoral immune responses in dogs and raccoons when administered peripherally, but not when administered orally.

Journal ArticleDOI
TL;DR: Through analyses of nt diversity, protein co-variations, structural and functional constraints, and reconstruction of phylogenetic trees from comprehensive datasets, it is proposed lyssavirus genes probably are of similar value for phylogenetic analyses.


Journal ArticleDOI
TL;DR: Under model conditions, there is a robust non-clinical state that can be attained by the exposed individual that allows persistence of the disease in the population, characterized by relatively low prevalence of the virus in colonies and much higher prevalence of rabies virus-neutralizing antibodies.

Journal ArticleDOI
TL;DR: This preliminary study showed that the vaccinia-vectored oral rabies vaccine Raboral V-RG®, as formulated for use in raccoons, is capable of protecting a percentage of skunks against rabies, however, although the fishmeal-coated sachets were readily consumed, subsequent challenge of these animals revealed poor vaccine delivery efficiency.
Abstract: Twenty-four adult striped skunks (Mephitis mephitis) were administered the raccoon product formulation of Rabies Vaccine, Live Vaccinia-Vectored (Raboral V-RG®, Merial Limited, Athens, Georgia, USA), either by oral instillation or in vaccine-filled coated sachets either as single or multiple doses. A control group remained unvaccinated. Twenty-three of the skunks were challenged 116 days postvaccination with rabies virus (skunk isolate). Six of six naive skunks succumbed to challenge. Four of six skunks that received the vaccine by oral instillation survived challenge. The skunks that did not survive failed to seroconvert following vaccination. None of the skunks that accepted multiple doses of the vaccine offered in coated sachets survived challenge, nor were rabies virus-neutralizing antibodies (VNAs) detected in the sera. Likewise, none of the five skunks ingesting a single sachet developed VNA against rabies. However, in this group one skunk did survive rabies challenge. This preliminary study showed ...

Book ChapterDOI
01 Jan 2007
TL;DR: The ecologic advantages offered by flight enhance the potential for invasion of new areas and rapid dispersal of viruses by bats, much more readily than by terrestrial mammals.
Abstract: Publisher Summary Among mammals, bats are second only to rodents in their number of species. The order is subdivided into two suborders: flying foxes (Megachiroptera) that inhabit the Old World tropics and the smaller-bodied bats (Microchiroptera) that are distributed globally, except in Antarctica. Rabies is described in representatives of both suborders on all continents. Given the issue of size alone, one can expect a greater absolute number of rabid bats to account for disease prevalence as well as a greater density of the species occupying any given space, compared with larger-bodied carnivores. Considering the variety of divergent lyssaviruses, the order Chiroptera is proposed as being primarily affected during adaptation of plant and arthropod rhabdoviruses to mammalian hosts. Presumably, adaptation occurred somewhere in the Old World, perhaps in Africa or Eurasia, where most divergent non-RABV lyssaviruses are found. The ecologic advantages offered by flight enhance the potential for invasion of new areas and rapid dispersal of viruses by bats, much more readily than by terrestrial mammals. Two human cases of Australian bat lyssavirus infection are described to date and are discussed in this chapter.

Journal ArticleDOI
16 Oct 2007-Vaccine
TL;DR: The results of this preliminary study suggest that SPBNGAS-GAS provides comparable efficacy to V-RG, and additional studies will be needed to determine the duration of immunity and optimal dosage of SPB NGAS- GAS and to examine its efficacy in other reservoir species.

Journal ArticleDOI
TL;DR: The results confirmed the existence of RABV of unclassified AV in Colombia and confirmed that dogs and D. rotundus are the two major rabies reservoirs and vectors in Colombia.

Journal ArticleDOI
TL;DR: Although notable examples of successful wildlife immunisation programmes exist, depending upon key considerations, vaccination may or may not prove to be effective in the field, wildlife vaccination requires a combination of novel zoonosis pathogen management strategies and public education to balance conservation, economic, and public health issues.
Abstract: Unprecedented human population growth and anthropogenic environmental changes have resulted in increased numbers of people living in closer contact with more animals (wild, domestic, and peridomestic) than at any other time in history. Intimate linkage of human and animal health is not a new phenomenon. However, the global scope of contemporary zoonoses has no historical precedent. Indeed, most human infectious diseases classed as emerging are zoonotic, and many of these have spilled over from natural wildlife reservoirs into humans either directly or via domestic or peridomestic animals. Conservation medicine has recently emerged as a meaningful discipline to address the intersection of animal, human, and ecosystem health. Interest in the development of novel vaccines for wildlife encounters important challenges that may prevent progress beyond the conceptual phase. Although notable examples of successful wildlife immunisation programmes exist, depending upon key considerations, vaccination may or may not prove to be effective in the field. When implemented, wildlife vaccination requires a combination of novel zoonosis pathogen management strategies and public education to balance conservation, economic, and public health issues.

Journal ArticleDOI
TL;DR: It is suggested that these ectoparasites do not enhance exposure of big brown bats to RV, and Colony size and year sampled were the most important variables in these AICc models.
Abstract: Recently, bat ectoparasites have been demonstrated to harbor pathogens of potential importance to humans. We evaluated antirabies antibody seroprevalence and the presence of ectoparasites in big brown bats (Eptesicus fuscus) sampled in 2002 and 2003 in Colorado to investigate if an association existed between ectoparasite intensity and exposure to rabies virus (RV). We used logistic regression and Akaike's Information Criteria adjusted for sample size (AICc) in a post-hoc analysis to investigate the relative importance of three ectoparasite species, as well as bat colony size, year sampled, age class, colony size, and year interaction on the presence of rabies virus neutralizing antibodies (VNA) in serum of wild E. fuscus. We obtained serum samples and ectoparasite counts from big brown bats simultaneously in 2002 and 2003. Although the presence of ectoparasites (Steatonyssus occidentalis and Spinturnix bakeri) were important in elucidating VNA seroprevalence, their intensities were higher in seronegative...

Journal ArticleDOI
TL;DR: Since the inception of the profession veterinarians have played a key role in the management of this major disease of nature, and the recent history of rabies in the New World serves to exemplify the role of veterinarians in context.
Abstract: GIVEN its unmatched case fatality rate, global distribution, considerable health and agricultural burden, and horrible clinical manifestations, rabies remains the most significant viral zoonosis at large in the 21st century. Considering the antiquity and impact of the disease, since the inception of the profession veterinarians have played a key role in the management of this major disease of nature. As a backdrop, the recent history of rabies in the New World serves to exemplify the role of veterinarians in context. Before colonisation, only bat rabies may have existed in the Americas. In the USA and elsewhere in the region, canine rabies was enzootic from at least the 18th century through to the 20th century. During the 1940s, thousands of rabid dogs were reported in the USA each year. After World War II, the coordinated control of dog rabies in the USA began with the creation of the concept of applied veterinary public health (Steele 1952). Rather than relying only on classical population reduction, movement restrictions, and leash and muzzle regulations, the advent of mass canine vaccination heralded an improvement. It established throughout the country the use of a biological application at the local level (Tierkel and others 1950). Such intensified programmes in major urban areas during the 1950s and 1960s dramatically reduced the number of reported cases, leading to the virtual elimination of canine rabies by the 1970s. While earlier vaccination efforts relied on neural-based products, the adaptaVeterinary Record (2007) 161, 290-291