Papers by Charles Rupprecht
Emerging Infectious Diseases, 2006
Archives of Virology, 2008
The literature supports that unique rabies virus (RABV) variants are often compartmentalized in d... more The literature supports that unique rabies virus (RABV) variants are often compartmentalized in different species of bats. In Colorado, two divergent mtDNA lineages of big brown bats (Eptesicus fuscus) co-occur. RABV associated with this species also segregates into two clades. We hypothesized that unique RABV variants might be associated with mtDNA lineages of Colorado big brown bats. DNA was extracted from brain tissue of rabid big brown bats, the ND2 gene was amplified to determine mtDNA lineage, and the lineage was compared to a previously derived phylogenetic analysis of the RABV N gene.
Journal of the American Veterinary Medical Association, Sep 4, 2013
Emerging Infectious Diseases, 2012
Flagstaff, Arizona, USA, experienced notable outbreaks of rabies caused by a bat rabies virus var... more Flagstaff, Arizona, USA, experienced notable outbreaks of rabies caused by a bat rabies virus variant in carnivore species in 2001, 2004, 2005, 2008, and 2009. The most recent epizootic involved transmission among skunk and fox populations and human exposures. Multiple, wide ranging control efforts and health communications outreach were instituted in 2009, including a household survey given to community members. Although the Flagstaff community is knowledgeable about rabies and the ongoing outbreaks in general, gaps in knowledge about routes of exposure and potential hosts remain. Future educational efforts should include messages on the dangers of animal translocation
and a focus on veterinarians and physicians as valuable sources for outreach. These results will be useful to communities experiencing rabies outbreaks as well as those at current risk.
Virus Genes, 2013
Rabies, an acute progressive encephalomyelitis caused by viruses in the genus Lyssavirus, is one ... more Rabies, an acute progressive encephalomyelitis caused by viruses in the genus Lyssavirus, is one of the oldest known infectious diseases. Although dogs and other carnivores represent the greatest threat to public health as rabies reservoirs, it is commonly accepted that bats are the primary evolutionary hosts of lyssaviruses. Despite early historical documentation of rabies, molecular clock analyses indicate a quite young age of lyssaviruses, which is confusing. For example, the results obtained for partial and complete nucleoprotein gene sequences of rabies viruses (RABV), or for a limited number of glycoprotein gene sequences, indicated that the time of the most recent common ancestor (TMRCA) for current bat RABV diversity in the Americas lies in the seventeenth to eighteenth centuries and might be directly or indirectly associated with the European colonization. Conversely, several other reports demonstrated high genetic similarity between lyssavirus isolates, including RABV, obtained within a time interval of 25–50 years. In the present study, we attempted to re-estimate the age of several North American bat
RABV lineages based on the largest set of complete and partial glycoprotein gene sequences compiled to date (n = 201) employing a codon substitution model. Although our results overlap with previous estimates in marginal areas of the 95 % high probability density (HPD), they suggest a longer evolutionary history of American bat RABV lineages (TMRCA at least 732 years, with a 95 % HPD 436–1107 years).
Towards the Elimination of Rabies in Eurasia, 2008
In many areas of the world, only 30 to 50% of dogs are vaccinated against rabies. On some US Indi... more In many areas of the world, only 30 to 50% of dogs are vaccinated against rabies. On some US Indian Reservations, vaccination rates may be as low as 5 to 20%. In 2003 and 2004,we evaluated the effectiveness of commercially available baits to deliver oral rabies vaccine to feral and free-ranging dogs on the Navajo and Hopi Nations. Dogs were offered one of the following baits containing a plastic packet filledwith placebo vaccine: vegetable shortening-based Ontario slimbaits (Artemis Technologies, Inc.), fish-meal-crumble coated sachets (Merial, Ltd.), dog food polymer baits (Bait-Tek, Inc.), or fish meal polymer baits (Bait-Tek, Inc.). One bait was offered to each animal and its behaviour toward the bait was recorded. Behaviours included: bait ignored, bait swallowed whole, bait chewed and discarded (sachet intact), bait chewed and discarded (sachet punctured), or bait chewed and consumed (sachet punctured). Bait acceptance ranged from 30.7%to 77.8%with the fish-meal-crumble coated sachets having the
highest acceptance rate of the tested baits.
Vaccine, 2009
Parenteral vaccination campaigns are integral to the elimination of canine rabies. To maximize he... more Parenteral vaccination campaigns are integral to the elimination of canine rabies. To maximize herd immunity in dogs, immunocontraception provided at the time of rabies vaccination should reduce fecundity and dog abundance. GonaConTM has been used successfully as an immunocontraceptive in a variety
of mammals, and by inference, the dog would be an ideal candidate for testing. As an initial step in evaluating a combination-vaccination program, we assessed the effects of GonaConTM on rabies virus neutralizing antibody production in dogs after administration of a veterinary rabies vaccine. Eighteen
feral/free ranging dogs were included in this initial study: six were given GonaConTM only, six were given rabies vaccination only, and six received GonaConTM and rabies vaccination. Antibody levels were evaluated over 82 days. The use of the immunocontraceptive GonaConTM did not affect the ability of dogs to seroconvert in response to the rabies vaccine. Thus, GonaConTM provides a potential immunocontraceptive
for use in combination with rabies vaccine to increase herd immunity and address dog population over abundance to better manage rabies.
Developments in biologicals
rabies was confined to the southeastern US. Translocations led to emergence of this rabies varian... more rabies was confined to the southeastern US. Translocations led to emergence of this rabies variant in the mid-Atlantic states, followed by spread northerly to northeast Ohio and Ontario, Quebec, and New Brunswick, Canada. Raccoon rabies is currently contiguous from southwest Alabama to southeastern Canada. Since 1998, state, federal, county and municipal as well as Canadian and Mexican experts have collaborated on goals and strategies to prevent raccoon rabies spread in North America. Coordinated programmes have been established from Maine to Alabama. Successes have been realized through strategies that rely heavily on oral vaccination. International coordination targeting raccoon rabies continues in eastern Canada, where contingency actions have led to elimination or near elimination in Ontario and New Brunswick. However, increasingly, focus in the US has been directed toward contingency actions to "hold-the-line" where raccoon rabies threatens to 439 spread to new areas, rather than on raccoon rabies elimination. We report on the challenges of achieving enhanced rabies surveillance, containment of raccoon rabies, and local elimination of raccoon rabies, as well as the need for international coordination in meeting these challenges.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 10, 2015
As most newly characterized emerging infectious diseases are considered to be zoonotic, a modern ... more As most newly characterized emerging infectious diseases are considered to be zoonotic, a modern preeminence ascribed within this classification lies clearly within the viral taxonomic realm. In particular, RNA viruses deserve special concern given documented impact to conservation biology, veterinary medicine and public health, with an unprecedented ability to promote an evolutionary host-pathogen arms race from the ultimate infection and immunity perspective. However, besides the requisite molecular/gross anatomical and physiological basis for infectious diseases to transmit from one host to another, both viral pathogens and their reservoirs/vectors exploit a complex anthropological, cultural, historical, psychological and social suite that specifically defines the phylodynamics within Homo sapiens, unlike any other species. Some of these variables include the ecological benefits of living in groups, decisions on hunting and foraging behaviors and dietary preferences, myths and re...
F1000Research, 2014
GIS analysis was used to substantiate the use of a weighted variable for a study to explore how l... more GIS analysis was used to substantiate the use of a weighted variable for a study to explore how land-use patterns might affect the reservoir of a zoonotic disease.
Nucleic Acids Research, 2007
The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Cen... more The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, caliciand lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https:// patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.
Journal of the American Veterinary Medical Association
In 1991, 49 states, the District of Columbia, and Puerto Rico reported 6,972 cases of rabies in n... more In 1991, 49 states, the District of Columbia, and Puerto Rico reported 6,972 cases of rabies in nonhuman animals and 3 cases in human beings to the Centers for Disease Control. Ninety-one percent (6,354 cases) were wild animals, whereas 8.9% (618 cases) were domestic species. The total number of reported cases of rabies increased 42.9% over that of 1990 (4,881 cases), with most of the increase resulting from continued spread of the epizootic of rabies in raccoons in the mid-Atlantic and northeastern states. Large increases in cases of rabies in animals were reported from Connecticut (200 cases in 1991, compared with 3 in 1990, an increase of 6,567%), Delaware (197 cases in 1991, compared with 44 in 1990, an increase of 348%), New York (1,303 cases in 1991, compared with 242 in 1990, an increase of 326%), and New Jersey (994 cases in 1991, compared with 469 in 1990, an increase of 112%). Other noteworthy increases were reported by Wyoming (96.4%), Texas (69.7%), California (41.3%), Oklahoma (33.1%), Minnesota (31.4%), Georgia (26.7%), and Maryland (23.7%). Hawaii reported 1 imported case of rabies in a bat. Only 16 states reported decreases in rabies in animals in 1991, compared with 30 in 1990. Pennsylvania and Iowa reported decreases of 40.6% and 27.4%, respectively. Rhode Island was the only state that did not report a case of rabies in 1991.
A virus isolated from dead Chaerephon plicata bats collected near Kampot, Cambodia, was identifie... more A virus isolated from dead Chaerephon plicata bats collected near Kampot, Cambodia, was identified as a member of the family Bunyaviridae by electron microscopy. The only bunyavirus previously isolated from Chaerephon species bats in South-East Asia is Kaeng Khoi (KK) virus (genus Orthobunyavirus), detected in Thailand over 30 years earlier and implicated as a public health problem. Using RT-PCR, nucleotide
Revue scientifique et technique (International Office of Epizootics), 2007
Emerging infectious diseases represent a grave threat to animal and human populations in terms of... more Emerging infectious diseases represent a grave threat to animal and human populations in terms of their impact on global health, agriculture and the economy. Vaccines developed for emerging infections in animals can protect animal health and prevent transmission of zoonotic diseases to humans. Examples in this paper illustrate how industry and public health can collaborate to develop a vaccine to prevent an emerging disease in horses (West Nile virus vaccine), how poultry vaccination can protect animals and prevent transmission to people (avian influenza vaccine), how regulatory changes can pave the way for vaccines that will control the carrier state in animals and thus prevent infection in humans (Bartonella henselae vaccine in cats) and how novel technologies could be applied to vaccinate wildlife reservoir species for rabies. Stemming from the realisation that zoonotic diseases are the predominant source of human emerging infectious diseases, it behoves academic, public health, ...
Current opinion in virology, 2011
Rabies is propagated globally by viruses in the Family Rhabdoviridae, Genus Lyssavirus. These RNA... more Rabies is propagated globally by viruses in the Family Rhabdoviridae, Genus Lyssavirus. These RNA viruses utilize the mammalian central nervous system as their ultimate niche, and exploit routine social mechanisms, as well as host behavioral alterations, to facilitate transmission by neural transport and innervations of the salivary glands, and ultimately excretion via the saliva, towards circulation thereafter in host populations. All mammals are susceptible to infection, but lyssavirus reservoirs are represented by several species of Carnivora, with viral global diversity and distribution in toto driven by a wide variety of the Chiroptera. Pathogen diversity is maintained by multiple faunas, and facilitated by pronounced host vagility, as exemplified by the ease of routine daily and seasonal movements by bats. Viral 'ensembles', or subpopulations associated with productive transmission events, emerge locally in vivo through a combination of naive host infections in some in...
Current topics in microbiology and immunology, 2008
Rabies, being a major zoonotic disease, significantly impacts global public health. It is invaria... more Rabies, being a major zoonotic disease, significantly impacts global public health. It is invariably fatal once clinical signs are apparent. The majority of human rabies deaths occur in developing countries. India alone reports more than 50% of the global rabies deaths. Although it is a vaccine-preventable disease, effective rabies prevention in humans with category III bites requires the combined administration of rabies immunoglobulin (RIG) and vaccine. Cell culture rabies vaccines have become widely available in developing countries, virtually replacing the inferior and unsafe nerve tissue vaccines. Limitations inherent to the conventional RIG of either equine or human origin have prompted scientists to look for monoclonal antibody-based human RIG as an alternative. Fully human monoclonal antibodies have been found to be safer and equally efficacious than conventional RIG when tested in mice and hamsters. In this chapter, rabies epidemiology, reservoir control measures, post-expo...
Current topics in microbiology and immunology, 2007
Rabies has a long history of occurrence throughout Africa, spanning hundreds of years. At least f... more 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.
Vaccine, Jan 21, 2001
Rabies is the most important viral zoonosis from a global perspective. Modern human postexposure ... more Rabies is the most important viral zoonosis from a global perspective. Modern human postexposure prophylaxis consists of potent vaccines and local infiltration of rabies immune globulins (RIGs), but the latter biologicals are not widely available or affordable. Monoclonal antibodies (Mabs) offer several theoretical advantages over RIGs. To this end, several human and equine RIGS, alone or in combination with vaccine, were investigated for postexposure efficacy in a Syrian hamster model, compared with a single neutralizing murine Mab. Preliminary results suggest that: (1) animal models continue to provide utility as human surrogates in the demonstration of product efficacy against rabies; (2) RIG preparations differ substantially in experimental effectiveness and clearance; and (3) relevant alternatives, such as Mabs, should be pursued for future improvements to human rabies prevention.
The American journal of tropical medicine and hygiene, 1999
In the spring of 1996, multiple cases of an acute febrile illness resulting in several deaths in ... more In the spring of 1996, multiple cases of an acute febrile illness resulting in several deaths in remote locations in Peru were reported to the Centers for Disease Control and Prevention (CDC). The clinical syndromes for these cases included dysphagia and encephalitis. Because bat bites were a common occurrence in the affected areas, the initial clinical diagnosis was rabies. However, rabies was discounted primarily because of reported patient recovery. Samples of brain tissue from two of the fatal cases were received at CDC for laboratory confirmation of the rabies diagnosis. An extensive array of tests on the formalin-fixed tissues confirmed the presence of both rabies viral antigen and nucleic acid. The virus was shown to be most closely related to a vampire bat rabies isolate. These results indicate the importance of maintaining rabies in the differential diagnosis of acute febrile encephalitis, particularly in areas where exposure to vampire bats may occur.
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Papers by Charles Rupprecht
and a focus on veterinarians and physicians as valuable sources for outreach. These results will be useful to communities experiencing rabies outbreaks as well as those at current risk.
RABV lineages based on the largest set of complete and partial glycoprotein gene sequences compiled to date (n = 201) employing a codon substitution model. Although our results overlap with previous estimates in marginal areas of the 95 % high probability density (HPD), they suggest a longer evolutionary history of American bat RABV lineages (TMRCA at least 732 years, with a 95 % HPD 436–1107 years).
highest acceptance rate of the tested baits.
of mammals, and by inference, the dog would be an ideal candidate for testing. As an initial step in evaluating a combination-vaccination program, we assessed the effects of GonaConTM on rabies virus neutralizing antibody production in dogs after administration of a veterinary rabies vaccine. Eighteen
feral/free ranging dogs were included in this initial study: six were given GonaConTM only, six were given rabies vaccination only, and six received GonaConTM and rabies vaccination. Antibody levels were evaluated over 82 days. The use of the immunocontraceptive GonaConTM did not affect the ability of dogs to seroconvert in response to the rabies vaccine. Thus, GonaConTM provides a potential immunocontraceptive
for use in combination with rabies vaccine to increase herd immunity and address dog population over abundance to better manage rabies.
and a focus on veterinarians and physicians as valuable sources for outreach. These results will be useful to communities experiencing rabies outbreaks as well as those at current risk.
RABV lineages based on the largest set of complete and partial glycoprotein gene sequences compiled to date (n = 201) employing a codon substitution model. Although our results overlap with previous estimates in marginal areas of the 95 % high probability density (HPD), they suggest a longer evolutionary history of American bat RABV lineages (TMRCA at least 732 years, with a 95 % HPD 436–1107 years).
highest acceptance rate of the tested baits.
of mammals, and by inference, the dog would be an ideal candidate for testing. As an initial step in evaluating a combination-vaccination program, we assessed the effects of GonaConTM on rabies virus neutralizing antibody production in dogs after administration of a veterinary rabies vaccine. Eighteen
feral/free ranging dogs were included in this initial study: six were given GonaConTM only, six were given rabies vaccination only, and six received GonaConTM and rabies vaccination. Antibody levels were evaluated over 82 days. The use of the immunocontraceptive GonaConTM did not affect the ability of dogs to seroconvert in response to the rabies vaccine. Thus, GonaConTM provides a potential immunocontraceptive
for use in combination with rabies vaccine to increase herd immunity and address dog population over abundance to better manage rabies.