- My primary expertise is in virology, zoology, ecology and veterinary medicine.To date, I have contributed to more tha... moreMy primary expertise is in virology, zoology, ecology and veterinary medicine.To date, I have contributed to more than 370 peer-reviewed publications and multiple book chapters.Currently, I am an independent biomedical consultant for academia, government, industry and NGOs.edit
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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... 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.
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.
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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... 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).
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).
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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... 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.
highest acceptance rate of the tested baits.
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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... 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.
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.
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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... 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...
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Research Interests: Relational Database, Genomics, Data Analysis, Proteomics, RNA viruses, and 12 moreSystems Integration, Biological Sciences, Data Visualization, Environmental Sciences, Bioterrorism, Nucleic Acids, Computer User Interface Design, Very high throughput, Metabolic pathway, Experimental Data, Internet, and Proteobacteria
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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... 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.
Research Interests: Puerto Rico, Carnivora, Bangladesh, Zoonoses, Adolescent, and 39 moreChiroptera, Rodentia, Cats, India, Mexico, Dogs, Canada, Disease Outbreaks, Travel, Case Report, Humans, Child, Sheep, United States, Female, Animals, Male, Raccoons, Rabies, Data Collection, Horses, Incidence, Goats, Cattle, Aged, Middle Aged, Adult, Swine, Captive Wild Animals, Lagomorpha, MEXICO, Mephitidae, Veterinary Sciences, Seasons, Animal Diseases, Pilot Projects, Rabies Virus, Foxes, and Wild animal
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... 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
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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... 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, ...
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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... 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...
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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... 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...
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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... 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.
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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... 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.
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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... 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.
Research Interests: Peru, Chiroptera, In Situ Hybridization, Disease Outbreaks, Brain, and 16 moreHumans, Sequence alignment, Mice, Female, Animals, Nucleic acid hybridization, Polymerase Chain Reaction, Monoclonal Antibodies, Rabies, Differential Diagnosis, Base Sequence, Rabies Virus, Clinical Diagnosis, Nucleic Acid, Brain Diseases, and The American
Over the past decade, a vaccinia-rabies glycoprotein (V-RG) recombinant vaccine virus has been developed for the potential control of wildlife rabies through oral immunization via baits. Prior to widespread field applications in varying... more
Over the past decade, a vaccinia-rabies glycoprotein (V-RG) recombinant vaccine virus has been developed for the potential control of wildlife rabies through oral immunization via baits. Prior to widespread field applications in varying ecological settings, extensive laboratory safety testing is necessary in a number of target and non-target species to quantify real or perceived risks and to monitor potential adverse health effects. Moreover, in order to mitigate concerns over inadvertent human exposure to a vaccine targeted for environmental release and intended for wildlife consumption, it was necessary to document the safety of the vaccine in primates following direct consumption orally and indirectly through transdermal administration. In the ensuing study, no significant differences were observed in the comparative pathogenicity of vaccinia and vaccinia-recombinant viruses by intradermal scarification of squirrel monkeys. In addition, eight of eleven chimpanzees administered th...
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In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in... more
In nature, rabies virus (RABV; genus Lyssavirus, family Rhabdoviridae) represents an assemblage of phylogenetic lineages, associated with specific mammalian host species. Although it is generally accepted that RABV evolved originally in bats and further shifted to carnivores, mechanisms of such host shifts are poorly understood, and examples are rarely present in
surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly
during 2001–2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with
no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T242 in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain.
Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other
approaches.
surveillance data. Outbreaks in carnivores caused by a RABV variant, associated with big brown bats, occurred repeatedly
during 2001–2009 in the Flagstaff area of Arizona. After each outbreak, extensive control campaigns were undertaken, with
no reports of further rabies cases in carnivores for the next several years. However, questions remained whether all outbreaks were caused by a single introduction and further perpetuation of bat RABV in carnivore populations, or each outbreak was caused by an independent introduction of a bat virus. Another question of concern was related to adaptive changes in the RABV genome associated with host shifts. To address these questions, we sequenced and analyzed 66 complete and 20 nearly complete RABV genomes, including those from the Flagstaff area and other similar outbreaks in carnivores, caused by bat RABVs, and representatives of the major RABV lineages circulating in North America and worldwide. Phylogenetic analysis demonstrated that each Flagstaff outbreak was caused by an independent introduction of bat RABV into populations of carnivores. Positive selection analysis confirmed the absence of post-shift changes in RABV genes. In contrast, convergent evolution analysis demonstrated several amino acids in the N, P, G and L proteins, which might be significant for pre-adaptation of bat viruses to cause effective infection in carnivores. The substitution S/T242 in the viral glycoprotein is of particular merit, as a similar substitution was suggested for pathogenicity of Nishigahara RABV strain.
Roles of the amino acid changes, detected in our study, require additional investigations, using reverse genetics and other
approaches.
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We screened 217 bats of at least 20 species from 17 locations in Kenya during July and August of 2006 for the presence of adenovirus, rhabdovirus, and paramyxovirus nucleic acids using generic reverse transcription polymerase chain... more
We screened 217 bats of at least 20 species from 17 locations in Kenya during July and August of 2006 for the presence of adenovirus, rhabdovirus, and paramyxovirus nucleic acids using generic reverse transcription polymerase chain reaction (RT-PCR) and PCR assays. Of 217 bat fecal swabs examined, 4 bats were adenovirus DNA-positive, 11 bats were paramyxovirus RNA-positive, and 2 bats were rhabdovirus RNA-positive. Three bats were coinfected by two different viruses. By sequence comparison and phylogenetic analysis, the Kenya bat paramyxoviruses and rhabdoviruses from this study may represent novel viral lineages within their respective families; the Kenya bat adenoviruses could not be confirmed as novel, because the same region sequences from other known bat adenovirus genomes for comparison were lacking. Our study adds to previous evidence that bats carry diverse, potentially zoonotic viruses and may be coinfected with more than one virus.
Research Interests: Phylogeography, Kenya, Chiroptera, Phylogeny, Animals, and 4 moreCoinfection, Prevalence, Genotype, and Feces
New causative agents of rabies continue to emerge as shown by the recent description of four novel lyssaviruses from bats in Eurasia, Aravan (ARAV), Khujand (KHUV), Irkut (IRKV), and West Caucasian bat virus (WCBV). The effect of rabies... more
New causative agents of rabies continue to emerge as shown by the recent description of four novel lyssaviruses from bats in Eurasia, Aravan (ARAV), Khujand (KHUV), Irkut (IRKV), and West Caucasian bat virus (WCBV). The effect of rabies vaccination prior to exposure to these new lyssaviruses was investigated in two animal models (i.e., Syrian hamsters and ferrets). The hamsters were vaccinated intramuscularly with a commercial human or veterinary vaccine or with an experimental vaccinia-rabies glycoprotein recombinant vaccine. At 5 weeks after vaccination, animals were challenged with ARAV, KHUV, IRKV, or WCBV, or with a traditional rabies virus of dog/coyote origin. Previously vaccinated and rabies-naive ferrets were also challenged with the four new isolates. In addition, the combined effect of rabies immunoglobulin and vaccine after exposure to the four isolates was investigated in hamsters using commercially available human products or an experimental monoclonal antibody. Results showed reduced protection with pre-exposure vaccination and with conventional rabies post-exposure prophylaxis against all four new bat viruses. In general, protection was inversely related to the genetic distance between the new isolates and traditional rabies viruses. For example, the WCBV is the most divergent of these lyssaviruses, and neither pre-exposure vaccination nor conventional post-exposure prophylaxis provided significant protection. The potential impact of these new lyssaviruses on human and domestic animal health and the impact on the putative bat reservoir populations will require further field and laboratory investigation.
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Research Interests: Western Europe, Zoonoses, Biological Sciences, Virus, United States, and 15 moreAnimals, Wildlife Management, Rabies, Long Range, Vaccination, Red Fox, Vulpes vulpes, Control Strategy, Rabies Vaccines, Captive Wild Animals, North American, Canis latrans, Rabies Virus, Procyon Lotor, and Oral Vaccination
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Rabies in bats is considered enzootic throughout the New World, but few comparative data are available for most countries in the region. As part of a larger pathogen detection program, enhanced bat rabies surveillance was conducted in... more
Rabies in bats is considered enzootic throughout the New World, but few comparative data are available for most countries in the region. As part of a larger pathogen detection program, enhanced bat rabies surveillance was conducted in Guatemala, between 2009 and 2011. A total of 672 bats of 31 species were sampled and tested for rabies. The prevalence of rabies virus (RABV) detection among all collected bats was low (0.3%). Viral antigens were detected and infectious virus was isolated from the brains of two common vampire bats (Desmodus rotundus). RABV was also isolated from oral swabs, lungs and kidneys of both bats, whereas viral RNA was detected in all of the tissues examined by hemi-nested RT-PCR except for the liver of one bat. Sequencing of the nucleoprotein gene showed that both viruses were 100% identical, whereas sequencing of the glycoprotein gene revealed one non-synonymous substitution (302T,S). The two vampire bat RABV isolates in this study were phylogenetically relat...
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Summary—During 2006, 49 states and Puerto Rico reported 6,940 cases of rabies in animals and 3 cases in hu mans to the CDC, representing an 8.2% increase from the 6,417 cases in animals and 1 case in a human reported in 2005.... more
Summary—During 2006, 49 states and Puerto Rico reported 6,940 cases of rabies in animals and 3 cases in hu mans 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
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An opossum (Dideiphis virgi- nl,ana) live-trapped on Parramore Island, Vir- ginia was infected with the lung parasite Cap- illaria dideiphis. Lung lesions associated with this parasite were extensive and consisted of flu- merous areas... more
An opossum (Dideiphis virgi- nl,ana) live-trapped on Parramore Island, Vir- ginia was infected with the lung parasite Cap- illaria dideiphis. Lung lesions associated with this parasite were extensive and consisted of flu- merous areas with central necrosis deep within the parenchyma. Necrotic foci were present around airways and consisted of a mixture of inflammatory cells and cellular debris, adult nematodes and many bipolar eggs. This parasite causes severe verminous pneumonia in the opos- sum.
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Two common bat lyssavirus species have been identified in many European countries: European bat lyssavirus type-1 and -2 (EBLV-1 and EBLV-2). Only limited knowledge on the susceptibility of the natural EBLV-hosts, insectivorous bats, to... more
Two common bat lyssavirus species have been identified in many European countries: European bat lyssavirus type-1 and -2 (EBLV-1 and EBLV-2). Only limited knowledge on the susceptibility of the natural EBLV-hosts, insectivorous bats, to lyssavirus infection is available. Our study was undertaken to evaluate the susceptibility and pathology associated with an EBLV-1 infection in Eptesicus fuscus following different routes of virus inoculation including intracranial (n = 6), intramuscular (n = 14), oral (n = 7) and intranasal (n = 7). Blood and saliva samples were collected from all bats on a monthly basis. Four bats inoculated intracranially developed rabies with a mean of 11 days to death, whilst seven bats inoculated intramuscularly developed rabies, with an extended incubation period prior to death. We did not observe any mortality in the oral (p.o.) or intranasal (i.n.) groups and both groups had detectable levels of virus neutralizing antibodies (data not shown). Virus shedding was demonstrated in the saliva by virus isolation and the detection of viral RNA in ill bats, particularly immediately prior to the development of disease. In addition, the presence of virus and viral RNA was detected in the thyroid gland in bats challenged experimentally with EBLV-1, which exceeded that detected in all other extra-neural tissue. The significance of detecting EBLV-1 in the thyroid gland of rabid bats is not well understood. We speculate that the infection of the thyroid gland may cause subacute thyroiditis, a transient form of thyroiditis causing hyperthyroidism, resulting in changes in adrenocortical activity that could lead to hormonal dysfunction, thereby distinguishing the clinical presentation of rabies in the rabid host.
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Oral rabies virus (RV) vaccines are used to immunize a diversity of mammalian carnivores, but no single biological is effective for all major species. Recently, advances in reverse genetics have allowed the design of recombinant RV for... more
Oral rabies virus (RV) vaccines are used to immunize a diversity of mammalian carnivores, but no single biological is effective for all major species. Recently, advances in reverse genetics have allowed the design of recombinant RV for consideration as new vaccines. The objective of this experiment was to examine the safety, immunogenicity and efficacy of recombinant RV vaccines administered to captive dogs by the oral route, compared to a commercial vaccinia-rabies glycoprotein (V-RG) recombinant virus vaccine. Animals consisted of naive purpose-bred beagles of both sexes, and were 6 months of age or older. Dogs were randomly assigned to one of six groups, and received either diluent or vaccine (PBS; V-RG; RV SN10-333; RV SPBN-Cyto c; RV SPBNGA; RV SPBNGAGA), with at least six animals per group. On day 0, 1 ml of each vaccine (or PBS) was administered to the oral cavity of each dog, at an approximate concentration of 10(8) to 10(9) TCID50. After vaccination, dogs were observed daily and bled weekly, for 5 weeks, prior to RV challenge. No signs of illness related to vaccination were detected during the observation period. Excluding the controls, RV neutralizing antibodies were detected in the majority of animals within 1-2 weeks of primary vaccination. Thereafter, all dogs were inoculated in the masseter muscle with a street virus of canine origin. All control animals developed rabies, but no vaccinates succumbed, with the exception of a single dog in the V-RG group. Review of these preliminary data demonstrates the non-inferiority of recombinant RV products, as concerns both safety and efficacy, and supports the suggestion that these vaccines may hold promise for future development as oral immunogens for important carnivore species, such as dogs.
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The nucleoprotein (N), phosphoprotein (P) and glycoprotein (G) genes of Irkut and West Caucasian bat viruses (WCBV) were sequenced and compared with those of other lyssaviruses. N gene nucleotide identities provided unequivocal separation... more
The nucleoprotein (N), phosphoprotein (P) and glycoprotein (G) genes of Irkut and West Caucasian bat viruses (WCBV) were sequenced and compared with those of other lyssaviruses. N gene nucleotide identities provided unequivocal separation of all lyssavirus genotypes with an identity threshold of 82%. On this basis, Irkut virus should be considered as a new genotype with particular relatedness to genotypes 4 and 5 (78.0-78.6% identity for N gene nucleotides and 90.4-92.6% for amino acids). Furthermore, genotypes 4-6, together with Aravan, Khujand and Irkut viruses, present a solid phylogroup of Old World bat lyssaviruses. This relationship is apparent using all three viral genes, and causes overlap between intragenotype and intergenotype identities for the P gene (Aravan, Khujand viruses and genotype 6) and for the G gene (Aravan, Khujand, genotypes 5 and 6). WCBV is the most divergent of known lyssaviruses with only limited relatedness to genotypes 2 and 3.
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Relative to the developed world, rabies has been poorly studied in the vast African continent. The southern African countries of Zimbabwe and South Africa, however, are known to sustain a great diversity of lyssaviruses, with large... more
Relative to the developed world, rabies has been poorly studied in the vast African continent. The southern African countries of Zimbabwe and South Africa, however, are known to sustain a great diversity of lyssaviruses, with large biological variations amongst genotype 1 (rabies viruses) at present more apparent here than elsewhere on the continent. One recognized biotype of rabies virus in the subcontinent appears to be specifically adapted to a variety of mongooses, belonging to the Viverrinae subfamily (family Herpestidae) and are commonly referred to as viverrid viruses, although the term mongoose rabies would be more correct, considering the taxonomic status of the host species involved. It was our objective to study the genetic relationships of 77 rabies virus isolates of this mongoose biotype, isolated in South Africa and Zimbabwe, towards elucidation of the molecular epidemiology of this interesting group of African viruses. In our study of a 592 nucleotide sequence encompassing the cytoplasmic domain of the glycoprotein and the G-L intergenic region of the viral genomes, we provide the first comprehensive data on the molecular epidemiology of these viruses and indicate a history of extended evolutionary adaptation in this geographical domain. The molecular epidemiological observations reported here are highly unlikely to be limited to the small geographical areas of South Africa and Zimbabwe and illustrate the need for lyssavirus surveillance in the rest of sub-Saharan Africa and throughout the entire continent.
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Various studies have demonstrated the potential of immunization with DNA vaccines encoding the rabies virus glycoprotein (RV-G) to elicit humoral responses. In the present study, we have designed four constructs using a VR1020 vector,... more
Various studies have demonstrated the potential of immunization with DNA vaccines encoding the rabies virus glycoprotein (RV-G) to elicit humoral responses. In the present study, we have designed four constructs using a VR1020 vector, wherein the RV-G ectodomain has been cloned without the signal sequence (SS) and the trans-membrane domain (TD) (rGVR), without the SS but with the TD (rGVRt), with the SS but without the TD (rGVRs) and with the SS and the TD (rGVRst), under the control of a cytomegalovirus (CMV) promoter, and downstream of the tissue plasminogen activator (TPA) signal sequence. In addition, RV-G has been expressed as a His6 tag fusion protein, both in Escherichia coli as well as in baculovirus expression systems. Using a prime-boost strategy, BALB/cJ mice administered with the rGVRt construct either in saline (intramuscularly) or adsorbed onto gold microcarriers (delivered intradermally by gene gun) generated the highest rabies virus neutralizing antibody (RVNA) titers. Inclusion of the SS, in addition to the TD (rGVRst), led to a significant decrease in RVNA titers, compared to the rGVRt construct. The DNA vaccine construct lacking both the SS and the TD domain and the vaccine having only the SS generated lower antibody responses, compared to the rGVRt construct. After priming with DNA vaccine, boosting with both E. coli- as well as baculovirus-expressed rRV-G led to an increase in the RVNA titers. The present results demonstrate that a DNA vaccine encoding the full-length sequence of the ectodomain plus TD of the mature native RV-G is capable of expressing an 'ideal' immunogen to produce RVNA titers.
Research Interests: Biological Sciences, Gold, Virus, Escherichia coli, Mice, and 16 moreAnimals, Male, Cytomegalovirus, P-glycoprotein, Rabies, DNA vaccines, Vaccination, Glycoproteins, Rabies Vaccines, DNA vaccine, Tissue Plasminogen Activator, Rabies Virus, Fusion Protein, Sodium Chloride, Full Length Movies, and Neutralizing antibodies
Research Interests:
Research Interests: Biological Sciences, Protein Structure and Function, Phylogeny, Cell line, Sequence alignment, and 12 moreVirus, Animals, Reverse genetics, Phylogenetic analysis, Phylogenetic Tree, Genome sequence, Amino Acid Sequence, Base Sequence, RNA Dependent RNA Polymerase, Rabies Virus, Full Length Movies, and Nucleotides
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Demography, Vector-Borne Disease, Public Health, Chiroptera, Phylogeny, and 12 moreHumans, United States, Animals, Polymerase Chain Reaction, Rabies, Colorado, Public health systems and services research, Genetic Divergence, Genetic variation, Rabies Virus, Epidemiologic Studies, and Eptesicus Fuscus
The characteristics of rabies epizootics among raccoons were investigated in 11 eastern states along a North-South gradient from New York to North Carolina. Epizootics were defined as discrete intervals of time of at least 5 months in... more
The characteristics of rabies epizootics among raccoons were investigated in 11 eastern states along a North-South gradient from New York to North Carolina. Epizootics were defined as discrete intervals of time of at least 5 months in duration, when reported cases of raccoon rabies from an individual county exceeded the median value of raccoon rabies cases reported by that county over the entire period rabies was present among raccoons in the county. Over the approximately 20-year study period, 35,000 cases of raccoon rabies were reported, and epizootics were detected from 251 (64.4%) of 390 counties. The median annual incidence was 0.14 epizootics per year. During the first defined epizootic in a county, the median total number of raccoons reported rabid was 47, with a median monthly incidence of rabies in raccoons of 3.1. The median lag time from the first report of a rabid raccoon in a county to the beginning of the first epizootic was 4 months. Significant differences in the annual incidence of epizootics and monthly incidence of rabid raccoons during epizootics were observed among different states. Although human population density and per capita health spending within counties were positively associated with increasing magnitude of epizootics, a significant difference in the characteristics of rabies epizootics in northern and southern states was apparent. We hypothesize that environmental conditions and perhaps human influence resulted in rabies epizootics in southern states that were smaller, less-frequent, and lacking in well-defined temporal structure compared with those in northern states.