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Biomedical subjects

Charles E Rupprecht

Publications and source records attributed to Charles E Rupprecht.

At least 19 recordsLinked to original sources
PubMed2007

A human monoclonal antibody cocktail as a novel component of rabies postexposure prophylaxis.

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.

Antibodies, Monoclonal↗
PubMed2006

Rabies surveillance in the United States during 2005.

During 2005, 49 states and Puerto Rico reported 6,417 cases of rabies in nonhuman animals and 1 case in a human being to the CDC, representing a 6.2% decrease from the 6,836 cases in nonhuman animals and 8 cases in human beings reported in 2004. Approximately 92% of the cases were in wildlife, and 8% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,534 raccoons (39.5%), 1,478 skunks (23%), 1,408 bats (21.9%), 376 foxes (5.9%), 269 cats (4.2%), 93 cattle (1.5%), and 76 dogs (1.2%). Compared with numbers of reported cases in 2004, cases in 2005 decreased among all groups, except bats, horses, and other wild animals. Decreases in numbers of rabid raccoons during 2005 were reported by 10 of the 20 eastern states in which raccoon rabies was enzootic and decreased overall by 1.2%, compared with 2004. On a national level, the number of rabies cases in skunks during 2005 decreased 20.4% from the number reported in 2004. Once again, Texas reported the greatest number (n = 392) of rabid skunks and the greatest overall state total of rabies cases (741). Texas reported no cases of rabies associated with the dog/coyote rabies virus variant and only 8 cases associated with the Texas gray fox rabies virus variant (compared with 22 cases in 2004). The total number of cases of rabies reported nationally in foxes decreased 3.3%, compared with those reported in 2004. The 1,408 cases of rabies reported in bats represented a 3.5% increase over numbers reported in 2005. Cases of rabies in cats, dogs, cattle, and sheep and goats decreased 4.3%, 19.2%, 19.1%, and 10%, respectively, whereas cases reported in horses and mules increased 9.3%. In Puerto Rico, reported cases of rabies in mongooses increased 29.8%, and rabies in domestic animals decreased 37.5%. One case of human rabies was reported from Mississippi during 2005. This case was submitted by the state to the CDC's unexplained deaths project and diagnosed as rabies retrospectively.

Animals↗
PubMed2006

Integrative models of bat rabies immunology, epizootiology and disease demography.

Bats are natural reservoirs of rabies. We address the maintenance of the disease in bat colonies by developing individual and population models that generate indicators of risk of rabies to bats, that provide dynamic estimates of effects of rabies on population densities, and that suggest consequences of viral exposures and infections in bats relative to physiological and ecological characteristics of bats in different habitats. We present individual models (within host) for the immune responses to a rabies virus challenge, an immunotypic disease model that describes the evolution of the disease and a disease demographics model, which is structured by immunotypic response governed by immune system efficiency. Model simulations are consistent with available data, characterized by relatively low prevalence of the virus in colonies and much higher prevalence of rabies virus-neutralizing antibodies. 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.

Animals↗
PubMed2006

Development of a GIS-based, real-time Internet mapping tool for rabies surveillance.

BACKGROUND: Oral rabies vaccination programs have been implemented to control the spread of wildlife rabies in the United States. However, current surveillance systems are inadequate for the efficient management and evaluation of these large scale vaccine baiting programs. With this in mind, a GIS-based rabies surveillance database and Internet mapping application was created. This surveillance system, RabID, provides a new resource for the rapid mapping and dissemination of data on animal rabies cases in relation to unaffected, enzootic, and baited areas where current interventions are underway. RESULTS: RabID is a centralized database for diagnostic and demographic information collected by local, state, and federal agencies involved in rabies surveillance. The geo-referenced database remits data to an Internet-accessible mapping application that displays rabies surveillance data in relation to environmental and geographic features. CONCLUSION: RabID provides a pioneering example of the power of geographically based Internet-accessible, infectious disease surveillance. This surveillance system was developed from existing technology and is readily adaptable to other infectious diseases and may be particularly useful for zoonoses. The development and application of public health informatics technology may enhance the effectiveness of public health interventions and allow better evaluation of public health interventions.

Animals↗
PubMed2006

Comparison of an anti-rabies human monoclonal antibody combination with human polyclonal anti-rabies immune globulin.

The World Health Organization estimates human mortality from endemic canine rabies to be 55,000 deaths/year. Limited supply hampers the accessibility of appropriate lifesaving treatment, particularly in areas where rabies is endemic. Anti-rabies antibodies are key to protection against lethal rabies. Currently, only human and equine polyclonal anti-rabies immune globulin (HRIG and ERIG) is available. Replacement of HRIG and ERIG with a safer and more widely available product is recommended. We have recently identified a combination of 2 human monoclonal antibodies (MAbs), CR57 and CR4098, that has high potential. We here describe a head-to-head comparison between an CR57/CR4098 MAb cocktail and HRIG. The MAb cocktail neutralized all viruses from a panel of 26 representative street rabies virus isolates. In combination with vaccine, the MAb cocktail protected Syrian hamsters against lethal rabies when administered 24 h after exposure, comparable with the results obtained with HRIG. Furthermore, the MAb cocktail did not interfere with rabies vaccine differently from HRIG. These results demonstrate that the human MAb cocktail of CR57 and CR4098 is a safe and efficacious alternative to RIG in rabies postexposure prophylaxis.

Animals↗
PubMed2006

A new phylogenetic lineage of rabies virus associated with western pipistrelle bats (Pipistrellus hesperus).

Bats represent the major source of human rabies cases in the New World. In the USA, most cases are associated with species that are not commonly found or reported rabid. To understand better the epidemiology and public health significance of potentially important bat species, a molecular study was performed on samples collected from naturally infected rabid western pipistrelle (Pipistrellus hesperus), eastern pipistrelle (Pipistrellus subflavus) and silver-haired bats (Lasionycteris noctivagans) from different regions of their geographical distribution in the USA. A 264 bp fragment at the 5' end of the N gene coding region was sequenced and analysed in comparison with rabies virus variants circulating within other North American mammals. Phylogenetic analysis demonstrated that P. hesperus bats maintain a unique rabies virus variant. Preliminary data also suggest that P. subflavus and Lasionycteris noctivagans may harbour two different rabies virus variants (Ps and Ln) that are likely to be maintained independently by each bat species, which recently appear to have emerged as major vectors of human disease.

Amino Acid Sequence↗
PubMed2006

Molecular diversity of rabies viruses associated with bats in Mexico and other countries of the Americas.

Bat rabies and its transmission to humans and other species in Mexico were investigated. Eighty-nine samples obtained from rabid livestock, cats, dogs, and humans in Mexico were studied by antigenic typing and partial sequence analysis. Samples were further compared with enzootic rabies associated with different species of bats in the Americas. Patterns of nucleotide variation allowed the definition of at least 20 monophyletic clusters associated with 9 or more different bat species. Several lineages associated with distinctive antigenic patterns were found in rabies viruses related to rabies in vampire bats in Mexico. Vampire bat rabies virus lineages associated with antigenic variant 3 are widely spread from Mexico to South America, suggesting these lineages as the most likely ancestors of vampire bat rabies and the ones that have been moved by vampire bat populations throughout the Americas. Rabies viruses related to Lasiurus cinereus, Histiotus montanus, and some other not yet identified species of the genus Lasiurus were found circulating in Mexico. Long-range dissemination patterns of rabies are not necessarily associated with migratory bat species, as in the case of rabies in Desmodus rotundus and Histiotus montanus. Human rabies was associated with vampire bat transmission in most cases, and in one case, rabies transmission from free-tailed bats was inferred. The occurrence of rabies spillover from bats to domestic animals was also demonstrated. Genetic typing of rabies viruses allowed us to distinguish trends of disease dissemination and to address, in a preliminary fashion, aspects of the complex evolution of rabies viruses in different host-reservoir species.

Amino Acid Sequence↗
PubMed2006

Current and future trends in the prevention, treatment and control of rabies.

Rabies remains a global zoonosis of major public health, agricultural and economic significance. Dogs are the major animal reservoirs in developing regions, wildlife maintain cycles of infection even in developed countries and new viral etiological agents continue to emerge. Nearly all human rabies cases are related directly to animal bite and thus, primary disease prevention requires minimization of suspected exposures. Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. Pre-exposure vaccination should occur in selected population groups at risk of occupational exposure. Historically, survival from fatal rabies by at least five human patients, vaccinated prior to the onset of clinical signs, signaled initial optimism as to the theoretical utility of medical intervention. Recently, the heroic recovery of an unvaccinated teenager from clinical rabies offers hope of future specific therapy. Canine rabies elimination is the key towards ultimate reduction of the disease burden, as first illustrated in developed countries. Implementation of oral vaccination in free-ranging carnivore hosts demonstrates the feasibility of disease abatement in particular wildlife populations, such as demonstrated in Europe and North America, with an enhanced need for application to developing countries in the Americas, Africa and Eurasia.

Animals↗
PubMed2006

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.

Animals↗
PubMed2006

Lyssavirus surveillance in bats, Bangladesh.

Lyssavirus surveillance in bats was performed in Bangladesh during 2003 and 2004. No virus isolates were obtained. Three serum samples (all from Pteropus giganteus, n = 127) of 288 total serum samples, obtained from bats in 9 different taxa, neutralized lyssaviruses Aravan and Khujand. The infection occurs in bats in Bangladesh, but virus prevalence appears low.

Animals↗
PubMed2006

Lagos bat virus, South Africa.

Three more isolates of Lagos bat virus were recently recovered from fruit bats in South Africa after an apparent absence of this virus for 13 years. The sporadic occurrence of cases is likely due to inadequate surveillance programs for lyssavirus infections among bat populations in Africa.

Animals↗
PubMed2006

Bat-associated rabies virus in Skunks.

Rabies was undetected in terrestrial wildlife of northern Arizona until 2001, when rabies was diagnosed in 19 rabid skunks in Flagstaff. Laboratory analyses showed causative rabies viruses associated with bats, which indicated cross-species transmission of unprecedented magnitude. Public health infrastructure must be maintained to address emerging zoonotic diseases.

Animals↗
PubMed2006

Vaccination of small Asian mongoose (Herpestes javanicus) against rabies.

Oral vaccination of free-ranging wildlife is a promising technique in rabies control. The small Asian mongoose (Herpestes javanicus) is an important reservoir of rabies on several Caribbean islands, but no vaccines have been evaluated for this species. Captive mongooses were used to test the safety and efficacy of the commercially licensed vaccinia-rabies glycoprotein (V-RG) recombinant vaccine and a newly developed genetically engineered oral rabies virus vaccine (SPBNGA-S). In one study using V-RG, no vaccinated animals developed detectable rabies virus-neutralizing antibodies, and all but one died after experimental challenge with rabies virus. In contrast, all animals given SPBNGA-S demonstrated seroconversion within 7 to 14 days after vaccination and survived rabies virus challenge. On the basis of these preliminary results indicating the greater efficacy of SPBNGA-S vs. V-RG vaccine, additional investigations will be necessary to determine the optimal dose and duration of vaccination, as well as incorporation of the SPBNGA-S vaccine into edible bait.

Administration, Oral↗
PubMed2005

Rabies surveillance in the United States during 2004.

During 2004, 49 states and Puerto Rico reported 6,836 cases of rabies in nonhuman animals and 8 cases in human beings to the CDC, representing a 4.6% decrease from the 7,170 cases in nonhuman animals and 3 cases in human beings reported in 2003. Approximately 92% of the cases were in wildlife, and 8% were in domestic animals (compared with 91% and 9%, respectively, in 2003). Relative contributions by the major animal groups were as follows: 2,564 raccoons (37.5%), 1,856 skunks (27.1%), 1,361 bats (19.9%), 389 foxes (5.7%), 281 cats (4.1%), 115 cattle (1.7%), and 94 dogs (1.4%). Compared with the numbers of reported cases in 2003, cases in 2004 decreased among all groups, except bats, cattle, human beings, and "other domestics" (1 llama). Decreases in numbers of rabid raccoons during 2004 were reported by 12 of the 20 eastern states in which raccoon rabies was enzootic. In the East, Massachusetts reported the first cases of raccoon rabies detected beyond the Cape Cod oral rabies vaccine barrier. Along the western edge of the raccoon rabies epizootic (Ohio in the north and Tennessee in the south), cases of rabies were reported from unexpected new foci beyond oral rabies vaccine zones. On a national level, the number of rabies cases in skunks during 2004 decreased by 12.1% from the number reported in 2003. Once again, Texas reported the greatest number (n = 534) of rabid skunks and the greatest overall state total of rabies cases (913). Texas reported only 1 case of rabies in a dog that was infected with the dog/coyote rabies virus variant and only 22 cases associated with theTexas gray fox rabies virus variant (compared with 61 cases in 2003). The total number of cases of rabies reported nationally in foxes and raccoons declined 14.7% and 2.7%, respectively, during 2004. The 1,361 cases of rabies reported in bats during 2004 represented a 12.3% increase over the previous year's total of 1,212 cases for this group of mammals. Cases of rabies reported in cats, dogs, horses and mules, and sheep and goats decreased 12.5%, 19.7%, 31.8%, and 16.7%, respectively, whereas cases reported in cattle increased 174%. In Puerto Rico, reported cases of rabies in mongooses decreased 4.1% and rabies in dogs (9 cases) remained unchanged from those reported in 2003. Among the 8 cases of rabies in human beings, 1 person from Oklahoma and 3 from Texas died following receipt of infected organs and tissues from an Arkansas donor. In California, a person originally from El Salvador and, in Florida, a person originally from Haiti both died of canine rabies infections acquired outside the United States. In Wisconsin, a teenager contracted rabies from a bat bite and became the first known person to survive rabies despite not having received rabies vaccine prior to symptom onset.

Animals↗
PubMed2005

One-time intradermal DNA vaccination in ear pinnae one year prior to infection protects dogs against rabies virus.

Rabid dog exposures result in > 99% of human rabies deaths worldwide. Ninety-eight percent of these cases occur in developing countries. Thus, the best protection against human rabies would be prevention through adequate vaccination of the reservoir population. The difficulty in re-locating ownerless, freely roaming dogs for booster vaccinations, in addition to poor coverage with inadequate vaccines, suggests that a potentially inexpensive vaccine that elicits long-term protection after a single-dose could improve control of canine rabies in developing countries. One solution could be a DNA vaccine. We have previously determined that dogs vaccinated intradermally (i.d.) in ear pinnae with a rabies DNA vaccine expressing a rabies virus glycoprotein (G) produce high levels of neutralizing antibody that persist for at least 6 months. In the present study, we determined whether a one-time i.d. rabies DNA vaccination into ear pinnae 1 year before viral challenge would protect dogs against rabies virus. The dogs did not receive a booster vaccination. All dogs (100%) vaccinated i.d. in each ear pinna with 50 microg of rabies DNA vaccine, or intramuscular (i.m.) with a commercial canine rabies vaccine survived a lethal dose of rabies virus. In contrast, 100% of dogs vaccinated i.m. with 100 microg of rabies DNA developed rabies, as did 100% of negative control dogs that were vaccinated i.d. in each ear pinna or i.m. with DNA that did not express the rabies virus G. The data suggest that a one-time i.d. rabies DNA vaccination into ear pinnae offers a new approach to facilitate control of endemic canine rabies in developing countries.

Animals↗
PubMed2005

Survival after treatment of rabies with induction of coma.

We report the survival of a 15-year-old girl in whom clinical rabies developed one month after she was bitten by a bat. Treatment included induction of coma while a native immune response matured; rabies vaccine was not administered. The patient was treated with ketamine, midazolam, ribavirin, and amantadine. Probable drug-related toxic effects included hemolysis, pancreatitis, acidosis, and hepatotoxicity. Lumbar puncture after eight days showed an increased level of rabies antibody, and sedation was tapered. Paresis and sensory denervation then resolved. The patient was removed from isolation after 31 days and discharged to her home after 76 days. At nearly five months after her initial hospitalization, she was alert and communicative, but with choreoathetosis, dysarthria, and an unsteady gait.

Adolescent↗
PubMed2005

Efficacy of rabies biologics against new lyssaviruses from Eurasia.

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.

Animals↗