Showing papers by "Charles E. Rupprecht published in 2014"

Twenty year experience of the oral rabies vaccine SAG2 in wildlife: a global review

Abstract: The SAG2 vaccine (RABIGEN® SAG2) is a modified live attenuated rabies virus vaccine, selected from the SAD Bern strain in a two-step process of amino acid mutation using neutralizing monoclonal antibodies. The strain is genetically stable and does not spread in vivo or induce a persistent infection. Its absence of residual pathogenicity was extensively demonstrated in multiple target and non target species (such as wild carnivores and rodent species), including non-human primates. The efficacy of SAG2 baits was demonstrated according to the EU requirements for the red fox and raccoon dog. The use of safe and potent rabies vaccines such as SAG2 largely contributed to the elimination of rabies in Estonia, France, Italy and Switzerland. Importantly, these countries were declared free of rabies after few years of oral vaccination campaigns with SAG2 baits distributed with an appropriate strategy. The excellent tolerance of the SAG2 vaccine has been confirmed in the field since its first use in 1993. No safety issues have been reported, and in particular no vaccine-induced rabies cases were diagnosed, after the distribution of more than 20 million SAG2 baits in Europe.

Antigenic and genetic characterization of a divergent African virus, Ikoma lyssavirus

Abstract: In 2009, a novel lyssavirus (subsequently named Ikoma lyssavirus, IKOV) was detected in the brain of an African civet (Civettictis civetta) with clinical rabies in the Serengeti National Park of Tanzania. The degree of nucleotide divergence between the genome of IKOV and those of other lyssaviruses predicted antigenic distinction from, and lack of protection provided by, available rabies vaccines. In addition, the index case was considered likely to be an incidental spillover event, and therefore the true reservoir of IKOV remained to be identified. The advent of sensitive molecular techniques has led to a rapid increase in the discovery of novel viruses. Detecting viral sequence alone, however, only allows for prediction of phenotypic characteristics and not their measurement. In the present study we describe the in vitro and in vivo characterization of IKOV, demonstrating that it is (1) pathogenic by peripheral inoculation in an animal model, (2) antigenically distinct from current rabies vaccine strains and (3) poorly neutralized by sera from humans and animals immunized against rabies. In a laboratory mouse model, no protection was elicited by a licensed rabies vaccine. We also investigated the role of bats as reservoirs of IKOV. We found no evidence for infection among 483 individuals of at least 13 bat species sampled across sites in the Serengeti and Southern Kenya.

Safety and immunogenicity of Ontario Rabies Vaccine Bait (ONRAB) in the first us field trial in raccoons (Procyon lotor)

Abstract: In 2011, we conducted a field trial in rural West Virginia, USA to evaluate the safety and immunogenicity of a live, recombinant human adenovirus (AdRG13) rabies virus glycoprotein vaccine (Ontario Rabies Vaccine Bait; ONRAB) in wild raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) We selected ONRAB for evaluation because of its effectiveness in raccoon rabies management in Ontario and Quebec, Canada, and significantly higher antibody prevalence rates in raccoons compared with a recombinant vaccinia-rabies glycoprotein (V-RG) vaccine, Raboral V-RG®, in US–Canada border studies Raccoon rabies was enzootic and oral rabies vaccination (ORV) had never been used in the study area We distributed 79,027 ONRAB baits at 75 baits/km2 mostly by fixed-wing aircraft along parallel flight lines at 750-m intervals Antibody prevalence was significantly higher at 492% (n = 262) in raccoons after ONRAB was distributed than the 96% (n = 395) before ORV This was the highest antibody prevalence

A Conceptual Model for the Impact of Climate Change on Fox Rabies in Alaska, 1980–2010

Abstract: The direct and interactive effects of climate change on host species and infectious disease dynamics are likely to initially manifest\ at latitudinal extremes. As such, Alaska represents a region in the United States for introspection on climate change and disease. Rabies is enzootic among arctic foxes (Vulpes lagopus) throughout the northern polar region. In Alaska, arctic and red foxes (Vulpes vulpes) are reservoirs for rabies, with most domestic animal and wildlife cases reported from northern and western coastal Alaska. Based on passive surveillance, a pronounced seasonal trend in rabid foxes occurs in Alaska, with a peak in winter and spring. This study describes climatic factors that may be associated with reported cyclic rabies occurrence. Based upon probabilistic modelling, a stronger seasonal effect in reported fox rabies cases appears at higher latitudes in Alaska, and rabies in arctic foxes appear disproportionately affected by climatic factors in comparison with red foxes. As temperatures continue a warming trend, a decrease in reported rabid arctic foxes may be expected. The overall epidemiology of rabies in Alaska is likely to shift to increased viral transmission among red foxes as the primary reservoir in the region. Information on fox and lemming demographics, in addition to enhanced rabies surveillance among foxes at finer geographic scales, will be critical to develop more comprehensive models for rabies virus transmission in the region.

Comparison of biotinylated monoclonal and polyclonal antibodies in an evaluation of a direct rapid immunohistochemical test for the routine diagnosis of rabies in southern Africa.

Abstract: The major etiological agent of rabies, rabies virus (RABV), accounts for tens of thousands of human deaths per annum. The majority of these deaths are associated with rabies cycles in dogs in resource-limited countries of Africa and Asia. Although routine rabies diagnosis plays an integral role in disease surveillance and management, the application of the currently recommended direct fluorescent antibody (DFA) test in countries on the African and Asian continents remains quite limited. A novel diagnostic assay, the direct rapid immunohistochemical test (dRIT), has been reported to have a diagnostic sensitivity and specificity equal to that of the DFA test while offering advantages in cost, time and interpretation. Prior studies used the dRIT utilized monoclonal antibody (MAb) cocktails. The objective of this study was to test the hypothesis that a biotinylated polyclonal antibody (PAb) preparation, applied in the dRIT protocol, would yield equal or improved results compared to the use of dRIT with MAbs. We also wanted to compare the PAb dRIT with the DFA test, utilizing the same PAb preparation with a fluorescent label. The PAb dRIT had a diagnostic sensitivity and specificity of 100%, which was shown to be marginally higher than the diagnostic efficacy observed for the PAb DFA test. The classical dRIT, relying on two-biotinylated MAbs, was applied to the same panel of samples and a reduced diagnostic sensitivity (83.50% and 90.78% respectively) was observed. Antigenic typing of the false negative samples indicated all of these to be mongoose RABV variants. Our results provided evidence that a dRIT with alternative antibody preparations, conjugated to a biotin moiety, has a diagnostic efficacy equal to that of a DFA relying on the same antibody and that the antibody preparation should be optimized for virus variants specific to the geographical area of focus.

Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies

Abstract: Eight years after emigrating from Brazil, an otherwise healthy man developed rabies. An exposure prior to immigration was reported. Genetic analysis revealed a canine rabies virus variant found only in the patient's home country, and the patient had not traveled internationally since immigrating to the United States. We describe how epidemiological, phylogenetic, and viral sequencing data provided confirmation that rabies encephalomyelitis may present after a long, multiyear incubation period, a consideration that previously has been hypothesized without the ability to exclude a more recent exposure. Accordingly, rabies should be considered in the diagnosis of any acute encephalitis, myelitis, or encephalomyelitis.

Rabies prevention and management of cats in the context of trap-neuter-vaccinate-release programmes.

Abstract: Impacts  Trap–neuter–vaccinate–return (TNVR) programmes are growing in popularity as alternatives to euthanizing feral cats  Their ability to adequately address disease threats and population growth within managed cat colonies is not clear  Appropriate animal control laws including removal of stray or unwanted cats should be enforced rather than relying on indirect population management strategies (e.g. trap-neuter-vaccinate-release programmes) in order to control feral cat populations and reduce the risk of zoonotic diseases such as rabies.

Bat Rabies in Guatemala

Abstract: 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 related to viruses associated with vampire bats in the eastern states of Mexico and El Salvador. Additionally, 7% of sera collected from 398 bats demonstrated RABV neutralizing antibody. The proportion of seropositive bats varied significantly across trophic guilds, suggestive of complex intraspecific compartmentalization of RABV perpetuation.

Molecular Detection of Adenoviruses, Rhabdoviruses, and Paramyxoviruses in Bats from Kenya

Abstract: 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.

Variability in Seroprevalence of Rabies Virus Neutralizing Antibodies and Associated Factors in a Colorado Population of Big Brown Bats (Eptesicus fuscus)

Abstract: In 2001-2005 we sampled permanently marked big brown bats (Eptesicus fuscus) at summer roosts in buildings at Fort Collins, Colorado, for rabies virus neutralizing antibodies (RVNA) Seroprevalence was higher in adult females (179%, n = 2,332) than males (94%, n = 128; P = 0007) or volant juveniles (102%, n = 738; P<00001) Seroprevalence was lowest in a drought year with local insecticide use and highest in the year with normal conditions, suggesting that environmental stress may suppress RVNA production in big brown bats Seroprevalence also increased with age of bat, and varied from 62 to 267% among adult females at five roosts sampled each year for five years Seroprevalence of adult females at 17 other roosts sampled for 1 to 4 years ranged from 00 to 471% Using logistic regression, the only ranking model in our candidate set of explanatory variables for serological status at first sampling included year, day of season, and a year by day of season interaction that varied with relative drought conditions The presence or absence of antibodies in individual bats showed temporal variability Year alone provided the best model to explain the likelihood of adult female bats showing a transition to seronegative from a previously seropositive state Day of the season was the only competitive model to explain the likelihood of a transition from seronegative to seropositive, which increased as the season progressed We found no rabies viral RNA in oropharyngeal secretions of 261 seropositive bats or in organs of 13 euthanized seropositive bats Survival of seropositive and seronegative bats did not differ The presence of RVNA in serum of bats should not be interpreted as evidence for ongoing rabies infection

Current laboratory techniques in rabies diagnosis, research and prevention

Abstract: Laboratory Techniques in Rabies Diagnosis, Research and Prevention provides a basic understanding of the current trends in rabies. It establishes a new facility for rabies surveillance, vaccine and antibody manufacturing. It offers clarity about the choice of laboratory methods for diagnosis and virus typing, of systems for producing monoclonal and polyclonal antibodies and of methods for testing potency of vaccines and antibodies. The book covers advancements in the classical methods described as well as recent methods and approaches pertaining to rabies diagnosis and research. * Supplies techniques pertaining to rabies diagnosis and research* Provides an update on the conventional and modern vaccines for rabies prevention* Offers updates on the full length antibodies and antibody fragments for post exposure prophylaxis of rabies* Presents technique descriptions that can be used to be compared to industry protocols to identify and establish potential new techniques

Efficacy of a Direct Rapid Immunohistochemical Test (DRIT) For Rabies Detection in Nigeria

Abstract: Rabies is an acute, infectious disease mostly transmitted through bites from an infected animal. Dogs majorly transmit rabies to humans. Human rabies is not curable once clinical signs commence, but can be prevented. The aim of this study was to find an appropriate diagnostic test suitable for use in Nigeria and other developing countries with infrastructural challenges. Thirty dog brain samples collected from dog markets in Kaduna State were analysed using four tests direct fluorescent antibody test (DFA), mouse inoculation test (MIT), Seller’s staining test, the reverse transcriptase-polymerase chain reaction test (RT-PCR) and the direct rapid immunohistochemistry test (dRIT). A total of 15 (50%) of the samples tested positive using DFA, dRIT, RT-PCR and MIT, while the remaining 15 (50%) were negative. The results obtained using these four different tests showed concordance between those that were positive and negative. There was no statistical difference (P > 0.05) among the four tests. An appropriate diagnostic test must be prompt, cheap, sensitive, field-based and reliable. The direct rapid immunohistochemistry test is a new diagnostic test established by the Centers for Disease Control and prevention, Atlanta, Georgia, USA. It does not require sophisticated equipment so it can be used on the field especially in the rural areas where most of the rabies exposures occur. It is also as sensitive as the DFA and the result can be obtained within an hour. In Nigeria and most developing countries, prompt diagnosis play a major role in the prevention and control of rabies. Key words : rabies diagnosis, direct rapid immunohistochemistry test, mouse inoculation test, RT-PCR

Prevention and control of rabies in an age of global travel: a review of travel- and trade-associated rabies events--United States, 1986-2012.

Abstract: Summary Rabies prevention and control efforts have been successful in reducing or eliminating virus circulation regionally through vaccination of specific reservoir populations. A notable example of this success is the elimination of canine rabies virus variant from the United States and many other countries. However, increased international travel and trade can pose risks for rapid, long-distance movements of ill or infected persons or animals. Such travel and trade can result in human exposures to rabies virus during travel or transit and could contribute to the re-introduction of canine rabies variant or transmission of other viral variants among animal host populations. We present a review of travel- and trade-associated rabies events that highlight international public health obligations and collaborative opportunities for rabies prevention and control in an age of global travel. Rabies is a fatal disease that warrants proactive coordination among international public health and travel industry partners (such as travel agents, tour companies and airlines) to protect human lives and to prevent the movement of viral variants among host populations.

Rabies in rodents and lagomorphs in the United States, 1995–2010

Abstract: Objective—To assess the epidemiology of rabies in rodents and lagomorphs and provide information that will enable public health officials to make recommendations regarding postexposure prophylaxis for humans after contact with these animals. Design—Cross-sectional epidemiological analysis. Sample—Rodents and lagomorphs submitted to state laboratories for rabies diagnosis from 1995 through 2010. Procedures—Positive samples were identified by use of direct fluorescent antibody testing, typed by sequencing of viral genes, and quantified via titration in mice or cell culture. Results—737 rabid rodents and lagomorphs were reported from 1995 through 2010, which represented a 62.3% increase, compared with the number of rabid rodents and lagomorphs reported from 1979 through 1994. The most commonly reported rodents or lagomorphs were groundhogs (Marmota monax). All animals submitted to the CDC for additional viral characterization were positive for the raccoon rabies virus variant. Infectious virus or viral RNA was detected in salivary glands or oral cavity tissues in 11 of 13 rabid rodents. Conclusions and Clinical Relevance—The increase in reported rabid rodents, compared with results of previous studies, appeared to be associated with spillover infections from the raccoon rabies epizootic during the first half of the study period. Analysis supported the assumption that rabies remained rare in rodents and lagomorphs. However, transmission of rabies virus via exposure to a rabid rodent or lagomorph may be possible. Given the rarity of rabies in these species, diagnostic testing and consideration of postexposure prophylaxis for humans with potential exposures should be considered on a case-by-case basis. (J Am Vet Med Assoc 2014;245:333–337)

Demonstration of Lyssavirus Antigens by a Direct Rapid Immunohistochemical Test

Abstract: Laboratory-based surveillance is of primary importance in controlling disease and in evaluating the success of disease management strategies. Accurate laboratory diagnosis is critical to effective surveillance and is seriously neglected in most of the developing world. Towards solving this problem, the development of simpler, cost-effective novel diagnostic assays that nevertheless offer sensitivity and specificity equal to gold standard assays will offer much benefit. One such diagnostic assay, the direct rapid immunohistochemical test (DRIT), has been applied in a number of global studies, where it has been shown to have utility equal to that of the gold standard direct fluorescent antibody test (DFA). Overall, the DRIT is easier to interpret and more cost-effective than the DFA, and is likely to find widespread application in the developing world, where dog rabies is most prevalent. With this in mind, we provide a DRIT standard operating procedure (SOP) with reagents and equipment needed to implement this assay for laboratory confirmation of rabies.

Detection of Some Lyssaviruses from Fruigivorous and Insectivorous Bats in Nigeria

Abstract: We report the first evidence of Shimoni bat virus (SHBV) and the detection of Lagos bat virus (LBV)and Mokola virus (MOKV) in bats from Nigeria. In total, 356 bats representing 7 genera and 8 species, collected in 8 locations of northern Nigeria. None of the 356 bat brains screened by direct fluorescent antibody (DFAT) test were positive for lyssavirus antigens. Of the 76 sera screened by modified rapid fluorescent focus inhibition test (RFFIT) 24 (31.6%) had neutralizing activity; 22(29.0%) neutralized LBV, 6(7.9%) neutralized MOKV and 18(23.7%) neutralized SHBV). Lyssaviruses may be circulating in bats or other wild animals in Nigeria.

Forecasting the spread of raccoon rabies using a purpose-specific group decision- making process

Abstract: : The Centers for Disease Control (CDC) and USDA Wildlife Services (WS) have been involved in an oral rabies vaccination (ORV) program for raccoons ( Procyon lotor ) that has slowed the westward spread of raccoon rabies. The objective of this study was to forecast the spread of the disease if an ORV zone was not maintained. A group decision-making process was designed to address the forecasting problem and was implemented using a group of 15 experts and 4 support personnel at a meeting at the USDA National Wildlife Research Center. Ten expansion regions were constructed that described the spread of disease at 2-year intervals. This forecast may provide for more accurate cost-benefit analysis of the ORV barrier. Key words : forecast, human–wildlife conflict, oral rabies vaccination, Procyon lotor , raccoon, rabies, United States, zoonotic disease Worldwide, >55,000 people are estimated to die from rabies each year (World Health Organization 2013). Most of these deaths occur in Africa and Asia where canine rabies virus variants have not been controlled (World Health Organization 2004). However, in the United States, canine rabies virus variant transmission has been eliminated, and wildlife are now the primary reservoir of rabies. In 2010, wildlife accounted for approximately 92% of all reported rabid animals in the United States (Blanton et al. 2011). The raccoon (