Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 105 Records) |
Query Trace: Rupprecht CE[original query] |
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Factors influencing canine rabies vaccination among dog-owning households in Nigeria
Mshelbwala PP , Rupprecht CE , Osinubi MO , Njoga EO , Orum TG , Weese JS , Clark NJ . One Health 2024 18 Rabies perpetuates in Nigeria despite initiatives like the Regional Disease Surveillance System Enhancement Project, with evidence indicating suboptimal canine vaccination rates as a contributing factor. To inform effective planning of mass dog vaccination campaigns, it is crucial to understand the factors associated with variation in canine vaccination rates. We conducted a cross-sectional study in 2022 to understand factors associated with canine vaccination. We used stratified random sampling of the streets and dog-owning households to survey 4162 households from three states and the Federal Capital Territory (FCT). We then built a joint probabilistic model to understand factors associated with dog vaccination and non-vaccination. First, we modelled rabies knowledge as a latent variable indirectly measured with several targeted survey questions. This method allowed a respondent's unobserved understanding of rabies to be estimated using their responses to a collection of survey questions that targeted different aspects of rabies epidemiology and took various possible response distributions (i.e., ordinal, categorical, binary). Second, we modelled factors influencing pet owners' decisions to vaccinate their dogs against rabies and barriers to dog vaccination among dog owners whose dogs were not vaccinated against rabies. Posterior distributions revealed that the probability of dog vaccination was positively associated with the owner's latent knowledge of rabies, civil servant service employment, residence in the FCT, ownership of a single dog, providing care to dogs, and a preference for contemporary treatment following a dog bite. Conversely, non-vaccination was positively associated with private employment, residing in Anambra and Enugu states, owning multiple dogs, allowing dogs to search for leftovers, and a preference for traditional treatment after a dog bite. Cost was the primary barrier against vaccination for dog owners in Anambra and Enugu, while mistrust posed a major challenge for those in the FCT. Owners in areas with veterinary establishments cited cost as a barrier, while those without a veterinary establishment cited access as the primary barrier. Our study underscores the need to enhance rabies knowledge, tailor vaccination campaigns to specific demographics, address financial and access barriers, and combat hesitancy to improve rabies vaccination rates in Nigeria. © 2024 The Authors |
Reemergence of a big brown bat lyssavirus rabies variant in striped skunks in Flagstaff, Arizona, USA, 2021-2023
Gilbert AT , Van Pelt LI , Hastings LA , Gigante CM , Orciari LA , Kelley S , Fitzpatrick K , Condori REC , Li Y , Brunt S , Davis A , Hopken MW , Mankowski CCP , Wallace RM , Rupprecht CE , Chipman RB , Bergman DL . Vector Borne Zoonotic Dis 2024 ![]() ![]() Background: Throughout the Americas, Lyssavirus rabies (RV) perpetuates as multiple variants among bat and mesocarnivore species. Interspecific RV spillover occurs on occasion, but clusters and viral host shifts are rare. The spillover and host shift of a big brown bat (Eptesicus fuscus) RV variant Ef-W1 into mesocarnivores was reported previously on several occasions during 2001-2009 in Flagstaff, Arizona, USA, and controlled through rabies vaccination of target wildlife. During autumn 2021, a new cluster of Ef-W1 RV cases infecting striped skunks (Mephitis mephitis) was detected from United States Department of Agriculture enhanced rabies surveillance in Flagstaff. The number of Ef-W1 RV spillover cases within a short timeframe suggested the potential for transmission between skunks and an emerging host shift. Materials and Methods: Whole and partial RV genomic sequencing was performed to evaluate the phylogenetic relationships of the 2021-2023 Ef-W1 cases infecting striped skunks with earlier outbreaks. Additionally, real-time reverse-transcriptase PCR (rtRT-PCR) was used to opportunistically compare viral RNA loads in brain and salivary gland tissues of naturally infected skunks. Results: Genomic RV sequencing revealed that the origin of the 2021-2023 epizootic of Ef-W1 RV was distinct from the multiple outbreaks detected from 2001-2009. Naturally infected skunks with the Ef-W1 RV showed greater viral RNA loads in the brain, but equivalent viral RNA loads in the mandibular salivary glands, compared to an opportunistic sample of skunks naturally infected with a South-Central skunk RV from northern Colorado, USA. Conclusion: Considering a high risk for onward transmission and spread of the Ef-W1 RV in Flagstaff, public outreach, enhanced rabies surveillance, and control efforts, focused on education, sample characterization, and vaccination, have been ongoing since 2021 to mitigate and prevent the spread and establishment of Ef-W1 RV in mesocarnivores. |
Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices
Rupprecht CE , Briggs D , Brown CM , Franka R , Katz SL , Kerr HD , Lett SM , Levis R , Meltzer MI , Schaffner W , Cieslak PR . MMWR Recomm Rep 2010 59 1-9 This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies (CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57[No. RR-3]). Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. The reduction in doses recommended for PEP was based in part on evidence from rabies virus pathogenesis data, experimental animal work, clinical studies, and epidemiologic surveillance. These studies indicated that 4 vaccine doses in combination with rabies immune globulin (RIG) elicited adequate immune responses and that a fifth dose of vaccine did not contribute to more favorable outcomes. For persons previously unvaccinated with rabies vaccine, the reduced regimen of 4 1-mL doses of HDCV or PCECV should be administered intramuscularly. The first dose of the 4-dose course should be administered as soon as possible after exposure (day 0). Additional doses then should be administered on days 3, 7, and 14 after the first vaccination. ACIP recommendations for the use of RIG remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for pre-exposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell-culture vaccine continue to be highly effective in preventing human rabies. |
Rabies in rodents and lagomorphs in the USA, 2011-20
Hareza DA , Langley R , Ma X , Wallace R , Rupprecht CE . J Wildl Dis 2023 59 (4) 734-742 Rabies is an acute progressive encephalitis caused by infection with rabies viruses, with reservoirs among bats and mesocarnivores, but all mammals are susceptible. Despite its distribution and abundance, cases of rabies are much less common in rodents and lagomorphs. Familiarity with current rabies prevalence data is important for informed decisions on human postexposure prophylaxis after rodent and lagomorph bites. This study is an update of rabies cases reported in rodents and lagomorphs in the US from 2011 to 2020. Rabies reports were collected passively from laboratory testing agencies in the US and Puerto Rico from 2011 to 2020. Descriptive analysis was conducted to determine the percent positivity of rabies cases by species. A total of 401 cases of rabies in rodents and lagomorphs were reported from 2011 to 2020. Most reported cases were in groundhogs (Marmota monax), representing >90% of cases, and the trend closely aligned with rabies in raccoons (Procyon lotor). In any given year, the percent positivity of rabies in rodents and lagomorphs was <2.5%, and the trend of percent positivity from 2011 to 2020 was stable. Groundhog and North American beaver (Castor canadensis) percent positivity was significantly higher than the rest of the rodents and lagomorphs. Most rabies cases occurred during the months of May-September. Documented cases of rabies in rodents and lagomorphs are generally rare, but with variation between species. Groundhogs and North American beavers had rabies percent positivity similar to high-risk species, such as bats and raccoons, and constituted 97% of all rodent and lagomorph positive cases. Since 1993, the trend in rabies cases in groundhogs has significantly declined. These results can be used to help inform public health officials on rodent and lagomorph prevention and control efforts, as well as rabies postexposure prophylaxis. |
Elimination of human rabies in Goa, India through an integrated One Health approach
Gibson AD , Yale G , Corfmat J , Appupillai M , Gigante CM , Lopes M , Betodkar U , Costa NC , Fernandes KA , Mathapati P , Suryawanshi PM , Otter N , Thomas G , Ohal P , Airikkala-Otter I , Lohr F , Rupprecht CE , King A , Sutton D , Deuzeman I , Li Y , Wallace RM , Mani RS , Gongal G , Handel IG , Bronsvoort M , Naik V , Desai S , Mazeri S , Gamble L , Mellanby RJ . Nat Commun 2022 13 (1) 2788 Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India. |
Special issue Innovative Techniques And Approaches In The Control And Prevention Of Rabies Virus
Gilbert AT , Wallace RM , Rupprecht CE . Viruses 2022 14 (5) Rabies is an ancient lethal scourge that has plagued humankind for centuries [...]. |
A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis.
Kim PK , Ahn JS , Kim CM , Seo JM , Keum SJ , Lee HJ , Choo MJ , Kim MS , Lee JY , Maeng KE , Shin JY , Yi KS , Osinubi MOV , Franka R , Greenberg L , Shampur M , Rupprecht CE , Lee SY . PLoS One 2021 16 (9) e0256779 ![]() Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human. |
Bat and Lyssavirus exposure among humans in area that celebrates bat festival, Nigeria, 2010 and 2013
Vora NM , Osinubi MOV , Davis L , Abdurrahman M , Adedire EB , Akpan H , Aman-Oloniyo AF , Audu SW , Blau D , Dankoli RS , Ehimiyein AM , Ellison JA , Gbadegesin YH , Greenberg L , Haberling D , Hutson C , Idris JM , Kia GSN , Lawal M , Matthias SY , Mshelbwala PP , Niezgoda M , Ogunkoya AB , Ogunniyi AO , Okara GC , Olugasa BO , Ossai OP , Oyemakinde A , Person MK , Rupprecht CE , Saliman OA , Sani M , Sanni-Adeniyi OA , Satheshkumar PS , Smith TG , Soleye MO , Wallace RM , Yennan SK , Recuenco S . Emerg Infect Dis 2020 26 (7) 1399-1408 Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions. |
Towards rabies elimination in the Asia-Pacific region: From theory to practice
Rupprecht CE , Abela-Ridder B , Abila R , Amparo AC , Banyard A , Blanton J , Chanachai K , Dallmeier K , de Balogh K , Del Rio Vilas V , Ertl H , Freuling C , Hill R , Houillon G , Jakava-Viljanen M , Kasemsuwan S , Lechenet J , Nel L , Panichabhongse P , Rahman SA , Tantawichien T , Vandeputte J , Viriyabancha W , Vos A , Wallace R , Yale G , Yurachai O , Mueller T . Biologicals 2020 64 83-95 Rabies is a major neglected zoonotic disease and causes a substantial burden in the Asian region. Currently, Pacific Oceania is free of rabies but enzootic areas throughout southeast Asia represent a major risk of disease introduction to this region. On September 25-26, 2019, researchers, government officials and related stakeholders met at an IABS conference in Bangkok, Thailand to engage on the topic of human rabies mediated by dogs. The objective of the meeting was focused upon snowballing efforts towards achieving substantial progress in rabies prevention, control and elimination within Asia by 2030, and thereby to safeguard the Pacific region. Individual sessions focused upon domestic animal, wildlife and human vaccination; the production and evaluation of quality, safety and efficacy of existing rabies biologics; and the future development of new products. Participants reviewed the progress to date in eliminating canine rabies by mass vaccination, described supportive methods to parenteral administration by oral vaccine application, considered updated global and local approaches at human prophylaxis and discussed the considerable challenges ahead. Such opportunities provide continuous engagement on disease management among professionals at a trans-disciplinary level and promote new applied research collaborations in a modern One Health context. |
Safety, immunogenicity, and efficacy of intramuscular and oral delivery of ERA-g333 recombinant rabies virus vaccine to big brown bats (Eptesicus fuscus)
Gilbert AT , Wu X , Jackson FR , Franka R , McCracken GF , Rupprecht CE . J Wildl Dis 2020 56 (3) 620-630 Attenuated strains of rabies virus (RABV) have been used for oral vaccination of wild carnivores in Europe and North America. However, some RABV vaccines caused clinical rabies in target animals. To improve the safety of attenuated RABV as an oral vaccine for field use, strategies using selection of escape mutants under monoclonal antibody neutralization pressure and reverse genetics-defined mutations have been used. We tested the safety, immunogenicity, and efficacy of one RABV construct, ERA-g333, developed with reverse genetics by intramuscular (IM) or oral (PO) routes in big brown bats (Eptesicus fuscus). Twenty-five bats received 5x10(6) mouse intracerebral median lethal doses (MICLD50) of ERA-g333 by IM route, 10 received 5x10(6) MICLD50 of ERA-g333 by PO route, and 22 bats served as unvaccinated controls. Twenty-one days after vaccination, 44 bats were infected by IM route with 10(2.9) MICLD50 of E. fuscus RABV. We report both the immunogenicity and efficacy of ERA-g333 delivered by the IM route; no induction of humoral immunity was detected in bats vaccinated by the PO route. Two subsets of bats vaccinated IM (n=5) and PO (n=3) were not challenged, and none developed clinical rabies from ERA-g333. Scarce reports exist on the evaluation of oral rabies vaccines in insectivorous bats, although the strategy evaluated here may be feasible for future application to these important RABV reservoirs. |
Additional progress in the development and application of a direct, rapid immunohistochemical test for rabies diagnosis
Rupprecht CE , Xiang Z , Servat A , Franka R , Kirby J , Ertl HCJ . Vet Sci 2018 5 (2) Laboratory-based surveillance is fundamental to effective rabies prevention and control. The direct fluorescent antibody (AB) test (FAT) is the gold standard for rabies diagnosis. Recently, additional tests besides the FAT have been developed, such as the direct rapid immunohistochemical test (DRIT). In this study, our objective was to further refine technical aspects of the DRIT using a combination of two monoclonal ABs (MABs), 502 and 802, conduct additional testing among rabies reference laboratories using a diversity of animal species and rabies virus (RV) variants and compare the potential utility of the DRIT for end users via proficiency testing (PT) against the FAT. Considering the ideal molar ratios of biotin to AB in formulation of the DRIT conjugate, 3.9 was found to be superior to 7.4, for detection of RV antigens in the brain of a naturally infected raccoon. Optimization of the DRIT conjugate may also be dependent upon the apparent choice of specific viral antigens for testing, as a gray fox RV variant reacted less strongly than a raccoon RV variant in determining the working dilution of the MAB cocktail. Using the same MABs and protocol, the DRIT was compared to the FAT using more than 800 samples of mammalian brains, representative of more than 25 taxa, including in excess of 250 animal rabies cases from Europe and North America. Sensitivity was determined at 98% (96(-)100%, 95% CI) and specificity was calculated at 95% (92(-)96%, 95% CI). In a comparison among end users, PT of laboratory personnel resulted in values of 77(-)100% sensitivity and 86-100% specificity. Based upon these and previously reported results, the DRIT appears to be a suitable alternative to the FAT for use in lyssavirus diagnosis. |
Cost-effectiveness of dog rabies vaccination programs in East Africa
Borse RH , Atkins CY , Gambhir M , Undurraga EA , Blanton JD , Kahn EB , Dyer JL , Rupprecht CE , Meltzer MI . PLoS Negl Trop Dis 2018 12 (5) e0006490 BACKGROUND: Dog rabies annually causes 24,000-70,000 deaths globally. We built a spreadsheet tool, RabiesEcon, to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa. METHODS: RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission to estimate dog rabies cases averted, the cost per human rabies death averted and cost per year of life gained (YLG) due to dog vaccination programs (US 2015 dollars). We used an East African human population of 1 million (approximately 2/3 living in urban setting, 1/3 rural). We considered, using data from the literature, three vaccination options; no vaccination, annual vaccination of 50% of dogs and 20% of dogs vaccinated semi-annually. We assessed 2 transmission scenarios: low (1.2 dogs infected per infectious dog) and high (1.7 dogs infected). We also examined the impact of annually vaccinating 70% of all dogs (World Health Organization recommendation for dog rabies elimination). RESULTS: Without dog vaccination, over 10 years there would a total of be approximately 44,000-65,000 rabid dogs and 2,100-2,900 human deaths. Annually vaccinating 50% of dogs results in 10-year reductions of 97% and 75% in rabid dogs (low and high transmissions scenarios, respectively), approximately 2,000-1,600 human deaths averted, and an undiscounted cost-effectiveness of $451-$385 per life saved. Semi-annual vaccination of 20% of dogs results in in 10-year reductions of 94% and 78% in rabid dogs, and approximately 2,000-1,900 human deaths averted, and cost $404-$305 per life saved. In the low transmission scenario, vaccinating either 50% or 70% of dogs eliminated dog rabies. Results were most sensitive to dog birth rate and the initial rate of dog-to-dog transmission (Ro). CONCLUSIONS: Dog rabies vaccination programs can control, and potentially eliminate, dog rabies. The frequency and coverage of vaccination programs, along with the level of dog rabies transmission, can affect the cost-effectiveness of such programs. RabiesEcon can aid both the planning and assessment of dog rabies vaccination programs. |
Meeting the urgent need for rabies education in Haiti
Osinubi MOV , Fenelon N , Dyer JL , Franka R , Etheart M , Ali A , Birhane M , Phaimyr Jn Charles N , Destine A , Saleme N , Newman C , Crowdis K , Lutfy C , Rupprecht CE , Wallace RM , Johnson VR . Zoonoses Public Health 2018 65 (6) 662-668 The highest rate of human rabies deaths reported in the Americas is in Haiti, and most of these deaths result from rabies virus infections that occur after individuals are bitten by infected dogs and do not receive rabies post-exposure prophylaxis. One barrier to rabies prevention in Haiti is a lack of knowledge about this disease among healthcare professionals and community members. During the past 4 years, The US Centers for Disease Control and Prevention has collaborated with public health officials and partners to develop, test and refine educational materials aimed at filling this need for rabies education. This report summarizes the use of feedback from knowledge, attitudes and practises surveys; key informant interviews; and focus groups to develop culturally appropriate rabies prevention materials for community members, health officials, clinicians, laboratory professionals, veterinary professionals, government officials and national and local district leaders about ways to prevent rabies. These formative research methods were critically important in ensuring that the materials would be culturally appropriate and would stand the greatest likelihood of motivating Haitians to protect themselves from rabies. Centers for Disease Control and Prevention is using lessons learned in Haiti to develop and test materials in other countries with high rates of canine rabies. |
In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants
Franka R , Carson WC , Ellison JA , Taylor ST , Smith TG , Kuzmina NA , Kuzmin IV , Marissen WE , Rupprecht CE . Trop Med Infect Dis 2017 2 (3) Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42⁻100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19⁻95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally. |
Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus
Kim PK , Keum SJ , Osinubi MOV , Franka R , Shin JY , Park ST , Kim MS , Park MJ , Lee SY , Carson W , Greenberg L , Yu P , Tao X , Lihua W , Tang Q , Liang G , Shampur M , Rupprecht CE , Chang SJ . PLoS One 2017 12 (10) e0186380 Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity. |
Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG(R)): a global review
Maki J , Guiot AL , Aubert M , Brochier B , Cliquet F , Hanlon CA , King R , Oertli EH , Rupprecht CE , Schumacher C , Slate D , Yakobson B , Wohlers A , Lankau EW . Vet Res 2017 48 (1) 57 RABORAL V-RG(R) is an oral rabies vaccine bait that contains an attenuated ("modified-live") recombinant vaccinia virus vector vaccine expressing the rabies virus glycoprotein gene (V-RG). Approximately 250 million doses have been distributed globally since 1987 without any reports of adverse reactions in wildlife or domestic animals since the first licensed recombinant oral rabies vaccine (ORV) was released into the environment to immunize wildlife populations against rabies. V-RG is genetically stable, is not detected in the oral cavity beyond 48 h after ingestion, is not shed by vaccinates into the environment, and has been tested for thermostability under a range of laboratory and field conditions. Safety of V-RG has been evaluated in over 50 vertebrate species, including non-human primates, with no adverse effects observed regardless of route or dose. Immunogenicity and efficacy have been demonstrated under laboratory and field conditions in multiple target species (including fox, raccoon, coyote, skunk, raccoon dog, and jackal). The liquid vaccine is packaged inside edible baits (i.e., RABORAL V-RG, the vaccine-bait product) which are distributed into wildlife habitats for consumption by target species. Field application of RABORAL V-RG has contributed to the elimination of wildlife rabies from three European countries (Belgium, France and Luxembourg) and of the dog/coyote rabies virus variant from the United States of America (USA). An oral rabies vaccination program in west-central Texas has essentially eliminated the gray fox rabies virus variant from Texas with the last case reported in a cow during 2009. A long-term ORV barrier program in the USA using RABORAL V-RG is preventing substantial geographic expansion of the raccoon rabies virus variant. RABORAL V-RG has also been used to control wildlife rabies in Israel for more than a decade. This paper: (1) reviews the development and historical use of RABORAL V-RG; (2) highlights wildlife rabies control programs using the vaccine in multiple species and countries; and (3) discusses current and future challenges faced by programs seeking to control or eliminate wildlife rabies. |
Diversity and phylogenetic relationships among Bartonella strains from Thai bats.
McKee CD , Kosoy MY , Bai Y , Osikowicz LM , Franka R , Gilbert AT , Boonmar S , Rupprecht CE , Peruski LF . PLoS One 2017 12 (7) e0181696 ![]() Bartonellae are phylogenetically diverse, intracellular bacteria commonly found in mammals. Previous studies have demonstrated that bats have a high prevalence and diversity of Bartonella infections globally. Isolates (n = 42) were obtained from five bat species in four provinces of Thailand and analyzed using sequences of the citrate synthase gene (gltA). Sequences clustered into seven distinct genogroups; four of these genogroups displayed similarity with Bartonella spp. sequences from other bats in Southeast Asia, Africa, and Eastern Europe. Thirty of the isolates representing these seven genogroups were further characterized by sequencing four additional loci (ftsZ, nuoG, rpoB, and ITS) to clarify their evolutionary relationships with other Bartonella species and to assess patterns of diversity among strains. Among the seven genogroups, there were differences in the number of sequence variants, ranging from 1-5, and the amount of nucleotide divergence, ranging from 0.035-3.9%. Overall, these seven genogroups meet the criteria for distinction as novel Bartonella species, with sequence divergence among genogroups ranging from 6.4-15.8%. Evidence of intra- and intercontinental phylogenetic relationships and instances of homologous recombination among Bartonella genogroups in related bat species were found in Thai bats. |
A single center, open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults
Recuenco S , Warnock E , Osinubi MOV , Rupprecht CE . Vaccine 2017 35 (34) 4315-4320 In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14-21days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naive and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic. |
A systematic review of human bat rabies virus variant cases: Evaluating unprotected physical contact with claws and teeth in support of accurate risk assessments
Dato VM , Campagnolo ER , Long J , Rupprecht CE . PLoS One 2016 11 (7) e0159443 In the United States and Canada, the most recent documented cases of rabies have been attributed to bat rabies viruses (RABV). We undertook this systematic review in an effort to summarize and enhance understanding of the risk of infection for individuals who have been potentially exposed to a suspect or confirmed rabid bat. United States rabies surveillance summaries documented a total of 41 human bat-rabies virus variant verified non-transplant cases between 1990 and 2015. All cases were fatal. Seven (17.1%) of 41 cases reported a bite from a bat. Ten (24.3%) cases had unprotected physical contact (UPC); these included seven cases that had a bat land or crawl on them (contact with claws) and one case that touched a bat's teeth. Seven (17.1%) cases had probable UPC. Insectivorous bat teeth are extremely sharp and highly efficient for predation upon arthropod prey. Bats also have sharp claws on the end of their thumbs and feet. One of the most common bat RABV variants has an ability to replicate in non-neural cells. Questioning individuals about unprotected contact with bat teeth and claws (including a bat landing or crawling on a person) may help identify additional exposures. |
Estimating the global burden of endemic canine rabies
Hampson K , Coudeville L , Lembo T , Sambo M , Kieffer A , Attlan M , Barrat J , Blanton JD , Briggs DJ , Cleaveland S , Costa P , Freuling CM , Hiby E , Knopf L , Leanes F , Meslin FX , Metlin A , Miranda ME , Muller T , Nel LH , Recuenco S , Rupprecht CE , Schumacher C , Taylor L , Vigilato MA , Zinsstag J , Dushoff J . PLoS Negl Trop Dis 2015 9 (4) e0003709 BACKGROUND: Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). CONCLUSIONS/SIGNIFICANCE: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts. |
The feasibility of rabies virus-vectored immunocontraception in a mouse model
Wu XF , Smith TG , Franka R , Wang M , Carson WC , Rupprecht CE . Trials Vaccinol 2014 3 11-18 Immunocontraceptive vaccines may be an alternative to surgical sterilization. Dual rabies vaccination and dog population management is a helpful tool for rabies prevention. A synthetic gonadotropin-releasing hormone (GnRH) peptide coupled to a carrier protein or T cell epitope is efficacious in inducing immunocontraception in a variety of mammals. However, virus-vectored GnRH recombinant vaccines have advantages over the conjugation method. In a previous in vitro study, we were able to insert a GnRH-coding sequence into the rabies virus (RABV) glycoprotein (G) gene, and the recombinant viruses grew to high titers in cells. Here, we further focused on the RABV G in accepting various copy numbers of GnRH. We demonstrated although RABV G protein with up to 4 copies of GnRH was well expressed, the recombinant virus was recovered only when 2 copies of GnRH (20 amino acids) were incorporated into the G, indicating a possible insertion limit in making a full infectious clone. The investigation provides insight into the utility of RABV G as a carrier for small peptides and its suitability for vaccine studies. Following our previous study, we selected ERAg3p/2 GnRH and tested the construct in mice. The vaccine induced >=80% infertility after three doses without any adjuvant, in live (8 of 10 mice infertility) or inactivated (13 of 14 mice infertility) formulations; while the pregnancy rate was 100% (10 of 10 mice) in the controls. This initial success of immunocontraception in mice is promising, and we are now optimizing the vaccine formulation by using adjuvants and exploring novel delivery methods to minimize the dosage. |
Bat rabies in Guatemala
Ellison JA , Gilbert AT , Recuenco S , Moran D , Alvarez DA , Kuzmina N , Garcia DL , Peruski LF , Mendonca MT , Lindblade KA , Rupprecht CE . PLoS Negl Trop Dis 2014 8 (7) e3070 ![]() 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. |
Rabies in rodents and lagomorphs in the United States, 1995-2010
Fitzpatrick JL , Dyer JL , Blanton JD , Kuzmin IV , Rupprecht CE . J Am Vet Med Assoc 2014 245 (3) 333-7 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. |
Molecular detection of adenoviruses, rhabdoviruses, and paramyxoviruses in bats from Kenya.
Conrardy C , Tao Y , Kuzmin IV , Niezgoda M , Agwanda B , Breiman RF , Anderson LJ , Rupprecht CE , Tong S . Am J Trop Med Hyg 2014 91 (2) 258-266 ![]() 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. |
Community survey of rabies knowledge and exposure to bats in homes - Sumter County, South Carolina, USA
Lankau EW , Cox SW , Ferguson SC , Blanton JD , Tack DM , Petersen BW , Rupprecht CE . Zoonoses Public Health 2014 62 (3) 190-8 Subsequent to a human rabies death in Sumter County, South Carolina, we assessed the frequency of exposures to bats in homes and citizens' rabies knowledge. A self-administered survey was mailed to 6033 randomly selected Sumter County addresses. The survey inquired about household exposures to bats and respondents' rabies knowledge. Surveys were returned by mail for descriptive analysis. Of 597 respondents, 3.5% (21/597) reported having bats living in (2.8% or 17/597) or entering their homes (2.5% or 15/597) during 2010-2012. Respondents generally understood that mammals transmit rabies virus through bites, but were less aware of the severity of rabies illness and modern post-exposure vaccine administration. Respondents were unsure about how to exclude bats from homes and ranked highly both healthcare and non-healthcare entities as preferred resources for obtaining assistance with bat-related concerns. We found potential for human exposures to bats in Sumter County households and gaps in citizen knowledge of rabies and bat exclusion. Public health officials should engage non-healthcare partners in assistance disseminating rabies educational materials and for providing appropriate referral for persons potentially exposed to bats. |
Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies.
Boland TA , McGuone D , Jindal J , Rocha M , Cumming M , Rupprecht CE , Barbosa TF , de Novaes Oliveira R , Chu CJ , Cole AJ , Kotait I , Kuzmina NA , Yager PA , Kuzmin IV , Hedley-Whyte ET , Brown CM , Rosenthal ES . Ann Neurol 2014 75 (1) 155-60 ![]() 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. |
The global availability of rabies immune globulin and rabies vaccine in clinics providing indirect care to travelers
Jentes ES , Blanton JD , Johnson KJ , Petersen BW , Lamias MJ , Robertson K , Franka R , Muhm D , Rupprecht CE , Marano N , Brunette GW . J Travel Med 2014 21 (1) 62-6 We assessed rabies vaccine (RV) and immune globulin (RIG) availability on the local market by querying US Embassy medical staff worldwide. Of 112 responses, 23% were from West, Central, and East Africa. RV and RIG availability varied by region. Possible rabies exposures accounted for 2% of all travelers' health inquiries. |
Variability in seroprevalence of rabies virus neutralizing antibodies and associated factors in a Colorado population of big brown bats (Eptesicus fuscus)
O'Shea TJ , Bowen RA , Stanley TR , Shankar V , Rupprecht CE . PLoS One 2014 9 (1) e86261 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 (17.9%, n = 2,332) than males (9.4%, n = 128; P = 0.007) or volant juveniles (10.2%, n = 738; P<0.0001). 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 6.2 to 26.7% 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 0.0 to 47.1%. 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. |
Protection of non-human primates against rabies with an adenovirus recombinant vaccine
Xiang ZQ , Greenberg L , Ertl HC , Rupprecht CE . Virology 2014 450-451 243-249 Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. |
Costs of raccoon rabies incidents in cattle herds in Hampshire County, West Virginia, and Guernsey County, Ohio
Chipman RB , Cozzens TW , Shwiff SA , Biswas R , Plumley J , O'Quin J , Algeo TP , Rupprecht CE , Slate D . J Am Vet Med Assoc 2013 243 (11) 1561-7 OBJECTIVE: To determine direct and indirect costs associated with raccoon rabies incidents involving cattle herds in Hampshire County, WV, in 2008 and Guernsey County, Ohio, in 2010. DESIGN: Ex post cost analysis. ANIMALS: 1 cattle herd in Hampshire County, WV, in 2008 and 1 cattle herd in Guernsey County, Ohio, in 2010. PROCEDURES: Data were collected for each incident through telephone and email interviews with 16 federal, state, and county agency personnel involved in the case investigations and coordinated responses for rabies in the cattle herds. To characterize the economic impact associated with rabies in the 2 cattle herds, cost analysis was conducted with 7 cost variables (salary and benefits for personnel involved in the response, human postexposure prophylaxis, indirect patient costs, rabies diagnostic testing, cattle carcass disposal, market value of euthanized cattle, and enhanced rabies surveillance). Estimates of direct costs were determined on the basis of agency records and other relevant data obtained from notes and reports made by agency staff at the time of the incident and from a review of the literature. RESULTS: Primary costs included the market value of euthanized cattle ($51,461 in West Virginia; $12,561 in Ohio), human postexposure prophylaxis ($17,959 in West Virginia; $11,297 in Ohio), and salary and benefits for personnel involved in the response ($19,792 in West Virginia; $14,496 in Ohio). CONCLUSIONS AND CLINICAL RELEVANCE:These results should provide a basis for better characterization of the economic impact of wildlife rabies in cattle in the United States. |
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