EVALUATION OF ORAL RABIES VACCINATION: PROTECTION AGAINST RABIES IN WILD CAUGHT RACCOONS ( PROCYON LOTOR).

Oral rabies vaccination (ORV) is an effective tactic for wildlife rabies control, particularly for containment of disease spread along epizootic fronts. As part of the continuing evaluation of the ORV program in free-ranging raccoons ( Procyon lotor) in the US, 37 raccoons from ORV-baited areas in Pennsylvania were live-trapped and transferred to captivity to evaluate protection against rabies in animals with varying levels of existing neutralizing antibodies, expressed in international units per milliliter (IU/mL). Among the 37 raccoons at the date of capture, 24% (9/37) of raccoons were seronegative (<0.05 IU/mL), 22% (8/37) were low positive (≥0.05-0.11 IU/mL), 27% (10/37) were medium positive (>0.11-<0.5 IU/mL), and 27% (10/37) were high positive (≥0.5 IU/mL). Raccoons were held for 86-199 d between the date of capture and rabies virus challenge. At challenge, 68% (25/37) raccoons were seronegative. The overall survival rate among challenged animals was 46% (17/37). Based on the antibody titers at the time of challenge, survivorship was 24% (6/25) among seronegative animals, 100% (4/4) among low positive animals, 83% (5/6) among medium positive animals, and 100% (2/2) among high positive animals. Evidence of high-titer seroconversion after vaccination is a good surrogate indicator of rabies survival; however, survival rates of approximately 45% (15/35) were found among raccoons with detectable titers below 0.5 IU/mL. In contrast, any detectable titer at the time of challenge (>3 mo after vaccination) appeared to be a surrogate indicator of survival. Overall, we illustrated significant differences in the value of specific titers as surrogates for survival based on the timing of measurement relative to vaccination. However, survivorship was generally greater than 45% among animals with any detectable titer regardless of the timing of measurement. These findings suggest that lower titer cutoffs may represent a valid approach to measuring immunization coverage within ORV management zones, balancing both sensitivity and specificity for estimating herd immunity.

Oral vaccination of wildlife using a vaccinia-rabies-glycoprotein recombinant virus vaccine (RABORAL V-RG®): a global review.

RABORAL V-RG® 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.

Assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (Urocyon cinereoargenteus).

OBJECTIVE To assess the immunogenicity of thermostable live-attenuated rabies virus (RABV) preserved by vaporization (PBV) and delivered to the duodenal mucosa of a wildlife species targeted for an oral vaccination program. ANIMALS 8 gray foxes (Urocyon cinereoargenteus). PROCEDURES Endoscopy was used to place RABV PBV (n = 3 foxes), alginate-encapsulated RABV PBV (3 foxes), or nonpreserved RABV (2 foxes) vaccine into the duodenum of foxes. Blood samples were collected weekly to monitor the immune response. Saliva samples were collected weekly and tested for virus shedding by use of a conventional reverse-transcriptase PCR assay. Foxes were euthanized 28 days after vaccine administration, and relevant tissues were collected and tested for presence of RABV. RESULTS 2 of 3 foxes that received RABV PBV and 1 of 2 foxes that received nonpreserved RABV seroconverted by day 28. None of the 3 foxes receiving alginate-encapsulated RABV PBV seroconverted. No RABV RNA was detected in saliva at any of the time points, and RABV antigen or RNA was not detected in any of the tissues obtained on day 28. None of the foxes displayed any clinical signs of rabies. CONCLUSIONS AND CLINICAL RELEVANCE Results for this study indicated that a live-attenuated RABV vaccine delivered to the duodenal mucosa can induce an immune response in gray foxes. A safe, potent, thermostable RABV vaccine that could be delivered orally to wildlife or domestic animals would enhance current rabies control and prevention efforts.

Bayesian Spatiotemporal Pattern and Eco-climatological Drivers of Striped Skunk Rabies in the North Central Plains.

Striped skunks are one of the most important terrestrial reservoirs of rabies virus in North America, and yet the prevalence of rabies among this host is only passively monitored and the disease among this host remains largely unmanaged. Oral vaccination campaigns have not efficiently targeted striped skunks, while periodic spillovers of striped skunk variant viruses to other animals, including some domestic animals, are routinely recorded. In this study we evaluated the spatial and spatio-temporal patterns of infection status among striped skunk cases submitted for rabies testing in the North Central Plains of US in a Bayesian hierarchical framework, and also evaluated potential eco-climatological drivers of such patterns. Two Bayesian hierarchical models were fitted to point-referenced striped skunk rabies cases [n = 656 (negative), and n = 310 (positive)] received at a leading rabies diagnostic facility between the years 2007-2013. The first model included only spatial and temporal terms and a second covariate model included additional covariates representing eco-climatic conditions within a 4 km(2) home-range area for striped skunks. The better performing covariate model indicated the presence of significant spatial and temporal trends in the dataset and identified higher amounts of land covered by low-intensity developed areas [Odds ratio (OR) = 3.41; 95% Bayesian Credible Intervals (CrI) = 2.08, 3.85], higher level of patch fragmentation (OR = 1.70; 95% CrI = 1.25, 2.89), and diurnal temperature range (OR = 0.54; 95% CrI = 0.27, 0.91) to be important drivers of striped skunk rabies incidence in the study area. Model validation statistics indicated satisfactory performance for both models; however, the covariate model fared better. The findings of this study are important in the context of rabies management among striped skunks in North America, and the relevance of physical and climatological factors as risk factors for skunk to human rabies transmission and the space-time patterns of striped skunk rabies are discussed.

Rabies vaccine preserved by vaporization is thermostable and immunogenic.

A rabies vaccine that is thermostable over a range of ambient environmental temperatures would be highly advantageous, especially for tropical regions with challenging cold-chain storage where canine rabies remains enzootic resulting in preventable human mortality. Live attenuated rabies virus (RABV) strain ERAG333 (R333E) was preserved by vaporization (PBV) in a dry, stable foam. RABV stabilized using this process remains viable for at least 23 months at 22°C, 15 months at 37°C, and 3h at 80°C. An antigen capture assay revealed RABV PBV inactivated by irradiation contained similar levels of antigen as a commercial vaccine. Viability and antigen capture testing confirmed that the PBV process stabilized RABV with no significant loss in titer or antigen content. Live attenuated and inactivated RABV PBV both effectively induced RABV neutralizing antibodies and protected mice from peripheral RABV challenge. These results demonstrate that PBV is an efficient method for RABV stabilization.

Comparison of anamnestic responses to rabies vaccination in dogs and cats with current and out-of-date vaccination status.

OBJECTIVE: To compare anamnestic antibody responses of dogs and cats with current versus out-of-date vaccination status. DESIGN: Cross-sectional study. ANIMALS: 74 dogs and 33 cats. PROCEDURES: Serum samples were obtained from dogs and cats that had been exposed to rabies and brought to a veterinarian for proactive serologic monitoring or that had been brought to a veterinarian for booster rabies vaccination. Blood samples were collected on the day of initial evaluation (day 0) and then again 5 to 15 days later. On day 0, a rabies vaccine was administered according to label recommendations. Paired serum samples were analyzed for antirabies antibodies by means of a rapid fluorescent focus inhibition test. RESULTS: All animals had an antirabies antibody titer ≥ 0.5 IU/mL 5 to 15 days after booster vaccination. Dogs with an out-of-date vaccination status had a higher median increase in titer, higher median fold increase in titer, and higher median titer following booster vaccination, compared with dogs with current vaccination status. Most (26/33) cats, regardless of rabies vaccination status, had a titer ≥ 12 IU/mL 5 to 15 days after booster vaccination. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dogs with out-of-date vaccination status were not inferior in their antibody response following booster rabies vaccination, compared with dogs with current vaccination status. Findings supported immediate booster vaccination followed by observation for 45 days of dogs and cats with an out-of-date vaccination status that are exposed to rabies, as is the current practice for dogs and cats with current vaccination status.

Rabies surveillance in the United States during 2013.

During 2013, 53 reporting jurisdictions reported 5,865 rabid animals and 3 human rabies cases to the CDC, representing a 4.8% decrease from the 6,162 rabid animals and 1 human case reported in 2012. Ninety-two percent of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 1,898 raccoons (32.4%), 1,598 bats (27.2%), 1,447 skunks (24.7%), 344 foxes (5.9%), 247 cats (4.2%), 86 cattle (1.5%), and 89 dogs (1.5%). One human case was reported from Maryland. The infection was determined to have been transmitted via organ transplantation. Infection in the organ donor, a North Carolina resident, was retrospectively diagnosed. Both the organ donor and the organ recipient were infected with the raccoon rabies virus variant. The third human case, reported by Texas, involved a Guatemalan resident who was detained while crossing the US border. The infection was determined to be caused by a canine rabies virus variant that circulates in Central America.

Rabies death attributed to exposure in Central America with symptom onset in a U.S. detention facility - Texas, 2013.

On June 7, 2013, a man was diagnosed in a Texas hospital with rabies. He had been detained in a U.S. detention facility during his infectious period. To identify persons exposed to rabies who might require rabies postexposure prophylaxis (PEP), CDC and the Texas Department of State Health Services (DSHS) conducted investigations at four detention facilities, one medical clinic, and two hospitals. In all, 25 of 742 persons assessed for rabies exposure were advised to receive PEP. Early diagnosis of rabies is essential for implementation of appropriate hospital infection control measures and for rapid assessment of potential contacts for PEP recommendations.

Tail vaccination in cats: a pilot study.

Feline injection site sarcomas affect 1-10 cats per every 10,000 vaccinated and are associated with high mortality. Radical resection may be curative, but is often associated with prolonged recovery, disfigurement and loss of function when tumors occur at currently recommended injection sites. The objective of this study was to assess alternatives to currently recommended vaccination sites in terms of preference by oncology practitioners, ease of injection and serological responses. Surgical, radiation and medical oncology practitioners were surveyed regarding their preference for vaccination sites based on the ease of tumor resection. A six-point Likert scale was used to measure each cat's behavioral reaction to vaccination when injected subcutaneously in the distal hind limb or the distal tail. Serum collected before and 1-2 months after vaccination was tested for antibody titers against feline panleukopenia virus (FPV) and rabies virus (RV). The preferred sites for vaccination by 94 oncology practitioners were below the stifle (41%) and the tail (30%). There were no significant differences in the cats' behavioral reaction to vaccination below the stifle (n = 31) and in the distal tail (n = 29). Of the cats seronegative for FPV at the time of vaccination, 100% developed protective antibody titers (≥40) against FPV 1-2 months following vaccination. For cats seronegative for RV, all but one cat (tail vaccine) developed acceptable antibody titers (≥0.5 IU/ml) against RV. Tail vaccination was well tolerated and elicited similar serological responses to vaccination in the distal limbs.

Rabies, canine distemper, and canine parvovirus exposure in large carnivore communities from two Zambian ecosystems.

Disease transmission within and among wild and domestic carnivores can have significant impacts on populations, particularly for threatened and endangered species. We used serology to evaluate potential exposure to rabies virus, canine distemper virus (CDV), and canine parvovirus (CPV) for populations of African lions (Panthera leo), African wild dogs (Lycaon pictus), and spotted hyenas (Crocuta crocuta) in Zambia's South Luangwa National Park (SLNP) and Liuwa Plain National Park (LPNP) as well as community lands bordering these areas. In addition, domestic dogs in the study region were evaluated for exposure to CDV and rabies. We provide the first comprehensive disease exposure data for these species in these ecosystems. Twenty-one lions, 20 hyenas, 13 wild dogs, and 38 domestic dogs were sampled across both regions from 2009 to 2011. Laboratory results show 10.5% of domestic dogs, 5.0% of hyenas, and 7.7% of wild dogs sampled were positive for CDV exposure. All lions were negative. Exposure to CPV was 10.0% and 4.8% for hyenas and lions, respectively. All wild dogs were negative, and domestic dogs were not tested due to insufficient serum samples. All species sampled were negative for rabies virus neutralizing antibodies except lions. Forty percent of lions tested positive for rabies virus neutralizing antibodies. Because these lions appeared clinically healthy, this finding is consistent with seroconversion following exposure to rabies antigen. To our knowledge, this finding represents the first ever documentation of rabies virus neutralizing antibodies consistent with rabies exposure that did not lead to clinical disease in free-ranging African lions from this region. With ever-increasing human pressure on these ecosystems, understanding disease transmission dynamics is essential for proper management and conservation of these carnivore species.

Humoral immune response to oral rabies vaccination in raccoon kits: problems and implications.

Little is known about the immunogenicity of RABORAL V-RG(®) (V-RG), an oral rabies vaccine, in raccoon kits (Procyon lotor). The objectives of this study were to characterize the immunogenicity of V-RG in young kits and investigate the potential impact of maternal antibodies on response to vaccination of nursing raccoon kits. Raccoon kits (n=30) were vaccinated at either 3 weeks of age, 7 weeks of age, or assigned as contact controls. Nineteen kits (73%) that were whelped by unvaccinated mothers responded to V-RG exposure (orally or indirect contact) by production of detectable rabies virus neutralizing antibodies (RVNA) while 7 (27%) kits did not respond to V-RG exposure. Four kits were whelped by a mother with high levels of RVNA and all four kits acquired maternal rabies antibodies. At approximately 9 months of age, all kits were inoculated with a killed rabies vaccine, IMRAB3(®). The kits which initially responded to V-RG oral vaccination or contact with vaccinated littermates demonstrated a rapid anamnestic response. In contrast, the V-RG non-responders and those with acquired maternal antibodies exhibited a primary immune response to IMRAB3(®), where RVNA levels were substantially lower on days 5 and 7 than the levels in the animals with an anamnestic response. These findings suggest that the naïve contact kits and the nonresponsive kits most likely remained susceptible to rabies virus infection whereas the ones demonstrating response to V-RG would not have been susceptible to a rabies virus infection.

Prenatal passive transfer of maternal immunity in Asian elephants (Elephas maximus).

Asian (Elephas maximus) and African (Loxodonta africana) elephants exhibit characteristics of endotheliochorial placentation, which is common in carnivore species and is associated with modest maternal to fetal transplacental antibody transfer. However, it remains unknown whether the bulk of passive immune transfer in elephants is achieved prenatally or postnatally through ingestion of colostrum, as has been documented for horses, a species whose medical knowledgebase is often extrapolated for elephants. To address this issue, we took advantage of the fact that many zoo elephants are immunized with tetanus toxoid and/or rabies vaccines as part of their routine health care, allowing a comparison of serum antibody levels against these antigens between dams and neonates. Serum samples were collected from 3 newborn Asian elephant calves at birth (before ingestion of colostrum); 2-4 days after birth; and 2-3 months of age. The findings indicate that the newborns had anti-tetanus toxoid and anti-rabies titers that were equivalent to or higher than the titers of their dams from birth to approximately 3 months of age, suggesting that the majority of maternal-to-fetal transfer is transplacental and higher than expected based on the architecture of the Asian elephant placenta.

Genetic characterization and phylogenetic analysis of skunk-associated rabies viruses in North America with special emphasis on the central plains.

Across North America the skunk acts as a reservoir for several rabies virus variants. Some of these variants are geographically restricted in range as is the case for the California skunk variant and two distinct variants present in Mexico. In contrast the North Central and South Central skunk rabies viruses are dispersed in overlapping ranges over large areas of the Midwestern region of the United States with the former extending into southern parts of the Canadian prairies. Despite this extensive range, there has been only very limited molecular characterization of these two viral variants. This study has examined the genetic diversity of the rabies viruses associated with North American skunks, with particular emphasis on the South Central skunk variant which was found to comprise three distinct geographically restricted groups of viruses that could in some cases be further sub-divided. The phylogenetic relationships of these groups and sub-groups allowed us to infer the likely direction of spread of these variants in some instances. Patterns of amino acid replacement of North American skunk-associated rabies viruses for both the nucleoprotein and glycoprotein products are also examined. These patterns reflect the virus phylogeny but no amino acid residues associated specifically with the skunk host were identified.

Validation of the rapid fluorescent focus inhibition test for rabies virus-neutralizing antibodies in clinical samples.

Monoclonal antibodies are successful biologics in treating a variety of diseases, including the prevention or treatment of viral infections. CL184 is a 1:1 combination of two human monoclonal IgG1 antibodies (CR57 and CR4098) against rabies virus, produced in the PER.C6 human cell line. The two antibodies are developed as replacements of human rabies immune globulin (HRIG) and equine rabies immune globulin (ERIG) in postexposure prophylaxis (PEP). The rapid fluorescent focus inhibition test (RFFIT) is a cell-based virus neutralization assay which is usually performed to determine the biological potency of a vaccine and to measure the levels of protection against rabies in humans and animals. In order to confirm the suitability of this assay as a pharmacodynamic assay, we conducted a validation using both HRIG- and CL184-spiked serum samples and sera from vaccinated donors. The validation results met all analytical acceptance criteria and showed that HRIG and CL184 serum concentrations can be compared. Stability experiments showed that serum samples were stable in various suboptimal conditions but that rabies virus should be handled swiftly once thawed. We concluded that the assay is suitable for the measurement of polyclonal and monoclonal rabies neutralizing antibodies in clinical serum samples.

Contrasting landscape epidemiology of two sympatric rabies virus strains.

Viral strain evolution and disease emergence are influenced by anthropogenic change to the environment. We investigated viral characteristics, host ecology, and landscape features in the rabies-striped skunk disease system of the central Great Plains to determine how these factors interact to influence disease emergence. We amplified portions of the N and G genes of rabies viral RNA from 269 samples extracted from striped skunk brains throughout the distribution of two different rabies strains for which striped skunks were the reservoir. Because the distribution of these two strains overlapped on the landscape and were present in the same host population, we could evaluate how viral properties influenced epidemiological patterns in the area of sympatry. We found that South Central Skunk rabies (SCSK) exhibited intense purifying selection and high infectivity, which are both characteristics of an epizootic virus. Conversely, North Central Skunk rabies (NCSK) exhibited relaxed purifying selection and comparatively lower infectivity, suggesting the presence of an enzootic virus. The host population in the area of sympatry was highly admixed, and skunks among allopatric and sympatric areas had similar effective population sizes. Spatial analysis indicated that landscape features had minimal influence on NCSK movement across the landscape, but those same features were partial barriers to the spread of SCSK. We conclude that NCSK and SCSK have different epidemiological properties that interact differently with both host and landscape features to influence rabies spread in the central Great Plains. We suggest a holistic approach for future studies of emerging infectious diseases that includes studies of viral properties, host characteristics, and spatial features.

Rabies-specific antibodies: measuring surrogates of protection against a fatal disease.

Antibodies play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies, the Fc- and complement-dependent activities of these multifunctional proteins may also be critical in their ability to provide protection against most viruses. Protection against viral pathogens in vivo is complex, and while virus neutralization--the ability of antibody to inactivate virus infectivity, often measured in vitro--is important, it is often only a partial contributor in protection. The rapid fluorescent focus inhibition test (RFFIT) remains the "gold standard" assay to measure rabies virus-neutralizing antibodies. In addition to neutralization, the rabies-specific antigen-binding activity of antibodies may be measured through enzyme-linked immunosorbent assays (ELISAs), as well as other available methods. For any disease, in selecting the appropriate assay(s) to use to assess antibody titers, assay validation and how they are interpreted are important considerations-but for a fatal disease like rabies, they are of paramount importance. The innate limitations of a one-dimensional laboratory test for rabies antibody measurement, as well as the validation of the method of choice, must be carefully considered in the selection of an assay method and for the interpretation of results that might be construed as a surrogate of protection.

Rabies in vaccinated dogs and cats in the United States, 1997-2001.

OBJECTIVE: To identify cases of rabies involving vaccinated dogs and cats in the United States. DESIGN: Retrospective data review. SAMPLE POPULATION: 41 states that reported >or= 1 rabid dog or cat between 1997 and 2001. PROCEDURES: States were contacted to request information on numbers of dogs and cats tested for rabies between 1997 and 2001. For animals with a history of rabies vaccination, respondents were asked to provide details of the vaccination history, age, history of exposure to rabid animals, time between exposure and onset of clinical signs, clinical signs, duration of clinical signs, and whether the animal had died or was euthanatized. RESULTS: 21 of the 41 (51%) states agreed to participate in the study. A total of 264 rabid dogs and 840 rabid cats were identified during the study period. Thirteen (4.9%) rabid dogs and 22 (2.6%) rabid cats had a history of rabies vaccination. Of these, 2 dogs and 3 cats were classified as currently vaccinated. Overall, 6 animals (1 dog and 5 cats) had a history of receiving 2 doses of rabies vaccine in their lifetime, including 2 cats that were classified as currently vaccinated. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that rabies is uncommon in vaccinated dogs and cats but can occur. Veterinarians should include rabies in the differential diagnosis for any dog or cat with clinical signs compatible with rabies regardless of vaccination history. Continued surveillance is imperative to document vaccination failure and identify trends related to vaccination failure.

Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices.

These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention--United States, 1999: recommendations of the Advisory Committee on Immunization Practices. MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients. These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine: one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and 21 or 28). Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.

Rabies virus in raccoons, Ohio, 2004.

In 2004, the raccoon rabies virus variant emerged in Ohio beyond an area where oral rabies vaccine had been distributed to prevent westward spread of this variant. Our genetic investigation indicates that this outbreak may have begun several years before 2004 and may have originated within the vaccination zone.

Rabies surveillance in the United States during 2006.

During 2006, 49 states and Puerto Rico reported 6,940 cases of rabies in animals and 3 cases in humans to the CDC, representing an 8.2% increase from the 6,417 cases in animals and 1 case in a human reported in 2005. Approximately 92% of the cases were in wildlife, and 8% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,615 raccoons (37.7%), 1,692 bats (24.4%), 1,494 skunks (21.5%), 427 foxes (6.2%), 318 cats (4.6%), 82 cattle (1.2%), and 79 dogs (1.1%). Compared with numbers of reported cases in 2005, cases in 2006 increased among all groups except cattle. Increases in numbers of rabid raccoons during 2006 were reported by 11 of the 20 eastern states where raccoon rabies was enzootic, and reported cases increased by 3.2% overall, compared with 2005. On a national level, the number of rabies cases in skunks during 2006 increased by 6.1% from the number reported in 2005. Once again, Texas reported the greatest number (n = 351) of rabid skunks and the greatest overall state total of animal rabies cases (889). No cases of rabies associated with the dog/coyote rabies virus variant were reported. The last identified case of this canine rabies virus variant was identified in March 2004, along the US/Mexico border. With 2006 marking the second year of no apparent transmission of the dog/coyote variant, these findings from surveillance data support the contention that the canine rabies virus variant is no longer in circulation in the United States. Total number of cases of rabies reported nationally in foxes increased 13.6%, compared with 2005. Increases in the number of reported rabid foxes were attributable to greater numbers of foxes reported with the Arctic fox rabies virus variant in Alaska, the Texas gray fox rabies virus variant in Texas, and the raccoon rabies virus variant in Virginia. The 1,692 cases of rabies reported in bats represented a 14.5% increase, compared with numbers reported in 2005, making bats the second most reported rabid animal behind raccoons. Cases of rabies in cats, dogs, horses and mules, and sheep and goats increased 18.2%, 3.9%, 12.8%, and 22.2%, respectively, whereas cases reported in cattle decreased 11.8%. In Puerto Rico, reported cases of rabies in mongooses increased 9.2%, and rabies in domestic animals, presumably attributable to spillover infection from mongooses, increased 20%. Three cases of human rabies were reported from Texas, Indiana, and California during 2006. The cases in Indiana and Texas were attributed to bat rabies virus variants, whereas the case in California was attributed to an exposure to a dog in the Philippines.