21 CFR 640.100 - Immune Globulin (Human).

Code of Federal Regulations, 2012 CFR

2012-04-01

... (Human). The product is defined as a sterile solution containing antibodies derived from human plasma. (b) Source material. The source material of Immune Globulin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in...

21 CFR 640.100 - Immune Globulin (Human).

Code of Federal Regulations, 2011 CFR

2011-04-01

... (Human). The product is defined as a sterile solution containing antibodies derived from human plasma. (b) Source material. The source material of Immune Globulin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in...

21 CFR 640.100 - Immune Globulin (Human).

Code of Federal Regulations, 2013 CFR

2013-04-01

... (Human). The product is defined as a sterile solution containing antibodies derived from human plasma. (b) Source material. The source material of Immune Globulin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in...

21 CFR 640.100 - Immune Globulin (Human).

Code of Federal Regulations, 2014 CFR

2014-04-01

... (Human). The product is defined as a sterile solution containing antibodies derived from human plasma. (b) Source material. The source material of Immune Globulin (Human) shall be plasma recovered from Whole Blood prepared as prescribed in §§ 640.1 through 640.5, or Source Plasma prepared as prescribed in...

[Acute renal pain as an adverse reaction of the rabies immunization].

PubMed

Lalosević, Dusan

2009-01-01

HRIG is the best preparate in rabies prophylaxis, and it's considered that optimal dose is 20 international units per kilogram and must not been reduced or overdosed. HRIG have to be injected infiltrative around bite wounds, and if after that remains a part of the dose, it has to be given in gluteal muscle. Application only in gluteus is vitium artis. At one patient immunized against rabies has occured acute bilateral renal pain and fever at time of immunization against rabies, and because of that vaccination must been stopped after the 3rd dose of vaccine. Patient was a 26-year-old female without significant pre-existing disease, bitten by stray dog. After the start of immunization, because the wrong direction, she received about 2.5 more amount of human rabies immunoglobuline (HRIG) then is recommended on declaration at etiquette of ampoule, and only in gluteus in quantity of 10.5 ml. Glomerulonephritis after rabies vaccination until now was described just once by Singhal et al. in 1981. year. Acute renal pain, after rabies vaccine, which aggravated after repeated vaccine doses in our patient who received overdosed HRIG, may be explained by immunopathological mechanism, rather with formation of circulating immune complexes, their precipitation on the glomerular basement membrane and developing glomerulonephritis. Low weight soluble molecular immune complexes formed when antigen is in excess, as in case after repeated doses of rabies vaccine, circulate and precipitate on glomerular membrane and causes glomerulonephritis. As contribution to this explanation, is that symptoms as renal pain disappeared after interrupting vaccination protocol in our patient.

A single immunization with a recombinant canine adenovirus expressing the rabies virus G protein confers protective immunity against rabies in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Jianwei; Faber, Milosz; Papaneri, Amy

2006-12-20

Rabies vaccines based on live attenuated rabies viruses or recombinant pox viruses expressing the rabies virus (RV) glycoprotein (G) hold the greatest promise of safety and efficacy, particularly for oral immunization of wildlife. However, while these vaccines induce protective immunity in foxes, they are less effective in other animals, and safety concerns have been raised for some of these vaccines. Because canine adenovirus 2 (CAV2) is licensed for use as a live vaccine for dogs and has an excellent efficacy and safety record, we used this virus as an expression vector for the RVG. The recombinant CAV2-RV G produces virusmore » titers similar to those produced by wild-type CAV2, indicating that the RVG gene does not affect virus replication. Comparison of RVG expressed by CAV2-RV G with that of vaccinia-RV G recombinant virus (V-RG) revealed similar amounts of RV G on the cell surface. A single intramuscular or intranasal immunization of mice with CAV2-RVG induced protective immunity in a dose-dependent manner, with no clinical signs or discomfort from the virus infection regardless of the route of administration or the amount of virus.« less

21 CFR 640.102 - Manufacture of Immune Globulin (Human).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Manufacture of Immune Globulin (Human). 640.102 Section 640.102 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...) Microbial contamination. Low temperatures or aseptic techniques shall be used to minimize contamination by...

Assessment of 200 pediatric patients exposed to rabies risk.

PubMed

Koksal, Ali Osman; Yilmaz, Aslihan Arasli; Ozdemir, Osman; Cicek, Seyma; Yilmaz, Serife

2015-10-01

Rabies is still an important health problem particularly in underdeveloped or developing countries. In this study, the aim was to investigate demographic characteristics and vaccination schedules of cases suspected of having rabies and admitted to the Pediatric Emergency Clinic of our hospital, which serves as one of the Rabies Vaccination Centers in our province. In our study, medical records of 200 patients admitted to the Pediatric Emergency Clinic with suspicion of risk of contact with the rabies virus were retrospectively analyzed. Of those 200 cases, rabies risk was found to be greater in the 5-9 year old group. There was a history of having been bitten by dogs in 68.5% of cases, cat scratch in 29.5%, and contact with other animals in 2%. While 76% of animals were stray animals, only 11% of them had an owner and had been vaccinated, and were under supervision. Rabies vaccination only had been administered to 42.5% of admitted patients, tetanus and rabies vaccination to 51.5%, tetanus; rabies vaccination and human rabies immune globulin were administered to 6%. Post-exposure prophylaxis was found to have been given as recommended to 83.5% of cases. Rabies remains an important public health problem in developing countries Like ours. We consider that public awareness should be raised; local authorities should devote efforts to control stray animals and supervise such services, and updated guidance and training should be provided to the concerned health staff to reduce the risk of rabies.

Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

PubMed

da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

2017-04-15

The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received

Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens

PubMed Central

da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping

2017-01-01

ABSTRACT The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that

Development and characterization of novel chimeric monoclonal antibodies for broad spectrum neutralization of rabies virus.

PubMed

Kim, Pan Kyeom; Keum, Sun Ju; Osinubi, Modupe O V; Franka, Richard; Shin, Ji Young; Park, Sang Tae; Kim, Man Su; Park, Mi Jung; Lee, Soo Young; Carson, William; Greenberg, Lauren; Yu, Pengcheng; Tao, Xiaoyan; Lihua, Wang; Tang, Qing; Liang, Guodong; Shampur, Madhusdana; Rupprecht, Charles E; Chang, Shin Jae

2017-01-01

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.

Brief Report: Dysregulated Immune System in Children with Autism: Beneficial Effects of Intravenous Immune Globulin on Autistic Characteristics.

ERIC Educational Resources Information Center

Gupta, Sudhir; And Others

1996-01-01

Children (ages 3-12) with autism (n=25) were given intravenous immune globulin (IVIG) treatments at 4-week intervals for at least 6 months. Marked abnormality of immune parameters was observed in subjects, compared to age-matched controls. IVIG treatment resulted in improved eye contact, speech, behavior, echolalia, and other autistic features.…

Rabies Vaccine Hesitancy and Deaths Among Pregnant and Breastfeeding Women - Vietnam, 2015-2016.

PubMed

Nguyen, Huong T T; Tran, Cuc H; Dang, Anh D; Tran, Huong G T; Vu, Thiem D; Pham, Thach N; Nguyen, Hoang V; Nguyen, Anh N K; Pieracci, Emily G; Tran, Duong N

2018-03-02

Human rabies deaths are preventable through prompt administration of postexposure prophylaxis (PEP) with rabies immune globulin and rabies vaccine after exposure to a rabid animal (1); there are no known contraindications to receiving PEP (1,2). Despite widespread availability of PEP in Vietnam, in 2015 the Ministry of Health (MoH) received reports of pregnant and breastfeeding women with clinically diagnosed rabies. MoH investigated factors associated with these rabies cases. MoH found that, during 2015-2016, among 169 cases reported in Vietnam, two probable cases of rabies were reported in breastfeeding mothers and four in pregnant women, all of whom had been bitten by dogs. All six patients died. Three of the four pregnant women had cesarean deliveries. One of the three newborns died from complications believed to be unrelated to rabies; the fourth pregnant woman contracted rabies too early in pregnancy for the fetus to be viable. Two of the patients sought care from a medical provider or traditional healer; however, none sought PEP after being bitten. In each case, families reported the patient's fear of risk to the fetus or breastfed child as the primary barrier to receiving PEP. These findings highlight the need for public health messaging about the safety and effectiveness of PEP in preventing rabies among all persons with exposures, including pregnant and breastfeeding women.

Achieving Population-Level Immunity to Rabies in Free-Roaming Dogs in Africa and Asia

PubMed Central

Morters, Michelle K.; McKinley, Trevelyan J.; Horton, Daniel L.; Cleaveland, Sarah; Schoeman, Johan P.; Restif, Olivier; Whay, Helen R.; Goddard, Amelia; Fooks, Anthony R.; Damriyasa, I. Made; Wood, James L. N.

2014-01-01

Canine rabies can be effectively controlled by vaccination with readily available, high-quality vaccines. These vaccines should provide protection from challenge in healthy dogs, for the claimed period, for duration of immunity, which is often two or three years. It has been suggested that, in free-roaming dog populations where rabies is endemic, vaccine-induced protection may be compromised by immuno-suppression through malnutrition, infection and other stressors. This may reduce the proportion of dogs that seroconvert to the vaccine during vaccination campaigns and the duration of immunity of those dogs that seroconvert. Vaccination coverage may also be limited through insufficient vaccine delivery during vaccination campaigns and the loss of vaccinated individuals from populations through demographic processes. This is the first longitudinal study to evaluate temporal variations in rabies vaccine-induced serological responses, and factors associated with these variations, at the individual level in previously unvaccinated free-roaming dog populations. Individual-level serological and health-based data were collected from three cohorts of dogs in regions where rabies is endemic, one in South Africa and two in Indonesia. We found that the vast majority of dogs seroconverted to the vaccine; however, there was considerable variation in titres, partly attributable to illness and lactation at the time of vaccination. Furthermore, >70% of the dogs were vaccinated through community engagement and door-to-door vaccine delivery, even in Indonesia where the majority of the dogs needed to be caught by net on successive occasions for repeat blood sampling and vaccination. This demonstrates the feasibility of achieving population-level immunity in free-roaming dog populations in rabies-endemic regions. However, attrition of immune individuals through demographic processes and waning immunity necessitates repeat vaccination of populations within at least two years to ensure

[Effect of specific antibodies on active immunity development in those inoculated with an antirabies vaccine].

PubMed

Kravchenko, A T; Latypova, R G; Morpgova, V M; Movsesiants, A A

1980-11-01

The study of the effect of gamma globulin introduced in different doses (0.5 and 0.25 ml/mg) in combination with Fermi rabies vaccine (observations on humans were made) and with cerebral rabies vaccine inactivated by UV irradiation (in animal experiments) demonstrated that the injection of the higher doses of gamma globulin resulted in lower geometrical mean of antibody titers. Therefore, in combined administration of rabies vaccine and gamma globulin for postexposure rabies prevention it is advisable to reduce the dose of gamma globulin by one-half.

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

PubMed

Rupprecht, Charles E; Willoughby, Rodney; Slate, Dennis

2006-12-01

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

Experimental immunization of cats with a recombinant rabies-canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies.

PubMed

Hu, R L; Liu, Y; Zhang, S F; Zhang, F; Fooks, A R

2007-07-20

During the past decade, human rabies caused by cats has ranked the second highest in China. Several recombinant rabies vaccines have been developed for dogs. However, seldom have these vaccines been assessed or used in cats. In this trial, we report the experimental immunization of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Delta-RGP, in cats. Thirty cats were inoculated with the recombinant vaccine intramuscularly, orally and intranasally, respectively. Safety and efficacy studies were undertaken using the fluorescent antibody virus neutralization (FAVN) test and evaluated. Results showed that this recombinant vaccine is safe for cats as demonstrated by the three different routes of administration. The vaccine stimulated an efficient humoral response in the vaccinated cats when 10(8.5)PFU/ml of the recombinant vaccine was injected intramuscularly in a single dose. The neutralizing antibody level increased above 0.5IU/ml at 4 weeks after the vaccination. The mean antibody level ranged from 0.96+/-0.26 to 4.47+/-1.57IU/ml among individuals, and the antibody levels were elicited for at least 12 months. After this period, the immunized cats survived the challenge of CVS-24 and an obvious anemnestic and protective immune response was stimulated after the challenge. The immune response occurred later than the inactivated vaccine and the overall antibody level in the vaccinated cats was lower, but it was sufficient to confer protection of cats against infection. This demonstrated that a single, intramuscular dose of CAV-2-E3Delta-RGP stimulated a long-lasting protective immune response in cats and suggested that CAV-2-E3Delta-RGP could be considered as a potential rabies vaccine candidate for cats.

Inferior rabies vaccine quality and low immunization coverage in dogs (Canis familiaris) in China

PubMed Central

HU, R. L.; FOOKS, A. R.; ZHANG, S. F.; LIU, Y.; ZHANG, F.

2008-01-01

SUMMARY Human rabies in China continues to increase exponentially, largely due to an inadequate veterinary infrastructure and poor vaccine coverage of naive dogs. We performed an epidemiological survey of rabies both in humans and animals, examined vaccine quality for animal use, evaluated the vaccination coverage in dogs, and checked the dog samples for the presence of rabies virus. The lack of surveillance in dog rabies, together with the low immunization coverage (up to 2·8% in rural areas) and the high percentage of rabies virus prevalence (up to 6·4%) in dogs, suggests that the dog population is a continual threat for rabies transmission from dogs to humans in China. Results also indicated that the quality of rabies vaccines for animal use did not satisfy all of the requirements for an efficacious vaccine capable of fully eliminating rabies. These data suggest that the factors noted above are highly correlated with the high incidence of human rabies in China. PMID:18177524

Trends in anti-D immune globulin for childhood immune thrombocytopenia: Usage, response rates, and adverse effects

PubMed Central

Long, Michelle; Kalish, Leslie A.; Neufeld, Ellis J.; Grace, Rachael F.

2013-01-01

In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years. PMID:22190130

Rabies post-exposure prophylaxis for a child with severe allergic reaction to rabies vaccine.

PubMed

Fang, Yuan; Liu, Man-Qing; Chen, Li; Zhu, Zheng-Gang; Zhu, Ze-Rong; Hu, Quan

2016-07-02

Most adverse events (AEs) during the immunization of rabies vaccine were slight, there was little information about the allergic reaction induced by rabies vaccines and had to stop or change the immunization program. Here, we reported a case that a 4-year-old boy had category II exposure to rabies and showed severe allergic reaction after being immunized with lyophilized purified vero cell rabies vaccine (PVRV). After the anti-allergy therapy with hormone, allergy testing indicated medium allergy to egg and milk, and implied the allergic reaction most likely associated with animal-sourced gelatin in lyophilized PVRV. Therefore, a new immunization program with liquid PVRV without stabilizers under the Zegrab regimen (2-1-1) was enrolled at day 7 post-exposure. Although lower than the levels of normal <5 -year population at day 14 and 45, the neutralizing antibody (RVNA) titers of this boy showed adequate protective antibody (≥ 0.5 IU/ml), even after 365 d post-immunization. This study not only highlighted the importance of several types of rabies vaccines co-existing in the market, but also implied the necessary for doctors to fully understand the allergies history of patients prior to immunize rabies vaccine.

Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination.

PubMed

Li, Yingying; Zhou, Ming; Luo, Zhaochen; Zhang, Yachun; Cui, Min; Chen, Huanchun; Fu, Zhen F; Zhao, Ling

2017-04-01

Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. There is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination. In this study, a recombinant rabies virus (RABV) that expressed murine interleukin-7 (IL-7), referred to here as rLBNSE-IL-7, was constructed, and its effectiveness was evaluated in a mouse model. rLBNSE-IL-7 induced higher rates of T follicular helper (Tfh) cells and germinal center (GC) B cells from draining lymph nodes (LNs) than the parent virus rLBNSE. Interestingly, rLBNSE-IL-7 improved the percentages of long-lived memory B cells (Bmem) in the draining LNs and plasma cells (PCs) in the bone marrow (BM) for up to 360 days postimmunization (dpi). As a result of the presence of the long-lived PCs, it also generated prolonged virus-neutralizing antibodies (VNAs), resulting in better protection against a lethal challenge than that seen with rLBNSE. Moreover, consistent with the increased numbers of Bmem and PCs after a boost with rLBNSE, rLBNSE-IL-7-immunized mice promptly produced a more potent secondary anti-RABV neutralizing antibody response than rLBNSE-immunized mice. Overall, our data suggest that overexpressing IL-7 improved the induction of long-lasting primary and secondary antibody responses post-RABV immunization. IMPORTANCE Extending humoral immune responses using adjuvants is an important method to develop long-lasting and efficient vaccines against rabies. However, little information is currently available regarding prolonged immunological

78 FR 79469 - Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

...] Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop AGENCY: Food and... Infusions.'' The purpose of the public workshop is to identify and discuss potential risk mitigation...) (Human) infusion. Complications of hemolysis include severe anemia requiring transfusion, renal failure...

Humoral immune response in dogs and cats vaccinated against rabies in southeastern Brazil

PubMed Central

2013-01-01

Background Brazil holds annual nationwide public campaigns to vaccinate dogs and cats against rabies. The presence of rabies antibodies in these animals, which are among the main transmitters of rabies to humans, is a good indicator that they are immunized and protected. Methods In the present study we analyzed 834 serum samples from dogs and cats from the Southeast of Brazil (Presidente Prudente and Dracena cities), 12 months after the 2009 vaccination campaign. We used the technique known as rapid fluorescent focus inhibition test (RFFIT) and considered reactant those sera with values higher 0.5 IU/mL. Results and discussion Reactant sample results in Presidente Prudente were 153 (51.0%) for dogs and 59 (32.6%) for cats, and in Dracena 110 (52.1%) for dogs and 71 (50.0%) for cats. We discussed vaccine coverage of animals involved in this experiment, and observed low titers < 0.5 IU/mL, especially in cats from Presidente Prudente. Conclusion According to the results presented in our experiment, we suggest that titers below 0.5 IU/mL are worrisome and that, for multiple reasons, animals should be immunized against rabies in the period between public vaccination campaigns. Hence, the desired vaccine coverage was not accomplished, especially among cats from Presidente Prudente. PMID:23899101

Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus.

PubMed

Faber, Milosz; Li, Jianwei; Kean, Rhonda B; Hooper, D Craig; Alugupalli, Kishore R; Dietzschold, Bernhard

2009-07-07

Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.

Three-year duration of immunity in cats vaccinated with a canarypox-vectored recombinant rabies virus vaccine.

PubMed

Jas, D; Coupier, C; Toulemonde, C Edlund; Guigal, P-M; Poulet, H

2012-11-19

Despite the availability of efficacious vaccines for animals and humans, rabies is still a major zoonosis. Prevention of rabies in dogs and cats is key for reducing the risk of transmission of this deadly disease to humans. Most veterinary vaccines are adjuvanted inactivated vaccines and have been shown to provide one to four-year duration of immunity. In response to debates about the safety of adjuvanted vaccines in cats, a non-adjuvanted feline rabies vaccine with one-year duration of immunity claim was specifically developed using the canarypoxvirus vector technology. The objective of this study was to validate a vaccination program based on primary vaccination, revaccination one year later and boosters every three years. Seronegative cats were vaccinated at 12 weeks of age and received a booster vaccination one year later. This vaccination regimen induced a strong and sustained antibody response, and all vaccinated animals were protected against virulent rabies challenge carried out 3 years after vaccination. These results validated 3-year duration of immunity after a complete basic vaccination program consisting in primary vaccination from 12 weeks of age followed by revaccination one year later with a non-adjuvanted canarypox-vectored vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

Developments in rabies vaccines.

PubMed

Hicks, D J; Fooks, A R; Johnson, N

2012-09-01

The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection. © 2012 Crown copyright. Clinical and Experimental Immunology © 2012 British Society for Immunology.

High dose Intravenous Anti-D Immune Globulin is More Effective and Safe in Indian Paediatric Patients of Immune Thrombocytopenic Purpura

PubMed Central

Jena, Rabindra Kumar; Swain, Kali Prasanna

2016-01-01

Introduction Immune Thrombocytopenia (ITP) is characterised by an autoimmune antibody-mediated destruction of platelets and impaired platelet production. Few controlled trials exist to guide management of patients with ITP in Indian scenario for which patients require an individualized approach. Anti-D (Rho (D) immune globulin) at a higher dose can prove to be a cost effective and safe alternative for Indian patients with ITP. Aim To compare the safety and efficacy of higher dose (75μg/kg) intravenous Anti-D immune globulin against the standard dose of 50μg/kg for the management of ITP in Indian patients. Materials and Methods One hundred and sixty four children with newly diagnosed ITP between 4-14 years were randomly selected for inclusion and were treated with 50μg/kg (standard dose) or 75μg /kg (higher dose) of Anti-D to compare the efficacy and safety of higher dose intravenous anti-D immune globulin. Efficacy of Anti-D was measured in terms of rate of response and median time to response for increase in platelet counts. Any adverse event was noted. A decrease in haemoglobin concentration suggested accompanying haemolysis. Results Seventy one out of 84 patients treated with Anti-D at 75μg/kg produced complete response (85%) with median time of response being 2.5 days. On the contrary, 45 patients (70%) patients treated with 50μg/kg had complete response. However, there was no significant increase in haemolysis with higher dose. A significant correlation was found between dose and peak increase in platelet count measured at 7th day following administration. However, there was no relationship between the decrease in haemoglobin and the dose given, or between the increase in platelet count and fall in haemoglobin. Conclusion A 75μg/kg dose of Anti-D is more effective with acceptable side effect in comparison to 50μg dose for treatment of newly diagnosed Indian patients of ITP. PMID:28208873

Safety, tolerability and efficacy of intradermal rabies immunization with DebioJect™.

PubMed

Vescovo, Paul; Rettby, Nils; Ramaniraka, Nirinarilala; Liberman, Julie; Hart, Karen; Cachemaille, Astrid; Piveteau, Laurent-Dominique; Zanoni, Reto; Bart, Pierre-Alexandre; Pantaleo, Giuseppe

2017-03-27

In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Infant botulism and indications for administration of botulism immune globulin.

PubMed

Pifko, Elysha; Price, Amanda; Sterner, Sarah

2014-02-01

Infant botulism is caused by the ingestion of Clostridium botulinum spores and leads to a life-threatening descending motor weakness and flaccid paralysis in infant children. This disease presents with symptoms such as constipation, weakness, and hypotonia and can lead to respiratory failure. Botulism immune globulin (BIG) was created to treat this deadly disease and functions by neutralizing all systemically circulating botulism toxins. It is indicated in children with clinically diagnosed infant botulism, before diagnostic confirmation, and has been shown to lead to a significant reduction in intensive care unit and hospital stay for these patients. This review article discusses the epidemiology, clinical presentation, history of BIG, and indications for administration of BIG.

[Rabies in France: an update].

PubMed

Jaussaud, R; Strady, C; Liénard, M; Strady, A

2000-08-01

In 1996, rabies was responsible for more than 35,000 deaths worldwide. Three cases of human rabies that had been contracted abroad were diagnosed in France during the same year. Cases notified in 1997 followed exposure outside the country. Fox, bat, and dog rabies are reviewed on the basis of the latest epidemiological data obtained in France. Two cases of fox rabies diagnosed in 1998 occurred at the border between France and Germany, thus preventing five French departments bordering Germany from being officially declared rabies-free in 1999. The campaigns for oral immunization of foxes that are led since 1986 are responsible for the decrease in rabies incidence. Though not well known, bat rabies is a reality in France, involving either European virus strains (five cases all over the country) or African virus strains that are carried along by imported tropical bats. Dogs rabies is also today an imported disease. The decrease in risk for rabies has resulted from the conjunction of multiple efforts: extensive programs aimed at oral vaccination of foxes in France and its neighboring countries, efficient epidemiological survey, sanitary controls at borders, ban on importing tropical bats. Furthermore, recommendations for preventive pre-exposure immunization have recently been changed, leading to modifications of the French licensing form.

Detection of rabies-specific antigens by egg yolk antibody (IgY) to the recombinant rabies virus proteins produced in Escherichia coli.

PubMed

Motoi, Yurie; Inoue, Satoshi; Hatta, Hajime; Sato, Kozue; Morimoto, Kinjiro; Yamada, Akio

2005-04-01

We obtained rabies-specific egg yolk antibodies (IgY) by immunizing hens with recombinant His-tagged nucleoprotein and phosphoprotein (rN, rP) of the rabies virus (CVS-11 strain) expressed in Escherichia coli. The anti-rN and rP IgY were shown to bind specifically to the respective proteins of the CVS-11 strain of rabies virus by Western blotting, immune fluorescent assay and immunohistochemistry, indicating that IgY to rabies recombinant proteins could serve as a reagent for diagnosis of rabies virus infection.

Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.

PubMed

Zhou, Ming; Wang, Lei; Zhou, Songqin; Wang, Zhao; Ruan, Juncheng; Tang, Lijun; Jia, Ziming; Cui, Min; Zhao, Ling; Fu, Zhen F

2015-11-17

Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.

Protective immune response of oral rabies vaccine in stray dogs, corsacs and steppe wolves after a single immunization.

PubMed

Zhugunissov, K; Bulatov, Ye; Taranov, D; Yershebulov, Z; Koshemetov, Zh; Abduraimov, Ye; Kondibayeva, Zh; Samoltyrova, A; Amanova, Zh; Khairullin, B; Sansyzbay, A

2017-11-01

In this study the safety and protective immunity of an oral rabies vaccine, based on the live, modified rabies virus strain VRC-RZ2, was examined in stray dogs (Canis Sp.), corsacs (Vulpes corsac) and steppe wolves (Canis lupus campestris). In the safety group (dogs, n=6; corsacs, n=3; wolves, n=3) which was vaccinated with a 10-times field dose/animal, no animals showed any signs of disease or changes in behavior or appetite during the period of clinical observation, similar to the animals in the negative control group. Saliva samples taken from animals prior and post (5 th and 10 th days) vaccination failed to demonstrate rabies virus antigen. Observations of immunogenicity in vaccinated carnivores (dogs, corsacs and wolves) during a 180 day period showed the titers of virus neutralizing antibodies (VNA) in the blood sera of vaccinated dogs to be within 0.59-1.37 IU/mL. On 14 days post vaccination (dpv), all the wild carnivores had detectable levels of neutralizing antibodies, with mean titers ranging from 0.50 ± 0.07 IU/mL (for wolves) to 0.59 ± 0.10 IU/mL (for corsacs). Weeks after vaccination, all the vaccinated wolves and corsacs had higher levels of neutralizing antibodies: 0.70 ± 0.10 - 0.71 ± 0.08 IU/mL at 30 dpv, 1.06 ± 0.08 - 1.28 ± 0.21 IU/mL at 60 dpv and 0.41 ± 0.09 - 047 ± 0.06 at 180 dpv. The highest level of VNA (˃1.0 IU/ml) was detected at 60 dpv, in all vaccinated animals. After challenge all vaccinated dogs remained healthy for 180 days. Control animals (unvaccinated dogs) developed symptoms of rabies on day 6 post administration of a virulent virus and died of rabies on days 11-13. Of note, the VNA titers in all the wild carnivores (corsacs and wolves) immunized with VRC-RZ2 were higher than 0.5 IU/ml (0.59 ± 0.11 IU/ml), even as early as 14 days post vaccination. These, presumably protective, titers of antibodies to rabies virus were present in the dogs and wild carnivores examined in this study for at

[Rabies].

PubMed

Ribadeau-Dumas, Florence; Dacheux, Laurent; Bourhy, Hervé

2013-01-01

Rabies virus, a neurotropic lyssavirus responsible for unavoidable fatal encephalitis, is transmitted by saliva of infected animals through bite, scratch or licking of broken skin or a mucous membrane. Infection can be prevented by timely prevention (wash for several minutes, antisepsis and vaccination completed by antirabies immunoglobulins [Ig] according to the severity of exposure). The 55,000 human deaths estimated annually worldwide result mainly from uncontrolled canine rabies in enzootic countries (particularly in Africa and in Asia), attributable to a lack of resources or interest for this disease. Bat rabies, henceforth first cause of human's rabies in many countries in America, affects a very small number of individuals but seems more difficult to control. Shortened vaccine protocols, rationalized use of Ig and development of products of substitution should enhance access of exposed patients to prevention. Finally, research on the biological cycle, the pathogeny and on escape of virus-induced mechanisms from the immune system should continue to pave the way for presently unknown treatments of clinical rabies. © 2013 médecine/sciences – Inserm / SRMS.

Kinetics of rabies antibodies as a strategy for canine active immunization

PubMed Central

2014-01-01

Background Rabies, a zoonosis found throughout the globe, is caused by a virus of the Lyssavirus genus. The disease is transmitted to humans through the inoculation of the virus present in the saliva of infected mammals. Since its prognosis is usually fatal for humans, nationwide public campaigns to vaccinate dogs and cats against rabies aim to break the epidemiological link between the virus and its reservoirs in Brazil. Findings During 12 months we evaluated the active immunity of dogs first vaccinated (booster shot at 30 days after first vaccination) against rabies using the Fuenzalida-Palácios modified vaccine in the urban area of Botucatu city, São Pauto state, Brazil. Of the analyzed dogs, 54.7% maintained protective titers (≥0.5 IU/mL) for 360 days after the first vaccination whereas 51.5% during all the study period. Conclusions The present results suggest a new vaccination schedule for dogs that have never been vaccinated. In addition to the first dose of vaccine, two others are recommended: the second at 30 days after the first and the third dose at 180 days after the first for the maintenance of protective titers during 12 months. PMID:26413082

Prevalence of immunity presumed using rabies vaccination history and household factors associated with vaccination status among domestic dogs in Japan.

PubMed

Hidano, Arata; Hayama, Yoko; Tsutsui, Toshiyuki

2012-01-01

Rabies was eliminated in Japan over 50 years ago; however, the recent increase in the movement of humans and animals across the world highlights the potential threat of disease reentry into the country. The immune status against rabies among the dog population in Japan is not well known; thus, the purpose of this study was to estimate the prevalence of dogs with effective immunity from the vaccination history using a web-based survey. We found that 76.9% (95% confidence interval, 75.8-78.1) of dogs in this study population belonged to the population in which 90% were assumed to have the internationally accepted antibody titer. We showed that dogs taken less frequently for walks were less likely to be vaccinated. Additionally, the frequency of encounters with other dogs during walks and the number of individuals in households were associated with vaccination history. To our knowledge, this study is the first report estimating the prevalence of dogs in Japan with effective immunity against rabies. Further, we identified the population with low vaccination coverage as well as the heterogeneous characteristics of vaccination history among the dog population. These findings contribute to the implementation of an efficient strategy for improving the overall vaccination coverage in Japan and the development of a quantitative risk assessment of rabies.

Effect of anthrax immune globulin on response to BioThrax (anthrax vaccine adsorbed) in New Zealand white rabbits.

PubMed

Malkevich, Nina V; Basu, Subhendu; Rudge, Thomas L; Clement, Kristin H; Chakrabarti, Ajoy C; Aimes, Ronald T; Nabors, Gary S; Skiadopoulos, Mario H; Ionin, Boris

2013-11-01

Development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a component of anthrax toxins. We evaluated the interaction between AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits. While pharmacokinetics of AIGIV were not altered by vaccination, the vaccine-induced immune response was abrogated in AIGIV-treated animals.

WinRho: Rh immune globulin prepared by ion exchange for intravenous use.

PubMed Central

Bowman, J M; Friesen, A D; Pollock, J M; Taylor, W E

1980-01-01

An Rh immune globulin [Rh IgG] for intravenous use, WinRho, has been prepared by the Winnipeg Rh Institute by a modification of the ion-exchange column method of Hoppe and colleagues. When administered to Rh-negative male and nonpregnant female volunteers WinRho was found to be nonpyrogenic, nontoxic, safe and protective against Rh alloimmunization. In a clinical trial with 240 microgram given at about 28 weeks' gestation and 120 microgram given after delivery to Rh-negative women at risk of Rh immunization WinRho was effective in preventing Rh immunization. Of the 870 women carrying Rh-positive fetuses who were treated with WinRho during pregnancy and were not tested several months after delivery 14 would have shown evidence of Rh immunization by the time of delivery if WinRho had been ineffective; none showed such evidence. Of the 1122 women carrying Rh-positive fetuses who were retested 4 to 6 months after delivery 83 would have shown evidence of Rh immunization at that time if WinRho had been ineffective; only 1 showed such evidence. The efficiency of yield of anti-D with the modified method of production, the fct that it can be given intravenously (a route that causes the patient less discomfort and immediately results in high anti-D levels) and the lower levels of contaminating IgA and IgM make WinRho the preparation of choice for preventing Rh immunization. PMID:6161687

Rabies: changing prophylaxis and new insights in pathophysiology.

PubMed

Ugolini, Gabriella; Hemachudha, Thiravat

2018-02-01

Despite great progress in decoding disease mechanisms, rabies remains one of the leading causes of human death worldwide. Towards the elimination of human rabies deaths by 2030, feasible and affordable post (PEP) and pre-exposure prophylaxis (PrEP) must be available with expansion to rural areas in rabies endemic countries. Vaccination and population control of dogs, principal reservoirs and transmitters, must be done in concert. Advances in the understanding of rabies neuropathogenesis and pathophysiology are reviewed, including recent experimental findings on host- and virus-specific mechanisms mediating neuronal survival and explaining clinical differences in furious and paralytic rabies. The forthcoming World Health Organization guide on rabies based on pathogenesis and immunization mechanisms data with support by clinical evidence provide new accelerated 1 week intradermal PrEP and PEP schedules. Rabies immunoglobulin injected into the wound only is endorsed at amounts not exceeding the dose interfering with active immunization. Potential therapeutics as designed in accord with rabies neuro-pathophysiology are plausible. Clinical practice and rabies awareness can be leveraged by transboundary collaboration among different areas. Advancement in prophylaxis and perspectives on animal control offer a new path to conquer rabies by 2030.

Antigenic Structure of Rabbit γ Globulin

PubMed Central

Dubiski, S.; Dubiska, Anna; Skalba, Danuta; Kelus, A.

1961-01-01

By iso-immunization, antisera to five rabbit γ globulin antigens were obtained. They are called A (former Da), B, C, D and E. Individual sera of 670 rabbits belonging to six separate populations were tested by precipitation methods. The distribution of the iso-antigens and their combinations into serum groups were studied. Each particular γ globulin iso-antigen was found to be of hereditary character; they seem to form three genetic systems: A, C and BDE, statistically independent. Various antisera from England, Poland and U.S.A were compared. PMID:13724581

Local infiltration of rabies immunoglobulins without systemic intramuscular administration: An alternative cost effective approach for passive immunization against rabies

PubMed Central

Bharti, Omesh Kumar; Madhusudana, Shampur Narayan; Gaunta, Pyare Lal; Belludi, Ashwin Yajaman

2016-01-01

ABSTRACT Presently the dose of rabies immunoglobulin (RIG) which is an integral part of rabies post exposure prophylaxis (PEP) is calculated based on body weight though the recommendation is to infiltrate the wound(s). This practice demands large quantities of RIG which may be unaffordable to many patients. In this background, we conducted this study to know if the quantity and cost of RIG can be reduced by restricting passive immunization to local infiltration alone and avoiding systemic intramuscular administration based on the available scientific evidence. Two hundred and sixty nine category III patients bitten by suspect or confirmed rabid dogs/animals were infiltrated with equine rabies immunoglobulin (ERIGs) in and around the wound. The quantity of ERIG used was proportionate to the size and number of wounds irrespective of their body weight. They were followed with a regular course of rabies vaccination by intra-dermal route. As against 363 vials of RIGs required for all these cases as per current recommendation based on body weight, they required only 42 vials of 5ml RIG. Minimum dose of RIGs given was 0.25 ml and maximum dose given was 8 ml. On an average 1.26 ml of RIGs was required per patient that costs Rs. 150 ($3). All the patients were followed for 9 months and they were healthy and normal at the end of observation period. With local infiltration, that required small quantities of RIG, the RIGs could be made available to all patients in times of short supply in the market. A total of 30 (11%) serum samples of patients were tested for rabies virus neutralizing antibodies by the rapid fluorescent focus inhibition test (RFFIT) and all showed antibody titers >0.5 IU/mL by day 14. In no case the dose was higher than that required based on body weight and no immunosuppression resulted. To conclude, this pilot study shows that local infiltration of RIG need to be considered in times of non-availability in the market or unaffordability by poor patients

[A historical view of rabies in Chile].

PubMed

Laval R, Enrique; Lepe I, Paulina

2008-04-01

In this review international and national historical features of rabies are presented remarking the start of preventive immunization in Chile, at year 1896, with the creation of the first service for rabies vaccination and la descentralización of preventive treatment from year 1929. Figures of human cases produced by this zoonosis between 1950 and 1986 are described, señalándose changes that occurred in local epidemiology of rabies since 1990, with an endemic pattern in bats and almost disappearance of canine rabies.

Rabies virus vaccine as an immune adjuvant against cancers and glioblastoma: new studies may resurrect a neglected potential.

PubMed

Altinoz, M A; Guloksuz, S; Elmaci, I

2017-07-01

To review the literature about the use of Rabies Virus-Vaccine (RV-V) as an anticancer immunotherapeutic modality in the light of recent findings. The literature search in relevant databases with the following key words: Rabies virus, cancer, remission. Remissions occured following RV-V injections in patients with cervical cancer and melanoma. Pilot clinical studies showed that RV-V injections enhanced survival in glioblastoma patients, which is supported by findings in GL261 mouse glioma model. If public health studies demonstrate protective role of RV-V against certain types of cancers, it can be benefitted as a novel immune adjuvant in clinic.

[Production of the monoclonal antibodies to the rabies virus nucleoprotein].

PubMed

Gribencha, S V; Kozlov, A Iu; Kostina, L V; Elakov, A L; Losich, M A; Tsibezov, V V; Zaberezhnyĭ, A D; Aliper, T I

2013-01-01

Five hybridomas secreting monoclonal antibodies (MAbs) for the nucleocapsid protein of the rabies virus were obtained through the fusion of the SP2/0 murine myeloma cells with splenocytes of BALB/c mice immunized with fixed rabies virus (CVS strain). All hybridomas secret MAbs of the IgG class that display different specificity to the nucleocapsids of rabies and rabies-related viruses. MAbs 2ell showed the specificity for the prevalent in Russia rabies viruses that are similar to commercially available anti-rabies conjugate.

Epidemiology, clinical features and risk factors for human rabies and animal bites during an outbreak of rabies in Maputo and Matola cities, Mozambique, 2014: Implications for public health interventions for rabies control.

PubMed

Salomão, Cristolde; Nacima, Amílcar; Cuamba, Lutero; Gujral, Lorna; Amiel, Olga; Baltazar, Cynthia; Cliff, Julie; Gudo, Eduardo Samo

2017-07-01

In Mozambique, the majority of rabies outbreaks are unreported and data on the epidemiological features of human rabies and animal bites are scarce. An outbreak of human rabies in adjacent Maputo and Matola cities in 2014 prompted us to investigate the epidemiology, clinical features and risk factors of human rabies and animal bites in the two cities. We reviewed cases of human rabies and animal bites from April to July 2014, and carried out a community investigation in July and August in the neighborhoods where cases of human rabies resided. This investigation included collection of clinical, demographic and epidemiological information and a case control study to investigate the risk factors associated with human rabies. Fourteen cases of human rabies were detected in Maputo (n = 10) and Matola (n = 3) cities and neighbouring Boane district (n = 1) between April and August 2014, all of whom had been admitted to hospital. All had a recent history of dog bite. Of the 14 rabid dogs, only one had been immunized. 819 cases of animal bites were registered, of which 64.6% (529/819) were from Maputo City. Dogs were responsible for 97.8% (801/819) of all animal bites, but only 27.0% (126/467) were immunized. Factors significantly associated with human rabies were: age <15 years (p = 0.05), bite by stray dog (p = 0.002), deep wound (p = 0.02), bite in the head (p = 0.001), bite by unimmunized dog (p = 0.01), no use of soap and water (p = 0.001), and no post-exposure prophylaxis (p = 0.01). Implementation of control measures for rabies is poor in Maputo and Matola cities, where cases of human rabies were strongly associated with bites by stray and unvaccinated dogs and irregular implementation of post-exposure measures.

Epidemiology, clinical features and risk factors for human rabies and animal bites during an outbreak of rabies in Maputo and Matola cities, Mozambique, 2014: Implications for public health interventions for rabies control

PubMed Central

Salomão, Cristolde; Nacima, Amílcar; Cuamba, Lutero; Gujral, Lorna; Amiel, Olga; Baltazar, Cynthia; Cliff, Julie

2017-01-01

Background In Mozambique, the majority of rabies outbreaks are unreported and data on the epidemiological features of human rabies and animal bites are scarce. An outbreak of human rabies in adjacent Maputo and Matola cities in 2014 prompted us to investigate the epidemiology, clinical features and risk factors of human rabies and animal bites in the two cities. Methodology/Principal findings We reviewed cases of human rabies and animal bites from April to July 2014, and carried out a community investigation in July and August in the neighborhoods where cases of human rabies resided. This investigation included collection of clinical, demographic and epidemiological information and a case control study to investigate the risk factors associated with human rabies. Fourteen cases of human rabies were detected in Maputo (n = 10) and Matola (n = 3) cities and neighbouring Boane district (n = 1) between April and August 2014, all of whom had been admitted to hospital. All had a recent history of dog bite. Of the 14 rabid dogs, only one had been immunized. 819 cases of animal bites were registered, of which 64.6% (529/819) were from Maputo City. Dogs were responsible for 97.8% (801/819) of all animal bites, but only 27.0% (126/467) were immunized. Factors significantly associated with human rabies were: age <15 years (p = 0.05), bite by stray dog (p = 0.002), deep wound (p = 0.02), bite in the head (p = 0.001), bite by unimmunized dog (p = 0.01), no use of soap and water (p = 0.001), and no post-exposure prophylaxis (p = 0.01). Conclusions/Significance Implementation of control measures for rabies is poor in Maputo and Matola cities, where cases of human rabies were strongly associated with bites by stray and unvaccinated dogs and irregular implementation of post-exposure measures. PMID:28742094

A recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice.

PubMed

Li, Zhili; Wang, Jigui; Yuan, Daoli; Wang, Shuang; Sun, Jiazeng; Yi, Bao; Hou, Qiang; Mao, Yaping; Liu, Weiquan

2015-06-01

Canine distemper virus (CDV) and rabies virus (RV) are two important pathogens of the dog. CDV, a member of the morbillivirus genus, has shown promise as an expression vector. The glycoprotein from RV is a main contributor to protective immunity and capable of eliciting the production of virus-neutralizing antibodies. In this study, we recovered an attenuated strain of canine distemper virus and constructed a recombinant virus, rCDV-RV-G, expressing a modified (R333Q) rabies virus glycoprotein (RV-G) of RV Flury strain LEP. RV-G expression by the recombinant viruses was confirmed. Furthermore, G was proved to be incorporated into the surface of CDV particles. While replication of the recombinant virus was slightly reduced compared with the parental CDV, it stably expressed the RV-G over ten serial passages. Inoculation of mice induced specific neutralizing antibodies against both RV-G and CDV. Therefore, the rCDV-RV-G has the potential as a vaccine that may be used to control rabies virus infection in dogs and other animals.

Immune reconstitution with two different rabbit polyclonal anti-thymocytes globulins.

PubMed

Bamoulid, Jamal; Crepin, Thomas; Gaiffe, Emilie; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Courivaud, Cécile; Ducloux, Didier

2017-12-01

Broad T cell depletion by polyclonal anti-thymocyte globulins (ATG) has been used for many years as a part of immunosuppressive treatment in transplantation. Currently, two different ATG are used in clinical practice, Thymoglobulin and Grafalon. Due to differences in the immunization source, these products contain different specificities and quantity of antibodies. These differences may have clinical consequences. We conducted a nested study in a large prospective multicentric cohort of kidney transplant to determine whether Grafalon-treated and Thymoglobulin-treated patients experience different lymphocyte reconstitution and clinical outcomes. 182 patients matched for age, gender, CMV status, CMV prophylaxis, number of previous transplantation, and maintenance immunosuppressive treatment were included (Thymoglobulin, [n=91]; Grafalon®, [n=91]). One-year post-transplant, recent thymic emigrants were significantly decreased (12±10% vs 21±12%; p<0.001) in Grafalon-treated patients. By contrast, T cell activation (CD38+DR+Ki67+) and senescence (CD8+CD57+CD28-) was increased in Thymoglobulin-treated patients. Compared to Grafalon, Thymoglobulin was not associated with a significantly different rate of acute rejection. CMV disease (p=0.013) was more frequent in Thymoglobulin-treated patients. Grafalon and Thymoglobulin seem to be equivalent to prevent acute rejection. CMV disease is more frequent in Thymoglobulin-treated patients. One year post-transplant immune profile profoundly differs according to the type of ATG. Copyright © 2017 Elsevier B.V. All rights reserved.

[Epidemiology of human rabies in China, 2016].

PubMed

Li, Y R; Zhu, L L; Zhu, W Y; Tao, X Y

2018-01-10

Objective: To understand the epidemiological characteristics of human rabies in China in 2016 and provide evidence for the control and prevention of human rabies. Methods: The incidence data of human rabies in China in 2016 were collected from national infectious disease reporting information management system. The surveillance data were collected from provinces of Shandong, Guizhou, Anhui, Hunan, Jiangsu and Guangxi Zhuang Autonomous Region. Excel 2013 software was used to process and summarize the data, the epidemiological characteristics of human rabies in China in 2016 were described by using indicators such as morbidity, mortality and constituent ratio. Results: A total of 644 human rabies cases were reported in 28 provinces in China in 2016, a decrease of 19.60% (157/801) compared with 2015. The provinces reporting high incidences of human rabies were Henan, Hunan, Guangxi and Guizhou, accounting for 39.44% (254/644) of the total cases. One case was reported in Qinghai province and Xinjiang Uygur Autonomous Region respectively. The male to female ratio of the cases was 2.14∶1 (439/205), and the majority of the patients were farmers (444/644). Surveillance points in 6 provinces reported 1 281 340 persons seeking post-exposure treatment, of whom 1 018 367 were treated for dog bite or scratch. A total of 764 234 persons completed the vaccination series, accounting for 63.90% (764 234/1 195 956) of the persons with grade Ⅱ and Ⅲ exposures, and 28.89% (165 677/573 571) of the persons with grade Ⅲ exposure were treated with passive immunization product. The average density of dogs in each surveillance area was 7.03/100 persons, the average canine immunization rate was 37.64%. Conclusion: The incidence of human rabies has remained decline in China in 2016, the number of the affected provinces has increased and that has the tendency of spreading to low-risk regions. The cases mainly occurred in men and farmers, and caused by dog bite or scratch. It is

Genetically modified rabies virus-vectored Ebola virus disease vaccines are safe and induce efficacious immune responses in mice and dogs.

PubMed

Shuai, Lei; Wang, Xijun; Wen, Zhiyuan; Ge, Jinying; Wang, Jinliang; Zhao, Dandan; Bu, Zhigao

2017-10-01

Ebola viruses (EBOVs) are zoonotic pathogens that cause EBOV disease (EVD) with high case fatality in humans. Currently, EVD vaccines are still under development in several countries. Here, we generated two recombinant rabies viruses (RABVs), rERAG 333E /ZGP and rERAG 333E /SGP, expressing the Zaire EBOV glycoprotein (ZGP) or Sudan EBOV glycoprotein (SGP) gene based on a modified ERA vaccine strain (rERAG 333E ) vector platform. The recombinant RABVs retained growth properties similar to those of the vector virus in BSR cell culture and efficiently expressed ZGP or SGP. After intracerebral (i.c.) inoculation with rERAG 333E /ZGP or rERAG 333E /SGP, all adult mice showed no signs of disease or weight loss and suckling mice maintained similar survivorship curve as those mice inoculated with control vector rERAG 333E , demonstrating that ZGP or SGP expression did not increase the virulence of the vector. Mouse immunization studies showed that vaccination with rERAG 333E /ZGP and rERAG 333E /SGP induced Zaire or Sudan EBOV neutralizing antibody (VNA) responses and IgG, IgG2a responses to ZGP or SGP, suggesting their potential as oral or inactivated bivalent vaccines against rabies and EVD. Most importantly, all dogs immunized orally with rERAG 333E /ZGP developed long-lasting ZEBOV and RABV VNA responses with or without previous rabies vaccine immunization history. Live rERAG 333E with EBOV GP thus appear to have the potential to be oral vaccines for free-roaming animals in endemic areas of EVD and rabies, and may serve as inactivated vaccines for use in humans. Copyright © 2017. Published by Elsevier B.V.

Glycoprotein from street rabies virus BD06 induces early and robust immune responses when expressed from a non-replicative adenovirus recombinant.

PubMed

Wang, Shuchao; Sun, Chenglong; Zhang, Shoufeng; Zhang, Xiaozhuo; Liu, Ye; Wang, Ying; Zhang, Fei; Wu, Xianfu; Hu, Rongliang

2015-09-01

The rabies virus (RABV) glycoprotein (G) is responsible for inducing neutralizing antibodies against rabies virus. Development of recombinant vaccines using the G genes from attenuated strains rather than street viruses is a regular practice. In contrast to this scenario, we generated three human adenovirus type 5 recombinants using the G genes from the vaccine strains SRV9 and Flury-LEP, and the street RABV strain BD06 (nrAd5-SRV9-G, nrAd5-Flury-LEP-G, and nrAd5-BD06-G). These recombinants were non-replicative, but could grow up to ~10(8) TCID50/ml in helper HEK293AD cells. Expression of the G protein was verified by immunostaining, quantitative PCR and cytometry. Animal experiments revealed that immunization with nrAd5-BD06-G can induce a higher seroconversion rate, a higher neutralizing antibody level, and a longer survival time after rabies virus challenge in mice when compared with the other two recombinants. Moreover, the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in mice immunized with nrAd5-BD06-G, which might also contribute to the increased protection. These results show that the use of street RABV G for non-replicative systems may be an alternative for developing effective recombinant rabies vaccines.

[Technical guideline for human rabies prevention and control (2016)].

PubMed

Zhou, H; Li, Y; Chen, R F; Tao, X Y; Yu, P C; Cao, S C; Li, L; Chen, Z H; Zhu, W Y; Yin, W W; Li, Y H; Wang, C L; Yu, H J

2016-02-01

In order to promote the prevention and control programs on rabies in our country, to regulate the prevention and disposition of rabies and to reduce the deaths caused by rabies, the Chinese Center for Disease Control and Prevention has organized a panel of experts, in the reference with Guidelines issued by WHO, American Advisory Committee on Immunization Practices, and the latest research progress from home and abroad, and compiled this document-"Technical Guidelines for Human Rabies Prevention and Control (2016)". The Guidelines conducted a systematic review on the etiology, clinical characteristics, laboratory diagnosis, epidemiology of rabies and provided evidence on varieties, mechanisms, effects, side-effects and security of rabies vaccine, as well as on other preparations on passive immunity of its kind, on methods related to prevention and disposition of exposure etc, finally to have come up with the recommendation on the above mentioned various techniques. The guidelines will be used by staff working on prevention and control of rabies from the Center for Disease Control and Prevention at all levels, from the departments of outpatient and divisions of infection and emergency control in all the medical institutions. The guideline will be updated and revised, following the research progress from home and abroad.

Controversies in rabies vaccination.

PubMed

Ghosh, Tapan Kr

2003-06-01

Rabies is a cent per cent fatal disease and there should not be any controversy in giving rabies vaccine to the victims. WHO has fixed schedules for doses for both pre and post-exposure in different category of cases, which also help us to avoid all controversies. But controversies arise in five main areas, which are related to the strategies of rabies prevention. These are: (i) Replacing use of NTV by MTCV. (ii) Intradermal schedule of MTCV, in place of Essen protocol of 5 i.m. doses to reduce the cost. (iii) Acceptability and inclusion of pre-exposure doses of MTCV in the immunization schedule of children as additional vaccine (iv) Schedule for re-exposure in already post-exposure vaccinated cases and schedule for exposure in pre-exposure vaccinated cases. (v) Uses of RIG in WHO category III cases. If these controversial issues are considered scientifically, rabies prophylaxis will see the light of success.

Globulin Test

MedlinePlus

... of cancer Why do I need a globulin test? Your health care provider may order globulin tests as part your ... Globulin tests are blood tests. During a blood test, a health care professional will take a blood sample from a ...

A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients.

PubMed

Davis, Gary L; Nelson, David R; Terrault, Norah; Pruett, Timothy L; Schiano, Thomas D; Fletcher, Courtney V; Sapan, Christine V; Riser, Laura N; Li, Yufeng; Whitley, Richard J; Gnann, John W

2005-08-01

Chronic hepatitis C is the most common indication for liver transplantation, but viral recurrence is universal and progressive graft injury occurs in most recipients. Our aim was to assess the safety, pharmacokinetics (PK), and antiviral effects of high doses of a human hepatitis C antibody enriched immune globulin product (HCIG) in patients undergoing liver transplantation for chronic hepatitis C. This was a multicenter, randomized, open-label, controlled trial conducted at 4 transplant centers in the United States. A total of 18 patients with chronic hepatitis C, who underwent liver transplantation, were randomized to receive low-dose HCIG (75 mg/kg) or high-dose HCIG (200 mg/kg), or no treatment. A total of 17 infusions of HCIG were administered in each treated patient over 14 weeks using a time-dependent dosing strategy based on the PK of anti-hepatitis B immune globulin in liver transplant recipients. Hepatitis C virus levels, liver enzymes, and liver biopsies were obtained serially throughout the study period. PK profiles of HCV antibodies were determined on days 4, 10, and 98. HCIG infusions were safe and tolerated. The infusion rate could not be maximized because of symptoms for 18% to 30% of the doses. The half-life of HCIG was extremely short immediately after transplantation but was gradually prolonged. In the high-dose group, serum alanine aminotransferase (ALT) levels normalized in most subjects and no patient developed hepatic fibrosis. However, serum HCV RNA levels were not suppressed at either dose. In conclusion, HCIG, an anti-HCV enriched immune globulin product, appears to be safe in patients with chronic hepatitis C undergoing liver transplantation. Further studies are required to determine whether the drug has beneficial effects in this group of patients.

What the world's religions teach, applied to vaccines and immune globulins.

PubMed

Grabenstein, John D

2013-04-12

For millennia, humans have sought and found purpose, solace, values, understanding, and fellowship in religious practices. Buddhist nuns performed variolation against smallpox over 1000 years ago. Since Jenner developed vaccination against smallpox in 1796, some people have objected to and declined vaccination, citing various religious reasons. This paper reviews the scriptural, canonical basis for such interpretations, as well as passages that support immunization. Populous faith traditions are considered, including Hinduism, Buddhism, Jainism, Judaism, Christianity, and Islam. Subjects of concern such as blood components, pharmaceutical excipients of porcine or bovine origin, rubella strain RA 27/3, and cell-culture media with remote fetal origins are evaluated against the religious concerns identified. The review identified more than 60 reports or evaluations of vaccine-preventable infectious-disease outbreaks that occurred within religious communities or that spread from them to broader communities. In multiple cases, ostensibly religious reasons to decline immunization actually reflected concerns about vaccine safety or personal beliefs among a social network of people organized around a faith community, rather than theologically based objections per se. Themes favoring vaccine acceptance included transformation of vaccine excipients from their starting material, extensive dilution of components of concern, the medicinal purpose of immunization (in contrast to diet), and lack of alternatives. Other important features included imperatives to preserve health and duty to community (e.g., parent to child, among neighbors). Concern that 'the body is a temple not to be defiled' is contrasted with other teaching and quality-control requirements in manufacturing vaccines and immune globulins. Health professionals who counsel hesitant patients or parents can ask about the basis for concern and how the individual applies religious understanding to decision-making about

Dog bites in Bosnia.

PubMed Central

Croft, A; Archer, R

1997-01-01

BACKGROUND: Rabies is a zoonosis that remains endemic in most parts of the world. Primary care physicians are in the first line of defence against the disease. An increasing number of British practitioners and medical students are being exposed to the dangers of rabies through humanitarian work on overseas attachments. Rabies is enzootic throughout Bosnia-Herzegovina and presents a hazard to the multinational troops currently deployed there. AIM: To describe the British Army's experience of animal bites and rabies prevention in Bosnia during the first six months of its current peace enforcement mission, and to make general recommendations on the good management of any rabies hazard at primary care level and under field conditions. METHODS: Routine data from the Army's epidemiological database (ARRC 97) were reviewed, and theatre issues of rabies vaccine and immune globulin were used as a proxy measure for administered post-exposure prophylaxis. RESULTS: A total of 62 animal bites were reported in British troops between December 1995 and May 1996, of which 28 were unprovoked bites and resulted in the administration of a course of rabies vaccine. Ten of these were severe bites and rabies immune globulin (RIG) was administered in addition. The total cost of rabies post-exposure prophylaxis was US$6914.00. CONCLUSION: The prevention of rabies has major human and resource implications, and primary care staff involved in rabies post-exposure management need to be well supported in their clinical decision-making. Rabies protocols should be clear and unambiguous. The effective medical surveillance of military or humanitarian missions in rabies-enzootic areas must include the prompt reporting of animal bites. The predeployment training of medical teams should include an up-to-date assessment of the local rabies threat. PMID:9281871

Virus neutralizing antibody response in mice and dogs with a bicistronic DNA vaccine encoding rabies virus glycoprotein and canine parvovirus VP2.

PubMed

Patial, Sonika; Chaturvedi, V K; Rai, A; Saini, M; Chandra, Rajesh; Saini, Y; Gupta, Praveen K

2007-05-16

A bicistronic DNA vaccine against rabies and parvovirus infection of dogs was developed by subcloning rabies glycoprotein and canine parvovirus (CPV) VP2 genes into a bicistronic vector. After characterizing the expression of both the proteins in vitro, the bicistronic DNA vaccine was injected in mice and induced immune response was compared with monocistronic DNA vaccines. There was no significant difference in ELISA and virus neutralizing (VN) antibody responses against rabies and CPV in mice immunized with either bicistronic or monocistronic DNA vaccine. Further, there was significantly similar protection in mice immunized with either bicistronic or monocistronic rabies DNA vaccine on rabies virus challenge. Similarly, dogs immunized with monocistronic and bicistronic DNA vaccines developed comparable VN antibodies against rabies and CPV. This study indicated that bicistronic DNA vaccine can be used in dogs to induce virus neutralizing immune responses against both rabies and CPV.

Familial cluster of exposure to a confirmed rabid dog in travelers to Algeria.

PubMed

Antwi, Sylvie; Parola, Philippe; Sow, Doudou; Sornin, Victoria; Henrion, Maxime; Gautret, Philippe

A 10 person-family originating from Algeria traveled in rural Algeria for the purpose of visiting friends and relatives without seeking pre-travel advice, did not received pre-travel rabies immunization, and were exposed to a confirmed rabid dog including 8 within less than 4 days of arrival. Three received suckling mouse brain rabies vaccine although WHO strongly recommends that its production and administration be discontinued and seven received insufficient doses of equine rabies immune globulin abroad. Rabies treatment was completed on returning to France. This reports underline the fact that travelers visiting friends and relatives in dog rabies endemic country are at high risk of rabies exposure and unaware of such a risk in most instances. Rabies risk warning should be reinforced and rabies pre-exposure vaccination should be considered in all individuals traveling to North Africa (and to sub-Saharan Africa) whatever the duration of stay. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral vaccination of captive small Indian mongoose (Herpestes auropunctatus) against rabies.

PubMed

Vos, Ad; Kretzschmar, Antje; Ortmann, Steffen; Lojkic, Ivana; Habla, Christiane; Müller, Thomas; Kaiser, Christian; Hundt, Boris; Schuster, Peter

2013-10-01

The small Indian mongoose (Herpestes auropunctatus), a rabies reservoir species on several Islands in the Caribbean, was successfully immunized against rabies for the first time by offering animals a vaccine bait specifically designed for this small carnivore. The bait contained on average 0.6 mL of the genetically modified replication-competent rabies virus construct SPBN GASGAS (10(8.5) focus-forming units/mL). Three of four mongooses offered a bait developed an immune response above 0.5 IU/mL, but the response was less pronounced than in two animals offered the vaccine by direct oral instillation.

Protection of Non-Human Primates against Rabies with an Adenovirus Recombinant Vaccine

PubMed Central

Xiang, Z.Q.; Greenberg, L.; Ertl, H. C.; Rupprecht, C.E.

2014-01-01

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. PMID:24503087

Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

PubMed

Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

2014-04-01

Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

Rabies postexposure prophylaxis. Human and domestic animal considerations.

PubMed

Fearneyhough, M G

2001-05-01

The emphasis on rabies control and prevention in the United States seems to be a function of our perception of proximity of the threat. Wildlife rabies epizootics within a state may be of little concern to the uninformed urban dweller. Additionally, many parts of the western United States are free of terrestrial rabies; were it not for the presence of bat rabies, people in those areas would likely interpret rabies control as a minor public health concern. It is essential that federal, state, and local public health programs emphasize the importance of rabies control through activities that include rabies education, sponsorship of legislated requirements for domestic animal vaccination, support for local animal control programs, and the promotion of recommendations that encourage the appropriate use of PEP. We are almost guaranteed that rabies is going to remain a major public health issue well into the next century because of expanding wildlife rabies epizootics, identification of new rabies viral variants with increased public health concern, emotional and legal concerns associated with rabies exposure, and increasing national cost associated with rabies control and prevention. Nevertheless, the development of new laboratory technology that allows an understanding of the epidemiologic nature of the rabies virus based on an evolving genetic history and the interrelationship with wildlife reservoirs should allow access to valuable tools for rabies control. When combined with programs using new developments in oral rabies vaccine that can immunize whole populations of wildlife reservoirs, that technology offers encouragement in our effort to control one of the diseases of antiquity.

Evaluation of intradermal vaccination at the anti rabies vaccination OPD.

PubMed

Mankeshwar, R; Silvanus, V; Akarte, S

2014-09-01

Rabies is a virtually 100% fatal acute viral encephalitis caused by an RNA virus belonging to family Rhabdoviridae and genus Lyssavirus. The virus can infect all warm blooded animals. The disease is transmitted to humans by the bite, lick or scratch of an infected animal. More than 99% of all human rabies deaths occur in the developing world. It is preventable with timely and proper usage of modern immunobiologicals (vaccines and immunoglobulins). Once exposure occurs, modern prophylaxis entails immediate wound care, local infiltration of rabies immune globulin and parenteral administration of modern cell culture vaccines in multiple doses. The annual medicinal (vaccines and other drugs) cost for animal bite treatment is Rs. 2 billion approximately (2004). The objective of the present study is to evaluate the performance of the Intradermal (i.d.) route visa vis the Intramuscular (i.m.) route in our clinical setting the Antirabies Vaccination (ARV) OPD, Sir J.J. Hospital, Mumbai. A total of 1460 patients were administered the Antirabies vaccine by the Intradermal route over the 1 year period as compared to 1075 patients who were administered the Antirabies vaccine by the Intramuscular route in the previous year. 1230 (84.2) of the patients who were administered the vaccine by the i.d. route completed the schedule and 230 (15.8%) partially completed the schedule. Four hundred thirty two (40%) of the patients who were administered the vaccine by the Intramuscular route completed the schedule and 643 (59.8%) partially completed the schedule. The vaccine cost for i.d. was Rs. 2,80,600. The vaccine cost for the intramuscular (i.m.) assuming 84% compliance was estimated as Rs. 15, 64, 000. Assuming 40% compliance the cost was estimated as Rs. 7, 82, 230. Thus a saving of Rs. 5, 01, 630 to Rs. 12, 83, 400 was effected. In our setting, the Intradermal regime was cost effective and increased patient adherence and enrolment. It has now been routinely adopted at the clinic.

A recombinant pseudorabies virus expressing rabies virus glycoprotein: safety and immunogenicity in dogs.

PubMed

Yuan, Ziguo; Zhang, Shoufeng; Liu, Ye; Zhang, Fei; Fooks, Anthony R; Li, Qianxue; Hu, Rongliang

2008-03-04

Several recombinant vaccines expressing the rabies virus glycoprotein have been developed, particularly for the oral vaccination of wildlife. While these vaccines induce protective immunity in some animal species such as foxes, they are less effective in others. Pseudorabies virus (PRV) has been licensed for use as a live vaccine in pigs and possesses an excellent safety and efficacy record. We have used it to construct a recombinant virus, rPRV/eGFP/rgp, expressing the rabies virus glycoprotein. This recombinant virus has been shown to be safe for dogs by oral and intramuscular routes of inoculation and was demonstrated to induce immune responses against both pseudorabies and rabies in dogs after a single oral dose of 2 x 10(7.0) plaque forming units (PFU). Neutralizing antibody titers against rabies reached > 0.5 IU/ml and 1:64-1:128 against pseudorabies by 5 weeks post-vaccination in all dogs, indicating that the pseudorabies virus vector infected dogs and replicated in vivo, and that the rabies virus glycoprotein had been expressed and an effective immune response elicited. Antibody titers were maintained for over 6 months. This suggests that pseudorabies virus could be an effective live vector for recombinant rabies oral vaccination.

Compendium of Animal Rabies Control, 1998. Vol. 47, No. RR-9

DTIC Science & Technology

1998-05-29

as necessary. Recommendations for parenteral immu- nization procedures are contained in Part I; all animal rabies vaccines licensed by the United...Part I: Recommendations for Parenteral Immunization Procedures A. Vaccine Administration All animal rabies vaccines should be restricted to use by...or under the direct super- vision of, a veterinarian. B. Vaccine Selection In comprehensive rabies-control programs, only vaccines with a 3-year

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

PubMed

Wittek, Riccardo

2006-05-01

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

[Biological characteristics of a chimeric rabies virus expressing canine parvovirus VP2 protein].

PubMed

Niu, Xue-Feng; Liu, Xiao-Hui; Sun, Zhao-Jin; Shi, He-He; Chen, Jing; Jiang, Bido; Sun, Jing-Chen; Guo, Xiao-Feng

2009-09-01

To obtain a bivalence vaccine against canine rabies virus and canine parvovirus, a chimeric rabies virus expressing canine parvovirus VP2 protein was generated by the technique of reverse genetics. It was shown that the chimeric virus designated as HEP-Flury (VP2) grew well on BHK-21 cells and the VP2 gene could still be stably expressed after ten passages on BHK-21 cells. Experiments on the mice immunized with the chimeric virus HEP-Flury (VP2) demonstrated that specific antibodies against rabies virus and canine parvovirus were induced in immunized mice after vaccination with the live chimeric virus.

A rapid immunochromatographic test strip for detecting rabies virus antibody.

PubMed

Wang, Hualei; Feng, Na; Yang, Songtao; Wang, Chengyu; Wang, Tiecheng; Gao, Yuwei; Su, Jianqing; Zheng, Xuexing; Hou, Xiaoqiang; Huang, Hainan; Yang, Ruimei; Zou, Xiaohuan; Huang, Geng; Xia, Xianzhu

2010-12-01

An immunochromatographic test strip (ICTS) for detecting antibodies to rabies virus was developed, using colloidal gold particles labeled with rabies virus glycoprotein as the tracer. The assay was evaluated using sera from dogs immunized with various commercial rabies vaccines, or from dogs in the clinics and sera from dogs immunized with vaccines against pathogens other than rabies virus, and negative sera from a wide variety of animal sources, including dogs, mice, and cats which had never been vaccinated. The ICTS was found to be highly specific for antibodies against rabies virus, with a detection limit of 0.5IU/ml as measured by the fluorescent antibody virus neutralization (FAVN) test. Compared with the FAVN test, the specificity and sensitivity of ICTS were 98.2% and 90.4%, respectively. There was an excellent agreement between results obtained by the ICTS and FAVN tests (kappa=0.888). Strips stored at 4°C in a plastic bag with a desiccant retained their specificity and sensitivity for at least 15 months, and strips stored at ambient temperature remained stable for 12 months. The immunochromatographic test strip may therefore be useful for clinical laboratories lacking specialized equipment and for diagnosis in the field for rapid detection of rabies virus-specific antibodies. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of Oral Rabies Vaccination: Protection Against Rabies in Wild Caught Raccoons ( Procyon lotor).

PubMed

Blanton, Jesse D; Niezgoda, Michael; Hanlon, Cathleen A; Swope, Craig B; Suckow, Jason; Saidy, Brandi; Nelson, Kathleen; Chipman, Richard B; Slate, Dennis

2018-03-29

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 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

Risk factors for human rabies in China.

PubMed

Gong, Z; He, F; Chen, Z

2012-02-01

In China, we have witnessed an increasing incidence of rabies in recent years and the number of deaths ranked first among the 39 notifiable infectious diseases. We conducted a case-control study to identify risk factors for human rabies infection and disease to recommend prevention and treatment among people exposed to rabies. Exposure site, pre-exposure prophylaxis and post-exposure prophylaxis were significantly associated with rabies infection. Exposure site at upper limb and trunk or at lower limb were at lower risk as compared with head-exposed patients. The OR was 0.09(95% CI: 0.009-0.93) and 0.01(95% CI: 0.001-0.115) respectively. Pre-exposure prophylaxis (OR = 0.05, 95% CI: 0.03-0.11) and post-exposure prophylaxis (OR = 0.02, 95% CI: 0.01-0.40) were both protective factors as compared with no prophylaxis. For patients who had post-exposure prophylaxis, dose for the first injection and immunity procedure were significantly associated with rabies infection. © 2011 Blackwell Verlag GmbH.

Virology, Immunology and Pathology of Human Rabies During Treatment

PubMed Central

Caicedo, Yolanda; Paez, Andres; Kuzmin, Ivan; Niezgoda, Michael; Orciari, Lillian A.; Yager, Pamela A.; Recuenco, Sergio; Franka, Richard; Velasco-Villa, Andres; Willoughby, Rodney E.

2016-01-01

Background Rabies is an acute fatal encephalitis caused by all members of the Lyssavirus genus. The first human rabies survivor without benefit of prior vaccination was reported from Milwaukee in 2005. We report a second unvaccinated patient who showed early recovery from rabies and then died accidentally during convalescence, providing an unparalleled opportunity to examine the histopathology as well as immune and virological correlates of early recovery from human rabies. Methods Case report, rapid fluorescent focus inhibition test, enzyme-linked immunosorbent assay, indirect and direct fluorescent antibody assays, reverse-transcriptase polymerase chain reaction, phylogenetic reconstruction, isolation in tissue culture, pathology and immunohistochemistry. Results The 9 year old died 76 days after presenting with rabies of vampire bat phylogeny transmitted by cat bite. Antibody response in serum and cerebrospinal fluid was robust and associated with severe cerebral edema. No rabies virus was cultured at autopsy. Rabies virus antigen was atypical in size and distribution. Rabies virus genome was present in neocortex but absent in brainstem. Conclusions Clinical recovery was associated with detection of neutralizing antibody and clearance of infectious rabies virus in the central nervous system by 76 days but not clearance of detectable viral subcomponents such as nucleoprotein antigen or RNA in brain. PMID:25405805

[Rabies].

PubMed

Nishizono, Akira

2009-02-01

Rabies is a fetal viral encephalitis caused by the rabies virus, that is mainly transmitted through the saliva of infected domestic or wild animals. Rabies remains an important public health issue worldwide due to the prevalence of endemic dog rabies in developing countries. The epidemiological impact is particularly still high in Asian and African countries. In contrast, in the developed countries, including Japan, rabies is a re-emerging disease. The Lyssaviruses (types EBLV and ABL) and rabies virus infections via bats have recently emerged in Europe and the United States. Although the incubation period averages 1-3 months, there is no known treatment once the symptoms of rabies appear. On the basis of clinical manifestations, rabies can be classified into 2 types: furious and paralytic rabies. The former is characterized by the well-known symptoms of hydrophobia, aerophobia, and hypersalivation. However the latter type is likely to be misdiagnosed because of its similarity to Guillian-Barré syndrome and neuropsychiatric illnesses. Therefore, post-exposure treatment (PET) using a tissue-culture vaccine is the only way to prevent the disease. In the case of exposure to severe bites (WHO category III), rabies immunoglobulin (RIG) is essential for PET. Although the mechanism underlying the pathogenesis of rabies remains poorly understood, the recent technique of reverse genetics can be a useful tool for understanding rabies pathogenesis at a genetic level. Japan has been free of rabies for over 50 years because of the proper registration of domestic animals and control over their vaccinations. However, it is necessary to always remember that rabies is still a global burden as a representative of a re-emerging disease.

Spatial control of rabies on heterogeneous landscapes.

PubMed

Russell, Colin A; Real, Leslie A; Smith, David L

2006-12-20

Rabies control in terrestrial wildlife reservoirs relies heavily on an oral rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in natural habitats, vaccine corridors have been constructed to control the spread; these corridors are often developed around natural barriers, such as rivers, to enhance the effectiveness of vaccine deployment. However, the question of how to optimally deploy ORV around a river (or other natural barrier) to best exploit the barrier for rabies control has not been addressed using mathematical models. Given an advancing epidemic wave, should the vaccine be distributed on both sides of barrier, behind the barrier, or in front of it? Here, we introduce a new mathematical model for the dynamics of raccoon rabies on a spatially heterogeneous landscape that is both simple and realistic. We demonstrate that the vaccine should always be deployed behind a barrier to minimize the recurrence of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce herd immunity inside the vaccinated area, it simultaneously creates a demographic refuge. When that refuge is in front of a natural barrier, seasonal dispersal from the vaccine corridor into an endemic region sustains epidemic oscillations of raccoon rabies. When the vaccine barrier creates a refuge behind the river, the low permeability of the barrier to host movement limits dispersal of the host population from the protected populations into the rabies endemic area and limits subsequent rabies epidemics.

Human rabies in India: epidemiological features, management and current methods of prevention.

PubMed

Dutta, J K

1999-10-01

In most endemic countries stray dogs are the main source of rabies infection in humans. In India 95-97% of rabies patients are infected by dogs. Most pet dogs do not regularly receive booster doses of vaccine. In Thailand, most rabies patients develop the disease within 1 month of exposure. Rabies immunoglobulin is costly and usually not available. So in India nervous tissue vaccine is commonly used--it is inexpensive and freely available despite frequent neurological complications. The cost of immunization by tissue culture vaccines may be reduced by nearly 60% by intradermal vaccination.

A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yi; Zhang, Shoufeng; Li, Wei

Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine groupmore » (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the

Practical significance of rabies antibodies in cats and dogs.

PubMed

Aubert, M F

1992-09-01

Doubt has sometimes been cast upon the protective effect of rabies antibodies in serum. Animals and humans suffering from fatal rabies often produce high antibody titres, while rabies cases are also observed in vaccinated animals. Cellular immunity is also largely involved in protection. Nevertheless, a large number of laboratory experiments and field observations clearly demonstrate that cats and dogs which develop antibodies after vaccination and before challenge have a very high probability of surviving any challenge, no matter how strong the dose and which virus strain was used. Rabies antibody titration can, therefore, afford a strong additional guarantee to the vaccination certificates accompanying domestic carnivores during transportation between countries. Quarantine rules should also be adapted to the epidemiological features in the exporting country, e.g. statistics of vaccination failure in cats and dogs and host-virus adaptation of the rabies strains circulating in these countries.

[Analysis of epidemiological features of human rabies in China, 2012].

PubMed

Zhou, Hang; Li, Yu; Mu, Di; Yin, Wenwu; Yu, Hongjie

2015-03-01

To analyze epidemiological characteristics and trends of rabies and explore control and prevention measures based on the rabies surveillance data of 2012 in China. Data of 2012 from China's infectious disease surveillance reporting and management system and sentinel surveillance systems in 6 provinces were used, for a retrospective analysis in descriptive epidemiological methods. 1 425 cases were reported in 731 counties of 27 provinces in 2012 and 1 361 deaths were reported due to rabies, with the rabies incidence rate and mortality rate of 0.11/100 000 and 0.10/100 000 respectively, decreasing by 26.0% and 27.9% respectively from 2011. Rabies epidemic was mainly found in southern regions, followed by middle and eastern regions in China. 49.6% of total rabies cases were found in Guangxi, Guangdong, Hunan, Guizhou, and Henan province, which were the top five provinces. The rabies cases were mainly peasants, students and scattered children, accounting for 70.9%, 8.3% and 5.8% of total cases respectively. The male-female ratio in rabies cases was 2.6 : 1. In 2012, 294 epidemiological questionnaires were collected, revealing that 92.1% of the exposure was caused by dogs and 6.8% by cats. The median of latent period was 70 days. 62.4% of the cases were exposed in upper limb, and only 6.9% of such cases were vaccinated after exposure while the proportion of passive immunity biological vaccination was 2.9% for cases with exposure of category III. Surveillance data from PEP (post-exposure prophylaxis) clinics showed that 81.7% of the visitors were hurt by dogs and the exposure categories I, II and III accounted for 7.0%, 50.5% and 42.5% respectively. The proportion of of the exposure categories varied by PEP surveillance clinics. Despite continuing decrease of rabies cases in China in 2012, the number of counties (districts) affected fall relatively slow, with a tendency of rabies spreading to the western and northern regions in China. There were more rabies cases in

Rabies.

PubMed

Burnett, Nark

2013-01-01

Rabies has been a scourge of mankind since antiquity. The name itself, ?rabies? is derived from the ancient Sanskrit rabhas meaning ?to do violence? and has been found described in medical writings several thousand years old. The rabies virus is an RNA virus of the family Rhabdoviridae (Greek for ?rod-shaped virus?), genus Lyssavirus (Lyssa being the Greek God of frenzy and rage). Rabies infections have a worldwide spread, with only a few, mostly island nations laying claim to being ?rabies free.? 2013.

Protection of non-human primates against rabies with an adenovirus recombinant vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiang, Z.Q.; Greenberg, L.; Ertl, H.C., E-mail: ertl@wistar.upenn.edu

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. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protectsmore » against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.« less

Costs analysis of a population level rabies control programme in Tamil Nadu, India.

PubMed

Abbas, Syed Shahid; Kakkar, Manish; Rogawski, Elizabeth Tacket

2014-02-01

The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu's efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was $0.7 million (Rs 36 million) and $2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be $ 44 million (Rs 2,350 million), $23 million (Rs 1,230 million) and $ 11 million (Rs 590 million), respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme.

Costs Analysis of a Population Level Rabies Control Programme in Tamil Nadu, India

PubMed Central

Abbas, Syed Shahid; Kakkar, Manish; Rogawski, Elizabeth Tacket

2014-01-01

The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadu's efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was $0.7 million (Rs 36 million) and $2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be $ 44 million (Rs 2,350 million), $23 million (Rs 1,230 million) and $ 11 million (Rs 590 million), respectively. Dog bite incidence, health systems coverage and cost of rabies biologicals were found to be important drivers of costs for human interventions. For the animal sector interventions, the size of dog catching team, dog population and vaccine costs were found to be driving the costs. Rabies control in Tamil Nadu seems a costly proposition the way it is currently structured. Policy makers in Tamil Nadu and other similar settings should consider the long-term financial sustainability before embarking upon a state or nation-wide rabies control programme. PMID:24587471

[The use of passive rabies immunotherapy: from the past to the future].

PubMed

Bourhy, Hervé; Dacheux, Laurent; Ribadeau-Dumas, Florence

2010-01-01

Rabies is a fatal disease transmitted by infected animals by bite, scratch, licking on broken skin or contamination of mucosis by saliva. The regimen of post-exposure prophylaxis for people not previously vaccinated, that is currently recommended by WHO, consists of a combination of wound cleaning, active immunization and passive immunization when the exposure is of category 3. Most of the products available on the market, in particular human rabies immunoglobulins, highly purified equine rabies immunoglobulins and the derived F(ab')(2) fragments, are now characterized by high potency and safety. Although the interest of passive anti-rabies immunization was first demonstrated in the first half of the 20th century, there is still an inadequate supply of these products to the target populations mostly in developing countries. Therefore, it is urgent to set-up training and information actions for healthcare personnel on the need to use passive immunotherapy and the lack of adverse effects of the related products. For the future, we hope that a scale up of production and a lower price will improve the accessibility to these products. The development of new products based on monoclonal antibodies and molecular biology, and which may be cheaper, is promising. © Société de Biologie, 2010.

Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain.

PubMed

Garg, Rajni; Kaur, Manpreet; Saxena, Ankur; Prasad, Rajendra; Bhatnagar, Rakesh

2017-05-01

Rabies is a serious concern world-wide. Despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. This calls for improvement of rabies vaccination strategies. DNA vaccination has immense potential in this regard. The DNA vaccine pgp.LAMP-1 conferred 60% protection to BALB/c mice against 20 LD 50 rabies challenge virus standard (CVS) strain challenge. Upon supplementation with Emulsigen-D, the vaccine formulation conferred complete protection against lethal challenge. To assess the feasibility of this vaccine formulation for human use, it was tested along with other FDA approved adjuvants, namely, Alum, Immuvac, Montanide ISA720 VG. Enhanced immune response correlated with high IgG antibody titer, Th2 biased response with a high level of rabies virus neutralizing antibodies (RVNAs) and IgG1/IgG2a ratio >1, observed upon alum supplementation of the rabies DNA vaccine. The total IgG antibody titer was 2IU/ml and total RVNA titer was observed to be 4IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD 50 of the rabies CVS strain, conducted in compliance with the potency test for rabies recommended by the National Institutes of Health (NIH), USA. Previously, we have established pre-clinical safety of this vaccine as per the guidelines of Schedule Y, FDA as well as The European Agency for evaluation of Medicinal Products. The vaccine showed no observable toxicity at the site of injection as well as at systemic level in Wistar rats when administered with 10X recommended dose. Therefore, supplementation of rabies DNA vaccine, pgp.LAMP-1 with alum would lead to development of a non-toxic, efficacious, stable and affordable vaccine that can be used to combat high numbers of fatal rabies infections tormenting developing countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Successful strategies implemented towards the elimination of canine rabies in the Western Hemisphere.

PubMed

Velasco-Villa, Andres; Escobar, Luis E; Sanchez, Anthony; Shi, Mang; Streicker, Daniel G; Gallardo-Romero, Nadia F; Vargas-Pino, Fernando; Gutierrez-Cedillo, Veronica; Damon, Inger; Emerson, Ginny

2017-07-01

Almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. During recent decades, many countries in the Western Hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsible pet ownership. This article reviews progress in eliminating canine rabies from the Western Hemisphere. After briefly summarizing the history of control efforts and describing the approaches listed above, we note that programs in some countries have been hindered by societal attitudes and severe economic disparities, which underlines the need to discuss measures that will be required to complete the elimination of canine rabies throughout the region. We also note that there is a constant threat for dog-maintained epizootics to re-occur, so as long as dog-maintained rabies "hot spots" are still present, free-roaming dog populations remain large, herd immunity becomes low and dog-derived rabies lyssavirus (RABLV) variants continue to circulate in close proximity to rabies-naïve dog populations. The elimination of dog-maintained rabies will be only feasible if both dog-maintained and dog-derived RABLV lineages and variants are permanently eliminated. This may be possible by keeping dog herd immunity above 70% at all times, fostering sustained laboratory-based surveillance through reliable rabies diagnosis and RABLV genetic typing in dogs, domestic animals and wildlife, as well as continuing to educate the population on the risk of rabies transmission, prevention and responsible pet ownership. Complete elimination of canine rabies requires permanent funding, with governments and people committed to make it a reality. An accompanying article reviews the history and epidemiology of canine rabies in the Western Hemisphere, beginning with its introduction during the period of European colonization, and discusses how spillovers of viruses between dogs and

Successful strategies implemented towards the elimination of canine rabies in the Western Hemisphere

PubMed Central

Velasco-Villa, Andres; Escobar, Luis E.; Sanchez, Anthony; Shi, Mang; Streicker, Daniel G.; Gallardo-Romero, Nadia F.; Vargas-Pino, Fernando; Gutierrez-Cedillo, Veronica; Damon, Inger; Emerson, Ginny

2017-01-01

Almost all cases of human rabies result from dog bites, making the elimination of canine rabies a global priority. During recent decades, many countries in the Western Hemisphere have carried out large-scale dog vaccination campaigns, controlled their free-ranging dog populations and enforced legislation for responsible pet ownership. This article reviews progress in eliminating canine rabies from the Western Hemisphere. After briefly summarizing the history of control efforts and describing the approaches listed above, we note that programs in some countries have been hindered by societal attitudes and severe economic disparities, which underlines the need to discuss measures that will be required to complete the elimination of canine rabies throughout the region. We also note that there is a constant threat for dog-maintained epizootics to re-occur, so as long as dog-maintained rabies “hot spots” are still present, free-roaming dog populations remain large, herd immunity becomes low and dog-derived rabies lyssavirus (RABLV) variants continue to circulate in close proximity to rabies-naïve dog populations. The elimination of dog-maintained rabies will be only feasible if both dog-maintained and dog-derived RABLV lineages and variants are permanently eliminated. This may be possible by keeping dog herd immunity above 70% at all times, fostering sustained laboratory-based surveillance through reliable rabies diagnosis and RABLV genetic typing in dogs, domestic animals and wildlife, as well as continuing to educate the population on the risk of rabies transmission, prevention and responsible pet ownership. Complete elimination of canine rabies requires permanent funding, with governments and people committed to make it a reality. An accompanying article reviews the history and epidemiology of canine rabies in the Western Hemisphere, beginning with its introduction during the period of European colonization, and discusses how spillovers of viruses between dogs

Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009-2010.

PubMed

Cui, Xizhong; Nolen, Leisha D; Sun, Junfeng; Booth, Malcolm; Donaldson, Lindsay; Quinn, Conrad P; Boyer, Anne E; Hendricks, Katherine; Shadomy, Sean; Bothma, Pieter; Judd, Owen; McConnell, Paul; Bower, William A; Eichacker, Peter Q

2017-01-01

We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009-2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0-5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6-11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak.

SHBG (Sex Hormone Binding Globulin)

MedlinePlus

... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

Rabies

MedlinePlus

... Staying Safe Videos for Educators Search English Español Rabies KidsHealth / For Kids / Rabies What's in this article? ... than getting a deadly disease. Protect Yourself From Rabies The best way to protect yourself from getting ...

Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae

PubMed Central

2012-01-01

Background Rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP). To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus. Methods Eight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R) and observed for >130 days. Oral and blood samples were collected and analyzed. Results Two monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D.) was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429). No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody. Discussion This study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically apparent disease and

Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis.

PubMed

Nelson, Noele P

2017-09-15

GamaSTAN S/D (Grifols Therapeutics, Inc., Research Triangle Park, North Carolina) is a sterile, preservative-free solution of immune globulin (IG) for intramuscular administration and is used for prophylaxis against disease caused by infection with hepatitis A, measles, varicella, and rubella viruses (1). GamaSTAN S/D is the only IG product approved by the Food and Drug Administration for hepatitis A virus (HAV) prophylaxis. In July 2017, GamaSTAN S/D prescribing information was updated with changes to the dosing instructions for hepatitis A preexposure and postexposure prophylaxis indications. These changes were made because of concerns about decreased HAV immunoglobulin G antibody (anti-HAV IgG) potency, likely resulting from decreasing prevalence of previous HAV infection among plasma donors, leading to declining anti-HAV antibody levels in donor plasma (2). No changes in dosing instructions were made for measles, varicella, or rubella preexposure or postexposure prophylaxis.

Experimental infection of Artibeus intermedius with a vampire bat rabies virus.

PubMed

Obregón-Morales, Cirani; Aguilar-Setién, Álvaro; Perea Martínez, Leonardo; Galvez-Romero, Guillermo; Martínez-Martínez, Flor Olivia; Aréchiga-Ceballos, Nidia

2017-06-01

Experimental infection of Artibeus intermedius, the great fruit-eating bat, was performed with vampire bat rabies isolates. Bats (n=35) were captured in the wild and quarantined prior to experimental infection. No rabies antibodies were detected by rapid fluorescent focus inhibition test (RFFIT) prior to infection. Three doses of rabies virus (RV) and three different routes of infection were used. One out of 35 bats died without showing any clinical signs at day 14 and was positive for rabies. None of the 34 other bats showed clinical signs for rabies, but high antibody titers were detected post-inoculation, suggesting either innate immune response to the vampire bat rabies virus or possible pre-exposure to RV and inoculation leading to a booster effect. Rabies virus was detected by hemi-nested RT-PCR (hnRT-PCR) in the brain (n=3), stomach (n=1) of bats that were negative by immunofluorescence and that survived rabies infection. The bat that died on day 14 was positive by hnRT-PCR on the brain, heart and liver. These results suggest that either previous non-lethal exposure to RV or natural low susceptibility to vampire bat viruses somehow protected Artibeus intermedius from clinical rabies infection leading to a marginal lethality effect on this bats species population in the wild. Copyright © 2017 Elsevier Ltd. All rights reserved.

Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus.

PubMed

Lakshmanan, Nallakannu; Gore, Thomas C; Duncan, Karen L; Coyne, Michael J; Lum, Melissa A; Sterner, Frank J

2006-01-01

Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.

Intravenous Immune Globulin in Children with Streptococcal Toxic Shock Syndrome

PubMed Central

Shah, Samir S.; Hall, Matthew; Srivastava, Raj; Subramony, Anupama; Levin, James E.

2009-01-01

Background Streptococcal toxic shock syndrome (TSS) is a rare and severe manifestation of group A streptococcal infection. The role of intravenous immune globulin (IVIG) for streptococcal TSS in children is controversial. Objective To describe the epidemiology of streptococcal TSS in children and to determine whether adjunctive therapy with IVIG is associated with improved outcomes. Methods A multicenter retrospective cohort study of children with streptococcal TSS from 2003-2007 was conducted. Propensity scores were used to determine each child's likelihood of receiving IVIG. Differences in the primary outcomes of death, hospital length of stay, and total hospital costs were compared after matching IVIG-recipients and non-recipients on propensity score. Results The median age was 8.2 years. IVIG was administered to 84 (44%) of 192. Overall mortality was 4.2% (95% confidence interval: 1.8% to 8.0%). Differences in mortality between IVIG recipients (n=3, 4.5%) and non-recipients (n=3, 4.5%) were not statistically significant (P=1.00). While patients receiving IVIG had higher total hospital and drug costs than non-recipients, differences in hospital costs were not significant once drug costs were removed (median difference between matched patients, $6,139; interquartile range: -$8,316 to $25,993; P=0.06). There were no differences in length of stay between matched IVIG recipients and non-recipients. Conclusion This multicenter study is the largest to describe the epidemiology and outcomes of children with streptococcal TSS and the first to explore the association between IVIG use and clinical outcomes. IVIG use was associated with increased costs of caring for children with streptococcal TSS but was not associated with improved outcomes. PMID:19788359

Antibody response to an anti-rabies vaccine in a dog population under field conditions in Bolivia.

PubMed

Suzuki, K; González, E T; Ascarrunz, G; Loza, A; Pérez, M; Ruiz, G; Rojas, L; Mancilla, K; Pereira, J A C; Guzman, J A; Pecoraro, M R

2008-10-01

Rabies remains an important public health issue in Bolivia, South America. Public concern and fears are most focussed on dogs as the source of rabies. The objective of the present study was to assess immunity of an inactivated suckling mouse brain vaccine against canine rabies used for the official vaccination campaigns under field conditions in an endemic area of rabies in Bolivia. A total of 236 vaccinated and 44 unvaccinated dogs in Santa Cruz de la Sierra, selected using stratified random sampling, were investigated in order to obtain owned dog characteristics and antibody titres against rabies in April 2007. The proportion of vaccinated dogs with an antibody titre exceeded the protection threshold value of 0.5 EU/ml was 58% [95% confidence intervals (CI): 52-65], indicating that vaccination is likely to elicit an antibody response (odds ratio 6.3, 95% CI: 1.2-11.5). The range of geometric mean of antibody titre for vaccinated dogs (0.89 EU/ml; 95% CI: 0.75-1.04) was considered to meet the minimal acceptable level indicating an adequate immune response to the vaccine. However, the titre level was not satisfactory in comparison with the results from other field investigations with inactivated tissue culture vaccines. It is recommended for public health authorities to (1) consider modernizing their vaccine manufacturing method because the level of immunity induced by the current vaccine is comparably low, (2) conduct frequent vaccination campaigns to maintain high levels of vaccination coverage, and (3) actively manage the domestic dog population in the study area, which is largely responsible for rabies maintenance.

Two potential recombinant rabies vaccines expressing canine parvovirus virion protein 2 induce immunogenicity to canine parvovirus and rabies virus.

PubMed

Luo, Jun; Shi, Hehe; Tan, Yeping; Niu, Xuefeng; Long, Teng; Zhao, Jing; Tian, Qin; Wang, Yifei; Chen, Hao; Guo, Xiaofeng

2016-08-17

Both rabies virus (RABV) and canine parvovirus (CPV) cause lethal diseases in dogs. In this study, both high egg passage Flury (HEP-Flury) strains of RABV and recombinant RABV carrying double RABV glycoprotein (G) gene were used to express the CPV virion protein 2 (VP2) gene, and were designated rHEP-VP2 and, rHEP-dG-VP2 respectively. The two recombinant RABVs maintained optimal virus titration according to their viral growth kinetics assay compared with the parental strain HEP-Flury. Western blotting indicated that G protein and VP2 were expressed in vitro. The expression of VP2 in Crandell feline kidney cells post-infection by rHEP-VP2 and rHEP-dG-VP2 was confirmed by indirect immunofluorescence assay with antibody against VP2. Immunogenicity of recombinant rabies viruses was tested in Kunming mice. Both rHEP-VP2 and rHEP-dG-VP2 induced high levels of rabies antibody compared with HEP-Flury. Mice immunized with rHEP-VP2 and rHEP-dG-VP2 both had a high level of antibodies against VP2, which can protect against CPV infection. A challenge experiment indicated that more than 80% mice immunized with recombinant RABVs survived after infection of challenge virus standard 24 (CVS-24). Together, this study showed that recombinant RABVs expressing VP2 induced protective immune responses to RABV and CPV. Therefore, rHEP-VP2 and rHEP-dG-VP2 might be potential combined vaccines for RABV and CPV. Copyright © 2016 Elsevier Ltd. All rights reserved.

The epidemiology of rabies in Zimbabwe. 1. Rabies in dogs (Canis familiaris).

PubMed

Bingham, J; Foggin, C M; Wandeler, A I; Hill, F W

1999-03-01

The epidemiology of rabies in dogs in Zimbabwe is described using data from 1950, when rabies was re-introduced after a 37-year absence, to 1996. Dogs constituted 45.7% of all laboratory-confirmed rabies cases and were the species most frequently diagnosed with the disease. Slightly more cases were diagnosed from June to November than in other months. From 1950 to the early 1980s, most dog cases were recorded from commercial farming areas, but since the early 1980s most have been recorded from communal (subsistence farming) areas. This change appears to be due to improved surveillance in communal areas and not to any change in the prevalence of rabies. Dog rabies therefore appears to be maintained mainly in communal area dog populations, particularly the large communal area blocks. Urban rabies was not important except in the city of Mutare. Where dog rabies prevalence was high, the disease was cyclic with periods between peak prevalence ranging from 4-7 years. Dog rabies cases were, on the whole, independent of jackal rabies and rabies in other carnivores. There was a significant negative relationship between the annual number of rabies vaccine doses administered nationally to dogs and the annual number of dog rabies cases lagged by one year, indicating that the past levels of immunisation coverage have had a significant effect on the number of rabies cases. However, dog vaccination coverage has clearly not been adequate to prevent the regular occurrence of rabies in dogs.

Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine.

PubMed

Blaney, Joseph E; Marzi, Andrea; Willet, Mallory; Papaneri, Amy B; Wirblich, Christoph; Feldmann, Friederike; Holbrook, Michael; Jahrling, Peter; Feldmann, Heinz; Schnell, Matthias J

2013-01-01

We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced antibodies against EBOV GP differ in their target, affinity, or the isotype. Our results show that IgG1-biased humoral responses as well as high levels of GP-specific antibodies were beneficial for the control of EBOV infection after immunization. These results further support the concept that a successful EBOV vaccine needs to induce strong antibodies against EBOV. We also showed that a dual vaccine against RABV and filoviruses is achievable; therefore addressing concerns for the marketability of this urgently needed vaccine.

Rabies

MedlinePlus

Rabies is a deadly animal disease caused by a virus. It can happen in wild animals, including ... of an infected animal. In people, symptoms of rabies include fever, headache and fatigue, then confusion, hallucinations ...

Should cell-free DNA testing be used to target antenatal rhesus immune globulin administration?

PubMed

Ma, Kimberly K; Rodriguez, Maria I; Cheng, Yvonne W; Norton, Mary E; Caughey, Aaron B

2016-01-01

To compare the rates of alloimmunization with the use of cell-free DNA (cfDNA) screening to target antenatal rhesus immune globulin (RhIG) prenatally, versus routine administration of RhIG in rhesus D (RhD)-negative pregnant women in a theoretic cohort using a decision-analytic model. A decision-analytic model compared cfDNA testing to routine antenatal RhIG administration. The primary outcome was maternal sensitization to RhD antigen. Sensitivity and specificity of cfDNA testing were assumed to be 99.8% and 95.3%, respectively. Univariate and bivariate sensitivity analyses, Monte Carlo simulation, and threshold analyses were performed. In a cohort of 10,000 RhD-negative women, 22.6 sensitizations would occur with utilization of cfDNA, while 20 sensitizations would occur with routine RhIG. Only when the sensitivity of the cfDNA test reached 100%, the rate of sensitization was equal for both cfDNA and RhIG. Otherwise, routine RhIG minimized the rate of sensitization, especially given RhIG is readily available in the United States. Adoption of cfDNA testing would result in a 13.0% increase in sensitization among RhD-negative women in a theoretical cohort taking into account the ethnic diversity of the United States' population.

Learning about Bats and Rabies

MedlinePlus

... Rabies Day Rabies and Kids! Rabies Learning about bats and rabies Recommend on Facebook Tweet Share Compartir ... areas where they might contact people and pets. Bats and human rabies in the United States Rabies ...

Human rabies: a descriptive observation of 21 children in Kinshasa, the Democratic Republic of Congo.

PubMed

Muyila, Delphin I; Aloni, Michel N; Lose-Ekanga, Marie Josée; Nzita, Jules M; Kalala-Mbikay, Alexandre; Bongo, Henri L; Esako, Mathilde N; Malonga-Biapi, Jean Pierre; Mputu-Dibwe, BenoÎt; Aloni, Muriel L; Ekila, Mathilde B

2014-10-01

Human rabies has recently emerged as a significant public health threat in Kinshasa, Democratic Republic of Congo (DRC). However, there is little epidemiological information on human rabies especially in children. We performed at Pediatrics Department of General Reference hospital of Kinshasa between December 2008 and July 2009, a retrospective study to assess the incidence and to describe their clinical aspects and outcome. A total of 21 cases were observed, rather three cases per month. There were 12 boys (57·1%) and 9 girls (42·9%). Biting animal was found to be dog in all cases (100%). The dog was not immunized in all of cases. On admission, all patients (100%) showed furious rabies manifestations. Only two (9·5%) had their wounds treated and received an anti-rabies vaccine (ARV) after the bite incident. Two (9·5%) patients received rabies immunoglobulin (RIG). The case-fatality rate was 100%. The disease emerges as a new major public health problem because of a lack of knowledge regarding rabies risk, the poor management of dog bites. Preventative vaccination for rabies should be recommended in the population of Kinshasa, area at high risk to contract rabies, particularly in children.

Dogs that develop rabies post-vaccination usually manifest the paralytic subtype.

PubMed

Tepsumethanon, Veera; Likitsuntonwong, Wanlop; Thorner, Paul Scott; Shuangshoti, Shanop

2016-09-01

Rabies infection can manifest as either encephalitic (furious) or paralytic (dumb) types, with a ratio of approximately 2:1 in dogs. The clinical type of rabies that develops post-vaccination has only been reported in studies from one country, all with similar findings. We report a study of 36 rabid dogs with obtainable vaccination history, presenting to The Queen Saovabha Memorial Institute, Bangkok, Thailand during 2002-2008. Dogs were classified into encephalitic or paralytic types. Of 22 non-vaccinated dogs, 16 (73%) had the encephalitic type. In contrast, of the 14 vaccinated dogs, 10 (71%) had the paralytic type, a difference that was significant (p=0.016). Recent studies on canine brains have shown that lymphocyte response is more pronounced in paralytic rabies at the brainstem level, whereas viral burden is greater in the encephalitic form. We postulate partial immune response in the vaccinated dogs might influence rabies to manifest as the paralytic type. These results can serve as a natural experiment that can help explain the basis for the differences between the paralytic and encephalitic forms of canine rabies. Copyright © 2016 Elsevier B.V. All rights reserved.

Experimental rabies in skunks: effects of immunosuppression induced by cyclophosphamide.

PubMed Central

Charlton, K M; Casey, G A; Campbell, J B

1984-01-01

Striped skunks (Mephitis mephitis) were inoculated with street rabies virus and immunosuppressed with several doses of cyclophosphamide. Control skunks were inoculated with street virus only. The skunks were killed in terminal stages of the disease and several tissues were collected for examination by immunofluorescence, light microscopy and viral titration. Sera collected at euthanasia from most of the principals did not contain detectable rabies neutralizing antibodies, whereas high titers occurred terminally in controls. Immunofluorescence was much more entensive in submandibular salivary glands of cyclophosphamide-treated than control skunks. Similarly, virus was isolated from this tissue more consistently and at higher titer from principals than from controls. Immunofluorescence was extensive in brains of all skunks (both groups), but virus was isolated consistently only from brains of cyclophosphamide-treated skunks. Most of the cyclophosphamide-treated skunks had very few inflammatory cells in brain and cerebrospinal ganglia. Neuronal degeneration occurred in dorsal root ganglia of both principals and controls. The results suggest that the immune response has no effect on the development of rabies-induced aggressive behavior, that the immune response may inhibit salivary gland infection and that it is not essential for the development of neuronal degeneration in dorsal root ganglia. PMID:6370390

Rabies in Kazakhstan.

PubMed

Sultanov, Akmetzhan A; Abdrakhmanov, Sarsenbay K; Abdybekova, Aida M; Karatayev, Bolat S; Torgerson, Paul R

2016-08-01

Rabies is a neglected zoonotic disease. There is a sparsity of data on this disease with regard to the incidence of human and animal disease in many low and middle income countries. Furthermore, rabies results in a large economic impact and a high human burden of disease. Kazakhstan is a large landlocked middle income country that gained independence from the Soviet Union in 1991 and is endemic for rabies. We used detailed public health and veterinary surveillance data from 2003 to 2015 to map where livestock rabies is occurring. We also estimate the economic impact and human burden of rabies. Livestock and canine rabies occurred over most of Kazakhstan, but there were regional variations in disease distribution. There were a mean of 7.1 officially recorded human fatalities due to rabies per year resulting in approximately 457 Disability Adjusted Life Years (DALYs). A mean of 64,289 individuals per annum underwent post exposure prophylaxis (PEP) which may have resulted in an additional 1140 DALYs annually. PEP is preventing at least 118 cases of human rabies each year or possibly as many as 1184 at an estimated cost of $1193 or $119 per DALY averted respectively. The estimated economic impact of rabies in Kazakhstan is $20.9 million per annum, with nearly half of this cost being attributed to the cost of PEP and the loss of income whilst being treated. A further $5.4 million per annum was estimated to be the life time loss of income for fatal cases. Animal vaccination programmes and animal control programmes also contributed substantially to the economic losses. The direct costs due to rabies fatalities of agricultural animals was relatively low. This study demonstrates that in Kazakhstan there is a substantial economic cost and health impact of rabies. These costs could be reduced by modifying the vaccination programme that is now practised. The study also fills some data gaps on the epidemiology and economic effects of rabies in respect to Kazakhstan.

Vitamin B6 status, immune response and inflammation markers in kidney transplant recipients treated with polyclonal anti-thymocyte globulin.

PubMed

Jankowska, M; Trzonkowski, P; Dębska-Ślizień, A; Marszałł, M; Rutkowski, B

2014-10-01

Vitamin B6 status has an impact on the body's inflammatory and immune responses. Immunosuppressive therapy may influence vitamin B6 metabolism in kidney transplant recipients. Treatment with polyclonal anti-thymocyte globulin (ATG) is associated with long-term changes in inflammatory and immune parameters. It is not known if ATG therapy also may have an impact on vitamin B6 status in kidney transplant recipients. We aimed to analyze the impact of therapy with ATG on vitamin B6 status, immune response, and the profile of inflammatory cytokines. This was a retrospective, observational study that included 44 kidney allograft recipients. Twenty patients received induction therapy with ATG (6 to 24 months before enrollment). Twenty-four patients constituted the control group, matched with respect to time since transplantation. The B6 vitamers, total lymphocyte count, CD3 percentage, interleukin (IL)-6, -7, and -10, transforming growth factor β, interferon γ, and chemokine ligand 21 were analyzed in a study group. All indicators of vitamin B6 status were lower in the ATG group than in the control group. There were also significant differences with respect to immune response (significantly lower total lymphocyte count and CD3 in the ATG group) and inflammatory status (significantly higher IL-6 and IL-10 in the ATG group). Vitamin B6 vitamers and derivatives were not related to lymphocyte count and cytokine levels or to estimated glomerular filtration rate and age of the study population. Vitamin B6 stores and active forms are lower in kidney transplant recipients treated with ATG. ATG therapy promotes CD3 and total lymphocyte depletion and increases indicators of inflammation. We found no associations between vitamers of B6, immune response cells, and inflammatory cytokines in study population.

Human rabies in India: an audit from a rabies diagnostic laboratory.

PubMed

Mani, Reeta Subramaniam; Anand, Ashwini Manoor; Madhusudana, Shampur Narayan

2016-04-01

Rabies, an acute progressive encephalomyelitis, continues to be a serious public health problem in India and many other countries in Asia and Africa. The low level of commitment to rabies control is partly attributable to challenges in laboratory diagnosis and lack of adequate surveillance to indicate the disease burden. A laboratory audit of human rabies cases was undertaken to disseminate information on the clinical, demographic, prophylactic and most importantly the laboratory diagnostic aspects of rabies. A retrospective analysis of all clinically suspected human rabies cases, whose samples were received at a rabies diagnostic laboratory in South India in the last 3 years, was performed. Clinical and demographic details of patients were obtained. The clinical samples included cerebrospinal fluid (CSF), serum, saliva and nuchal skin biopsy collected antemortem, and brain tissue obtained post-mortem. Various laboratory tests were performed for diagnosis. Clinical samples from 128 patients with suspected rabies, from 11 states in India, were received for diagnostic confirmation. About 94% of the victims reported dog-bites, more than a third of them were children and most of the victims did not receive adequate post-exposure prophylaxis. Antemortem confirmation of rabies by a combination of laboratory diagnostic assays (detection of viral RNA in CSF, skin and saliva, and neutralising antibodies in CSF) could be achieved in 40.6% cases. Increasing awareness about adequate post-exposure prophylaxis, additional rabies diagnostic facilities, and enhanced human and animal rabies surveillance to indicate the true disease burden are essential to control this fatal disease. © 2016 John Wiley & Sons Ltd.

Newcastle disease virus-vectored rabies vaccine is safe, highly immunogenic, and provides long-lasting protection in dogs and cats.

PubMed

Ge, Jinying; Wang, Xijun; Tao, Lihong; Wen, Zhiyuan; Feng, Na; Yang, Songtao; Xia, Xianzhu; Yang, Chinglai; Chen, Hualan; Bu, Zhigao

2011-08-01

Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10⁹·⁸ 50% egg infective doses (EID₅₀)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10⁸·³ EID₅₀ completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.

Postexposure prevention of progressive vaccinia in SCID mice treated with vaccinia immune globulin.

PubMed

Fisher, R W; Reed, J L; Snoy, P J; Mikolajczyk, M G; Bray, M; Scott, D E; Kennedy, M C

2011-01-01

A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV.

Expression of rabies glycoprotein and ricin toxin B chain (RGP-RTB) fusion protein in tomato hairy roots: a step towards oral vaccination for rabies.

PubMed

Singh, Ankit; Srivastava, Subhi; Chouksey, Ankita; Panwar, Bhupendra Singh; Verma, Praveen C; Roy, Sribash; Singh, Pradhyumna K; Saxena, Gauri; Tuli, Rakesh

2015-04-01

Transgenic hairy roots of Solanum lycopersicum were engineered to express a recombinant protein containing a fusion of rabies glycoprotein and ricin toxin B chain (rgp-rtxB) antigen under the control of constitutive CaMV35S promoter. Asialofetuin-mediated direct ELISA of transgenic hairy root extracts was performed using polyclonal anti-rabies antibodies (Ab1) and epitope-specific peptidal anti-RGP (Ab2) antibodies which confirmed the expression of functionally viable RGP-RTB fusion protein. Direct ELISA based on asialofetuin-binding activity was used to screen crude protein extracts from five transgenic hairy root lines. Expressions of RGP-RTB fusion protein in different tomato hairy root lines varied between 1.4 and 8 µg in per gram of tissue. Immunoblotting assay of RGP-RTB fusion protein from these lines showed a protein band on monomeric size of ~84 kDa after denaturation. Tomato hairy root line H03 showed highest level of RGP-RTB protein expression (1.14 %) and was used further in bench-top bioreactor for the optimization of scale-up process to produce large quantity of recombinant protein. Partially purified RGP-RTB fusion protein was able to induce the immune response in BALB/c mice after intra-mucosal immunization. In the present investigation, we have not only successfully scaled up the hairy root culture but also established the utility of this system to produce vaccine antigen which subsequently will reduce the total production cost for implementing rabies vaccination programs in developing nations. This study in a way aims to provide consolidated base for low-cost preparation of improved oral vaccine against rabies.

Neutralizing Antibody Response in Dogs and Cats Inoculated with Commercial Inactivated Rabies Vaccines

PubMed Central

SHIRAISHI, Rikiya; NISHIMURA, Masaaki; NAKASHIMA, Ryuji; ENTA, Chiho; HIRAYAMA, Norio

2013-01-01

ABSTRACT In Japan, the import quarantine regulation against rabies has required from 2005 that dogs and cats should be inoculated with the rabies vaccine and that the neutralizing antibody titer should be confirmed to be at least 0.5 international units (IU)/ml. The fluorescent antibody virus neutralization (FAVN) test is used as an international standard method for serological testing for rabies. To achieve proper immunization of dogs and cats at the time of import and export, changes in the neutralizing antibody titer after inoculation of the rabies vaccine should be understood in detail. However, few reports have provided this information. In this study, we aimed to determine evaluated, such changes by using sera from experimental dogs and cats inoculated with the rabies vaccine, and we tested samples using the routine FAVN test. In both dogs and cats, proper, regular vaccination enabled the necessary titer of neutralizing antibodies to be maintained in the long term. However, inappropriate timing of blood sampling after vaccination could result in insufficient detected levels of neutralizing antibodies. PMID:24389741

Neutralizing antibody response in dogs and cats inoculated with commercial inactivated rabies vaccines.

PubMed

Shiraishi, Rikiya; Nishimura, Masaaki; Nakashima, Ryuji; Enta, Chiho; Hirayama, Norio

2014-04-01

In Japan, the import quarantine regulation against rabies has required from 2005 that dogs and cats should be inoculated with the rabies vaccine and that the neutralizing antibody titer should be confirmed to be at least 0.5 international units (IU)/ml. The fluorescent antibody virus neutralization (FAVN) test is used as an international standard method for serological testing for rabies. To achieve proper immunization of dogs and cats at the time of import and export, changes in the neutralizing antibody titer after inoculation of the rabies vaccine should be understood in detail. However, few reports have provided this information. In this study, we aimed to determine evaluated, such changes by using sera from experimental dogs and cats inoculated with the rabies vaccine, and we tested samples using the routine FAVN test. In both dogs and cats, proper, regular vaccination enabled the necessary titer of neutralizing antibodies to be maintained in the long term. However, inappropriate timing of blood sampling after vaccination could result in insufficient detected levels of neutralizing antibodies.

PROPERTIES OF VARIOUS ANTI-γ-GLOBULIN FACTORS IN HUMAN SERA

PubMed Central

Harboe, Morten; Rau, Barbara; Aho, Kimmo

1965-01-01

The serological and physicochemical properties of the following three forms of human anti-γ-globulin factors were compared: (a) rheumatoid factors; (b) Milgrom type anti-γ-globulin factors; and (c) factors directed against an antigen in human γG-globulin that is hidden in the intact molecule and revealed by enzymatic digestion at low pH. The property common to these factors is ability to interact with human γG-globulin; they are distinguishable because they react with different antigenic groups on this molecule. In all of five sera, the Milgrom type anti-γ-globulin factors were γM-globulins. They reacted with various human γG-globulin antibodies but failed to interact with γM-globulin type antibodies in agglutination and absorption experiments. When isolated from other anti-γ-globulin factors, they agglutinated red cells coated with intact anti-Rh antibodies, but failed to react with cells cells coated with pepsin-digested anti-Rh antibody. These observations indicate that the agglutinator reacts with the crystallizable, inert fragment of γG-globulin. Anti-γ-globulin activity directed against an antigen in human γG-globulin revealed by pepsin digestion was demonstrated in γG-, γA-, and γM-globulins. This anti-γ-globulin factor could be absorbed by antigen-antibody precipitates containing human antibody, which shows that the hidden antigen in human γG-globulin is revealed not only by enzymatic digestion at low pH, but also when γG-globulin is present as antibody in an antigen-antibody precipitate. Rheumatoid factors and Milgrom type anti-γ-globulin factors were also absorbed by antigen-antibody precipitates containing human antibody. The results indicate that the three distinct forms of antiγ-globulin factors may all be produced as a result of antigenic stimulation by autologous antigen-antibody complexes. PMID:14276773

Rabies (image)

MedlinePlus

... messages between the brain and the body. The rabies virus spreads through the nerves, first causing flu- ... to hallucinations, delirium, and insomnia. If left untreated, rabies is nearly always fatal.

Genetics Home Reference: inherited thyroxine-binding globulin deficiency

MedlinePlus

... Health Conditions Inherited thyroxine-binding globulin deficiency Inherited thyroxine-binding globulin deficiency Printable PDF Open All Close ... to view the expand/collapse boxes. Description Inherited thyroxine-binding globulin deficiency is a genetic condition that ...

A rabies lesson improves rabies knowledge amongst primary school children in Zomba, Malawi.

PubMed

Burdon Bailey, Jordana L; Gamble, Luke; Gibson, Andrew D; Bronsvoort, Barend M deC; Handel, Ian G; Mellanby, Richard J; Mazeri, Stella

2018-03-01

Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children's knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p<0.001), and knowledge remained higher than baseline 9 weeks after the lesson (both p<0.001). Knowledge of rabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both p<0.001) indicating that the lesson itself was critical in improving knowledge. In summary, we have shown that a short, focused classroom-based lesson on rabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren.

A rabies lesson improves rabies knowledge amongst primary school children in Zomba, Malawi

PubMed Central

Burdon Bailey, Jordana L.; Gamble, Luke; Gibson, Andrew D.; Bronsvoort, Barend M. deC.; Handel, Ian G.; Mellanby, Richard J.; Mazeri, Stella

2018-01-01

Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children’s knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both p<0.001), and knowledge remained higher than baseline 9 weeks after the lesson (both p<0.001). Knowledge of rabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both p<0.001) indicating that the lesson itself was critical in improving knowledge. In summary, we have shown that a short, focused classroom-based lesson on rabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren. PMID:29522517

Lack of association between Rh status, Rh immune globulin in pregnancy and autism.

PubMed

Miles, Judith H; Takahashi, T Nicole

2007-07-01

Though causes of autism are considered largely genetic, considerable concern remains that exposure to Rh immune globulin (RhIg), which until 2001 in the United States contained the preservative thimerosal, can cause autism. To determine whether mothers of children with autism are more likely to be Rh negative (Rh(-)) or to have received RhIg preserved with thimerosal, which is 49.6% ethyl mercury, we surveyed families of children with an autism spectrum disorder (ASD) ascertained through a University-based autism clinic considered free of ascertainment biases related to type of autism or severity. Between 2004 and 2006, 305 mothers of 321 children with an ASD agreed to participate in a telephone interview. Analysis of complete records including the blood group status and RhIg exposure of 214 families showed that Rh(-) status is no higher in mothers of children with autism than in the general population, exposure to antepartum RhIg, preserved with thimerosal is no higher for children with autism and pregnancies are no more likely to be Rh incompatible. This was also true for autism subgroups defined by behavioral phenotype, gender, IQ, regressive onset, head circumference, dysmorphology, birth status, essential, or complex phenotype. These findings support the consensus that exposure to ethylmercury in thimerosal is not the cause of the increased prevalence of autism. These data are important not only for parents in this country but also for the international health community where thimerosal continues to be used to preserve multi-dose vials which in turn makes vaccines affordable. (c) 2007 Wiley-Liss, Inc.

Travel-Associated Rabies in Pets and Residual Rabies Risk, Western Europe.

PubMed

Ribadeau-Dumas, Florence; Cliquet, Florence; Gautret, Philippe; Robardet, Emmanuelle; Le Pen, Claude; Bourhy, Hervé

2016-07-01

In 2015, countries in western Europe were declared free of rabies in nonflying mammals. Surveillance data for 2001-2013 indicate that risk for residual rabies is not 0 because of pet importation from countries with enzootic rabies. However, the risk is so low (7.52 × 10(-10)) that it probably can be considered negligible.

Ecology of rabies in Southern Rhodesia.

PubMed

ADAMSON, J S

1954-01-01

The spread of rabies since 1950 in Southern Rhodesia is described, and its probable causes analysed; the outbreak is attributed chiefly to the vast domestic-dog population, but cases have been noted among many other species of animal. The difficulties encountered in enforcing general control measures are discussed; however, the advent of Flury-strain avianized vaccine has allowed of a successful inoculation campaign which, in spite of some failure in immunization, is satisfactorily controlling the disease in most of the areas involved.

An important date in rabies history.

PubMed

Dodet, Betty

2007-12-17

Rabies is estimated to cause 31,000 human deaths in Asia annually. Several recent events, including World Rabies Day have brought this neglected disease to the attention of the scientific community, governmental authorities, the media and the public. It is hoped that this will result in an increased collaboration between veterinary and human health authorities, and an involvement at all levels necessary for the control and elimination of rabies in dogs, the main reservoir and vector of rabies in Asia. Dog rabies elimination is considered as the most cost-effective solution to prevent rabies deaths in humans. Asian countries such as India and the Philippines have recently adopted the objective of eliminating rabies by 2020. To support World Rabies Day, the Asian Rabies Expert Bureau (AREB) had its 4th annual meeting from 5 to 7 September 2007, with the objective of debating strategies for lowering the human rabies toll. Human rabies deaths can already be prevented by improving the compliance to WHO post-exposure prophylaxis recommendations. In addition, in regions with a high incidence of canine rabies and where rabies control in dogs is not yet achieved or not effective, systematic pre-exposure vaccination of children who are the main victims of rabies, may prevent their premature deaths.

Rabies in Poland in 2011.

PubMed

Sadkowska-Todys, Malgorzata; Kucharczyk, Bozena

2013-01-01

To assess epidemiological situation of rabies in Poland in 2011. The assessment was based on the results of the data analysis from questionnaires (People vaccinated against rabies post-exposure surveys in Poland and people vaccinated against rabies after exposure in other countries) submitted by the Sanitary-Epidemiological Stations and data from the annual newsletter "Infectious diseases and poisonings in Poland in 2011" (Czarkowski MP et al., Warsaw, NIZP-PZH and GIS) and epizootic data provided by the General Veterinary Inspectorate. In 2011, in Poland, 160 cases of rabies (in 2010 - 152 cases) were reported. Animal cases occurred primarily in the Malopolska province, where an increase in animal rabies cases has been observed since September 2010 and in Podkarpackie province. A single case of fox rabies was reported in Silesia, where there was no disease for many years. Rabies among terrestrial animals also occurred in the provinces ofLubelskie, Warmińsko-Mazurskie and Podlaskie. In other regions of the country there were recorded only isolated cases of bat rabies. In 2011, number of people vaccinated against rabies was 7 543 (in 2010 - 7,243), of which 300 (4%) due to exposure to the animals that were confirmed to have rabies. Among those vaccinated because of contact with the rabid animal, 68 people (over 22%) were vaccinated after contact with fox. As in previous years, people were mainly vaccinated after exposure to dogs and cats in which rabies could not be ruled out - 5 874 persons (78%). The number of registered animals with confirmed rabies remains at the same level and the disease epizootic situation is good. This is a consequence of the implementation of the oral vaccination of wild animals introduced in the country in 1993. Epizootic situation in the country has a small influence on the number of people vaccinated against rabies who have come into contact with the animal potentially infected with the rabies. Serum is given in a few cases, including a

Duration of serum antibody response to rabies vaccination in horses.

PubMed

Harvey, Alison M; Watson, Johanna L; Brault, Stephanie A; Edman, Judy M; Moore, Susan M; Kass, Philip H; Wilson, W David

2016-08-15

OBJECTIVE To investigate the impact of age and inferred prior vaccination history on the persistence of vaccine-induced antibody against rabies in horses. DESIGN Serologic response evaluation. ANIMALS 48 horses with an undocumented vaccination history. PROCEDURES Horses were vaccinated against rabies once. Blood samples were collected prior to vaccination, 3 to 7 weeks after vaccination, and at 6-month intervals for 2 to 3 years. Serum rabies virus-neutralizing antibody (RVNA) values were measured. An RVNA value of ≥ 0.5 U/mL was used to define a predicted protective immune response on the basis of World Health Organization recommendations for humans. Values were compared between horses < 20 and ≥ 20 years of age and between horses inferred to have been previously vaccinated and those inferred to be immunologically naïve. RESULTS A protective RVNA value (≥ 0.5 U/mL) was maintained for 2 to 3 years in horses inferred to have been previously vaccinated on the basis of prevaccination RVNA values. No significant difference was evident in response to rabies vaccination or duration of protective RVNA values between horses < 20 and ≥ 20 years of age. Seven horses were poor responders to vaccination. Significant differences were identified between horses inferred to have been previously vaccinated and horses inferred to be naïve prior to the study. CONCLUSIONS AND CLINICAL RELEVANCE A rabies vaccination interval > 1 year may be appropriate for previously vaccinated horses but not for horses vaccinated only once. Additional research is required to confirm this finding and characterize the optimal primary dose series for rabies vaccination.

Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16–December 28, 2013

PubMed Central

Huang, Angela Song-En; Chen, Wan-Chin; Huang, Wan-Ting; Huang, Shih-Tse; Lo, Yi-Chun; Wei, Sung-Hsi; Kuo, Hung-Wei; Chan, Pei-Chun; Hung, Min-Nan; Liu, Yu-Lun; Mu, Jung-Jung; Yang, Jyh-Yuan; Liu, Ding-Ping; Chou, Jih-Haw; Chuang, Jen-Hsiang; Chang, Feng-Yee

2015-01-01

Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010–July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial

Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

PubMed Central

Sparks, Susan; Rakocevic, Goran; Joe, Galen; Manoli, Irini; Shrader, Joseph; Harris-Love, Michael; Sonies, Barbara; Ciccone, Carla; Dorward, Heidi; Krasnewich, Donna; Huizing, Marjan; Dalakas, Marinos C; Gahl, William A

2007-01-01

Background Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM. Methods We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. Results For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. Conclusion The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM. PMID:17261181

Ecology of rabies in Southern Rhodesia

PubMed Central

Adamson, J. S.

1954-01-01

The spread of rabies since 1950 in Southern Rhodesia is described, and its probable causes analysed; the outbreak is attributed chiefly to the vast domestic-dog population, but cases have been noted among many other species of animal. The difficulties encountered in enforcing general control measures are discussed; however, the advent of Flury-strain avianized vaccine has allowed of a successful inoculation campaign which, in spite of some failure in immunization, is satisfactorily controlling the disease in most of the areas involved. PMID:13182596

Factors associated with dog rabies vaccination in Bhol, Philippines: results of a cross-sectional cluster survey conducted following the island-wide rabies elimination campaign.

PubMed

Davlin, S; Lapiz, S M; Miranda, M E; Murray, K

2013-11-01

The Philippines has a long history of rabies control efforts in their dog populations; however, long-term success of such programmes and the goal of rabies elimination have not yet been realized. The Bohol Rabies Prevention and Elimination Program was developed as an innovative approach to canine rabies control in 2007. The objective of this study was to assess canine rabies vaccination coverage in the owned-dog population in Bohol and to describe factors associated with rabies vaccination 2 years after implementation of the programme. We utilized a cross-sectional cluster survey based on the World Health Organization's Expanded Programme on Immunization coverage survey technique. We sampled 460 households and collected data on 539 dogs residing within these households. Seventy-seven per cent of surveyed households reported owning at least one dog. The human-to-dog ratio was approximately 4 : 1, and the mean number of dogs owned per household was 1.6. Based on this ratio, we calculated an owned-dog population of almost 300 000. Overall, 71% of dogs were reported as having been vaccinated for rabies at some time in their lives; however, only 64% of dogs were reported as having been recently vaccinated. Dogs in our study were young (median age = 24 months). The odds of vaccination increased with increasing age. Dogs aged 12-23 months had 4.6 times the odds of vaccination compared to dogs aged 3-11 months (95% CI 1.8-12.0; P = 0.002). Confinement of the dog both day and night was also associated with increased odds of vaccination (OR = 2.1; 95% CI 0.9-4.9; P = 0.07), and this result approached statistical significance. While the programme is on track to meet its goal of 80% vaccination coverage, educational efforts should focus on the need to confine dogs and vaccinate young dogs. © 2012 Blackwell Verlag GmbH.

Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe

PubMed Central

Müller, Thomas F.; Schröder, Ronald; Wysocki, Patrick; Mettenleiter, Thomas C.; Freuling, Conrad M.

2015-01-01

In Europe, the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story. Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet, we evaluated the use of different vaccine baits over the entire period of ORV [1978–2014]. Our findings provide valuable insights into the complexity of ORV programs in terms of vaccine related issues. More than 10 oral vaccines against rabies were used over the past four decades. Depending on many factors, the extent to which oral rabies virus vaccines were used varied considerably resulting in huge differences in the number of vaccine doses disseminated in ORV campaigns as well as in large spatial and temporal overlaps. Although vaccine virus strains derived from the SAD rabies virus isolate were the most widely used, the success of ORV campaigns in Europe cannot be assigned to a single oral rabies virus vaccine alone. Rather, the successful elimination of fox rabies is the result of an interaction of different key components of ORV campaigns, i.e. vaccine strain, vaccine bait and strategy of distribution. PMID:26280895

SINGLE- VERSUS DOUBLE-DOSE RABIES VACCINATION IN CAPTIVE AFRICAN WILD DOGS (LYCAON PICTUS).

PubMed

Connolly, Maren; Thomas, Patrick; Woodroffe, Rosie; Raphael, Bonnie L

2015-12-01

The immune responses of 35 captive African wild dogs (Lycaon pictus) to an inactivated rabies virus vaccine were evaluated. Seventeen animals received one 1-ml dose of inactivated rabies vaccine administered intramuscularly, while 18 received two 1-ml doses given simultaneously but at different injection sites. Sera were collected from all animals prior to vaccination and intermittently from a subset of animals between 3 and 49 mo postvaccination. Rabies neutralizing serum antibody titers were measured by rapid fluorescent focus inhibition testing. Within 3 mo postvaccination, all 28 animals that were tested within that time period had seroconverted. Overall, titers were significantly higher among animals given two doses of vaccine than among those given a single dose, although this difference was no longer significant by 15 mo postvaccination. Regardless of initial dose, a single administration of inactivated rabies virus vaccine resulted in long-term elevation of titers in the African wild dogs in this study. In the two individuals followed for greater than 36 mo, both (one from each group) maintained detectable titers.

Oral vaccination of wildlife against rabies: opportunities and challenges in prevention and control.

PubMed

Rupprecht, C E; Hanlon, C A; Slate, D

2004-01-01

Rabies is an acute, progressive, fatal encephalitis caused by viruses in the Family Rhabdoviridae, Genus Lyssavirus. Rabies virus is the representative member of the group. Warm-blooded vertebrates are susceptible to experimental infection, but major primary hosts for disease perpetuation encompass bats and mammalian carnivores. The dog is the global reservoir, and important wild carnivores include foxes, raccoons, skunks, and mongoose, among others. Traditionally, reliance upon long-term, widespread, government-supported programmes aimed at population reduction of animals at risk has been unsuccessful as the sole means of rabies control, based in part upon economical, ecological and ethical grounds. In contrast, immunization of domestic dogs with traditional veterinary vaccines by the parenteral route led to the virtual extinction of canine-transmitted rabies in developed countries. Taken from this basic concept of applied herd immunity, the idea of wildlife vaccination was conceived during the 1960s, and modified-live rabies viruses were used for the experimental oral vaccination of carnivores by the 1970s. The development of safe and effective rabies virus vaccines applied in attractive baits resulted in the first field trials in Switzerland in 1978. Thereafter, technical improvements occurred in vaccine quality and production, including the design of recombinant viruses, as well as in the ease of mass distribution of millions of edible baits over large geographical areas. Over the past few decades, extensive oral vaccination programmes focusing upon the red fox, using hand and aerial distribution of vaccine-laden baits, have resulted in the virtual disappearance of rabies in Western Europe. The same dramatic observation held true for southern Ontario. During the 1990s in the United States, oral vaccination programmes concentrated upon raccoons, grey foxes, and coyotes, with similar success. For example, raccoon rabies has not spread west of the current focus in

Rabies in the Americas

Science.gov Websites

Rabies in the Americas Search this site Welcome Previous Meetings Steering Committee Contact Sitemap Welcome The Rabies in the Americas (RITA) meeting is an annual event that has been held since 1990 managers of rabies programs, wildlife biologists, laboratory personnel and other people interested in

Bat-borne rabies in Latin America.

PubMed

Escobar, Luis E; Peterson, A Townsend; Favi, Myriam; Yung, Verónica; Medina-Vogel, Gonzalo

2015-01-01

The situation of rabies in America is complex: rabies in dogs has decreased dramatically, but bats are increasingly recognized as natural reservoirs of other rabies variants. Here, bat species known to be rabies-positive with different antigenic variants, are summarized in relation to bat conservation status across Latin America. Rabies virus is widespread in Latin American bat species, 22.5%75 of bat species have been confirmed as rabies-positive. Most bat species found rabies positive are classified by the International Union for Conservation of Nature as "Least Concern". According to diet type, insectivorous bats had the most species known as rabies reservoirs, while in proportion hematophagous bats were the most important. Research at coarse spatial scales must strive to understand rabies ecology; basic information on distribution and population dynamics of many Latin American and Caribbean bat species is needed; and detailed information on effects of landscape change in driving bat-borne rabies outbreaks remains unassessed. Finally, integrated approaches including public health, ecology, and conservation biology are needed to understand and prevent emergent diseases in bats.

BAT-BORNE RABIES IN LATIN AMERICA

PubMed Central

Escobar, Luis E.; Peterson, A. Townsend; Favi, Myriam; Yung, Verónica; Medina-Vogel, Gonzalo

2015-01-01

The situation of rabies in America is complex: rabies in dogs has decreased dramatically, but bats are increasingly recognized as natural reservoirs of other rabies variants. Here, bat species known to be rabies-positive with different antigenic variants, are summarized in relation to bat conservation status across Latin America. Rabies virus is widespread in Latin American bat species, 22.5%75 of bat species have been confirmed as rabies-positive. Most bat species found rabies positive are classified by the International Union for Conservation of Nature as “Least Concern”. According to diet type, insectivorous bats had the most species known as rabies reservoirs, while in proportion hematophagous bats were the most important. Research at coarse spatial scales must strive to understand rabies ecology; basic information on distribution and population dynamics of many Latin American and Caribbean bat species is needed; and detailed information on effects of landscape change in driving bat-borne rabies outbreaks remains unassessed. Finally, integrated approaches including public health, ecology, and conservation biology are needed to understand and prevent emergent diseases in bats. PMID:25651328

Rabies and rabies virus in wildlife in mainland China, 1990-2013.

PubMed

Wang, Lihua; Tang, Qing; Liang, Guodong

2014-08-01

The number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions of mainland China. To better understand wildlife rabies and its role in human and livestock rabies, we reviewed what is known about wildlife rabies from the 1990s to 2013 in mainland China. In addition, the genetic diversity and phylogeny of available wildlife-originated rabies viruses (RABVs) were analyzed. Several wildlife species carry rabies including the bat, Chinese ferret badger, raccoon dog, rat, fox, and wolf. RABVs have been isolated or detected in the bat, Chinese ferret badger, raccoon dog, Apodemus, deer, and vole. Among them, the bat, Chinese ferret badger, and raccoon dog may play a role in the ecology of lyssaviruses in mainland China. All wildlife-originated RABVs were found to belong to genotype 1 RABV except for a bat-originated Irkut virus isolated in 2012. Several substitutions were found between the glycoprotein of wildlife-originated RABVs and vaccine strains. Whether these substitutions could affect the efficacy of currently used vaccines against infections caused by these wildlife-originated RABVs needs to be investigated further. Phylogenetic analysis showed that RABVs in the bat, Chinese ferret badger, and raccoon dog were distinct from local dog-originated RABVs, and almost all collected wildlife-originated isolates were associated with older China clades II to V, suggesting the possibility of wildlife reservoirs in mainland China through the ages. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Globulin. (a) Proper name and definition. The proper name of this product shall be Anti-Human Globulin... in tissue cultures or in secondary hosts. [50 FR 5579, Feb. 11, 1985, as amended at 65 FR 77499, Dec...

[Adverse reaction caused by rabies vaccine in China: a Meta-analysis].

PubMed

Zhang, X R; Wu, Z G; Zhang, W S

2017-06-10

Objective: To conduct a Meta-analysis on the rate of adverse reaction related to rabies vaccine, so as to provide reference for rabies vaccine immunization in China. Methods: We electronically searched databases including CNKI, VIP information resource integration service platform, WanFang Data, CBM, PubMed and The Cochrane Library, to collect studies on Chinese people who had received full rabies vaccination and recording all the adverse reactions, from January 2000 to July 2016. Inclusion and exclusion criteria were strictly followed. Meta-analysis for the adverse reaction rate was performed using the R software. Results: A total of 29 related papers had met the inclusion criteria, with no publication bias noticed. A total number of 11 020 cases had adverse reactions, among all the 94 222 respondents, with an incidence of adverse reactions as 1.04 % -47.78 % . The overall incidence rate of adverse reaction was 9.82 % (95 %CI : 7.58 % -12.72 % ). A combined local adverse reaction rate appeared as 12.05 % (95 % CI : 9.26 % -15.69 % ). The systemic adverse reaction rate was 9.06 % (95 %CI : 7.07 % -11.61 % ). The overall adverse reaction rate on aqueous vaccine was 32.39 % (95 %CI : 21.88 % -47.94 % ). Combined adverse reaction rate of freeze dried vaccine appeared as 8.65 % (95 %CI : 4.54 % -16.51 % ). Significant differences were seen between both groups ( P <0.05). Conclusions: The local adverse reaction rate caused by rabies vaccination was higher than the systemic adverse reaction rate. The adverse reaction rate of aqueous rabies vaccine was higher than that of freeze dried rabies vaccine. Our results suggested that the aqueous vaccine should gradually be eliminated.

Oral vaccination of wildlife against rabies: Differences among host species in vaccine uptake efficiency.

PubMed

Vos, Ad; Freuling, Conrad M; Hundt, Boris; Kaiser, Christiane; Nemitz, Sabine; Neubert, Andreas; Nolden, Tobias; Teifke, Jens P; Te Kamp, Verena; Ulrich, Reiner; Finke, Stefan; Müller, Thomas

2017-07-13

Oral vaccination using attenuated and recombinant rabies vaccines has been proven a powerful tool to combat rabies in wildlife. However, clear differences have been observed in vaccine titers needed to induce a protective immune response against rabies after oral vaccination in different reservoir species. The mechanisms contributing to the observed resistance against oral rabies vaccination in some species are not completely understood. Hence, the immunogenicity of the vaccine virus strain, SPBN GASGAS, was investigated in a species considered to be susceptible to oral rabies vaccination (red fox) and a species refractory to this route of administration (striped skunk). Additionally, the dissemination of the vaccine virus in the oral cavity was analyzed for these two species. It was shown that the palatine tonsils play a critical role in vaccine virus uptake. Main differences could be observed in palatine tonsil infection between both species, revealing a locally restricted dissemination of infected cells in foxes. The absence of virus infected cells in palatine tonsils of skunks suggests a less efficient uptake of or infection by vaccine virus which may lead to a reduced response to oral vaccination. Understanding the mechanisms of oral resistance to rabies virus vaccine absorption and primary replication may lead to the development of novel strategies to enhance vaccine efficacy in problematic species like the striped skunk. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

BERNA: a century of immunobiological innovation.

PubMed

Cryz, S J

1999-10-01

At the time the Swiss Serum and Vaccine Institute Berne (BERNA) was found in 1898, few vaccines or immune globulins were available. This short list included vaccines against cholera, typhoid fever, plague, smallpox and rabies and equine anti-tetanus and diphtheria immune globulins. Furthermore, their use was restricted due to limited production capacity, uncertainty regarding safety and no public health infrastructure to promote their utilization. Today, safe and effective vaccines exist for more than 30 infectious diseases while human hyperimmune globulins exist to treat or prevent rabies, tetanus, respiratory syncytial virus, cytomegalovirus, hepatitis A, hepatitis B, and herpes virus (Varicella zoster) infections. Throughout its 100 years of existence, BERNA has played a key role in the evolution of the field by introducing novel technology leading to safer, and more efficacious vaccines. It was a pioneer in the development of freeze dried smallpox vaccine free from bacterial contamination. The Salmonella typhi Ty21a typhoid fever vaccine strain demonstrated that oral immunization against enteric bacterial pathogens was not only feasible, but could be accomplished with a virtual lack of attendant adverse reactions. This finding has served as an impetus to develop other live attenuated bacterial strains not only as vaccines, but also as vectors for vaccine antigens and gene therapy. One such example is Vibrio cholerae CVD 103-HgR, the first live vaccine for human use derived through recombinant DNA technology. Subsequent studies have shown that these two vaccine strains can be combined without sacrificing safety or immunogenicity, setting the cornerstone for combined orally administered vaccines. Recently, a novel vaccine antigen delivery system, termed virosomes, has been utilized to construct hepatitis A and influenza vaccines. Such vaccines elicit fewer local adverse reactions than their classical counterparts and display enhanced immunogenicity. Virosome

Expression of the rabies virus glycoprotein in transgenic tomatoes.

PubMed

McGarvey, P B; Hammond, J; Dienelt, M M; Hooper, D C; Fu, Z F; Dietzschold, B; Koprowski, H; Michaels, F H

1995-12-01

We have engineered tomato plants (Lycopersicon esculentum Mill var. UC82b) to express a gene for the glycoprotein (G-protein), which coats the outer surface of the rabies virus. The recombinant constructs contained the G-protein gene from the ERA strain of rabies virus, including the signal peptide, under the control of the 35S promoter of cauliflower mosaic virus. Plants were transformed by Agrobacterium tumefaciens-mediated transformation of cotyledons and tissue culture on selective media. PCR confirmed the presence of the G-protein gene in plants surviving selection. Northern blot analysis indicated that RNA of the appropriate molecular weight was produced in both leaves and fruit of the transgenic plants. The recombinant G-protein was immunoprecipitated and detected by Western blot from leaves and fruit using different antisera. The G-protein expressed in tomato appeared as two distinct bands with apparent molecular mass of 62 and 60 kDa as compared to the 66 kDa observed for G-protein from virus grown in BHK cells. Electron microscopy of leaf tissue using immunogold-labeling and antisera specific for rabies G-protein showed localization of the G-protein to the Golgi bodies, vesicles, plasmalemma and cell walls of vascular parenchyma cells. In light of our previous demonstration that orally administered rabies G-protein from the same ERA strain elicits protective immunity in animals, these transgenic plants should provide a valuable tool for the development of edible oral vaccines.

Rabies in Poland in 2012.

PubMed

Sadkowska-Todys, Małgorzata; Kucharczyk, Bożena

2014-01-01

Evaluation of the epidemiological situation of rabies in Poland in 2012. Evaluation was based on the analysis of data from questionnaires sent by the Epidemiological-Sanitary Stations. The data are from questionnaires of persons who were administered vaccine against rabies following exposure in Poland and beyond its territory and data from annual bulletin "Infectious diseases and poisonings in Poland in 2012"(Czarkowski MP et al., Warsaw, NIH and CSI) and epizootic data provided by the General Veterinary Inspectorate. In 2012, a total of 257 animal rabies cases were registered in Poland, i.e. nearly 60% more compared to 2011. More than 83% of these cases were reported in Podkarpackie province. Compared to 2011, more than 3.5 increase was noted there. One rabid dog was reported in Śląskie province where one rabies infection in fox was noted there a year ago. Rabies infections in terrestrial animals were also reported in the following provinces: Małopolskie, Lubelskie, Warmińsko-mazurskie and Podlaskie. Single rabies infections in bats were registered in other regions of Poland. In 2012, a total of 7,753 persons were vaccinated against rabies, including 315, i.e. more than 4% due to the exposure to animals infected with rabies virus. Of persons vaccinated due to contact with a rabid animal, nearly 40% and more than 44% were vaccinated following contact with rabid fox and domestic animal, respectively. As with the previous years, humans were vaccinated mostly due to contact with dogs and cats in which rabies could not be excluded - 5,974 persons (77%). A reason for concern is an increase in the number of animal rabies cases reported in 2012, especially in Podkarpackie province. Epizootic situation in Poland affects slightly the number of persons vaccinated against rabies who had contact with an animal which potentially is a source of rabies virus. Since many years, this number remains stable, amounting to 7-8,000 annually.

Burden of Rabies

MedlinePlus

... contact with domestic animals such as cats or dogs. In the U.S., the animals that get rabies ... raccoons, skunks, foxes, and bats. Rabies cases among dogs and cats reported in the U.S. from 2010 ...

Protective Effect of Different Anti-Rabies Virus VHH Constructs against Rabies Disease in Mice

PubMed Central

Terryn, Sanne; Francart, Aurélie; Lamoral, Sophie; Hultberg, Anna; Rommelaere, Heidi; Wittelsberger, Angela; Callewaert, Filip; Stohr, Thomas; Meerschaert, Kris; Ottevaere, Ingrid; Stortelers, Catelijne; Vanlandschoot, Peter; Kalai, Michael; Van Gucht, Steven

2014-01-01

Rabies virus causes lethal brain infection in about 61000 people per year. Each year, tens of thousands of people receive anti-rabies prophylaxis with plasma-derived immunoglobulins and vaccine soon after exposure. Anti-rabies immunoglobulins are however expensive and have limited availability. VHH are the smallest antigen-binding functional fragments of camelid heavy chain antibodies, also called Nanobodies. The therapeutic potential of anti-rabies VHH was examined in a mouse model using intranasal challenge with a lethal dose of rabies virus. Anti-rabies VHH were administered directly into the brain or systemically, by intraperitoneal injection, 24 hours after virus challenge. Anti-rabies VHH were able to significantly prolong survival or even completely rescue mice from disease. The therapeutic effect depended on the dose, affinity and brain and plasma half-life of the VHH construct. Increasing the affinity by combining two VHH with a glycine-serine linker into bivalent or biparatopic constructs, increased the neutralizing potency to the picomolar range. Upon direct intracerebral administration, a dose as low as 33 µg of the biparatopic Rab-E8/H7 was still able to establish an anti-rabies effect. The effect of systemic treatment was significantly improved by increasing the half-life of Rab-E8/H7 through linkage with a third VHH targeted against albumin. Intraperitoneal treatment with 1.5 mg (2505 IU, 1 ml) of anti-albumin Rab-E8/H7 prolonged the median survival time from 9 to 15 days and completely rescued 43% of mice. For comparison, intraperitoneal treatment with the highest available dose of human anti-rabies immunoglobulins (65 mg, 111 IU, 1 ml) only prolonged survival by 2 days, without rescue. Overall, the therapeutic benefit seemed well correlated with the time of brain exposure and the plasma half-life of the used VHH construct. These results, together with the ease-of-production and superior thermal stability, render anti-rabies VHH into valuable

Rabies Epidemiology and Control in Ecuador.

PubMed

Ortiz-Prado, Esteban; Ponce-Zea, Jorge; Ramirez, Dario; Stewart-Ibarra, Anna M; Armijos, Luciana; Yockteng, Jaime; Cardenas, Washington Bolivar

2015-07-12

Describe the epidemiology and the control effort for rabies in Ecuador. This observational study included data from the Ecuadorian National Institute of Census and Statistics (INEC), and mortality and morbidity data reported by the Ministry of Public Health and the National Institute for Social Security. We conducted a phylogeny analyses to compare the N gene from the Challenge Virus Standard (CVS) vaccine strain used in Ecuador with published Cosmopolitan, Asian and Sylvatic strains. Descriptive and inferential statistics were used to determine the significance of the data. In 1996 Ecuador suffered the highest rate of rabies per capita in the Americas, with an incidence rate of 0.56 cases per 100 000 people per year. Human and canine rabies showed a sharp decline until 2012. Between 1994 and 2014, we found a correlation of 0.925 (p<0.01) between annual cases of dog and human rabies. In 2011, there was an epidemic of sylvatic rabies transmitted to people by vampire bats (Desmodus rotundus) in the Amazon region, specifically in Morona Santiago, leading to 11 fatalities. Phylogenetic analyses of the CVS vaccine N gene showed an association with urban canine rabies strains (the Cosmopolitan lineage and Asian strains), whereas sylvatic rabies, like those reported in the Amazon region, were found to be grouped in a different clade represented mainly by bat-derived strains. This study presents the first compilation of epidemiological data on rabies in Ecuador. The incidence of human and canine rabies, also known as urban rabies, has clearly decreased due to massive canine vaccination campaigns. Phylogenetic analysis of the prevailing vaccine used in the country showed a clear separation from bat-derived rabies, the source of recent rabies outbreaks. Efforts are ongoing to develop rabies vaccines that are highly specific to the rabies virus genotype circulating in the region, including sylvatic rabies. These efforts include the implementation of reverse genetics to

Rabies Epidemiology and Control in Ecuador

PubMed Central

Ortiz-Prado, Esteban; Ponce-Zea, Jorge; Ramirez, Dario; Stewart-Ibarra, Anna M.; Armijos, Luciana; Yockteng, Jaime; Cárdenas, Washington B.

2016-01-01

Objective: Describe the epidemiology and the control effort for rabies in Ecuador. Methods: This observational study included data from the Ecuadorian National Institute of Census and Statistics (INEC), and mortality and morbidity data reported by the Ministry of Public Health and the National Institute for Social Security. We conducted a phylogeny analyses to compare the N gene from the Challenge Virus Standard (CVS) vaccine strain used in Ecuador with published Cosmopolitan, Asian and Sylvatic strains. Descriptive and inferential statistics were used to determine the significance of the data. Results: In 1996 Ecuador suffered the highest rate of rabies per capita in the Americas, with an incidence rate of 0.56 cases per 100 000 people per year. Human and canine rabies showed a sharp decline until 2012. Between 1994 and 2014, we found a correlation of 0.925 (p<0.01) between annual cases of dog and human rabies. In 2011, there was an epidemic of sylvatic rabies transmitted to people by vampire bats (Desmodus rotundus) in the Amazon region, specifically in Morona Santiago, leading to 11 fatalities. Phylogenetic analyses of the CVS vaccine N gene showed an association with urban canine rabies strains (the Cosmopolitan lineage and Asian strains), whereas sylvatic rabies, like those reported in the Amazon region, were found to be grouped in a different clade represented mainly by bat-derived strains. Conclusions: This study presents the first compilation of epidemiological data on rabies in Ecuador. The incidence of human and canine rabies, also known as urban rabies, has clearly decreased due to massive canine vaccination campaigns. Phylogenetic analysis of the prevailing vaccine used in the country showed a clear separation from bat-derived rabies, the source of recent rabies outbreaks. Efforts are ongoing to develop rabies vaccines that are highly specific to the rabies virus genotype circulating in the region, including sylvatic rabies. These efforts include the

Cost-Effectiveness of Mass Dog Vaccination Campaigns against Rabies in Flores Island, Indonesia.

PubMed

Wera, E; Mourits, M C M; Siko, M M; Hogeveen, H

2017-12-01

A dynamic deterministic simulation model was developed to determine the cost-effectiveness of different mass dog vaccination strategies against rabies in a dog population representative of a typical village on Flores Island. Cost-effectiveness was measured as public cost per averted dog-rabies case. Simulations started with the introduction of one infectious dog into a susceptible dog population of 399 dogs and subsequently ran for a period of 10 years. The base scenario represented a situation without any control intervention. Evaluated vaccination strategies were as follows: annual vaccination campaigns with short-acting vaccine (immunity duration of 52 weeks) (AV_52), annual campaigns with long-acting vaccine (immunity duration of 156 weeks) (AV_156), biannual campaigns with short-acting vaccine (BV_52) and once-in-2-years campaigns with long-acting vaccine (O2V_156). The effectiveness of the vaccination strategies was simulated for vaccination coverages of 50% and 70%. Cumulative results were reported for the 10-year simulation period. The base scenario resulted in three epidemic waves, with a total of 1274 dog-rabies cases. The public cost of applying AV_52 at a coverage of 50% was US$5342 for a village. This strategy was unfavourable compared to other strategies, as it was costly and ineffective in controlling the epidemic. The costs of AV_52 at a coverage of 70% and AV_156 at a coverage of 70% were, respectively, US$3646 and US$3716, equivalent to US$3.00 and US$3.17 per averted dog-rabies case. Increasing the coverage of AV_156 from 50% to 70% reduced the number of cases by 7% and reduced the cost by US$1452, resulting in a cost-effectiveness ratio of US$1.81 per averted dog-rabies case. This simulation model provides an effective tool to explore the public cost-effectiveness of mass dog vaccination strategies in Flores Island. Insights obtained from the simulation results are useful for animal health authorities to support decision-making in rabies

Production and evaluation of a chromatographically purified Vero cell rabies vaccine (PVRV) in China using microcarrier technology

PubMed Central

Yu, Pengcheng; Huang, Ying; Zhang, Yibin; Tang, Qing; Liang, Guodong

2012-01-01

China is a high population country with millions of animal bite cases every year; thus, it is necessary to explore and develop more effective and productive rabies vaccines for human use. To establish a safe, effective, inexpensive and high-yield rabies vaccine, a non-adjuvant purified Vero cell rabies vaccine produced in the SPEEDA PVRV microcarrier bioreactor was developed by Liaoning Chengda Biology Co. Ltd. in China. This vaccine was produced using Vero cells that were cultured in a microcarrier bioreactor. A microcarrier bioreactor containing 25 g/L of Cytodex-1 was used for perfusion culture. The Vero cell culture density was up to 1.2–1.5 × 107 cells/ml, viruses could be constantly harvested for 18–22 days, and the resulting vaccine immunizing potency was ≥ 4.5 IU/ml. Vaccine safety and immunogenicity post-immunization were also assessed. A total of 602 volunteers were enrolled and divided into two groups that were vaccinated with either SPEEDA PVRV or VERORAB PVRV on days 0, 3, 7, 14 and 28. All subjects vaccinated with SPEEDA PVRV showed no serious local or systemic adverse effects. The positive conversion rate of serum neutralizing antibodies against the rabies virus reached 100% in both the test and control groups (inoculated with VERORAB PVRV) at 14 days and 45 days after vaccination, and no significant difference was found between the neutralizing antibody geometric mean titers (GMTs) of the two groups. SPEEDA PVRV is appropriate for mass production and shows satisfactory clinical safety and immunogenicity for human post-exposure prophylaxis of rabies. PMID:22894963

[Rabies contingency plan in Japan].

PubMed

Inoue, Satoshi

2005-12-01

In Japan, rabies has been culled out since 1957 thanks to the strong implementation of measures against rabies, such as vaccination of dogs, quarantine and control of wild dogs under the 'Rabies Prevention Law' enacted in 1950. Nevertheless one cannot deny the possibility of introduction of rabies into Japan in view of the recent increase in the international movements of people and animals. Should an outbreak of rabies be suspected now in Japan, the society would probably overreact due to a decreased awareness of risks and a lack of correct knowledge about this disease. Officials of the government and the municipalities, veterinarians and doctors should exchange correct information on rabies and on prevention control and raise their awareness, while providing also information to the public on a timely basis. Besides it is needless to say that it is important to set up a crisis management system allowing a quick and adequate response in case of an outbreak of rabies and to continue to implement appropriate prevention measures in normal times.

Human rabies in Tianjin, China.

PubMed

Montgomery, J P; Zhang, Y; Wells, E V; Liu, Y; Clayton, J L; Wang, X; Boulton, M L

2012-12-01

Human rabies has recently re-emerged as a significant public health threat in Tianjin, China. Using surveillance data compiled by the Tianjin Centers for Disease Control and Prevention, we describe 60 cases of human rabies reported from 2005 to 2011 in the municipality of Tianjin, China. All 60 cases of human rabies resulted in death. Cases were primarily male (80%), middle aged (mean 40.6 years), and exposed to rabies in a rural setting (82%). Most exposures were associated with dog bites (93%) and no animal had a history of rabies vaccination; no cases were laboratory confirmed. Fifteen percent of patients sought medical attention for their wound, and none received a complete regimen of WHO-recommended post-exposure prophylaxis (PEP). These findings suggest the need for China's public health authority to improve animal rabies surveillance and control strategies through laboratory case confirmation, more rapid response to potential exposures with provision of appropriate PEP, and education to the public and to health care providers on identifying and reducing rabies risk.

Langerhans Cell Histiocytosis in an Adult with Involvement of the Calvarium, Cerebral Cortex and Brainstem: Discussion of Pathophysiology and Rationale for the Use of Intravenous Immune Globulin

PubMed Central

Dardis, Christopher; Aung, Thandar; Shapiro, William; Fortune, John; Coons, Stephen

2015-01-01

We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin. PMID:25873887

Using serology to assist with complicated post-exposure prophylaxis for rabies and Australian bat lyssavirus.

PubMed

Conroy, Niall; Vlack, Susan; Williams, Julian M; Patten, John J; Horvath, Robert L; Lambert, Stephen B

2013-01-01

Australia uses a protocol combining human rabies immunoglobulin (HRIG) and rabies vaccine for post-exposure prophylaxis (PEP) of rabies and Australian bat lyssavirus (ABLV), with the aim of achieving an antibody titre of ≥0.5 IU/ml, as per World Health Organization (WHO) guidelines, as soon as possible. We present the course of PEP administration and serological testing for four men with complex requirements. Following dog bites in Thailand, two men (62 years old, 25 years old) received no HRIG and had delayed vaccine courses: 23 days between dose two and three, and 18 days between dose one and two, respectively. Both seroconverted following dose four. Another 62-year-old male, who was HIV-positive (normal CD4 count), also suffered a dog bite and had delayed care receiving i.m. rabies vaccine on days six and nine in Thailand. Back in Australia, he received three single and one double dose i.m. vaccines followed by another double dose of vaccine, delivered intradermally and subcutaneously, before seroconverting. A 23-year-old male with a history of allergies received simultaneous HRIG and vaccine following potential ABLV exposure, and developed rash, facial oedema and throat tingling, which was treated with a parenteral antihistamine and tapering dose of steroids. Serology showed he seroconverted following dose four. These cases show that PEP can be complicated by exposures in tourist settings where reliable prophylaxis may not be available, where treatment is delayed or deviates from World Health Organization recommendations. Due to the potentially short incubation time of rabies/ABLV, timely prophylaxis after a potential exposure is needed to ensure a prompt and adequate immune response, particularly in patients who are immune-suppressed or who have not received HRIG. Serology should be used to confirm an adequate response to PEP when treatment is delayed or where a concurrent immunosuppressing medical condition or therapy exists.

Animal rabies in Massachusetts, 1985-2006.

PubMed

Wang, Xingtai; Werner, Barbara G; Konomi, Raimond; Hennigan, Dennis; Fadden, David; Caten, Evan; Soliva, Susan; DeMaria, Alfred

2009-04-01

In this study, we review annual rabies data from Massachusetts from 1985 to 2006, spanning the introduction of raccoon strain rabies in 1992. Of 52,034 animals tested, 9.7% (5,049/52,034) were rabid, representing 26 of over 67 species submitted. Bats were the most common rabid animals prior to 1992 (50 of 52), but raccoons (Procyon lotor) became the most common rabies-positive species upon arrival of raccoon strain rabies virus (38.2%, 2,728 of 7,138 tested), followed by striped skunks (Mephitis mephitis, 34.4%, 1,489 of 4,332), bats (5.3%, 427 of 8,053), foxes (red fox, Vulpes vulpes, and gray fox, Urocyon cinereoargenteus, 16.3%, 135 of 827), cats (0.8%, 136 of 18,050), and woodchucks (Marmota monax, 5.7%, 82 of 1,446). Cats were the most frequently tested animal (34.7%). Raccoon strain rabies spread from two foci of introduction with an initial epizootic phase of 4 yr, by which time most of the state was affected. In 1992, there was a transition from enzootic bat rabies, with little spillover to other animals, to terrestrial rabies associated with raccoon strain virus. Although raccoons were most affected by the raccoon strain virus, there was spillover to other species, particularly to skunks. The eastern United States raccoon rabies epizootic led to a marked increase in submissions for rabies testing and the number of positive animals detected; however, bat rabies cases remained at their previous levels. Wild animal rabies presents a significant threat to humans and domestic/companion animals and increased costs related to increased demand for rabies testing, postexposure prophylaxis as well as euthanasia of valuable domestic animals.

ACTIVITY OF DISSOCIATED AND REASSOCIATED 19S ANTI-γ-GLOBULINS

PubMed Central

Schrohenloher, Ralph E.; Kunkel, Henry G.; Tomasi, Thomas B.

1964-01-01

19S anti-γ-globulins were isolated in a high state of purity from the sera of two patients with rheumatoid arthritis. Following reduction with ethyl mercaptan and alkylation by iodoacetamide, fragments were produced which retained the capacity to combine with 7S γ-globulin. The fragments from one of the 19S anti-γ-globulins agglutinated red cells coated with incomplete anti-Rh antibodies. This activity was shown by density gradient ultracentrifugation to be associated with low molecular weight fractions. The agglutination of the coated red cells by the fragments was strongly inhibited by normal and myeloma 7S γ-globulins and showed a greater specificity than the parent 19S material. Analytical ultracentrifuge experiments demonstrated that the fragments from either of the 19S anti-γ-globulins formed complexes with 7S γ-globulin. Reassociation of the dissociated fragments through reformation of disulfide bonds resulted in the formation of fast sedimenting molecules having properties similar to those of the untreated 19S material in respect to precipitation with aggregated γ-globulin and agglutination of coated red cells. PMID:14238936

Bat rabies surveillance in France: first report of unusual mortality among serotine bats.

PubMed

Picard-Meyer, Evelyne; Servat, Alexandre; Wasniewski, Marine; Gaillard, Matthieu; Borel, Christophe; Cliquet, Florence

2017-12-13

Rabies is a fatal viral encephalitic disease that is caused by lyssaviruses which can affect all mammals, including human and bats. In Europe, bat rabies cases are attributed to five different lyssavirus species, the majority of rabid bats being attributed to European bat 1 lyssavirus (EBLV-1), circulating mainly in serotine bats (Eptesicus serotinus). In France, rabies in bats is under surveillance since 1989, with 77 positive cases reported between 1989 and 2016. In the frame of the bat rabies surveillance, an unusual mortality of serotine bats was reported in 2009 in a village in North-East France. Six juvenile bats from an E. serotinus maternity colony counting ~200 individuals were found to be infected with EBLV-1. The active surveillance of the colony by capture sessions of bats from July to September 2009 showed a high detection rate of neutralising EBLV-1 antibodies (≈ 50%) in the colony. Moreover, one out of 111 animals tested was found to shed viable virus in saliva, while lyssavirus RNA was detected by RT-PCR for five individuals. This study demonstrated that the lyssavirus infection in the serotine maternity colony was followed by a high rate of bat rabies immunity after circulation of the virus in the colony. The ratio of seropositive bats is probably indicative of an efficient virus transmission coupled to a rapid circulation of EBLV-1 in the colony.

Animal and human rabies in Mongolia.

PubMed

Odontsetseg, N; Uuganbayar, D; Tserendorj, Sh; Adiyasuren, Z

2009-12-01

The prevalence of animal rabies differs in each area of Mongolia. Wolves (Canis lupus Linnaeus, 1758), foxes ( Vulpes vulpes Linnaeus, 1758), corsac foxes (Vulpes corsac Linnaeus, 1768) and manuls (Felis manul Pallas, 1778) are considered to be the infective wild animals in natural foci. Amongst livestock, cattle have had the most rabies cases, followed by camels, sheep, goats and horses. The peak prevalence of animal rabies occurred in the 1970s. Dundgovi Province had the highest incidence during that period. The number of rabies cases in animals decreased during the 1980s. This may have been due to a decrease in the number of wild reservoir animals and the improvement of appropriate veterinary measures. In recent years, animal rabies has prevailed in the Khangai and western provinces. The infection source of most human rabies cases is the dog. In order to minimise the incidence of human rabies, canine vaccination programmes need to be improved. This paper describes the epizootiology and epidemiology of animal and human rabies in Mongolia. It describes rabies control programmes, including diagnosis, conducted in Mongolia in an effort to control the disease.

Restoration of the antibody response upon rabies vaccination in HIV-infected patients treated with HAART.

PubMed

Gelinck, Luc B S; Jol-van der Zijde, Cornelia M; Jansen-Hoogendijk, Anja M; Brinkman, Daniëlle M C; van Dissel, Jaap T; van Tol, Maarten J D; Kroon, Frank P

2009-11-27

Rabies vaccine was used as a T-cell-dependent neoantigen to investigate several aspects of the primary and booster immune response in vivo in HIV-infected individuals receiving antiretroviral treatment. Study participants received rabies vaccination twice, within a 3-month interval. Serum samples were taken before and 1, 2 and 4 weeks after both vaccinations and 1 and 5 years after the primary vaccination. Antirabies antibodies [immunoglobulin G (IgG), IgG subclasses, immunoglobulin A (IgA) and immunoglobulin M (IgM)] were determined; antibody avidity was measured after both vaccinations. T-cell subsets were characterized by flow cytometry. Eighteen healthy controls and 30 HIV-infected adults, treated with HAART for almost 4 years, with a median CD4(+) T-cell count of 537 cells/microl, were immunized. The postvaccination concentrations of antirabies IgG and IgM were significantly lower in HIV-infected individuals as compared with controls. Three T-cell-dependent processes, a true booster response, a class switch from IgM to IgG and avidity maturation were present in both healthy controls and HIV-infected individuals. Higher age was associated with lower postvaccination antirabies IgG and IgM titers. Five years after the primary vaccination, 63% of the HIV-infected individuals still had antibody titers above the protection threshold. Immune restoration in HIV-infected individuals treated with HAART, resulting in a CD4(+) T-cell count greater than 500 cells/microl, is incomplete. However, the majority of HIV-infected individuals are capable of mounting a long-lasting immune response, including several pivotal T-cell-dependent processes, upon vaccination with a neoantigen such as the rabies vaccine.

Rabies in Europe in 2005.

PubMed

Bourhy, H; Dacheux, L; Strady, C; Mailles, A

2005-11-01

Rabies is still present in Europe in 2005. Its incidence in humans remains limited (fewer than 5 human cases per year) through the application of strict prophylactic measures (anti-rabies treatment) and by means of veterinary rabies control measures in the domesticated and wild animal populations. The main indigenous animal reservoirs are: the dog in eastern European countries and on the borders with the Middle East; the fox in central and eastern Europe; the racoon dog in northeastern Europe; and the insectivorous bat throughout the entire territory. Finally, each year, cases of animals with rabies imported from enzootic areas are reported, showing the permeability of borders and traveller's lack of consideration of the rabies risk. These importations constantly threaten the rabies-free status of terrestrial animals in western European countries and complicate the therapeutic decisions taken by physicians in the absence of information regarding the biting animal.

Rabies in Thailand.

PubMed Central

Mitmoonpitak, C.; Tepsumethanon, V.; Wilde, H.

1998-01-01

The prevalence of canine and human rabies in Thailand has decreased significantly during the last decade. This has been associated with an increasing number of human post-exposure treatments. Educational efforts, mass vaccination of dogs and cats and the use of safe and effective vaccines have all made an impact. The proportion of fluorescent antibody positive dogs, among those examined for rabies averaged 54% indicating that rabies is still a major public health threat. Canine rabies vaccination is not usually performed in animals < 3 months old. However, this study revealed that 14% of rabid dogs were < 3 months old and 42% were < or = 6 months old. This is the age group most likely to interact with humans and other dogs. Our study also supports the World Health Organization's recommendation that observing suspected rabid dogs for 10 days is an adequate and safe practice. PMID:9593486

Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus.

PubMed

Zhang, Daiting; He, Feilong; Bi, Shuilian; Guo, Huixia; Zhang, Baoshi; Wu, Fan; Liang, Jiaqi; Yang, Youtian; Tian, Qin; Ju, Chunmei; Fan, Huiying; Chen, Jinding; Guo, Xiaofeng; Luo, Yongwen

2016-01-01

Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from the fatal encephalitis caused by the virulent RABV strain CVS-11. To understand the neuropathogenesis of rabies and the mechanisms of viral clearance, we applied RNA sequencing (RNA-Seq) to compare the brain transcriptomes of normal mice vs. HEP-Flury or CVS-11 intranasally inoculated mice. Our results revealed that both RABV strains altered positively and negatively the expression levels of many host genes, including genes associated with innate and adaptive immunity, inflammation and cell death. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes involved in synaptic transmission and ion transport were significantly down-regulated. On the other hand, several genes involved in the MHC class II-mediated antigen presentation pathway were activated to a greater extent after the HEP-Flury infection as compared with the CVS-11 infection suggesting that the collaboration of CD4(+) T cells and MHC class II-mediated antigen presentation is critical for the clearance of attenuated RABV from the CNS. The differentially regulated genes reported here are likely to include potential therapeutic targets for expanding the post-exposure treatment window for RABV

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

21 CFR 660.50 - Anti-Human Globulin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Anti-Human Globulin. 660.50 Section 660.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Anti-Human Globulin § 660.50 Anti-Human...

A new rabies vaccine based on a recombinant ORF virus (parapoxvirus) expressing the rabies virus glycoprotein.

PubMed

Amann, Ralf; Rohde, Jörg; Wulle, Ulrich; Conlee, Douglas; Raue, Rudiger; Martinon, Olivier; Rziha, Hanns-Joachim

2013-02-01

The present study describes the generation of a new Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. One single immunization with recombinant ORFV can stimulate high RABV-specific virus-neutralizing antibody (VNA) titers in mice, cats, and dogs, representing all nonpermissive hosts for the ORFV vector. The protective immune response against severe lethal challenge infection was analyzed in detail in mice using different dosages, numbers, and routes for immunization with the ORFV recombinant. Long-term levels of VNA could be elicited that remained greater than 0.5 IU per ml serum, indicative for the protective status. Single applications of higher doses (10(7) PFU) can be sufficient to confer complete protection against intracranial (i.c.) challenge, whereas booster immunization was needed for protection by the application of lower dosages. Anamnestic immune responses were achieved by each of the seven tested routes of inoculation, including oral application. Finally, in vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T cell subpopulations during immunization and/or challenge infection attested the importance of CD4 T cells for the induction of protective immunity by D1701-V-RabG. This report demonstrates another example of the potential of the ORFV vector and also indicates the capability of the new recombinant for vaccination of animals.

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

PubMed Central

Amann, Ralf; Rohde, Jörg; Wulle, Ulrich; Conlee, Douglas; Raue, Rudiger; Martinon, Olivier

2013-01-01

The present study describes the generation of a new Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. One single immunization with recombinant ORFV can stimulate high RABV-specific virus-neutralizing antibody (VNA) titers in mice, cats, and dogs, representing all nonpermissive hosts for the ORFV vector. The protective immune response against severe lethal challenge infection was analyzed in detail in mice using different dosages, numbers, and routes for immunization with the ORFV recombinant. Long-term levels of VNA could be elicited that remained greater than 0.5 IU per ml serum, indicative for the protective status. Single applications of higher doses (107 PFU) can be sufficient to confer complete protection against intracranial (i.c.) challenge, whereas booster immunization was needed for protection by the application of lower dosages. Anamnestic immune responses were achieved by each of the seven tested routes of inoculation, including oral application. Finally, in vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T cell subpopulations during immunization and/or challenge infection attested the importance of CD4 T cells for the induction of protective immunity by D1701-V-RabG. This report demonstrates another example of the potential of the ORFV vector and also indicates the capability of the new recombinant for vaccination of animals. PMID:23175365

Rabies postexposure consultations in New Zealand from 1998 to 2012.

PubMed

Shaw, Marc T M; Visser, Jenny; Edwards, Ciaran

2015-01-01

Rabies is an invariably fatal zoonotic viral disease. New Zealanders going abroad are largely unaware of the risk of contracting the disease. Prevention is the key to controlling the spread of this disease. Data from 363 individuals presenting to New Zealand travel health clinics between 1998 and 2012 for post-travel consultations on potential rabies exposure were collated retrospectively. The data focused on traveler demographics, the country and nature of exposure, the purpose of travel, and pre-travel rabies awareness. The female-to-male ratio of subject travelers presenting was almost equal (1.1 : 1 ratio, respectively); the subjects were typically between 16 and 30 years (44.6%), tourists (64.5%), traveling less than 1 month (55.3%), and likely to have been exposed to animal contact in either Thailand (31.1%), China (13.2%), or Indonesia (12.3%). The animals to which they were exposed were usually dogs (59.5%) or monkeys (28.7%). Most potential exposures were penetrating (69.9%). Injury caused by the animal was more common in the lower limbs (50%) than in the upper limbs (43.4%); 89.4% of exposures were of World Health Organization (WHO) category III. Travelers were more likely to have received pre-travel rabies advice if they had been seen by a travel medicine specialist (96.1%) compared to a general practitioner (GP) (53.3%). Sixteen percent of travelers received rabies preexposure prophylaxis. Of the subjects who were managed following exposure, 79.7% did not receive immunoglobulin when indicated, and 21.5% did not receive any vaccine. Of the travelers that did receive a vaccine, 62.5% did so on the day of exposure. Of the travelers assessed, 16.7% had traveled without insurance. New Zealanders require better guidance in understanding the need for travel-related rabies vaccination, as they are not managed abroad according to WHO guidelines. Few travelers had had pre-travel immunization, and only 20.3% of them had received WHO-advised postexposure

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5400 Alpha-globulin immuno-logical test system. (a) Identification. An alpha-globulin immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866...

G-protein based ELISA as a potency test for rabies vaccines.

PubMed

Chabaud-Riou, Martine; Moreno, Nadège; Guinchard, Fabien; Nicolai, Marie Claire; Niogret-Siohan, Elisabeth; Sève, Nicolas; Manin, Catherine; Guinet-Morlot, Françoise; Riou, Patrice

2017-03-01

The NIH test is currently used to assess the potency of rabies vaccine, a key criterion for vaccine release. This test is based on mice immunization followed by intracerebral viral challenge. As part of global efforts to reduce animal experimentation and in the framework of the development of Sanofi Pasteur next generation, highly-purified vaccine, produced without any material of human or animal origin, we developed an ELISA as an alternative to the NIH test. This ELISA is based on monoclonal antibodies recognizing specifically the native form of the viral G-protein, the major antigen that induces neutralizing antibody response to rabies virus. We show here that our ELISA is able to distinguish between potent and different types of sub-potent vaccine lots. Satisfactory agreement was observed between the ELISA and the NIH test in the determination of the vaccine titer and their capacity to discern conform from non-conform batches. Our ELISA meets the criteria for a stability-indicating assay and has been successfully used to develop the new generation of rabies vaccine candidates. After an EPAA international pre-collaborative study, this ELISA was selected as the assay of choice for the EDQM collaborative study aimed at replacing the rabies vaccine NIH in vivo potency test. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[C-terminal lysosome targeting domain of CD63 modifies cellular localization of rabies virus glycoprotein].

PubMed

Starodubova, E S; Kuzmenko, Y V; Latanova, A A; Preobrazhenskaya, O V; Karpov, V L

2017-01-01

The glycoprotein of rabies virus is the central antigen elicited the immune response to infection; therefore, the majority of developing anti-rabies vaccines are based on this protein. In order to increase the efficacy of DNA immunogen encoding rabies virus glycoprotein, the construction of chimeric protein with the CD63 domain has been proposed. The CD63 is a transmembrane protein localized on the cell surface and in lysosomes. The lysosome targeting motif GYEVM is located at its C-terminus. We used the domain that bears this motif (c-CD63) to generate chimeric glycoprotein in order to relocalize it into lysosomes. Here, it was shown that, in cells transfected with plasmid that encodes glycoprotein with c-CD63 motif at the C-terminus, the chimeric protein was predominantly observed in lysosomes and at the cell membrane where the unmodified glycoprotein is localized in the endoplasmic reticulum and at the cell surface. We suppose that current modification of the glycoprotein may improve the immunogenicity of anti-rabies DNA vaccines due to more efficient antibody production.

Role of intravenous immune globulin in streptococcal toxic shock syndrome and Clostridium difficile infection.

PubMed

Shah, Punit J; Vakil, Niyati; Kabakov, Anna

2015-06-15

The use of intravenous immune globulin (IVIG) in the management of streptococcal toxic shock syndrome (STSS) and Clostridium difficile infection (CDI) is reviewed. IVIG has a wide range of uses in clinical practice, including STSS and CDI. It is an attractive option for these two infections because both infections are toxin mediated, and IVIG may contain antibodies that neutralize these toxins. For STSS and CDI, IVIG is often considered for use in critically ill patients who are not responding to traditional therapies. Several encouraging case reports and retrospective chart reviews have been published, highlighting the potential benefit of IVIG in such patients. However, its definitive role remains unclear, mainly due to the lack of high-level evidence. Data supporting its use have been extrapolated from retrospective chart reviews and case reports in which profound heterogeneity in patient populations and treatment modalities exist. The use of IVIG must be weighed carefully because it is not a benign product. As with the use of IVIG for STSS, the role of IVIG for CDI is unclear. Nonetheless, IVIG may serve as a useful adjunct therapy for patients suffering from severe complicated CDI (shock, ileus, or megacolon) who do not respond to conventional treatment. Adverse reactions to IVIG are mild and transitory and occur during or immediately after drug infusion. Although randomized, controlled trials supporting the use of IVIG for STSS and CDI are lacking, IVIG may be considered a last-line adjunct therapy in those patients for whom the clinical benefit outweighs the potential adverse effects of therapy. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Classification of Blood-Group Antibodies as β2M or γ Globulin

PubMed Central

Adinolfi, M.; Polley, Margaret J.; Hunter, Denise A.; Mollison, P. L.

1962-01-01

Thirty selected blood-group antibodies (excluding anti-A and anti-B) have been classified as β2M (19S γ) globulin, γ (7S γ) globulin or mixtures, using the following three methods: fractionation on a DEAE-cellulose column; indirect anti-globulin tests, using specific anti-β2M-globulin and anti-γ-globulin sera; and treatment with 2-mercapto-ethanol. With only minor exceptions, results obtained with the three methods were in agreement. Most blood-group antibodies within the Le, MNSs and P systems appear to be `naturally occurring' and these were found to be β2M globulin. Blood-group antibodies within the Rh, K and Jk systems, which had arisen after an antigenic stimulus, were usually γ globulin but were occasionally β2M globulin. Antibodies composed of β2M globulin usually behave as agglutinins but may behave as incomplete antibodies (e.g. some examples of anti-Jka); conversely, antibodies composed of γ globulin usually behave as incomplete antibodies but may behave as agglutinins (e.g. an example of anti-M). The ability to bind complement seems to be related more to the blood-group specificity of the particular antibody than to its molecular size. For example, anti-Jka, when composed either of γ or β2M globulin, seems invariably to bind complement, whereas potent anti-M or anti-Rh, whether composed of γ or β2M globulin, do not bind complement. PMID:14011076

[Rabies in a cat in Greenland].

PubMed

Christensen, Laurids Siig; Jacobsen, Keld; Maersk-Møller, Elisabeth

2008-08-18

We describe the first case of rabies diagnosed in a cat in Greenland. The cat showed aggressive behaviour one month after the visit of a rabid fox on the premises. Rabies is enzootic in Greenland, the arctic fox being the natural host of rabies virus. Cats are imported in increasing numbers to Greenland and the reported case stresses the need for concern in relation to a hitherto unrecognised risk of exposure to rabies virus and stresses the need to comply with the obligatory anti-rabies vaccination regimes for cats in Greenland.

Apparent effect of immune serum globulin prophylaxis in the military on viral hepatitis incidence in the civilian population in Israel.

PubMed

Green, M S; Block, C

1989-06-01

Since 1969, extensive use of immune serum globulin in the Israel Defence Force for prophylaxis against hepatitis A virus (HAV) infection has produced a sharp decline in the incidence of the disease. However, it is not clear whether this policy has affected the susceptibility of Israeli adults to HAV infection. In this study, we examined the effect of the immunisation policy on the incidence of hepatitis A virus infection in the civilian population in the 15-44 year age group, which includes all those who have completed compulsory military service since vaccination was introduced. The incidence of viral hepatitis in the Jewish civilian population aged 15-44 increased by approximately 50% 3-4 years after the implementation of the immunisation policy. This rise was not seen in the non-Jewish population of the same age nor among Jews aged 45-64. These findings strongly suggest that the immunisation policy in the military prevents both clinical and sub-clinical disease, but has had the effect of producing more susceptible people at an older age in the civilian population.

Safety and Serological Response to a Matrix Gene-deleted Rabies Virus-based Vaccine Vector in Dogs

PubMed Central

McGettigan, James P.; David, Frederic; Figueiredo, Monica Dias; Minke, Jules; Mebatsion, Teshome; Schnell, Matthias J.

2014-01-01

Dogs account for the majority of human exposures and deaths due to rabies virus (RABV) worldwide. In this report, we show that a replication-deficient RABV-based vaccine in which the matrix gene is deleted (RABV- M) is safe and induces rapid and potent VNA titers after a single inoculation in dogs. Average VNA titers peaked at 3.02 or 5.11 International Units (IU/ml) by 14 days post-immunization with a single dose of 106 or 107 focus forming units (ffu), respectively, of RABV- M. By day 70 post immunization, all dogs immunized with either dose of vaccine showed VNA titers >0.5 IU/ml, the level indicative of a satisfactory immunization. Importantly, no systemic or local reactions were noted in any dog immunized with RABV- M. The elimination of dog rabies through mass vaccination is hindered by limited resources, requirement for repeat vaccinations often for the life of a dog, and in some parts of the world, inferior vaccine quality. Our preliminary safety and immunogenicity data in dogs suggest that RABV- M might complement currently used inactivated RABV-based vaccines in vaccination campaigns by helping to obtain 100% response in vaccinated dogs, thereby increasing overall vaccination coverage. PMID:24508037

21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160 Beta-globulin immunolog-ical test system. (a) Identification. A beta-globulin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160...

Tools for rabies serology to monitor the effectiveness of rabies vaccination in domestic and wild carnivores.

PubMed

Servat, A; Wasniewski, M; Cliquet, F

2006-01-01

Serology remains the only way to monitor the effectiveness of vaccination of humans and animals against rabies. Many techniques for determining the level of rabies antibodies have been described, including seroneutralisation techniques such as tests for fluorescent antibody virus neutralisation (FAVN) and rapid fluorescent focus inhibition (RFFIT), enzyme-linked immunosorbent assay (ELISA), and in-vivo tests (the mouse neutralisation test, MNT). The need to verify the effectiveness of rabies vaccination has become widespread, particularly in the context of international trading of domestic carnivores from infected to rabies-free territories. The standardisation of serological techniques, approval of laboratories and proficiency tests are key concepts to ensure the practicability of such systems. Serological tests for rabies are also often used by laboratories in infected territories to assess the efficacy of campaigns aimed at the eradication of the disease via oral vaccination of wildlife. The adaptation of these methods should provide the means to titrate specific antibodies in dogs during mass parenteral vaccination in countries infected by canine rabies. However, in most cases these serological tests are carried without any standardised procedure. On the basis of our experience in rabies serology and its harmonisation throughout laboratories worldwide, we propose here an adapted standard technique for the serological monitoring for rabies in wildlife at the European level. Such harmonisation would allow the monitoring of vaccination campaigns to be enhanced by increasing the exchange of epidemiological data, with the ultimate goal being the eradication of rabies in Europe.

Community rabies knowledge and pet vaccination practices after a skunk rabies outbreak in Eddy County, New Mexico.

PubMed

McNeil, Carrie S; Nagy, Samantha; Moonan, Catherine; Wallace, Ryan M; Vora, Neil M; Dyer, Jessie L; Blanton, Jesse D; Dorado, Tina; Heinrich, Mark L; Sankey, Robin; Uhrig, Samantha; Cary, Angela; Houghton, Woods; Ettestad, Paul

2015-06-01

To determine percentages of domestic cats and dogs vaccinated against rabies, identify barriers to vaccination, and assess knowledge about rabies in a semirural New Mexico community after a skunk rabies outbreak. Cross-sectional, door-to-door, bilingual, community-based participatory survey. 366 residential properties in Eddy County, NM. The New Mexico Department of Health and CDC administered surveys and analyzed data. Individuals at 247 of the 366 residential properties participated in the survey. One hundred eighty of the 247 (73%) households owned a dog (n = 292) or cat (163). Cats were more likely than dogs to not have an up-to-date rabies vaccination status (prevalence ratio, 3.2; 95% confidence interval, 2.3 to 4.4). Cost and time or scheduling were the most frequently identified barriers to vaccination. One hundred sixty (65%) respondents did not know livestock can transmit rabies, 78 (32%) did not know rabies is fatal, and 89 (36%) did not know a bat scratching a person can be an exposure. Only 187 (76%) respondents indicated they would contact animal control if they saw a sick skunk, and only 166 (67%) indicated they would contact animal control if bitten by a dog they did not own. Findings indicated that rabies vaccination prevalence among pet dogs and cats was low, despite the fact that the region had experienced a skunk rabies outbreak during the previous 2 years. In addition, substantial percentages of respondents did not have correct knowledge of rabies or rabies exposure.

The effect of age on serum antibody titers after rabies and influenza vaccination in healthy horses.

PubMed

Muirhead, T L; McClure, J T; Wichtel, J J; Stryhn, H; Frederick Markham, R J; McFarlane, D; Lunn, D P

2008-01-01

The proportion of geriatric horses within the equine population has increased in the past decade, but there is limited information on the immune function of these animals. Aged horses will have a lesser increase in serum antibody response to vaccination. Thirty-four aged healthy horses (> or = 20 years) and 29 younger adult horses (4-12 years) of various breeds. All horses were vaccinated with vaccines of killed rabies and influenza virus. Horses in each age group were allocated to receive either rabies or influenza booster vaccine 4 weeks after the initial vaccination. Serum samples were taken at 0, 4, 8, and 24 weeks. Rabies serum neutralization titers and equine influenza virus specific antibody sub-isotypes (IgGa, IgGb, IgG(T), and IgA) as well as single radial hemolysis (SRH) titers were determined. Rabies antibody titers were similar in the 2 age groups at all sampling times. Aged horses had higher IgGa and IgGb influenza antibody titers before vaccination than younger horses but similar titers after vaccination (P= .004 and P= .0027, respectively). Younger horses had significantly greater increases in titer than aged horses at all sampling times for IgGa (P= .001) and at 8 and 24 weeks for IgGb (P= .041 and .01, respectively). There was no detectable serum IgG(T) at any time point. A significant booster vaccine effect was seen for both antirabies and anti-influenza titers. Anti-influenza titer before vaccination also had a significant effect on subsequent antibody response. Healthy aged horses generated a primary immune response to a killed rabies vaccine similar to that of younger adult horses. Aged horses had a significantly reduced anamnestic response to influenza vaccine.

World Rabies Day - a decade of raising awareness.

PubMed

Balaram, Deepashree; Taylor, Louise H; Doyle, Kim A S; Davidson, Elizabeth; Nel, Louis H

2016-01-01

World Rabies Day was set up in 2007 to raise global awareness about rabies, to provide information on how to prevent the disease in at-risk communities and support advocacy for increased efforts in rabies control. It is held annually on September 28th, with events, media outreach and other initiatives carried out by individuals, professionals, organisations and governments from the local to the international level. The Global Alliance for Rabies Control coordinates World Rabies Day, amplifying the campaign's reach through the provision of a central event platform and resources to support events across the world, the promotion of messages through key rabies stakeholders, and the implementation of specific activities to highlight particular issues. Over the last decade, more than 1,700 registered events have been held across the world and shared with others in the global rabies community. Events in canine rabies endemic countries, particularly in Africa and Asia, have increased over time. Beyond the individual events, World Rabies Day has gained the support of governments and international agencies that recognise its value in supporting existing rabies control initiatives and advocating for improvements. As the rabies landscape has changed, World Rabies Day remains a general day of awareness but has also become an integral part of national, regional and global rabies elimination strategies. The global adoption of 2030 as the goal for the elimination of rabies as a public health threat has led to even greater opportunities for World Rabies Day to make a sustainable impact on rabies, by bringing the attention of policy makers and donors to the ongoing situation and elimination efforts in rabies-endemic countries.

Update on human rabies in a dog- and fox-rabies-free country.

PubMed

Stahl, J-P; Gautret, P; Ribadeau-Dumas, F; Strady, C; Le Moal, G; Souala, F; Maslin, J; Fremont, B; Bourhy, H

2014-07-01

Rabies is responsible for 50,000 deaths per year worldwide. Mainland France has been officially freed from rabies in non-flying animals since 2001. We wanted to provide an update on the French situation, using published data, and describe possible options since official guidelines are lacking. Post-exposure prophylaxis (PEP) (early and careful cleaning and dressing of the wound, vaccination, and in case of high-risk exposure, injection of specific anti-rabies immunoglobulins) is known to be efficient except in rare cases. It is recommended after grade II contact (+specific immunoglobulins in immunodepressed patients), or grade III contact (vaccination+immunoglobulins). Mainland France being rabies-free, 3 options may be considered in case of bite by a dog or a cat that cannot be monitored in France: (a) consider the risk of rabies as null, so no PEP should be administrated, whatever the severity of bites; (b) consider there is a weak but lethal risk, so the international recommendations should be applied, using immunoglobulins in some cases; (c) consider that the risk is extremely low but cannot be excluded, and that the patient should be vaccinated to be protected, but without adding immunoglobulins (whether in case of grade II or III bites). There are no national guidelines for rabies in France, and so the physician managing the patient is the one who will decide to treat or not. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Rabies - epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review.

PubMed

Singh, Rajendra; Singh, Karam Pal; Cherian, Susan; Saminathan, Mani; Kapoor, Sanjay; Manjunatha Reddy, G B; Panda, Shibani; Dhama, Kuldeep

2017-12-01

Rabies is a zoonotic, fatal and progressive neurological infection caused by rabies virus of the genus Lyssavirus and family Rhabdoviridae. It affects all warm-blooded animals and the disease is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. Over 60,000 peoples die every year due to rabies, while approximately 15 million people receive rabies post-exposure prophylaxis (PEP) annually. Bite of rabid animals and saliva of infected host are mainly responsible for transmission and wildlife like raccoons, skunks, bats and foxes are main reservoirs for rabies. The incubation period is highly variable from 2 weeks to 6 years (avg. 2-3 months). Though severe neurologic signs and fatal outcome, neuropathological lesions are relatively mild. Rabies virus exploits various mechanisms to evade the host immune responses. Being a major zoonosis, precise and rapid diagnosis is important for early treatment and effective prevention and control measures. Traditional rapid Seller's staining and histopathological methods are still in use for diagnosis of rabies. Direct immunofluoroscent test (dFAT) is gold standard test and most commonly recommended for diagnosis of rabies in fresh brain tissues of dogs by both OIE and WHO. Mouse inoculation test (MIT) and polymerase chain reaction (PCR) are superior and used for routine diagnosis. Vaccination with live attenuated or inactivated viruses, DNA and recombinant vaccines can be done in endemic areas. This review describes in detail about epidemiology, transmission, pathogenesis, advances in diagnosis, vaccination and therapeutic approaches along with appropriate prevention and control strategies.

Molecular and mathematical modeling analyses of inter-island transmission of rabies into a previously rabies-free island in the Philippines.

PubMed

Tohma, Kentaro; Saito, Mariko; Demetria, Catalino S; Manalo, Daria L; Quiambao, Beatriz P; Kamigaki, Taro; Oshitani, Hitoshi

2016-03-01

Rabies is endemic in the Philippines and dog bites are a major cause of rabies cases in humans. The rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. Therefore, more effective and feasible strategies for rabies control are urgently required in the country. To control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously had no reported cases. Our molecular epidemiological study suggests that inter-island transmission events can occur; therefore, we further investigated these inter-island transmission using phylogenetic and modeling approaches. We investigate inter-island transmission between Luzon and Tablas Islands in the Philippines. Phylogenetic analysis and mathematical modeling demonstrate that there was a time lag of several months to a year from rabies introduction to initial case detection, indicating the difficulties in recognizing the initial rabies introductory event. There had been no rabies cases reported in Tablas Island; however, transmission chain was sustained on this island after the introduction of rabies virus because of low vaccination coverage among dogs. Across the islands, a rabies control program should include control of inter-island dog transportation and rabies vaccination to avoid viral introduction from the outside and to break transmission chains after viral introduction. However, this program has not yet been completely implemented and transmission chains following inter-island virus transmission are still observed. Local government units try to control dog transport; however, it should be more strictly controlled, and a continuous rabies control program should be implemented to prevent rabies spread even in rabies-free areas. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Strategic model of national rabies control in Korea.

PubMed

Cheong, Yeotaek; Kim, Bongjun; Lee, Ki Joong; Park, Donghwa; Kim, Sooyeon; Kim, Hyeoncheol; Park, Eunyeon; Lee, Hyeongchan; Bae, Chaewun; Oh, Changin; Park, Seung-Yong; Song, Chang-Seon; Lee, Sang-Won; Choi, In-Soo; Lee, Joong-Bok

2014-01-01

Rabies is an important zoonosis in the public and veterinary healthy arenas. This article provides information on the situation of current rabies outbreak, analyzes the current national rabies control system, reviews the weaknesses of the national rabies control strategy, and identifies an appropriate solution to manage the current situation. Current rabies outbreak was shown to be present from rural areas to urban regions. Moreover, the situation worldwide demonstrates that each nation struggles to prevent or control rabies. Proper application and execution of the rabies control program require the overcoming of existing weaknesses. Bait vaccines and other complex programs are suggested to prevent rabies transmission or infection. Acceleration of the rabies control strategy also requires supplementation of current policy and of public information. In addition, these prevention strategies should be executed over a mid- to long-term period to control rabies.

Arctic-like Rabies Virus, Bangladesh

PubMed Central

Jamil, Khondoker Mahbuba; Hossain, Moazzem; Matsumoto, Takashi; Ali, Mohammad Azmat; Hossain, Sohrab; Hossain, Shakhawat; Islam, Aminul; Nasiruddin, Mohammad; Nishizono, Akira

2012-01-01

Arctic/Arctic-like rabies virus group 2 spread into Bangladesh ≈32 years ago. Because rabies is endemic to and a major public health problem in this country, we characterized this virus group. Its glycoprotein has 3 potential N-glycosylation sites that affect viral pathogenesis. Diversity of rabies virus might have public health implications in Bangladesh. PMID:23171512

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... alpha-globulin (a serum protein) in serum and other body fluids. Measurement of alpha-globulin may aid... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Rabies in Iraq: trends in human cases 2001-2010 and characterisation of animal rabies strains from Baghdad.

PubMed

Horton, Daniel L; Ismail, Mashair Z; Siryan, Eman S; Wali, Abdul Raheem A; Ab-dulla, Husam E; Wise, Emma; Voller, Katja; Harkess, Graeme; Marston, Denise A; McElhinney, Lorraine M; Abbas, Salah F; Fooks, Anthony R

2013-01-01

Control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. These are challenging in any circumstances, but particularly during conflict. Here we describe available human rabies surveillance data from Iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from Iraq. Human rabies is notifiable, with reported cases increasing since 2003, and a marked increase in Baghdad between 2009 and 2010. These changes coincide with increasing numbers of reported dog bites. There is no laboratory confirmation of disease or virus characterisation and no systematic surveillance for rabies in animals. To address these issues, brain samples were collected from domestic animals in the greater Baghdad region and tested for rabies. Three of 40 brain samples were positive using the fluorescent antibody test and hemi-nested RT-PCR for rabies virus (RABV). Bayesian phylogenetic analysis using partial nucleoprotein gene sequences derived from the samples demonstrated the viruses belong to a single virus variant and share a common ancestor with viruses from neighbouring countries, 22 (95% HPD 14-32) years ago. These include countries lying to the west, north and east of Iraq, some of which also have other virus variants circulating concurrently. These results suggest possible multiple introductions of rabies into the Middle East, and regular trans-boundary movement of disease. Although 4000 years have passed since the original description of disease consistent with rabies, animals and humans are still dying of this preventable and neglected zoonosis.

Rabies in South Asia: fighting for elimination.

PubMed

Chowdhury, Fazle-Rabbi; Basher, Ariful; Amin, Mohammad R; Hassan, Nazia; Patwary, Mohammad I

2015-01-01

South Asia is regarded as the hot spot for the tourist and travelers. Unfortunately, three big countries (India, Pakistan and Bangladesh) of this region belong to top five rabies endemic countries of the world. Around 55,000 people die of rabies every year globally and 45% of them belong to South and South East Asia. Countries are now working on the elimination of rabies by the year 2020. Elimination of animal rabies is the pivotal of controlling human rabies. Dog (primary source) registration, population control and mass vaccination are the different ways of eliminating animal rabies. Pre (for risk groups including travelers) and post-exposure vaccine is the core for controlling human rabies. Post-exposure vaccine consists of nerve tissue vaccine and tissue culture vaccine. Due to low antigenicity and post-vaccine neurological complications all countries of South Asia except Pakistan have phased out the production and use of nerve tissue vaccine. To reduce the cost intramuscular regimen is now largely replaced by intradermal regimen and equine rabies immunoglobulin will probably replace human immunoglobulin in future for category III animal bite. 'SAARC' took initiatives for rabies elimination through 'SAARC development fund' which would hopefully play a vital role in regional collaboration to make the region rabies free.

Acquired Immunological Tolerance to a Fraction of Bovine Gamma Globulin

PubMed Central

Dresser, D. W.

1961-01-01

A state of acquired immunological tolerance to bovine gamma globulin (BGG) has been observed in CBA mice injected with 10 mg. BGG within 12 hours of birth. Tolerance was demonstrated by a lack of immune elimination of 131I labelled BGG (BGG-131I) after prior challenge with Freund's adjuvant containing BGG. The degree of tolerance was found to diminish when the time between the tolerance injection and the challenge injection with adjuvant was increased. Mice were found to be tolerant 4 months after injection of 10 mg. BGG at birth but other similarly treated mice were found to be partially immune when challenged 6 months after the tolerance injection. This diminution of tolerance could be prevented by injections of antigen into adult mice whilst they were still tolerant. Precipitin and haemagglutination tests showed that antibody to BGG was present in mice shown to be tolerant to BGG by the antigen-elimination technique. The Ouchterlony double-diffusion technique showed that the mice were tolerant to one fraction of BGG but immune to at least one other fraction. The tolerated fraction of BGG was identified by means of starch-gel electrophoresis. ImagesFIG. 2 PMID:13724353

Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin.

PubMed

Sauter, Craig; Abboud, Michelle; Jia, Xiaoyu; Heller, Glenn; Gonzales, Anne-Marie; Lubin, Marissa; Hawke, Rebecca; Perales, Miguel-Angel; van den Brink, Marcel R; Giralt, Sergio; Papanicolaou, Genovefa; Scaradavou, Andromachi; Small, Trudy N; Barker, Juliet N

2011-10-01

Factors contributing to infection risk after cord blood transplantation (CBT) include the use of anti-thymocyte globulin (ATG), prolonged neutropenia, and failure to transfer immunity. In the present study, we investigated the potential of double-unit CBT without ATG to reduce the risk of infection and evaluated the nature of serious infections in the first year after CBT using this approach. Seventy-two predominantly adult patients underwent CBT for hematologic malignancies; of these, 52 patients received myeloablative conditioning, and 20 received nonmyeloablative conditioning. The peak incidences of bacterial infections (32%), fungal infections (14%), and bacterial/fungal pneumonias (10%) occurred in the first 30 days posttransplantation. Three such infections contributed to early mortality. The peak incidence of viral infections was 31-60 days posttransplantation, affecting 30% of patients. Cytomegalovirus (CMV) was the most common viral infection. CMV infections occurring before day 120 (n = 23) had no relationship with graft-versus-host disease (GVHD), whereas CMV infections occurring after day 120 (n = 5), along with all cases of Epstein-Barr virus viremia (n = 5) and adenoviral enteritis (n = 2), occurred exclusively in the context of GVHD therapy or corticosteroid use for another indication. Viral infections had the highest lethality: 2 were a direct cause of death, and 3 contributed to death. Patients exhibited steady immune recovery, achieving a median CD3(+)4(+) T cell count >200 cells/μL by day 120 post-CBT, and no infection-related deaths occurred after day 120. Our results suggest that double-unit CBT without ATG is associated with prompt T cell recovery, and, unlike in CBT incorporating ATG, infection is rarely a primary cause of death. However, CBT without ATG is associated with a significant risk of GVHD, and serious infections remain a challenge, especially in the setting of GVHD. New strategies are needed to further reduce infectious

STUDIES ON STRUCTURAL UNITS OF THE γ-GLOBULINS

PubMed Central

Edelman, G. M.; Poulik, M. D.

1961-01-01

When human and rabbit 7S γ-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately ⅓ of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S γ-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components. A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal γ-globulins. Reduction of normal and abnormal γ-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules. PMID:13725659

Control and prevention of rabies in animals: paradigm shifts.

PubMed

Rupprecht, C E; Hanlon, C A; Slate, D

2006-01-01

in which wildlife rabies persists despite the elimination of canine rabies, e.g. in North America and Europe, cats can pose a significant public health risk requiring consideration of alternative approaches. In any model system, the threat of translocation of infected animals, unintentional or otherwise, provides a strong rationale for the creation of barriers to prevent reintroduction or exacerbation of the disease, and the maintenance of a minimum body of expertise related to surveillance, diagnosis, and the enactment of mitigating measures. While control activities have traditionally focused upon certain Carnivora species, bats represent another worldwide rabies reservoir. Indiscriminate killing of bats and destruction of roosts was once the norm, but such activities are not sanctioned by reputable organizations today. Even vampire bats, responsible for substantial effects on health and agricultural losses in the New World (Mexico to Argentina), should be targeted only by specific control applications, rather than by more widespread, unconventional, non-specific methodology. Bats should be excluded from human living quarters. Implementing measures to prevent bats from gaining access to homes should occur at an appropriate time when the bats are absent, especially to avoid sealing the non-flying young within a building. Although great progress has been made during the past four decades in the induction of herd immunity among free-ranging carnivores via oral vaccination against rabies, similar novel solutions have not been readily applied to bat populations. Given these challenges, new paradigm shifts are eagerly anticipated as additional biotechnological applications (including contraceptives and anticoagulants) are developed to deal with domestic animals and wildlife.

Rabies direct fluorescent antibody test does not inactivate rabies or eastern equine encephalitis viruses.

PubMed

Jarvis, Jodie A; Franke, Mary A; Davis, April D

2016-08-01

An examination using the routine rabies direct fluorescent antibody test was performed on rabies or Eastern equine encephalitis positive mammalian brain tissue to assess inactivation of the virus. Neither virus was inactivated with acetone fixation nor the routine test, thus laboratory employees should treat all samples as rabies and when appropriate Eastern equine encephalitis positive throughout the whole procedure. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

Maki, Joanne; Guiot, Anne-Laure; Aubert, Michel; Brochier, Bernard; Cliquet, Florence; Hanlon, Cathleen A; King, Roni; Oertli, Ernest H; Rupprecht, Charles E; Schumacher, Caroline; Slate, Dennis; Yakobson, Boris; Wohlers, Anne; Lankau, Emily W

2017-09-22

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

Eliminating Rabies in Estonia

PubMed Central

Cliquet, Florence; Robardet, Emmanuelle; Must, Kylli; Laine, Marjana; Peik, Katrin; Picard-Meyer, Evelyne; Guiot, Anne-Laure; Niin, Enel

2012-01-01

The compulsory vaccination of pets, the recommended vaccination of farm animals in grazing areas and the extermination of stray animals did not succeed in eliminating rabies in Estonia because the virus was maintained in two main wildlife reservoirs, foxes and raccoon dogs. These two species became a priority target therefore in order to control rabies. Supported by the European Community, successive oral vaccination (OV) campaigns were conducted twice a year using Rabigen® SAG2 baits, beginning in autumn 2005 in North Estonia. They were then extended to the whole territory from spring 2006. Following the vaccination campaigns, the incidence of rabies cases dramatically decreased, with 266 cases in 2005, 114 in 2006, four in 2007 and three in 2008. Since March 2008, no rabies cases have been detected in Estonia other than three cases reported in summer 2009 and one case in January 2011, all in areas close to the South-Eastern border with Russia. The bait uptake was satisfactory, with tetracycline positivity rates ranging from 85% to 93% in foxes and from 82% to 88% in raccoon dogs. Immunisation rates evaluated by ELISA ranged from 34% to 55% in foxes and from 38% to 55% in raccoon dogs. The rabies situation in Estonia was compared to that of the other two Baltic States, Latvia and Lithuania. Despite regular OV campaigns conducted throughout their territory since 2006, and an improvement in the epidemiological situation, rabies has still not been eradicated in these countries. An analysis of the number of baits distributed and the funding allocated by the European Commission showed that the strategy for rabies control is more cost-effective in Estonia than in Latvia and Lithuania. PMID:22393461

Human antibodies to bovine alpha-globulin.

PubMed

Foucard, T; Bennich, H; Johansson, S G; Lundkvist, U

1975-01-01

Antibodies to bovine gamma-globulin (anti-BGG antibodies) were detectable by a radio-immunoassay in 70% of healthy blood donors but, generally, the titres were low. Significantly increased concentrations of anti-BGG antibodies were found in patients lacking IgA but not in patients with allergic disorders. The anti-BGG antibodies were shown to give rise to falsely high IgE values in the radio-immunosorbent test for IgE determination (RIST) when a sheep anti-IgE antiserum was used. Furthermore, falsely positive results can sometimes be caused by such antibodies in the determination of cow-dander- or cow's-milk-specific IgE by the radio-allergosorbent test (RAST). When a rabbit anti-IgE antiserum was used instead of the sheep anti-IgE, normal IgE levels and negative RAST results were obtained. The difference is explained by the higher degree of cross-reactivity between the anti-BGG antibodies and sheep alpha-globulin than between anti-BGG antibodies and rabbit alpha-globulin.

Rabies in a Dog Imported from Egypt with a Falsified Rabies Vaccination Certificate--Virginia, 2015.

PubMed

Sinclair, Julie R; Wallace, Ryan M; Gruszynski, Karen; Freeman, Marilyn Bibbs; Campbell, Colin; Semple, Shereen; Innes, Kristin; Slavinski, Sally; Palumbo, Gabriel; Bair-Brake, Heather; Orciari, Lillian; Condori, Rene E; Langer, Adam; Carroll, Darin S; Murphy, Julia

2015-12-18

Canine rabies virus variant has been eliminated in the United States and multiple other countries. Globally, however, dogs remain the principal source for human rabies infections. The World Health Organization recommends that when dogs cross international borders, national importing authorities should require an international veterinary certificate attesting that the animal did not show signs of rabies at the time of shipment, was permanently identified, vaccinated, or revaccinated, and had been subjected to a serologic test for rabies before shipment. On June 8, 2015, an adult female dog that had recently been picked up from the streets of Cairo, Egypt, and shipped by a U.S. animal rescue organization to the United States was confirmed to have rabies by the Virginia Department of General Services Division of Consolidated Laboratory Services (DCLS). This dog was part of a large shipment of dogs and cats from Egypt that rescue organizations had distributed to multiple states for adoption. During the investigation, public health officials learned that the rabies vaccination certificate used for entry of the rabid dog into the United States had intentionally been falsified to avoid exclusion of the dog from entry under CDC's current dog importation regulations. This report underscores the ongoing risk posed by U.S. importation of domestic animals that have not been adequately vaccinated against rabies.

Livestock rabies outbreaks in Shanxi province, China.

PubMed

Feng, Ye; Shi, Yanyan; Yu, Mingyang; Xu, Weidi; Gong, Wenjie; Tu, Zhongzhong; Ding, Laixi; He, Biao; Guo, Huancheng; Tu, Changchun

2016-10-01

Dogs play an important role in rabies transmission throughout the world. In addition to the severe human rabies situation in China, spillover of rabies virus from dogs in recent years has caused rabies outbreaks in sheep, cattle and pigs, showing that there is an increasing threat to other domestic animals. Two livestock rabies outbreaks were caused by dogs in Shanxi province, China from April to October in 2015, resulting in the deaths of 60 sheep, 10 cattle and one donkey. Brain samples from one infected bovine and the donkey were determined to be rabies virus (RABV) positive by fluorescent antibody test (FAT) and reverse transcription polymerase chain reaction (RT-PCR). The complete RABV N genes of the two field strains, together with those of two previously confirmed Shanxi dog strains, were amplified, sequenced and compared phylogenetically with published sequences of the N gene of RABV strains from Shanxi and surrounding provinces. All of the strains from Shanxi province grouped closely, sharing 99.6 %-100 % sequence identity, indicating the wide distribution and transmission of dog-mediated rabies in these areas. This is the first description of donkey rabies symptoms with phylogenetic analysis of RABVs in Shanxi province and surrounding regions. The result emphasizes the need for mandatory dog rabies vaccination and improved public education to eradicate dog rabies transmission.

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

21 CFR 862.1685 - Thyroxine-binding globulin test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... globulin test system is a device intended to measure thyroxine (thyroid)-binding globulin (TBG), a plasma protein which binds thyroxine, in serum and plasma. Measurements obtained by this device are used in the...

Post-exposure rabies prophylaxis in humans exposed to animals in Lublin province (Eastern Poland) in 2012-2015 - A retrospective study.

PubMed

Krzowska-Firych, Joanna; Tomasiewicz, Krzysztof; Kozøowska, Agata

2017-06-03

Rabies continues to be one of the most important viral diseases and remains a significant threat to public health across the globe. The post-exposure prophylaxis in humans can effectively prevent death after exposure to a potentially infected animal. In Poland, recommendations for rabies PEP followed the national guidelines which recommend that people should receive PEP when bitten by an animal suspected to be infected by rabies. PEP in humans includes cleansing and disinfecting the wound or point of contact, and administering anti-rabies immunization. Rabies vaccine should be given for contacts of category II and category III exposures. RIG should be given for category III contact. The vaccination schedule includes 5 doses given within a 30 day period (the Essen regimen). The aim of our study was to determine the frequency of post-exposure prophylaxis among patients exposed to animals and also to assess the animal species suspected as a source of rabies exposure. We have retrospectively analyzed medical records from the years 2012-2015 of all adult patients who were exposed to animals and consulted at the Dispensary of Rabies Prophylaxis in the Department of Infectious Diseases at the Medical University in Lublin, Poland. All consulted patients were asked to give an informed consent in case of decision to use collected data for future research work. Ethical approval was obtained from the Ethics Committee of the Medical University of Lublin, Poland, and all patients included in this study gave an informed consent during consultation after the exposure to animals. During the studied 4-year period, 511 persons exposed to animals were consulted and prophylactic procedure consisting of active immunization were applied in 54.2% of the total consulted. Dogs and cats were the most common animal species suspected as the source of the rabies exposure. Anti-rabies prophylaxis was applied in 45.8% of all vaccinated patients exposed to dogs, and in 24.2% exposed to cats. All

Molecular epidemiology of rabies in northern Colombia 1994-2003. Evidence for human and fox rabies associated with dogs.

PubMed Central

Páez, A.; Saad, C.; Núñez, C.; Bóshell, J.

2005-01-01

During the period 2000-2003, wild grey foxes (Urocyon cinereoargenteus) in northern Colombia became infected with rabies. In order to derive phylogenetic relationships between rabies viruses isolated in foxes, dogs and humans in this region, 902 nt cDNA fragments containing the G-L intergenic region and encoding the cytoplasmic domain of protein G and a fragment of protein L were obtained by RT-PCR, sequenced and compared. Phylogenetic analysis showed that rabies viruses isolated in foxes, dogs and humans belonged to a single genetic variant. Speculative analysis together with epidemiological data indicated that rabies in foxes may have been due to contact with rabid dogs. Rabies transmission between dogs, wild foxes and humans may happen in natural conditions in northern Colombia. This finding is the first to suggest dog-to-fox rabies transmission in South America, and provides another example of dog rabies variants being able to successfully colonize wildlife hosts. PMID:15962560

Laboratory Diagnosis of Human Rabies: Recent Advances

PubMed Central

Mani, Reeta Subramaniam; Madhusudana, Shampur Narayan

2013-01-01

Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre- or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future. PMID:24348170

Incidence of human rabies and characterization of rabies virus nucleoprotein gene in dogs in Fujian Province, Southeast China, 2002-2012.

PubMed

Zhang, Jian-Ming; Zhang, Zhi-Shan; Deng, Yan-Qin; Wu, Shou-Li; Wang, Wei; Yan, Yan-Sheng

2017-08-30

Rabies is a global fatal infectious viral disease that is characterized by a high mortality after onset of clinical symptoms. Recently, there has been an increase in the incidence of rabies in China. The aim of this study was to investigate the incidence of human rabies and characterize the rabies virus nucleoprotein gene in dogs sampled from Fujian Province, Southeast China from 2002 to 2012. Data pertaining to human rabies cases in Fujian Province during the period from 2002 through 2012 were collected, and the epidemiological profiles were described. The saliva and brain specimens were collected from dogs in Quanzhou, Longyan and Sanming cities of the province, and the rabies virus antigen was determined in the canine saliva specimens using an ELISA assay. Rabies virus RNA was extracted from canine brain specimens, and rabies virus nucleoprotein gene was amplified using a nested RT-PCR assay, followed by sequencing and genotyping. A total of 226 human rabies cases were reported in Fujian Province from 2002 to 2012, in which 197 cases were detected in three cities of Quanzhou, Longyan and Sanming. ELISA assay revealed positive rabies virus antigen in six of eight rabid dogs and 165 of 3492 seemingly healthy dogs. The full-length gene fragment of the rabies virus nucleoprotein gene was amplified from the brain specimens of seven rabid dogs and 12 seemingly healthy dogs. Sequence alignment and phylogenetic analysis revealed that these 19 rabies virus nucleoprotein genes all belonged to genotype I, and were classified into three genetic groups. Sequencing analysis showed a 99.7% to 100% intra-group and an 86.4% to 89.3% inter-group homology. This study is the first description pertaining to the epidemiological characteristics of human rabies cases and characterization of the rabies virus nucleoprotein gene in dogs in Fujian Province, Southeast China. Our findings may provide valuable knowledge for the development of strategies targeting the prevention and control of

Rabies in Iraq: Trends in Human Cases 2001–2010 and Characterisation of Animal Rabies Strains from Baghdad

PubMed Central

Horton, Daniel L.; Ismail, Mashair Z.; Siryan, Eman S.; Wali, Abdul Raheem A.; Ab-dulla, Husam E.; Wise, Emma; Voller, Katja; Harkess, Graeme; Marston, Denise A.; McElhinney, Lorraine M.; Abbas, Salah F.; Fooks, Anthony R.

2013-01-01

Control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. These are challenging in any circumstances, but particularly during conflict. Here we describe available human rabies surveillance data from Iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from Iraq. Human rabies is notifiable, with reported cases increasing since 2003, and a marked increase in Baghdad between 2009 and 2010. These changes coincide with increasing numbers of reported dog bites. There is no laboratory confirmation of disease or virus characterisation and no systematic surveillance for rabies in animals. To address these issues, brain samples were collected from domestic animals in the greater Baghdad region and tested for rabies. Three of 40 brain samples were positive using the fluorescent antibody test and hemi-nested RT-PCR for rabies virus (RABV). Bayesian phylogenetic analysis using partial nucleoprotein gene sequences derived from the samples demonstrated the viruses belong to a single virus variant and share a common ancestor with viruses from neighbouring countries, 22 (95% HPD 14–32) years ago. These include countries lying to the west, north and east of Iraq, some of which also have other virus variants circulating concurrently. These results suggest possible multiple introductions of rabies into the Middle East, and regular trans-boundary movement of disease. Although 4000 years have passed since the original description of disease consistent with rabies, animals and humans are still dying of this preventable and neglected zoonosis. PMID:23469303

Imported human rabies -New Jersey, 2011.

PubMed

2012-01-06

On July 8, 2011, the New Jersey Department of Health and Senior Services (NJDHSS) contacted CDC about possible rabies in a hospitalized Haitian woman aged 73 years. Rabies was included in the differential diagnosis because she had acute, progressive encephalitis of unknown etiology. No history of animal exposure had been reported at the time of hospitalization. On July 18, CDC confirmed rabies virus infection, later identified as a canine rabies virus variant present in Haiti. The patient's neurologic status continued to deteriorate, leading to her death on July 20. This report summarizes the patient's clinical course and the associated public health investigation. This is the third report of human rabies in the United States acquired in Haiti since 2000 and highlights the importance of obtaining a detailed history for patients who have traveled from a rabies-endemic country and the value of consultation with medical and public health professionals regarding any animal bites.

Arctic rabies--a review.

PubMed

Mørk, Torill; Prestrud, Pål

2004-01-01

Rabies seems to persist throughout most arctic regions, and the northern parts of Norway, Sweden and Finland, is the only part of the Arctic where rabies has not been diagnosed in recent time. The arctic fox is the main host, and the same arctic virus variant seems to infect the arctic fox throughout the range of this species. The epidemiology of rabies seems to have certain common characteristics in arctic regions, but main questions such as the maintenance and spread of the disease remains largely unknown. The virus has spread and initiated new epidemics also in other species such as the red fox and the racoon dog. Large land areas and cold climate complicate the control of the disease, but experimental oral vaccination of arctic foxes has been successful. This article summarises the current knowledge and the typical characteristics of arctic rabies including its distribution and epidemiology.

Compendium of animal rabies prevention and control, 2011.

PubMed

2011-11-04

Rabies has one of the highest case-fatality ratios of any infectious disease. This report provides recommendations for public health officials, veterinarians, animal control officials, and other parties engaged in rabies prevention and control activities and should serve as the basis for standardizing procedures among jurisdictions. The recommendations regarding domestic animal vaccination, management of animals exposed to rabies, and management of animals that bite humans are the core elements of animal rabies control and human rabies prevention. These updated 2011 guidelines include the national case definition for animal rabies and clarify the role of the CDC rabies laboratory in providing confirmatory testing of suspect animals. The table of rabies vaccines licensed and marketed in the United States has been updated, and additional references have been included to provide scientific support for information in this report.

Notes from the field: wildlife rabies on an island free from canine rabies for 52 years--Taiwan, 2013.

PubMed

Wu, Hsiu; Chang, Su-San; Tsai, Hsiang-Jung; Wallace, Ryan M; Recuenco, Sergio E; Doty, Jeffrey B; Vora, Neil M; Chang, Feng-Yee

2014-02-28

Dog-to-dog transmission of rabies in Taiwan was eliminated in 1961; the island was considered canine rabies-free for 52 years. On July 16, 2013, three ferret-badgers (Melogale moschata) tested positive for rabies by fluorescent antibody testing at the Animal Health Research Institute, Council of Agriculture of Taiwan. This was the first time wild animals other than bats were tested. During 1999-2012, a total of 6,841 clinically healthy dogs and five apparently normal cats from shelters were tested and found negative for rabies. During 2009-2012, a total of 322 bats were tested and found negative for rabies.

Molecular characterization of KGH, the first human isolate of rabies virus in Korea.

PubMed

Park, Jun-Sun; Kim, Chi-Kyeong; Kim, Su Yeon; Ju, Young Ran

2013-04-01

The complete genome sequence of the KGH strain of the first human rabies virus, which was isolated from a skin biopsy of a patient with rabies, whose symptoms developed due to bites from a raccoon dog in 2001. The size of the KGH strain genome was determined to be 11,928 nucleotides (nt) with a leader sequence of 58 nt, nucleoprotein gene of 1,353 nt, phosphoprotein gene of 894 nt, matrix protein gene of 609 nt, glycoprotein gene of 1,575 nt, RNA-dependent RNA polymerase gene of 6,384 nt, and trailer region of 69 nt. Sequence similarity was compared with 39 fully sequenced rabies virus genomes currently available, and the result showed 70.6-91.6 % at the nucleotide level, and 82.8-97.9 % at the amino acid level. The deduced amino acids in the viral protein were compared with those of other rabies viruses, and various functional regions were investigated. As a result, we found that the KGH strain only had a unique amino acid substitution that was identified to be associated either with host immune response and pathogenicity in the N protein, or with a related region regulating STAT1 in the P protein, and related to pathogenicity in G protein. Based on phylogenetic analyses using the complete genome of 39 rabies viruses, the KGH strain was determined to be closely related with the NNV-RAB-H strain and transplant rabies virus serotype 1, which are Indian isolates, and was confirmed to belong to the Arctic-like 2 clade. The KGH strain was most closely related to the SKRRD0204HC and SKRRD0205HC strain when compared with Korean animal isolates, which was separated around the same time and place, and belonged to the Gangwon III subgroup.

Rabies: Questions and Answers

MedlinePlus

... years. What should I do if a neighborhood dog bites my child? Rabies is not common in dogs, cats, ferrets, and live- stock in the United ... situation. If rabies isn't common in U.S. dogs and cats anymore, is there anything to worry ...

Expression of interleukin-6 by a recombinant rabies virus enhances its immunogenicity as a potential vaccine.

PubMed

Luo, Jun; Zhang, Boyue; Wu, Yuting; Tian, Qin; Zhao, Jing; Lyu, Ziyu; Zhang, Qiong; Mei, Mingzhu; Luo, Yongwen; Guo, Xiaofeng

2017-02-07

Several studies have confirmed that interleukin-6 (IL6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. In the present study, recombinant rabies virus (RABV) expressing canine IL6 (rHEP-CaIL6) was rescued and its pathogenicity and immunogenicity were investigated in mice. We demonstrated that mice received a single intramuscular immunization with rHEP-CaIL6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (VNA) as well as anti-RABV antibodies compared with mice immunized with the parent strain. Moreover, survival rates of mice immunized with rHEP-CaIL6 were higher compared with mice immunized with parent HEP-Flury according to the challenge assay. Flow cytometry further confirmed that immunization with rHEP-CaIL6 induced the strong recruitment of mature B cells and CD8 + T cells to lymph nodes, which may partially explain the high levels of VNA and enhanced cellular immunity. Quantitative real-time PCR indicated that rHEP-CaIL6 induced stronger inflammatory and immune responses in the central nervous system, which might have allowed virus clearance in the early infection phase. Furthermore, mice infected intranasally with rHEP-CaIL6 developed no clinical symptoms while mice infected with HEP-Flury showed piloerection. In summary, these data indicate that rHEP-CaIL6 induces a strong, protective immune response with a good safety profile. Therefore, a recombinant RABV strain expressing canine IL6 may aid the development of an effective, safe attenuated rabies vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Attaining raccoon rabies management goals: history and challenges.

PubMed

Slate, D; Rupprecht, C E; Donovan, D; Badcock, J; Messier, A; Chipman, R; Mendoza, M; Nelson, K

2008-01-01

Prior to 1977, raccoon (Procyon lotor) rabies was confined to the southeastern US. Translocations led to emergence of this rabies variant in the mid-Atlantic states, followed by spread northerly to northeast Ohio and Ontario, Quebec, and New Brunswick, Canada. Raccoon rabies is currently contiguous from southwest Alabama to southeastern Canada. Since 1998, state, federal, county and municipal as well as Canadian and Mexican experts have collaborated on goals and strategies to prevent raccoon rabies spread in North America. Coordinated programmes have been established from Maine to Alabama. Successes have been realized through strategies that rely heavily on oral vaccination. International coordination targeting raccoon rabies continues in eastern Canada, where contingency actions have led to elimination or near elimination in Ontario and New Brunswick. However, increasingly, focus in the US has been directed toward contingency actions to "hold-the-line" where raccoon rabies threatens to spread to new areas, rather than on raccoon rabies elimination. We report on the challenges of achieving enhanced rabies surveillance, containment of raccoon rabies, and local elimination of raccoon rabies, as well as the need for international coordination in meeting these challenges.

Genomic organization of the rat alpha 2u-globulin gene cluster.

PubMed

McFadyen, D A; Addison, W; Locke, J

1999-05-01

The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

Fighting rabies in Eastern Europe, the Middle East and Central Asia--experts call for a regional initiative for rabies elimination.

PubMed

Aikimbayev, A; Briggs, D; Coltan, G; Dodet, B; Farahtaj, F; Imnadze, P; Korejwo, J; Moiseieva, A; Tordo, N; Usluer, G; Vodopija, R; Vranješ, N

2014-05-01

MEEREB is an informal network of rabies experts from the Middle East, Eastern Europe and Central Asia, seeking to eliminate rabies from the region. They met for the second time to review the current rabies situation, both globally and in their respective countries, highlighting current rabies control problems and potential solutions. Success stories in Latin America, in Western Europe, in some Asian countries, as well as in Croatia and Serbia prove that elimination of human rabies is achievable in the MEEREB region. It requires political willingness and cooperation of all stakeholders, including Ministries of Health and of Agriculture; adequate management of animal bites through post-exposure prophylaxis; pre-exposure prophylaxis for populations at high risk of rabies exposure, animal vaccination and humane control of stray dog populations. MEEREB members called for a regional initiative for rabies elimination in Eastern Europe and the Middle East. They are confident that the elimination of human rabies of canine origin can be achieved in the region through adopting a One Health approach, and that campaigns for rabies elimination will have significant benefit for public health, including strengthening the structure for control of other zoonoses. © 2013 Blackwell Verlag GmbH.

Rabies in Poland in 2013 and 2014

PubMed

Sadkowska-Todys, Małgorzata; Kucharczyk, Bożena

Evaluation of the epidemiological situation of rabies in Poland in 2013 and 2014 in comparison to the previous years. The evaluation was based on analysis of the data from individual report sent by the Epidemiological-Sanitary Stations. The data are from questionnaires of persons who were administered vaccine against rabies following exposure in Poland and beyond its territory, data from annual bulletin “Infectious diseases and poisonings in Poland in 2012-2014”(Czarkowski MP et al., Warsaw, NIH and CSI) and epizootic data provided by the General Veterinary Inspectorate. Number of animal rabies cases reported in Poland in 2013 and in 2014 was 204 and 105, respectively. This was 30% and 60% less compared to 2012. In 2013 more than 59% of animal rabies cases occurred in Podkarpackie veivodeship and more than 28% in Malopolskie. In 2014 more than 77% of rabid animals were found in the Małopolskie veivodeship, but Podkarpackie accounted for less than 9%. Rabies in terrestrial animals in 2013-2014 was also found in Lubelskie, Podlaskie and Świętokrzyskie veivodeships. In other regions of the country there were reported only single cases of rabies in bats. In 2013, a total of 7 317 people were vaccinated against rabies in 2013 and 7 679 in 2014 including 295 (4%) and 145 (1.9%) persons vaccinated due to exposure to the animals with confirmed rabies, respectively. Among those vaccinated after contact with rabid animal 26% and 29% were vaccinated after contact with a fox in 2013 and 2014, respectively and 64% and 57% as a result of exposure to the domestic animals with confirmed rabies. As with the previous years, people were vaccinated mostly due to exposure to dogs and cats, in which rabies could not be excluded - 5 725 people in 2013 (88%) and 6 057 (87%) in 2014. After the increase in the number of animal rabies cases that occurred in 2012, in the next two years there has been a gradual decline in its number. In 2014 the number of animal rabies cases was lower

In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines.

PubMed

Pfaff, Florian; Müller, Thomas; Freuling, Conrad M; Fehlner-Gardiner, Christine; Nadin-Davis, Susan; Robardet, Emmanuelle; Cliquet, Florence; Vuta, Vlad; Hostnik, Peter; Mettenleiter, Thomas C; Beer, Martin; Höper, Dirk

2018-02-10

Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their parental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection. Copyright © 2018. Published by Elsevier Ltd.

Molecular epidemiology of rabies viruses circulating in two rabies endemic provinces of Laos, 2011-2012: regional diversity in Southeast Asia.

PubMed

Ahmed, Kamruddin; Phommachanh, Phouvong; Vorachith, Phengphet; Matsumoto, Takashi; Lamaningao, Pheophet; Mori, Daisuke; Takaki, Minako; Douangngeun, Bounlom; Khambounheuang, Bounkhouang; Nishizono, Akira

2015-03-01

Although rabies is endemic in Laos, genetic characterization of the viruses in this country is limited. There are growing concerns that development in the region may have increased transport of dog through Laos for regional dog meat consumption, and that this may cause spillover of the viruses from dogs brought here from other countries. This study was therefore undertaken to evaluate the current rabies situation and the genetic characteristics of rabies viruses currently circulating in Laos. We determined the rate of rabies-positive samples by analyzing data from animal samples submitted to the Lao Ministry of Agriculture and Forestry's National Animal Health Centre rabies laboratory from 2004 through 2011. Twenty-three rabies-positive samples were used for viral genetic characterization. Full genome sequencing was performed on two rabies viruses. Rabies-positive samples increased substantially from 40.5% in 2004 to 60.2% in 2009 and continued at this level during the study period. More than 99% of the samples were from dogs, followed by cats and monkeys. Phylogenetic analyses showed that three rabies virus lineages belonging to the Southeast Asian cluster are currently circulating in Laos; these are closely related to viruses from Thailand, Cambodia and Vietnam. Lineages of the circulating Laos rabies viruses diverged from common ancestors as recently as 44.2 years and as much as 55.3 years ago, indicating periodic virus invasions. There is an increasing trend of rabies in Laotian animals. Similar to other rabies-endemic countries, dogs are the main viral reservoir. Three viral lineages closely related to viruses from neighboring countries are currently circulating in Laos. Data provide evidence of periodic historic exchanges of the viruses with neighboring countries, but no recent invasion.

Rabies in Asia: the classical zoonosis.

PubMed

Wilde, Henry; Hemachudha, Thiravat; Wacharapluesadee, Supaporn; Lumlertdacha, Boonlert; Tepsumethanon, Veera

2013-01-01

Rabies remains a constant threat to humans throughout much of Asia. The dog is the main reservoir and vector with wildlife playing a very minor role. No Asian country or region has been declared rabies free by WHO in over two decades and there is evidence of canine rabies spread to new regions during the past 10 years. We now have the knowledge and technology to control canine rabies. The main barrier in managing this costly endemic is lack of motivation by authorities to address this issue along with regional inability of public health and livestock (agriculture) officials to tackle this issue in cooperation and coordination. Rabies is one of the first recognized zoonoses and a model for a true "One Health" management goal where human; veterinary, and government officials must work together in harmony to defeat this disease.

Estimated protective effectiveness of intramuscular immune serum globulin post-exposure prophylaxis during a measles outbreak in British Columbia, Canada, 2014.

PubMed

Bigham, Mark; Murti, Michelle; Fung, Christina; Hemming, Felicity; Loadman, Susan; Stam, Robert; Van Buynder, Paul; Lem, Marcus

2017-05-09

Intramuscular Immune Serum Globulin (IM ISG) is recommended as post-measles exposure prophylaxis (PEP) when administered within 6days of initial exposure, with variable effectiveness in preventing measles disease. Effectiveness of IM ISG PEP in preventing clinical measles was assessed during a 2014 measles outbreak among a religious-affiliated community in British Columbia, Canada. Fifty-five self-reporting measles susceptible contacts were offered exclusively IM ISG PEP within an eligibility period best surmised to be within 6days of initial measles case exposure. Clinical outcome of IM ISG PEP recipients was determined by selective active surveillance and case self-reporting. IM ISG PEP failure was defined as onset of a measles-like rash 8-21days post-IM ISG PEP. Post-IM ISG PEP measles IgG antibody level was tested in 8 recipients. Factors associated with measles disease were analyzed. Seventeen of 55 IM ISG PEP recipients developed clinically consistent measles in the following 8-21days, corresponding to an estimated crude protective effectiveness of 69%. In school aged children 5-18years, among whom potential exposure intensity and immune status confounders were considered less likely, estimated IM ISG PEP protective effectiveness was 50%. Age <25years was significantly associated with breakthrough clinical measles in bivariate analysis (p=0.0217). Among 8 tested contacts of 17 considered IM ISG PEP failures, post-IM ISG PEP measles IgG antibody levels (mean 16.3days (range 16-17days) post-PEP) were all <150mIU/ml. The estimated crude IM ISG PEP protective effectiveness against measles disease within 8-21days post-ISG administration was 69%. Accuracy of this estimated protective effectiveness is vulnerable to assumptions and uncertainties in ascertaining exposure details and pre-exposure immune status. Increasing the Canadian recommended measles IM ISG PEP dose from 0.25 to 0.5ml/kg (up to 15ml maximum volume) may increase protective effectiveness. Copyright �

Post-exposure rabies prophylaxis in humans exposed to animals in Lublin province (Eastern Poland) in 2012–2015 – A retrospective study

PubMed Central

Krzowska-Firych, Joanna; Tomasiewicz, Krzysztof; Kozøowska, Agata

2017-01-01

ABSTRACT Rabies continues to be one of the most important viral diseases and remains a significant threat to public health across the globe. The post-exposure prophylaxis in humans can effectively prevent death after exposure to a potentially infected animal. In Poland, recommendations for rabies PEP followed the national guidelines which recommend that people should receive PEP when bitten by an animal suspected to be infected by rabies. PEP in humans includes cleansing and disinfecting the wound or point of contact, and administering anti-rabies immunization. Rabies vaccine should be given for contacts of category II and category III exposures. RIG should be given for category III contact. The vaccination schedule includes 5 doses given within a 30 day period (the Essen regimen). The aim. The aim of our study was to determine the frequency of post-exposure prophylaxis among patients exposed to animals and also to assess the animal species suspected as a source of rabies exposure. Methods. We have retrospectively analyzed medical records from the years 2012–2015 of all adult patients who were exposed to animals and consulted at the Dispensary of Rabies Prophylaxis in the Department of Infectious Diseases at the Medical University in Lublin, Poland. All consulted patients were asked to give an informed consent in case of decision to use collected data for future research work. Ethical approval was obtained from the Ethics Committee of the Medical University of Lublin, Poland, and all patients included in this study gave an informed consent during consultation after the exposure to animals. Results. During the studied 4-year period, 511 persons exposed to animals were consulted and prophylactic procedure consisting of active immunization were applied in 54.2% of the total consulted. Dogs and cats were the most common animal species suspected as the source of the rabies exposure. Anti-rabies prophylaxis was applied in 45.8% of all vaccinated patients exposed to

Feasibility and efficacy of oral rabies vaccine SAG2 in endangered Ethiopian wolves.

PubMed

Sillero-Zubiri, Claudio; Marino, Jorgelina; Gordon, Christopher H; Bedin, Eric; Hussein, Alo; Regassa, Fekede; Banyard, Ashley; Fooks, Anthony R

2016-09-14

Diseases are a major cause of population declines in endangered populations of several canid species. Parenteral vaccination efforts to protect Ethiopian wolves (Canis simensis) from rabies have targeted the domestic dog reservoir, or the wolves themselves in response to confirmed outbreaks. Oral vaccination offers a more cost-efficient, safe and proactive approach to protect Ethiopian wolves and other threatened canids from rabies. Field trials of the oral vaccine Rabigen® SAG2Dog were undertaken in the Bale Mountains of southeastern Ethiopia. Four different bait types and three delivery methods were tested in twelve Ethiopian wolf packs, and the oral vaccine (using the preferred bait) was trialled in three packs. Vaccine uptake and immunization rates were measured through direct observations and in live-trapped animals through the assessment of biomarker levels and serological status. Commercial baits were never taken by wolves; goat meat baits had the highest uptake, compared to rodent and intestine baits. Targeted delivery from horseback and nocturnal delivery within a pack's territory performed favourably compared to random bait distribution. Bait uptake by non-target species was lowest during the nocturnal blind distribution. Of 21 wolves trapped after vaccination, 14 were positive for the biomarker iophenoxic acid (i.e. ingested the bait and most likely pierced the sachet with the vaccine). Of these, 86% (n=12/14) had levels considered sufficient to provide protective immunity to wildlife (⩾0.20IU/ml), and 50% (n=7/14) demonstrated antibody titres above the universally recognised threshold (⩾0.5IU/ml) -the baseline average was 0.09IU/ml (n=12 wolves). All but one of the wolves vaccinated in 2014 were alive 14months later. Our trials confirm the potential for SAG2, delivered in a goat meat bait, to effectively protect Ethiopian wolves against rabies, supporting the initiative for a more efficient and proactive approach to manage and eventually eliminate

Rabies surveillance in the United States during 2007.

PubMed

Blanton, Jesse D; Palmer, Dustyn; Christian, Kira A; Rupprecht, Charles E

2008-09-15

During 2007, 49 states and Puerto Rico reported 7,258 cases of rabies in animals and 1 case in a human to the CDC, representing a 4.6% increase from the 6,940 cases in animals and 3 cases in humans reported in 2006. Approximately 93% of the cases were in wildlife, and 7% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,659 raccoons (36.6%), 1,973 bats (27.2%), 1,478 skunks (20.4%), 489 foxes (6.7%), 274 cats (3.8%), 93 dogs (1.3%), and 57 cattle (0.8%). Compared with numbers of reported cases in 2006, cases in 2007 increased among dogs, bats, foxes, and skunks while decreases were reported among cattle, cats, and skunks. Increases in numbers of rabid raccoons during 2007 were reported by 11 of the 20 eastern states where raccoon rabies was enzootic, and reported cases increased by 1.7% overall, compared with 2006. On a national level, the number of rabies cases in skunks during 2007 decreased by 1.1% from the number reported in 2006. Texas reported the greatest number (n = 362) of rabid skunks and the greatest overall state total of animal rabies cases (969). No cases of rabies associated with the dog/coyote rabies virus variant were reported. The United States remains free of dog-to-dog transmission of canine rabies virus variants. The total number of cases of rabies reported nationally in foxes increased 14.5%, compared with 2006. 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 1,973 cases of rabies reported in bats represented a 16.6% increase over numbers reported in 2006. Cases of rabies in dogs and in sheep and goats increased 17.7% and 18.2%, respectively, whereas cases reported in cattle, cats, and horses and mules decreased 30.5%, 13.8%, and 20.8%, respectively. In Puerto Rico, reported cases of rabies

First Report on the Efficiency of Oral Vaccination of Foxes against Rabies in Serbia.

PubMed

Lupulovic, D; Maksimovic Zoric, J; Vaskovic, N; Bugarski, D; Plavsic, B; Ivanovic, N; Petrovic, T; Pusic, I; Marcic, D; Grgic, Z; Lazic, S

2015-12-01

Rabies is one of the oldest known zoonotic diseases that has significant impact on public health, but still remains neglected in Serbia. Rabies virus can infect humans and other mammals and causes inflammation of the brain associated with encephalomyelitis and neurological symptoms. In 2010, Veterinary Directorate (national Competent Authority for animal health in Serbia) has started multi-annual project of oral rabies vaccination of foxes and other wild carnivores (e.g. jackals), as support of long-term programme of eradication of rabies in Serbia, co-funded by EU (financed by Instrument for Pre-Accession Assistance). Monitoring of the effectiveness of oral vaccination campaigns has been carried out in continuation from 2011 and was based on: (i) post-mortem laboratory examination of brain tissue of target animals (foxes, jackals and other carnivores) by fluorescent antibody test (FAT), (ii) detection of antibodies against rabies virus in serum samples by ELISA and (iii) detection of tetracycline biomarker in the mandibles for the evaluation of vaccine bait uptake. From September 2011 to May 2014, the total number of 4943 brain tissue samples, 4241 sera and 4971 mandibles were analysed. Confirmed rabies-positive brains decreased from 10 in 2011/2012 to 6 in 2012/2013 and eventually to 1 positive case in 2013/2014. The seroconversion rate increased from 10.48% (133/1269) in 2011/2012 to 20.11% (362/1800) in 2012/2013 and 42.23% (495/1172) in 2013/2014. Along with the seroconversion, the number of detected tetracycline-positive mandibles demonstrated an increasing tendency in the same period, being 49.67% (682/1373) in 2011/2012, 62.60% (1294/2067) in 2012/2013 and 90.33% (1383/1531) in the monitoring programme carried out in 2013/2014. Presented results confirmed that ORV of foxes and other wildlife in Serbia against rabies was successful and characterized by steady increase of vaccine baits uptake and immunization of animals. © 2015 Blackwell Verlag GmbH.

Rabies

MedlinePlus

... transdermal bites or scratches, licks on broken skin; contamination of mucous membrane with saliva from licks, contacts ... vaccines and rabies immunoglobulin, to understand the global manufacturing capacity and to explore bulk purchasing options for ...

Rabies surveillance in the United States during 2006.

PubMed

Blanton, Jesse D; Hanlon, Cathleen A; Rupprecht, Charles E

2007-08-15

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

9 CFR 113.312 - Rabies Vaccine, Live Virus.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing... administration. (iii) Observe all animals for signs of rabies until scheduled time to sacrifice. If animals show...

Molecular epidemiology of rabies virus in Poland.

PubMed

Orłowska, Anna; Żmudziński, Jan Franciszek

2014-08-01

The paper describes a phylogenetic study of 58 Polish isolates of rabies virus collected between 1992 and 2010. Sequences of the nucleoprotein (N) and glycoprotein (G) genes approximately 600 bp long were compared with reference sequences (GenBank) of European rabies viruses from neighbouring countries. The study confirmed a very high level of homology (94.4-100 %) of the Polish rabies virus strains irrespective of the date of isolation. Two variants of rabies virus: NEE (Northeastern Europe variant) and CE (Central Europe variant), depending on the geographical place of isolation, were circulating in Poland from 1992 to 2010. The Polish rabies virus isolates showed high similarity to European RABV strains, especially those collected in Ukraine and Romania. They were clearly different from vaccine strains SAD B19 and SAD Bern, which have been used for oral vaccination of foxes against rabies in Poland since 1993.

[Hematophagous bats as reservoirs of rabies].

PubMed

Scheffer, Karin Corrêa; Iamamoto, Keila; Asano, Karen Miyuki; Mori, Enio; Estevez Garcia, Andrea Isabel; Achkar, Samira M; Fahl, Williande Oliveira

2014-04-01

Rabies continues to be a challenge for public health authorities and a constraint to the livestock industry in Latin America. Wild and domestic canines and vampire bats are the main transmitter species and reservoirs of the disease. Currently, variations observed in the epidemiological profile of rabies, where the species of hematophagous bat Desmodus rotundus constitutes the main transmitting species. Over the years, knowledge has accumulated about the ecology, biology and behavior of this species and the natural history of rabies, which should lead to continuous development of methods of population control of d. Rotundus as well as prevention and diagnostic tools for rabies. Ecological relationships of this species with other hematophagous and non-hematophagous bats is unknown, and there is much room for improvement in reporting systems and surveillance, as well as creating greater awareness among the farming community. Understanding the impact of human-induced environmental changes on the rabies virus in bats should be cause for further investigation. This will require a combination of field studies with mathematical models and new diagnostic tools. This review aims to present the most relevant issues on the role of hematophagous bats as reservoirs and transmitters of the rabies virus.

Physicochemical, functional and angiotensin converting enzyme inhibitory properties of amaranth (Amaranthus hypochondriacus) 7S globulin.

PubMed

Quiroga, Alejandra V; Aphalo, Paula; Ventureira, Jorge L; Martínez, E Nora; Añón, María C

2012-01-30

Amaranth 7S globulin is a minor globulin component and its impact on the properties of an amaranth protein ingredient depends on its proportion in the variety of amaranth being considered. Some physicochemical, functional and angiotesin I-converting enzyme (ACE) inhibitory properties of amaranth vicilin were studied in this work and compared with the 11S globulin. Fluorescence spectroscopy results indicated that 7S globulin tryptophans were more exposed to the solvent and, by calorimetry, the 7S globulin denaturation temperature (T(d) ) was found lower than the 11S globulin T(d) , suggesting a more flexible structure. The 7S globulin surface hydrophobicity was higher than that of the 11S globulin, which is in agreement with the better emulsifying properties of the 7S globulin. The solubility in neutral buffer of the 7S globulin (851 ± 25 g kg(-1) ) was also higher than that of the 11S globulin (195 ± 6 g kg(-1) ). Bioinformatic analyses showed the presence of ACE inhibitory peptides encrypted in 7S tryptic sequences and peptides released after in vitro gastrointestinal digestion showed a high ACE-inhibitory capacity (IC(50) = 0.17 g L(-1) ), similar to that of 11S globulin peptides. Compared with the 11S globulin, the 7S globulin presents similar ACE inhibitory activity and some functional advantages, better solubility and emulsifying activity, which suits some food requirements. The functional behavior has been related with the structural properties. Copyright © 2011 Society of Chemical Industry.

Rabies: Rare Human Infection - Common Questions.

PubMed

Willoughby, Rodney E

2015-12-01

Rabies is an acute, rapidly progressive encephalitis that is almost always fatal. Prophylaxis is highly effective but economics limits disease control. The mechanism of death from rabies is unclear. It is poorly cytopathic and poorly inflammatory. Rabies behaves like an acquired metabolic disorder. There may be a continuum of disease severity. History of animal bite is rare. The diagnosis is often missed. Intermittent encephalopathy, dysphagia, hydrophobia and aerophobia, and focal paresthesias or myoclonic jerks suggest rabies. Laboratory diagnosis is cumbersome but sensitive. Treatment is controversial but survivors are increasingly reported, with good outcomes in 4 of 8 survivors. Copyright © 2015 Elsevier Inc. All rights reserved.

Rabies Situation in Cambodia

PubMed Central

Ly, Sowath; Buchy, Philippe; Heng, Nay Yim; Ong, Sivuth; Chhor, Nareth; Bourhy, Hervé; Vong, Sirenda

2009-01-01

Background Rabies, a fatal but preventable zoonosis, is a major public health problem in developing countries. In Cambodia the disease burden is largely underestimated because patients with encephalitis following dog bites are rarely hospitalized and die at home. Since 1998 Institut Pasteur in Cambodia (IPC), Phnom Penh has been the only source of free post-exposure prophylaxis (PEP) and post-mortem diagnosis. Methods The 1998–2007 data compiled by IPC was analyzed to describe all treated patients for PEP, results of human testing and confirmed rabies cases, and results of animal testing. From dog bites' characteristics, we defined a suspected rabid dog bite injury (SRDBI) in humans as a bite that was unprovoked, from a dog that died spontaneously, or from a dog that was reported sick. We applied a deterministic probability model to estimate 2007 rabies human mortality nationwide from the estimated incidence of rabid dog bites, the body distribution of bite wounds, and the probability of PEP access. Results During 1998–2007, 124,749 patients received PEP at IPC (average 12,470; range 8,907–14,475), and 63 fatal human cases presenting with encephalitis following a dog bite were reported, in which 73% were confirmed positive for rabies by direct immunofluorescence assay or by reverse-transcriptase polymerase chain reaction. During 1998–2007, IPC tested 1,255 animal brain samples; 1,214 (97%) were from dogs including 610 (49%) positive samples. In 2007, 14,475 patients received PEP (100 PEP/100,000 people in Cambodia) including 95% who resided in Phnom Penh (615 PEP/100,000) or five neighboring provinces. The predictive model estimated 810 human rabies deaths would occur in 2007 (95%confidence interval [CI] 394–1,607), an incidence of 5.8/100,000 (95% CI 2.8–11.5). Conclusions Access to PEP is only sufficient for Phnom Penh residents. In 2007, the estimated rabies related mortality exceeded that of malaria and that of dengue. A national rabies control

Molecular epidemiology of human rabies viruses in Sri Lanka.

PubMed

Matsumoto, Takashi; Ahmed, Kamruddin; Karunanayake, Dushantha; Wimalaratne, Omala; Nanayakkara, Susilakanthi; Perera, Devika; Kobayashi, Yuji; Nishizono, Akira

2013-08-01

Rabies is a lethal zoonotic disease caused by the rabies virus, which is transmitted by rabid animals to humans. Rabies is prevalent in all continents, with over 60% of human deaths occurring in Asia. Sri Lanka is a rabies-endemic country. This study shows that rabies afflicted more older individuals than children in Sri Lanka between 2008 and 2010. This novel finding indicates that older people in Sri Lanka should be more aware of the risk of rabies. Phylogenetic analyses of the rabies N and G genes showed that the Sri Lankan rabies viruses are distinct and probably originated from a single clone. The G-L noncoding region is highly diverse, and is suitable for the analysis of virus evolution within a country. A phylogenetic analysis of this region showed high diversity in the currently circulating Sri Lankan rabies viruses, which can be divided into seven clades. Some clades are unique to a specific geographic region, whereas others occur at multiple locations. This indicates that the movement of dogs, the main rabies-transmitting animal in Sri Lanka, is restricted in some areas but less limited in others. These data may help to formulate a more efficient rabies control program in Sri Lanka. Copyright © 2013 Elsevier B.V. All rights reserved.

Population Dynamics of Owned, Free-Roaming Dogs: Implications for Rabies Control

PubMed Central

Conan, Anne; Akerele, Oluyemisi; Simpson, Greg; Reininghaus, Bjorn; van Rooyen, Jacques; Knobel, Darryn

2015-01-01

Background Rabies is a serious yet neglected public health threat in resource-limited communities in Africa, where the virus is maintained in populations of owned, free-roaming domestic dogs. Rabies elimination can be achieved through the mass vaccination of dogs, but maintaining the critical threshold of vaccination coverage for herd immunity in these populations is hampered by their rapid turnover. Knowledge of the population dynamics of free-roaming dog populations can inform effective planning and implementation of mass dog vaccination campaigns to control rabies. Methodology/Principal Findings We implemented a health and demographic surveillance system in dogs that monitored the entire owned dog population within a defined geographic area in a community in Mpumalanga Province, South Africa. We quantified demographic rates over a 24-month period, from 1st January 2012 through 1st January 2014, and assessed their implications for rabies control by simulating the decline in vaccination coverage over time. During this period, the population declined by 10%. Annual population growth rates were +18.6% in 2012 and -24.5% in 2013. Crude annual birth rates (per 1,000 dog-years of observation) were 451 in 2012 and 313 in 2013. Crude annual death rates were 406 in 2012 and 568 in 2013. Females suffered a significantly higher mortality rate in 2013 than males (mortality rate ratio [MRR] = 1.54, 95% CI = 1.28–1.85). In the age class 0–3 months, the mortality rate of dogs vaccinated against rabies was significantly lower than that of unvaccinated dogs (2012: MRR = 0.11, 95% CI = 0.05–0.21; 2013: MRR = 0.31, 95% CI = 0.11–0.69). The results of the simulation showed that achieving a 70% vaccination coverage during annual campaigns would maintain coverage above the critical threshold for at least 12 months. Conclusions and Significance Our findings provide an evidence base for the World Health Organization’s empirically-derived target of 70% vaccination coverage

Rabies in the Americas: 1998-2014

PubMed Central

Vigilato, Marco A. N.; Pompei, Julio A.; Rocha, Felipe; Vokaty, Alexandra; Molina-Flores, Baldomero; Cosivi, Ottorino; Del Rio Vilas, Victor J.

2018-01-01

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998–2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence. PMID:29558465

Rabies in the Americas: 1998-2014.

PubMed

Freire de Carvalho, Mary; Vigilato, Marco A N; Pompei, Julio A; Rocha, Felipe; Vokaty, Alexandra; Molina-Flores, Baldomero; Cosivi, Ottorino; Del Rio Vilas, Victor J

2018-03-01

Through national efforts and regional cooperation under the umbrella of the Regional Program for the Elimination of Rabies, dog and human rabies have decreased significantly in Latin America and Caribbean (LAC) countries over the last three decades. To achieve this decline, LAC countries had to develop national plans, and consolidate capabilities such as regular mass dog vaccination, opportune post-exposure prophylaxis and sensitive surveillance. This paper presents longitudinal data for 21 LAC countries on dog vaccination, PEP and rabies surveillance collected from the biannual regional meeting for rabies directors from 1998-2014 and from the Regional Epidemiologic Surveillance System for Rabies (SIRVERA). Differences in human and dog rabies incidence rates and dog vaccination rates were shown between low, middle and high-income countries. At the peak, over 50 million dogs were vaccinated annually in national campaigns in the countries represented. The reported number of animal exposures remained fairly stable during the study period with an incidence rate ranging from 123 to 191 reported exposures per 100,000 people. On average, over 2 million doses of human vaccine were applied annually. In the most recent survey, only 37% of countries reported that they had sufficient financial resources to meet the program objectives. The data show a sufficient and sustained effort of the LAC countries in the area of dog vaccination and provide understanding of the baseline effort required to reduce dog-mediated rabies incidence.

The history of rabies in the Western Hemisphere

PubMed Central

Velasco-Villa, Andres; Mauldin, Matthew R.; Shi, Mang; Escobar, Luis E.; Gallardo-Romero, Nadia F.; Damon, Inger; Olson, Victoria A.; Streicker, Daniel G.; Emerson, Ginny

2017-01-01

Before the introduction of control programs in the 20th century, rabies in domestic dogs occurred throughout the Western Hemisphere. However, historical records and phylogenetic analysis of multiple virus isolates indicate that, before the arrival of the first European colonizers, rabies virus was likely present only in bats and skunks. Canine rabies was either rare or absent among domestic dogs of Native Americans, and first arrived when many new dog breeds were imported during the period of European colonization. The introduction of the cosmopolitan dog rabies lyssavirus variant and the marked expansion of the dog population provided ideal conditions for the flourishing of enzootic canine rabies. The shift of dog-maintained viruses into gray foxes, coyotes, skunks and other wild mesocarnivores throughout the Americas and to mongooses in the Caribbean has augmented the risk of human rabies exposures and has complicated control efforts. At the same time, the continued presence of bat rabies poses novel challenges in the absolute elimination of canine and human rabies. This article compiles existing historical and phylogenetic evidence of the origins and subsequent dynamics of rabies in the Western Hemisphere, from the era preceding the arrival of the first European colonizers through the present day. A companion article reviews the current status of canine rabies control throughout the Western Hemisphere and steps that will be required to achieve and maintain its complete elimination (Velasco-Villa et al., in press). PMID:28365457

The history of rabies in the Western Hemisphere.

PubMed

Velasco-Villa, Andres; Mauldin, Matthew R; Shi, Mang; Escobar, Luis E; Gallardo-Romero, Nadia F; Damon, Inger; Olson, Victoria A; Streicker, Daniel G; Emerson, Ginny

2017-10-01

Before the introduction of control programs in the 20th century, rabies in domestic dogs occurred throughout the Western Hemisphere. However, historical records and phylogenetic analysis of multiple virus isolates indicate that, before the arrival of the first European colonizers, rabies virus was likely present only in bats and skunks. Canine rabies was either rare or absent among domestic dogs of Native Americans, and first arrived when many new dog breeds were imported during the period of European colonization. The introduction of the cosmopolitan dog rabies lyssavirus variant and the marked expansion of the dog population provided ideal conditions for the flourishing of enzootic canine rabies. The shift of dog-maintained viruses into gray foxes, coyotes, skunks and other wild mesocarnivores throughout the Americas and to mongooses in the Caribbean has augmented the risk of human rabies exposures and has complicated control efforts. At the same time, the continued presence of bat rabies poses novel challenges in the absolute elimination of canine and human rabies. This article compiles existing historical and phylogenetic evidence of the origins and subsequent dynamics of rabies in the Western Hemisphere, from the era preceding the arrival of the first European colonizers through the present day. A companion article reviews the current status of canine rabies control throughout the Western Hemisphere and steps that will be required to achieve and maintain its complete elimination (Velasco-Villa et al., 2017). Published by Elsevier B.V.

Molecular Epidemiology of Rabies Viruses Circulating in Two Rabies Endemic Provinces of Laos, 2011–2012: Regional Diversity in Southeast Asia

PubMed Central

Ahmed, Kamruddin; Phommachanh, Phouvong; Vorachith, Phengphet; Matsumoto, Takashi; Lamaningao, Pheophet; Mori, Daisuke; Takaki, Minako; Douangngeun, Bounlom; Khambounheuang, Bounkhouang; Nishizono, Akira

2015-01-01

Background Although rabies is endemic in Laos, genetic characterization of the viruses in this country is limited. There are growing concerns that development in the region may have increased transport of dog through Laos for regional dog meat consumption, and that this may cause spillover of the viruses from dogs brought here from other countries. This study was therefore undertaken to evaluate the current rabies situation and the genetic characteristics of rabies viruses currently circulating in Laos. Methods We determined the rate of rabies-positive samples by analyzing data from animal samples submitted to the Lao Ministry of Agriculture and Forestry’s National Animal Health Centre rabies laboratory from 2004 through 2011. Twenty-three rabies-positive samples were used for viral genetic characterization. Full genome sequencing was performed on two rabies viruses. Results Rabies-positive samples increased substantially from 40.5% in 2004 to 60.2% in 2009 and continued at this level during the study period. More than 99% of the samples were from dogs, followed by cats and monkeys. Phylogenetic analyses showed that three rabies virus lineages belonging to the Southeast Asian cluster are currently circulating in Laos; these are closely related to viruses from Thailand, Cambodia and Vietnam. Lineages of the circulating Laos rabies viruses diverged from common ancestors as recently as 44.2 years and as much as 55.3 years ago, indicating periodic virus invasions. Conclusion There is an increasing trend of rabies in Laotian animals. Similar to other rabies-endemic countries, dogs are the main viral reservoir. Three viral lineages closely related to viruses from neighboring countries are currently circulating in Laos. Data provide evidence of periodic historic exchanges of the viruses with neighboring countries, but no recent invasion. PMID:25825907

Poxvirus-vectored vaccines for rabies--a review.

PubMed

Weyer, Jacqueline; Rupprecht, Charles E; Nel, Louis H

2009-11-27

Oral rabies vaccination of target reservoir species has proved to be one of the pillars of successful rabies elimination programs. The use of live attenuated rabies virus vaccines has been extensive but several limitations hamper its future use. A recombinant vaccinia-rabies vaccine has also been successfully used for the oral vaccination of several species. Nevertheless, its lack of efficacy in certain important rabies reservoirs and concerns on the use of this potent live virus as vaccine carrier (vector) impair the expansion of its use for new target species and new areas. Several attenuated and host-restricted poxvirus alternatives, which supposedly offer enhanced safety, have been investigated. Once again, efficacy in certain target species and innocuity through the oral route remain major limitations of these vaccines. Alternative recombinant vaccines using adenovirus as an antigen delivery vector have been extensively investigated and may provide an important addition to the currently available oral rabies vaccine repertoire, but are not the primary subject of this review.

Natural exposure of bats in Grenada to rabies virus

PubMed Central

Zieger, Ulrike; Cheetham, Sonia; Santana, Sharlene E.; Leiser-Miller, Leith; Matthew-Belmar, Vanessa; Goharriz, Hooman; Fooks, Anthony R.

2017-01-01

ABSTRACT Introduction: Grenada is a rabies endemic country, where terrestrial rabies is maintained in the small Indian mongoose (Herpestes auropunctatus). The role of bats in the epidemiology of rabies in Grenada is unknown. A 1974 report described one rabies virus positive Jamaican fruit bat (Artibeus jamaicensis), and a high seroprevalence in this species. In the current study, the natural exposure to rabies virus in Grenadian bats was re-evaluated. It is postulated that bats serve as a natural rabies reservoir, probably circulating a bat-specific rabies virus variant. Material and methods: Bats were trapped in 2015 in all six parishes of Grenada using mist- and hand nets. For the detection of rabies virus in brain tissue, the direct fluorescent antibody test (dFAT) and the reverse transcription polymerase chain reaction (RT-PCR) were used. Serum neutralizing antibodies were determined using the fluorescent antibody virus neutralization test (FAVN). Results and discussion: Brain tissue and sera from 111 insectivorous and frugivorous bats belonging to four species were tested (52 Artibeus jamaicensis, two Artibeus lituratus, 33 Glossophaga longirostris, 24 Molossus molossus). Rabies virus antigen and genomic RNA were not detected in brain tissues. Rabies virus neutralizing antibodies were detected in the sera of eight A. jamaicensis in four of the six parishes. Bats in Grenada continue to show natural exposure to rabies virus. As rabies virus was not isolated in this study, serology alone is not sufficient to determine the strain of rabies virus circulating in A. jamaicensis bats in Grenada. Conclusion: Artibeus jamaicensis appears to play a role as a reservoir bat species, which is of public health concern in Grenada. Dispersion of bats to neighboring islands is possible and serological bat surveys should be initiated in these neighboring states, especially in those areas that are free of rabies in terrestrial mammals. PMID:28804595

Bat Rabies and Other Lyssavirus Infections

USGS Publications Warehouse

Constantine, Denny G.; Blehert, David S.

2009-01-01

Bat Rabies and Other Lyssavirus Infections offers readers an overview of the virus variants that cause bat rabies, and geographical patterns in occurrence of this disease. The section Species Susceptibility describes infection rates and trends among bats, humans, and other animals. Disease Ecology considers the biological and environmental dynamics of the disease in various species of bats. Points to Ponder: Interspecies Interactions in Potential Bat Rabies Transmission Settings discusses the narrowing interface of bat colonies and human society and how humans and domestic animals play a role in transmission of bat rabies. Disease Prevention and Control outlines how to limit exposure to rabid bats and other animals. Appendixes include extensive tables of reported infections in bat species and in humans, and a glossary of technical terms is included. The author, Denny G. Constantine, helped define rabies infection in insect-eating bats and has investigated bat rabies ecology for more than half a century. He has authored more than 90 papers during the course of his career and is widely considered to be the world's foremost authority on the disease. Currently, Dr. Constantine is a public health officer emeritus and veterinary epidemiologist for the California Department of Health Services Viral and Rickettsial Disease Laboratory. Milt Friend, first director of the USGS National Wildlife Health Center, wrote the foreword. David Blehert, a USGS microbiologist who is investigating the emergence and causes of bat white-nose syndrome, edited the volume. Bat Rabies is intended for scholars and the general public. Dr. Constantine presents the material in a simple, straightforward manner that serves both audiences. The goal of the author is to increase people's understanding of both bat and disease ecology and also provide a balanced perspective on human risks pertaining to bat rabies.

Dog-Mediated Human Rabies Death, Haiti, 2016.

PubMed

Wallace, Ryan M; Etheart, Melissa D; Doty, Jeff; Monroe, Ben; Crowdis, Kelly; Augustin, Pierre Dilius; Blanton, Jesse; Fenelon, Natael

2016-11-01

Haiti has experienced numerous barriers to rabies control over the past decades and is one of the remaining Western Hemisphere countries to report dog-mediated human rabies deaths. We describe the circumstances surrounding a reported human rabies death in 2016 as well as barriers to treatment and surveillance reporting.

Arctic Rabies – A Review

PubMed Central

Mørk, Torill; Prestrud, Pål

2004-01-01

Rabies seems to persist throughout most arctic regions, and the northern parts of Norway, Sweden and Finland, is the only part of the Arctic where rabies has not been diagnosed in recent time. The arctic fox is the main host, and the same arctic virus variant seems to infect the arctic fox throughout the range of this species. The epidemiology of rabies seems to have certain common characteristics in arctic regions, but main questions such as the maintenance and spread of the disease remains largely unknown. The virus has spread and initiated new epidemics also in other species such as the red fox and the racoon dog. Large land areas and cold climate complicate the control of the disease, but experimental oral vaccination of arctic foxes has been successful. This article summarises the current knowledge and the typical characteristics of arctic rabies including its distribution and epidemiology. PMID:15535081

A thermostable messenger RNA based vaccine against rabies.

PubMed

Stitz, Lothar; Vogel, Annette; Schnee, Margit; Voss, Daniel; Rauch, Susanne; Mutzke, Thorsten; Ketterer, Thomas; Kramps, Thomas; Petsch, Benjamin

2017-12-01

Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G). Prolonged storage of the vaccine from -80°C to up to +70°C for several months did not impact the protective capacity of the mRNA vaccine. Efficacy after storage was demonstrated by the induction of rabies specific virus neutralizing antibodies and protection in mice against lethal rabies infection. Moreover, storing the vaccine at oscillating temperatures between +4° and +56°C for 20 cycles in order to simulate interruptions of the cold chain during vaccine transport, did not affect the vaccine's immunogenicity and protective characteristics, indicating that maintenance of a cold chain is not essential for this vaccine.

Dog-Mediated Human Rabies Death, Haiti, 2016

PubMed Central

Etheart, Melissa D.; Doty, Jeff; Monroe, Ben; Crowdis, Kelly; Augustin, Pierre Dilius; Blanton, Jesse; Fenelon, Natael

2016-01-01

Haiti has experienced numerous barriers to rabies control over the past decades and is one of the remaining Western Hemisphere countries to report dog-mediated human rabies deaths. We describe the circumstances surrounding a reported human rabies death in 2016 as well as barriers to treatment and surveillance reporting. PMID:27767911

Rabies

MedlinePlus

... and remove any foreign objects. Most of the time, stitches should not be used for animal bite wounds. If there is any risk of rabies, you will be given a series of a preventive vaccine . The vaccine is generally ...

Canine Rabies: A Looming Threat to Public Health

PubMed Central

Burgos-Cáceres, Sigfrido

2011-01-01

Simple Summary This review is guided by three questions: What is canine rabies? Why is it a looming threat to public health? Why should we care about canine rabies being a public health threat? It seeks to answer these questions and notes that canine rabies is viral zoonosis with dogs being the major vectors. The disease is a looming threat to public health because rabid dogs bite humans, resulting in thousands of deaths every year. We should care about this evolving situation because, in general, rabies is a neglected disease for which there are vaccines, preventive measures, post-exposure prophylaxis, and control protocols. Abstract Rabies is an acute, fatal viral disease that infects domestic and wild animals and is transmissible to humans. Worldwide, rabies kills over 55,000 people every year. The domestic dog plays a pivotal role in rabies transmission. Domestic dogs are not only part of our daily lives but also of our immediate surroundings, and this is reflected in the rise in pet dog ownership in developed and developing countries. This is important given that more frequent exposures and interactions at the animal-human interface increases the likelihood of contracting zoonotic diseases of companion animals. Despite existing vaccines and post-exposure prophylactic treatment, rabies remains a neglected disease that is poorly controlled throughout much of the developing world, particularly Africa and Asia, where most human rabies deaths occur. It is believed that with sustained international commitments, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal. PMID:26486619

Phylogeographic analysis of rabies viruses in the Philippines.

PubMed

Tohma, Kentaro; Saito, Mariko; Kamigaki, Taro; Tuason, Laarni T; Demetria, Catalino S; Orbina, Jun Ryan C; Manalo, Daria L; Miranda, Mary E; Noguchi, Akira; Inoue, Satoshi; Suzuki, Akira; Quiambao, Beatriz P; Oshitani, Hitoshi

2014-04-01

Rabies still remains a public health threat in the Philippines. A significant number of human rabies cases, about 200-300 cases annually, have been reported, and the country needs an effective strategy for rabies control. To develop an effective control strategy, it is important to understand the transmission patterns of the rabies viruses. We conducted phylogenetic analyses by considering the temporal and spatial evolution of rabies viruses to reveal the transmission dynamics in the Philippines. After evaluating the molecular clock and phylogeographic analysis, we estimated that the Philippine strains were introduced from China around the beginning of 20th century. Upon this introduction, the rabies viruses evolved within the Philippines to form three major clades, and there was no indication of introduction of other rabies viruses from any other country. However, within the Philippines, island-to-island migrations were observed. Since then, the rabies viruses have diffused and only evolved within each island group. The evolutionary pattern of these viruses was strongly shaped by geographical boundaries. The association index statistics demonstrated a strong spatial structure within the island group, indicating that the seas were a significant geographical barrier for viral dispersal. Strong spatial structure was also observed even at a regional level, and most of the viral migrations (79.7% of the total median number) in Luzon were observed between neighboring regions. Rabies viruses were genetically clustered at a regional level, and this strong spatial structure suggests a geographical clustering of transmission chains and the potential effectiveness of rabies control that targets geographical clustering. Dog vaccination campaigns have been conducted independently by local governments in the Philippines, but it could be more effective to implement a coordinated vaccination campaign among neighboring areas to eliminate geographically-clustered rabies

Rabies Control: Could Innovative Financing Break the Deadlock?

PubMed

Welburn, Susan C; Coleman, Paul G; Zinsstag, Jakob

2017-01-01

The neglected zoonotic diseases (NZDs) have been all but eradicated in wealthier countries but remain major causes of ill-health and mortality in over 80 countries across Africa, Asia, and Latin America. The nature of neglect for the NZDs has been ascribed, in part, to underreporting resulting in an underestimation of their global burden that, together with a lack of advocacy, downgrades their relevance to policy-makers and funding agencies. While this may be the case for many NZDs, for rabies this is not the case. The global burden estimates for rabies (931,600 DALYs) more than justify prioritizing rabies control building on the strong advocacy platforms, functioning at local, regional, and global levels (including the Global Alliance for Rabies Control), and commitments from WHO, OIE, and FAO. Simple effective tools for rabies control exist together with blueprints for operationalizing control, yet, despite elimination targets being set, no global affirmative action has been taken. Rabies control demands activities both in the short term and over a long period of time to achieve the desired cumulative gains. Despite the availability of effective vaccines and messaging tools, rabies will not be sustainably controlled in the near future without long-term financial commitment, particularly as disease incidence decreases and other health priorities take hold. While rabies control is usually perceived as a public good, public private partnerships could prove equally effective in addressing endemic rabies through harnessing social investment and demonstrating the cost-effectiveness of control. It is acknowledged that greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably. In the shadows of resource and institutional limitations in the veterinary sector in low- and middle-income countries, sufficient funding is required so that top-down interventions

Rabies Control: Could Innovative Financing Break the Deadlock?

PubMed Central

Welburn, Susan C.; Coleman, Paul G.; Zinsstag, Jakob

2017-01-01

The neglected zoonotic diseases (NZDs) have been all but eradicated in wealthier countries but remain major causes of ill-health and mortality in over 80 countries across Africa, Asia, and Latin America. The nature of neglect for the NZDs has been ascribed, in part, to underreporting resulting in an underestimation of their global burden that, together with a lack of advocacy, downgrades their relevance to policy-makers and funding agencies. While this may be the case for many NZDs, for rabies this is not the case. The global burden estimates for rabies (931,600 DALYs) more than justify prioritizing rabies control building on the strong advocacy platforms, functioning at local, regional, and global levels (including the Global Alliance for Rabies Control), and commitments from WHO, OIE, and FAO. Simple effective tools for rabies control exist together with blueprints for operationalizing control, yet, despite elimination targets being set, no global affirmative action has been taken. Rabies control demands activities both in the short term and over a long period of time to achieve the desired cumulative gains. Despite the availability of effective vaccines and messaging tools, rabies will not be sustainably controlled in the near future without long-term financial commitment, particularly as disease incidence decreases and other health priorities take hold. While rabies control is usually perceived as a public good, public private partnerships could prove equally effective in addressing endemic rabies through harnessing social investment and demonstrating the cost-effectiveness of control. It is acknowledged that greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably. In the shadows of resource and institutional limitations in the veterinary sector in low- and middle-income countries, sufficient funding is required so that top-down interventions

Rabies in the Baltic States: Decoding a Process of Control and Elimination

PubMed Central

Robardet, Emmanuelle; Picard-Meyer, Evelyne; Dobroštana, Marianna; Jaceviciene, Ingrida; Mähar, Katrin; Muižniece, Zita; Pridotkas, Gediminas; Masiulis, Marius; Niin, Enel; Olševskis, Edvīns; Cliquet, Florence

2016-01-01

Rabies is a fatal zoonosis that still causes nearly 70, 000 human deaths every year. In Europe, the oral rabies vaccination (ORV) of red foxes (Vulpes vulpes) was developed in the late 1970s and has demonstrated its effectiveness in the eradication of the disease in Western and some Central European countries. Following the accession of the three Baltic countries—Estonia, Latvia and Lithuania—to the European Union in 2004, subsequent financial support has allowed the implementation of regular ORV campaigns since 2005–2006. This paper reviews ten years of surveillance efforts and ORV campaigns in these countries resulting in the near eradication of the disease. The various factors that may have influenced the results of vaccination monitoring were assessed using generalized linear models (GLMs) on bait uptake and on herd immunity. As shown in previous studies, juveniles had lower bait uptake level than adults. For the first time, raccoon dogs (Nyctereutes procyonoides) were shown to have significantly lower bait uptake proportion compared with red foxes. This result suggests potentially altered ORV effectiveness in this invasive species compared to the red foxes. An extensive phylogenetic analysis demonstrated that the North-East European (NEE) rabies phylogroup is endemic in all three Baltic countries. Although successive oral vaccination campaigns have substantially reduced the number of detected rabies cases, sporadic detection of the C lineage (European part of Russian phylogroup) underlines the risk of reintroduction via westward spread from bordering countries. Vaccine induced cases were also reported for the first time in non-target species (Martes martes and Meles meles). PMID:26849358

Immunizations, neonatal hyperbilirubinemia and animal-induced injuries.

PubMed

Bennett, Sean R; Brennan, Beth; Bernstein, Henry H

2007-08-01

To report recent research findings and new recommendations on immunizations, neonatal hyperbilirubinemia, and animal-induced injuries. Vaccines against rotavirus and human papilloma virus have entered clinical use. Varicella outbreaks among previously vaccinated children have prompted the recommendation for a two-dose varicella vaccine series. Broader coverage for influenza vaccination is now recommended in the US and Canada. Diagnosis and treatment of neonatal hyperbilirubinemia uses population and hour-based norms for total serum bilirubin and assessment of risk factors. Delayed cord clamping is not apparently a risk factor for jaundice but warrants more study. Universal predischarge screening shows promise but is not yet officially recommended. New treatments for hyperbilirubinemia are being evaluated. Dogs are the chief cause of animal bites in children and the largest reservoir for rabies worldwide. In North America and Europe, cats and wild animals cause most human rabies. Postexposure prophylaxis should follow region-appropriate guidelines. New vaccines are available against rotavirus and human papilloma virus. Changes have been made to official immunization recommendations. Appropriate vaccine use can reduce the pediatric disease burden further. Hyperbilirubinemia is the subject of ongoing study, which may lead to improved diagnosis and treatment protocols and reduce the incidence of acute bilirubin encephalopathy. The best tool for rabies prevention after an animal bite is prompt postexposure prophylaxis.

Role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, A.; Morse, H.C. III; Winkelstein, J.

1978-07-01

The avirulent high egg passage (HEP) strain of rabies virus produces an inapparent infection limited to the central nervous system (CNS) in intracerebrally inoculated adult mice. Heavy chain isotype (anti-..mu.. antiserum) immunosuppression potentiates the infection, with a mortality of about 60% and with elevated virus titers in the brain. Anti-..mu..-treated mice fail to raise antibody responses to rabies virus although their T cell function is normal when measured by the concanavalin A response of splenic lymphocytes. This indicates that the B cell response plays an important role in clearance of rabies virus from the neuroparenchyma. Treatment with cyclophosphamide or bymore » adult thymectomy, x-irradiation, and bone marrow reconstitution potentiates HEP infection to a greater extent than does isotype supression. Since these suppressive techniques impair both T and B lymphocyte responses, the data suggest that cellular immune mechanisms may also contribute to host defenses against this central nervous system (CNS) virus infection.« less

Implementation of an Intersectoral Program to Eliminate Human and Canine Rabies: The Bohol Rabies Prevention and Elimination Project

PubMed Central

Lapiz, Stella Marie D.; Miranda, Mary Elizabeth G.; Garcia, Romulo G.; Daguro, Leonida I.; Paman, Meydalyn D.; Madrinan, Frederick P.; Rances, Polizena A.; Briggs, Deborah J.

2012-01-01

Background The province of Bohol, located in the Visayas islands region in the Philippines has a human population of 1.13 million and was the 4th highest region for human rabies deaths in the country, averaging 10 per year, prior to the initiation of the Bohol Rabies Prevention and Elimination Project (BRPEP). Aims The BRPEP was initiated in 2007 with the goal of building a sustainable program that would prevent human rabies by eliminating rabies at its source, in dogs, by 2010. This goal was in line with the Philippine National Rabies Program whose objective is to eliminate rabies by 2020. Methods The intersectoral BRPEP was launched in 2007 and integrated the expertise and resources from the sectors of agriculture, public health and safety, education, environment, legal affairs, interior and local government. The program included: increasing local community involvement; implementing dog population control; conducting mass dog vaccination; improving dog bite management; instituting veterinary quarantine; and improving diagnostic capability, surveillance and monitoring. Funding was secured from the national government, provincial, municipal and village units, dog owners, NGOs, the regional office of the WHO, the UBS Optimus Foundation, and the Global Alliance for Rabies Control. The BRPEP was managed by the Bohol Rabies Prevention and Eradication Council (BRPEC) under the jurisdiction of the Governor of Bohol. Parallel organizations were created at the municipal level and village level. Community volunteers facilitated the institution of the program. Dog population surveys were conducted to plan for sufficient resources to vaccinate the required 70% of the dogs living in the province. Two island-wide mass vaccination campaigns were conducted followed by “catch up” vaccination campaigns. Registration of dogs was implemented including a small fee that was rolled back into the program to maintain sustainability. Children were educated by introducing rabies

Clinical features of dog- and bat-acquired rabies in humans.

PubMed

Udow, Sean J; Marrie, Ruth Ann; Jackson, Alan C

2013-09-01

Clinical differences in rabies due to canine and bat rabies virus variants have been noted, but no detailed studies have been reported to support these observations. Using the Morbidity and Mortality Weekly Report and PubMed, we identified 142 case reports of rabies from North America, South America, Europe, Africa, and Asia. We systematically abstracted 126 selected data elements and compared clinical features and investigation results in dog- and bat-acquired cases of rabies. Survivors and cases acquired from aerosolized viral exposure or tissue/organ transplant were excluded (n = 20). Of 122 cases, 49 (40.2%) were dog-acquired and 54 (44.3%) were bat-acquired. Bat-acquired cases of rabies were more often misdiagnosed and lacked a bite history. Encephalopathy, hydrophobia, and aerophobia were more common in dog-acquired rabies. Abnormal cranial nerve, motor, and sensory examinations, tremor, myoclonus, local sensory symptoms, symptoms at the exposure site, and local symptoms in the absence of a bite or scratch were more common in patients with bat-acquired rabies, as was increased cerebrospinal fluid protein (P = .031). Patients with paralytic rabies had longer survival times than those with encephalitic rabies, and also had shorter incubation periods if they had received postexposure prophylaxis. Clinical differences in dog- and bat-acquired rabies may reflect differences in the route of viral spread of rabies virus variants in the nervous system, although certain variants could cause more severe dysfunction in neuronal subpopulations. Recognition that bat-acquired rabies may present with different clinical manifestations than dog-acquired rabies may help improve the early diagnosis of rabies.

The effects of ALG on the murine immune response to sheep erythrocytes

PubMed Central

Anderson, Hilary R.; Dresser, D. W.; Iverson, G. M.; Lance, E. M.; Wortis, H. H.; Zebra, J.

1972-01-01

Antilymphocyte globulin (ALG), and to a lesser extent normal rabbit globulin (NRG), when given to mice prior to immunization with sheep-RBC suppress both the γM and γG2a responses. Globulin injected after the antigen suppresses the γG2a response, augments the γG1 response and has little effect on the γM response. These effects are also observed in mice partially paralysed to rabbit γ globulin. In another system—the response to hapten—protein conjugates precursors of antibody producing cells were found to be more resistant to ALS treatment in vivo than were helper cells. It is concluded that the suppressive effects of ALG treatment are largely due to the direct action of ALG on helper cells (T-cells). The mechanism of the adjuvant-like effect is unclear. PMID:4550853

Challenges and needs for China to eliminate rabies.

PubMed

Yin, Wenwu; Dong, Jie; Tu, Changchun; Edwards, John; Guo, Fusheng; Zhou, Hang; Yu, Hongjie; Vong, Sirenda

2013-10-02

In China, rabies is a significant public health concern where dogs remain the main reservoir of disease transmission to humans; rabies-related mortality ranks second in the world.We compiled all published articles and official documents on rabies in mainland China to examine challenges and needs to eliminate rabies in the country. The Chinese authorities have identified rabies as a priority, recognized rabies control in dogs as key to control rabies in humans and required intersectoral collaborations. Efforts have been made to respond effectively to the latest re-emergence of rabies, which peaked in 2007 with >3,300 cases. Despite these outcomes and the increasing volume of publications and regulations in the recent years, our review points to some major information gaps to improve rabies control activities and envisage elimination program. An emphasis on laboratory or pathogen-associated and basic epidemiology research in the literature has contrasted with the absence of information to monitor various systems in humans and animals (e.g. quality of surveillance, response and post-exposure prophylaxis). Information is also lacking to appropriately inform policymakers (e.g. economic disease burden, impact of policies) and assist program managers (e.g. comprehensive and strategic guidance for cost-effective prevention and control activities, public education and dog population management).In conclusion, strategic planning is needed to provide a sense of direction, demonstrate feasibility of elimination in China, and develop a research agenda, addressing country's operational needs and constraints. The planning should be a multisectoral effort.

Design of different strategies of multivalent DNA-based vaccination against rabies and canine distemper in mice and dogs.

PubMed

Touihri, Leila; Ahmed, Sami Belhaj; Chtourou, Yacine; Daoud, Rahma; Bahloul, Chokri

2012-12-27

During the vaccination campaigns, puppies younger than 3 months old are not targeted and remain unvaccinated for at least the first year of their lives. Almost half of the reported rabid dogs are 6 months or younger. Hence, we should recommend the vaccination against rabies of young puppies. Unfortunately, owing to the exposure of puppies to infections with either canine parvovirus (CPV) or distemper virus (CDV) after the intervention of the vaccinators, owners are reluctant to vaccinate puppies against rabies. Therefore, it is necessary to include the CPV and CDV valences in the vaccine against rabies. Multivalent DNA-based vaccination in dogs, including rabies and distemper valences, could help in raising vaccine coverage. We have designed monovalent and multivalent DNA-based vaccine candidates for in vitro and in vivo assays. These plasmids encode to the rabies virus glycoprotein and/or the canine distemper virus hemagglutinin. The first strategy of multivalent DNA-based vaccination is by mixing plasmids encoding to a single antigen each. The second is by simply fusing the genes of the antigens together. The third is by adding the foot and mouth disease virus (FMDV) 2A oligopeptide gene into the antigen genes. The last strategy is by the design and use of a bicistronic plasmid with an "Internal Ribosome Entry Site" (IRES) domain. The monovalent construct against canine distemper was efficiently validated by inducing higher humoral immune responses compared to cell-culture-derived vaccine both in mice and dogs. All multivalent plasmids efficiently expressed both valences after in vitro transfection of BHK-21 cells. In BALB/c mice, the bicistronic IRES-dependant construct was the most efficient inducer of virus-neutralizing antibodies against both valences. It was able to induce better humoral immune responses compared to the administration of either cell-culture-derived vaccines or monovalent plasmids. The FMDV 2A was also efficient in the design of multivalent

Assessment of acquired immune response to Rhipicephalus appendiculatus tick infestation in different goat breeds.

PubMed

Gopalraj, Jeyanthi B P; Clarke, Francoise C; Donkin, Edward F

2013-01-01

Changes in serum gamma globulin levels, numbers of replete female ticks and engorged tick mass were used as parameters to monitor the acquired immune response (antibody mediated immune response) elicited by Rhipicephalus appendiculatus adult tick infestations. Three consecutive Rhipicephalus appendiculatus adult tick infestations were applied to South African Indigenous goats (Nguni), Saanen goats and cross-bred goats (Saanen goats crossed with South African Indigenous goats [Nguni]) under laboratory conditions. During the three consecutive Rhipicephalus appendiculatus adult tick infestations the serum gamma globulin levels increased in all three breeds, whilst the mean replete female tick numbers and engorged tick mass decreased. Even though all three goat breeds exhibited an acquired immune response, the South African Indigenous goats (Nguni) response was significantly higher than that of the Saanen and cross-bred goats. However, the acquired immune response elicited by Saanen goats was significantly lower when compared with cross-bred goats.

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

PubMed

Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

2017-09-01

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

The Mad Fox Disease: Rabies.

ERIC Educational Resources Information Center

Keller, Rosanne

One of a series of instructional materials produced by the Literacy Council of Alaska, this booklet provides information about the control of rabies. Using both simplified sentence structure and vocabulary, it describes how rabies may be spread, its symptoms, its treatment, and ways it can be prevented. (FL)

Structural, Functional and Evolutionary Aspects of Seed Globulins.

PubMed

Kesari, Pooja; Neetu; Sharma, Anchal; Katiki, Madhusudhanarao; Kumar, Pramod; Gurjar, Bhola R; Tomar, Shailly; Sharma, Ashwani K; Kumar, Pravindra

2017-01-01

Globulins are a major class of seed storage proteins which were thought to be enzymatically inactive. These proteins belong to the most ancient cupin superfamily. They can be graded into 11S legumin type and 7S vicilin type based on their sedimentation coefficients. Members from both classes share structural homology are thought to have evolved from either one-domain germin predecessor by duplication or by horizontal gene transfer of two-domain gene from bacteria to eukaryotes. Globulins are known to define the nutritional quality of the seeds, however, they are also involved in sucrose binding, desiccation, defense against microbes, hormone binding and oxidative stress etc. Major drawback with globulins is their tendency to bind to IgE. Studying structural-functional behavior of such protein can help in modifying proteins for enhanced functionality in food processing industries. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Rabies: Diagnosis in Animals and Humans

MedlinePlus

... Dogs Reported in the United States, 2008 Rabid Cattle Reported in the United States, 2008 Terrestrial Rabies ... Texas December 23, 2005: Rabies in a Dairy Cow; Oklahoma November 15, 2004: Clinician Information Line July ...

Rabies: What Care Will I Receive?

MedlinePlus

... Dogs Reported in the United States, 2008 Rabid Cattle Reported in the United States, 2008 Terrestrial Rabies ... Texas December 23, 2005: Rabies in a Dairy Cow; Oklahoma November 15, 2004: Clinician Information Line July ...

Preparation and mass spectrometric study of egg yolk antibody (IgY) against rabies virus.

PubMed

Sun, S; Mo, W; Ji, Y; Liu, S

2001-01-01

Rabies virus was used as the antigen to immunize laying chickens. Anti-rabies virus immunoglobulin Y(IgY) was isolated from yolks of the eggs laid by these chickens using a two-step salt precipitation and one-step gel filtration protocol. The purified IgY was reduced with dithiothreitol, and heavy chains (HC) and light chains (LC) were obtained. In addition, the purified IgY was digested with pepsin and the fragment with specific antigen binding properties (Fab) was produced. Using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOFMS), the average molecular weights of IgY, HC, LC, and Fab were determined as 167 250, 65 105, 18 660, and 45,359 Da, respectively. IgY has two structural differences compared with mammalian IgGs. First, the molecular weight of the heavy chain of IgY is larger than that of its mammalian counterpart, while the molecular weight of the light chain of IgY is smaller. Second, upon pepsin digestion, anti-rabies virus IgY is degraded into Fab, in contrast to mammalian IgG, which has been reported to be degraded into F(ab')(2) under the same conditions. Copyright 2001 John Wiley & Sons, Ltd.

Epidemiological Profile of Wild Rabies in Brazil (2002-2012).

PubMed

Rocha, S M; de Oliveira, S V; Heinemann, M B; Gonçalves, V S P

2017-04-01

Rabies is one of the most important zoonosis in the world with high impact on public health. Studies report the presence of Lyssavirus in reservoirs of the wild cycle, highlighting the role of wild canines, marmosets, and vampire and non-vampire bats as potential vectors of the disease to domestic animals and human beings. Therefore, the reintroduction of rabies in urban environments from reservoirs of the wild cycle is a matter of concern. This study describes the profile of rabies cases documented in Brazil from 2002 to 2012, with emphasis on the wild transmission cycle of the disease. We carried out a descriptive study using records with information on the time of infection, persons with infection and location of confirmed cases of rabies in humans and animals, as well as data on anti-rabies treatments obtained from the Information System of Notifiable Diseases (Sinan) database. Within the study period, 82 cases of rabies transmitted by wild animals to humans were reported, predominantly in rural areas of the northern and north-eastern regions. Of the cases in humans, 72% did not receive post-exposure prophylaxis. Among wild mammals, vampire bats were the most frequent vectors of the disease. In the north-east region, 460 terrestrial wild mammals were reported with confirmed rabies. Over the study period, 1703 bats were reported to carry the rabies virus. In the south-east region, the most frequently reported carriers of the virus were non-vampire bats. The midwest and northern regions presented a lower number of records of rabies cases among terrestrial wild mammals. However, the high number of rabies cases among bovines reflects the role of the vampire bat as a maintainer of the rabies virus in the rural cycle. The present results are key to adjust the planning of rabies control in Brazil to the current epidemiological trends. © 2015 Blackwell Verlag GmbH.

Rabies in the critical care unit: diagnostic and therapeutic approaches.

PubMed

Jackson, Alan C

2011-09-01

Worldwide, human rabies is prevalent where there is endemic dog rabies, but the disease may present unexpectedly in critical care units when suggestive clinical features have passed. In North America transmission from bats is most common and there is often no history of a bat bite or even contact with bats. Laboratory diagnostic evaluation for rabies includes serology plus skin biopsy, cerebrospinal fluid, and saliva specimens for rabies virus antigen and/or RNA detection. Rare patients have survived rabies, and most received rabies vaccine prior to the onset of illness. Therapeutic coma (midazolam and phenobarbital), ketamine, and antiviral therapies (dubbed the "Milwaukee Protocol") were given to a rabies survivor, but this therapy was likely not directly responsible for the favorable outcome. There have been many subsequent failures of similar therapeutic approaches. There is no scientific rationale for the use of therapeutic coma in human rabies. New approaches to treating human rabies need to be developed.

[Epizootic characteristic of rabies today].

PubMed

Makarov, V V; Dzhupina, S I; Vedernikov, V A; Zavodskikh, A V; Afonin, V N

2002-01-01

During the 23 year period rabies was registered in the Moscow region in 163 cases among foxes, 22 cases among racoon-like dogs, 92 cases among dogs, 54 cases among cats. In 1991-2000 ten cases of rabies were registered among other wild animal other than foxes and raccoon-like dogs (hares, hedge-hogs, polecats, badgers, hamsters, martens, rats). Under today conditions the generalized epizootological pattern of rabies is characterized by the vector "natural foci-->anthropurgic foci" with wild and domestic animals playing an alternative role in the epizootic process and the circulation of the infective agent. Wild carnivorous animals maintain natural focal infection in time and space, while all domestic animals are a direct or indirect ecological impasse and took no part in the maintenance of the infection. Foxes are the main source of infection for the animals of the anthropurgic cycle: they play a special role in the development of the epizootic situation in the region as the main reservoir and source of the causative agent of rabies as a natural focal infection. Among other wild animals, raccoon-like dogs are involved into epizootic and epidemic chains. Dogs are the main objects to be infected in the anthropurgic cycles, while cats--a progressing group of risk. During the period of 25 years a decrease in the probability of natural rabies was noted.

Challenges and needs for China to eliminate rabies

PubMed Central

2013-01-01

In China, rabies is a significant public health concern where dogs remain the main reservoir of disease transmission to humans; rabies-related mortality ranks second in the world. We compiled all published articles and official documents on rabies in mainland China to examine challenges and needs to eliminate rabies in the country. The Chinese authorities have identified rabies as a priority, recognized rabies control in dogs as key to control rabies in humans and required intersectoral collaborations. Efforts have been made to respond effectively to the latest re-emergence of rabies, which peaked in 2007 with >3,300 cases. Despite these outcomes and the increasing volume of publications and regulations in the recent years, our review points to some major information gaps to improve rabies control activities and envisage elimination program. An emphasis on laboratory or pathogen-associated and basic epidemiology research in the literature has contrasted with the absence of information to monitor various systems in humans and animals (e.g. quality of surveillance, response and post-exposure prophylaxis). Information is also lacking to appropriately inform policymakers (e.g. economic disease burden, impact of policies) and assist program managers (e.g. comprehensive and strategic guidance for cost-effective prevention and control activities, public education and dog population management). In conclusion, strategic planning is needed to provide a sense of direction, demonstrate feasibility of elimination in China, and develop a research agenda, addressing country’s operational needs and constraints. The planning should be a multisectoral effort. PMID:24088366

Bat Rabies in Guatemala

PubMed Central

Ellison, James A.; Gilbert, Amy T.; Recuenco, Sergio; Moran, David; Alvarez, Danilo A.; Kuzmina, Natalia; Garcia, Daniel L.; Peruski, Leonard F.; Mendonça, Mary T.; Lindblade, Kim A.; Rupprecht, Charles E.

2014-01-01

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. PMID:25080103

Animal bites and rabies exposure in Australian travellers.

PubMed

Mills, Deborah J; Lau, Colleen L; Weinstein, Philip

2011-12-19

To examine the circumstances of animal exposure in a case series of Australian travellers who required rabies postexposure prophylaxis, and to assess the appropriateness of current guidelines for rabies pre-exposure vaccination. Prospective case series of 65 returned travellers who presented to four Australian travel medicine clinics between 1 April 2009 and 31 July 2010 for rabies post-exposure prophylaxis. Demographic characteristics associated with risk of injury; countries where injuries occurred; circumstances of the injuries; and travellers' experiences of obtaining postexposure prophylaxis overseas. Animal bites and scratches occurred most commonly among travellers aged 20-29 years. Most injuries occurred in Bali, Indonesia (30 [46%]) and Thailand (21 [32%]), and the most common animals responsible for the injuries to the 65 travellers were monkeys (29 travellers [45%]) and dogs (27 [42%]). Thirty-nine of the travellers (60%) initiated contact with the animal. Forty travellers (62%) were able to commence rabies vaccination overseas, but only nine (14%) were able to obtain rabies immunoglobulin overseas. Most travellers had difficulty obtaining rabies postexposure prophylaxis overseas, resulting in significant delays in appropriate treatment. We recommend that current National Health and Medical Research Council guidelines for at-risk persons be broadened, and that the risk of rabies and the option of pre-exposure vaccination be discussed with all travellers to rabies-endemic areas.

Discrepancies in Data Reporting for Rabies, Africa

PubMed Central

2013-01-01

Human rabies is an ancient disease but in modern times has primarily been associated with dog rabies–endemic countries of Asia and Africa. From an African perspective, the inevitable and tragic consequences of rabies require serious reflection of the factors that continue to drive its neglect. Established as a major disease only after multiple introductions during the colonial era, rabies continues to spread into new reservoirs and territories in Africa. However, analysis of reported data identified major discrepancies that are indicators of poor surveillance, reporting, and cooperation among national, international, and global authorities. Ultimately, the absence of reliable and sustained data compromises the priority given to the control of rabies. Appropriate actions and changes, in accordance to the One Health philosophy and including aspects such as synchronized, shared, and unified global rabies data reporting, will not only be necessary, but also should be feasible. PMID:23628197

[The macrophage disappearance reaction in guinea pigs sensitized with bovine gamma globulin or human scrum albumin (author's transl)].

PubMed

Schimke, R; Bernstein, B; Ambrosius, H

1977-01-01

The macrophage disappearance reaction (MDR) is a suitable test for detection of cell mediated immunity against bovine gamma globulin (BGG) and human serum albumin (HSA) in guinea pigs. The MDR is a technical simple, good manipulable, and quantifiable test. The optimal test conditions for the antigens BGC and HSA are the following: Peritoneal exudat cells (PEC) were stimulated with paraffin oil. On the 5th day after receiving oil the animals were injected with 80 microgram BGG or 30 microgram HSA i.p. 5 hours later the PEC were harvested and counted. With the MDR it is possible to detect differences with respect to degree of cell-mediated immunity. Supernatants of sensitized lymphocytes produces the MDR too.

Development of a Mouse Monoclonal Antibody Cocktail for Post-exposure Rabies Prophylaxis in Humans

PubMed Central

Müller, Thomas; Dietzschold, Bernhard; Ertl, Hildegund; Fooks, Anthony R.; Freuling, Conrad; Fehlner-Gardiner, Christine; Kliemt, Jeannette; Meslin, Francois X.; Rupprecht, Charles E.; Tordo, Noël; Wanderler, Alexander I.; Kieny, Marie Paule

2009-01-01

As the demand for rabies post-exposure prophylaxis (PEP) treatments has increased exponentially in recent years, the limited supply of human and equine rabies immunoglobulin (HRIG and ERIG) has failed to provide the required passive immune component in PEP in countries where canine rabies is endemic. Replacement of HRIG and ERIG with a potentially cheaper and efficacious alternative biological for treatment of rabies in humans, therefore, remains a high priority. In this study, we set out to assess a mouse monoclonal antibody (MoMAb) cocktail with the ultimate goal to develop a product at the lowest possible cost that can be used in developing countries as a replacement for RIG in PEP. Five MoMAbs, E559.9.14, 1112-1, 62-71-3, M727-5-1, and M777-16-3, were selected from available panels based on stringent criteria, such as biological activity, neutralizing potency, binding specificity, spectrum of neutralization of lyssaviruses, and history of each hybridoma. Four of these MoMAbs recognize epitopes in antigenic site II and one recognizes an epitope in antigenic site III on the rabies virus (RABV) glycoprotein, as determined by nucleotide sequence analysis of the glycoprotein gene of unique MoMAb neutralization-escape mutants. The MoMAbs were produced under Good Laboratory Practice (GLP) conditions. Unique combinations (cocktails) were prepared, using different concentrations of the MoMAbs that were capable of targeting non-overlapping epitopes of antigenic sites II and III. Blind in vitro efficacy studies showed the MoMab cocktails neutralized a broad spectrum of lyssaviruses except for lyssaviruses belonging to phylogroups II and III. In vivo, MoMAb cocktails resulted in protection as a component of PEP that was comparable to HRIG. In conclusion, all three novel combinations of MoMAbs were shown to have equal efficacy to HRIG and therefore could be considered a potentially less expensive alternative biological agent for use in PEP and prevention of rabies in humans

Sero-prevalence of virus neutralizing antibodies for rabies in different groups of dogs following vaccination.

PubMed

Pimburage, R M S; Gunatilake, M; Wimalaratne, O; Balasuriya, A; Perera, K A D N

2017-05-18

Mass vaccination of dogs is considered fundamental for national rabies control programmes in Sri Lanka, as dog is the main reservoir and transmitter of the disease. Dogs were followed to determine the sero-prevalence of antibodies to the rabies virus. Altogether 510 previously vaccinated and unvaccinated dogs with owners (domestic dogs) and dogs without owners (stray dogs) of the local guard dog breed in different age groups recruited from Kalutara District, Sri Lanka. The dogs were vaccinated with a monovalent inactivated vaccine intramuscularly and serum antibody titres on days 0, 30, 180 and 360 were determined by the Rapid Fluorescent Focus Inhibition Test (RFFIT). The results indicated, a single dose of anti-rabies vaccination fails to generate a protective level of immunity (0.5 IU/ml) which lasts until 1 year in 40.42% of dogs without owners and 57.14% of previously unvaccinated juvenile (age: 3 months to 1 year) dogs with owners. More than one vaccination would help to maintain antibody titres above the protective level in the majority of dogs. The pattern of antibody titre development in annually vaccinated and irregularly vaccinated (not annual) adult dogs with owners is closely similar irrespective of regularity in vaccination. Previously vaccinated animals have higher (2 IU/ml) antibody titres to begin with and have a higher antibody titre on day 360 too. They show a very good antibody titre by day 180. Unvaccinated animals start with low antibody titre and return to low titres by day 360, but have a satisfactory antibody titre by day 180. A single dose of anti-rabies vaccination is not sufficient for the maintenance of antibody titres for a period of 1 year in puppies, juvenile dogs with owners and in dogs without owners. Maternal antibodies do not provide adequate protection to puppies of previously vaccinated dams and puppies of previously unvaccinated dams. Immunity development after vaccination seems to be closely similar in both the groups

Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia.

PubMed

Hayakawa, Jin; Kanda, Junya; Akahoshi, Yu; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Yoshinobu

2017-05-01

Aplastic anemia patients who received rabbit antithymocyte globulin exhibited response and survival rates inferior to those who received horse antithymocyte globulin in several studies. Therefore, we conducted a meta-analysis to compare rabbit and horse antithymocyte globulin as immunosuppressive therapy for aplastic anemia. We searched online databases for studies that compared antithymocyte globulin regimens as first-line treatment for aplastic anemia, including both randomized and non-randomized controlled trials. The early mortality rate at 3 months and overall response rate at 6 months were evaluated. Thirteen studies were included in the analysis. The risk ratio (RR) of early mortality for rabbit vs. horse antithymocyte globulin was 1.33 [95% confidence interval (CI) 0.69-2.57; P = 0.39], with significant heterogeneity. A sensitivity analysis suggested higher early mortality rate in patients who received rabbit antithymocyte globulin. The overall response rate was significantly higher in patients who received horse antithymocyte globulin (RR 1.27; 95% CI 1.05-1.54; P = 0.015). In conclusion, in aplastic anemia patients treated with ATG, early mortality rate was not significantly different in patients receiving horse or rabbit ATG, although a sensitivity analysis showed higher early mortality in the rabbit ATG group. Horse ATG was associated with significantly higher response rate than rabbit ATG.

Oral Rabies Vaccination in North America: Opportunities, Complexities, and Challenges

PubMed Central

Slate, Dennis; Algeo, Timothy P.; Nelson, Kathleen M.; Chipman, Richard B.; Donovan, Dennis; Blanton, Jesse D.; Niezgoda, Michael; Rupprecht, Charles E.

2009-01-01

Steps to facilitate inter-jurisdictional collaboration nationally and continentally have been critical for implementing and conducting coordinated wildlife rabies management programs that rely heavily on oral rabies vaccination (ORV). Formation of a national rabies management team has been pivotal for coordinated ORV programs in the United States of America. The signing of the North American Rabies Management Plan extended a collaborative framework for coordination of surveillance, control, and research in border areas among Canada, Mexico, and the US. Advances in enhanced surveillance have facilitated sampling of greater scope and intensity near ORV zones for improved rabies management decision-making in real time. The value of enhanced surveillance as a complement to public health surveillance was best illustrated in Ohio during 2007, where 19 rabies cases were detected that were critical for the formulation of focused contingency actions for controlling rabies in this strategically key area. Diverse complexities and challenges are commonplace when applying ORV to control rabies in wild meso-carnivores. Nevertheless, intervention has resulted in notable successes, including the elimination of an arctic fox (Vulpes lagopus) rabies virus variant in most of southern Ontario, Canada, with ancillary benefits of elimination extending into Quebec and the northeastern US. Progress continues with ORV toward preventing the spread and working toward elimination of a unique variant of gray fox (Urocyon cinereoargenteus) rabies in west central Texas. Elimination of rabies in coyotes (Canis latrans) through ORV contributed to the US being declared free of canine rabies in 2007. Raccoon (Procyon lotor) rabies control continues to present the greatest challenges among meso-carnivore rabies reservoirs, yet to date intervention has prevented this variant from gaining a broad geographic foothold beyond ORV zones designed to prevent its spread from the eastern US. Progress continues

The rise and fall of rabies in Japan: A quantitative history of rabies epidemics in Osaka Prefecture, 1914-1933.

PubMed

Kurosawa, Aiko; Tojinbara, Kageaki; Kadowaki, Hazumu; Hampson, Katie; Yamada, Akio; Makita, Kohei

2017-03-01

Japan has been free from rabies since the 1950s. However, during the early 1900s several large-scale epidemics spread throughout the country. Here we investigate the dynamics of these epidemics between 1914 and 1933 in Osaka Prefecture, using archival data including newspapers. The association between dog rabies cases and human population density was investigated using Mixed-effects models and epidemiological parameters such as the basic reproduction number (R0), the incubation and infectious period and the serial interval were estimated. A total of 4,632 animal rabies cases were reported, mainly in dogs (99.0%, 4,584 cases) during two epidemics from 1914 to 1921, and 1922 to 1933 respectively. The second epidemic was larger (3,705 cases) than the first (879 cases), but had a lower R0 (1.50 versus 2.42). The first epidemic was controlled through capture of stray dogs and tethering of pet dogs. Dog mass vaccination began in 1923, with campaigns to capture stray dogs. Rabies in Osaka Prefecture was finally eliminated in 1933. A total of 3,805 rabid dog-bite injuries, and 75 human deaths were reported. The relatively low incidence of human rabies, high ratio of post-exposure vaccines (PEP) and bite injuries by rabid dogs (minimum 6.2 to maximum 73.6, between 1924 and 1928), and a decline in the proportion of bite victims that developed hydrophobia over time (slope = -0.29, se = 3, p < 0.001), indicated that increased awareness and use of PEP might have prevented disease. Although significantly more dog rabies cases were detected at higher human population densities (slope = 0.66, se = 0.03, p < 0.01), there were fewer dog rabies cases detected per capita (slope = -0.34, se = 0.03, p < 0.01). We suggest that the combination of mass vaccination and restriction of dog movement enabled by strong legislation was key to eliminate rabies. Moreover, the prominent role of the media in both reporting rabies cases and efforts to control the disease likely contributed to

Possible rabies exposures in Peace Corps volunteers, 2011.

PubMed

Harvey, Kira; Jentes, Emily S; Charles, Myrna; Johnson, Katherine J; Petersen, Brett; Lamias, Mark J; Blanton, Jesse D; Sotir, Mark J; Brunette, Gary W

2014-05-01

We surveyed Peace Corps Medical Officers (PCMOs) to determine the frequency of and responses to possible rabies exposures of U.S. Peace Corps volunteers (PCVs). Surveys were sent to 56 PCMOs serving in countries with moderate or high rabies vaccine recommendations from the U.S. Centers for Disease Control and Prevention (CDC), of which 38 (68%) responded. Thirty-seven PCMOs reported that, of 4,982 PCVs, 140 (3%) experienced possible rabies exposures. Of these, 125 (89%) had previously received rabies vaccination, 129 (92%) presented with adequately cleansed wounds, and 106 (76%) were deemed to require and were given post-exposure prophylaxis (PEP). Of 35 respondents, 30 (86%) reported that rabies vaccine was always accessible to PCVs in their country within 24 hours. Overall, the Peace Corps is successful at preventing and treating possible rabies exposures. However, this study identified a few gaps in policy implementation. The Peace Corps should continue and strengthen efforts to provide education, preexposure vaccination, and PEP to PCVs.

Possible Rabies Exposures in Peace Corps Volunteers, 2011

PubMed Central

Harvey, Kira; Jentes, Emily S.; Charles, Myrna; Johnson, Katherine J.; Petersen, Brett; Lamias, Mark J.; Blanton, Jesse D.; Sotir, Mark J.; Brunette, Gary W.

2014-01-01

We surveyed Peace Corps Medical Officers (PCMOs) to determine the frequency of and responses to possible rabies exposures of U.S. Peace Corps volunteers (PCVs). Surveys were sent to 56 PCMOs serving in countries with moderate or high rabies vaccine recommendations from the U.S. Centers for Disease Control and Prevention (CDC), of which 38 (68%) responded. Thirty-seven PCMOs reported that, of 4,982 PCVs, 140 (3%) experienced possible rabies exposures. Of these, 125 (89%) had previously received rabies vaccination, 129 (92%) presented with adequately cleansed wounds, and 106 (76%) were deemed to require and were given post-exposure prophylaxis (PEP). Of 35 respondents, 30 (86%) reported that rabies vaccine was always accessible to PCVs in their country within 24 hours. Overall, the Peace Corps is successful at preventing and treating possible rabies exposures. However, this study identified a few gaps in policy implementation. The Peace Corps should continue and strengthen efforts to provide education, preexposure vaccination, and PEP to PCVs. PMID:24639304

Surveillance of Human Rabies by National Authorities--A Global Survey.

PubMed

Taylor, L H; Knopf, L

2015-11-01

Effective prevention of deaths due to human rabies is currently hampered by a lack of understanding of the scale of the problem, and the distribution of both animal and human cases across countries, regions and continents. Unfortunately, despite the severity of the disease, accurate data on which to assess these questions and to prioritize and direct public health interventions are not available for many parts of the world. This survey sought to understand the current global situation regarding the surveillance of human rabies. Data were collected from 91 countries across all continents and all categories of human rabies risk, generating the most complete and representative global data set currently available. Respondents were asked key questions about whether human rabies was a notifiable disease, how the surveillance system for human rabies operated and whether the respondent considered that the surveillance system was working effectively. Across the 91 countries from which data were collated, human rabies was a notifiable disease in all but eight. Despite international guidance, surveillance systems were very varied. Even where rabies is a notifiable disease, many countries had surveillance system judged to be ineffective, almost all of these being high and moderate rabies risk countries in Africa and Asia. Overall, 41% of the population covered by this survey (around 2.5 billion people) live in countries where there is no or ineffective rabies surveillance. The lack of robust surveillance is hindering rabies control efforts. However, whilst worldwide rabies surveillance would be improved if rabies were notifiable in all countries, many other challenges to the implementation of effective global human rabies surveillance systems remain. © 2015 Blackwell Verlag GmbH.

Regulatory systems for prevention and control of rabies, Japan.

PubMed

Takahashi-Omoe, Hiromi; Omoe, Katsuhiko; Okabe, Nobuhiko

2008-09-01

Japan is one of the few rabies-free countries. Although 3 imported cases of human rabies were seen in 1970 and 2006, no other cases have been reported for approximately 50 years. The elimination of rabies in Japan is attributed to not only its geographic isolation but also to effective prevention and control measures, such as registration and vaccination of domestic dogs, required quarantine of susceptible imported animals, and national plans of action based on scientific research. Countermeasures against rabies have been upgraded; an improved management system for domestic dogs under the amended Enforcement Regulations of the Rabies Prevention Law has been in effect since April 2007. The latest regulatory systems for preventing and controlling rabies provide an effective model for elimination of the disease worldwide.

Association between cancer chemotherapy and canine distemper virus, canine parvovirus, and rabies virus antibody titers in tumor-bearing dogs.

PubMed

Henry, C J; McCaw, D L; Brock, K V; Stoker, A M; Tyler, J W; Tate, D J; Higginbotham, M L

2001-11-01

To determine the association between cancer chemotherapy and serum canine distemper virus (CDV), canine parvovirus (CPV), and rabies virus antibody titers in tumor-bearing dogs. Prospective study. 21 client-owned dogs with various malignancies and 16 client-owned dogs with lymphoma. In study A, serum antibody titers were measured by use of hemagglutination inhibition (CPV titers) or serum neutralization (CDV titers) before and at least 1 month after initiation of chemotherapy. Baseline values were compared with values obtained from a control population of 122 healthy dogs seen for routine revaccination. Titers were considered protective at > or = 1:96 for CDV and > or = 1:80 for CPV. In study B, serum IgG titers were measured by use of immunofluorescent assay (CDV and CPV titers) and rapid fluorescent focus inhibition test (RFFIT, rabies titers) at baseline and again at weeks 5, 8, and 24 of a standard chemotherapy protocol for treatment of lymphoma. An IgG titer of > or = 1:50 was considered protective for CPV and CDV. An RFFIT titer of > or = 0.5 U/ml was considered protective for rabies virus. Significant changes were not detected in CDV, CPV, and rabies virus titers following chemotherapy in tumor-bearing dogs. Results suggest that established immunity to CDV, CPV, and rabies virus from previous vaccination is not significantly compromised by standard chemotherapy used to treat tumor-bearing dogs.

Dog-transmitted Rabies in Beijing, China.

PubMed

Zhang, Jing Yuan; Zhang, Bi; Zhang, Shou Feng; Zhang, Fei; Li, Nan; Liu, Ye; Hu, Rong Liang

2017-07-01

Rabies remains a continuous threat to public health in Beijing. In this study, a total of 224 brain tissues were collected from suspected infected stray dogs within Beijing between January 2015 and December 2016. Among them, total of 67 samples were diagnosed positive for rabies. In the phylogenetic analysis, rabies in Beijing is currently a relatively independent public health issue originating from local rabid dogs apart from the imported cases from elsewhere in the country. Because vaccination of unregistered dogs against rabies is still neglected in Beijing and other regions of China, national and local authorities should play central roles in all related aspects, such as development of policies, engagement of stakeholders for public and professional education, entire vaccination process, and animal management. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

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

PubMed

Blanton, Jesse D; Meadows, Anastasia; Murphy, Staci M; Manangan, Jamie; Hanlon, Cathleen A; Faber, Marie-Luise; Dietzschold, Bernhard; Rupprecht, Charles E

2006-07-01

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

Rabbit anti-rabies immunoglobulins production and evaluation.

PubMed

Liu, Xinjian; Liu, Qiongqiong; Feng, Xiaomin; Tang, Qi; Wang, Zhongcan; Li, Suqing; Feng, Zhenqing; Zhu, Jin; Guan, Xiaohong

2011-04-01

Due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for HRIG and ERIG, especially for those people living in the developing countries. Because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by ELISA, affinity assay, immunofluorescence assay (IFA), immunocytochemistry, rapid fluorescent focus inhibition test (RFFIT). ELISA, affinity assay and IFA showed that rabbit RIG (RRIG) bound specifically to rabies virions. RFFIT result showed that RRIG has neutralization activity. This result was confirmed in vivo in a Kunming mouse challenge model and the protection rate of the treatment with RRIG was higher (25%) than that offered by HRIG when mice were challenged with a lethal RV dose. Our results demonstrate that RRIG is safe and efficacious as a candidate drug to replace rabies immunoglobulin in post-exposure prophylaxis.

Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control

PubMed Central

Lembo, Tiziana; Attlan, Michaël; Bourhy, Hervé; Cleaveland, Sarah; Costa, Peter; de Balogh, Katinka; Dodet, Betty; Fooks, Anthony R.; Hiby, Elly; Leanes, Fernando; Meslin, François-Xavier; Miranda, Mary Elizabeth; Müller, Thomas; Nel, Louis H.; Rupprecht, Charles E.; Tordo, Noël; Tumpey, Abbigail; Wandeler, Alexander; Briggs, Deborah J.

2011-01-01

Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this “incurable wound” persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector. Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect. Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs. Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination. PMID:21776359

Rabies elimination research: juxtaposing optimism, pragmatism and realism

PubMed Central

Hampson, Katie

2017-01-01

More than 100 years of research has now been conducted into the prevention, control and elimination of rabies with safe and highly efficacious vaccines developed for use in human and animal populations. Domestic dogs are a major reservoir for rabies, and although considerable advances have been made towards the elimination and control of canine rabies in many parts of the world, the disease continues to kill tens of thousands of people every year in Africa and Asia. Policy efforts are now being directed towards a global target of zero human deaths from dog-mediated rabies by 2030 and the global elimination of canine rabies. Here we demonstrate how research provides a cause for optimism as to the feasibility of these goals through strategies based around mass dog vaccination. We summarize some of the pragmatic insights generated from rabies epidemiology and dog ecology research that can improve the design of dog vaccination strategies in low- and middle-income countries and which should encourage implementation without further delay. We also highlight the need for realism in reaching the feasible, although technically more difficult and longer-term goal of global elimination of canine rabies. Finally, we discuss how research on rabies has broader relevance to the control and elimination of a suite of diseases of current concern to human and animal health, providing an exemplar of the value of a ‘One Health’ approach. PMID:29263285

9 CFR 113.209 - Rabies Vaccine, Killed Virus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

9 CFR 113.209 - Rabies Vaccine, Killed Virus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

9 CFR 113.209 - Rabies Vaccine, Killed Virus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

9 CFR 113.209 - Rabies Vaccine, Killed Virus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Rabies Vaccine, Killed Virus. 113.209... Killed Virus Vaccines § 113.209 Rabies Vaccine, Killed Virus. Rabies Vaccine (Killed Virus) shall be..., safe, and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

Polyclonal antithymocyte globulin and cardiovascular disease in kidney transplant recipients.

PubMed

Ducloux, Didier; Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

2014-06-01

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. Copyright © 2014 by the American Society of Nephrology.

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

PubMed Central

Courivaud, Cécile; Bamoulid, Jamal; Crepin, Thomas; Chalopin, Jean-Marc; Tiberghien, Pierre; Saas, Philippe

2014-01-01

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)–induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8+ T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs. PMID:24511120

Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

PubMed Central

Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

2012-01-01

BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

9 CFR 113.312 - Rabies Vaccine, Live Virus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

9 CFR 113.312 - Rabies Vaccine, Live Virus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

9 CFR 113.312 - Rabies Vaccine, Live Virus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

9 CFR 113.312 - Rabies Vaccine, Live Virus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Rabies Vaccine, Live Virus. 113.312... Virus Vaccines § 113.312 Rabies Vaccine, Live Virus. Rabies Vaccine shall be prepared from virus-bearing..., safe and immunogenic shall be used for preparing the production seed virus for vaccine production. All...

Modeling the transmission dynamics and control of rabies in China.

PubMed

Ruan, Shigui

2017-04-01

Human rabies was first recorded in ancient China in about 556 BC and is still one of the major public-health problems in China. From 1950 to 2015, 130,494 human rabies cases were reported in Mainland China with an average of 1977 cases per year. It is estimated that 95% of these human rabies cases are due to dog bites. The purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in China. We first construct a basic susceptible, exposed, infectious, and recovered (SEIR) type model for the spread of rabies virus among dogs and from dogs to humans and use the model to simulate the human rabies data in China from 1996 to 2010. Then we modify the basic model by including both domestic and stray dogs and apply the model to simulate the human rabies data from Guangdong Province, China. To study the seasonality of rabies, in Section 4 we further propose a SEIR model with periodic transmission rates and employ the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health from January 2004 to December 2010. To understand the spatial spread of rabies, in Section 5 we add diffusion to the dog population in the basic SEIR model to obtain a reaction-diffusion equation model and determine the minimum wave speed connecting the disease-free equilibrium to the endemic equilibrium. Finally, in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, in Section 6 we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans and use the two-patch submodel to investigate the rabies virus clades lineages and to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. Some discussions are provided in Section 7. Copyright © 2017 Elsevier Inc. All rights reserved.

[Current status of animal rabies in France].

PubMed

Aubert, M

1997-01-01

The main host reservoir and vector of rabies in Western Europe is the red fox (Vulpes vulpes). A vaccination strategy for this species has been developed and tested in Switzerland since 1978. Results indicate that the vaccine which is administered in spring and autumn for at least two consecutive years is more effective than destruction by shooting or gassing the animals. The same approach using bait containing increasingly effective and safe vaccines has been in use in France since 1986. By creating an immunological barrier from the English channel to the Swiss border, it has been possible to stop the southern progression of the disease. In the following years the vaccination program was extended to all contaminated areas in France (141,700 km2). From 1989 to 1996 rabies decreased in incidence by 99.7% and disappeared from 95% of the previously contaminated area. Although no case of rabies involving a non-flying mammal has been reported since October 1996, rabies cannot be considered as eradicated as long as places of active disease subsist in neighboring areas of Belgium and the Sarreland. Bat rabies in Europe is caused by two viral genotypes that have never been isolated in any species other than bats and man. A total of four cases of bat rabies have been diagnosed in France since 1989. All four cases occurred in the Serotine community including one in 1997. All cases of canine rabies reported in the last 20 years have been observed in imported animals. The last was in 1995 and could have been prevented by stricter border control.

Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

PubMed

Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

2017-07-01

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P <0.001) and chronic (20% versus 9%, P <0.001) graft- versus -host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3-year overall survival, 87% and 92%, P =0.76, respectively. Among recipients of unrelated donor transplants, acute graft- versus -host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P <0.001) but not chronic graft- versus -host disease (38% versus 32%, P =0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P =0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia. Copyright© 2017 Ferrata Storti Foundation.

Rabies in the arctic fox population, Svalbard, Norway.

PubMed

Mørk, Torill; Bohlin, Jon; Fuglei, Eva; Åsbakk, Kjetil; Tryland, Morten

2011-10-01

Arctic foxes, 620 that were trapped and 22 found dead on Svalbard, Norway (1996-2004), as well as 10 foxes trapped in Nenets, North-West Russia (1999), were tested for rabies virus antigen in brain tissue by standard direct fluorescent antibody test. Rabies antigen was found in two foxes from Svalbard and in three from Russia. Blood samples from 515 of the fox carcasses were screened for rabies antibodies with negative result. Our results, together with a previous screening (1980-1989, n=817) indicate that the prevalence of rabies in Svalbard has remained low or that the virus has not been enzootic in the arctic fox population since the first reported outbreak in 1980. Brain tissues from four arctic foxes (one from Svalbard, three from Russia) in which rabies virus antigen was detected were further analyzed by reverse-transcriptase polymerase chain reaction direct amplicon sequencing and phylogenetic analysis. Sequences were compared to corresponding sequences from rabies virus isolates from other arctic regions. The Svalbard isolate and two of the Russian isolates were identical (310 nucleotides), whereas the third Russian isolate differed in six nucleotide positions. However, when translated into amino acid sequences, none of these substitutions produced changes in the amino acid sequence. These findings suggest that the spread of rabies virus to Svalbard was likely due to migration of arctic foxes over sea ice from Russia to Svalbard. Furthermore, when compared to other Arctic rabies virus isolates, a high degree of homology was found, suggesting a high contact rate between arctic fox populations from different arctic regions. The high degree of homology also indicates that other, and more variable, regions of the genome than this part of the nucleoprotein gene should be used to distinguish Arctic rabies virus isolates for epidemiologic purposes.

Assessing the Risk of a Canine Rabies Incursion in Northern Australia

PubMed Central

Hudson, Emily G.; Brookes, Victoria J.; Ward, Michael P.

2017-01-01

Rabies is a globally distributed virus that causes approximately 60,00 human deaths annually with >99% of cases caused by dog bites. Australia is currently canine rabies free. However, the recent eastward spread of rabies in the Indonesian archipelago has increased the probability of rabies entry into northern Australian communities. In addition, many northern Australian communities have large populations of free-roaming dogs, capable of maintaining rabies should an incursion occur. A risk assessment of rabies entry and transmission into these communities is needed to target control and surveillance measures. Illegal transportation of rabies-infected dogs via boat landings is a high-risk entry pathway and was the focus of the current study. A quantitative, stochastic, risk assessment model was developed to evaluate the risk of rabies entry into north-west Cape York Peninsula, Australia, and rabies introduction to resident dogs in one of the communities via transport of rabies-infected dogs on illegal Indonesian fishing boats. Parameter distributions were derived from expert opinion, literature, and analysis of field studies. The estimated median probability of rabies entry into north-west Cape York Peninsula and into Seisia from individual fishing boats was 1.9 × 10−4/boat and 8.7 × 10−6/boat, respectively. The estimated annual probability that at least one rabies-infected dog enters north-west Cape York Peninsula and into Seisia was 5.5 × 10−3 and 3.5 × 10−4, respectively. The estimated median probability of rabies introduction into Seisia was 4.7 × 10−8/boat, and the estimated annual probability that at least one rabies-infected dog causes rabies transmission in a resident Seisia dog was 8.3 × 10−5. Sensitivity analysis using the Sobol method highlighted some parameters as influential, including but not limited to the prevalence of rabies in Indonesia, the probability of a dog on board an Indonesian fishing boat, and the

Elimination of terrestrial rabies in Germany using oral vaccination of foxes.

PubMed

Müller, Thomas; Bätza, Hans-Joachim; Freuling, Conrad; Kliemt, Anke; Kliemt, Jeannette; Heuser, Rolf; Schlüter, Hartmut; Selhorst, Thomas; Vos, Adriaan; Mettenleiter, Thomas C

2012-01-01

Oral rabies vaccination (ORV) has become the method of choice in fox rabies control in Europe. During the past three decades fox-mediated rabies virtually disappeared from Western and Central Europe. Following Switzerland, Germany was the second European country to launch ORV field trials on its territory in 1983. This paper provides a historical overview on the emergence of fox rabies in Germany; describing the basic principles and milestones of the German rabies eradication programme and presenting results of two decades of efforts to control the disease in foxes. Also, setbacks as well as country-specific differences and particularities on Germany's long way to rabies elimination in comparison to other European countries are addressed. Since the first field trials in Germany the number of rabies cases steadily decreased from 10 484 in 1983 to three cases recorded in 2006. On February 3rd 2006 the last case of terrestrial rabies in Germany was detected in a fox near the town of Mainz, Rhineland-Palatinate. In 2008, ORV ceased after 25 years and Germany was officially declared as free from terrestrial rabies. The German rabies eradication programme did cost approximately 100 million euro of which 37 million euro were covered by the EU. For the future, efforts should focus on maintaining a rabies free status by implementing measures to prevent reintroduction of terrestrial rabies from endemic countries.

Spatial and temporal trends of bat-borne rabies in Chile.

PubMed

Escobar, L E; Restif, O; Yung, V; Favi, M; Pons, D J; Medina-Vogel, G

2015-05-01

In Chile, while dog rabies has decreased markedly over the last 30 years, bat rabies is still reported frequently. In order to shed new light on the spatiotemporal trends of these reports, we analysed active and passive data from years 1985 and 2012, which included 61 076 samples from 289 counties of Chile. We found that from 1994 to 2012, more than 15 000 bat samples were submitted for diagnostics through passive surveillance, 9·5% of which tested positive for rabies. By contrast, the prevalence of infection was only ~0·4% among the nearly 12 000 bat samples submitted through active surveillance. We found that the prevalence of dog rabies dropped steadily over the same period, with just a single confirmed case since 1998. None of the 928 samples from wild animals, other than bats, were positive for rabies. Although there has been only one confirmed case of human rabies in Chile since 1985, and a single confirmed case in a dog since 1998, bats remain a reservoir for rabies viruses. While active surveillance indicates that rabies prevalence is low in bat colonies, the high proportion of positive bats submitted through passive surveillance is a concern. To prevent human rabies, local public health agencies should increase research on the basic ecology of bats and the role of stray dogs and cats as potential rabies amplifiers.

The rise and fall of rabies in Japan: A quantitative history of rabies epidemics in Osaka Prefecture, 1914–1933

PubMed Central

Kurosawa, Aiko; Tojinbara, Kageaki; Kadowaki, Hazumu; Hampson, Katie; Yamada, Akio

2017-01-01

Japan has been free from rabies since the 1950s. However, during the early 1900s several large-scale epidemics spread throughout the country. Here we investigate the dynamics of these epidemics between 1914 and 1933 in Osaka Prefecture, using archival data including newspapers. The association between dog rabies cases and human population density was investigated using Mixed-effects models and epidemiological parameters such as the basic reproduction number (R0), the incubation and infectious period and the serial interval were estimated. A total of 4,632 animal rabies cases were reported, mainly in dogs (99.0%, 4,584 cases) during two epidemics from 1914 to 1921, and 1922 to 1933 respectively. The second epidemic was larger (3,705 cases) than the first (879 cases), but had a lower R0 (1.50 versus 2.42). The first epidemic was controlled through capture of stray dogs and tethering of pet dogs. Dog mass vaccination began in 1923, with campaigns to capture stray dogs. Rabies in Osaka Prefecture was finally eliminated in 1933. A total of 3,805 rabid dog-bite injuries, and 75 human deaths were reported. The relatively low incidence of human rabies, high ratio of post-exposure vaccines (PEP) and bite injuries by rabid dogs (minimum 6.2 to maximum 73.6, between 1924 and 1928), and a decline in the proportion of bite victims that developed hydrophobia over time (slope = -0.29, se = 3, p < 0.001), indicated that increased awareness and use of PEP might have prevented disease. Although significantly more dog rabies cases were detected at higher human population densities (slope = 0.66, se = 0.03, p < 0.01), there were fewer dog rabies cases detected per capita (slope = -0.34, se = 0.03, p < 0.01). We suggest that the combination of mass vaccination and restriction of dog movement enabled by strong legislation was key to eliminate rabies. Moreover, the prominent role of the media in both reporting rabies cases and efforts to control the disease likely contributed to

The SARE tool for rabies control: Current experience in Ethiopia.

PubMed

Coetzer, A; Kidane, A H; Bekele, M; Hundera, A D; Pieracci, E G; Shiferaw, M L; Wallace, R; Nel, L H

2016-11-01

The Stepwise Approach towards Rabies Elimination (SARE) tool was developed through a joint effort of the Food and Agriculture Organization (FAO) of the United Nations and the Global Alliance for Rabies Control (GARC), to provide a standard mechanism for countries to assess their rabies situation and measure progress in eliminating the disease. Because the African continent has the highest per capita death rate from rabies, and Ethiopia is estimated to have the second largest number of rabies deaths of all African countries, Ethiopia undertook a self-assessment by means of the Stepwise Approach towards Rabies Elimination (SARE) tool. In February 2016, the Ethiopian government hosted an intersectoral consultative meeting in an effort to assess the progress that has been made towards the control and elimination of canine rabies. The SARE assessment identified a number of critical gaps, including poor inter-sectoral collaboration and limited availability and access to dog vaccine, while the existence of a surveillance system for rabies and legislation for outbreak declaration and response were among the strengths identified. The SARE tool enabled key criteria to be prioritized, thereby accelerating the National Strategy and ensuring that Ethiopia will progress rapidly in line with the goals set by the global community for the elimination of human rabies deaths by 2030. Although the analysis showed that Ethiopia is still in the early stages of rabies control (Stage 0.5/5), the country shows great promise in terms of developing a SARE-guided National Rabies Prevention and Control Strategy. Copyright © 2016 Elsevier B.V. All rights reserved.

Type 1 immune mechanisms driven by the response to infection with attenuated rabies virus result in changes in the immune bias of the tumor microenvironment and necrosis of mouse GL261 brain tumors

PubMed Central

Bongiorno, Emily K.; Garcia, Samantha A.; Sauma, Sami; Hooper, D. Craig

2017-01-01

Immunotherapeutic strategies for malignant glioma have to overcome the immunomodulatory activities of M2 monocytes that appear in the circulation and as tumor associated macrophages (TAM). M2 cell products contribute to the growth-promoting attributes of the tumor microenvironment (TME) and bias immunity towards type 2, away from the type 1 mechanisms with anti-tumor properties. To drive type 1 immunity in CNS tissues we infected GL261 tumor-bearing mice with attenuated rabies virus (RABV). These neurotropic viruses spread to CNS tissues trans-axonally where they induce a strong type 1 immune response that involves Th1, CD8 and B cell entry across the blood brain barrier and virus clearance in the absence of overt sequelae. Intranasal infection with attenuated RABV prolonged the survival of mice bearing established GL261 brain tumors. Despite the failure of virus spread to the tumor, infection resulted in significantly enhanced tumor necrosis, extensive CD4 T cell accumulation and high levels of the proinflammatory factors IFNy, TNFa, and iNOS in the TME merely 4 days after infection, before significant virus spread or the appearance of RABV-specific immune mechanisms in CNS tissues. While the majority of g CD4 cells appeared functionally inactive, the proinflammatory changes in the TME later resulted in the loss of accumulating M2 and increased M1 TAM. Mice deficient in the Th1 transcription factor Tbet did not gain any survival advantage from RABV infection, exhibiting only limited tumor necrosis and no change in TME cytokines or TAM phenotype, highlighting the importance of type 1 mechanisms in this process. PMID:28461570

Population Structure of Two Rabies Hosts Relative to the Known Distribution of Rabies Virus Variants in Alaska

PubMed Central

Goldsmith, Elizabeth W.; Renshaw, Benjamin; Clement, Christopher J.; Himschoot, Elizabeth A.; Hundertmark, Kris J.; Hueffer, Karsten

2015-01-01

For pathogens that infect multiple species the distinction between reservoir hosts and spillover hosts is often difficult. In Alaska, three variants of the arctic rabies virus exist with distinct spatial distributions. We test the hypothesis that rabies virus variant distribution corresponds to the population structure of the primary rabies hosts in Alaska, arctic foxes (Vulpes lagopus) and red foxes (V. vulpes) in order to possibly distinguish reservoir and spill over hosts. We used mitochondrial DNA (mtDNA) sequence and nine microsatellites to assess population structure in those two species. mtDNA structure did not correspond to rabies virus variant structure in either species. Microsatellite analyses gave varying results. Bayesian clustering found 2 groups of arctic foxes in the coastal tundra region, but for red foxes it identified tundra and boreal types. Spatial Bayesian clustering and spatial principal components analysis identified 3 and 4 groups of arctic foxes, respectively, closely matching the distribution of rabies virus variants in the state. Red foxes, conversely, showed eight clusters comprising 2 regions (boreal and tundra) with much admixture. These results run contrary to previous beliefs that arctic fox show no fine-scale spatial population structure. While we cannot rule out that the red fox is part of the maintenance host community for rabies in Alaska, the distribution of virus variants appears to be driven primarily by the artic fox Therefore we show that host population genetics can be utilized to distinguish between maintenance and spillover hosts when used in conjunction with other approaches. PMID:26661691

Population structure of two rabies hosts relative to the known distribution of rabies virus variants in Alaska.

PubMed

Goldsmith, Elizabeth W; Renshaw, Benjamin; Clement, Christopher J; Himschoot, Elizabeth A; Hundertmark, Kris J; Hueffer, Karsten

2016-02-01

For pathogens that infect multiple species, the distinction between reservoir hosts and spillover hosts is often difficult. In Alaska, three variants of the arctic rabies virus exist with distinct spatial distributions. We tested the hypothesis that rabies virus variant distribution corresponds to the population structure of the primary rabies hosts in Alaska, arctic foxes (Vulpes lagopus) and red foxes (Vulpes vulpes) to possibly distinguish reservoir and spillover hosts. We used mitochondrial DNA (mtDNA) sequence and nine microsatellites to assess population structure in those two species. mtDNA structure did not correspond to rabies virus variant structure in either species. Microsatellite analyses gave varying results. Bayesian clustering found two groups of arctic foxes in the coastal tundra region, but for red foxes it identified tundra and boreal types. Spatial Bayesian clustering and spatial principal components analysis identified 3 and 4 groups of arctic foxes, respectively, closely matching the distribution of rabies virus variants in the state. Red foxes, conversely, showed eight clusters comprising two regions (boreal and tundra) with much admixture. These results run contrary to previous beliefs that arctic fox show no fine-scale spatial population structure. While we cannot rule out that the red fox is part of the maintenance host community for rabies in Alaska, the distribution of virus variants appears to be driven primarily by the arctic fox. Therefore, we show that host population genetics can be utilized to distinguish between maintenance and spillover hosts when used in conjunction with other approaches. © 2015 John Wiley & Sons Ltd.

Emergence of a sylvatic enzootic formosan ferret badger-associated rabies in Taiwan and the geographical separation of two phylogenetic groups of rabies viruses.

PubMed

Tsai, K J; Hsu, W C; Chuang, W C; Chang, J C; Tu, Y C; Tsai, H J; Liu, H F; Wang, F I; Lee, S H

2016-01-01

Taiwan had been declared rabies-free in humans and domestic animals for five decades until July 2013, when surprisingly, three Formosan ferret badgers (FB) were diagnosed with rabies. Since then, a variety of wild carnivores and other wildlife species have been found dead, neurologically ill, or exhibiting aggressive behaviors around the island. To determine the affected animal species, geographic areas, and environments, animal bodies were examined for rabies by direct fluorescent antibody test (FAT). The viral genomes from the brains of selected rabid animals were sequenced for the phylogeny of rabies viruses (RABV). Out of a total of 1016 wild carnivores, 276/831 (33.2%) Formosan FBs were FAT positive, with occasional biting incidents in 1 dog and suspected spillover in 1 house shrew. All other animals tested, including dogs, cats, bats, mice, house shrews, and squirrels, were rabies-negative. The rabies was badger-associated and confined to nine counties/cities in sylvatic environments. Phylogeny of nucleoprotein and glycoprotein genes from 59 Formosan FB-associated RABV revealed them to be clustered in two distinct groups, TWI and TWII, consistent with the geographic segregation into western and eastern Taiwan provided by the Central Mountain Range and into northern rabies-free and central-southern rabies-affected regions by a river bisecting western Taiwan. The unique features of geographic and genetic segregation, sylvatic enzooticity, and FB-association of RABV suggest a logical strategy for the control of rabies in this nation. Copyright © 2015 Elsevier B.V. All rights reserved.

Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review

PubMed Central

Devleesschauwer, Brecht; Aryal, Arjun; Sharma, Barun Kumar; Ale, Anita; Declercq, Anne; Depraz, Stephanie; Gaire, Tara Nath; Gongal, Gyanendra; Karki, Surendra; Pandey, Basu Dev; Pun, Sher Bahadur; Duchateau, Luc; Dorny, Pierre; Speybroeck, Niko

2016-01-01

Background Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal. Methods We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal. Findings So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10–100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray

Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review.

PubMed

Devleesschauwer, Brecht; Aryal, Arjun; Sharma, Barun Kumar; Ale, Anita; Declercq, Anne; Depraz, Stephanie; Gaire, Tara Nath; Gongal, Gyanendra; Karki, Surendra; Pandey, Basu Dev; Pun, Sher Bahadur; Duchateau, Luc; Dorny, Pierre; Speybroeck, Niko

2016-02-01

Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal. We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal. So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10-100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true

Twelve years of rabies surveillance in Sri Lanka, 1999-2010.

PubMed

Karunanayake, Dushantha; Matsumoto, Takashi; Wimalaratne, Omala; Nanayakkara, Susilakanthi; Perera, Devika; Nishizono, Akira; Ahmed, Kamruddin

2014-10-01

Rabies is endemic in Sri Lanka, but little is known about the temporal and spatial trends of rabies in this country. Knowing these trends may provide insight into past control efforts and serve as the basis for future control measures. In this study, we analyzed distribution of rabies in humans and animals over a period of 12 years in Sri Lanka. Accumulated data from 1999 through 2010 compiled by the Department of Rabies Diagnosis and Research, Medical Research Institute (MRI), Colombo, were used in this study. The yearly mean percentage of rabies-positive sample was 62.4% (47.6-75.9%). Three-fourths of the rabies-positive samples were from the Colombo, Gampaha, and Kalutara districts in Western province, followed by Galle in Southern province. A high percentage of the rabies samples were from dogs (85.2%), followed by cats (7.9%), humans (3.8%), wild animals (2.0%), and livestock (1.1%). Among wild animals, mongooses were the main victims followed by civets. The number of suspect human rabies cases decreased gradually in Sri Lanka, although the number of human samples submitted for laboratory confirmation increased. The number of rabid dogs has remained relatively unchanged, but the number of suspect human rabies is decreasing gradually in Sri Lanka. These findings indicate successful use of postexposure prophylaxis (PEP) by animal bite victims and increased rabies awareness. PEP is free of charge and is supplied through government hospitals by the Ministry of Health, Sri Lanka. Our survey shows that most positive samples were received from Western and Southern provinces, possibly because of the ease of transporting samples to the laboratory. Submissions of wild animal and livestock samples should be increased by creating more awareness among the public. Better rabies surveillance will require introduction of molecular methods for detection and the establishment of more regional rabies diagnostic laboratories.

[Rabies vaccines: Current status and prospects for development].

PubMed

Starodubova, E S; Preobrazhenskaia, O V; Kuzmenko, Y V; Latanova, A A; Yarygina, E I; Karpov, V L

2015-01-01

Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. Since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. Progress in molecular biology and biotechnology enabled the development of effective and safe technologies of vaccine production. Currently, new-generation vaccines are being developed based on recombinant rabies virus strains or on the production of an individual recombinant rabies antigen-glycoprotein (G protein), either as a component of nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this review, the main modern trends in the development of rabies vaccines have been discussed.

Rabies surveillance in the United States during 2010

PubMed Central

Blanton, Jesse D.; Palmer, Dustyn; Dyer, Jessie; Rupprecht, Charles E.

2016-01-01

Summary During 2010, 48 states and Puerto Rico reported 6,154 rabid animals and 2 human rabies cases to the CDC, representing an 8% decrease from the 6,690 rabid animals and 4 human cases reported in 2009. Hawaii and Mississippi did not report any laboratory-confirmed rabid animals during 2010. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,246 raccoons (36.5%), 1,448 skunks (23.5%), 1,430 bats (23.2%), 429 foxes (6.9%), 303 cats (4.9%), 71 cattle (1.1%), and 69 dogs (1.1%). Compared with 2009, number of reported rabid animals decreased across all animal types with the exception of a 1% increase in the number of reported rabid cats. Two cases of rabies involving humans were reported from Louisiana and Wisconsin in 2010. Louisiana reported an imported human rabies case involving a 19-year-old male migrant farm worker who had a history of a vampire bat (Desmodus rotundus) bite received while in Mexico. This represents the first human rabies case reported in the United States confirmed to have been caused by a vampire bat rabies virus variant. Wisconsin reported a human rabies case involving a 70-year-old male that was confirmed to have been caused by a rabies virus variant associated with tri-colored bats (Perimyotis subflavus). PMID:21916759

Rabies surveillance in the United States during 2010.

PubMed

Blanton, Jesse D; Palmer, Dustyn; Dyer, Jessie; Rupprecht, Charles E

2011-09-15

During 2010, 48 states and Puerto Rico reported 6,154 rabid animals and 2 human rabies cases to the CDC, representing an 8% decrease from the 6,690 rabid animals and 4 human cases reported in 2009. Hawaii and Mississippi did not report any laboratory-confirmed rabid animals during 2010. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,246 raccoons (36.5%), 1,448 skunks (23.5%), 1,430 bats (23.2%), 429 foxes (6.9%), 303 cats (4.9%), 71 cattle (1.1 %), and 69 dogs (1.1 %). Compared with 2009, number of reported rabid animals decreased across all animal types with the exception of a 1 % increase in the number of reported rabid cats. Two cases of rabies involving humans were reported from Louisiana and Wisconsin in 2010. Louisiana reported an imported human rabies case involving a 19-year-old male migrant farm worker who had a history of a vampire bat (Desmodus rotundus) bite received while in Mexico. This represents the first human rabies case reported in the United States confirmed to have been caused by a vampire bat rabies virus variant. Wisconsin reported a human rabies case involving a 70-year-old male that was confirmed to have been caused by a rabies virus variant associated with tri-colored bats (Perimyotis subflavus).

Cost-effectiveness of dog rabies vaccination programs in East Africa

PubMed Central

Borse, Rebekah H.; Atkins, Charisma Y.; Gambhir, Manoj; Undurraga, Eduardo A.; Blanton, Jesse D.; Kahn, Emily B.; Dyer, Jessie L.; Rupprecht, Charles E.

2018-01-01

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

Rabies in the face of the 21st century.

PubMed

Koprowski, H

2009-08-01

Reference to an ancient Hindu picture of a snarling dog may be a convincing enough proof to consider the fact that rabies has been known in the world for the past 50 centuries. Prior to the monumental observation about rabies of Fracastoro in the 16th century, facts and fantasies were intermingled in the study of rabies. In the realm of fantasy, consider the statement of Aristotle (otherwise a great philosopher) that only animals and not humans die of rabies. It took 19 centuries before Fracastoro finally established that infection with rabies is lethal for all warm-blooded beings including humans. The new era of rabies dates from the time of Galtier who isolated the virus and Pasteur who was able to create a somewhat attenuated strain of virus fixe which became the tool of laboratory studies for many decades after Pasteur. During the last 50 years of the past century, our knowledge of rabies increased by leaps and bounds. First of all, using molecular biology as a tool, it was possible to ‘take the virus apart’, so to speak and describe and analyse all of its components. Establishment of multivariability among viruses as ‘de la rue’ permitted not only a construct of a genetic linkage among lyssa family but also solved some puzzles of pathogenesis of rabies which defied solution when all work concentrated on one laboratory strain of the virus. As an example, we know much more now about the genetic background regulating virulence of the virus. In addition, it is now possible to use rabies as a vector of biological materials such as vaccines or sera. There is no progress in the treatment of the uniformly lethal disease. Perhaps, optimistically speaking, the 21st century will bring us a glimmer of hope for the successful treatment of human rabies.

A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

PubMed Central

Konduru, Krishnamurthy; Virata-Theimer, Maria Luisa; Yu, Mei-ying W; Kaplan, Gerardo G

2008-01-01

Background Hepatitis A virus (HAV), the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA) based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd) resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG) preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the endpoint dilution ELISA

Rabies Post-Exposure Prophylaxis in the Philippines: Health Status of Patients Having Received Purified Equine F(ab')2 Fragment Rabies Immunoglobulin (Favirab)

PubMed Central

Quiambao, Beatriz P.; DyTioco, Hazel Z.; Dizon, Ruby M.; Crisostomo, Marilyn E.; Laot, Thelma M.; Teuwen, Dirk E.

2008-01-01

Background Recommended treatment for severe rabies exposure in unvaccinated individuals includes wound cleaning, administration of rabies immunoglobulins (RIG), and rabies vaccination. We conducted a survey of rabies treatment outcomes in the Philippines. Methods This was a case series involving 7,660 patients (4 months to 98 years of age) given purified equine RIG (pERIG) at the Research Institute for Tropical Medicine (Muntinlupa, Philippines) from July 2003 to August 2004 following Category II or III exposures. Data on local and systemic adverse reactions (AR) within 28 days and biting animal status were recorded; outcome data were obtained by telephone or home visit 6–29 months post-exposure. Results Follow-up data were collected for 6,464 patients. Of 151 patients with laboratory-confirmed rabies exposure, 143 were in good health 6–48 months later, seven could not be contacted, and one 4-year-old girl died. Of 16 deaths in total, 14 were unrelated to rabies exposure or treatment. Two deaths were considered PEP failures: the 4-year old girl, who had multiple deep lacerated wounds from a rabid dog of the nape, neck, and shoulders requiring suturing on the day of exposure, and an 8-year-old boy who only received rabies PEP on the day of exposure. Conclusions This extensive review of outcomes in persons with Category III exposure shows the recommended treatment schedule at RITM using pERIG is well tolerated, while survival of 143 laboratory-confirmed rabies exposures confirms the intervention efficacy. Two PEP intervention failures demonstrate that sustained education and training is essential in rabies management. PMID:18509475

Posttransplant Immune Activation

PubMed Central

Bamoulid, Jamal; Crepin, Thomas; Rebibou, Jean-Michel; Courivaud, Cecile; Saas, Philippe

2017-01-01

Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8+ T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8+ T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence. PMID:29113470

How Can You Prevent Rabies in Animals?

MedlinePlus

... Dogs Reported in the United States, 2008 Rabid Cattle Reported in the United States, 2008 Terrestrial Rabies ... Texas December 23, 2005: Rabies in a Dairy Cow; Oklahoma November 15, 2004: Clinician Information Line July ...

Anti-thymocyte globulins in kidney transplantation: focus on current indications and long-term immunological side effects.

PubMed

Bamoulid, Jamal; Staeck, Oliver; Crépin, Thomas; Halleck, Fabian; Saas, Philippe; Brakemeier, Susanne; Ducloux, Didier; Budde, Klemens

2017-10-01

Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

GENETIC CHARACTERISATION OF RABIES VIRUS ISOLATES IN BOSNIA AND HERZEGOVINA

PubMed Central

Velić, Ramiz; Bajrović, Tarik; Zvizdić, Šukrija; Velić, Lejla; Hamzić, Sadeta

2008-01-01

Serotyping of five rabies virus isolates with monoclonal anti-nucleoprotein antibodies for classical rabies virus and rabies-related viruses and phylogenetic relationships among sequences indicate that viruses circulating in population of animals in Bosnia and Herzegovina belong to the sero-genotype 1 of classical rabies virus. Phylogenetic relationships among sequences of our viruses have shown the presence of two phylogenetic lines, one which is present in the northwestern part and other which is present in the northeastern part of the country. Our viruses are closely related to Westeuropean isolates of rabies virus. PMID:18816256

Rabies surveillance in the United States during 2008.

PubMed

Blanton, Jesse D; Robertson, Kis; Palmer, Dustyn; Rupprecht, Charles E

2009-09-15

During 2008, 49 states and Puerto Rico reported 6,841 cases of rabies in animals and 2 cases in humans to the CDC, representing a 3.1% decrease from the 7,060 cases in animals and 1 case in a human reported in 2007. Approximately 93% of the cases were in wildlife, and 7% were in domestic animals. Relative contributions by the major animal groups were as follows: 2,389 (34.9%) raccoons, 1,806 (26.4%) bats, 1,589 (23.2%) skunks, 454 (6.6%) foxes, 294 (4.3%) cats, 75 (1.1%) dogs, and 59 (0.9%) cattle. Compared with numbers of cases reported in 2007, numbers of cases reported in 2008 increased among cats, cattle, and skunks and decreased among dogs, raccoons, bats, and foxes. Numbers of rabid raccoons reported during 2008 decreased in 11 of the 20 eastern states where raccoon rabies was enzootic; overall number of rabid raccoons reported decreased by 8.6% during 2008, compared with 2007. On a national level, the number of rabies cases involving skunks increased by 7.7% during 2008, compared with the number reported in 2007; this was the first increase in the number of reported rabid skunks since 2006. The total number of cases of rabies reported nationally in foxes decreased 1.7% in 2008, compared with 2007. The 1,806 cases of rabies reported in bats represented a 6.7% decrease, compared with the number reported in 2007. One case of rabies in a dog imported from Iraq was reported at a quarantine station in New Jersey during 2008. Follow-up of potentially exposed animals in the same shipment did not reveal any secondary transmission. The United States remained free from dog-to-dog transmission of canine rabies virus variants. Total number of rabid dogs reported decreased 19.4% in 2008, compared with 2007. Two human rabies cases were reported from California and Missouri during 2008. The California case involved a recent immigrant from Mexico and was attributed to a newly identified rabies virus variant most likely associated with Mexican free-tailed bats. The case in

Rabies and African wild dogs in Kenya.

PubMed

Kat, P W; Alexander, K A; Smith, J S; Munson, L

1995-11-22

Three packs of African wild dogs (Lycaon pictus) ranging to the north of the Masai Mara National Reserve in southwestern Kenya were monitored from 1988 to 1990. During a six week period (August 2-September 14, 1989), 21 of 23 members of one of these packs died. Histological examination of two brain samples revealed eosinophilic intracytoplasmic inclusions (Negri bodies), supporting a diagnosis of rabies viral encephalitis. An additional brain sample tested positive for rabies with a fluorescent antibody test. Nucleotide sequence of the rabies viral N and G genes from isolates of four African wild dogs (including an individual from Tanzania) indicated that infection was with a viral variant common among domestic dogs in Kenya and Tanzania. A hypothesis linking African wild dog rabies deaths to researcher handling is evaluated and considered implausible.

Predicted Spatial Spread of Canine Rabies in Australia

PubMed Central

Fleming, Peter J. S.; Ward, Michael P.; Davis, Stephen A.

2017-01-01

Modelling disease dynamics is most useful when data are limited. We present a spatial transmission model for the spread of canine rabies in the currently rabies-free wild dog population of Australia. The introduction of a sub-clinically infected dog from Indonesia is a distinct possibility, as is the spillover infection of wild dogs. Ranges for parameters were estimated from the literature and expert opinion, or set to span an order of magnitude. Rabies was judged to have spread spatially if a new infectious case appeared 120 km from the index case. We found 21% of initial value settings resulted in canine rabies spreading 120km, and on doing so at a median speed of 67 km/year. Parameters governing dog movements and behaviour, around which there is a paucity of knowledge, explained most of the variance in model outcomes. Dog density, especially when interactions with other parameters were included, explained some of the variance in whether rabies spread 120km, but dog demography (mean lifespan and mean replacement period) had minimal impact. These results provide a clear research direction if Australia is to improve its preparedness for rabies. PMID:28114327

Recent data on the epidemiology and prophylaxis of human rabies in France.

PubMed

Sureau, P

1990-01-01

Rabies is an animal disease which is transmitted to man only by accident, most often through the bite (more rarely after scratches or licks of mucosa) of a rabid animal, domestic or wild. A good knowledge of the epizootiology of animal rabies is therefore necessary to establish, on solid grounds, the prophylaxis of human rabies. Inter-human transmission of rabies being an exceptional event which will be considered separately, the epidemiology of human rabies mainly studies the sources and circumstances of human exposure to rabid animals, which differ according to the epizootiology of animal rabies in a given country: either enzootic (or hyperenzootic) canine rabies, or enzootic selvatic rabies. It appears that the risk of human rabies is higher in the first situation for two reasons: (i) rabies viruses show an increased virulence due to numerous serial passages in dogs (viruses with short incubation period) and (ii) high frequency of dog-man contacts due to the high density of both populations.

MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

PubMed

Kip, E; Staal, J; Verstrepen, L; Tima, H G; Terryn, S; Romano, M; Lemeire, K; Suin, V; Hamouda, A; Kalai, M; Beyaert, R; Van Gucht, S

2018-04-15

MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1 -/- mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1 -/- mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1 -/- mice at 10 dpi compared to MALT1 +/+ infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1 +/+ mice. Moreover, MALT1 -/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain. IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular

A Case of Fatal Serotonin Syndrome-Like Human Rabies Caused by Tricolored Bat-Associated Rabies Virus.

PubMed

Regunath, Hariharan; Chinnakotla, Bhavana; Rojas-Moreno, Christian; Salzer, William; Hughes, Natalie J; Sangha, Harbaksh

2016-06-01

Human rabies is a fatal disease, transmitted by saliva of infected animals, and the diagnosis requires a high index of suspicion. Very few cases are reported annually in the United States. We present a case of human rabies without a clear exposure history that masqueraded as serotonin syndrome. © The American Society of Tropical Medicine and Hygiene.

THE DECADE OF THE RABiT (2005–15)

PubMed Central

Garty, G.; Turner, H. C.; Salerno, A.; Bertucci, A.; Zhang, J.; Chen, Y.; Dutta, A.; Sharma, P.; Bian, D.; Taveras, M.; Wang, H.; Bhatla, A.; Balajee, A.; Bigelow, A. W.; Repin, M.; Lyulko, O. V.; Simaan, N.; Yao, Y. L.; Brenner, D. J.

2016-01-01

The RABiT (Rapid Automated Biodosimetry Tool) is a dedicated Robotic platform for the automation of cytogenetics-based biodosimetry assays. The RABiT was developed to fulfill the critical requirement for triage following a mass radiological or nuclear event. Starting from well-characterized and accepted assays we developed a custom robotic platform to automate them. We present here a brief historical overview of the RABiT program at Columbia University from its inception in 2005 until the RABiT was dismantled at the end of 2015. The main focus of this paper is to demonstrate how the biological assays drove development of the custom robotic systems and in turn new advances in commercial robotic platforms inspired small modifications in the assays to allow replacing customized robotics with ‘off the shelf’ systems. Currently, a second-generation, RABiT II, system at Columbia University, consisting of a PerkinElmer cell::explorer, was programmed to perform the RABiT assays and is undergoing testing and optimization studies. PMID:27412510

Animal-associated exposure to rabies virus among travelers, 1997-2012.

PubMed

Gautret, Philippe; Harvey, Kira; Pandey, Prativa; Lim, Poh Lian; Leder, Karin; Piyaphanee, Watcharapong; Shaw, Marc; McDonald, Susan C; Schwartz, Eli; Esposito, Douglas H; Parola, Philippe

2015-04-01

Among travelers, rabies cases are rare, but animal bites are relatively common. To determine which travelers are at highest risk for rabies, we studied 2,697 travelers receiving care for animal-related exposures and requiring rabies postexposure prophylaxis at GeoSentinel clinics during 1997-2012. No specific demographic characteristics differentiated these travelers from other travelers seeking medical care, making it challenging to identify travelers who might benefit from reinforced pretravel rabies prevention counseling. Median travel duration was short for these travelers: 15 days for those seeking care after completion of travel and 20 days for those seeking care during travel. This finding contradicts the view that preexposure rabies vaccine recommendations should be partly based on longer travel durations. Over half of exposures occurred in Thailand, Indonesia, Nepal, China, and India. International travelers to rabies-endemic regions, particularly Asia, should be informed about potential rabies exposure and benefits of pretravel vaccination, regardless of demographics or length of stay.

Evaluation of a rapid immunodiagnostic test kit for rabies virus.

PubMed

Kang, BoKyu; Oh, JinSik; Lee, ChulSeung; Park, Bong-Kyun; Park, YoungNam; Hong, KyungSoo; Lee, KyungGi; Cho, ByungKi; Song, DaeSub

2007-10-01

A rapid immunodiagnostic test kit for rabies virus detection was evaluated using 51 clinical samples and 4 isolates of rabies virus. The quick detection of rabies virus under field conditions may be helpful in determining if post-exposure prophylaxis is needed, thereby avoiding unnecessary treatments, as well as undue economic burden. There are several widely used diagnostic methods for rabies, including fluorescent antibody tests, reverse transcription polymerase chain reaction, and electron microscopy; however, these methods include time-consuming, intricate, and costly procedures. The rapid immunodiagnostic test was able to detect rabies virus in clinical samples, including brain tissue and saliva, in addition to 10(3.2) 50% lethal dose (LD(50))/mL cell-adapted rabies virus. The assay was not cross-reactive with non-rabies virus microbes. When the performance of the rapid immunodiagnostic test was compared to a fluorescent antibody test, the rapid immunodiagnostic test had a sensitivity of 91.7% and specificity of 100% (95.8% CI).

21 CFR 862.1330 - Globulin test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862... other disorders of blood globulins. (b) Classification. Class I (general controls). The device is exempt...

Rabies surveillance in the United States during 2009.

PubMed

Blanton, Jesse D; Palmer, Dustyn; Rupprecht, Charles E

2010-09-15

During 2009, 49 states and Puerto Rico reported 6,690 rabid animals and 4 human rabies cases to the CDC, representing a 2.2% decrease from the 6,841 rabid animals and 2 human cases reported in 2008. Approximately 92% of reported rabid animals were wildlife. Relative contributions by the major animal groups were as follows: 2,327 (34.8%) raccoons, 1,625 (24.3%) bats, 1,603 (24.0%) skunks, 504 (75%) foxes, 300 (4.5%) cats, 81 (1.2%) dogs, and 74 (1.1%) cattle. Compared with 2008, numbers of rabid raccoons and bats that were reported decreased, whereas numbers of rabid skunks, foxes, cats, cattle, dogs, and horses that were reported increased. Fewer rabid raccoons, compared with 2008, were reported by 12 of the 20 eastern states where raccoon rabies is enzootic, and number of rabid raccoons decreased by 2.6% overall nationally. Despite a 10% decrease in the number of rabid bats that were reported and a decrease in the total number of bats submitted for testing, bats were the second most commonly submitted animal, behind cats, during 2009. The number of rabid skunks that were reported increased by 0.9% overall. The proportion of rabid skunks in which infection was attributed to the raccoon rabies virus variant decreased from 473% in 2008 to 40.9% in 2009, resulting in a 12.7% increase in the number of rabid skunks infected with a skunk rabies virus variant. The number of rabid foxes increased 11.0% overall from the previous year. Four cases of rabies involving humans were reported from Texas, Indiana, Virginia, and Michigan. The Texas case represented the first presumptive abortive human rabies case, with the patient recovering after the onset of symptoms without intensive care. The Indiana and Michigan cases were associated with bat rabies virus variants. The human rabies case in Virginia was associated with a canine rabies virus variant acquired during the patient's travel to India.

Advancements in web-database applications for rabies surveillance.

PubMed

Rees, Erin E; Gendron, Bruno; Lelièvre, Frédérick; Coté, Nathalie; Bélanger, Denise

2011-08-02

Protection of public health from rabies is informed by the analysis of surveillance data from human and animal populations. In Canada, public health, agricultural and wildlife agencies at the provincial and federal level are responsible for rabies disease control, and this has led to multiple agency-specific data repositories. Aggregation of agency-specific data into one database application would enable more comprehensive data analyses and effective communication among participating agencies. In Québec, RageDB was developed to house surveillance data for the raccoon rabies variant, representing the next generation in web-based database applications that provide a key resource for the protection of public health. RageDB incorporates data from, and grants access to, all agencies responsible for the surveillance of raccoon rabies in Québec. Technological advancements of RageDB to rabies surveillance databases include (1) automatic integration of multi-agency data and diagnostic results on a daily basis; (2) a web-based data editing interface that enables authorized users to add, edit and extract data; and (3) an interactive dashboard to help visualize data simply and efficiently, in table, chart, and cartographic formats. Furthermore, RageDB stores data from citizens who voluntarily report sightings of rabies suspect animals. We also discuss how sightings data can indicate public perception to the risk of racoon rabies and thus aid in directing the allocation of disease control resources for protecting public health. RageDB provides an example in the evolution of spatio-temporal database applications for the storage, analysis and communication of disease surveillance data. The database was fast and inexpensive to develop by using open-source technologies, simple and efficient design strategies, and shared web hosting. The database increases communication among agencies collaborating to protect human health from raccoon rabies. Furthermore, health agencies have real

Advancements in web-database applications for rabies surveillance

PubMed Central

2011-01-01

Background Protection of public health from rabies is informed by the analysis of surveillance data from human and animal populations. In Canada, public health, agricultural and wildlife agencies at the provincial and federal level are responsible for rabies disease control, and this has led to multiple agency-specific data repositories. Aggregation of agency-specific data into one database application would enable more comprehensive data analyses and effective communication among participating agencies. In Québec, RageDB was developed to house surveillance data for the raccoon rabies variant, representing the next generation in web-based database applications that provide a key resource for the protection of public health. Results RageDB incorporates data from, and grants access to, all agencies responsible for the surveillance of raccoon rabies in Québec. Technological advancements of RageDB to rabies surveillance databases include 1) automatic integration of multi-agency data and diagnostic results on a daily basis; 2) a web-based data editing interface that enables authorized users to add, edit and extract data; and 3) an interactive dashboard to help visualize data simply and efficiently, in table, chart, and cartographic formats. Furthermore, RageDB stores data from citizens who voluntarily report sightings of rabies suspect animals. We also discuss how sightings data can indicate public perception to the risk of racoon rabies and thus aid in directing the allocation of disease control resources for protecting public health. Conclusions RageDB provides an example in the evolution of spatio-temporal database applications for the storage, analysis and communication of disease surveillance data. The database was fast and inexpensive to develop by using open-source technologies, simple and efficient design strategies, and shared web hosting. The database increases communication among agencies collaborating to protect human health from raccoon rabies

Survey of bat populations from Mexico and Paraguay for rabies.

PubMed

Sheeler-Gordon, L L; Smith, J S

2001-07-01

A mammalian survey was conducted in Mexico (October 1994-January 1996) and in Paraguay (August 1996-March 1997); a complete specimen was collected for each bat in the survey, including primary voucher specimen, ectoparasites, karyotype, and various frozen tissues. The surveys combined provided 937 brain samples (65 bat species) for rabies diagnosis. One male Lasiurus ega, collected in Paraguay, tested positive for the rabies virus (overall prevalence rate of 0.1%). Nucleotide sequence from a 300 bp region of the rabies nucleoprotein gene was compared with sequence obtained from representative rabies virus samples in the repository at the Centers for Disease Control and Prevention (Atlanta, Georgia, USA). Rabies virus extracted from the brain material of L. ega differed by only one nucleotide from a 300 bp consensus sequence (>99% homology) derived from samples for the variant of rabies virus transmitted by Lasiurus cinereus. Lasiurus ego differed by approximately 15% for the variant transmitted by Desmodus rotundus. Phylogenetic analysis found no evidence to suggest L. ego is a reservoir for rabies antigenic variant 6. The most likely explanation for rabies in L. ega was infection following contact with a rabid L. cinereus.

Multihormonal induction of hepatic α2u-globulin mRNA as measured by hybridization to complementary DNA

PubMed Central

Kurtz, David T.; Feigelson, Philip

1977-01-01

A procedure is presented for the preparation of a 3H-labeled complementary DNA (cDNA) specific for the mRNA coding for α2u-globulin, a male rat liver protein under multihormonal control that represents approximately 1% of hepatic protein synthesis. Rat liver polysomes are incubated with monospecific rabbit antiserum to α2u-globulin, which binds to the nascent α2u-globulin chains on the polysomes. These antibody-polysome complexes are then adsorbed to goat antiserum to rabbit IgG that is covalently linked to p-aminobenzylcellulose. mRNA preparations are thus obtained that contain 30-40% α2u-globulin mRNA. A labeled cDNA is made to this α2u-globulin-enriched mRNA preparation by using RNA-dependent DNA polymerase (reverse transcriptase). To remove the non-α2u-globulin sequences, this cDNA preparation is hybridized to an RNA concentration × incubation time (R0t) of 1000 mol of ribonucleotide per liter × sec with female rat liver mRNA, which, though it shares the vast majority of mRNA sequences with male liver, contains no α2u-globulin mRNA sequences. The cDNA remaining single-stranded is isolated by hydroxylapatite chromatography and is shown to be specific for α2u-globulin mRNA by several criteria. Good correlation was found in all endocrine states studied between the hepatic level of α2u-globulin, the level of functional α2u-globulin mRNA as assayed in a wheat germ cell-free translational system, and the level of α2u-globulin mRNA sequences as measured by hybridization to the α2u-globulin cDNA. Thus, the hormonal control of hepatic α2u-globulin synthesis by sex steroids and thyroid hormone occurs through modulation of the cellular level of α2u-globulin mRNA sequences, presumably by hormonal control of transcriptive synthesis. PMID:73184

[The fight against rabies in Africa: from recognition to action].

PubMed

Dodet, B; Adjogoua, E V; Aguemon, A-R; Baba, B A; Bara Adda, S; Boumandouki, P; Bourhy, H; Brahimi, M; Briggs, D; Diallo, M K; Diarra, L; Diop, B; Diop, S A G; Fesriry, B; Gosseye, S; Kharmachi, H; Le Roux, K; Nakoune Yandoko, E; Nel, L; Ngome, J-M; Nzengue, E; Ramahefalalao, E F; Ratsitorahina, M; Rich, H; Simpore, L; Soufi, A; Tejiokem, M C; Thiombiano, R; Tiembre, I; Traore, A K; Wateba, M I; Yahaye, H; Zaouia, I

2010-02-01

As a follow-up to the first AfroREB (Africa Rabies Expert Bureau) meeting, held in Grand-Bassam (Côte-d'Ivoire) in March 2008, African rabies experts of the Afro-REB network met a second time to complete the evaluation of the rabies situation in Africa and define specific action plans. About forty French speaking rabies specialists from Northern, Western and Central Africa and Madagascar met in Dakar (Senegal), from March 16th to 19th, 2009. With the participation of delegates from Tunisia, who joined the AfroREB network this year, 15 French speaking African countries were represented. Experts from the Institut Pasteur in Paris, the Alliance for Rabies Control, and the Southern and Eastern African Rabies Group (SEARG, a network of rabies experts from 19 English speaking Southern and Eastern African countries) were in attendance, to participate in the discussion and share their experiences. AfroREB members documented 146 known human rabies cases in all represented countries combined for 2008, for a total population of 209.3 million, or an incidence of 0.07 cases per 100,000 people. Even admitting that the experts do not have access to all reported cases, this is far from the WHO estimation of 2 rabies deaths per 100,000 people in urban areas and 3.6 per 100,000 in rural Africa. It was unanimously agreed that the priority is to break the vicious cycle of indifference and lack of information which is the main barrier to human rabies prevention.

Vampire Bat Rabies: Ecology, Epidemiology and Control

PubMed Central

Johnson, Nicholas; Aréchiga-Ceballos, Nidia; Aguilar-Setien, Alvaro

2014-01-01

Extensive surveillance in bat populations in response to recent emerging diseases has revealed that this group of mammals acts as a reservoir for a large range of viruses. However, the oldest known association between a zoonotic virus and a bat is that between rabies virus and the vampire bat. Vampire bats are only found in Latin America and their unique method of obtaining nutrition, blood-feeding or haematophagy, has only evolved in the New World. The adaptations that enable blood-feeding also make the vampire bat highly effective at transmitting rabies virus. Whether the virus was present in pre-Columbian America or was introduced is much disputed, however, the introduction of Old World livestock and associated landscape modification, which continues to the present day, has enabled vampire bat populations to increase. This in turn has provided the conditions for rabies re-emergence to threaten both livestock and human populations as vampire bats target large mammals. This review considers the ecology of the vampire bat that make it such an efficient vector for rabies, the current status of vampire-transmitted rabies and the future prospects for spread by this virus and its control. PMID:24784570

PATHOLOGY AND MOLECULAR DETECTION OF RABIES VIRUS IN FERRET BADGERS ASSOCIATED WITH A RABIES OUTBREAK IN TAIWAN.

PubMed

Chiou, Hue-Ying; Jeng, Chian-Ren; Wang, Hurng-Yi; Inoue, Satoshi; Chan, Fang-Tse; Liao, Jiunn-Wang; Chiou, Ming-Tang; Pang, Victor Fei

2016-01-01

Until Rabies virus (RABV) infection in Taiwan ferret badgers (TWFB; Melogale moschata subaurantiaca) was diagnosed in mid-June 2013, Taiwan had been considered rabies free for >50 yr. Although rabies has also been reported in ferret badgers in China, the pathologic changes and distribution of viral antigens of ferret badger-associated rabies have not been described. We performed a comprehensive pathologic study and molecular detection of rabies virus in three necropsied rabid TWFBs and evaluated archival paraffin-embedded tissue blocks of six other TWFBs necropsied during 2004 and 2012. As in other RABV-infected species, the characteristic pathologic changes in TWFBs were nonsuppurative meningoencephalomyelitis, ganglionitis, and the formation of typical intracytoplasmic Negri bodies, with the brain stem most affected. There was also variable spongiform degeneration, primarily in the perikaryon of neurons and neuropil, in the cerebral cortex, thalamus, and brain stem. In nonnervous system tissues, representative lesions included adrenal necrosis and lymphocytic interstitial sialadenitis. Immunohistochemical staining and fluorescent antibody test demonstrated viral antigens in the perikaryon of the neurons and axonal or dendritic processes throughout the nervous tissue and in the macrophages in various tissues. Similar to raccoons (Procyon lotor) and skunks (Mephitidae), the nervous tissue of rabid TWFBs displayed widely dispersed lesions, RABV antigens, and large numbers of Negri bodies. We traced the earliest rabid TWFB case back to 2004.

Human Rabies - Puerto Rico, 2015.

PubMed

Styczynski, Ashley; Tran, Cuc; Dirlikov, Emilio; Zapata, María Ramos; Ryff, Kyle; Petersen, Brett; Sanchez, Anibal Cruz; Mayshack, Marrielle; Martinez, Laura Castro; Condori, Rene; Ellison, James; Orciari, Lillian; Yager, Pamela; Peña, Rafael González; Sanabria, Dario; Velázquez, Julio Cádiz; Thomas, Dana; García, Brenda Rivera

2017-01-06

On December 1, 2015, the Puerto Rico Department of Health (PRDH) was notified by a local hospital of a suspected human rabies case. The previous evening, a Puerto Rican man aged 54 years arrived at the emergency department with fever, difficulty swallowing, hand paresthesia, cough, and chest tightness. The next morning the patient left against medical advice but returned to the emergency department in the afternoon with worsening symptoms. The patient's wife reported that he had been bitten by a mongoose during the first week of October, but had not sought care for the bite. While being transferred to the intensive care unit, the patient went into cardiac arrest and died. On December 3, rabies was confirmed from specimens collected during autopsy. PRDH conducted an initial rapid risk assessment, and five family members were started on rabies postexposure prophylaxis (PEP).

Rabies surveillance in the United States during 2015.

PubMed

Birhane, Meseret G; Cleaton, Julie M; Monroe, Ben P; Wadhwa, Ashutosh; Orciari, Lillian A; Yager, Pamela; Blanton, Jesse; Velasco-Villa, Andres; Petersen, Brett W; Wallace, Ryan M

2017-05-15

OBJECTIVE To describe rabies and rabies-related events occurring during 2015 in the United States. DESIGN Observational study based on passive surveillance data. ANIMALS All animals submitted for rabies testing in the United States during 2015. PROCEDURES State and territorial public health programs provided data on animals submitted for rabies testing in 2015. Data were analyzed temporally and geographically to assess trends in domestic and sylvatic animal rabies cases. RESULTS During 2015, 50 states and Puerto Rico reported 5,508 rabid animals to the CDC, representing an 8.7% decrease from the 6,033 rabid animals reported in 2014. Of the 5,508 cases of animal rabies, 5,088 (92.4%) involved wildlife. Relative contributions by the major animal groups were as follows: 1,704 (30.9%) bats, 1,619 (29.4%) raccoons, 1,365 (24.8%) skunks, 325 (5.9%) foxes, 244 (4.4%) cats, 85 (1.5%) cattle, and 67 (1.2%) dogs. There was a 4.1% decrease in the number of samples submitted for testing in 2015, compared with the number submitted in 2014. Three human rabies deaths were reported in 2015, compared with only 1 in 2014. A 65-year-old man in Massachusetts was bitten by a rabid dog while abroad. A 77-year-old woman in Wyoming had contact with a bat. A 54-year-old man in Puerto Rico was bitten by a mongoose. The only connection among these 3 cases was that none received postexposure prophylaxis. CONCLUSIONS AND CLINICAL RELEVANCE Laboratory testing of animals suspected to be rabid remains a critical public health function and continues to be a cost-effective method to directly influence human rabies postexposure prophylaxis recommendations. (J Am Vet Med Assoc 2017;250:1117-1130).

Estimating the Global Burden of Endemic Canine Rabies

PubMed Central

Hampson, Katie; Coudeville, Laurent; Lembo, Tiziana; Sambo, Maganga; Kieffer, Alexia; Attlan, Michaël; Barrat, Jacques; Blanton, Jesse D.; Briggs, Deborah J.; Cleaveland, Sarah; Costa, Peter; Freuling, Conrad M.; Hiby, Elly; Knopf, Lea; Leanes, Fernando; Meslin, François-Xavier; Metlin, Artem; Miranda, Mary Elizabeth; Müller, Thomas; Nel, Louis H.; Recuenco, Sergio; Rupprecht, Charles E.; Schumacher, Carolin; Taylor, Louise; Vigilato, Marco Antonio Natal; Zinsstag, Jakob; Dushoff, Jonathan

2015-01-01

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

Experimental rabies in a great horned owl.

PubMed

Jorgenson, R D; Gough, P M; Graham, D L

1976-07-01

A great horned owl (Bubo virginianus) was fed the carcass of an experimentally infected rabid skunk. The bird developed antibody titer to rabies, detected by passive haemagglutination, 27 days after oral inoculation by ingestion. The owl suppressed the infection until corticosteroid administration, after which a maximum antibody titer was attained. Evidence of active rabies viral infection was seen by fluorescent antibody staining of oral swabs, corneal impression smears and histologic tissue smears, by suckling mouse inoculation of oral swab washings, and by transmission electron microcopy. No clinical signs of rabies virus infection were observed.

RDIS: The Rabies Disease Information System.

PubMed

Dharmalingam, Baskeran; Jothi, Lydia

2015-01-01

Rabies is a deadly viral disease causing acute inflammation or encephalitis of the brain in human beings and other mammals. Therefore, it is of interest to collect information related to the disease from several sources including known literature databases for further analysis and interpretation. Hence, we describe the development of a database called the Rabies Disease Information System (RDIS) for this purpose. The online database describes the etiology, epidemiology, pathogenesis and pathology of the disease using diagrammatic representations. It provides information on several carriers of the rabies viruses like dog, bat, fox and civet, and their distributions around the world. Information related to the urban and sylvatic cycles of transmission of the virus is also made available. The database also contains information related to available diagnostic methods and vaccines for human and other animals. This information is of use to medical, veterinary and paramedical practitioners, students, researchers, pet owners, animal lovers, livestock handlers, travelers and many others. The database is available for free http://rabies.mscwbif.org/home.html.

Human Rabies - Wyoming and Utah, 2015.

PubMed

Harrist, Alexia; Styczynski, Ashley; Wynn, DonRaphael; Ansari, Safdar; Hopkin, Justin; Rosado-Santos, Harry; Baker, JoDee; Nakashima, Allyn; Atkinson, Annette; Spencer, Melanie; Dean, Debbie; Teachout, Leslie; Mayer, Jeanmarie; Condori, Rene E; Orciari, Lillian; Wadhwa, Ashutosh; Ellison, James; Niezgoda, Michael; Petersen, Brett; Wallace, Ryan; Musgrave, Karl

2016-06-03

In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk.

Economic evaluation of an oral rabies vaccination program for control of a domestic dog-coyote rabies epizootic: 1995-2006.

PubMed

Shwiff, Stephanie A; Kirkpatrick, Katy N; Sterner, Ray T

2008-12-01

To conduct a benefit-cost analysis of the results of the domestic dog and coyote (DDC) oral rabies vaccine (ORV) program in Texas from 1995 through 2006 by use of fiscal records and relevant public health data. Retrospective benefit-cost analysis. Procedures-Pertinent economic data were collected in 20 counties of south Texas affected by a DDC-variant rabies epizootic. The costs and benefits afforded by a DDC ORV program were then calculated. Costs were the total expenditures of the ORV program. Benefits were the savings associated with the number of potentially prevented human postexposure prophylaxis (PEP) treatments and animal rabies tests for the DDC-variant rabies virus in the epizootic area and an area of potential disease expansion. Total estimated benefits of the program approximately ranged from $89 million to $346 million, with total program costs of $26,358,221 for the study period. The estimated savings (ie, damages avoided) from extrapolated numbers of PEP treatments and animal rabies tests yielded benefit-cost ratios that ranged from 3.38 to 13.12 for various frequen-cies of PEP and animal testing. In Texas, the use of ORV stopped the northward spread and led to the progressive elimination of the DDC variant of rabies in coyotes (Canis latrans). The decision to implement an ORV program was cost-efficient, although many unknowns were involved in the original decision, and key economic variables were identified for consideration in future planning of ORV programs.

Enhanced Efficacy of Cidofovir Combined with Vaccinia Immune Globulin in Treating Progressive Cutaneous Vaccinia Virus Infections in Immunosuppressed Hairless Mice

PubMed Central

Dagley, Ashley; Downs, Brittney; Hagloch, Joseph; Tarbet, E. Bart

2014-01-01

The treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so sparing the use of VIG during treatment is an important objective. VIG sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV combined with VIG to determine the effective treatments that delayed the time to death, reduced cutaneous lesion severity, and/or decreased tissue viral titers. SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and VIG) were initiated 2 days postinfection and were given every 3 to 4 days through day 11. The efficacy assessment included survival rate, cutaneous lesion severity, and viral titers. Delays in the time to death and the reduction in lesion severity occurred in the following order of efficacy: triple therapy had greater efficacy than double combinations (CDV plus VIG or topical plus parenteral CDV), which had greater efficacy than VIG alone. Parenteral administration of CDV or VIG was necessary to suppress virus titers in internal organs (liver, lung, and spleen). The skin viral titers were significantly reduced by triple therapy only. The greatest efficacy was achieved by triple therapy. In humans, this regimen should translate to a faster cure rate, thus sparing the amount of VIG used for treatment. PMID:25385098

Human rabies: still a neglected preventable disease in Nigeria.

PubMed

Eke, C B; Omotowo, I B; Ukoha, O M; Ibe, B C

2015-01-01

Adequate surveillance and monitoring of dog bite incidents are veritable tools in the determination of the epidemiology of human rabies infections. There is a paucity of data with regards to rabies in Nigeria. Hence, this study was aimed at describing the pattern and outcomes of dog bites and rabies infections among patients presenting to University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. This was a 10-year (January 1, 2004 to December 31, 2013) observational retrospective study. Case definition of rabies was based on ICD 10 criteria, while relevant clinical data were retrieved from individual folders of registered victims using a semi-structured questionnaire. Data were analyzed using SPSS version 17.0 while the level of statistical significance was set at P < 0.05. A total of 149 cases of dog bites were reported during the period under review, of which 6 (4.0%) had confirmed rabies. Ninety-six (64.4%) cases presented more than 24 h after the bites. Majority of the offending dogs were stray dogs 86 (57.7%), which attacked their victims unprovoked, in 54.6% of cases. Furthermore, most of the bites were from dogs with unknown history of rabies vaccination 72 (52.3%), while the case fatality rate was 100%. All the cases of rabies reported were as a result of bites from stray dogs with unknown history of rabies vaccinations, and the outcome was 100% fatality in all cases. Efforts should be made to create and strengthen awareness campaigns on control of rabies infections through responsible dog ownership including their regular vaccinations as well as provision and use of prompt postexposure prophylaxis in human cases of dog bites at all levels of health care.

Response to a rabies epidemic, Bali, Indonesia, 2008-2011.

PubMed

Putra, Anak Agung Gde; Hampson, Katie; Girardi, Janice; Hiby, Elly; Knobel, Darryn; Mardiana, I Wayan; Townsend, Sunny; Scott-Orr, Helen

2013-04-01

Emergency vaccinations and culling failed to contain an outbreak of rabies in Bali, Indonesia, during 2008-2009. Subsequent island-wide mass vaccination (reaching 70% coverage, >200,000 dogs) led to substantial declines in rabies incidence and spread. However, the incidence of dog bites remains high, and repeat campaigns are necessary to eliminate rabies in Bali.

Engineering of a recombinant trivalent single-chain variable fragment antibody directed against rabies virus glycoprotein G with improved neutralizing potency.

PubMed

Turki, Imène; Hammami, Akil; Kharmachi, Habib; Mousli, Mohamed

2014-02-01

Human and equine rabies immunoglobulins are currently available for passive immunization against rabies. However, these are hampered by the limited supply and some drawbacks. Advances in antibody engineering have led to overcome issues of clinical applications and to improve the protective efficacy. In the present study, we report the generation of a trivalent single-chain Fv (scFv50AD1-Fd), that recognizes the rabies virus glycoprotein, genetically fused to the trimerization domain of the bacteriophage T4 fibritin, termed 'foldon' (Fd). scFv50AD1-Fd was expressed as soluble recombinant protein in bacterial periplasmic space and purified through affinity chromatography. The molecular integrity and stability were analyzed by polyacrylamide gradient-gel electrophoresis, size-exclusion chromatography and incubation in human sera. The antigen-binding properties of the trimeric scFv were analyzed by direct and competitive-ELISA. Its apparent affinity constant was estimated at 1.4 ± 0.25 × 10(9)M(-1) and was 75-fold higher than its monovalent scFv (1.9 ± 0.68 × 10(7)M(-1)). The scFv50AD1-Fd neutralized rabies virus in a standard in vitro and in vivo neutralization assay. We showed a high neutralization activity up to 75-fold compared with monovalent format and the WHO standard serum. The gain in avidity resulting from multivalency along with an improved biological activity makes the trivalent scFv50AD1-Fd construct an important reagent for rabies protection. The antibody engineering approach presented here may serve as a strategy for designing a new generation of anti-rabies for passive immunotherapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human Rabies in the WHO Southeast Asia Region: Forward Steps for Elimination

PubMed Central

Gongal, Gyanendra; Wright, Alice E.

2011-01-01

There are eleven Member States in the WHO southeast Asia region (Bangladesh, Bhutan, Democratic People's Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, Timor-Leste) of which eight are endemic for rabies. More than 1.4 billion people in the Region are at risk of rabies infection, and approximately 45% of worldwide rabies deaths occur in Asia. Dog bites account for 96% of human rabies cases. Progress in preventing human rabies through control of the disease in dogs has been slow due to various factors. Innovative control tools and techniques have been developed and standardized in recent years. The introduction of cost-effective intradermal rabies vaccination regimens in Asian countries has increased the availability and affordability of postexposure prophylaxis. Elimination of rabies is not possible without regional and intersectoral cooperation. Considering the importance of consolidating achievements in rabies control in Member countries, the WHO Regional Office for southeast Asia has developed a regional strategy for elimination of human rabies transmitted by dogs in the Region. They have committed to provide technical leadership, to advocate national health authorities to develop major stakeholder consensus for a comprehensive rabies elimination programme, and to implement national strategies for elimination of human rabies. PMID:21991437

Molecular epidemiology of rabies in Southern People's Republic of China.

PubMed

Tao, Xiao Yan; Tang, Qing; Li, Hao; Mo, Zhao Jun; Zhang, Hong; Wang, Ding Ming; Zhang, Qiang; Song, Miao; Velasco-Villa, Andres; Wu, Xianfu; Rupprecht, Charles E; Liang, Guo-Dong

2009-08-01

In recent years, the number of human rabies cases in the People's Republic of China has increased during severe epidemics in 3 southern provinces (Guizhou, Guangxi, and Hunan). To analyze the causes of the high incidence of human rabies in this region, during 2005-2007, we collected 2,887 brain specimens from apparently healthy domestic dogs used for meat consumption in restaurants, 4 specimens from suspected rabid dogs, and 3 from humans with rabies in the 3 provinces. Partial nucleoprotein gene sequences were obtained from rabies-positive specimens. Phylogenetic relationships and distribution of viruses were determined. We infer that the spread of rabies viruses from high-incidence regions, particularly by long-distance movement or transprovincial translocation of dogs caused by human-related activities, may be 1 cause of the recent massive human rabies epidemics in southern China.

Comparison of G protein sequences of South African street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.

PubMed

Seo, Wonhyo; Servat, Alexandre; Cliquet, Florence; Akinbowale, Jenkins; Prehaud, Christophe; Lafon, Monique; Sabeta, Claude

Rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. In South Africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. In this study, pathogenicity differences of South African canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. Comparison of glycoprotein gene sequences revealed amino acid differences that may underpin the observed pathogenicity differences. Cumulatively, our results suggest that the canid rabies virus may be more neurovirulent in mice than the mongoose rabies variant. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Serum IgG, IgM and slow alpha-globulin levels in carrageenan-treated rats.

PubMed Central

Fowler, E. F.; Thomson, A. W.

1979-01-01

Serum levels of IgM, IgG, slow alpha 1- and slow alpha 2-globulins were measured either by quantitative radial immunodiffusion (IgG) or immunoelectrophoresis (IgM and slow alpha-globulins) during the 3-week period after i.p. injection of 50 mg potassium carrageenan. There was a significant elevation in levels of IgM and slow alpha 1-globulin, maximal on Day 4 and returning to normal by Day 14. Slow alpha 2-globulin was detectable within 24 h, reached a peak at Day 2, and was no longer measurable in most rats by Day 14. Levels of IgG however, were unaffected by carrageenan injection. PMID:92333

Predictive spatial dynamics and strategic planning for raccoon rabies emergence in Ohio.

PubMed

Russell, Colin A; Smith, David L; Childs, James E; Real, Leslie A

2005-03-01

Rabies is an important public health concern in North America because of recent epidemics of a rabies virus variant associated with raccoons. The costs associated with surveillance, diagnostic testing, and post-exposure treatment of humans exposed to rabies have fostered coordinated efforts to control rabies spread by distributing an oral rabies vaccine to wild raccoons. Authorities have tried to contain westward expansion of the epidemic front of raccoon-associated rabies via a vaccine corridor established in counties of eastern Ohio, western Pennsylvania, and West Virginia. Although sporadic cases of rabies have been identified in Ohio since oral rabies vaccine distribution in 1998, the first evidence of a significant breach in this vaccine corridor was not detected until 2004 in Lake County, Ohio. Herein, we forecast the spatial spread of rabies in Ohio from this breach using a stochastic spatial model that was first developed for exploratory data analysis in Connecticut and next used to successfully hind-cast wave-front dynamics of rabies spread across New York. The projections, based on expansion from the Lake County breach, are strongly affected by the spread of rabies by rare, but unpredictable long-distance translocation of rabid raccoons; rabies may traverse central Ohio at a rate 2.5-fold greater than previously analyzed wildlife epidemics. Using prior estimates of the impact of local heterogeneities on wave-front propagation and of the time lag between surveillance-based detection of an initial rabies case to full-blown epidemic, specific regions within the state are identified for vaccine delivery and expanded surveillance effort.

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

PubMed

Lankau, E W; Cohen, N J; Jentes, E S; Adams, L E; Bell, T R; Blanton, J D; Buttke, D; Galland, G G; Maxted, A M; Tack, D M; Waterman, S H; Rupprecht, C E; Marano, N

2014-08-01

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. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus.

PubMed

Martina, Byron E E; Smreczak, Marcin; Orlowska, Anna; Marzec, Anna; Trebas, Pawel; Roose, Jouke M; Zmudzinski, Jan; Gerhauser, Ingo; Wohlsein, Peter; Baumgärtner, Wolfgang; Osterhaus, Albert D M E; Koraka, Penelope

2018-05-26

Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at day 4 post infection, containing anti-viral drugs and immune modulators in infected mice. Combination therapy resulted in significant increase in survival time (P < 0.05) and significantly lowers viral RNA in the brain and spinal cord (P < 0.05). Furthermore, treatment influenced markers of pyroptosis and apoptosis and early inflammatory response as measured by the levels of TNF-α. Morphological lesions were absent in rabies virus infected mice with few signs of inflammation. However, these were not significant between the different groups. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Rabies: risk, prognosis and prevention.

PubMed

Driver, Carolyn

While the UK was declared free from rabies over 100 years ago, the disease remains a significant cause of death in many other countries around the world. It is hoped that eradication programmes in affected countries will succeed in the long term but, until then, prompt and thorough treatment can prevent people who have potentially been in contact with the rabies virus from developing this infection. This article provides a review of the disease and its prevention.

Human Rabies in China, 1960-2014: A Descriptive Epidemiological Study

PubMed Central

Liu, Kai; Li, Yu; Mu, Di; Wang, Liping; Yin, Wenwu; Yu, Hongjie

2016-01-01

Background Rabies in China remains a public health problem. In 2014, nearly one thousand rabies-related deaths were reported while rabies geographic distribution has expanded for the recent years. This report used surveillance data to describe the epidemiological characteristics of human rabies in China including determining high-risk areas and seasonality to support national rabies prevention and control activities. Methods We analyzed the incidence and distribution of human rabies cases in mainland China using notifiable surveillance data from 1960–2014, which includes a detailed analysis of the recent years from 2004 to 2014. Results From 1960 to 2014, 120,913 human rabies cases were reported in mainland China. The highest number was recorded in 1981(0.7/100,000; 7037 cases), and in 2007(0.3/100,000; 3300 cases). A clear seasonal pattern has been observed with a peak in August (11.0% of total cases), Human rabies cases were reported in all provinces with a yearly average of 2198 from 1960 to 2014 in China, while the east and south regions were more seriously affected compared with other regions. From2004 to 2014, although the number of cases decreased by 65.2% since 2004 from 2651 to 924 cases, reported areas has paradoxically expanded from 162 prefectures to 200 prefectures and from southern to the central and northern provinces of China. Farmers accounted most of the cases (65.0%); 50–59 age group accounted for the highest proportion (20.5%), and cases are predominantly males with a male-to-female ratio of 2.4:1 on average. Conclusions Despite the overall steady decline of cases since the peak in 2007, the occurrence of cases in new areas and the spread trend were obvious in China in recent years. Further investigations and efforts are warranted in the areas have high rabies incidence to control rabies by interrupting transmission from dogs to humans and in the dog population. Furthermore, elimination of rabies should be eventually the ultimate goal for

Rabies, readiness, and role 1 medical care.

PubMed

Dainty, Louis A; Morgan, Shafid A; Parker, Michael E; Burke, Ronald L

2013-10-01

As medics and doctors prepare for deployment to a combat zone, there are countless specified and implied tasks needed to prepare the medical support of an Infantry unit in theater. Appropriately, units spend the lion share of their efforts in trauma training and medical readiness (vaccinations, medication prescriptions, eye glasses, etc.) while ensuring that the sets, kits, and outfits are all fully stocked with the required items needed to execute the mission. Unfortunately, this training and preparation included little on the major challenges units currently face from rabies. With the unfortunate recent death of a soldier from rabies, medical personnel were required to become experts in animal control, the prevention of animal bites and scratches, and the most appropriate treatment of service members with potential exposure to rabid animals. This article will discuss the challenges of rabies management in Afghanistan, appropriate provider and unit preparation to minimize risk of developing rabies, the need for establishment of an animal control team and prerequisite training of soldiers, leaders, and medics before and during deployment. Finally, we will review published guidelines for treating individuals exposed to rabies with a discussion of our units experience with postexposure prophylaxis. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Rabies deaths in Pakistan: results of ineffective post-exposure treatment.

PubMed

Parviz, Shehzad; Chotani, Rashid; McCormick, Joseph; Fisher-Hoch, Sue; Luby, Stephen

2004-11-01

To estimate the incidence of rabies and the effectiveness of post-exposure treatment (PET) in Pakistan. Rabies cases admitted from July 1993 to December 1994 to a public rabies isolation hospital were analyzed. Two samples (one sample each from a separate peripheral site) of a single batch of sheep brain vaccine (SBV) were also tested for potency by the National Institute of Health (NIH) test in May 1997. Forty patients were admitted with a history of clinical rabies. The median age was 22 years and 55% were under 15. Thirteen (23%) victims did not receive any vaccine; the remaining 27 (67%) received SBV only, and of these, 16 (40%) received a full course of SBV. No rabies immunoglobulins (RIG) or cell culture vaccines were administered. There were frequent power blackouts and no back-up supply at the public hospital. In-house potency testing of the vaccine batch by the manufacturer was adequate, although it was not tested by the World Health Organization (WHO) recommended NIH test. Samples of SBV of the same batch collected at the peripheral sites showed no potency. Rabies incidence was estimated to range between 7.0 to 9.8 cases per million annually. A multi-sectorial approach is needed to decrease rabies incidence in Pakistan. Public and healthcare practitioner education on prompt and appropriate PET, especially the use of cost-effective cell culture intradermal regimens, is needed urgently. The NIH test should be employed for vaccine potency testing. An independent agency is needed for monitoring vaccine quality and strategies are needed for maintaining cold chain. SBV should be replaced by locally manufactured second-generation cell culture rabies vaccine. Purified equine rabies immunoglobulin (ERIG) should be manufactured locally to meet national needs. Furthermore, effective dog control strategies should be implemented to decrease the rabies reservoir.

The control of rabies in Eurasia: overview, history and background.

PubMed

Blancou, J

2008-01-01

After a short overview of the present and past epidemiological situation regarding animal and human rabies in Eurasia, the general characteristics of the disease are described in each vector. Three main rabies cycles are presently established in Eurasia: in dogs, wild carnivores and insectivorous bats. Because of the strong barrier that exists between species-adapted rabies viruses and various potential hosts, these cycles are quite independent. They are perceived in many countries in Eurasia not to have a significant impact on animal health or the rural economy in general; the loss of dogs (or cattle) is not a priority animal health issue at the national level. Wildlife rabies has almost been eliminated in Western Eurasia by oral vaccination campaigns. Bats do not represent a real threat for a well informed public. Rabies is thus essentially a public health issue. Human rabies of canine origin has continued unabated for centuries in Eastern Eurasia, despite the Pasteur treatment and subsequent improvements of rabies post-exposure prophylaxis and biological products. Dog rabies, which is the main source of human contamination, remains practically uncontrolled. The Ministries of Health of all infected countries of Eurasia should focus their attention on canine rabies first, as it incurs endless expenses for treating humans that have been exposed to dog bites. These Ministries should use the competence of Veterinary Services and all other national bodies involved in dog rabies control, and contribute all necessary resources to support them to control this reservoir. This goal seems achievable in less than five years in a country, provided that cost-shared and well-planed mass canine oral vaccination campaigns are organised and coordinated at the regional and international levels. The conditions for the success of such campaigns are presented.

Barriers to dog rabies vaccination during an urban rabies outbreak: Qualitative findings from Arequipa, Peru.

PubMed

Castillo-Neyra, Ricardo; Brown, Joanna; Borrini, Katty; Arevalo, Claudia; Levy, Michael Z; Buttenheim, Alison; Hunter, Gabrielle C; Becerra, Victor; Behrman, Jere; Paz-Soldan, Valerie A

2017-03-01

Canine rabies was reintroduced to the city of Arequipa, Peru in March 2015. The Ministry of Health has conducted a series of mass dog vaccination campaigns to contain the outbreak, but canine rabies virus transmission continues in Arequipa's complex urban environment, putting the city's 1 million inhabitants at risk of infection. The proximate driver of canine rabies in Arequipa is low dog vaccination coverage. Our objectives were to qualitatively assess barriers to and facilitators of rabies vaccination during mass campaigns, and to explore strategies to increase participation in future efforts. We conducted 8 focus groups (FG) in urban and peri-urban communities of Mariano Melgar district; each FG included both sexes, and campaign participants and non-participants. All FG were transcribed and then coded independently by two coders. Results were summarized using the Social Ecological Model. At the individual level, participants described not knowing enough about rabies and vaccination campaigns, mistrusting the campaign, and being unable to handle their dogs, particularly in peri-urban vs. urban areas. At the interpersonal level, we detected some social pressure to vaccinate dogs, as well as some disparaging of those who invest time and money in pet dogs. At the organizational level, participants found the campaign information to be insufficient and ill-timed, and campaign locations and personnel inadequate. At the community level, the influence of landscape and topography on accessibility to vaccination points was reported differently between participants from the urban and peri-urban areas. Poor security and impermanent housing materials in the peri-urban areas also drives higher prevalence of guard dog ownership for home protection; these dogs usually roam freely on the streets and are more difficult to handle and bring to the vaccination points. A well-designed communication campaign could improve knowledge about canine rabies. Timely messages on where and

Barriers to dog rabies vaccination during an urban rabies outbreak: Qualitative findings from Arequipa, Peru

PubMed Central

Brown, Joanna; Borrini, Katty; Arevalo, Claudia; Levy, Michael Z.; Buttenheim, Alison; Hunter, Gabrielle C.; Becerra, Victor; Behrman, Jere; Paz-Soldan, Valerie A.

2017-01-01

Background Canine rabies was reintroduced to the city of Arequipa, Peru in March 2015. The Ministry of Health has conducted a series of mass dog vaccination campaigns to contain the outbreak, but canine rabies virus transmission continues in Arequipa’s complex urban environment, putting the city’s 1 million inhabitants at risk of infection. The proximate driver of canine rabies in Arequipa is low dog vaccination coverage. Our objectives were to qualitatively assess barriers to and facilitators of rabies vaccination during mass campaigns, and to explore strategies to increase participation in future efforts. Methodology/Principal findings We conducted 8 focus groups (FG) in urban and peri-urban communities of Mariano Melgar district; each FG included both sexes, and campaign participants and non-participants. All FG were transcribed and then coded independently by two coders. Results were summarized using the Social Ecological Model. At the individual level, participants described not knowing enough about rabies and vaccination campaigns, mistrusting the campaign, and being unable to handle their dogs, particularly in peri-urban vs. urban areas. At the interpersonal level, we detected some social pressure to vaccinate dogs, as well as some disparaging of those who invest time and money in pet dogs. At the organizational level, participants found the campaign information to be insufficient and ill-timed, and campaign locations and personnel inadequate. At the community level, the influence of landscape and topography on accessibility to vaccination points was reported differently between participants from the urban and peri-urban areas. Poor security and impermanent housing materials in the peri-urban areas also drives higher prevalence of guard dog ownership for home protection; these dogs usually roam freely on the streets and are more difficult to handle and bring to the vaccination points. Conclusions A well-designed communication campaign could improve

High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.

PubMed

Wright, N; Jackson, F R; Niezgoda, M; Ellison, J A; Rupprecht, C E; Nel, L H

2013-08-28

Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Viruses and bats: rabies and Lyssavirus].

PubMed

Tordo, N; Marianneau, M Ph

2009-01-01

Recent emerging zoonoses (hemorrhagic fevers due to Ebola or Marburg virus, encephalitis due to Nipah virus, severe acute respiratory syndrome due to SRAS virus...) outline the potential of bats as vectors for transmission of infectious disease to humans. Such a potential is already known for rabies encephalitis since seven out of the eight genotypes of Lyssavirus are transmitted by bats. In addition, phylogenetic reconstructions indicate that Lyssavirus have evolved in chiropters before their emergence in carnivores. Nevertheless, carnivores remain the most critical vectors for public health, in particular dogs that are originating 55.000 rabies deaths per year, essentially in developing countries. Rabies control in carnivores by parenteral (dog) or oral (wild carnivores) vaccination is efficacious and campaigns start to be more widely applied. On the other hand, rabies control in bat still remains non realistic, particularly as the pathogenicity of bat Lyssavirus for bats is still under debate, suggesting that a "diplomatic relationship" between partners would have arisen from a long term cohabitation. While comparing the interactions that humans and bats establish with Lyssavirus, scientists try to understand the molecular basis ofpathogenicity in man, a indispensable prerequisite to identify antiviral targets in a perspective of therapy.

Animal-Associated Exposure to Rabies Virus among Travelers, 1997–2012

PubMed Central

Harvey, Kira; Pandey, Prativa; Lim, Poh Lian; Leder, Karin; Piyaphanee, Watcharapong; Shaw, Marc; McDonald, Susan C.; Schwartz, Eli; Esposito, Douglas H.; Parola, Philippe

2015-01-01

Among travelers, rabies cases are rare, but animal bites are relatively common. To determine which travelers are at highest risk for rabies, we studied 2,697 travelers receiving care for animal-related exposures and requiring rabies postexposure prophylaxis at GeoSentinel clinics during 1997–2012. No specific demographic characteristics differentiated these travelers from other travelers seeking medical care, making it challenging to identify travelers who might benefit from reinforced pretravel rabies prevention counseling. Median travel duration was short for these travelers: 15 days for those seeking care after completion of travel and 20 days for those seeking care during travel. This finding contradicts the view that preexposure rabies vaccine recommendations should be partly based on longer travel durations. Over half of exposures occurred in Thailand, Indonesia, Nepal, China, and India. International travelers to rabies-endemic regions, particularly Asia, should be informed about potential rabies exposure and benefits of pretravel vaccination, regardless of demographics or length of stay. PMID:25811076

Government Response to the Discovery of a Rabies Virus Reservoir Species on a Previously Designated Rabies-Free Island, Taiwan, 1999-2014.

PubMed

Chang, S-S; Tsai, H-J; Chang, F-Y; Lee, T-S; Huang, K-C; Fang, K-Y; Wallace, R M; Inoue, S; Fei, C-Y

2016-08-01

Taiwan had been considered rabies free since 1961. In 2013, Taiwan confirmed the detection of rabies virus in wild Taiwan ferret-badgers. Up to December 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. Genetic analysis indicates that TFBV is distinct from all other known rabies virus variants. To date, ferret-badger rabies is known to occur only in China and Taiwan. The temporal dynamics of rabid ferret-badgers in Taiwan suggests that the epizootic appears to have subsided to enzootic levels as of December 2014. According to the current epidemiologic data, there is only one TFBV strain in Taiwan. TFBV is still sequestered to the mountainous regions. Humans are at risk mainly through exposure to the virus from infected domestic meso-carnivores, mainly dogs and cats. Dogs and cats should be vaccinated to establish an immunological barrier to stop the spread of the disease from mountainous regions to domestic meso-carnivores. © 2015 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.

What Is the Rabies Risk for My Pet?

MedlinePlus

... Dogs Reported in the United States, 2008 Rabid Cattle Reported in the United States, 2008 Terrestrial Rabies ... Texas December 23, 2005: Rabies in a Dairy Cow; Oklahoma November 15, 2004: Clinician Information Line July ...

What Are the Signs and Symptoms of Rabies?

MedlinePlus

... Dogs Reported in the United States, 2008 Rabid Cattle Reported in the United States, 2008 Terrestrial Rabies ... Texas December 23, 2005: Rabies in a Dairy Cow; Oklahoma November 15, 2004: Clinician Information Line July ...

Targeting Vaccine-Induced Extrafollicular Pathway of B Cell Differentiation Improves Rabies Postexposure Prophylaxis

PubMed Central

Haley, Shannon L.; Tzvetkov, Evgeni P.; Meuwissen, Samantha; Plummer, Joseph R.

2017-01-01

ABSTRACT Vaccine-induced B cells differentiate along two pathways. The follicular pathway gives rise to germinal centers (GCs) that can take weeks to fully develop. The extrafollicular pathway gives rise to short-lived plasma cells (PCs) that can rapidly secrete protective antibodies within days of vaccination. Rabies virus (RABV) postexposure prophylaxis (PEP) requires rapid vaccine-induced humoral immunity for protection. Therefore, we hypothesized that targeting extrafollicular B cell responses for activation would improve the speed and magnitude of RABV PEP. To test this hypothesis, we constructed, recovered, and characterized a recombinant RABV-based vaccine expressing murine B cell activating factor (BAFF) (rRABV-mBAFF). BAFF is an ideal molecule to improve early pathways of B cell activation, as it links innate and adaptive immunity, promoting potent B cell responses. Indeed, rRABV-mBAFF induced a faster, higher antibody response in mice and enhanced survivorship in PEP settings compared to rRABV. Interestingly, rRABV-mBAFF and rRABV induced equivalent numbers of GC B cells, suggesting that rRABV-mBAFF augmented the extrafollicular B cell pathway. To confirm that rRABV-mBAFF modulated the extrafollicular pathway, we used a signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)-deficient mouse model. In response to antigen, SAP-deficient mice form extrafollicular B cell responses but do not generate GCs. rRABV-mBAFF induced similar anti-RABV antibody responses in SAP-deficient and wild-type mice, demonstrating that BAFF modulated immunity through the extrafollicular and not the GC B cell pathway. Collectively, strategies that manipulate pathways of B cell activation may facilitate the development of a single-dose RABV vaccine that replaces current complicated and costly RABV PEP. IMPORTANCE Effective RABV PEP is currently resource- and cost-prohibitive in regions of the world where RABV is most prevalent. In order to diminish the

Difficulties in estimating the human burden of canine rabies.

PubMed

Taylor, Louise H; Hampson, Katie; Fahrion, Anna; Abela-Ridder, Bernadette; Nel, Louis H

2017-01-01

Current passive surveillance data for canine rabies, particularly for the regions where the burden is highest, are inadequate for appropriate decision making on control efforts. Poor enforcement of existing legislation and poor implementation of international guidance reduce the effectiveness of surveillance systems, but another set of problems relates to the fact that canine rabies is an untreatable condition which affects very poor sectors of society. This results in an unknown, but potentially large proportion of rabies victims dying outside the health system, deaths that are unlikely to be recorded by surveillance systems based on health center records. This article critically evaluates the potential sources of information on the number of human deaths attributable to canine rabies, and how we might improve the estimates required to move towards the goal of global canine rabies elimination. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Rabies (For Parents)

MedlinePlus

... mostly in developing countries where programs for vaccinating dogs against rabies don't exist. But the good ... vaccination programs in the United States, transmission from dogs to people is very rare. Outside the United ...

Immunizations for foreign travel.

PubMed Central

Hill, D. R.

1992-01-01

One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations. Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications. There are three categories of immunizations for foreign travel. The first category includes immunizations which are routinely recommended whether or not the individual is traveling. Many travelers are due for primary vaccination or boosting against tetanus-diphtheria, measles-mumps-rubella, pneumococcal pneumonia, and influenza, for example, and the pre-travel visit is an ideal time to administer these. The second category are immunizations which might be required by a country as a condition for entry; these are yellow fever and cholera. The final category contains immunizations which are recommended because there is a risk of acquiring a particular disease during travel. Typhoid fever, meningococcal disease, rabies, and hepatitis are some examples. Travelers who are pregnant or who are infected with the human immunodeficiency virus require special consideration. Provision of appropriate immunizations for foreign travel is an important aspect of preventing illness in travelers. PMID:1337807

A simplified immune suppression scheme leads to persistent micro-dystrophin expression in Duchenne muscular dystrophy dogs.

PubMed

Shin, Jin-Hong; Yue, Yongping; Srivastava, Arun; Smith, Bruce; Lai, Yi; Duan, Dongsheng

2012-02-01

Highly abbreviated micro-dystrophin genes have been intensively studied for Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus (AAV) gene transfer, robust microgene expression is achieved in murine DMD models in the absence of immune suppression. Interestingly, a recent study suggests that AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued immune suppression is not only costly but also may cause untoward reactions. Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily available. To overcome these limitations, we developed a novel 5-week immune suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase gene, or AV.CMV.μDys that expresses the canine R16-17/H3/ΔC microgene) at 2.85×10(12) vg particles were injected into adult dystrophic dog limb muscles under the new immune suppression protocol. Sustained transduction was observed for nearly half year (the end of the study). The simplified immune suppression strategy described here may facilitate preclinical studies in the dog model.

Rabies virus quasispecies: Implications for pathogenesis

PubMed Central

Morimoto, Kinjiro; Hooper, D. Craig; Carbaugh, Heather; Fu, Zhen Fang; Koprowski, Hilary; Dietzschold, Bernhard

1998-01-01

Passage of the mouse-adapted rabies virus strain CVS-24 (where CVS is challenge virus standard) in BHK cells results in the rapid selection of a dominant variant designated CVS-B2c that differs genotypically and phenotypically from the dominant variant CVS-N2c present in mouse-brain- or neuroblastoma-cell-passaged CVS-24. The glycoprotein of CVS-B2c has 10 amino acid substitutions compared with that of CVS-N2c. Because CVS-B2c can be reproducibly selected in BHK cells, it is likely to be a conserved minor subpopulation of CVS-24. CVS-N2c is more neurotropic in vitro and in vivo than CVS-B2c, which replicates more readily in nonneuronal cells in vitro and in vivo. These characteristics appear to be relevant to the pathogenicity of the two variants. CVS-N2c is more pathogenic for adult mice than CVS-B2c. In contrast, CVS-B2c is more pathogenic for neonatal mice. These differences in pathogenicity are reflected in the selection pattern when mixtures of CVS-N2c and CVS-B2c were used to infect neonatal and adult mice. Although CVS-N2c was highly selected in adult mice, no selection for either variant was seen in neonates, suggesting that certain aspects of development, such as maturation of the nervous and immune systems, may contribute to the selection process. We speculate that the existence of different variants within a rabies virus strain may facilitate the virus in overcoming barriers to its spread, both within the host and between species. PMID:9501231

Rabies virus quasispecies: implications for pathogenesis.

PubMed

Morimoto, K; Hooper, D C; Carbaugh, H; Fu, Z F; Koprowski, H; Dietzschold, B

1998-03-17

Passage of the mouse-adapted rabies virus strain CVS-24 (where CVS is challenge virus standard) in BHK cells results in the rapid selection of a dominant variant designated CVS-B2c that differs genotypically and phenotypically from the dominant variant CVS-N2c present in mouse-brain- or neuroblastoma-cell-passaged CVS-24. The glycoprotein of CVS-B2c has 10 amino acid substitutions compared with that of CVS-N2c. Because CVS-B2c can be reproducibly selected in BHK cells, it is likely to be a conserved minor subpopulation of CVS-24. CVS-N2c is more neurotropic in vitro and in vivo than CVS-B2c, which replicates more readily in nonneuronal cells in vitro and in vivo. These characteristics appear to be relevant to the pathogenicity of the two variants. CVS-N2c is more pathogenic for adult mice than CVS-B2c. In contrast, CVS-B2c is more pathogenic for neonatal mice. These differences in pathogenicity are reflected in the selection pattern when mixtures of CVS-N2c and CVS-B2c were used to infect neonatal and adult mice. Although CVS-N2c was highly selected in adult mice, no selection for either variant was seen in neonates, suggesting that certain aspects of development, such as maturation of the nervous and immune systems, may contribute to the selection process. We speculate that the existence of different variants within a rabies virus strain may facilitate the virus in overcoming barriers to its spread, both within the host and between species.

Pre-exposure rabies prophylaxis: a systematic review.

PubMed

Kessels, Jocelyn A; Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

2017-03-01

To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost-effectiveness and recommendations for use, particularly in high-risk settings. We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities.

Pre-exposure rabies prophylaxis: a systematic review

PubMed Central

Recuenco, Sergio; Navarro-Vela, Ana Maria; Deray, Raffy; Vigilato, Marco; Ertl, Hildegund; Durrheim, David; Rees, Helen; Nel, Louis H; Abela-Ridder, Bernadette; Briggs, Deborah

2017-01-01

Abstract Objective To review the safety and immunogenicity of pre-exposure rabies prophylaxis (including accelerated schedules, co-administration with other vaccines and booster doses), its cost–effectiveness and recommendations for use, particularly in high-risk settings. Methods We searched the PubMed, Centre for Agriculture and Biosciences International, Cochrane Library and Web of Science databases for papers on pre-exposure rabies prophylaxis published between 2007 and 29 January 2016. We reviewed field data from pre-exposure prophylaxis campaigns in Peru and the Philippines. Findings Pre-exposure rabies prophylaxis was safe and immunogenic in children and adults, also when co-administered with routine childhood vaccinations and the Japanese encephalitis vaccine. The evidence available indicates that shorter regimens and regimens involving fewer doses are safe and immunogenic and that booster intervals could be extended up to 10 years. The few studies on cost suggest that, at current vaccine and delivery costs, pre-exposure prophylaxis campaigns would not be cost-effective in most situations. Although pre-exposure prophylaxis has been advocated for high-risk populations, only Peru and the Philippines have implemented appropriate national programmes. In the future, accelerated regimens and novel vaccines could simplify delivery and increase affordability. Conclusion Pre-exposure rabies prophylaxis is safe and immunogenic and should be considered: (i) where access to postexposure prophylaxis is limited or delayed; (ii) where the risk of exposure is high and may go unrecognized; and (iii) where controlling rabies in the animal reservoir is difficult. Pre-exposure prophylaxis should not distract from canine vaccination efforts, provision of postexposure prophylaxis or education to increase rabies awareness in local communities. PMID:28250534

Complex genetic structure of the rabies virus in Bangkok and its surrounding provinces, Thailand: implications for canine rabies control.

PubMed

Lumlertdacha, Boonlert; Wacharapluesadee, Supaporn; Denduangboripant, Jessada; Ruankaew, Nipada; Hoonsuwan, Wirongrong; Puanghat, Apirom; Sakarasaeranee, Plyyonk; Briggs, Deborrah; Hemachudha, Thiravat

2006-03-01

Dog vaccination and population management have been suggested as priorities in attempts at disease control in canine rabies-endemic countries. Budget limitations and the complexity of social, cultural and religious variables have complicated progress in the developing world. In Bangkok, Thailand, an intensive canine vaccination and sterilization programme has been in place since November 2002. Our objective was to determine if the rabies virus could be mapped according to its genetic variations and geographical location on the small localized scale of Bangkok and its surrounding provinces. Phylogenetic characterization of 69 samples from Bangkok and five neighbouring and two remote provinces, by limited sequence analysis of the rabies virus nucleoprotein gene, distinguished six different clades. Rabies viruses of four clades were intermixed in Bangkok and in the surrounding highly populated regions whereas the other two clades were confined to rural and less populated provinces. Such a complex pattern of gene flow, particularly in Bangkok, may affect the outcome of canine control programmes.

Controlling rabies through a multidisciplinary, public health system in Trujillo, La Libertad, Peru

PubMed Central

Seneschall, Charlotte; Luna-Farro, Maria

2013-01-01

Rabies remains endemic in Peru. In 1983, Latin America and the Caribbean promised to eliminate canine-transmitted rabies from the continent. This led to Peru introducing a multidisciplinary public health system for controlling and managing rabies across the country. The system consists of mass canine vaccination campaigns, post exposure prophylaxis and monitoring aggressor animals for signs of rabies. The Peruvian city of Trujillo, La Libertad, is an urban area where dogs are the principal reservoir for rabies. The disease burden of rabies in Trujillo, La Libertad is currently minimal, with no rabies cases in humans for over 10 years, and only three canine cases. No human deaths due to rabies have occurred for several decades. From this it can be inferred that antirabies systems such as this do have real effects in reducing cases of human rabies at a grass roots level. PMID:24392679

Rabies Virus Transmission in Solid Organ Transplantation, China, 2015-2016.

PubMed

Chen, Shuilian; Zhang, Heng; Luo, Meiling; Chen, Jingfang; Yao, Dong; Chen, Faming; Liu, Ruchun; Chen, Tianmu

2017-09-01

We report rabies virus transmission among solid organ transplantation recipients in Changsha, China, in 2016. Two recipients were confirmed to have rabies and died. Our findings suggest that more attention should be paid to the possibility of rabies virus transmission through organ transplantation for clinical and public health reasons.

Twelve Years of Rabies Surveillance in Sri Lanka, 1999–2010