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1.
BMC Vet Res ; 14(1): 90, 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29534727

RESUMO

BACKGROUND: Oral vaccination of the small Indian mongoose against rabies has been suggested as a potential tool to eliminate mongoose-mediated rabies on several Caribbean islands. A recently developed oral rabies virus vaccine strain, SPBN GASGAS, has already been shown to be efficacious in this reservoir species. Since, all available oral rabies vaccines are based on replication-competent viruses and vaccine baits are distributed unsupervised in the environment, enhanced safety standards for such vaccine types are required. RESULTS: The results of safety studies, including overdose, repeated doses, dissemination and different routes of administration, in the target species are presented. It was shown that the construct was apathogenic, irrespective of dose and route of administration. Even when it was inoculated directly in the brain, it did not induce rabies infection. Furthermore, the vaccine strain did not spread within the target species after direct oral instillation beyond the site of entry. CONCLUSION: The vaccine strain SPBN GASGAS meets the safety requirements for live rabies virus vaccines in this target species, the small Indian mongoose.


Assuntos
Herpestidae/imunologia , Vacina Antirrábica/uso terapêutico , Vírus da Raiva/imunologia , Raiva/veterinária , Animais , Herpestidae/virologia , Masculino , Raiva/imunologia , Raiva/prevenção & controle , Vacina Antirrábica/efeitos adversos , Vacina Antirrábica/imunologia
2.
Eur J Wildl Res ; 64(6): 62, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-32214946

RESUMO

Rabies in the greater kudu (Tragelaphus strepsiceros), one of the largest African antelopes, is a phenomenon unique to Namibia. Since the mid-1970s, the country has been plagued by two epizootics that claimed thousands of casualties among the indigenous kudu population. Reasons as to why kudus appear to be exceptionally susceptible to the disease still remain speculative at best. Because the Namibian economy relies heavily on trophy hunting, game meat hunting, and ecotourism, the current severe spread of rabies among kudus calls for effective measures to protect these antelopes. Oral vaccination of kudus may offer a possibility provided efficacious oral rabies vaccines are available. In this screening study, we explored options for attractive baits that facilitate optimal vaccine uptake by the target species and a bait distribution system that maximizes bait availability to the target species meanwhile minimizing bait depletion by non-target species. The results show that gelatin-based baits mixed with local (pods of the camel thorn tree) but also imported (apple-flavored corn meal) attractants are highly attractive for kudus providing a basis for future oral rabies vaccine baits.

3.
J Clin Med ; 13(6)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38541946

RESUMO

(1) Background: Unclear sonographic findings without adequate specialist expertise in abdominal ultrasound (AU) may harm patients in rural areas, due to overlooked diagnoses, unnecessary additional imaging (e.g., CT scan), and/or patient transport to referral expert centers. Appropriate telemedical sonography assistance could lead to corresponding savings. (2) Methods: The study was designed as a randomized trial. Selected study centers performed AU with the best local expertise. Patients were selected and monitored according to the indication that they required AU. The study depicted three basic scenarios. Group 1 corresponds to the telemedically assisted cohort, group 2 corresponds to the non-telemedically assisted cohort, and group 3 corresponds to a telemedically supported cohort for teaching purposes. The target case number of all three groups was 400 patients (20 calculated dropouts included). (3) Discussion: This study might help to clarify whether telemedicine-assisted ultrasound by a qualified expert is non-inferior to presence sonography concerning technical success and whether one of the interventions is superior in terms of efficacy and safety in one or more secondary endpoints. Randomization was provided, as every patient who needed an AU was included and then randomized to one of the groups. The third group consisted of a lower number of patients who were selected from group 1 or 2 for teaching purposes in case of rare diseases or findings. (4) Conclusions: The study investigates whether there are benefits of telemedical ultrasound for patients, medical staff, and the health care system.

4.
Vaccines (Basel) ; 11(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36851185

RESUMO

(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies.

5.
PLoS Negl Trop Dis ; 16(8): e0010422, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35994498

RESUMO

Dog-mediated rabies is responsible for tens of thousands of human deaths annually, and in resource-constrained settings, vaccinating dogs to control the disease at source remains challenging. Currently, rabies elimination efforts rely on mass dog vaccination by the parenteral route. To increase the herd immunity, free-roaming and stray dogs need to be specifically addressed in the vaccination campaigns, with oral rabies vaccination (ORV) of dogs being a possible solution. Using a third-generation vaccine and a standardized egg-flavoured bait, bait uptake and vaccination was assessed under field conditions in Namibia. During this trial, both veterinary staff as well as dog owners expressed their appreciation to this approach of vaccination. Of 1,115 dogs offered a bait, 90% (n = 1,006, 95%CI:91-94) consumed the bait and 72.9% (n = 813, 95%CI:70.2-75.4) of dogs were assessed as being vaccinated by direct observation, while for 11.7% (n = 130, 95%CI:9.9-17.7) the status was recorded as "unkown" and 15.4% (n = 172, 95%CI: 13.4-17.7) were considered as being not vaccinated. Smaller dogs and dogs offered a bait with multiple other dogs had significantly higher vaccination rates, while other factors, e.g. sex, confinement status and time had no influence. The favorable results of this first large-scale field trial further support the strategic integration of ORV into dog rabies control programmes. Given the acceptance of the egg-flavored bait under various settings worldwide, ORV of dogs could become a game-changer in countries, where control strategies using parenteral vaccination alone failed to reach sufficient vaccination coverage in the dog population.


Assuntos
Doenças do Cão , Vacina Antirrábica , Raiva , Administração Oral , Animais , Doenças do Cão/epidemiologia , Doenças do Cão/prevenção & controle , Cães , Humanos , Namíbia , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterinária , Vacinação/métodos , Vacinação/veterinária
6.
Viruses ; 13(7)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34372588

RESUMO

Oral vaccination of dogs against rabies has the potential to achieve mass coverage and thus deplete the virus of its most important reservoir host species. There is, however, no established non-invasive method to evaluate vaccine release in the oral cavity, following bait ingestion. In this study, two pre-selected marker methods in conjunction with their acceptance were assessed in local Thai dogs. Shelter dogs (n = 47) were offered one of four randomized bait formulations; bait type A-, containing Green S (E142) in a fructose solution; type B-, containing Patent Blue V (E131) in a fructose solution; type C-, containing the medium used for delivery of oral rabies vaccine in baits commercially produced; and type D-, containing denatonium benzoate, which was to serve as the negative control, due to its perceived bitterness. Patent Blue V was found to possess overall stronger dyeing capacities compared to Green S. Furthermore, there was no significant difference in the acceptance or bait handling of Patent Blue V baits compared to those containing the oral rabies vaccine medium alone, suggesting the potential use of this dye as a surrogate for rabies vaccine when testing newly developed bait formats.


Assuntos
Vacina Antirrábica/administração & dosagem , Vacinação/métodos , Vacinas/administração & dosagem , Administração Oral , Animais , Corantes/administração & dosagem , Doenças do Cão/prevenção & controle , Cães , Boca , Raiva/prevenção & controle , Vacinação/veterinária
7.
Front Vet Sci ; 8: 737250, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760958

RESUMO

Dog-mediated rabies is endemic throughout Africa. While free-roaming dogs that play a crucial role in rabies transmission are often inaccessible for parenteral vaccination during mass dog vaccination campaigns, oral rabies vaccination (ORV) is considered to be a promising alternative to increase vaccination coverage in these hard-to-reach dogs. The acceptance of ORV as an efficient supplementary tool is still low, not least because of limited immunogenicity and field trial data in local dogs. In this study, the immunogenicity of the highly attenuated 3rd-generation oral rabies vaccine strain SPBN GASGAS in local free-roaming dogs from Namibia was assessed by determining the immune response in terms of seroconversion for up to 56 days post-vaccination. At two study sites, free-roaming dogs were vaccinated by administering the vaccine either by direct oral administration or via a vaccine-loaded egg bait. Pre- and post-vaccination blood samples were tested for rabies virus neutralizing as well as binding antibodies using standard serological assays. A multiple logistic regression (MLR) analysis was performed to determine a possible influence of study area, vaccination method, and vaccine dose on the seroconversion rate obtained. About 78% of the dogs vaccinated by the oral route seroconverted (enzyme-linked immunosorbent assay, ELISA), though the seroconversion as determined by a rapid fluorescence focus inhibition test (RFFIT) was much lower. None of the factors examined had a significant effect on the seroconversion rate. This study confirms the immunogenicity of the vaccine strain SPBN GASGAS and the potential utility of ORV for the control of dog-mediated rabies in African dogs.

8.
Vaccines (Basel) ; 9(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466701

RESUMO

The live genetically-engineered oral rabies virus (RABV) variant SPBN GASGAS induces long-lasting immunity in foxes and protection against challenge with an otherwise lethal dose of RABV field strains both after experimental oral and parenteral routes of administration. Induction of RABV-specific binding antibodies and immunoglobulin isotypes (IgM, total IgG, IgG1, IgG2) were comparable in orally and parenterally vaccinated foxes. Differences were only observed in the induction of virus-neutralizing (VNA) titers, which were significantly higher in the parenterally vaccinated group. The dynamics of rabies-specific antibodies pre- and post-challenge (365 days post vaccination) suggest the predominance of type-1 immunity protection of SPBN GASGAS. Independent of the route of administration, in the absence of IgG1 the immune response to SPBN GAGAS was mainly IgG2 driven. Interestingly, vaccination with SPBN GASGAS does not cause significant differences in inducible IFN-γ production in vaccinated animals, indicating a relatively weak cellular immune response during challenge. Notably, the parenteral application of SPBN GASGAS did not induce any adverse side effects in foxes, thus supporting safety studies of this oral rabies vaccine in various species.

9.
Sci Rep ; 10(1): 2919, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076025

RESUMO

Oral rabies vaccination (ORV) is highly effective in foxes and raccoon dogs, whereas for unknown reasons the efficacy of ORV in other reservoir species is less pronounced. To investigate possible variations in species-specific cell tropism and local replication of vaccine virus, different reservoir species including foxes, raccoon dogs, raccoons, mongooses, dogs and skunks were orally immunised with a highly attenuated, high-titred GFP-expressing rabies virus (RABV). Immunofluorescence and RT-qPCR screenings revealed clear differences among species suggesting host specific limitations to ORV. While for responsive species the palatine tonsils (tonsilla palatina) were identified as a main site of virus replication, less virus dissemination was observed in the tonsils of rather refractory species. While our comparison of vaccine virus tropism emphasizes the important role that the tonsilla palatina plays in eliciting an immune response to ORV, our data also indicate that other lymphoid tissues may have a more important role than originally anticipated. Overall, these data support a model in which the susceptibility to oral live RABV vaccine infection of lymphatic tissue is a major determinant in vaccination efficacy. The present results may help to direct future research for improving vaccine uptake and efficacy of oral rabies vaccines under field conditions.


Assuntos
Reservatórios de Doenças/virologia , Tecido Linfoide/imunologia , Mucosa/imunologia , Vacina Antirrábica/imunologia , Raiva/imunologia , Vacinação , Administração Oral , Animais , Anticorpos Antivirais/imunologia , Raposas/imunologia , Raposas/virologia , Proteínas de Fluorescência Verde/metabolismo , Tecido Linfoide/virologia , Mucosa/virologia , Especificidade de Órgãos , Tonsila Palatina/imunologia , Tonsila Palatina/virologia , RNA Viral/genética , Raiva/sangue , Raiva/veterinária , Raiva/virologia , Vírus da Raiva/fisiologia , Especificidade da Espécie , Tropismo , Carga Viral , Replicação Viral/fisiologia
10.
J Wildl Dis ; 56(2): 452-456, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31750771

RESUMO

The small Indian mongoose (Herpestes auropunctatus) is a rabies reservoir in areas of the Caribbean including Puerto Rico, but no rabies vaccination program targeting this host exists. We used two derivatives of iophenoxic acid (IPA) to evaluate placebo oral rabies vaccine bait uptake by mongooses in southwestern Puerto Rico. We hand-distributed baits at an application rate of 200 baits/km2 at three, 400 ha, sites during autumn 2016 and spring 2017. Each site contained 90-100 cage traps in a 100 ha central trapping area. We used ethyl-IPA as a biological marker during the autumn and methyl-IPA during the spring. We live captured mongooses for 10 consecutive days, beginning 1 wk following bait application. We obtained a serum sample from captured mongooses and analyzed the sera for ethyl- and methyl-IPA by liquid chromatography-mass spectrometry. During autumn 2016, 63% (55/87) mongooses sampled were positive for ethyl-IPA. In spring 2017, 69% (85/123) of mongooses were positive for methyl-IPA. Pooling seasons, accounting for recaptures between years, and disregarding marker type, 74% (133/179) unique mongooses were positive for IPA biomarker, indicating bait consumption during either the autumn, spring, or both trials. We conclude that distributing baits at an application rate of 200 baits/km2 is sufficient to reach over 60% of the target mongoose population in dry forest habitats of Puerto Rico.


Assuntos
Reservatórios de Doenças/veterinária , Vacina Antirrábica/imunologia , Raiva/veterinária , Administração Oral , Animais , Biomarcadores/sangue , Reservatórios de Doenças/virologia , Herpestidae , Hispânico ou Latino , Ácido Iopanoico/administração & dosagem , Ácido Iopanoico/metabolismo , Porto Rico , Raiva/prevenção & controle , Vacina Antirrábica/administração & dosagem , Vacinação
11.
J Allergy Clin Immunol Pract ; 8(6): 1972-1979.e8, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32142961

RESUMO

BACKGROUND: Self-management programs have beneficial effects on asthma control, but their implementation in clinical practice is poor. Mobile health (mHealth) could play an important role in enhancing self-management. OBJECTIVE: To assess the clinical effectiveness and technology acceptance of myAirCoach-supported self-management on top of usual care in patients with asthma using inhalation medication. METHODS: Patients were recruited in 2 separate studies. The myAirCoach system consisted of an inhaler adapter, an indoor air-quality monitor, a physical activity tracker, a portable spirometer, a fraction exhaled nitric oxide device, and an app. The primary outcome was asthma control; secondary outcomes were exacerbations, quality of life, and technology acceptance. In study 1, 30 participants were randomized to either usual care or myAirCoach support for 3 to 6 months; in study 2, 12 participants were provided with the myAirCoach system in a 3-month before-after study. RESULTS: In study 1, asthma control improved in the intervention group compared with controls (Asthma Control Questionnaire difference, 0.70; P = .006). A total of 6 exacerbations occurred in the intervention group compared with 12 in the control group (hazard ratio, 0.31; P = .06). Asthma-related quality of life improved (mini Asthma-related Quality of Life Questionnaire difference, 0.53; P = .04), but forced expiratory volume in 1 second was unchanged. In study 2, asthma control improved by 0.86 compared with baseline (P = .007) and quality of life by 0.16 (P = .64). Participants reported positive attitudes toward the system. DISCUSSION: Using the myAirCoach support system improves asthma control and quality of life, with a reduction in severe asthma exacerbations. Well-validated mHealth technologies should therefore be further studied.


Assuntos
Asma , Autogestão , Telemedicina , Asma/terapia , Humanos , Qualidade de Vida , Espirometria
12.
Trop Med Infect Dis ; 4(3)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487795

RESUMO

Introduction: To achieve the global goal of canine-mediated human rabies elimination by 2030 there is an urgent need to scale-up mass dog vaccination activities in regions with large dog populations that are difficult to access; a common situation in much of India. Oral rabies vaccination may enable the vaccination of free-roaming dogs that are inaccessible to parenteral vaccination, and is considered a promising complementary measure to parenteral mass dog vaccination campaigns. WHO and OIE have published detailed minimum requirements for rabies vaccines and baits to be used for this purpose, requiring that baits must not only be well-accepted by the target population but must also efficiently release the vaccine in the oral cavity. For oral rabies vaccination approaches to be successful, it is necessary to develop baits which have a high uptake by the target population, are culturally accepted and amenable to mass production. The aim of this study was to compare the interest and uptake rates of meat-based and an egg-based prototype bait constructs by free roaming dogs in Goa, India. Methods: Three teams randomly distributed two prototype baits; an egg-flavoured bait and a commercial meat dog food (gravy) flavoured bait. The outcomes of consumption were recorded and compared between baits and dog variables. Results: A total of 209 egg-bait and 195 gravy-bait distributions were recorded and analysed. No difference (p = 0.99) was found in the percentage of dogs interested in the baits when offered. However, significantly more dogs consumed the egg-bait than the gravy-bait; 77.5% versus 68.7% (p = 0.04). The release of the blue-dyed water inside the sachet in the oral cavity of the animals was significant higher in the dogs consuming an egg-bait compared to the gravy-bait (73.4% versus 56.7%, p = 0.001). Conclusions: The egg-based bait had a high uptake amongst free roaming dogs and also enabled efficient release of the vaccine in the oral cavity, whilst also avoiding culturally relevant materials of bovine or porcine meat products.

13.
Vaccine ; 37(33): 4750-4757, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-29042202

RESUMO

To test the immunogenicity and efficacy of a new oral rabies virus vaccine strain SPBN GASGAS in wildlife target species, one group of foxes and two groups of raccoon dogs were offered a bait containing 1.7 ml of the vaccine (106.6 FFU/ml; 106.8 FFU/dose) and subsequently challenged approximately 180 days later with a fox rabies virus isolate. One group of raccoon dogs (n=30) received the same challenge dose (100.7 MICLD50/ml) as the red foxes (n=29). The other group with raccoon dogs (n=28) together with 8 animals that received the vaccine dose by direct instillation into the oral cavity (DIOC) were infected with a 40-fold higher dose of the challenge virus (102.3 MICLD50/ml). All but one of the 29 vaccinated foxes survived the challenge infection; meanwhile all 12 control foxes succumbed to rabies. Twenty-eight of 30 vaccinated raccoon dogs challenged with the same dose survived the infection, however only six of 12 control animals succumbed. When the higher challenge dose was administered, all 12 control animals died from rabies and all 36 vaccinated animals (28 baited plus 8 DIOC) survived. Blood samples were collected at different time points post vaccination and examined by both RFFIT and ELISA. The kinetics of the measured immune response was similar for both species, although in RFFIT slightly higher values were observed in foxes than in raccoon dogs. However, the immune response as measured in ELISA was identical for both species. The oral rabies virus vaccine SPBN GASGAS meets the efficacy requirements for live rabies virus vaccines as laid down by the European Pharmacopoeia.


Assuntos
Vacina Antirrábica/uso terapêutico , Vírus da Raiva/imunologia , Vírus da Raiva/patogenicidade , Raiva/imunologia , Raiva/prevenção & controle , Administração Oral , Animais , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Raposas , Imunidade Humoral/fisiologia , Masculino , Raiva/virologia , Vacina Antirrábica/imunologia , Cães Guaxinins
14.
J Vis Exp ; (147)2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-31205294

RESUMO

The small Indian mongoose (Herpestes auropunctatus) is a reservoir of rabies virus (RABV) in Puerto Rico and comprises over 70% of animal rabies cases reported annually. The control of RABV circulation in wildlife reservoirs is typically accomplished by a strategy of oral rabies vaccination (ORV). Currently no wildlife ORV program exists in Puerto Rico. Research into oral rabies vaccines and various bait types for mongooses has been conducted with promising results. Monitoring the success of ORV relies on estimating bait uptake by target species, which typically involves evaluating a change in RABV neutralizing antibodies (RVNA) post vaccination. This strategy may be difficult to interpret in areas with an active wildlife ORV program or in areas where RABV is enzootic and background levels of RVNA are present in reservoir species. In such situations, a biomarker incorporated with the vaccine or the bait matrix may be useful. We offered 16 captive mongooses placebo ORV baits containing ethyl-iophenoxic acid (et-IPA) in concentrations of 0.4% and 1% inside the bait and 0.14% in the external bait matrix. We also offered 12 captive mongooses ORV baits containing methyl-iophenoxic acid (me-IPA) in concentrations of 0.035%, 0.07% and 0.14% in the external bait matrix. We collected a serum sample prior to bait offering and then weekly for up to eight weeks post offering. We extracted Iophenoxic acids from sera into acetonitrile and quantified using liquid chromatography/mass spectrometry. We analyzed sera for et-IPA or me-IPA by liquid chromatography-mass spectrometry. We found adequate marking ability for at least eight and four weeks for et- and me-IPA, respectively. Both IPA derivatives could be suitable for field evaluation of ORV bait uptake in mongooses. Due to the longevity of the marker in mongoose sera, care must be taken to not confound results by using the same IPA derivative during consecutive evaluations.


Assuntos
Herpestidae/sangue , Ácido Iopanoico/análise , Vacina Antirrábica/administração & dosagem , Vacina Antirrábica/imunologia , Raiva/imunologia , Vacinação , Administração Oral , Animais , Biomarcadores/sangue , Calibragem , Controle de Qualidade , Vírus da Raiva/imunologia , Padrões de Referência
15.
Viruses ; 11(9)2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461981

RESUMO

: To evaluate the long-term immunogenicity of the live-attenuated, oral rabies vaccine SPBN GASGAS in a full good clinical practice (GCP) compliant study, forty-six (46) healthy, seronegative red foxes (Vulpesvulpes) were allocated to two treatment groups: group 1 (n = 31) received a vaccine bait containing 1.7 ml of the vaccine of minimum potency (106.6 FFU/mL) and group 2 (n = 15) received a placebo-bait. In total, 29 animals of group 1 and 14 animals of group 2 were challenged at 12 months post-vaccination with a fox rabies virus isolate (103.0 MICLD50/mL). While 90% of the animals offered a vaccine bait resisted the challenge, only one animal (7%) of the controls survived. All animals that had seroconverted following vaccination survived the challenge infection at 12 months post-vaccination. Rabies specific antibodies could be detected as early as 14 days post-vaccination. Based on the kinetics of the antibody response to SPBN GASGAS as measured in ELISA and RFFIT, the animals maintained stable antibody titres during the 12-month pre-challenge observation period at a high level. The results indicate that successful vaccination using the oral route with this new rabies virus vaccine strain confers long-term duration of immunity beyond one year, meeting the same requirements as for licensure as laid down by the European Pharmacopoeia.


Assuntos
Anticorpos Antivirais/sangue , Vacina Antirrábica/administração & dosagem , Vírus da Raiva/imunologia , Raiva/veterinária , Administração Oral , Animais , Raposas , Imunogenicidade da Vacina , Raiva/imunologia , Raiva/prevenção & controle , Vacinação/veterinária , Vacinas Atenuadas/administração & dosagem
16.
Vaccine ; 36(6): 811-817, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29325820

RESUMO

A safety requirement for live vaccines is investigating possible shedding in recipients since the presence of replication competent vaccine in secretions could result in direct and indirect horizontal transmission. This is especially relevant for oral rabies vaccine baits that are deliberately distributed into the environment. In the current study, survival of an oral rabies virus vaccine, SPBN GASGAS, was examined in excretions from different target and non-target species; red fox, raccoon dog, small Indian mongoose, raccoon, striped skunk, domestic dog, domestic cat and domestic pig. Saliva - and (pooled) fecal samples collected at different time points after oral administration of the vaccine strain were examined for the presence of viral RNA (rt-PCR). All PCR-positive and a subset of PCR-negative samples were subsequently investigated for the presence of infectious virus by isolation in cell culture (RTCIT). Up to 7 days post vaccine administration viral RNA could be detected in 50 of 758 fecal samples but no infectious virus was detected in any of the examined PCR-positive fecal samples. In contrast, RNA-fragments were detected in 248 of 1053 saliva swabs for an extended period (up to 10 days) after vaccine administration, but viable virus was only present during the first hours post vaccine administration in 38 samples. No infectious vaccine virus was isolated in saliva swabs taken 24 h or more after vaccine administration. Hence, no active shedding of the vaccine virus SPBN GASGAS after oral administration occurred and the virus isolated during the initial hours was material originally administered and not a result of virus replication within the host. Thus, potential horizontal transmission of this vaccine virus is limited to a short period directly after vaccine bait uptake. It can be concluded that the environmental risks associated with shedding after distributing vaccine baits containing SPBN GASGAS are negligible.


Assuntos
Vacina Antirrábica/imunologia , Vírus da Raiva/imunologia , Raiva/imunologia , Raiva/virologia , Eliminação de Partículas Virais , Administração Oral , Animais , Raposas , Imunização , Mephitidae , Raiva/prevenção & controle , Vacina Antirrábica/administração & dosagem , Guaxinins , Suínos
17.
Front Vet Sci ; 5: 91, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29868616

RESUMO

In order to obtain Marketing Authorization for an oral rabies vaccine in the European Union, not only safety studies in the target species, red fox and raccoon dog, are required. Since baits are distributed unsupervised in the environment, specific safety studies in selected non-target species are compulsory. Furthermore, oral rabies vaccines are based on live, replication-competent viruses and thus distinct safety studies in the target species for such type of vaccines are also mandatory. Here, the results of these safety studies in target and selected non-target species for a 3rd generation oral rabies virus vaccine construct, SPBN GASGAS (Rabitec), are presented. The studies included the following species; red fox, raccoon dog, domestic dog, domestic cat, domestic pig, wild rodents. The following safety topics were investigated; overdose, repeated dose, dissemination, shedding, horizontal and vertical transmission. It was shown that SPBN GASGAS did not cause disease or any other adverse reaction in vaccinated animals and naïve contact animals. The vaccine did not disseminate within the host beyond the site of entry. No horizontal transmission was observed in wild rodents. In the target species, there was evidence that in a few cases horizontal transmission of vaccine virus could have occurred under these experimental conditions; most likely immediately after vaccine administration. The vaccine construct SPBN GASGAS meets therefore the latest revised minimal safety requirements as laid down in the European Pharmacopoeia.

18.
IEEE J Biomed Health Inform ; 20(4): 1088-99, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-25966489

RESUMO

This paper reports an algorithm for the detection of three elementary upper limb movements, i.e., reach and retrieve, bend the arm at the elbow and rotation of the arm about the long axis. We employ two MARG sensors, attached at the elbow and wrist, from which the kinematic properties (joint angles, position) of the upper arm and forearm are calculated through data fusion using a quaternion-based gradient-descent method and a two-link model of the upper limb. By studying the kinematic patterns of the three movements on a small dataset, we derive discriminative features that are indicative of each movement; these are then used to formulate the proposed detection algorithm. Our novel approach of employing the joint angles and position to discriminate the three fundamental movements was evaluated in a series of experiments with 22 volunteers who participated in the study: 18 healthy subjects and four stroke survivors. In a controlled experiment, each volunteer was instructed to perform each movement a number of times. This was complimented by a seminaturalistic experiment where the volunteers performed the same movements as subtasks of an activity that emulated the preparation of a cup of tea. In the stroke survivors group, the overall detection accuracy for all three movements was 93.75% and 83.00%, for the controlled and seminaturalistic experiment, respectively. The performance was higher in the healthy group where 96.85% of the tasks in the controlled experiment and 89.69% in the seminaturalistic were detected correctly. Finally, the detection ratio remains close ( ±6%) to the average value, for different task durations further attesting to the algorithms robustness.


Assuntos
Monitorização Fisiológica/métodos , Movimento/fisiologia , Extremidade Superior/fisiologia , Acelerometria/métodos , Idoso , Algoritmos , Fenômenos Biomecânicos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação
19.
Hum Mov Sci ; 40: 59-76, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25528632

RESUMO

In this paper we present a methodology for recognizing three fundamental movements of the human forearm (extension, flexion and rotation) using pattern recognition applied to the data from a single wrist-worn, inertial sensor. We propose that this technique could be used as a clinical tool to assess rehabilitation progress in neurodegenerative pathologies such as stroke or cerebral palsy by tracking the number of times a patient performs specific arm movements (e.g. prescribed exercises) with their paretic arm throughout the day. We demonstrate this with healthy subjects and stroke patients in a simple proof of concept study in which these arm movements are detected during an archetypal activity of daily-living (ADL) - 'making-a-cup-of-tea'. Data is collected from a tri-axial accelerometer and a tri-axial gyroscope located proximal to the wrist. In a training phase, movements are initially performed in a controlled environment which are represented by a ranked set of 30 time-domain features. Using a sequential forward selection technique, for each set of feature combinations three clusters are formed using k-means clustering followed by 10 runs of 10-fold cross validation on the training data to determine the best feature combinations. For the testing phase, movements performed during the ADL are associated with each cluster label using a minimum distance classifier in a multi-dimensional feature space, comprised of the best ranked features, using Euclidean or Mahalanobis distance as the metric. Experiments were performed with four healthy subjects and four stroke survivors and our results show that the proposed methodology can detect the three movements performed during the ADL with an overall average accuracy of 88% using the accelerometer data and 83% using the gyroscope data across all healthy subjects and arm movement types. The average accuracy across all stroke survivors was 70% using accelerometer data and 66% using gyroscope data. We also use a Linear Discriminant Analysis (LDA) classifier and a Support Vector Machine (SVM) classifier in association with the same set of features to detect the three arm movements and compare the results to demonstrate the effectiveness of our proposed methodology.


Assuntos
Braço/fisiologia , Aceleração , Atividades Cotidianas , Adulto , Idoso , Algoritmos , Fenômenos Biomecânicos , Análise por Conglomerados , Feminino , Voluntários Saudáveis , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/métodos , Movimento , Doenças Neurodegenerativas/fisiopatologia , Reconhecimento Automatizado de Padrão , Máquina de Vetores de Suporte , Telemedicina , Tecnologia sem Fio , Punho/fisiologia , Adulto Jovem
20.
Physiol Meas ; 35(9): 1751-68, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25119720

RESUMO

In this paper we present a method for recognising three fundamental movements of the human arm (reach and retrieve, lift cup to mouth, rotation of the arm) by determining the orientation of a tri-axial accelerometer located near the wrist. Our objective is to detect the occurrence of such movements performed with the impaired arm of a stroke patient during normal daily activities as a means to assess their rehabilitation. The method relies on accurately mapping transitions of predefined, standard orientations of the accelerometer to corresponding elementary arm movements. To evaluate the technique, kinematic data was collected from four healthy subjects and four stroke patients as they performed a number of activities involved in a representative activity of daily living, 'making-a-cup-of-tea'. Our experimental results show that the proposed method can independently recognise all three of the elementary upper limb movements investigated with accuracies in the range 91-99% for healthy subjects and 70-85% for stroke patients.


Assuntos
Acelerometria/métodos , Atividade Motora , Punho , Acelerometria/instrumentação , Atividades Cotidianas , Adulto , Idoso , Algoritmos , Fenômenos Biomecânicos , Calibragem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Rotação , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral , Punho/fisiologia , Punho/fisiopatologia , Adulto Jovem
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