The use of GIS to evaluate traffic-related pollution.
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Air Pollutants↗
Biomedical subjects
D J Briggs
Publications and source records attributed to D J Briggs.
Rabies post-exposure prophylaxis in malnourished children exposed to suspect rabid animals.
Over half of the world's malnourished children live in Asia where more than 90% of reported human rabies deaths occur. In order to determine the effect of malnutrition on the immune response to rabies post-exposure prophylaxis (PEP), 45 children with moderate to severe protein energy malnutrition (PEM) who were exposed to potentially rabid animals were enrolled in a clinical trial. Patients received purified chick embryo cell rabies vaccine (PCECV) on days 0, 3, 7, 14 and 30. Blood was drawn on days 0, 14 and 30 and evaluated for the presence of rabies virus neutralizing antibody. All children that met the protocol criteria developed rabies virus neutralizing antibody titers above the acceptable level of 0.5 IU/mL by day 14 and no serious adverse events were reported. We conclude that children in this study that received four or five doses of rabies vaccine intramuscularly developed an acceptable immune response despite their severe degree of protein energy malnutrition.
Adolescent↗
Time activity modelling of domestic exposures to radon.
Radon gas occurs naturally in the environment with a variable distribution. In some areas radon concentrates sufficiently within the built environment that it is considered as a public health risk. It is possible, successfully, to reduce radon levels in the built environment, and it has been shown that such remediation programmes can be justified in terms of the costs and benefits accruing. However, the estimated dose received by people in their homes depends on the time spent indoors. The research presented here uses data derived from time activity surveys in Northamptonshire, together with radon data from a representative home, to model potential exposures for different population sub-groups. Average home occupancy ranged from 14.8h (probable error 2.5h) for students to 17.7 (3.1) h for adults; schoolchildren spent an average of 14.9 (1.2) h at home. Over a quarter of adults, however, were in the home for 22 h on more. These differences in occupancy patterns lead to substantial differences in radon exposure. In a home with an average hourly ground floor radon concentration of 467 Bqm(-3), modelled hourly average exposures ranged from ca. 250 Bqm(-3) for students and school children, to over 340 Bqm(-3), for women based at home. Modelled exposures show a non-linear association with total time spent at home, suggesting that exposure estimates based on linear models may provide misleading estimates of health risks from radon and the potential benefits of radon remediation. Highest hourly exposures are likely to be experienced by people with highly occupancy, living in single-storey, ground floor accommodation (for example, the elderly the infirm and non-working young mothers). Since these may be least aware of radon risks, and least able to take up remediation measures, they should be specifically targeted for radon monitoring and for assistance in remediation schemes.
Activities of Daily Living↗
No excess risk of adverse birth outcomes in populations living near special waste landfill sites in Scotland.
A recent study showed small excess risks of low birth weight, very low birth weight and certain congenital anomalies in populations living near landfill sites in Great Britain. The objective of the current study was to investigate the risk of adverse birth outcomes associated with residence near special waste landfill sites in Scotland. We studied risks of adverse birth outcomes in populations living within 2 km of 61 Scottish special waste landfill sites operational at some time between 1982 and 1997 compared with those living further away. 324,167 live births, 1,849 stillbirths, and 11,138 congenital anomalies (including terminations) were included in the study. Relative risks were computed for all congenital anomalies combined, some specific anomalies and prevalence of stillbirth and low and very low birth weight (< 2500 g and < 1500 g). For all anomalies combined, relative risk of residence near special waste landfill sites was 0.96 (99% confidence interval 0.89 to 1.02) adjusted for confounders. Adjusted risks were 0.71 (0.36 to 1.42) for neural tube defects, 1.03 (0.85 to 1.26) for cardiovascular defects, 0.84 (0.58 to 1.22) for hypospadias and epispadias (with no excess of surgical corrections), 0.78 (0.27 to 2.23) for abdominal wall defects (1.32 (0.42-4.17) for hospital admissions), 1.22 (0.28 to 5.38) for surgical correction of gastroschisis and exomphalos and 1.01 (0.96 to 1.07) and 1.01 (0.90 to 1.15) for low and very low birth weight respectively. There was no excess risk of stillbirth. In conclusion, we found no statistically significant excess risks of congenital anomalies or low birth weight in populations living near special waste landfill sites in Scotland.
Adolescent↗
Immunogenicity, safety and lot consistency in adults of a chromatographically purified Vero-cell rabies vaccine: a randomized, double-blind trial with human diploid cell rabies vaccine.
The immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) was evaluated using US veterinary medical students. In the first study, 242 healthy adults were enrolled in a randomized, modified double-blind, multicenter trial and received five doses of either CPRV or human diploid cell vaccine (HDCV) by intramuscular injection on days 0, 3, 7, 14, and 28 concurrently with human rabies immunoglobulin in a simulated post-exposure prophylaxis regimen. Post-immunization titers in the CPRV and HDCV groups reached 0.5 IU/ml (the WHO-recommended minimally acceptable titer) or greater in all subjects in both vaccine groups by day 14 and remained above that level through day 90. In the second study, 438 healthy adults were enrolled in a randomized, double-blind, multicenter trial and assigned to receive five doses from one of three lots of CPRV by intramuscular injection on days 0, 3, 7, 14, and 28 in a simulated post-exposure prophylaxis regimen to evaluate lot consistency. Post-immunization titers rapidly increased to over 0.5 IU/ml by day 14 for all subjects and remained above that level through day 42 when the study was terminated. The three lots were considered equivalent. The percentage of subjects with at least one local reaction during the five-dose regimen was slightly lower in the CPRV group than in the HDCV group (P=0.06). The most frequently reported local reaction for all doses of vaccine was pain at the injection site. Headache, myalgia, and malaise were the most frequently reported systemic events. The percentage of subjects with at least one systemic event was significantly lower for CPRV (P=0.0084). No vaccine-related serious adverse reaction was reported in these studies. The results of these studies indicate that CPRV administered intramuscularly to healthy adults is immunogenic and is associated with fewer local and systemic reactions than HDCV.
Adult↗
Importation of dogs and cats to rabies-free areas of the world.
Public pressure from a very mobile society has caused the governments of many rabies-free areas to reevaluate lengthy quarantine systems. In some areas a policy of vaccination, certification, and rabies antibody testing have been implemented to reduce the length of time a dog or cat must spend in quarantine. This has caused an increasing need for pet owners and veterinarians to understand quarantine regulations and shipping methods.
Animals↗
Socio-economic and locational determinants of accessibility and utilization of primary health-care.
Differences in levels of utilization vary and are a function of socio-economic and geographical factors. This paper presents the results of a questionnaire study involving twelve GP practices in Northamptonshire, UK, of factors which affect access and utilization in asthmatics and diabetics; these groups were selected to control for differences in utilization behaviour, as a result of different aetiologies. The questionnaire sought data on: residential location of patients, utilization characteristics of primary health-care, personal circumstances and mobility and hindrances to access and utilization. Key themes were identified relating to age, gender, social class, employment, ethnicity and proximity to the GP surgery. The young, elderly and females report higher rates of utilization, as do nonmanual workers and those who are unemployed. However, accessibility and utilization vary greatly in response to mobility and locational characteristics; these variations tend to be masked by data on overall rates of usage. Optimal scaling techniques were used to investigate the interactions between the factors affecting accessibility and utilization, and to characterize patients in terms of their levels of utilization. Results confirmed that current service provision afforded a differential level of service to patients, which does not directly reflect their level of need.
Adolescent↗
Human lymphocyte proliferation responses following primary immunization with rabies vaccine as neoantigen.
Evaluation of the T-cell immune response following primary antigenic challenge with a neoantigen is a critical aspect of assessment of the cellular immune response. While many antigens can be used to accurately assess in vitro T-cell proliferation to a recall antigen, only a few neoantigens have been tested for their capacities to measure T-cell responses in vitro to a primary immunization. Rabies vaccination is an excellent candidate for the testing of T-cell proliferation responses to a primary immunization because few individuals have been exposed to rabies virus antigens. In the present study 14 rabies vaccine-naïve, healthy adult volunteers were immunized against rabies virus, and T-cell proliferation and antibody responses were measured before and after vaccination. Optimal lymphocyte proliferation to soluble rabies virus antigen occurred after 8 days in culture. The average level of uptake of tritiated thymidine postimmunization was 29,620 +/- 4,448 cpm, whereas preimmunization levels were 12,660 +/- 3,448 cpm (P = 0.002). All individuals showed increases in rabies virus antibody titers from <0.05 to 5.59 +/- 1.64 IU/ml. The degree of proliferation to tetanus toxoid as a recall antigen was similar to the response to rabies virus antigen among the cohort. Due to high levels of preimmunization proliferation, four subjects failed to demonstrate a twofold increase in response to rabies virus antigen. The high levels of T-cell responses may be due to a viral superantigen effect in some individuals. Rabies vaccination offers a safe and effective means for measurement of both T- and B-cell immune responses to a neoantigen in healthy and immune suppressed individuals.
Adult↗
Exposure of hooded capuchin monkeys (Cebus apella cay) to a rabid bat at a zoological park.
On 27 May 1999, a big brown bat (Eptesicus fuscus) was discovered on an island exhibit at the Denver Zoo that contained a troop of 15 hooded capuchin monkeys (Cebus apella cay). The monkeys were attacking the bat when it was discovered. The bat was collected and humanely euthanatized without direct handling and submitted to the Colorado Department of Public Health and Environment Virology Laboratory for rabies evaluation. The monkeys had not been vaccinated against rabies virus. The next day, the laboratory confirmed that the bat was positive for rabies. The recommendations from the Colorado Department of Public Health and Environment and the Centers for Disease Control and Prevention were to euthanatize the monkeys or quarantine them and comply with the human nonvaccinated postexposure protocol. A 1-ml dose of a killed rabies vaccine was administered i.m. in the hip on each of days 2, 7, 12, 19, and 33 postexposure, and a single dose of human rabies immune globulin was administered i.m. 5 days postexposure. Blood was collected under anesthesia in order to evaluate the immune response after rabies vaccination from six monkeys 5 days postexposure, six monkeys 19 days postexposure (five of the six monkeys were the same monkeys bled 5 days postexposure), 15 monkeys 67 days postexposure, and 13 monkeys approximately 1 yr postexposure. All of the monkeys developed and maintained levels of rabies virus neutralizing antibody above 0.05 IU/ml by 67 days postexposure. Although a serologic titer of 0.05 IU/ml indicates an adequate human response after rabies vaccination, no similar information is available for nonhuman primates. To date, none of the monkeys has succumbed to rabies.
Animals↗
Purified Chick Embryo Cell Culture Rabies Vaccine: interchangeability with Human Diploid Cell Culture Rabies Vaccine and comparison of one versus two-dose post-exposure booster regimen for previously immunized persons.
The equivalence and interchangeability of Purified Chick Embryo Cell Culture Rabies Vaccine (PCECV) to Human Diploid Cell Culture Rabies Vaccine (HDCV) and the immunogenicity of a reduced post-exposure regimen with PCECV was investigated. Statistical analyses revealed no difference (P</=0.05) between the geometric mean titers (GMT) on day 49 of subjects that received PCECV or HDCV. In Year 2, subjects were boosted with one or two dose(s) of PCECV. No significant difference (P</=0.05) was detected between the GMT of the two groups on days 7 and 365 post-booster. Subjects that received HDCV initially developed an adequate anamnestic response to PCECV. On day 21 post-booster, the GMT of subjects that received two boosters was higher (151.6 IU/ml) than those that received one booster (120.9 IU/ml). However, this difference may not be clinically significant.
Adult↗
Adult dogs receiving a rabies booster dose with a recombinant adenovirus expressing rabies virus glycoprotein develop high titers of neutralizing antibodies.
Retired greyhound dogs, with low or absent antibody titers to rabies virus following previous vaccinations with commercially available vaccines, were immunized either subcutaneously or intramuscularly with a replication-defective recombinant adenovirus expressing the rabies virus glycoprotein termed Adrab.gp. Immunized animals developed high titers (geometric mean titers of 2630 and 5329) of viral neutralizing antibodies (VNA) against rabies virus by 10 days after vaccination. The antibody titers were even higher (geometric mean titers of 19349 and 122086) by 21 days after vaccination. The results indicate that the recombinant adenovirus expressing rabies virus glycoprotein is capable of inducing antibody immune responses in dogs and therefore may be developed as a rabies virus vaccine for dogs.
Adenoviruses, Human↗
A regression-based method for mapping traffic-related air pollution: application and testing in four contrasting urban environments.
Accurate, high-resolution maps of traffic-related air pollution are needed both as a basis for assessing exposures as part of epidemiological studies, and to inform urban air-quality policy and traffic management. This paper assesses the use of a GIS-based, regression mapping technique to model spatial patterns of traffic-related air pollution. The model--developed using data from 80 passive sampler sites in Huddersfield, as part of the SAVIAH (Small Area Variations in Air Quality and Health) project--uses data on traffic flows and land cover in the 300-m buffer zone around each site, and altitude of the site, as predictors of NO2 concentrations. It was tested here by application in four urban areas in the UK: Huddersfield (for the year following that used for initial model development), Sheffield, Northampton, and part of London. In each case, a GIS was built in ArcInfo, integrating relevant data on road traffic, urban land use and topography. Monitoring of NO2 was undertaken using replicate passive samplers (in London, data were obtained from surveys carried out as part of the London network). In Huddersfield, Sheffield and Northampton, the model was first calibrated by comparing modelled results with monitored NO2 concentrations at 10 randomly selected sites; the calibrated model was then validated against data from a further 10-28 sites. In London, where data for only 11 sites were available, validation was not undertaken. Results showed that the model performed well in all cases. After local calibration, the model gave estimates of mean annual NO2 concentrations within a factor of 1.5 of the actual mean (approx. 70-90%) of the time and within a factor of 2 between 70 and 100% of the time. r2 values between modelled and observed concentrations are in the range of 0.58-0.76. These results are comparable to those achieved by more sophisticated dispersion models. The model also has several advantages over dispersion modelling. It is able, for example, to provide high-resolution maps across a whole urban area without the need to interpolate between receptor points. It also offers substantially reduced costs and processing times compared to formal dispersion modelling. It is concluded that the model might thus be used as a means of mapping long-term air pollution concentrations either in support of local authority air-quality management strategies, or in epidemiological studies.
Air Pollutants↗
Antibody response of patients after postexposure rabies vaccination with small intradermal doses of purified chick embryo cell vaccine or purified Vero cell rabies vaccine.
Although the introduction of tissue culture vaccines for rabies has dramatically improved the immunogenicity and safety of rabies vaccines, they are often prohibitively expensive for developing countries. To examine whether smaller doses of these vaccines could be used, we tested the safety and immunogenicity of purified chick embryo cell vaccine (PCECV) on 211 patients in Thailand with World Health Organization (WHO) category II and III exposures to rabies. The patients presented at two Thai hospitals and were randomized into three groups. Patients in Group 1 received 0.1 ml PCECV intradermally at two sites on days 0, 3, 7, and at one site on days 30 and 90. Group 2 was treated similarly, except that purified Vero cell rabies vaccine (PVRV) was used instead of PCECV. Group 3 received 1.0 ml PCECV intramuscularly on days 0, 3, 7, 14, 30 and 90. After 0, 3, 7, 14, 30 and 90 days serum was collected from the subjects and the geometric mean titres (GMTs) of rabies virus neutralizing antibody determined. After 14 days the GMT of 59 patients vaccinated intradermally with PCECV was equivalent to that of patients who received PVRV. Adverse reactions were more frequent in patients who received vaccines intradermally, indicating the reactions were associated with the route of injection, rather than the vaccine per se. We conclude that PCECV is a safe and highly immunogenic vaccine for postexposure rabies vaccination when administered intradermally in 0.1-ml doses using the two-site method ("2,2,2,0,1,1") recommended by WHO.
Adolescent↗
A comparison of two serological methods for detecting the immune response after rabies vaccination in dogs and cats being exported to rabies-free areas.
Levels of rabies virus neutralizing antibody in sera from dogs and cats were titrated to endpoint by the Rapid Fluorescent Focus Inhibition Test (RFFIT) and retested by the RFFIT and the Fluorescent Antibody Virus Neutralization test (FAVN). The two tests were compared for their ability to detect the 0.5 international units/ml (I.U.) of antibody required by the World Health Organization and the Office International des Epizooties as the minimum response for proof of rabies immunization. No difference was observed in sensitivity or specificity for either method in tests of 168 sera from unvaccinated animals or 70 sera from vaccinated animals with high levels of neutralizing antibody (an initial RFFIT titre of > or = 1.0 I.U.). Test to test variation occurred for results obtained by both RFFIT and FAVN for 95 sera from vaccinated animals with low to moderate levels of neutralizing antibody (RFFIT titre < 1.0 I.U.). No significant differences were detected for the 95 sera in the frequency for one methodology more often than the other to have a positive response (> or = 0.5 I.U.), nor were significant differences detected for the symmetry (P = 0.43) or the marginal homogeneity (P = 0.39) of results obtained by the two methods. Both methods can adequately identity unvaccinated animals, but false positive and false negative results are possible for either method when a single test is used to measure the antibody response of low-responding vaccinated animals. Nucleotide sequence analysis identified several amino acid differences in stocks of the challenge rabies virus from different laboratories. The small differences in neutralizing antibody titre that may result from mutations in the challenge virus are not important for evaluating immunity induced by vaccines which are themselves prepared from a variety of different rabies virus strains, but differences in the challenge virus, rather than differences in methodology, may account for at least some of the discrepant results reported in inter-laboratory surveys. Comparative studies of serological methods for measuring rabies antibodies should use well-characterized unpassaged virus stocks obtained from a single reference laboratory.
Amino Acid Sequence↗
Viral excretion in domestic ferrets (Mustela putorius furo) inoculated with a raccoon rabies isolate.
OBJECTIVE: To determine susceptibility, incubation and morbidity periods, clinical signs of infection, serologic response, and excretion of virus in domestic ferrets inoculated with rabies virus of raccoon origin. ANIMALS: 54 domestic ferrets. PROCEDURE: 5 groups of ferrets were inoculated IM with the rabies virus. Oral cavity swab specimens and saliva were obtained for virus isolation. Blood was obtained for virus-neutralizing antibody determination. If clinical signs were severe, ferrets were euthanatized immediately. Salivary gland and brain tissue was collected for virus isolation and rabies diagnosis, respectively. RESULTS: Of 51 inoculated ferrets, 19 (37%) were euthanatized with clinical signs of rabies. Mean incubation period was 28 days (range, 17 to 63 days). Clinical signs included ataxia, cachexia, inactivity, paresis, paraparesis, bladder atony, tremors, hypothermia, lethargy, constipation, paralysis, and anorexia. Two rabid ferrets manifested aggressive behavior. Mean morbidity period was 4 to 5 days (range, 1 to 8 days). Virus antigen was detected in brain tissue from all rabid ferrets (n = 19). Two rabid ferrets had detectable virus-neutralizing antibody. Of 32 ferrets that survived, only 1 seroconverted; survivors remained clinically normal throughout the observation period. Rabies virus was isolated from salivary glands of 12 of 19 (63%) rabid ferrets, and 9 (47%) shed virus in saliva. Initiation of virus excretion ranged from 2 days before onset of illness to 6 days after onset. CONCLUSIONS AND CLINICAL RELEVANCE: Rabies should be considered in the differential diagnosis for ferrets that have acute onset of paralysis or behavioral changes and a condition that rapidly deteriorates despite intense medical intervention.
Animals↗
Pathogenesis of experimentally induced rabies in domestic ferrets.
OBJECTIVE: To determine susceptibility, incubation and morbidity periods, clinical signs, serologic response, and excretion of virus in domestic ferrets inoculated with rabies virus. ANIMALS: 55 domestic ferrets. PROCEDURE: 5 groups of 10 ferrets were inoculated with rabies virus, IM, at doses of 10(5.5) to 10(1.5) median mouse intracerebral lethal dose. Ferrets were observed and behavior was recorded. Rectal temperature, body weight, and samples from the oral cavity and samples of saliva and blood were obtained. Virus isolation was attempted, using intracranial mouse inoculation and cell culture. Virus neutralizing antibodies were determined by rapid fluorescent focus inhibition test. Ferrets were euthanatized immediately if clinical signs were severe. Rabies was confirmed by direct immunofluorescent antibody test. RESULTS: Mean incubation period was 33 days (range, 16 to 96 days). Clinical signs included ascending paralysis, ataxia, cachexia, bladder atony, fever, hyperactivity, tremors, and paresthesia. Mean morbidity period was 4 to 5 days (range, 2 to 10 days). Virus antigen was detected in brain tissue from all clinically rabid ferrets. Ferrets given the highest viral dose were euthanatized and had VNA; ferrets receiving the next dilution also were euthanatized, but only 4 had seroconverted. Of 17 ferrets that survived, 5 seroconverted. Survivors remained clinically normal except for 1 that recovered with severe paralytic sequelae. Rabies virus was isolated from the salivary gland of 1 ferret that was euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE: Rabies should be considered as a differential diagnosis in any ferret that has acute onset of paralysis or behavioral changes and a condition that rapidly deteriorates despite intense medical intervention.
Animals↗
Safety and immunogenicity of Lyssavac Berna human diploid cell rabies vaccine in healthy adults.
A clinical trial testing the safety and immunogenicity of a newly developed human diploid cell rabies vaccine (Lyssavac-HDC) was conducted on subjects at three colleges of veterinary medicine in the United States. Lyssavac-HDC is a sterile lyophilized vaccine containing no antibiotics or preservatives and is administered intramuscularly as a 0.5 ml dose of vaccine containing at least 2.5 i.u. of rabies inactivated antigen per dose. Subjects were given either a three dose pre-exposure series (days 0, 7, and 28), followed by one booster dose of vaccine (day 360); or a five dose simulated post-exposure series of injections (days 0, 3, 7, 14, and 28). All subjects in the post-exposure and pre-exposure groups possessed adequate levels of rabies neutralizing antibody (> or = 5) when tested on day 14 and day 28, respectively. Subjects in the pre-exposure group demonstrated a vigorous anamnestic response after the administration of one booster dose of vaccine on day 360. The type and severity of local and systemic reactions observed were comparable to other primary cell culture rabies vaccines. Significantly, there were no type III hypersensitivity reactions reported in subjects previously immunized with Lyssavac-HDC after the administration of a booster dose of vaccine on day 360.
Adult↗
Vaccination of racing greyhounds: effects on humoral and cellular immunity.
Greyhound kennel owners frequently employ multiple vaccination schedules in an attempt to reduce financial losses incurred as a result of infectious diseases. In order to determine the effects of multiple vaccination schedules on the immune system of racing greyhounds, three litters of greyhound pups raised in laboratory conditions were divided into two groups and subjected to either a maximum or a minimum vaccination schedule. Blood samples were collected biweekly for 6 months beginning at 2 weeks of age and analyzed to establish 'baseline' values for the lymphatic system of greyhounds. Lymphocyte transformation, total and differential leukocyte counts, and flow cytometry were used to evaluate cellular immunity. Humoral immunity was evaluated using serum neutralization and hemagglutination inhibition tests. Proliferation of peripheral blood lymphocytes in response to the mitogen concanavalin A (Con A) was higher for the maximum vaccination groups. The frequency distribution of circulating CD4 and IgG labeled lymphocytes was higher in the minimum vaccination groups. A significant treatment by time interaction in CD4, IgG, and IgM labeled cells was observed, This interaction, however, was not significant at any point in time for CD4 and IgG labeled cells. The percentage of lymphocytes expressing surface IgM was significantly higher in the minimum vaccination groups at 10 and 14 weeks of age. No significant differences were detected in humoral immunity between the maximum and minimum groups of each litter. Results of this study indicate that maximum vaccination schedules do not appear to be more effective or more immunosuppressive than minimum vaccination schedules.
Animals↗