Search PubMed⌕ Search

Biomedical subjects

R M Anderson

Publications and source records attributed to R M Anderson.

At least 91 records · Page 5Linked to original sources

The distribution of Schistosoma japonicum eggs in faeces and the effect of stirring faecal specimens.

Experiments were performed to determine whether Schistosoma japonicum eggs are randomly dispersed in faeces and the effect of stirring faecal specimens prior to sampling. For each of 13 patients infected with S. japonicum, eggs were counted in 150 subsamples from a single stool specimen, using the Kato-Katz smear technique. Eggs were non-randomly distributed in all 13 stools, and showed an aggregated distribution. In most patients there were significant differences in the distribution of eggs between the centre and the surface of the stool. Stirring of the stool prior to sampling decreased the variability of counts.

Animals↗

Population biology, evolution, and immunology of vaccination and vaccination programs.

The purpose of prophylactic vaccination is to reduce morbidity and mortality in a population. Many questions related to the design of vaccines and vaccination programs require a population standpoint for their sharp formulation and laboratory and field studies to understand their immunologic background. Practical suggestions of the workshop included increased studies of age-specific immunity, better immunoepidemiologic surveillance, better design of efficacy studies, and more systematic sampling of parasite strains to study the evolutionary pressure exerted by vaccines. Theoretical immunology has much to contribute. One of the realizations of the workshop was the value of a strong interdisciplinary approach in vaccine development, utilizing relevant contributions from immunology, population biology, mathematical modeling, epidemiology, molecular biology, and virology.

Animals↗

Comparative neuropathology of Kuru with the new variant of Creutzfeldt-Jakob disease: evidence for strain of agent predominating over genotype of host.

The three major influences on the phenotype of the transmissible spongiform encephalopathies are believed to be strain of agent, route of infection and host genotype. We have compared the pathologic profiles and genotypes of the new variant of Creutzfeldt-Jakob disease (vCJD) and kuru. The comparison reveals that there are distinct lesional differences particularly in the prion protein (PrP) load and distribution as seen by immunohistochemistry. The clinico-pathologic phenotypes and the genotypes of these two diseases are sufficiently different to suggest that the strain of agent may play a greater role than any presumptive common route of peripherally acquired infection.

Adolescent↗

The reliability of the Diabetes Care Profile for African Americans.

The Diabetes Care Profile (DCP) is an instrument used to assess social and psychological factors related to diabetes and its treatment. The reliability of the DCP was established in populations consisting primarily of Caucasians with type 2 diabetes. This study tests whether the DCP is a reliable instrument for African Americans with type 2 diabetes. Both African American (n = 511) and Caucasian (n = 235) patients with type 2 diabetes were recruited at six sites located in the metropolitan Detroit area. Scale reliability was calculated by Cronbach's coefficient alpha. The scale reliabilities ranged from .70 to .97 for African Americans. These reliabilities were similar to those of Caucasians, whose scale reliabilities ranged from .68 to .96. The Feldt test was used to determine differences between the reliabilities of the two patient populations. No significant differences were found. The DCP is a reliable survey instrument for African American and Caucasian patients with type 2 diabetes.

Black or African American↗

The reliability and validity of a brief diabetes knowledge test.

OBJECTIVE: To examine the reliability and validity of a brief diabetes knowledge test. The diabetes knowledge test has two components: a 14-item general test and a 9-item insulin-use subscale. RESEARCH DESIGN AND METHODS: Two populations completed the test. In one population, patients received diabetes care in their community from a variety of providers, while the other population received care from local health departments. Cronbach's coefficient alpha was used to calculate scale reliability for each sample. To determine validity, patient group differences were examined. It was hypothesized that test scores would be higher for patients with type 1 diabetes, for patients with more education, and for patients who had received diabetes education. RESULTS: The coefficient alpha s for the general test and the insulin-use subscale indicate that both are reliable, alpha > or = 0.70. In the community sample, patients with type 1 diabetes scored higher than patients with type 2 diabetes on the general test and the insulin-use subscale. In the health department sample, patients with type 1 scored higher than patients with type 2 on the insulin-use subscale. For both samples, scores increased as the years of formal education completed increased, and patients who received diabetes education scored higher than patients who did not. CONCLUSIONS: Although the samples differed demographically, the reliability and validity of the test were supported in both the community and the health department samples. This suggests that the test is appropriate for a variety of settings and patient populations.

Adult↗

The third version of the Diabetes Attitude Scale.

OBJECTIVE: The objective of this study was to develop a third version of the Diabetes Attitude Scale (DAS-3) that is congruent with current scientific knowledge about diabetes, has improved subscale internal reliability scores, and is shorter than the earlier versions of this instrument. RESEARCH DESIGN AND METHODS: The second DAS was revised and rewritten by a panel of diabetes experts, including patients, associated with the University of Michigan Diabetes Research and Training Center. The revised version of the instrument was sent to physicians, nurses, dietitians, and patients with diabetes. Completed and usable questionnaires were obtained from 384 patients with diabetes, 321 physicians, 540 nurses, and 569 dietitians. The total number of surveys used for these analyses was 1,814. RESULTS: The study resulted in a revised DAS with 33 items and five discrete subscales. The subscales were attitudes toward the following: 1) need for special training to provide diabetes care, 2) seriousness of type 2 diabetes, 3) value of tight glucose control, 4) pyschosocial impact of diabetes, and 5) attitude toward patient autonomy. Overall, the subscale reliabilities of the DAS-3 were superior to the earlier versions of the scale. CONCLUSIONS: The DAS-3 is a valid and reliable general measure of diabetes-related attitudes and is most suitable for comparisons across different groups of health care professionals and/or patients. The DAS-3 is also suitable for the evaluation of patient and/or professional education programs if those programs focus on the specific topic areas measured by the five DAS-3 subscales.

Attitude of Health Personnel↗

Genetic analysis of farmed deer hybrids.

Molecular methods which identify species-specific genetic markers are valuable for identification and genetic analysis of hybrid deer. We have used a variety of molecular techniques to compare Père David's deer Elaphurus davidianus, red deer Cervus elaphus scotticus and North American wapiti C. e. manatobensis. In total, these analyses have identifed over 300 markers in which Père David's deer sires are distinct from farmed red deer and over 100 markers in which wapiti sires differ from red deer. Subsets of these markers have been used to identify hybrids on farms, and to estimate the proportion of red deer and wapiti in hybrid animals. Analysis of the segregation of the species-specific alleles in 352 backcross 1/4 Père David's, 3/4 red deer hybrids has produced a deer genetic linkage map which describes the chromosomal grouping and order of the markers. Correlation of the variability in phenotypic traits with marker segregation in the back-cross hybrids has located genes which influence variation in gestation length, pedicle-initiation, birth weight, growth rate and a variety of morphological traits in Père David's deer x red deer hybrids. Such genetic analyses can now be extended, using new marker technologies, to more closely related taxa, such as farmed red deer and wapiti hybrids, and potentially analyse natural hybrid zones.

Animal Husbandry↗

The transmission dynamics of antibiotic-resistant bacteria: the relationship between resistance in commensal organisms and antibiotic consumption.

We propose a mathematical model of the transmission dynamics of colonization by commensal bacteria within a human community subject to varying levels of antibiotic use designed to control morbidity induced by pathogenic strains of the normally commensal organisms. Colonization is assumed not to induce morbidity in the majority of cases, and antibiotic use is assumed to be related to the arrival and growth of pathogenic strains that give rise to infections including clinical symptoms of disease. In the absence of antibiotic resistance, the model shows how the pattern of antibiotic prescription and use can eliminate the non-pathogenic commensal strains from the host community if the fraction of people taking antibiotics with a defined efficacy exceeds some critical level. The model is extended to take account of the evolution of antibiotic resistance in the commensal population. We assume resistance may be either plasmid-mediated or conferred by selection of low-level pre-existing mutants, and that resistant organisms may experience reduced reproductive fitness. Invasion of the host community by drug-resistant commensals is possible if certain antibiotic prescribing patterns pertain. We calculate these conditions in terms of the transmission parameter of the organism and the level of antibiotic prescription and use. The model is employed to address the issues of how best to use antibiotics in populations harbouring resistant organisms, and when resistant bacteria will out-compete sensitive strains.

Bacterial Infections↗

On the critical behaviour of simple epidemics.

We show how ideas and models which were originally introduced to gain an understanding of critical phenomena can be used to interpret the dynamics of epidemics of communicable disease in real populations. Specifically, we present an analysis of the dynamics of disease outbreaks for three common communicable infections from a small isolated island population. The strongly fluctuating nature of the temporal incidence of disease is captured by the model, and comparisons between exponents calculated from the data and from simulations are made. A forest-fire model with sparks is used to classify the observed scaling dynamics of the epidemics and provides a unified picture of the epidemiology which conventional epidemiological analysis is unable to reproduce. This study suggests that power-law scaling can emerge in natural systems when they are driven on widely separated time-scales, in accordance with recent analytic renormalization group calculations.

Disease Outbreaks↗

Analysis of dam-calf pairs of BSE cases: confirmation of a maternal risk enhancement.

We investigate whether a calf born to a dam that develops bovine spongiform encephalopathy (BSE) (prior or subsequent to the birth) is itself at an enhanced risk of developing BSE. Analyses utilize the main database on reported BSE cases in the British cattle herd maintained by the Central Veterinary Laboratory in Weybridge to trace the dams of BSE-affected animals born following the ruminant feed ban in July 1988. The data reveal a significantly enhanced risk of disease in calves born to BSE-affected dams, with the risk being greatest when birth occurs after the onset of clinical signs of disease in the dam. The dependence of the maternally enhanced risk on the maternal incubation stage at birth argues for a significant component of direct maternal transmission of the aetiological agent of BSE, and offers little support for the hypothesis of genetic predisposition. Using a statistical likelihood model, we obtain estimates of the rate of direct maternal transmission by maternal incubation stage; however, biases in the available data make these values minimum estimates.

Animals↗

Vaccine design, evaluation, and community-based use for antigenically variable infectious agents.

A major challenge for vaccine design and development, and for trials of new vaccines, is to tackle antigenically variable infectious agents. Here we outline a few general conceptual issues and then discuss new frameworks that are being developed to help understand how vaccination might change the distribution, abundance, and type of strains in a population. Herd Immunity is a key concept in population-based immunisation programmes and has to be considered in vaccine design and use even though it may cause a conflict between the needs of the individual versus those of the community. This issue is of increasing importance since once common infections are becoming rare due to effective vaccination. Concomitantly, adverse effects arising from immunisation are becoming more apparent as infection-induced morbidity declines to very low levels. Efficacy is widely regarded as a key criterion in vaccine design but duration of protection is of equal importance. Whether it is possible to produce effective vaccines to antigenically diverse pathogens remains uncertain but progress towards this goal will be enhanced by a better understanding of the population genetics of the target infectious agent facilitated by molecular epidemiological studies to assess the genetic constitution of pathogen populations and changes therein over time.

Antigenic Variation↗

Vaccination and the population structure of antigenically diverse pathogens that exchange genetic material.

Populations of antigenically diverse pathogens undergoing genetic exchange may be categorized into strains on the basis of a set of principal protective antigens. The extent to which polyvalent vaccines based on these protective antigens can alter the population structure of the pathogen is determined by the degree of cross-protection between strains. In the case where there is no cross-protection, vaccinating against a particular strain will have no effect on the others. As cross-protection increases, the strains containing the antigenic variants included in the vaccine will be diminished in prevalence, and those that do not will increase in prevalence. The rise in prevalence of the latter will become more and more exaggerated as cross-protection increases. However, beyond a critical level of cross-protection, in the absence of vaccination, the steady state of the system is asymmetric in that a certain subset of strains (with non-overlapping repertoires of antigenic variants) will dominate over the others in terms of prevalence. Under these circumstances, a vaccine consisting of the most immunogenic combinations of antigenic variants can cause a dramatic increase in frequency of a subset of rare strains.

Alleles↗

A genetic interpretation of heightened risk of BSE in offspring of affected dams.

An analysis is presented of the results of a cohort study designed to test whether or not the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle can be transmitted maternally (vertically) from dam offspring. Various genetic models are fitted to the data under the assumption that the results could be explained entirely by genetic predisposition to disease (as opposed to maternal transmission) given exposure of offspring of diseased and unaffected dams to contaminated cattle feed. The analyses suggest that the results could be explained by the hypothesis of genetic predisposition, provided a large difference exists in the susceptibility of resistant and susceptible hosts, and explore the range of genotypic parameters and frequencies consistent with the limited currently available data. The results presented are broadly robust, even under the scenario that a portion of the observed maternally enhanced risk of BSE is due to a low level of maternal transmission in late incubation stage dams.

Alleles↗

Conclusions--scientific research and its implications.

The organizers of this meeting felt that it would be appropriate to have two short papers at the end of this volume to summarize the key points that are of relevance to scientists and the insurance and actuarial professions. This was felt to be of particular importance given the very heterogeneous backgrounds of members of the audience at the meeting, namely, scientific, medical, legal, social and financial. The objectives are to summarize the key issues in layman's terms-trying to avoid jargon, exaggeration and a partisan approach. In some ways my task is somewhat easier than Chris Daykin's job, since there are only four scientific and medical presentations compared with seven from the actuarial, social and legal side. I will organize this brief report, which by definition will involve repetition of some of the points made in the scientific and medical papers in this volume, into three areas: (1) introductory comments on demography and evolution relevant to human genetics; (2) the scientific opportunities; and (3) a brief comment on their implications for the health and care of individuals.

Genetic Testing↗

The epidemiology of BSE in cattle herds in Great Britain. I. Epidemiological processes, demography of cattle and approaches to control by culling.

This paper explores the key epidemiological processes and demographic factors that determined the pattern of transmission of the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle herds in Great Britain (GB). The analyses presented utilize data from published and unpublished experimental studies and from the GB central database of confirmed BSE cases. We review the experimental and epidemiological evidence that has both confirmed indirect horizontal transmission via the consumption of infectious material as the major transmission route and provided information on the duration and variability of the dose-dependent incubation period of BSE in cattle. The epidemiological and genetic data pertaining to the possible existence of maternal transmission and/or genetically variable susceptibility to infection is discussed. The demography of British cattle is characterized and the impacts of key demographic features on the observed epidemic profile are discussed. In the main BSE case database, analyses reveal that BSE cases cluster significantly at both the holding and county scale. Furthermore, analysis of longitudinal patterns reveal substantial temporal within-holding correlation. Such clustering of cases suggests a highly heterogeneous infection process. The paper ends with a discussion of how analyses of spatio-temporal clustering inform the design of targeted culling programmes aimed at reducing future disease incidence. We show how the retrospective implementation of culling policies on the BSE case database allows the qualitative evaluation of policy performance, but that model predictions of future trends in case incidence are required to estimate the precise impact of any current or future programme.

Age Factors↗

The epidemiology of BSE in cattle herds in Great Britain. II. Model construction and analysis of transmission dynamics.

Mathematical model that describe the key processes determining the pattern of the bovine spongiform encephalopathy (BSE) epidemic in British cattle are derived that allow for infection from feed as well as maternal and direct horizontal transmission. Heterogeneous susceptibility classes are also incorporated into the analysis. Maximum likelihood methods are used to estimate parameters and to obtain confidence intervals from available experimental and epidemiological data. A comprehensive sensitivity analysis of all model parameters and distributional assumptions is presented. Additional validation is provided by fitting the model to independent data collected in Northern Ireland. Model estimates and predictions based on BSE case data for Great Britain and Northern Ireland, together with their implications, are reviewed, and future research priorities discussed.

Age Distribution↗