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Biomedical subjects

R M Anderson

Publications and source records attributed to R M Anderson.

At least 55 records · Page 3Linked to original sources
PubMed2000

The transmission dynamics of the aetiological agent of scrapie in a sheep flock.

We formulate and investigate the properties of a model framework to mimic the transmission dynamics of the aetiological agent of scrapie in a sheep flock. We derive expressions for summary parameters that characterize transmission scenarios, notably the basic reproduction number R(0) and the mean generation time T(g). The timescale of epidemic outbreaks is expressed in terms of R(0) and cumulants of the generation time distribution. We discuss the relative contributions to the overall rate of transmission of horizontal and vertical routes during invasion and in endemicity. Simplified models are used to obtain analytical insight into the characteristics of the endemic state.

Animals↗
PubMed2000

Complex chromosome aberrations in peripheral blood lymphocytes as a potential biomarker of exposure to high-LET alpha-particles.

PURPOSE: To determine the induction and transmission, to second and third division cells, of complex chromosome aberrations in peripheral blood lymphocytes after exposure to high-LET alpha-particles in vitro. MATERIALS AND METHODS: Separated peripheral blood lymphocytes collected from four healthy donors were irradiated in vitro with either high-LET alpha-particles (121 keV/microm; 0.5 Gy) or low-LET X-rays (250kV constant potential; 3 Gy). Cells were harvested in first, second and third division post-irradiation and chromosome aberrations observed at each cell division were analysed by combining the techniques of FISH and DAPI/Hoechst 33258 harlequin staining. Whole chromosome probes were used for chromosomes 1, 2 and 5, together with a pan-centromeric probe and the resulting chromosome 'painting' patterns were classified according to the Savage and Simpson (S & S) scheme (Savage and Simpson 1994a, Savage and Tucker 1996). RESULTS: A greater proportion of complex chromosome aberrations was observed, defined as involving three or more breaks in two or more chromosomes, relative to total exchanges, after exposure to 0.5 Gy alpha-particles (mean 1 track/cell) than after the high reference dose of 3 Gy X-rays (49-56% and 20-22%, respectively). Qualitatively, alpha-particles induced chromosome aberrations of far greater complexity than those observed after X-rays. This was reflected by both the rapid reduction in the percentage of damaged cells between first and second division indicative of cell death, and the spectrum of aberration types observed in second and third division cells post-irradiation. Regardless of this complexity, 15% of the complexes induced by alpha-particles at first division were potentially transmissible and by third division, transmissible-type complexes, specifically insertions, represented the predominant complex type (65%). CONCLUSION: Transmissible-type complexes were observed, specifically insertions, in both second and third division cells after exposure to high-LET alpha-particles (0.5 Gy) in vitro. The authors predict these cells to be stable and to be capable of persisting through many cell generations. Considering that the induction of complex chromosome aberrations by low-LET radiation is strongly dependent on dose, so that they are expected to be undetectable at environmental exposures, insertions are much more likely to be a characteristic feature of high-LET radiation at all doses. From this the usefulness of insertions as biomarkers of past exposure to environmentally relevant doses of high-LET alpha-particles is supported.

Alpha Particles↗
PubMed2000

Mathematical models of the transmission and control of sexually transmitted diseases.

BACKGROUND: The development of mathematical models to describe and interpret the epidemiology of sexually transmitted infections has involved the incremental addition of various forms of biological and behavioral complexity to simple mathematical templates. GOAL: To review simple and complex models used in study of observed epidemiologic pattern. STUDY DESIGN: An overview of modeling in sexually transmitted disease epidemiology identifies the function of different types of models. RESULTS: Simple models have the advantage of transparency and analytical tractability and can illustrate the relative merits of different intervention options. However, real life is replete with complexities that can have effects that are difficult to predict in the absence of a mathematical framework. CONCLUSIONS: Research should increasingly be based on robust parameterization of model structures and try to capture individual behaviors. Progress will be most rapid by interdisciplinary work where the clinician, epidemiologist, and mathematician work collaboratively to help improve our knowledge of how to best control infection and disease.

Female↗
PubMed2000

The influence of treatment modality and ethnicity on attitudes in type 2 diabetes.

OBJECTIVE: The study examines diabetes attitude differences by treatment modality (insulin vs. no insulin), race/ethnicity, and the interaction of these two variables for people with type 2 diabetes. RESEARCH DESIGN AND METHODS: Data were collected with the Diabetes Care Profile (DCP), an instrument that assesses psychosocial factors related to diabetes. Participants (n = 672) were recruited in the metropolitan Detroit, Michigan, area from 1993 to 1996. A total of 68% of these participants were African-Americans with type 2 diabetes, and 32% were Caucasians with type 2 diabetes. Analyses of covariance were performed to examine the effects of race/ethnicity, treatment, and their interaction for each DCP scale. RESULTS: The four patient categories (two ethnicities by two treatment modalities) differed by age, years with diabetes, education, and sex distribution. Treatment modality had a significant effect on 6 of the 16 DCP scales (Control, Social and Personal Factors, Positive Attitude, Negative Attitude, Self-Care Ability, and Exercise Barriers). Ethnicity was a significant effect for three scales (Control, Support, and Support Attitudes). The interaction of race/ethnicity and treatment modality was a significant effect for two related attitude scales (Positive Attitude and Negative Attitude). CONCLUSIONS: The results suggest that attitudes toward diabetes are similar for African-American and Caucasian patients with type 2 diabetes. The results also suggest that treatment modality has a greater effect on attitudes than either race/ethnicity or the interaction effect. However, Caucasian patients using insulin differed from the other patient groups by having the least positive and the most negative attitudes regarding diabetes.

Adolescent↗
PubMed2000

The Diabetes Empowerment Scale: a measure of psychosocial self-efficacy.

OBJECTIVE: The purpose of this study was to assess the validity, reliability, and utility of the Diabetes Empowerment Scale (DES), which is a measure of diabetes-related psychosocial self-efficacy. RESEARCH DESIGN AND METHODS: In this study (n = 375), the psychometric properties of the DES were calculated. To establish validity, DES subscales were compared with 2 previously validated subscales of the Diabetes Care Profile (DCP). Factor and item analyses were conducted to develop subscales that were coherent, meaningful, and had an acceptable coefficient alpha. RESULTS: The psychometric analyses resulted in a 28-item DES (alpha = 0.96) with 3 subscales: Managing the Psychosocial Aspects of Diabetes (alpha = 0.93), Assessing Dissatisfaction and Readiness To Change (alpha = 0.81), and Setting and Achieving Diabetes Goals (alpha = 0.91). Consistent correlations in the expected direction between DES subscales and DCP subscales provided evidence of concurrent validity. CONCLUSIONS: This study provides preliminary evidence that the DES is a valid and reliable measure of diabetes-related psychosocial self-efficacy. The DES should be a useful outcome measure for various educational and psychosocial interventions related to diabetes.

Adult↗
PubMed1999

Antigen-driven CD4+ T cell and HIV-1 dynamics: residual viral replication under highly active antiretroviral therapy.

Antigen-induced stimulation of the immune system can generate heterogeneity in CD4+ T cell division rates capable of explaining the temporal patterns seen in the decay of HIV-1 plasma RNA levels during highly active antiretroviral therapy. Posttreatment increases in peripheral CD4+ T cell counts are consistent with a mathematical model in which host cell redistribution between lymph nodes and peripheral blood is a function of viral burden. Model fits to patient data suggest that, although therapy reduces HIV replication below replacement levels, substantial residual replication continues. This residual replication has important consequences for long-term therapy and the evolution of drug resistance and represents a challenge for future treatment strategies.

Anti-HIV Agents↗
PubMed1999

Vancomycin-resistant enterococci in intensive-care hospital settings: transmission dynamics, persistence, and the impact of infection control programs.

Vancomycin-resistant enterococci (VRE) recently have emerged as a nosocomial pathogen especially in intensive-care units (ICUs) worldwide. Transmission via the hands of health-care workers is an important determinant of spread and persistence in a VRE-endemic ICU. We describe the transmission of nosocomial pathogens by using a micro-epidemiological framework based on the transmission dynamics of vector-borne diseases. By using the concept of a basic reproductive number, R0, defined as the average number of secondary cases generated by one primary case, we show quantitatively how infection control measures such as hand washing, cohorting, and antibiotic restriction affect nosocomial cross-transmission. By using detailed molecular epidemiological surveillance and compliance monitoring, we found that the estimated basic reproductive number for VRE during a study at the Cook County Hospital, Chicago, was approximately 3-4 without infection control and 0.7 when infection control measures were included. The impact of infection control was to reduce the prevalence from a predicted 79% to an observed 36%. Hand washing and staff cohorting are the most powerful control measures although their efficacy depends on the magnitude of R0. Under the circumstances tested, endemicity of VRE was stabilized despite infection control measures, by the constant introduction of colonized patients. Multiple stochastic simulations of the model revealed excellent agreement with observed pattern. In conjunction with detailed microbiological surveillance, a mathematical framework provides a precise template to describe the colonization dynamics of VRE in ICUs and impact of infection control measures. Our analyses suggest that compliance for hand washing significantly in excess of reported levels, or the cohorting of nursing staff, are needed to prevent nosocomial transmission of VRE in endemic settings.

Anti-Bacterial Agents↗
PubMed1999

Studies of antibiotic resistance within the patient, hospitals and the community using simple mathematical models.

The emergence of antibiotic resistance in a wide variety of important pathogens of humans presents a worldwide threat to public health. This paper describes recent work on the use of mathematical models of the emergence and spread of resistance bacteria, on scales ranging from within the patient, in hospitals and within communities of people. Model development starts within the treated patient, and pharmacokinetic and pharmacodynamic principles are melded within a framework that mirrors the interaction between bacterial population growth, drug treatment and the immunological responses targeted at the pathogen. The model helps identify areas in which more precise information is needed, particularly in the context of how drugs influence pathogen birth and death rates (pharmacodynamics). The next area addressed is the spread of multiply drug-resistant bacteria in hospital settings. Models of the transmission dynamics of the pathogen provide a framework for assessing the relative merits of different forms of intervention, and provide criteria for control or eradication. The model is applied to the spread of vancomycin-resistant enterococci in an intensive care setting. This model framework is generalized to consider the spread of resistant organisms between hospitals. The model framework allows for heterogeneity in hospital size and highlights the importance of large hospitals in the maintenance of resistant organisms within a defined country. The spread of methicillin resistant Staphylococcus aureus (MRSA) in England and Wales provides a template for model construction and analysis. The final section addresses the emergence and spread of resistant organisms in communities of people and the dependence on the intensity of selection as measured by the volume or rate of drug use. Model output is fitted to data for Finland and Iceland and conclusions drawn concerning the key factors determining the rate of spread and decay once drug pressure is relaxed.

Anti-Bacterial Agents↗
PubMed1999

Transmission dynamics and epidemiology of dengue: insights from age-stratified sero-prevalence surveys.

The relationship between infection with the four major serotypes of dengue virus and the occurrence of different forms of disease is complex and not fully understood. Interpreting longitudinal records of the incidence of serious disease to gain insight into the transmission dynamics and epidemiology of the virus is therefore complicated. Since age reflects duration of exposure, age-stratified, strain-specific serological surveys carried out at one point in time, or over a short time interval, can potentially provide a rich source of information on longitudinal patterns. This paper describes the development and application (to data collected in Thailand) of statistically rigorous methods designed to estimate time-varying, strain-specific forces of infection, and thus basic reproduction numbers, from cross-sectional serological data. The analyses provide support for the hypothesis that antibody-dependent enhancement of transmission influences observed epidemiological pattern. Age-stratified serological data also reveal evidence of a propensity for the annual incidence of infection to oscillate over time with a frequency of several years. The latter observation is consistent with the predictions of simple mathematical models of the transmission dynamics of the virus. The estimates of the basic reproduction numbers obtained are similar in magnitude for each dengue serotype, being in the range of four to six. Such values are higher than those obtained from earlier analyses, and the implications of this for dengue control are discussed.

Dengue↗
PubMed1999

Some important issues in the planning of phase III HIV vaccine efficacy trials.

Given that interesting HIV vaccine candidates, including live preparations and DNA plasmids, exist and that the first phase III vaccine (AIDSVAX) testing is due to begin this summer, 1998, in the U.S., adequately addressing trial preparedness is a pressing issue. Despite double-blind randomized controlled clinical trial design, there may be difficulties with interpretation and use of the usual measures of vaccinal efficacy and calculation of sample size. Difficulties arise from vaccine characteristics (e.g. mode of action, time-lag, waning) and population heterogeneities (e.g. differences in susceptibility, sexual behaviour, mixing preferences) causing frailty effects that can exacerbate bias and time-dependent effects already known to exist in simple cases. Since vaccine properties, particularly mode of action, are unlikely to be known before the onset of clinical trials, choosing an efficacy measure and the associated analyses and sample size calculations will be problematic. Interim analyses designed to decide whether a study will be prolonged may be tenuous if based on a time-dependent measure and will influence sample size determination. Despite shortcomings, general recommendations can be made to minimise pernicious effects. The objectives of this paper are principally to review the current state of knowledge of the different stages in the preparation of large phase III HIV vaccine efficacy trials, the methodological difficulties related to their design, and the analysis of data collected from them. Mathematical models and trial simulations are used to demonstrate that further research is necessary to study the behaviour of vaccine efficacy measures under heterogeneous conditions of population, vaccine action, and trial design and identify a time-independent efficacy measure. Alternative methods to validate sample size calculations have to be developed in older to reduce the chances of unnecessary economic and human cost in phase III HIV vaccine trials.

AIDS Vaccines↗
PubMed1999

The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance.

The threat to human health posed by antibiotic resistance is of growing concern. Many commensal and pathogenic organisms have developed resistance to well established and newer antibiotics. The major selection pressure driving changes in the frequency of antibiotic resistance is the volume of drug use. However, establishing a quantitative relationship between the frequency of resistance and volume of drug use has proved difficult. Using population genetic methods and epidemiological observations, we report an analysis of the influence of the selective pressure imposed by the volume of drug use on temporal changes in resistance. Analytical expressions are derived to delineate key relationships between resistance and drug consumption. The analyses indicate that the time scale for emergence of resistance under a constant selective pressure is typically much shorter than the decay time after cessation or decline in the volume of drug use and that significant reductions in resistance require equally significant reductions in drug consumption. These results highlight the need for early intervention once resistance is detected.

Anti-Bacterial Agents↗
PubMed1999

Estimation of the basic reproduction number of BSE: the intensity of transmission in British cattle.

The basic reproduction number, R0, of an infectious agent is a key factor determining the rate of spread and the proportion of the host population affected. We formulate a general mathematical framework to describe the transmission dynamics of long incubation period diseases with complex pathogenesis. This is used to derive expressions for R0 of bovine spongiform encephalopathy (BSE) in British cattle, and back-calculation methods are used to estimate R0 throughout the time-course of the BSE epidemic. We show that the 1988 meat and bonemeal ban was effective in rapidly reducing R0 below 1, and demonstrate that this indicates that BSE will be unable to become endemic in the UK cattle population even when case clustering is taken into account. The analysis provides some insight into absolute infectiousness for bovine-to-bovine transmission, indicating maximally infectious animals may have infected up to 400 animals each. The relationship between R0 and the early stages of the BSE epidemic and the requirements for additional research are also discussed.

Animal Feed↗
PubMed1999

Population structure of pathogens: the role of immune selection.

Sunetra Gupta and Roy Anderson discuss how the balance between host immune responses against conserved and variable antigens shapes the population structure of pathogens. At one extreme, immune selection against polymorphic determinants can cause pathogen populations to self-organize spontaneously into discrete antigenic types that may either be maintained over long periods or undergo cyclical or chaotic fluctuations. At the other extreme, diversity may be drastically reduced by competition induced by a strong immune response against a conserved determinant. Where does each pathogen lie along this continuum? How would this knowledge influence our attempts to control an infectious disease?

Alleles↗
PubMed1999

Simulation studies of phase III clinical trials to test the efficacy of a candidate HIV-1 vaccine.

One question of particular importance in phase III HIV vaccine trials is the choice of efficacy measure (EM) to validly and precisely estimate the true vaccinal efficacy. Traditional EMs, based on hazard rate ratio (HRR) or cumulative incidence ratio (CIR) are time-sensitive to mode of vaccine action and population heterogeneities. Through Monte-Carlo simulation, the performance of HRR and CIR based EMs are examined across different trial designs and vaccine and population characteristics. A new EM based on log-spline hazard regression (HARE) is proposed. Given that vaccinal properties (mode of action, time-lag, waning) are unknown a priori, appropriate selection of EM is problematic, and HRR and CIR can be unreliable to estimate the true maximum efficacy of candidate products. Non-random sexual mixing can exacerbate biases in HRR and CIR. HARE can offer valid estimation across different modes of vaccine action and in presence of frailty effects, contrary to its traditional counterparts. Our simulation studies highlight the weaknesses of widely used EMs while offering guidelines for trial design and suggesting new avenues for statistical analysis.

AIDS Vaccines↗
PubMed1999

Apostles and Zionists: the influence of religion on demographic change in rural Zimbabwe.

Religion has acted as a brake on demographic transition in a number of historical and contemporary populations. In a study in two rural areas of Zimbabwe, we found substantial differences in recent demographic trends between Mission and Independent or "Spirit-type" churches. Birth rates are higher in some Spirit-type churches and, until recently, infant mortality was also higher. Recent increases in mortality were seen within Mission churches but not in Spirit-type churches. Missiological and ethnographic data indicate that differences in religious teaching on healthcare-seeking and sexual behaviour and differences in church regulation could explain this contrast in demographic patterns. More restrictive norms on alcohol consumption and extra-marital relationships in Spirit-type churches may limit the spread of HIV and thereby reduce its impact on mortality. These contrasting trends will influence the future religious and demographic profile of rural populations in Zimbabwe.

History, 20th Century↗