Group did give timely foot-and-mouth analysis.
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Foot-and-Mouth Disease↗
Biomedical subjects
R M Anderson
Publications and source records attributed to R M Anderson.
Comparison of the effectiveness of non-nucleoside reverse transcriptase inhibitor-containing and protease inhibitor-containing regimens using observational databases.
OBJECTIVES: To compare the effectiveness of first protease inhibitor (PI)-containing and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: Data were analysed from three large HIV patient databases: Apache HIV Insight (APACHE), Target Management Services (TMS) and Clinical Partners (CP). The effectiveness of therapy was the time taken for HIV-1 RNA to fall below detectable levels on first highly active antiretroviral therapy regimen (PI- or NNRTI-containing) and the subsequent time to failure (two consecutive detectable measurements). Comparisons were made using proportional hazards models, adjusting for differences in age, sex, previous reverse transcriptase inhibitor use, calendar year and baseline viral load and CD4 T-cell count. RESULTS: The type of regimen was not associated with time to undetectable viral load in any of the three databases, all of which had high power to detect a difference. PI-containing regimens were significantly less likely to fail after reaching undetectable viral loads for APACHE and CP patients (relative hazard, 1.7; 95% confidence interval, 1.3--2.1 and relative hazard, 1.6; 95% confidence interval, 1.0--2.5 respectively). These results remained significant after allowing for an unmeasured confounder with moderate effect on risk. No significant association between time to failure and regimen was found for TMS patients, possibly due to low power (67% to detect a relative hazard of 1.5). No difference was found between regimens in the time taken for an increase of > 100 x 10(9)cells/l in CD4 T-cell count. In the APACHE database, those on NNRTI-containing regimens were more likely to have a failing CD4 T-cell response. CONCLUSIONS: PI-containing regimens have a lower risk of treatment failure than NNRTI-containing regimens.
Adult↗
The foot-and-mouth epidemic in Great Britain: pattern of spread and impact of interventions.
We present an analysis of the current foot-and-mouth disease epidemic in Great Britain over the first 2 months of the spread of the virus. The net transmission potential of the pathogen and the increasing impact of control measures are estimated over the course of the epidemic to date. These results are used to parameterize a mathematical model of disease transmission that captures the differing spatial contact patterns between farms before and after the imposition of movement restrictions. The model is used to make predictions of future incidence and to simulate the impact of additional control strategies. Hastening the slaughter of animals with suspected infection is predicted to slow the epidemic, but more drastic action, such as "ring" culling or vaccination around infection foci, is necessary for more rapid control. Culling is predicted to be more effective than vaccination.
Animals↗
Dynamics of seminal plasma HIV-1 decline after antiretroviral treatment.
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Alkynes↗
Using decision analysis to choose phosphorus targets for Lake Erie.
Lake Erie water quality has improved dramatically since the degraded conditions of the 1960s. Additional gains could be made, but at the expense of further investment and reductions in fishery productivity. In facing such cross-jurisdictional issues, natural resource managers in Canada and the United States must grapple with conflicting objectives and important uncertainties, while considering the priorities of the public that live in the basin. The techniques and tools of decision analysis have been used successfully to deal with such decision problems in a range of environmental settings, but infrequently in the Great Lakes. The objective of this paper is to illustrate how such techniques might be brought to bear on an important, real decision currently facing Lake Erie resource managers and stakeholders: the choice of new phosphorus loading targets for the lake. The heart of our approach is a systematic elicitation of stakeholder preferences and an investigation of the degree to which different phosphorus-loading policies might satisfy ecosystem objectives. Results show that there are potential benefits to changing the historical policy of reducing phosphorus loads in Lake Erie.
Conservation of Natural Resources↗
Viral dynamics and anti-viral pharmacodynamics: rethinking in vitro measures of drug potency.
Most current assays used to quantitate the pharmacodynamic effect of anti-viral agents measure the net inhibitory effect of a drug on virus replication over several days in an in vitro cell culture. Such endpoint experiments give cumulative measures of inhibition that vary with the assay used and therefore provide suboptimal information on likely in vivo drug performance. We argue that instantaneous inhibition (proportion of cell infection prevented at a point in time) is a more robust pharmacodynamic measure, and propose techniques to estimate this quantity from endpoint data. Implications for the quantification of drug interactions are discussed.
Animals↗
Persistence patterns of scrapie in a sheep flock.
The epidemiology and transmission dynamics of sheep scrapie is as yet poorly understood. Here we present a theoretical analysis of the transmission dynamics within a sheep flock, concentrating on how persistence properties depend on transmission scenario and flock size. Patterns of disease persistence and extinction are studied analytically using branching-process approximations and numerically using stochastic model simulations. For a given basic reproduction number, disease extinction is most likely when late-stage infected animals are responsible for most of the transmission. This effect can be understood in terms of aggregation in the distribution of the number of secondary infections arising from a single primary infection. The presence of an environmental reservoir reduces the probability of extinction.
Animals↗
A rural HIV epidemic in Zimbabwe? Findings from a population-based survey.
The aim of the study was to use population-based data from 689 adults to describe the socio-demographic, behavioural and biomedical correlates of HIV infection and aid identification of effective HIV control strategies for rural Zimbabwe. Dried blood spot and urine samples were collected for HIV and sexually transmitted disease (STD) testing and participants were interviewed on socio-demographic characteristics, sexual behaviour and experience of STD symptoms. HIV seroprevalence was 23.3% and was higher in females, divorcees, widows, working men, estate residents, and respondents reporting histories of STD symptoms. Female HIV seroprevalence rises sharply at ages 16-25. A third of sexually-active adults had experienced STD-associated symptoms but there were delays in seeking treatment. Herpes simplex virus type 2 (HSV-2) and Trichomonas vaginalis are more common causes than syphilis, gonorrhoea, and chlamydia, and are strongly associated with HIV infection. Local programmes promoting safer sexual behaviour and fast and effective STD treatment among young women, divorcees and working men could reduce the extensive HIV transmission in rural communities.
Adolescent↗
Report of the health care delivery work group: behavioral research related to the establishment of a chronic disease model for diabetes care.
As one of four work groups for the November 1999 conference on Behavioral Science Research in Diabetes, sponsored by the National Institute on Diabetes and Digestive and Kidney Diseases, the health care delivery work group evaluated the status of research on quality of care, patient-provider interactions, and health care systems' innovations related to improved diabetes outcomes. In addition, we made recommendations for future research. In this article, which was developed and modified at the November conference by experts in health care delivery, diabetes and behavioral science, we summarize the literature on patient-provider interactions, diabetes care and self-management support among underserved and minority populations, and implementation of chronic care management systems for diabetes. We conclude that, although the quality of care provided to the vast majority of diabetic patients is problematic, this is principally not the fault of either individual patients or health care professionals. Rather, it is a systems issue emanating from the acute illness model of care, which still predominates. Examples of proactive population-based chronic care management programs incorporating behavioral principles are discussed. The article concludes by identifying barriers to the establishment of a chronic care model (e.g., lack of supportive policies, understanding of population-based management, and information systems) and priorities for future research in this area needed to overcome these barriers.
Behavioral Medicine↗
The effectiveness of HIV prevention and the epidemiological context.
Planning an intervention to prevent infections with the human immunodeficiency virus (HIV) should be guided by local epidemiological and socioeconomic conditions. The socioeconomic setting and existing public service capacity determine whether an intervention can have a significant outcome in terms of a reduction in a defined risk. The epidemiological context determines whether such risk reduction translates into a measurable impact on HIV incidence. Measurement of variables describing the epidemiological context can be used to determine the local suitability of interventions, thereby guiding planners and policy-makers in their choice of intervention. Such measurements also permit the retrospective analysis of the impact of interventions where HIV incidence was not recorded. The epidemiological context is defined for four different categories of intervention, shown to be effective in lower-income countries by randomized controlled trials. Appropriate indicators for the epidemiological context and methodological guidelines for their measurement are proposed. Their use in the transfer of a successful intervention from one context to another and in scaling up the effort to control HIV infection is explored. These indicators should provide a useful resource for those involved in planning HIV prevention interventions.
Developing Countries↗
Slower decline of plasma HIV-1 RNA following highly suppressive antiretroviral therapy in primary compared with chronic infection.
OBJECTIVES: To study the effect of highly suppressive antiretroviral therapy on the slopes of HIV-1 RNA decline in primary compared with chronic HIV-1 infection. METHODS: Slopes of HIV-1 RNA decline in plasma were compared before and after the start of highly suppressive antiretroviral therapy from five acutely infected patients who started treatment 2 to 5 weeks following the onset of clinical symptoms. Slopes of decline after the initiation of therapy were also compared with those found in 12 chronically infected individuals on the same therapy. Numbers and percentages of activated CD4 and CD8 T cells at baseline were compared as well. RESULTS: The pre-treatment slopes of HIV-1 RNA decline in the acutely infected individuals increased significantly (P = 0.0001) after the start of anti-retroviral therapy. However, these post-treatment slopes were lower than those found in the chronically infected individuals (P= 0.012). Slopes were inversely correlated (P= 0.012) with baseline HIV-1 RNA. Although the number of CD38+HLA-DR+ CD4 cells was higher in primary infection (P= 0.02), the percentage did not differ between primary and chronic infection. CONCLUSIONS: These findings indicate that antiretroviral therapy contributes significantly to the clearance of HIV-1 during primary infection. Based on the mathematical model the less steep RNA slope following the start of treatment in primary infection can be predicted to be the result of lower clearance of productively infected cells and higher burst size per cell per unit time. This may indicate a growing immune response to HIV-1 in this very early stage of infection.
Acute Disease↗
MSJAMA: the problem with compliance in diabetes.
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Chronic Disease↗
Effects of prefrontal cortex microinjection of neurotensin-(8-13) on midbrain dopamine and non-dopamine cell firing.
Effects of prefrontal cortex microinjections of 0.3 and 3 nmol/0.5 microl of neurotensin-(8-13) on the firing rate of midbrain dopamine and non-dopamine cells were studied in urethane-anesthetized rats. Neurotensin produced an increase in firing in 14 of 26 dopamine cells tested, an effect that peaked between 15 and 20 min after the injection at both doses. On the other hand, a majority of non-dopamine cells (7/10) tested with the higher dose of neurotensin showed a statistically significant decrease in firing when compared to saline, an effect that also peaked between 15 and 20 min. These results show that prefrontal cortex neurotensin can modulate both dopamine and non-dopamine neurotransmission in the ventral midbrain.
Action Potentials↗
Predicted vCJD mortality in Great Britain.
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Adult↗
Reduction of the HIV-1-infected T-cell reservoir by immune activation treatment is dose-dependent and restricted by the potency of antiretroviral drugs.
BACKGROUND: Treatments combining T-cell activating agents and potent antiretroviral drugs have been proposed as a possible means of reducing the reservoir of long-lived HIV-1 infected quiescent CD4 T-cells. OBJECTIVE: To analyse the effect of such therapies on HIV-1 dynamics and T-cell homeostasis. DESIGN AND METHODS: A mathematical framework describing HIV-1 dynamics and T-cell homeostasis was developed. Three patients who were kept on a particularly potent course of highly active antiretroviral therapy (HAART) were treated with the anti-CD3 monoclonal antibody OKT3 and interleukin (IL)-2. Plasma HIV-RNA, and HIV-RNA and DNA in peripheral blood mononuclear cells and lymph node mononuclear cells were measured. These results and other published studies on the use of IL-2 alone were assessed using our mathematical framework. RESULTS: We show that outcome of treatment is determined by the relative rates of depletion of the infected quiescent T-cell population by activation and of its replenishment through new infection. Which of these two processes dominates is critically dependent on both the potency of HAART and also the degree of T-cell activation induced. We demonstrate that high-level T-cell stimulation is likely to produce negative outcomes, both by failing to reduce viral reservoirs and by depleting the CD4 T-cell pool and disrupting CD4/CD8 T-cell homeostasis. In contrast, repeated low-level stimulation may both aid CD4 T-cell pool expansion and achieve a substantial reduction in the long-lived HIV-1 reservoir. CONCLUSIONS: Our analysis suggests that although treatment that activates T-cells can reduce the long-lived HIV-1 reservoir, caution should be used as high-level stimulation may result in a negative outcome.
Anti-HIV Agents↗
The organizer factors Chordin and Noggin are required for mouse forebrain development.
In mice, there is evidence suggesting that the development of head and trunk structures is organized by distinctly separated cell populations. The head organizer is located in the anterior visceral endoderm (AVE) and the trunk organizer in the node and anterior primitive streak. In amphibians, Spemann's organizer, which is homologous to the node, partially overlaps with anterior endoderm cells expressing homologues of the AVE markers cerberus, Hex and Hesx1. For mice, this raises the question of whether the AVE and node are independent of each other, as suggested by their anatomical separation, or functionally interdependent as is the case in amphibians. Chordin and Noggin are secreted bone morphogenetic protein (BMP) antagonists expressed in the mouse node, but not in the AVE. Here we show that mice double-homozygous mutants that are for chordin and noggin display severe defects in the development of the prosencephalon. The results show that BMP antagonists in the node and its derivatives are required for head development.
Animals↗
Feed-borne transmission and case clustering of BSE.
An unresolved issue in the epidemiology of bovine spongiform encephalopathy (BSE) in the UK is what precisely determines the degree to which cases of disease in cattle are clustered within herds throughout the course of the epidemic. This paper presents an analysis of feed-borne transmission at the herd level and tests various models of case-clustering mechanisms, associated with heterogeneity in exposure to infectious feed, against observed epidemic pattern. We use an age-structured metapopulation framework in which the recycling of animal tissue between herds via feed producers is explicitly described. We explore two alternative assumptions for the scaling with herd size of the within-herd risk of exposure of an animal to infectious material. We find that whereas exposure heterogeneity caused by variation in feed and offal processing methods and by variation in per-animal feed uptake can explain the pattern of case clustering seen in the BSE epidemic, exposure heterogeneity due to the aggregation of infectivity within feed cannot.
Animal Feed↗
Assessment of the prevalence of vCJD through testing tonsils and appendices for abnormal prion protein.
The objective of this study was to determine the age group or groups which will provide the most information on the potential size of the vCJD epidemic in Great Britain via the sampling of tonsil and appendix material to detect the presence of abnormal prion protein (PrP(Sc)). A subsidiary aim was to determine the degree to which such an anonymous age-stratified testing programme will reduce current uncertainties in the size of the epidemic in future years. A cohort- and time-stratified model was used to generate epidemic scenarios consistent with the observed vCJD case incidence. These scenarios, together with data on the age distribution of tonsillectomies and appendectomies, were used to evaluate the optimal age group and calendar time for undertaking testing and to calculate the range of epidemic sizes consistent with different outcomes. The analyses suggested that the optimal five-year age group to test is 25-29 years, although a random sample of appendix tissue from all age groups is nearly as informative. A random sample of tonsil tissue from all age groups is less informative, but the information content is improved if sampling is restricted to tissues removed from those over ten years of age. Based on the assumption that the test is able to detect infection in the last 75% of the incubation period, zero detected infections in an initial random sample of 1000 tissues would suggest that the epidemic will be less than 870,000 cases. If infections are detected, then the model prediction suggests that both relatively small epidemics (800+ cases if one is detected or 8300+ if two are detected) and larger epidemics (21,000+ cases if three or more are detected) are possible. It was concluded that testing will be most informative if undertaken using appendix tissues or tonsil tissues removed from those over ten years of age. Large epidemics can only be excluded if a small number of infections are detected and the test is able to detect infection early in the incubation period.
Adolescent↗