TB policy and the badger culling trials.
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Animals↗
Biomedical subjects
C A Donnelly
Publications and source records attributed to C A Donnelly.
Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's ability to alter host behaviour.
With increasing pressure to understand transmissible agents, renewed recognition of infectious causation of both acute and chronic diseases is occurring. Epidemiological and neuropathological studies indicate that some cases of schizophrenia may be associated with environmental factors, such as exposure to the ubiquitous protozoan Toxoplasma gondii. Reasons for this include T. gondii's ability to establish persistent infection within the central nervous system, its ability to manipulate intermediate host behaviour, the occurrence of neurological and psychiatric symptoms in some infected individuals, and an association between infection with increased incidence of schizophrenia. Moreover, several of the medications used to treat schizophrenia and other psychiatric disease have recently been demonstrated in vitro to possess anti-parasitic, and in particular anti-T. gondii, properties. Our aim here was thus to test the hypothesis that the anti-psychotic and mood stabilizing activity of some medications may be achieved, or at least augmented, through their in vivo inhibition of T. gondii replication and invasion in infected individuals. In particular we predicted, using the epidemiologically and clinically applicable rat-T. gondii model system, and following a previously described and neurologically characterized 'feline attraction' protocol that haloperidol (an anti-psychotic used in the treatment of mental illnesses including schizophrenia) and/or valproic acid (a mood stabilizer used in the treatment of mental illnesses including schizophrenia), would be, at least, as effective in preventing the development of T. gondii-associated behavioural and cognitive alterations as the standard anti-T. gondii chemotherapeutics pyrimethamine with Dapsone. We demonstrate that, while T. gondii appears to alter the rats' perception of predation risk turning their innate aversion into a 'suicidal' feline attraction, anti-psychotic drugs prove as efficient as anti-T. gondii drugs in preventing such behavioural alterations. Our results have important implications regarding the aetiology and treatment of such disorders.
Animals↗
TB policy and the badger culling trials.
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Animals↗
Seroprevalence of IgG antibodies to SARS-coronavirus in asymptomatic or subclinical population groups.
We systematically reviewed the current understanding of human population immunity against SARS-CoV in different groups, settings and geography. Our meta-analysis, which included all identified studies except those on wild animal handlers, yielded an overall seroprevalence of 0.10% [95% confidence interval (CI) 0.02-0.18]. Health-care workers and others who had close contact with SARS patients had a slightly higher degree of seroconversion (0.23%, 95% CI 0.02-0.45) compared to healthy blood donors, others from the general community or non-SARS patients recruited from the health-care setting (0.16%, 95% CI 0-0.37). When analysed by the two broad classes of testing procedures, it is clear that serial confirmatory test protocols resulted in a much lower estimate (0.050%, 95% CI 0-0.15) than single test protocols (0.20%, 95% CI 0.06-0.34). Potential epidemiological and laboratory pitfalls are also discussed as they may give rise to false or inconsistent results in measuring the seroprevalence of IgG antibodies to SARS-CoV.
Antibody Formation↗
Epidemiological analysis of data for scrapie in Great Britain.
In recent years, the control or eradication of scrapie and any other transmissible spongiform encephalopathies (TSEs) possibly circulating in the sheep population has become a priority in Britain and elsewhere in Europe. A better understanding of the epidemiology of scrapie would greatly aid the development and evaluation of control and eradication strategies. Here we bound the range of key epidemiological parameters using a combination of relatively detailed pathogenesis and demography data, more limited data on susceptibility and incubation times, and recent survey data on scrapie incidence in Great Britain. These data are simultaneously analysed using mathematical models describing scrapie transmission between sheep and between flocks. Our analysis suggests that occurrence of scrapie in a flock typically provokes changes in flock management that promote termination of the outbreak, such as the adoption of selective breeding, and that a large fraction of cases (possibly over 80%) goes undetected. We show that the data analysed are consistent with the within-flock reproduction number of scrapie lying in the range 1.5-6, consistent with previous epidemiological studies.
Age Factors↗
Adherence to antiretroviral therapy and its impact on clinical outcome in HIV-infected patients.
We analyse data on patient adherence to prescribed regimens and surrogate markers of clinical outcome for 168 human immunodeficiency virus infected patients treated with antiretroviral therapy. Data on patient adherence consisted of dose-timing measurements collected for an average of 12 months per patient via electronic monitoring of bottle opening events. We first discuss how such data can be presented to highlight suboptimal adherence patterns and between-patient differences, before introducing two novel methods by which such data can be statistically modelled. Correlations between adherence and subsequent measures of viral load and CD4+T-cell counts are then evaluated. We show that summary measures of short-term adherence, which incorporate pharmacokinetic and pharmacodynamic data on the monitored regimen, predict suboptimal trends in viral load and CD4+T-cell counts better than measures based on adherence data alone.
Antiretroviral Therapy, Highly Active↗
Methods for estimating the case fatality ratio for a novel, emerging infectious disease.
During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital.
Communicable Diseases, Emerging↗
Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot-and-mouth disease epidemic.
A case-control study of the factors associated with the risk of a bovine tuberculosis (TB) breakdown in cattle herds was undertaken within the randomized badger culling trial (RBCT). TB breakdowns occurring prior to the 2001 foot-and-mouth disease epidemic in three RBCT triplets were eligible to be cases; controls were selected from the same RBCT area. Data from 151 case farms and 117 control farms were analysed using logistic regression. The strongest factors associated with an increased TB risk were movement of cattle onto the farm from markets or farm sales, operating a farm over multiple premises and the use of either covered yard or 'other' housing types. Spreading artificial fertilizers or farmyard manure on grazing land were both associated with decreased risk. These first case-control results from the RBCT will be followed by similar analyses as more data become available.
Animals↗
Environmental and management factors affecting the welfare of chickens on commercial farms in the United Kingdom and Denmark stocked at five densities.
Data from a large commercial-scale experiment in which 10 major broiler producer companies stocked whole houses of birds at 30, 34, 38, 42, and 46 kg/m2 were analyzed to identify 1) temperature and humidity profiles achieved throughout the growth cycle, 2) management practices and equipment that contributed to observed variation in environmental conditions, and 3) the extent to which environmental variables affected bird welfare. The study involved a total of 2.7 million birds in 114 houses on commercial farms with measurement of a wide range of environmental and bird variables. Much of the variation in broiler health and welfare was associated with the percentage of time a company could maintain house temperature and RH within limits recommended by the breeder company. RH in the first week of life was particularly important to later health, suggesting that better control of humidity might lead to improved welfare. Key management factors affecting bird welfare were those relating to good ventilation and air control such as the type of ventilation, type of drinker, numbers of stockmen, and litter type. Controlling the environment, particularly temperature, humidity, and air and litter quality, is crucial to broiler chicken welfare. This does not mean that stocking density is unimportant, but lowering stocking density on its own, without regard to the environment the birds experience, is not sufficient. Genuine improvements in bird welfare will come from setting standards that combine stocking density, safeguards on the environment, and the genetic makeup of the birds.
Animal Husbandry↗
Gender difference in HIV-1 RNA viral loads.
OBJECTIVES: To test and characterize the dependence of viral load on gender in different countries and racial groups as a function of CD4 T-cell count. METHODS: Plasma viral load data were analysed for > 30,000 HIV-infected patients attending clinics in the USA [HIV Insight (Cerner Corporation, Vienna, VA, USA) and Plum Data Mining LLC (East Meadow, NY, USA) databases] and the Netherlands (Athena database; HIV Monitoring Foundation, Amsterdam, Netherlands). Log-normal regression models were used to test for an effect of gender on viral load while adjusting for covariates and allowing the effect to depend on CD4 T-cell count. Sensitivity analyses were performed to test the robustness of conclusions to assumptions regarding viral loads below the lower limit of quantification (LLOQ). RESULTS: After adjusting for covariates, women had (nonsignificantly) lower viral loads than men (HIV Insight: -0.053 log(10) HIV-1 RNA copies/mL, P = 0.202; Athena: -0.005 log(10) copies/mL, P = 0.667; Plum: -0.072 log(10) copies/mL, P = 0.273). However, further investigation revealed that the gender effect depended on CD4 T-cell count. Women had consistently higher viral loads than men when CD4 T-cell counts were at most 50 cells/microL, and consistently lower viral loads than men when CD4 T-cell counts were greater than 350 cells/microL. These effects were remarkably consistent when estimated independently for the racial groups with sufficient data available in the HIV Insight and Plum databases. CONCLUSIONS: The consistent relationship between gender-related differences in viral load and CD4 T-cell count demonstrated here explains the diverse findings previously published.
Adult↗
Patterns of uptake of treatment for self reported sexually transmitted infection symptoms in rural Zimbabwe.
OBJECTIVES: To determine the extent of self reported symptoms perceived to be related to sexually transmitted infections and the patterns of subsequent treatment seeking behaviour in a predominantly rural population of Zimbabwe. METHODS: A population based survey of 4331 men and 5149 women was conducted in rural Zimbabwe during 1998-2000. Structured confidential interviews collected data on self reported sexually transmitted infection symptoms, treatment seeking behaviour, sociodemographic characteristics, and sexual behaviour. RESULTS: 25% of men aged 17-54 years report experiencing genital sores and 25% of men report experiencing urethral discharge; 30% of women aged 15-44 years report experiencing vaginal discharge. The lifetime number of sexual partners, age, and years of sexual activity were all significant predictors of symptoms for both men and women (all p values <0.001). 92% of men and 62% of women had sought treatment for their symptoms in the past year (p value <0.001). Men and women were equally likely to have sought treatment at a local hospital or clinic, but women were much less likely than men to have sought treatment at a different hospital or clinic. Among those who had sought treatment, men sought treatment faster than women and were more likely to report being "very satisfied" with their treatment than women. CONCLUSIONS: The gender differences in treatment seeking are of major concern for control efforts and further work on determining the reasons for these should be a priority. This would inform the likely impact of both increasing availability of local services and further reducing the stigma faced by those wishing to access such services.
Adolescent↗
Spatial heterogeneity and the persistence of infectious diseases.
The endemic persistence of infectious diseases can often not be understood without taking into account the relevant heterogeneities of host mixing. Here, we consider spatial heterogeneity, defined as 'patchiness' of the host population. After briefly reviewing how disease persistence is influenced by population size, reproduction number and infectious period, we explore its dependence on the level of spatial heterogeneity. Analysis and simulation of disease transmission in a symmetric meta-population suggest that disease persistence typically becomes worse as spatial heterogeneity increases, although local persistence optima can occur for infections with oscillatory population dynamics. We obtain insight into the dynamics that underlie the observed persistence patterns by studying the infection prevalence correlation between patches and by comparing full-model simulations to results obtained using simplified patch-level descriptions of the interplay between local extinctions and between-patch transmissions. The observed patterns are interpreted in terms of rescue effects for strong spatial heterogeneity and in terms of between-patch coherence and synchronization effects at intermediate and weak levels of heterogeneity.
Communicable Diseases↗
Potential use of vaccination in cattle or badgers to control bovine tuberculosis.
The application of regular herd testing to identify and remove infected animals has proved to be a highly successful method of controlling bovine tuberculosis (TB) in many parts of the world. However, in some countries, notably the United Kingdom, Ireland and New Zealand, the disease has continued to pose a significant problem, despite intensive herd testing. Persistence of disease in these countries is associated with the presence of wildlife reservoirs of infection. Attempts to control bovine TB by culling of wildlife have been, at best, only partially successful and have proved difficult to sustain. This has led to considering of vaccination either of wildlife or cattle as a potential control measure. However, there are a number of obstacles that need to be overcome before vaccination can be considered a practical option. Vaccine efficacy, methods used for vaccine delivery in wildlife, potential interference of vaccination with diagnostic tests for cattle and appropriate design of field trials are among the issues that need to be addressed.
Animals↗
vCJD risk in the Republic of Ireland.
BACKGROUND: The Republic of Ireland has the second highest incidence of BSE worldwide. Only a single case of vCJD has been identified to date. METHODS: We estimate the total future number of clinical cases of vCJD using an established mathematical model, and based on infectivity of bovine tissue calculated from UK data and on the relative exposure to BSE contaminated meat. RESULTS: We estimate 1 future clinical case (95% CI 0-15) of vCJD in the Republic of Ireland. Irish exposure is from BSE infected indigenous beef products and from imported UK beef products. Additionally, 2.5% of the Irish population was exposed to UK beef through residing in the UK during the 'at-risk' period. The relative proportion of risk attributable to each of these three exposures individually is 2:2:1 respectively. CONCLUSIONS: The low numbers of future vCJD cases estimated in this study is reassuring for the Irish population and for other countries with a similar level of BSE exposure.
Animals↗
Estimating the number of helminthic infections in the Republic of Cameroon from data on infection prevalence in schoolchildren.
INTRODUCTION: The prevalence of infection with helminths is markedly dependent on age, yet estimates of the total number of infections are typically based on data only from school-aged children. Such estimates, although useful for advocacy, provide inadequate information for planning control programmes and for quantifying the burden of disease. Using readily available data on the prevalence of infection in schoolchildren, the relation between the prevalence of infection in school-aged children and prevalence in the wider community can be adequately described using species-specific models. This paper explores the reliability of this approach to predict the prevalence infection in the community and provides a model for estimating the total number of people infected in the Republic of Cameroon. METHODS: Using data on the prevalence of helminthic infection in school-aged children in Cameroon, the prevalence of infection in pre-school children and adults was estimated from species-specific linear and logistic regression models developed previously. The model predictions were then used to estimate the number of people infected in each district in each age group in Cameroon. RESULTS: For Cameroon, if only the prevalence of infection in schoolchildren is used, the number of people infected with each helminthic species will be overestimated by up to 32% when compared with the estimates provided by the species-specific models. The calculation of confidence intervals supports the statistical reliability of the model since a narrow range of parameter estimates is evident. Furthermore, this work suggests that estimation of national prevalence of infection and the number infected will be enhanced if data are stratified by age; this model represents a useful planning tool for obtaining more accurate estimates. Estimates based on data aggregated from three geographical levels (district, regional, and national) show that summarizing prevalence data at the national level will result in biases of up to 19%. Such biases reflect differences in the geographical distribution for the prevalence of each species. DISCUSSION: Developing more accurate estimates requires a better understanding of the differences in the spatial heterogeneity of each species and also better methods of incorporating this information when making estimates.
Adolescent↗
Dynamics of a scrapie outbreak in a flock of Romanov sheep--estimation of transmission parameters.
Knowledge of epidemiological mechanisms and parameters underlying scrapie transmission in sheep flocks remains very limited at present. Here we introduce a method for fitting stochastic transmission models to outbreak data to estimate bounds on key transmission parameters. We apply this method to data describing an outbreak of scrapie in a closed flock of Romanov sheep. The main findings are that the relative infectiousness of infected animals in this outbreak becomes appreciable early into disease incubation and that the mean incubation period is less than 1.5 years. We also find that the data are consistent with a broad range of values for the basic reproduction number R0 and describe how the boundaries of this range depend on assumptions about the mean incubation period and the contribution to transmission of a long-lived environmental reservoir of infectivity.
Animals↗
Patterns of antiretroviral use in the United States of America: analysis of three observational databases.
OBJECTIVE: To characterize patterns of antiretroviral use in HIV-infected patients and explore variation by patient characteristics and disease stage. METHODS: Three large patient databases recording information derived from routine clinical attendance were analyzed: HIV Insight (n = 10 873), Target Management Services (n = 2226) and Clinical Partners (n = 1505). Each database records the dates of starting and stopping individual antiretroviral agents over time, measurements of CD4 T-cell counts and HIV-RNA levels at approximately 6-monthly intervals, and the demographic characteristics of patients. The number, frequency and duration of different antiretroviral combinations over time and their relationship to stage of HIV-disease and demographic characteristics were explored. RESULTS: Over 2000 different combinations of antiretroviral agents are recorded. From 1987 onwards, the use of zidovudine increased, with 23% of patients receiving monotherapy by 1990. The majority of treated patients remained on monotherapy until the introduction of highly active antiretroviral therapy (HAART) in 1996. By 1999, the standard of care was HAART, with 84% of patients beginning antiretroviral therapy with HAART. Those of African American race (odds ratio 0.59) and funded by Medicaid (odds ratio 0.72) were significantly less likely to begin antiretroviral therapy on HAART. Until 1995, there was a significant decrease in CD4 T-cell count when starting antiretroviral therapy. No significant trend was observed in either CD4 T-cell count or viral load after this time. Those starting on HAART therapies were significantly less likely to stop or switch regimens than those on nucleoside reverse transcriptase inhibitor (NRTI)-only therapies (P < 0.001). CONCLUSIONS: Complex patterns of antiretroviral treatment are observed in this large population. Changes over time mirror the introduction of the new antiretroviral agents.
Adult↗
Extending backcalculation to analyse BSE data.
We review the origins of backcalculation (or back projection) methods developed for the analysis of AIDS (acquired immunodeficiency syndrome) incidence data. These techniques have been used extensively for >15 years to deconvolute clinical case incidence, given knowledge of the incubation period distribution, to obtain estimates of past HIV (human immunodeficiency virus) infection incidence and short-term predictions of future AIDS incidence. Adaptations required for the analysis of bovine spongiform encephalopathy (BSE) incidence included: stratification of BSE incidence by age as well as birth cohort; allowance for incomplete survival between infection and the onset of clinical signs of disease; and decomposition of the age- and time-related infection incidence into a time-dependent feed risk component and an age-dependent exposure/susceptibility function. The most recent methodological developments focus on the incorporation of data from clinically unaffected cattle screened using recently developed tests for preclinical BSE infection. Backcalculation-based predictions of future BSE incidence obtained since 1996 are examined. Finally, future directions of epidemiological analysis of BSE epidemics are discussed taking into account ongoing developments in the science of BSE and possible changes in BSE-related policies.
Animals↗