15 results found
Lochen A, Truscott JE, Croucher NJ, 2022, Analysing pneumococcal invasiveness using Bayesian models of pathogen progression rates, PLOS COMPUTATIONAL BIOLOGY, Vol: 18, ISSN: 1553-734X
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- Citations: 3
Vikentjeva M, Geller J, Remm J, et al., 2021, Forecasting the effectiveness of the DeWorm3 trial in interrupting the transmission of soil-transmitted helminths in three study sites in Benin, India and Malawi, Parasites and Vectors, Vol: 14, ISSN: 1756-3305
BackgroundThe DeWorm3 project is an ongoing cluster-randomised trial assessing the feasibility of interrupting the transmission of soil-transmitted helminths (STH) through mass drug administration (MDA) using study sites in India, Malawi and Benin. In this article, we describe an approach which uses a combination of statistical and mathematical methods to forecast the outcome of the trial with respect to its stated goal of reducing the prevalence of infection to below 2%.MethodsOur approach is first to define the local patterns of transmission within each study site, which is achieved by statistical inference of key epidemiological parameters using the baseline epidemiological measures of age-related prevalence and intensity of STH infection which have been collected by the DeWorm3 trials team. We use these inferred parameters to calibrate an individual-based stochastic simulation of the trial at the cluster and study site level, which is subsequently run to forecast the future prevalence of STH infections. The simulator takes into account both the uncertainties in parameter estimation and the variability inherent in epidemiological and demographic processes in the simulator. We interpret the forecast results from our simulation with reference to the stated goal of the DeWorm3 trial, to achieve a target of ≤2%prevalence at a point 24 months post-cessation of MDA.ResultsSimulated output predicts that the two arms will be distinguishable from each other in all three country sites at the study end point. In India and Malawi, measured prevalence in the intervention arm is below the threshold with a high probability (90% and 95%, respectively), but in Benin the heterogeneity between clusters prevents the arm prevalence from being reduced below the threshold value. At the level of individual study arms within each site, heterogeneity among clusters leads to a very low probability of achieving complete elimination in an intervention arm, yielding a post-study scenario w
Truscott J, Hardwick RJ, Werkman M, et al., 2020, Forecasting the Effectiveness of the DeWorm3 Trial in Interrupting the Transmission of Soil-transmitted Helminths in Three Study Sites in Benin, India and Malawi
<jats:title>Abstract</jats:title> <jats:p>Background The DeWorm3 project is an ongoing cluster-randomised trial assessing the feasibility of interrupting the transmission of soil-transmitted helminths (STH) through mass drug administration (MDA) using study sites in India, Malawi and Benin. In this paper, we describe an approach which uses a combination of statistical and mathematical methods to forecast the outcome of the trial with respect to its stated goal of reducing the prevalence of infection to below 2%. Methods Our approach is firstly to define the local patterns of transmission within each study site, which is achieved by statistical inference of key epidemiological parameters using the baseline epidemiological measures of age-related prevalence and intensity of STH infection which have been collected by the DeWorm3 trials team. We use these inferred parameters to calibrate an individual-based stochastic simulation of the trial at the cluster and study site level which is subsequently run to forecast the future prevalence of STH infections. The simulator takes into account both the uncertainties in parameter estimation and the variability inherent in epidemiological and demographic processes in the simulator. We interpret the forecast results from our simulation with reference to the stated goal of the DeWorm3 trial, to achieve a target of ≤ 2% prevalence at a point 24 months post-cessation of MDA. Results Simulated output predicts that the two arms will be distinguishable from each other in all three country sites at the study endpoint. In India and Malawi, measured prevalence in the intervention arm is below the threshold with a high probability (90% and 95%, respectively), but that in Benin the heterogeneity between clusters prevents the arm prevalence being reduced below the threshold value. At the level of individual study arms within each site, heterogeneity among clusters leads to a very low probability of achieving compl
Truscott JE, Ower AK, Werkman M, et al., 2019, Heterogeneity in transmission parameters of hookworm infection within the baseline data from the TUMIKIA study in Kenya, Parasites and Vectors, Vol: 12, ISSN: 1756-3305
BACKGROUND: As many countries with endemic soil-transmitted helminth (STH) burdens achieve high coverage levels of mass drug administration (MDA) to treat school-aged and pre-school-aged children, understanding the detailed effects of MDA on the epidemiology of STH infections is desirable in formulating future policies for morbidity and/or transmission control. Prevalence and mean intensity of infection are characterized by heterogeneity across a region, leading to uncertainty in the impact of MDA strategies. In this paper, we analyze this heterogeneity in terms of factors that govern the transmission dynamics of the parasite in the host population. RESULTS: Using data from the TUMIKIA study in Kenya (cluster STH prevalence range at baseline: 0-63%), we estimated these parameters and their variability across 120 population clusters in the study region, using a simple parasite transmission model and Gibbs-sampling Monte Carlo Markov chain techniques. We observed great heterogeneity in R0 values, with estimates ranging from 1.23 to 3.27, while k-values (which vary inversely with the degree of parasite aggregation within the human host population) range from 0.007 to 0.29 in a positive association with increasing prevalence. The main finding of this study is the increasing trend for greater parasite aggregation as prevalence declines to low levels, reflected in the low values of the negative binomial parameter k in clusters with low hookworm prevalence. Localized climatic and socioeconomic factors are investigated as potential drivers of these observed epidemiological patterns. CONCLUSIONS: Our results show that lower prevalence is associated with higher degrees of aggregation and hence prevalence alone is not a good indicator of transmission intensity. As a consequence, approaches to MDA and monitoring and evaluation of community infection status may need to be adapted as transmission elimination is aimed for by targeted treatment approaches.
Truscott JE, Dunn JC, Papaiakovou M, et al., 2019, Calculating the prevalence of soil-transmitted helminth infection through pooling of stool samples: Choosing and optimizing the pooling strategy, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727
Prevalence is a common epidemiological measure for assessing soil-transmitted helminthburden and forms the basis for much public-health decision-making. Standard diagnostictechniques are based on egg detection in stool samples through microscopy and these techniques are known to have poor sensitivity for individuals with low infection intensity, leadingto poor sensitivity in low prevalence populations. PCR diagnostic techniques offer very highsensitivities even at low prevalence, but at a greater cost for each diagnostic test in terms ofequipment needed and technician time and training. Pooling of samples can allow prevalence to be estimated while minimizing the number of tests performed. We develop a modelof the relative cost of pooling to estimate prevalence, compared to the direct approach oftesting all samples individually. Analysis shows how expected relative cost depends on boththe underlying prevalence in the population and the size of the pools constructed. A criticalprevalence level (approx. 31%) above which pooling is never cost effective, independent ofpool size. When no prevalence information is available, there is no basis on which to choosebetween pooling and testing all samples individually. We recast our model of relative cost ina Bayesian framework in order to investigate how prior information about prevalence in agiven population can be used to inform the decision to choose either pooling or full testing.Results suggest that if prevalence is below 10%, a relatively small exploratory prevalencesurvey (10–15 samples) can be sufficient to give a high degree of certainty that pooling maybe relatively cost effective.
Truscott JE, Werkman M, Wright JE, et al., 2017, Identifying optimal threshold statistics for elimination of hookworm using a stochastic simulation model, Parasites & Vectors, Vol: 10, ISSN: 1756-3305
BackgroundThere is an increased focus on whether mass drug administration (MDA) programmes alone can interrupt the transmission of soil-transmitted helminths (STH). Mathematical models can be used to model these interventions and are increasingly being implemented to inform investigators about expected trial outcome and the choice of optimum study design. One key factor is the choice of threshold for detecting elimination. However, there are currently no thresholds defined for STH regarding breaking transmission.MethodsWe develop a simulation of an elimination study, based on the DeWorm3 project, using an individual-based stochastic disease transmission model in conjunction with models of MDA, sampling, diagnostics and the construction of study clusters. The simulation is then used to analyse the relationship between the study end-point elimination threshold and whether elimination is achieved in the long term within the model. We analyse the quality of a range of statistics in terms of the positive predictive values (PPV) and how they depend on a range of covariates, including threshold values, baseline prevalence, measurement time point and how clusters are constructed.ResultsEnd-point infection prevalence performs well in discriminating between villages that achieve interruption of transmission and those that do not, although the quality of the threshold is sensitive to baseline prevalence and threshold value. Optimal post-treatment prevalence threshold value for determining elimination is in the range 2% or less when the baseline prevalence range is broad. For multiple clusters of communities, both the probability of elimination and the ability of thresholds to detect it are strongly dependent on the size of the cluster and the size distribution of the constituent communities. Number of communities in a cluster is a key indicator of probability of elimination and PPV. Extending the time, post-study endpoint, at which the threshold statistic is measured improves
Truscott JE, Gurarie D, Alsallaq R, et al., 2017, A comparison of two mathematical models of the impact of mass drug administration on the transmission and control of schistosomiasis, Epidemics, Vol: 18, Pages: 29-37, ISSN: 1878-0067
The predictions of two mathematical models describing the transmission dynamics of schistosome infection and the impact of mass drug administration are compared. The models differ in their description of the dynamics of the parasites within the host population and in their representation of the stages of the parasite lifecycle outside of the host. Key parameters are estimated from data collected in northern Mozambique from 2011 to 2015. This type of data set is valuable for model validation as treatment prior to the study was minimal. Predictions from both models are compared with each other and with epidemiological observations. Both models have difficulty matching both the intensity and prevalence of disease in the datasets and are only partially successful at predicting the impact of treatment. The models also differ from each other in their predictions, both quantitatively and qualitatively, of the long-term impact of 10 years’ school-based mass drug administration. We trace the dynamical differences back to basic assumptions about worm aggregation, force of infection and the dynamics of the parasite in the snail population in the two models and suggest data which could discriminate between them. We also discuss limitations with the datasets used and ways in which data collection could be improved.
Turner HC, Truscott JE, Bettis AA, et al., 2015, An economic evaluation of expanding hookworm control strategies to target the whole community., Parasites & Vectors, Vol: 8, ISSN: 1756-3305
BACKGROUND: The WHO treatment guidelines for the soil-transmitted helminths (STH) focus on targeting children for the control of morbidity induced by heavy infections. However, unlike the other STHs, the majority of hookworm infections are harboured by adults. This untreated burden may have important implications for controlling both hookworm's morbidity and transmission. This is particularly significant in the context of the increased interest in investigating STH elimination strategies. METHODS: We used a deterministic STH transmission model and parameter estimates derived from field epidemiological studies to evaluate the impact of child-targeted (2-14 year olds) versus community-wide treatment against hookworm in terms of preventing morbidity and the timeframe for breaking transmission. Furthermore, we investigated how mass treatment may influence the long-term programmatic costs of preventive chemotherapy for hookworm. RESULTS: The model projected that a large proportion of the overall morbidity due to hookworm was unaffected by the current child-targeted strategy. Furthermore, driving worm burdens to levels low enough to potentially break transmission was only possible when using community-wide treatment. Due to these projected reductions in programme duration, it was possible for community-wide treatment to generate cost savings - even if it notably increases the annual distribution costs. CONCLUSIONS: Community-wide treatment is notably more cost-effective for controlling hookworm's morbidity and transmission than the current child-targeted strategies and could even be cost-saving in many settings in the longer term. These calculations suggest that it is not optimum to treat using the same treatment strategies as other STH. Hookworm morbidity and transmission control require community-wide treatment.
Truscott JE, Turner HC, Anderson RM, 2015, What impact will the achievement of the current World Health Organisation targets for anthelmintic treatment coverage in children have on the intensity of soil transmitted helminth infections?, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
BackgroundIt is the aim of the World Health Organisation to eliminate soil-transmitted helminths (STH) as a health problem in children. To this end, the goal is to increase anthelmintic treatment coverage for soil transmitted helminths to reach 75 % in pre-school aged and school aged children by 2020 in endemic countries. In this paper, we use mathematical models to investigate the impact of achieving this goal on the burdens of Ascaris lumbricoides, Trichuris trichuria and hookworm.MethodsWe employ a deterministic fully age-structured model of STH transmission and mass drug administration to examine the changes in worm burden in response to the known and projected coverage trends in children up to 2020 and beyond. Parameters are estimated from worm expulsion data and age intensity profiles before treatment using maximum likelihood methods. Model validation is performed using reinfection studies for Ascaris and analyses are conducted to assess the sensitivity of the predicted outcomes to variation in parameter estimates including transmission intensity (R0), children’s contributions to the pool of infective stages and drug coverage levels.ResultsThe impact of the required increase in coverage trends are quite different across the three species. Ascaris burdens are reduced dramatically by 2020 with elimination predicted within studied the setting a further 10 years. For Trichuris and hookworm, however, impact is more limited, due to issues of drug efficacy (Trichuris) and distribution of worms in the population (hookworm). Sensitivity analysis indicates that results are largely robust. However, validation against Ascaris data indicates that assumptions concerning re-infection among children may have to be revised.ConclusionsThe 2020 coverage target is predicted to have a major impact on Ascaris levels by 2020. However, there is evidence from model validation that Ascaris in children is more resilient to treatment than currently assumed in the model. Broader cov
Anderson RM, Turner HC, Farrell SH, et al., 2015, What is required in terms of mass drug administration to interrupt the transmission of schistosome parasites in regions of endemic infection?, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
Background: Schistosomiasis is endemic in 54 countries, but has one of the lowest coverages by mass drugadministration of all helminth diseases. However, with increasing drug availability through donation, the WorldHealth Organisation has set a goal of increasing coverage to 75 % of at-risk children in endemic countries andelimination in some regions. In this paper, we assess the impact on schistosomiasis of the WHO goals in terms ofcontrol and elimination.Methods: We use an age-structured deterministic model of schistosome transmission in a human community andthe effect of mass drug administration. The model is fitted to baseline data from a longitudinal re-infection study inKenya and validated against the subsequent re-infection data. We examine the impact on host worm burden of thecurrent treatment trend, extrapolated to meet the WHO goals, and its sensitivity to uncertainty in importantparameters. We assess the feasibility of achieving elimination.Results: Model results show that the current treatment trend, extrapolated to the WHO goals, is able to greatlyreduce host worm burdens. If coverage is continued at the same level beyond 2020, elimination is possible for lowto moderate transmission settings, where transmission intensity is defined by the basic reproduction number, R0.Low levels of adult coverage have a significant impact on worm burden in all settings. Model validation against there-infection survey demonstrates that the age-structured model is able to match post-treatment data well in termsof egg output, but that some details of re-infection among school children and young adults are not currently wellrepresented.Conclusions: Our work suggests that the current WHO treatment goals should be successful in bringing about amajor reduction in schistosome infection in treated communities. If continued over a 15 year period, they are likelyto result in elimination, at least in areas with lower transmission.
Turner HC, Truscott JE, Hollingsworth TD, et al., 2015, Cost and cost-effectiveness of soil-transmitted helminth treatment programmes: systematic review and research needs., Parasites & Vectors, Vol: 8, ISSN: 1756-3305
BACKGROUND: In this time of rapidly expanding mass drug administration (MDA) coverage and the new commitments for soil-transmitted helminth (STH) control, it is essential that resources are allocated in an efficient manner to have the greatest impact. However, many questions remain regarding how best to deliver STH treatment programmes; these include which age-groups should be targeted and how often. To perform further analyses to investigate what the most cost-effective control strategies are in different settings, accurate cost data for targeting different age groups at different treatment frequencies (in a range of settings) are essential. METHODS: Using the electronic databases PubMed, MEDLINE, and ISI Web of Knowledge, we perform a systematic review of costing studies and cost-effectiveness evaluations for potential STH treatment strategies. We use this review to highlight research gaps and outline the key future research needs. RESULTS: We identified 29 studies reporting costs of STH treatment and 17 studies that investigated its cost-effectiveness. The majority of these pertained to programmes only targeting school-aged children (SAC), with relatively few studies investigating alternative preventive chemotherapy (PCT) treatment strategies. The methods of cost data collection, analysis and reporting were highly variable among the different studies. Only four of the costing studies were found to have high applicability for use in forthcoming economic evaluations. There are also very few studies quantifying the costs of increasing the treatment frequency. CONCLUSIONS: The absence of cost data and inconsistencies in the collection and analysis methods constitutes a major research gap for STH control. Detailed and accurate costs of targeting different age groups or increasing treatment frequency will be essential to formulate cost-effective public health policy. Defining the most cost-effective control strategies in different settings is of high significance durin
Truscott J, Ferguson NM, 2012, Evaluating the Adequacy of Gravity Models as a Description of Human Mobility for Epidemic Modelling, PLOS COMPUTATIONAL BIOLOGY, Vol: 8, ISSN: 1553-734X
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- Citations: 57
Truscott J, Fraser C, Cauchemez S, et al., 2012, Essential epidemiological mechanisms underpinning the transmission dynamics of seasonal influenza, Journal of the Royal Society Interface, Vol: 9, Pages: 304-312, ISSN: 1742-5662
Seasonal influenza has considerable impact around the world, both economically and in mortality among risk groups, but there is considerable uncertainty as to the essential mechanisms and their parametrization. In this paper, we identify a number of characteristic features of influenza incidence time series in temperate regions, including ranges of annual attack rates and outbreak durations. By constraining the output of simple models to match these characteristic features, we investigate the role played by population heterogeneity, multiple strains, cross-immunity and the rate of strain evolution in the generation of incidence time series. Results indicate that an age-structured model with non-random mixing and co-circulating strains are both required to match observed time-series data. Our work gives estimates of the seasonal peak basic reproduction number, R0, in the range 1.6–3. Estimates of R0 are strongly correlated with the timescale for waning of immunity to current circulating seasonal influenza strain, which we estimate is between 3 and 8 years. Seasonal variation in transmissibility is largely confined to 15–30% of its mean value. While population heterogeneity and cross-immunity are required mechanisms, the degree of heterogeneity and cross-immunity is not tightly constrained. We discuss our findings in the context of other work fitting to seasonal influenza data.
Truscott JE, Ferguson NM, 2009, Transmission dynamics and mechanisms of endemicity of scrapie in the UK sheep population, EPIDEMIOLOGY AND INFECTION, Vol: 137, Pages: 762-774, ISSN: 0950-2688
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- Citations: 5
Truscott J, Garske T, Chis-Ster I, et al., 2007, Control of a highly pathogenic H5N1 avian influenza outbreak in the GB poultry flock, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 274, Pages: 2287-2295, ISSN: 0962-8452
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- Citations: 55
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