Imperial College London

DrMarleenWerkman

Faculty of MedicineSchool of Public Health

Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 7120m.werkman

 
 
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Location

 

LG36Praed StreetSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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29 results found

Truscott JE, Ower AK, Werkman M, Halliday K, Oswald WE, Gichuki PM, Mcharo C, Brooker S, Njenga SM, Mwandariwo C, Walson JL, Pullan R, Anderson Ret al., 2019, Heterogeneity in transmission parameters of hookworm infection within the baseline data from the TUMIKIA study in Kenya., Parasit Vectors, Vol: 12

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.

Journal article

Toor J, Truscott JE, Werkman M, Turner HC, Phillips AE, King CH, Medley GF, Anderson RMet al., 2019, Determining post-treatment surveillance criteria for predicting the elimination of Schistosoma mansoni transmission., Parasit Vectors, Vol: 12

BACKGROUND: The World Health Organization (WHO) has set elimination (interruption of transmission) as an end goal for schistosomiasis. However, there is currently little guidance on the monitoring and evaluation strategy required once very low prevalence levels have been reached to determine whether elimination or resurgence of the disease will occur after stopping mass drug administration (MDA) treatment. METHODS: We employ a stochastic individual-based model of Schistosoma mansoni transmission and MDA impact to determine a prevalence threshold, i.e. prevalence of infection, which can be used to determine whether elimination or resurgence will occur after stopping treatment with a given probability. Simulations are run for treatment programmes with varying probabilities of achieving elimination and for settings where adults harbour low to high burdens of infection. Prevalence is measured based on using a single Kato-Katz on two samples per individual. We calculate positive predictive values (PPV) using PPV ≥ 0.9 as a reliable measure corresponding to ≥ 90% certainty of elimination. We analyse when post-treatment surveillance should be carried out to predict elimination. We also determine the number of individuals across a single community (of 500-1000 individuals) that should be sampled to predict elimination. RESULTS: We find that a prevalence threshold of 1% by single Kato-Katz on two samples per individual is optimal for predicting elimination at two years (or later) after the last round of MDA using a sample size of 200 individuals across the entire community (from all ages). This holds regardless of whether the adults have a low or high burden of infection relative to school-aged children. CONCLUSIONS: Using a prevalence threshold of 0.5% is sufficient for surveillance six months after the last round of MDA. However, as such a low prevalence can be difficult to measure in the field using Kato-Katz, we recommend using 1% two ye

Journal article

Tildesley MJ, Brand S, Brooks Pollock E, Bradbury NV, Werkman M, Keeling MJet al., 2019, The role of movement restrictions in limiting the economic impact of livestock infections, Nature Sustainability, ISSN: 2398-9629

Livestock movements are essential for the economic success of the industry. However, these movements come with the risk of long-range spread of infection, potentially bringing infection to previously disease-free areas where subsequent localized transmission can be devastating. Mechanistic predictive models usually consider controls that minimize the number of livestock affected without considering other costs of an ongoing epidemic. However, it is more appropriate to consider the economic burden, as movement restrictions have major consequences for the economic revenue of farms. Here, using mechanistic models of foot-and-mouth disease, bluetongue virus and bovine tuberculosis in the UK, we compare the economically optimal control strategies for these diseases. We show that for foot-and-mouth disease, the optimal strategy is to ban movements in a small radius around infected farms; the balance between disease control and maintaining ‘business as usual’ varies between regions. For bluetongue virus and bovine tuberculosis, we find that the cost of any movement ban is greater than the epidemiological benefits due to the low within-farm prevalence and slow rate of disease spread. This work suggests that movement controls need to be carefully matched to the epidemiological and economic consequences of the disease, and that optimal movement bans are often of far shorter duration than allowed under existing policy.

Journal article

Giardina F, Coffeng LE, Farrell SH, Vegvari C, Werkman M, Truscott JE, Anderson RM, de Vlas SJet al., 2019, Sampling strategies for monitoring and evaluation of morbidity targets for soil-transmitted helminths, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727

BackgroundThe current World Health Organization (WHO) target for the three major soil-transmitted helminth (STH) infections is to reduce prevalence of moderate-to-heavy infections to below 1% by 2020. In terms of monitoring and evaluation (M&E), the current WHO guidelines for control of STHs recommend evaluation of infection levels in school-age children (SAC) after five to six years of preventive chemotherapy (PC), using the standard Kato-Katz faecal smear. Here, we assess the predictive performance of various sampling designs for the evaluation of the morbidity target.Methodology/Principal findingsUsing two mathematical models for STH transmission and control, we simulate how the number of villages and SAC sampled affect the ability of survey results in sentinel villages to predict the achievement of the morbidity target in PC implementation units (e.g. districts). As PC is stopped when the prevalence of infection in SAC in sentinel villages is less than 1%, we estimate the positive predictive value (PPV) of this indicator for meeting the morbidity target in the whole district. The PPV varies by species and PC strategy, and it is generally higher in areas with lower pre-control prevalence. Sampling a fixed number of SAC spread out over 10 instead of 5 sentinel villages may increase the PPV by up to 20 percentage points. If every SAC in a village is tested, a higher number of villages may increase the PPV by up to 80 percentage points. Increasing the proportion of SAC tested per village does not result in a relevant increase of PPV.Conclusions/SignificanceAlthough the WHO guidelines provide a combined strategy to control the three STH species, the efficacy of PC strategies clearly differs by species. There is added value in considering more villages within implementation units for M&E of morbidity targets, the extent varying by STH species. A better understanding of pre- and post-control local STH prevalence levels is essential for an adequate M&E strat

Journal article

Truscott JE, Dunn JC, Papaiakovou M, Schaer F, Werkman M, Littlewood DTJ, Walson JL, Anderson RMet 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.

Journal article

Toor J, Turner HC, Truscott JE, Werkman M, Phillips AE, Alsallaq R, Medley GF, King CH, Anderson RMet al., 2018, The design of schistosomiasis monitoring and evaluation programmes: The importance of collecting adult data to inform treatment strategies for Schistosoma mansoni, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727

Monitoring and evaluation (M&E) programmes are used to collect data which are required to assess the impact of current interventions on their progress towards achieving the World Health Organization (WHO) goals of morbidity control and elimination as a public health problem for schistosomiasis. Prevalence and intensity of infection data are typically collected from school-aged children (SAC) as they are relatively easy to sample and are thought to be most likely to be infected by schistosome parasites. However, adults are also likely to be infected. We use three different age-intensity profiles of infection for Schistosoma mansoni with low, moderate and high burdens of infection in adults to investigate how the age distribution of infection impacts the mathematical model generated recommendations of the preventive chemotherapy coverage levels required to achieve the WHO goals. We find that for moderate prevalence regions, regardless of the burden of infection in adults, treating SAC only may achieve the WHO goals. However, for high prevalence regions with a high burden of infection in adults, adult treatment is required to meet the WHO goals. Hence, we show that the optimal treatment strategy for a defined region requires consideration of the burden of infection in adults as it cannot be based solely on the prevalence of infection in SAC. Although past epidemiological data have informed mathematical models for the transmission and control of schistosome infections, more accurate and detailed data are required from M&E programmes to accurately determine the optimal treatment strategy for a defined region. We highlight the importance of collecting prevalence and intensity of infection data from a broader age-range, specifically the inclusion of adult data at baseline (prior to treatment) and throughout the treatment programme if possible, rather than SAC only, to accurately determine the treatment strategy for a defined region. Furthermore, we discuss addition

Journal article

Werkman M, Toor J, Vegvari C, Wright JE, Truscott JE, Asbjornsdottir KH, Means AR, Walson JL, Anderson RMet al., 2018, Defining stopping criteria for ending randomized clinical trials that investigate the interruption of transmission of soil-transmitted helminths employing mass drug administration, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727

The current World Health Organization strategy to address soil-transmitted helminth (STH) infections in children is based on morbidity control through routine deworming of school and pre-school aged children. However, given that transmission continues to occur as a result of persistent reservoirs of infection in untreated individuals (including adults) and in the environment, in many settings such a strategy will need to be continued for very extended periods of time, or until social, economic and environmental conditions result in interruption of transmission. As a result, there is currently much discussion surrounding the possibility of accelerating the interruption of transmission using alternative strategies of mass drug administration (MDA). However, the feasibility of achieving transmission interruption using MDA remains uncertain due to challenges in sustaining high MDA coverage levels across entire communities. The DeWorm3 trial, designed to test the feasibility of interrupting STH transmission, is currently ongoing. In DeWorm3, three years of high treatment coverage—indicated by mathematical models as necessary for breaking transmission—will be followed by two years of surveillance. Given the fast reinfection (bounce-back) rates of STH, a two year no treatment period is regarded as adequate to assess whether bounce-back or transmission interruption have occurred in a given location. In this study, we investigate if criteria to determine whether transmission interruption is unlikely can be defined at earlier timepoints. A stochastic, individual-based simulation model is employed to simulate core aspects of the DeWorm3 community-based cluster-randomized trial. This trial compares a control arm (annual treatment of children alone with MDA) with an intervention arm (community-wide biannual treatment with MDA). Simulations were run for each scenario for both Ascaris lumbricoides and hookworm (Necator americanus). A range of threshold prevalences meas

Journal article

Probert WJM, Jewell CP, Werkman M, Fonnesbeck CJ, Goto Y, Runge MC, Sekiguchi S, Shea K, Keeling MJ, Ferrari MJ, Tildesley MJet al., 2018, Real-time decision-making during emergency disease outbreaks, PLoS Computational Biology, Vol: 14, ISSN: 1553-734X

In the event of a new infectious disease outbreak, mathematical and simulation models are commonly used to inform policy by evaluating which control strategies will minimize the impact of the epidemic. In the early stages of such outbreaks, substantial parameter uncertainty may limit the ability of models to provide accurate predictions, and policymakers do not have the luxury of waiting for data to alleviate this state of uncertainty. For policymakers, however, it is the selection of the optimal control intervention in the face of uncertainty, rather than accuracy of model predictions, that is the measure of success that counts. We simulate the process of real-time decision-making by fitting an epidemic model to observed, spatially-explicit, infection data at weekly intervals throughout two historical outbreaks of foot-and-mouth disease, UK in 2001 and Miyazaki, Japan in 2010, and compare forward simulations of the impact of switching to an alternative control intervention at the time point in question. These are compared to policy recommendations generated in hindsight using data from the entire outbreak, thereby comparing the best we could have done at the time with the best we could have done in retrospect.Our results show that the control policy that would have been chosen using all the data is also identified from an early stage in an outbreak using only the available data, despite high variability in projections of epidemic size. Critically, we find that it is an improved understanding of the locations of infected farms, rather than improved estimates of transmission parameters, that drives improved prediction of the relative performance of control interventions. However, the ability to estimate undetected infectious premises is a function of uncertainty in the transmission parameters. Here, we demonstrate the need for both real-time model fitting and generating projections to evaluate alternative control interventions throughout an outbreak. Our results high

Journal article

Farrell SH, Coffeng LE, Truscott JE, Werkman M, Toor J, de Vlas SJ, Anderson RMet al., 2018, Investigating the Effectiveness of Current and Modified World Health Organization Guidelines for the Control of Soil-Transmitted Helminth Infections, CLINICAL INFECTIOUS DISEASES, Vol: 66, Pages: S253-S259, ISSN: 1058-4838

BackgroundConsiderable efforts have been made to better understand the effectiveness of large-scale preventive chemotherapy therapy for the control of morbidity caused by infection with soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura, and the 2 hookworm species, Necator americanus and Ancylostoma duodenale. Current World Health Organization (WHO) guidelines for STH control include mass drug administration (MDA) programs based on prevalence measurements, aiming at reducing morbidity in pre–school-aged children (pre-SAC) and school-aged children (SAC) by lowering the prevalence of moderate- to heavy-intensity infections to <1%.MethodsWe project the likely impact of following the current WHO guidelines and assess whether the WHO morbidity goals will be achieved across a range of transmission settings. We also investigate modifications that could be made to the current WHO treatment guidelines, and project their potential impacts in achieving morbidity and transmission control.ResultsWhile the standard guidelines are sufficient at low transmission levels, community-wide treatment (ie, involving pre-SAC, SAC, and adults) is essential if WHO morbidity goals are to be met in moderate- to high-transmission settings. Moreover, removing the recommendation of decreasing the treatment frequency at midline (5–6 years after the start of MDA) further improves the likelihood of achieving morbidity control in SAC.ConclusionsWe meld analyses based on 2 mathematical models of parasite transmission and control by MDA for the dominant STH species, to generate a unified treatment approach applicable across all settings, regardless of which STH infection is most common. We recommend clearly defined changes to the current WHO guidelines.

Journal article

Toor J, Alsallaq R, Truscott JE, Turner HC, Werkman M, Gurarie D, King CH, Anderson RMet al., 2018, Are We on Our Way to Achieving the 2020 Goals for Schistosomiasis Morbidity Control Using Current World Health Organization Guidelines?, CLINICAL INFECTIOUS DISEASES, Vol: 66, Pages: S245-S252, ISSN: 1058-4838

BackgroundSchistosomiasis remains an endemic parasitic disease affecting millions of people around the world. The World Health Organization (WHO) has set goals of controlling morbidity to be reached by 2020, along with elimination as a public health problem in certain regions by 2025. Mathematical models of parasite transmission and treatment impact have been developed to assist in controlling the morbidity caused by schistosomiasis. These models can inform and guide implementation policy for mass drug administration programs, and help design monitoring and evaluation activities.MethodsWe use these models to predict whether the guidelines set by the WHO are on track for achieving their 2020 goal for the control of morbidity, specifically for Schistosoma mansoni. We examine whether programmatic adaptations; namely increases in treatment coverage and/or expansion to adult inclusion in treatment, will improve the likelihood of reaching the WHO goals.ResultsWe find that in low-prevalence settings, the goals are likely to be attainable under current WHO guidelines, but in moderate to high-prevalence settings, the goals are less likely to be achieved unless treatment coverage is increased and expanded to at least 85% for school-aged children and 40% for adults.ConclusionsTo improve the likelihood of reaching the WHO goals, programmatic adaptations are required, particularly for moderate- to high-prevalence settings. Furthermore, improvements in adherence to treatment, potential development of candidate vaccines, and enhanced snail control and WASH (water, sanitation, and hygiene) measures will all assist in achieving the goals.

Journal article

Wright JE, Werkman M, Dunn J, Anderson Ret al., 2018, Current epidemiological evidence for predisposition to high or low intensity human helminth infection: a systematic review, Parasites & Vectors, Vol: 11, ISSN: 1756-3305

Background: The human helminth infections include ascariasis, trichuriasis, hookworm infections, schistosomiasis,lymphatic filariasis (LF) and onchocerciasis. It is estimated that almost 2 billion people worldwide are infected withhelminths. Whilst the WHO treatment guidelines for helminth infections are mostly aimed at controlling morbidity,there has been a recent shift with some countries moving towards goals of disease elimination through mass drugadministration, especially for LF and onchocerciasis. However, as prevalence is driven lower, treating entire populationsmay no longer be the most efficient or cost-effective strategy. Instead, it may be beneficial to identify individuals ordemographic groups who are persistently infected, often termed as being “predisposed” to infection, and targettreatment at them.Methods: The authors searched Embase, MEDLINE, Global Health, and Web of Science for all English language, humanbasedpapers investigating predisposition to helminth infections published up to October 31st, 2017. Thevarying definitions used to describe predisposition, and the statistical tests used to determine its presence, are summarised.Evidence for predisposition is presented, stratified by helminth species, and risk factors for predisposition to infection areidentified and discussed.Results: In total, 43 papers were identified, summarising results from 34 different studies in 23 countries. Consistentevidence of predisposition to infection with certain species of human helminth was identified. Children were regularlyfound to experience greater predisposition to Ascaris lumbricoides, Schistosoma mansoni and S. haematobium than adults.Females were found to be more predisposed to A. lumbricoides infection than were males. Household clustering ofinfection was identified for A. lumbricoides, T. trichiura and S. japonicum. Ascaris lumbricoides and T. trichiura also showedevidence of familial predisposition. Whilst strong evidence for predisposition

Journal article

Asbjornsdottir KH, Rao Ajjampur SS, Anderson R, Bailey R, Gardiner I, Halliday KE, Ibikounle M, Kalua K, Kang G, Littlewood DTJ, Luty AJF, Rubin Means A, Oswald W, Pullan RL, Sarkar R, Schar F, Szpiro A, Truscott J, Werkman M, Yard E, Walson JLet al., 2018, Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protoco, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727

Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prev

Journal article

Werkman M, Wright JE, Truscott JE, Easton AV, Oliveira RG, Toor J, Ower A, Ásbjörnsdóttir KH, Means AR, Farrell SH, Walson JL, Anderson RMet al., 2018, Testing for soil-transmitted helminth transmission elimination: Analysing the impact of the sensitivity of different diagnostic tools., PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727

In recent years, an increased focus has been placed upon the possibility of the elimination of soil-transmitted helminth (STH) transmission using various interventions including mass drug administration. The primary diagnostic tool recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz (KK) method. However, detecting infected individuals using this method becomes increasingly difficult as the intensity of infection decreases. Newer techniques, such as qPCR, have been shown to have greater sensitivity than KK, especially at low prevalence. However, the impact of using qPCR on elimination thresholds is yet to be investigated. In this paper, we aim to quantify how the sensitivity of these two diagnostic tools affects the optimal prevalence threshold at which to declare the interruption of transmission with a defined level of confidence. A stochastic, individual-based STH transmission model was used in this study to simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan deworming study were used to parameterize the diagnostic model which was based on egg detection probabilities. The positive and negative predictive values (PPV and NPV) were calculated to assess the quality of any given threshold, with the optimal threshold value taken to be that at which both were maximised. The threshold prevalence of infection values for declaring elimination of Ascaris transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with greater sensitivity are becoming increasingly important as we approach the elimination of STH transmission in some regions of the world. For declaring the elimination of transmission, using qPCR to diagnose STH infection results in the definition of a higher prevalence, than when KK is used.

Journal article

Asbjornsdottir KH, Means AR, Werkman M, Walson JLet al., 2017, Prospects for elimination of soil-transmitted helminths, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 30, Pages: 482-488, ISSN: 0951-7375

Purpose of review: Soil-transmitted helminths (STH) are endemic in 120 countries and are associated with substantial morbidity and loss of economic productivity. Although current WHO guidelines focus on morbidity control through mass drug administration (MDA), there is global interest in whether a strategy targeting disease elimination might be feasible in some settings. This review summarizes the prospects for switching from control to an elimination strategy.Recent findings: STH control efforts have reduced the intensity of infections in targeted populations with associated reductions in morbidity. However, adults are not frequently targeted and remain important reservoirs for reinfection of treated children. Recent modeling suggests that transmission interruption may be possible through expanded community-wide delivery of MDA, the feasibility of which has been demonstrated by other programs. However, these models suggest that high levels of coverage and compliance must be achieved. Potential challenges include the risk of prematurely dismantling STH programs and the potential increased risk of antihelminthic resistance.Summary: Elimination of STH may offer an opportunity to eliminate substantial STH-related morbidity while reducing resource needs of neglected tropical disease programs. Evidence from large community trials is needed to determine the feasibility of interrupting the transmission of STH in some geographic settings.

Journal article

Truscott JE, Werkman M, Wright JE, Farrell SH, Sarkar R, Ásbjörnsdóttir K, Anderson RMet 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

Journal article

Werkman M, Truscott JE, Toor J, Wright JE, Anderson RMet al., 2017, The past matters: estimating intrinsic hookworm transmission intensity inareas with past mass drug administration to control lymphatic filariasis, Parasites & Vectors, Vol: 10, ISSN: 1756-3305

BackgroundCurrent WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme.ResultsAnalyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R0). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R0 value is predicted to be 1.67. The intrinsic R0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities.ConclusionTo design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R0). The b

Journal article

Webb CT, Ferrari M, Lindstrom T, Carpenter T, Duerr S, Garner G, Jewell C, Stevenson M, Ward MP, Werkman M, Backer J, Tildesley Met al., 2017, Ensemble modelling and structured decision-making to support Emergency Disease Management, PREVENTIVE VETERINARY MEDICINE, Vol: 138, Pages: 124-133, ISSN: 0167-5877

Journal article

Werkman M, Truscott JE, Wright JE, Toor J, Asbjornsdottir KH, Farrell SH, Walson JL, Anderson RMet al., 2017, ARE WE ON THE RIGHT TRACK? STOPPING CRITERIA FOR ENDING SOIL-TRANSMITTED HELMINTHS RANDOMIZED CLINICAL TRIALS, 66th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH)

Poster

Werkman M, Tildesley MJ, Brooks-Pollock E, Keeling MJet al., 2016, Preserving privacy whilst maintaining robust epidemiological predictions, Epidemics, Vol: 17, Pages: 35-41, ISSN: 1755-4365

Mathematical models are invaluable tools for quantifying potential epidemics and devising optimal control strategies in case of an outbreak. State-of-the-art models increasingly require detailed individual farm-based and sensitive data, which may not be available due to either lack of capacity for data collection or privacy concerns. However, in many situations, aggregated data are available for use. In this study, we systematically investigate the accuracy of predictions made by mathematical models initialised with varying data aggregations, using the UK 2001 Foot-and-Mouth Disease Epidemic as a case study. We consider the scenario when the only data available are aggregated into spatial grid cells, and develop a metapopulation model where individual farms in a single subpopulation are assumed to behave uniformly and transmit randomly. We also adapt this standard metapopulation model to capture heterogeneity in farm size and composition, using farm census data. Our results show that homogeneous models based on aggregated data overestimate final epidemic size but can perform well for predicting spatial spread. Recognising heterogeneity in farm sizes improves predictions of the final epidemic size, identifying risk areas, determining the likelihood of epidemic take-off and identifying the optimal control strategy. In conclusion, in cases where individual farm-based data are not available, models can still generate meaningful predictions, although care must be taken in their interpretation and use.

Journal article

Probert WJ, Shea K, Fonnesbeck CJ, Runge MC, Carpenter TE, Dürr S, Garner MG, Harvey N, Stevenson MA, Webb CT, Werkman M, Tildesley MJ, Ferrari MJet al., 2015, Decision-making for foot-and-mouth disease control: Objectives matter, Epidemics, Vol: 15, Pages: 10-19, ISSN: 1878-0067

Formal decision-analytic methods can be used to frame disease control problems, the first step of which is to define a clear and specific objective. We demonstrate the imperative of framing clearly-defined management objectives in finding optimal control actions for control of disease outbreaks. We illustrate an analysis that can be applied rapidly at the start of an outbreak when there are multiple stakeholders involved with potentially multiple objectives, and when there are also multiple disease models upon which to compare control actions. The output of our analysis frames subsequent discourse between policy-makers, modellers and other stakeholders, by highlighting areas of discord among different management objectives and also among different models used in the analysis. We illustrate this approach in the context of a hypothetical foot-and-mouth disease (FMD) outbreak in Cumbria, UK using outputs from five rigorously-studied simulation models of FMD spread. We present both relative rankings and relative performance of controls within each model and across a range of objectives. Results illustrate how control actions change across both the base metric used to measure management success and across the statistic used to rank control actions according to said metric. This work represents a first step towards reconciling the extensive modelling work on disease control problems with frameworks for structured decision making.

Journal article

Dawson PM, Werkman M, Brooks-Pollock E, Tildesley MJet al., 2015, Epidemic predictions in an imperfect world: modelling disease spread with partial data, Proceedings of the Royal Society B: Biological Sciences, Vol: 282, ISSN: 0962-8452

‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around the world, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.

Journal article

Dawson PM, Werkman M, Brooks-Pollock E, Tildesley MJet al., 2015, Epidemic predictions in an imperfect world: Modelling disease spread with partial data, Proceedings of the Royal Society B: Biological Sciences, Vol: 282, Pages: 1-9, ISSN: 0962-8452

© 2015 Royal Society of London. All rights reserved. ‘Big-data’ epidemic models are being increasingly used to influence government policy to help with control and eradication of infectious diseases. In the case of livestock, detailed movement records have been used to parametrize realistic transmission models. While livestock movement data are readily available in the UK and other countries in the EU, in many countries around theworld, such detailed data are not available. By using a comprehensive database of the UK cattle trade network, we implement various sampling strategies to determine the quantity of network data required to give accurate epidemiological predictions. It is found that by targeting nodes with the highest number of movements, accurate predictions on the size and spatial spread of epidemics can be made. This work has implications for countries such as the USA, where access to data is limited, and developing countries that may lack the resources to collect a full dataset on livestock movements.

Journal article

Buhnerkempe MG, Tildesley MJ, Lindstrom T, Grear DA, Portacci K, Miller RS, Lombard JE, Werkman M, Keeling MJ, Wennergren U, Webb CTet al., 2014, The Impact of Movements and Animal Density on Continental Scale Cattle Disease Outbreaks in the United States, PLOS ONE, Vol: 9, ISSN: 1932-6203

Journal article

Werkman M, Murray AG, Munro LA, Turnbull JF, Green DMet al., 2014, Seasonality in live fish movements and its effects on epidemic dynamics, AQUACULTURE, Vol: 418, Pages: 72-78, ISSN: 0044-8486

Journal article

Green DM, Werkman M, Munro LA, 2012, The potential for targeted surveillance of live fish movements in Scotland, JOURNAL OF FISH DISEASES, Vol: 35, Pages: 29-37, ISSN: 0140-7775

Journal article

Werkman M, Green DM, Munro LA, Murray AG, Turnbull JFet al., 2011, Seasonality and heterogeneity of live fish movements in Scottish fish farms, DISEASES OF AQUATIC ORGANISMS, Vol: 96, Pages: 69-82, ISSN: 0177-5103

Journal article

Green DM, Werkman M, Munro LA, Kao RR, Kiss IZ, Danon Let al., 2011, Tools to study trends in community structure: Application to fish and livestock trading networks, PREVENTIVE VETERINARY MEDICINE, Vol: 99, Pages: 225-228, ISSN: 0167-5877

Journal article

Werkman M, Green DM, Murray AG, Turnbull JFet al., 2011, The effectiveness of fallowing strategies in disease control in salmon aquaculture assessed with an SIS model, PREVENTIVE VETERINARY MEDICINE, Vol: 98, Pages: 64-73, ISSN: 0167-5877

Journal article

Ashworth CJ, Dwyer CM, McIlvaney K, Werkman M, Rooke JAet al., 2011, Breed differences in fetal and placental development and feto-maternal amino acid status following nutrient restriction during early and mid pregnancy in Scottish Blackface and Suffolk sheep, REPRODUCTION FERTILITY AND DEVELOPMENT, Vol: 23, Pages: 1024-1033, ISSN: 1031-3613

Journal article

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