Publications
13 results found
Farrell SH, Anderson RM, 2018, Helminth lifespan interacts with noncompliance in reducing the effectiveness of anthelmintic treatment, PARASITES & VECTORS, Vol: 11, ISSN: 1756-3305
BackgroundThe success of mass drug administration programmes targeting the soil-transmitted helminths and schistosome parasites is in part dependent on compliance to treatment at sequential rounds of mass drug administration (MDA). The impact of MDA is vulnerable to systematic non-compliance, defined as a portion of the eligible population remaining untreated over successive treatment rounds. The impact of systematic non-compliance on helminth transmission dynamics - and thereby on the number of treatment rounds required to interrupt transmission - is dependent on the parasitic helminth being targeted by MDA.ResultsHere, we investigate the impact of adult parasite lifespan in the human host and other factors that determine the magnitude of the basic reproductive number R 0 , on the number of additional treatment rounds required in a target population, using mathematical models of Ascaris lumbricoides and Schistosoma mansoni transmission incorporating systematic non-compliance. Our analysis indicates a strong interaction between helminth lifespan and the impact of systematic non-compliance on parasite elimination, and confirms differences in its impact between Ascaris and the schistosome parasites in a streamlined model structure.ConclusionsOur analysis suggests that achieving reductions in the level of systematic non-compliance may be of particular benefit in mass drug administration programmes treating the longer-lived helminth parasites, and highlights the need for improved data collection in understanding the impact of compliance.
Werkman M, Wright JE, Truscott JE, et 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.
Truscott J, Farrell S, Anderson R, 2017, USING TRANSMISSION MODELS IN STUDY DESIGN: DETECTING ELIMINATION AND THE IMPACT OF PRE-EXISTING TREATMENT PROGRAMS, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 542-542, ISSN: 0002-9637
Farrell SH, 2017, MODELLING THE EFFECT OF PATTERNS OF ADHERENCE AND NON-ADHERENCE TO TREATMENT IN PURSUIT OF HELMINTH ELIMINATION BY MASS DRUG ADMINISTRATION, 65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 355-355, ISSN: 0002-9637
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
Farrell SH, Truscott JE, Anderson RM, 2017, The importance of patient compliance in repeated rounds of mass drug administration (MDA) for the elimination of intestinal helminth transmission, PARASITES & VECTORS, Vol: 10, ISSN: 1756-3305
Background:Systematic non-compliance to chemotherapeutic treatment among a portion of the eligible population is thought to be a major obstacle to the elimination of helminth infections by mass drug administration (MDA). MDA for helminths is repeated at defined intervals such as yearly or every 2 years, as a consequence of the inability of the human host to develop fully protective immunity to reinfection. As such, how an individual complies to these repeated rounds of MDA can have a significant impact on parasite transmission. The importance of this factor is poorly understood at present. Few epidemiological studies have examined longitudinal trends in compliance in the many communities in areas of endemic helminth infection that are undergoing MDA. Reducing systematic non-compliance will obviously increase the number of individuals treated, but it may also alter the dynamics of parasite transmission.Methods:Here we develop an individual-based stochastic model of helminth transmission and MDA treatment to investigate how different patterns of compliance influence the impact of MDA for two groups of helminths, the soil transmitted nematode infections and the schistosome parasites. We study the effect of several alternative treatment and compliance patterns on the dynamics of transmission.Results:We find that the impact of different compliance patterns, ranging from random treatment at each round of chemotherapy to systematic non-compliance by a proportion of the population, is very dependent on both transmission intensity in a defined setting and the type of infection that the treatment is targeted at. Systematic non-compliance has a greater impact on the potential for elimination of Schistosoma mansoni transmission by intensive MDA, than it does on Ascaris lumbricoides.Conclusions:We discuss the implications of our findings for the prioritisation of resources in MDA programmes and for monitoring and evaluation programme design. The key message generated by the anal
Turner HC, Truscott JE, Bettis AA, et al., 2017, Evaluating the variation in the projected benefit of community-wide mass treatment for schistosomiasis: Implications for future economic evaluations, PARASITES & VECTORS, Vol: 10, ISSN: 1756-3305
Background:The majority of schistosomiasis control programmes focus on targeting school-aged children. Expanding the use of community-wide mass treatment to reach more adults is under consideration. However, it should be noted that this would require a further increase in programmatic resources, international aid, and commitment for the provision of praziquantel. Consequently, it is important to understand (i) where a change of strategy would have the greatest benefit, and (ii) how generalisable the conclusions of field trials and analytical studies based on mathematical models investigating the impact of community-wide mass treatment, are to a broad range of settings.Methods:In this paper, we employ a previously described deterministic fully age-structured schistosomiasis transmission model and evaluate the benefit of community-wide mass treatment both in terms of controlling morbidity and eliminating transmission for Schistosoma mansoni, across a wide range of epidemiological settings and programmatic scenarios. This included variation in the baseline relative worm pre-control burden in adults, the overall level of transmission in defined settings, choice of effectiveness metric (basing morbidity calculations on prevalence or intensity), the level of school enrolment and treatment compliance.Results:Community-wide mass treatment was found to be more effective for controlling the transmission of schistosome parasites than using a school-based programme only targeting school-aged children. However, in the context of morbidity control, the potential benefit of switching to community-wide mass treatment was highly variable across the different scenarios analysed. In contrast, for areas where the goal is to eliminate transmission, the projected benefit of community-wide mass treatment was more consistent.Conclusion:Whether community-wide mass treatment is appropriate will depend on the local epidemiological setting (i.e. the relative pre-control burden in adults and tr
Coffeng LE, Truscott JE, Farrell SH, et al., 2017, Comparison and validation of two mathematical models for the impact of mass drug administration on Ascaris lumbricoides and hookworm infection, Epidemics, Vol: 18, Pages: 38-47, ISSN: 1755-4365
The predictions of two mathematical models of the transmission dynamics of Ascaris lumbricoides and hookworm infection and the impact of mass drug administration (MDA) are compared, using data from India. One model has an age structured partial differential equation (PDE) deterministic framework for the distribution of parasite numbers per host and sexual mating. The second model is an individual-based stochastic model. Baseline data acquired prior to treatment are used to estimate key transmission parameters, and forward projections are made, given the known MDA population coverage. Predictions are compared with observed post-treatment epidemiological patterns. The two models could equally well predict the short-term impact of deworming on A. lumbricoides and hookworm infection levels, despite being fitted to different subsets and/or summary statistics of the data. As such, the outcomes give confidence in their use as aids to policy formulation for the use of PCT to control A. lumbricoides and hookworm infection. The models further largely agree in a qualitative sense on the added benefit of semi-annual vs. annual deworming and targeting of the entire population vs. only children, as well as the potential for interruption of transmission. Further, this study also illustrates that long-term predictions are sensitive to modelling assumptions about which age groups contribute most to transmission, which depends on human demography and age-patterns in exposure and contribution to the environmental reservoir of infection, the latter being notoriously difficult to empirically quantify.
Dyson L, Stolk WA, Farrell SH, et al., 2017, Measuring and modelling the effects of systematic non-adherence to mass drug administration, Epidemics, Vol: 18, Pages: 56-66, ISSN: 1755-4365
It is well understood that the success or failure of a mass drug administration campaign critically depends on the level of coverage achieved. To that end coverage levels are often closely scrutinised during campaigns and the response to underperforming campaigns is to attempt to improve coverage. Modelling work has indicated, however, that the quality of the coverage achieved may also have a significant impact on the outcome. If the coverage achieved is likely to miss similar people every round then this can have a serious detrimental effect on the campaign outcome. We begin by reviewing the current modelling descriptions of this effect and introduce a new modelling framework that can be used to simulate a given level of systematic non-adherence. We formalise the likelihood that people may miss several rounds of treatment using the correlation in the attendance of different rounds. Using two very simplified models of the infection of helminths and non-helminths, respectively, we demonstrate that the modelling description used and the correlation included between treatment rounds can have a profound effect on the time to elimination of disease in a population. It is therefore clear that more detailed coverage data is required to accurately predict the time to disease elimination. We review published coverage data in which individuals are asked how many previous rounds they have attended, and show how this information may be used to assess the level of systematic non-adherence. We note that while the coverages in the data found range from 40.5% to 95.5%, still the correlations found lie in a fairly narrow range (between 0.2806 and 0.5351). This indicates that the level of systematic non-adherence may be similar even in data from different years, countries, diseases and administered drugs.
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.
Anderson R, Farrell S, Turner H, et al., 2017, Assessing the interruption of the transmission of human helminths with mass drug administration alone: optimizing the design of cluster randomized trials, PARASITES & VECTORS, Vol: 10, ISSN: 1756-3305
Background:A method is outlined for the use of an individual-based stochastic model of parasite transmission dynamics to assess different designs for a cluster randomized trial in which mass drug administration (MDA) is employed in attempts to eliminate the transmission of soil-transmitted helminths (STH) in defined geographic locations. The hypothesis to be tested is: Can MDA alone interrupt the transmission of STH species in defined settings? Clustering is at a village level and the choice of clusters of villages is stratified by transmission intensity (low, medium and high) and parasite species mix (either Ascaris, Trichuris or hookworm dominant).Results:The methodological approach first uses an age-structured deterministic model to predict the MDA coverage required for treating pre-school aged children (Pre-SAC), school aged children (SAC) and adults (Adults) to eliminate transmission (crossing the breakpoint in transmission created by sexual mating in dioecious helminths) with 3 rounds of annual MDA. Stochastic individual-based models are then used to calculate the positive and negative predictive values (PPV and NPV, respectively, for observing elimination or the bounce back of infection) for a defined prevalence of infection 2 years post the cessation of MDA. For the arm only involving the treatment of Pre-SAC and SAC, the failure rate is predicted to be very high (particularly for hookworm-infected villages) unless transmission intensity is very low (R0, or the effective reproductive number R, just above unity in value).Conclusions:The calculations are designed to consider various trial arms and stratifications; namely, community-based treatment and Pre-SAC and SAC only treatment (the two arms of the trial), different STH transmission settings of low, medium and high, and different STH species mixes. Results are considered in the light of the complications introduced by the choice of statistic to define success or failure, varying adherence to treatment, mig
Truscott JE, Turner HC, Farrell SH, et al., 2016, Soil-Transmitted Helminths: Mathematical Models of Transmission, the Impact of Mass Drug Administration and Transmission Elimination Criteria, ADVANCES IN PARASITOLOGY, VOL 94: MATHEMATICAL MODELS FOR NEGLECTED TROPICAL DISEASES: ESSENTIAL TOOLS FOR CONTROL AND ELIMINATION, PT B, Vol: 94, Pages: 133-198, ISSN: 0065-308X
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.
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