ORCID Profile
0000-0001-8778-006X
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Publisher: Public Library of Science (PLoS)
Date: 02-11-2020
DOI: 10.1371/JOURNAL.PNTD.0008771
Abstract: Global efforts to control morbidity associated with soil-transmitted helminth infections (STH) have focused largely on the targeted treatment of high-risk groups, including children and pregnant women. However, it is not clear when such programs can be discontinued and there are concerns about the sustainability of current STH control programs. The DeWorm3 project is a large multi-country community cluster randomized trial in Benin, India and Malawi designed to determine the feasibility of interrupting the transmission of STH using community-wide delivery of mass drug administration (MDA) with anthelmintics over multiple rounds. Here, we present baseline data and estimate key epidemiological parameters important in determining the likelihood of transmission interruption in the DeWorm3 trial. A baseline census was conducted in October-December 2017 in India, November-December 2017 in Malawi and in January-February 2018 in Benin. The baseline census enumerated all members of each household and collected demographic data and information on occupation, assets, and access to water, sanitation and hygiene (WASH). Each study site was ided into 40 clusters of at least 1,650 in iduals per cluster. Clusters were randomized to receive twice yearly community-wide MDA with albendazole (GSK) targeting eligible in iduals of all ages (20 clusters), or to receive the standard-of-care deworming program targeting children provided in each country. In each site, a randomly selected group of 150 in iduals per cluster (6,000 total per site) was selected from the baseline census using stratified random s ling, and each in idual provided a single stool s le for analysis of STH infection using the Kato-Katz technique. Study site, household and in idual characteristics were summarized as appropriate. We estimated key epidemiological parameters including the force of infection and the degree of parasite aggregation within the population. The DeWorm3 sites range in population from 94,969 to 140,932. The population age distribution varied significantly by site, with the highest proportion of infants and young children in Malawi and the highest proportion of adults in India. The baseline age- and cluster-weighted prevalence, as measured by Kato-Katz, varied across sites and by species, Baseline hookworm prevalence in India was 21.4% (95% CI: 20.4–22.4%), while prevalence of Ascaris and Trichuris by Kato-Katz was low (0.1% and 0.3% overall). In Malawi, the overall age- and cluster-weighted STH prevalence was 7.7% (95% CI: 7.1–8.4%) predominantly driven by hookworm infections (7.4%) while Ascaris (0.1%) and Trichuris (0.3%) infections were rare. In Benin, the overall age- and cluster-weighted prevalence was significantly lower (5.6%, 95% CI: 5.1–6.2%) and Ascaris (2.0%, 95% CI: 1.6–2.3%) was more common than in other sites. Ascaris infections were more likely to be moderate- or heavy-intensity (43.7%, unweighted) compared to hookworm (5.0%). The force of infection for hookworm was highest in adults in India and Malawi but appeared relatively stable across age groups in Benin. These data demonstrate the significant variability between the sites in terms of demography, socio-economic status and environmental characteristics. In addition, the baseline prevalence and intensity data from DeWorm3 suggest that each site has unique epidemiologic characteristics that will be critical in determining correlates of achieving STH transmission interruption in the DeWorm3 trial. Trial registration: The trial was registered at ClinicalTrials.gov ( NCT03014167 ).
Publisher: IOP Publishing
Date: 19-11-2018
Publisher: Research Square Platform LLC
Date: 12-08-2020
DOI: 10.21203/RS.3.RS-55594/V1
Abstract: 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 in idual-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 in idual 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 with widespread elimination but a few `hot spot' areas of persisting STH transmission.Conclusions Our results suggest that geographical heterogeneities in transmission intensity and worm aggregation have a large impact on the effect of MDA. It is important to accurately assessing cluster-level, or even smaller scale, heterogeneities in factors which influence transmission and aggregation for a clearer perspective on projecting the outcomes of MDA control of STH and other neglected tropical diseases.
Publisher: Public Library of Science (PLoS)
Date: 25-08-2022
DOI: 10.1371/JOURNAL.PONE.0272600
Abstract: Much effort has been devoted by the World Health Organization (WHO) to eliminate soil-transmitted helminth (STH) infections by 2030 using mass drug administration targeted at particular risk groups alongside the availability to access water, sanitation and hygiene services. The targets set by the WHO for the control of helminth infections are typically defined in terms of the prevalence of infection, whereas the standard formulation of STH transmission models typically describe dynamic changes in the mean-worm burden. We develop a prevalence-based deterministic model to investigate the transmission dynamics of soil-transmitted helminthiasis in humans, subject to continuous exposure to infection over time. We analytically determine local stability criteria for all equilibria and find bifurcation points. Our model predicts that STH infection will either be eliminated (if the initial prevalence value, y (0), is sufficiently small) or remain endemic (if y (0) is sufficiently large), with the two stable points of endemic infection and parasite eradication separated by a transmission breakpoint. Two special cases of the model are analysed: (1) the distribution of the STH parasites in the host population is highly aggregated following a negative binomial distribution, and (2) no density-dependent effects act on the parasite population. We find that disease extinction is always possible for Case (1), but it is not so for Case (2) if y (0) is sufficiently large. However, by introducing stochastic perturbation into the deterministic model, we discover that chance effects can lead to outcomes not predicted by the deterministic model alone, with outcomes highly dependent on the degree of worm clumping, k . Specifically, we show that if the reproduction number and clumping are sufficiently bounded, then stochasticity will cause the parasite to die out. It follows that control of soil-transmitted helminths will be more difficult if the worm distribution tends towards clumping.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Robert J. Hardwick.