Forecasting the effectiveness of the DeWorm3 trial in interrupting the transmission of soil-transmitted helminths in three study sites in Benin, India and Malawi

James E. Truscott*, Robert J. Hardwick, Marleen Werkman, Puthupalayam Kaliappan Saravanakumar, Malathi Manuel, Sitara S.R. Ajjampur, Kristjana Hrönn Ásbjörnsdóttir, Kalua Khumbo, Stefan Witek-McManus, James Simwanza, Gilles Cottrell, Parfait Houngbégnon, Moudachirou Ibikounlé, Judd L. Walson, Roy M. Anderson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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 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%.

METHODS: Our 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 [Formula: see text] 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 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 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 assess 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.

Original languageEnglish
Article number67
Pages (from-to)67
JournalParasites and Vectors
Volume14
Issue number1
DOIs
Publication statusPublished - 20 Jan 2021

Bibliographical note

Funding Information:
The DeWorm3 study is funded through a grant to the Natural History Museum, London, from the Bill and Melinda Gates Foundation (OPP1129535). This award is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union.

Publisher Copyright:
© 2021, The Author(s).

Other keywords

  • Heterogeneity
  • Individual-based simulator
  • Soil-transmitted helminths
  • Transmission interruption
  • Helminths/classification
  • Models, Theoretical
  • India/epidemiology
  • Prevalence
  • Mass Drug Administration/methods
  • Humans
  • Benin/epidemiology
  • Models, Statistical
  • Forecasting
  • Malawi/epidemiology
  • Randomized Controlled Trials as Topic
  • Animals
  • Computer Simulation
  • Female
  • Anthelmintics/therapeutic use
  • Helminthiasis/epidemiology
  • Soil/parasitology

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