The DeWorm3 drivetrain model seeks to answer the question. The trial tests the hypothesis that frequent and massive administration of drugs with high coverage can interrupt the transmission of soil-borne helminths over a relatively short period of time. A new study aims to predict the outcome at the end point of the trial.
Collage of various helminth eggs. From left to right: egg of Trichosomoides, Ascaris lumbricoides with hatching larvae, sample of adult roundworms, Hymenolepis nana, Schistosoma mansoni and Toxocara canis with hatching of larvae
SusanA Secretariat, Catalina Maya Rendón, CC BY 2.0, via Wikimedia Commons
This blog post is one in a series of new articles published in the LCNTDR Collection: Advances in Scientific Research for the Control of NTDs, led by the London Center for Neglected Tropical Diseases (LCNTDR). Stay tuned for updates on Twitter @bugbittentweets and @NTDResearch. You can find other articles in the series here.
Soil-transmitted helminths (STH) are a group of parasitic worms that infect humans, causing a wide range of disease and morbidity in their hosts, including anemia, stunted growth, and delayed cognitive development in children. About 1.5 billion people are currently considered infected with HRTs around the world.
Anthelmintic (deworming) drugs such as albendazole are effective in reducing the burden of worms in individuals, but large-scale programs have generally failed to eliminate HRT infestation at the population level (see this previous Bugbitten blog for more on global efforts to reduce STDs). Indeed, the Objectives of the World Health Organization morbidity control (keeping the prevalence and intensity of infections low) in children and women of childbearing age compared to attempts to break the transmission and eliminate.
The DeWorm3 (DW3) trial, however, aims to test the hypothesis that frequent mass drug administration (MDA) (twice a year) with high coverage (> 90%) can interrupt parasite transmission over a relatively short period of three years. . If successful, this strategy would provide a clear endpoint to the current cycle of large-scale drug delivery for morbidity control. DW3 is a cluster-based randomized trial which compares intense six-monthly MDA to country-specific standards of care, and takes place at sites in India, Benin and Malawi. The main objective of the trial is to reduce the prevalence of HRT to less than 2% using MAID as an indicator of elimination.
The goal of our study was to use the data collected at the start of the study to predict the end point results of the DW3 test and also to predict the longer term impact of the test. The basic data was used to infer the values of the parameters (using a Bayesian approach) for a parasitic transmission model, independently for each cluster in each country of the study.
The adjusted parameters represent the intensity and variability of contact between individuals, processes that are most likely to vary from community to community and country to country. The adjusted parameters were then used in a simulation of the trial, including MA series and standard care interventions in the control and intervention arms and diagnostic sampling of the end-point follow-up population. .
The results of the adjustment process and the simulations highlight the importance of cluster-level variability in parasite transmission on the test results. Fitting the parameters to the baseline data indicates a wide range of transmission intensities and degrees of parasite aggregation in the population among clusters, as shown in this graph.
Overall, the primary objective of the DW3 trial should be achieved; that is, the reduction in the prevalence in the intervention arms of the study to less than 2%. However, the variability in the intensity of parasite transmission and aggregation across clusters leads to a range of responses among clusters to 6 cycles of MDA. The graph below shows that while some clusters should be free of pests, others are much less affected. The degree of impact is clearly not directly related to the baseline parasite prevalence in a cluster.
Once the trial is complete, the simulation predicts that clusters where transmission has not been interrupted will experience a “rebound” in their parasite prevalence. Therefore, the application of a high coverage and very uniform MDA may result in the generation of localized “hot spots” of pest transmission among pest free areas of a treated region.
It should also be recognized that the parasitic transmission model underlying the simulation contains hypotheses which still need to be tested, given the lack of appropriate field data. An important assumption is the detail of who infects whom during transmission events, which will be determined by behavioral patterns and social structure (eg, household structure).
When the DW3 data is fully available, it will provide modelers with valuable information on the nature of parasite transmission, especially at low prevalence, which will greatly enhance the ability of models to predict the effects of MDA in the future.
The study featured in this blog post was published in the LCNTDR Collection: Advances in scientific research for the fight against NTDs, led by the London Center for Neglected Tropical Diseases (LCNTDR). The collection was publish in Parasites and vectors since 2016, and periodically publishing new articles. This series presents recent advances in scientific research on NTDs carried out by LCNTDR member institutions and their collaborators. It aims to highlight the wide range of work undertaken by the LCNTDR to achieve the United Nations Sustainable Development Goals and support the goals of the World Health Organization Roadmap for Neglected Tropical Diseases 2021-2030. .
The LCNTDR was launched in 2013 with the aim of providing targeted operational and research support to NTDs. LCNTDR, a joint initiative of the Natural History Museum, the London School of Hygiene and Tropical Medicine, the Royal Veterinary College, the Partnership for Child Development, the SCI Foundation (formerly known as the Schistosomiasis Control Initiative) and Imperial College London, undertakes interdisciplinary research to build the evidence base around the design, implementation, monitoring and evaluation of NTD control programs.
You can find other blog posts in the series here.