The DeWorm3 transmission model attempts to answer the question. The study tests the hypothesis that frequent administration of high-coverage mass medication can disrupt the transmission of ground-borne helminths for a relatively short period of time. A new study aims to predict the results at the endpoint of the study.
Collage of different helminth eggs. From left to right: Trichosomoides egg, Ascaris lumbricoides with larvae hatch, specimen of adult roundworms, Hymenolepis nana, Schistosoma mansoni and Toxocara canis with larvae hatch
SusanA Secretariat, Catalina Maya Rendón, CC BY 2.0, via Wikimedia Commons
This blog post is part of a series of new articles published in the LCNTDR Collection: Advances in Scientific Research on NTD Control, directed by the London Center for Neglected Tropical Disease Research (LCNTDR). Stay tuned for updates on Twitter @bugbittentweets and @NTDResearch. You can find more articles in the series here.
Soil-borne helminths (STHs) are a group of parasitic worms that infect humans and cause a wide range of diseases and morbidities in their hosts, particularly anemia, stunted growth, and retarded cognitive development in children. It is currently estimated that around 1.5 billion people worldwide are infected with sexually transmitted diseases.
Anthelmintic (deworming) drugs like albendazole are effective at reducing worm pollution in individuals, but large-scale programs have generally failed to eradicate STH infestation at the population level (read this previous bugplease blog for more on that global efforts to experience STHs to reduce). Indeed, the World Health Organization aims to control morbidity (to keep the prevalence and intensity of infection low) in children and women of childbearing age when attempting to interrupt and eliminate transmission.
However, the DeWorm3 study (DW3) aims to test the hypothesis that frequent (twice-yearly) mass drug administration (MDA) with high coverage (> 90%) can disrupt transmission of the parasite over a relatively short period of three years . If successful, this strategy would provide a clear endpoint for the current cycle of drug delivery for large-scale morbidity control. DW3 is a cluster-based randomized study that compares an intensive 6-month MDA with a country-specific standard of care and is carried out at locations in India, Benin and Malawi. The main aim of the study is to reduce the GH prevalence due to MDA as an indicator of elimination to below 2%.
The purpose of our study was to use the data collected at the start of the study to predict the results at the endpoint of the DW3 study and to predict the longer term effects of the study. Base data were used to derive parameter values (using a Bayesian approach) for a parasite 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 between different communities and between countries. The adjusted parameters were then used in a simulation of the trial, including the MDA rounds and the standard of nursing interventions in both control and intervention arms, and the diagnostic sample of the trail population at the endpoint.
The results of the adaptation process and the simulations underline the importance of the variability at the cluster level in the transmission of parasites to the results of the experiment. Parameter adjustments to baseline data indicate a wide range of transmission intensities and levels of parasite aggregation in the population between clusters, as shown in this graph.
Overall, it is predicted that the main goal of the DW3 study will be achieved. that is, reducing the prevalence in the study intervention arms to less than 2%. However, the variability in transmission intensity and parasite aggregation between clusters leads to a number of inter-cluster responses to the 6 rounds of MDA. The graphic below shows that while some clusters are likely to be parasite-free, others are less affected. Clearly, the level of impact is not directly related to the baseline prevalence of parasites in a cluster.
Upon completion of the experiment, the simulation predicts that clusters in which transmission has not been interrupted will experience a “rebound” of their parasite prevalence. Therefore, the application of high coverage and high uniformity MDA can result in the creation of localized “hot spots” of parasite transmission between parasite-free areas within a treated region.
It must also be recognized that the parasite transmission model underlying the simulation contains assumptions that have yet to be tested as there is no suitable data from the field. An important assumption is the detail of who infects whom during transmission events, which is determined by behavioral patterns and social structure (e.g. household structure).
When fully available, DW3 data will provide modelers with valuable information about the nature of parasite transmission, especially when the prevalence is low, which will greatly improve the ability of models to predict the effects of MDA in the future.
The study presented in this blog post was published in the LCNTDR Collection: Advances in Scientific Research on NTD Control, directed by the London Center for Neglected Tropical Disease Research (LCNTDR). The collection was Publication in Parasites & Vectors since 2016 and regular publication of new articles. This series highlights the recent advances in scientific research for NTDs carried out by LCNTDR member institutions and their staff. The aim is to highlight the broad spectrum of work done by the LCNTDR to achieve the United Nations Sustainable Development Goals and to support the goals of the World Health Organization’s Roadmap for Neglected Tropical Diseases 2021-2030.
The LCNTDR was launched in 2013 with the aim of providing targeted support for NTDs in operation and research. LCNTDR, a joint initiative of the Natural History Museum, the London School of Hygiene & Tropical Medicine, the Royal Veterinary College, the Child Development Partnership, the SCI Foundation (formerly known as the Schistosomiasis Control Initiative) and Imperial College London, is interdisciplinary research on the Build the evidence base for the design, implementation, monitoring and evaluation of NTD programs.
More blog posts in the series can be found here.