Periodic Reporting for period 1 - SchiSTOP (Beyond mass drug administration: understanding Schistosomiasis dynamics to STOP transmission)
Reporting period: 2021-05-03 to 2023-05-02
Neglected tropical diseases (NTDs) are a diverse group of infections which are especially prevalent in low-income populations in tropical and subtropical areas in Africa, Asia and the Americas. Schistosomiasis is the deadliest NTD killing an estimated 280,000 people each year in the African region alone. The World Health Organization (WHO) 2030 target for schistosomiasis is its elimination as a public health problem (EPHP) in all endemic countries and the interruption of transmission in 32% of the endemic countries. Mass drug administration (MDA) with the anthelmintic drug praziquantel is the primary measure for the control of schistosomiasis. However, in areas of moderate and high prevalence the goal seems unlikely to be met as even with intensive biannual MDA, prevalence of infection has been seen to rebound rapidly after each round. The reasons are still poorly understood. The SchiSTOP project aims to advance our current understanding of schistosomiasis transmission dynamics investigating the mechanisms that cause the rapid rebound of prevalence after MDA and proposing optimal implementation of current and novel strategies to achieve schistosomiasis control and move towards elimination. In addition, this project builds a reference methodological framework to comprehensively study other MDA-targeted infectious diseases. The proposed project addresses one of the priorities of the EU, through global poverty reduction (SDG goal 1) by promoting ways of improving future health (SDG goal 3).
Mathematical models and statistical methods have proven to be essential to gain insights into the complex processes underlying the transmission dynamics of infectious diseases. The overarching goal of the SchiSTOP project is to advance our understanding of schistosomiasis transmission dynamics by developing a stochastic agent-based model (ABM) to simulate schistosomiasis transmission integrating cutting-edge mathematical models and statistical methods with recent advances in parasite genetics, epidemiology, diagnostics and immunology.
Mathematical models and statistical methods have proven to be essential to gain insights into the complex processes underlying the transmission dynamics of infectious diseases. The overarching goal of the SchiSTOP project is to advance our understanding of schistosomiasis transmission dynamics by developing a stochastic agent-based model (ABM) to simulate schistosomiasis transmission integrating cutting-edge mathematical models and statistical methods with recent advances in parasite genetics, epidemiology, diagnostics and immunology.
The research has been conducted at the Radboud University Medical Center in Nijmegen (Dr. Federica Giardina) in the Biostatistics group, department of Health Evidence, in collaboration with Dr. Poppy Lamberton at the University of Glasgow in the School of Biodiversity, One Health and Veterinary Medicine. The SchiSTOP project revolves around the development of an agent-based model (ABM) for the transmission dynamics of schistosomiasis. The ABM consistes of four main building blocks: the human population, the parasites living in the human host, the parasites living in the contaminated water environment, and the snail population. Briefly, the model includes: i) human demography (births, deaths, aging, and migration), ii) infection dynamics in human and intermediate hosts, including diagnostic schemes to assess infection in humans, iii) maturation, reproduction, and death of worms within the human host, iv) control interventions, such as MDA. Mechanisms regulating transmission have been considered at three different levels: worm (density dependent fecundity), human host (host-acquired immunity) and intermediate host (snail carrying capacity). Importantly, water contact data have been used to derive a new age-exposure function. We extracted frequency of water contacts adjusted for body surface and time of day of contact reported for three age groups (0-9, 10-19, 20+ years old) from an extensive data collection on direct water contact observations in a village in Northern Senegal. To better estimate exposure in the third and highest age-group, various age-exposure profiles from Kenya were used to inform the age at which we expected to show a decline in exposure. We calibrated the models to different settings and performed simulation studies to investigate the role played by the different regulating mechanisms and the extent to which they can explain different observed epidemiological patterns. After identifying the best model structures, we used the models to estimate the probability of reaching the WHO targets under different control strategies.
We find that regulating mechanisms alternative to the commonly assumed density dependence in worm fecundity can reproduce stable pre-control settings, including low endemicity settings. The dynamics in the snail population plays an important role in explaining sustained low transmission. All modelling scenarios agreed that treating school aged children (SAC) only with 10 years of annual MDA will not allow to reach the elimination of schistosomiasis as a public health problem (EPHP) in high or moderate endemicity settings, nor interruption of transmission in the low endemicity settings. Expanding MDA to all individuals older than 2 years of age, makes predictions much more optimistic.
The work performed by Federica Giardina (PI) and Veronica Malizia (PhD student) resulted in published papers, and more manuscripts submitted or in preparation. The results have been presented at national and international conferences, and during two invited talks. Also, a workshop on infectious disease models and a schistosomiasis expert meeting was organized on the topic of the action. SchiSTOP has also had the opportunity to be showcased in the Horizon magazine.
We find that regulating mechanisms alternative to the commonly assumed density dependence in worm fecundity can reproduce stable pre-control settings, including low endemicity settings. The dynamics in the snail population plays an important role in explaining sustained low transmission. All modelling scenarios agreed that treating school aged children (SAC) only with 10 years of annual MDA will not allow to reach the elimination of schistosomiasis as a public health problem (EPHP) in high or moderate endemicity settings, nor interruption of transmission in the low endemicity settings. Expanding MDA to all individuals older than 2 years of age, makes predictions much more optimistic.
The work performed by Federica Giardina (PI) and Veronica Malizia (PhD student) resulted in published papers, and more manuscripts submitted or in preparation. The results have been presented at national and international conferences, and during two invited talks. Also, a workshop on infectious disease models and a schistosomiasis expert meeting was organized on the topic of the action. SchiSTOP has also had the opportunity to be showcased in the Horizon magazine.
The SchiSTOP project has contributed to advancing our understanding of schistosomiasis dynamics and control, therefore addressing one of the priorities of the EU, by promoting ways of improving future health (SDG goal 3) and ultimately moving towards global poverty reduction (SDG goal 1). The work carried out during this action contributes towards European policy objectives to improve public health through tackling diseases, cross-border health threats, disease prevention and promotion of good health.
Different stakeholders, from academia to public and private institutions, have been involved. Results have been discussed with the academic community, the WHO, and several NGOs. The SchiSTOP project has produced high-quality scientific publications and open-source code, and has made both widely available to the scientific and wider community. In particular, the model developed in the project has formed the basis of a a web application (Shiny-app) that can be used to run simulations and explore the impact of different interventions and diagnostic tools. The web application can be used to explore the best combination of interventions guiding policy decisions and it also represents an innovative tool in supporting the design of field trials. The developed web-tool has been presented to different stakeholders and will be made operational to support the development of new projects. We will continue to collaborate with other research consortia and epidemiological experts in the production of informative and accessible content. Moreover, owing to the close collaboration established with schistosomiasis experts and researchers in several countries in Sub-Saharan Africa, we will continue to disseminate our results advising national and international policymakers and public health agencies.
Different stakeholders, from academia to public and private institutions, have been involved. Results have been discussed with the academic community, the WHO, and several NGOs. The SchiSTOP project has produced high-quality scientific publications and open-source code, and has made both widely available to the scientific and wider community. In particular, the model developed in the project has formed the basis of a a web application (Shiny-app) that can be used to run simulations and explore the impact of different interventions and diagnostic tools. The web application can be used to explore the best combination of interventions guiding policy decisions and it also represents an innovative tool in supporting the design of field trials. The developed web-tool has been presented to different stakeholders and will be made operational to support the development of new projects. We will continue to collaborate with other research consortia and epidemiological experts in the production of informative and accessible content. Moreover, owing to the close collaboration established with schistosomiasis experts and researchers in several countries in Sub-Saharan Africa, we will continue to disseminate our results advising national and international policymakers and public health agencies.