Maladies tropicales négligées

Les maladies tropicales négligées (souvent désignées sous l'acronyme anglo-saxon NTDs) sont un groupe de diverses maladies tropicales fréquentes au sein des populations à faible revenu dans les régions en développement d'Afrique, d'Asie et d'Amérique. Elles sont causées par divers pathogènes au premier rang desquels les parasites helminthes ou protozoaires, mais également les virus et les bactéries. En Afrique subsaharienne, l'impact de l'ensemble de ces pathologies est comparable au paludisme et à la tuberculose. Certaines de ces pathologies peuvent être prévenues ou traitées par des moyens accessibles aux pays les plus développés, mais non dans les régions les plus pauvres du globe. Dans certains cas pourtant, les traitements sont relativement peu onéreux. Par exemple, le traitement de la bilharziose est de par enfant et par an en 2007. Cependant, pour la période 2010-2017, le coût du contrôle de ces pathologies à l'échelle mondiale est estimé entre 2 et 3 milliards $US. Ces malad

A field-based modelling framework of the ecohydrology of schistosomiasis

Francisco Javier Perez Saez

Successful control of schistosomiasis, a water-borne parasitic disease, is challenged by the intricacy of the wormâs lifecycle, which depends on aquatic snail intermediate hosts, and involves environmental, ecologic, and socio-economic factors. Current strategies rely on deworming through mass drug administration which however do not protect against reinfection and the persistence of hotspots. It is recognized that multifaceted approaches will be necessary to reach elimination, whose development will require a renewed focus on the diseaseâs social-ecological drivers. Taking cue from the hydrological underpinning of these drivers, this Thesis aims at developing an ecohydrological approach to schistosomiasis with a view to identifying and exploiting the points in which its cycle can be broken. Schistosomiasis is a poverty-reinforcing disease affecting more than 150 million people in sub-Saharan Africa, being the parasitic disease causing the largest health burden after malaria. However, the impairing morbidity it causes has been undervalued in the past, qualifying it as a neglected tropical disease. Moreover, water resources development often exacerbate transmission, posing scientific and ethical challenges in addressing the ensuing trade-off between economic development and public health. The relevance of this Thesisâ work lies in furthering tools to offset this trade-off by unlocking the predictive appraisal of the social-ecological drivers of transmission. An integration of fieldwork applied in Burkina Faso (West Africa) and theoretical methods are employed to address this aim. This Thesis establishes the use of spatially explicit mathematical models of schistosomiasis at the national-scale, allowing to study the effect of human mobility and spatial heterogeneity of transmission parameters. Weekly ecological samplings of snail abundance and continuous environmental monitoring were preformed at three sites along the countryâs climatic gradient, leveraged through ecological modelling. A novel methodology for the large-scale prediction of river network ephemerality allowed for refined snail species distribution models, and the analysis of the diseaseâs geography in link with socio-economic covariates. Finally, surveys and participatory workshops shed light on local-scale water contact patterns. The obtained results substantiate the stance that hydrology is a first-order control of disease transmission. Stability analysis of the spatially explicit model generated additional insight into the impact of the expansion of suitable snail habitat due to water resources development, highlighting the interplay between local and country-wide effects driven by human mobility. Models of snail ecology revealed key hydrological drivers, and disputed density feedbacks. Uncovered phase shifts between permanent and ephemeral habitats were adequately reproduced at the national scale through model regionalization. Characterization and predictions of hydrological ephemerality improved the estimation of the snailsâ ecological range, mirroring the diseaseâs geography. Finally a national-scale association between ephemerality and disease risk was observed, possibly due to human-water contacts aggregation, as supported by preliminary results at village-level. The future incorporation of these ecohydrological findings into spatially explicit models of schistosomiasis is considered promising for optimizing control strategies and attaining disease elimination.

EPFL2018

Novel High-Throughput Fluorescence-Based Assay for the Identification of Nematocidal Compounds That Target the Blood-Feeding Pathway

Tiffany Babette Angélique Bouchery, Marc Chambon, Nicola Harris, Anthony Marchand, Mati André Marie Moyat, Gerardo Turcatti

Hookworm infections cause a neglected tropical disease (NTD) affecting ~740 million people worldwide, principally those living in disadvantaged communities. Infections can cause high morbidity due to their impact on nutrient uptake and their need to feed on host blood, resulting in a loss of iron and protein, which can lead to severe anaemia and impaired cognitive development in children. Currently, only one drug, albendazole is efficient to treat hookworm infection and the scientific community fears the rise of resistant strains. As part of on-going efforts to control hookworm infections and its associated morbidities, new drugs are urgently needed. We focused on targeting the blood-feeding pathway, which is essential to the parasite survival and reproduction, using the laboratory hookworm model Nippostrongylus brasiliensis (a nematode of rodents with a similar life cycle to hookworms). We established an in vitro-drug screening assay based on a fluorescent-based measurement of parasite viability during blood-feeding to identify novel therapeutic targets. A first screen of a library of 2654 natural compounds identified four that caused decreased worm viability in a blood-feeding-dependent manner. This new screening assay has significant potential to accelerate the discovery of new drugs against hookworms.

2022

A field-based modelling framework of the ecohydrology of schistosomiasis

Francisco Javier Perez Saez

EPFL2018