Predicting the risk and speed of drug resistance emerging in soil-transmitted helminths during preventive chemotherapy

Abstract

BACKGROUND: Control of soil-transmitted helminths (STH) relies heavily on regular large-scale deworming of high-risk groups (e.g., children) with benzimidazole derivatives. Although drug resistance has not yet been documented in human STH, regular deworming of cattle and sheep has led to widespread benzimidazole resistance in veterinary helminths. METHODS: Using a newly developed individual-based model, we predict the population dynamics of human STH infections and drug resistance during regular preventive chemotherapy (PC). We do this for a 20-year time period, considering different PC strategies and genetic mechanisms behind resistance. RESULTS: More intense PC strategies increase the prospects of STH elimination, but also increase selective pressure and thus the speed at which drug efficacy declines, especially when implementing community-based PC (population-wide deworming) instead of school-based PC (children only). The risk of resistance is highest when resistance is monogenic, especially with co-dominant or dominant inheritance. DISCUSSION: Even with the current PC strategy of mainly targeting children in schools, drug resistance may evolve within a decade. More intensive PC strategies would even further increase the risk and speed of resistance emerging. As such, our findings are timely and highlight the need to develop and implement strategies to monitor and mitigate the evolution of benzimidazole resistance.

Eco-evolutionary dynamics of anthelmintic resistance in soil-transmitted helminths

“…Conversely, empirical work to determine the genetic basis and associated costs of resistance can inform better models. Indeed, recent work uses simulations of a newly developed individual-based model shows that the rate of the resistance evolution depends on the whether the trait is monogenic or polygenic [49]. The genetic basis of these traits may be more complex than we typically assume in our models.…”

Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta

“…Anthelmintic resistance is a global problem and places a significant economic and animal health burden on livestock industries and the care of domestic animals (1,2). Furthermore, resistance threatens the large-scale control programmes that almost exclusively rely on anthelmintic drugs to manage human-infective helminths as a public health problem (3,4). Understanding how resistance emerges is critical to the sustainable control of helminth infections.…”