A Darwinian outlook on schistosomiasis elimination

Abstract

Schistosomiasis is a poverty-related chronic disease that affects over 240 million people across 78 countries worldwide. In order to control the disease, the World Health Organization (WHO) recommends the drug praziquantel against all forms of schistosomiasis. Mass Drug Administration (MDA) programs with praziquantel are successful on the short-term as they reduce the prevalence and infection intensity after treatment, and thus instantly relieve the patient from the burden of its disease. However, epidemiological and genetic studies suggest that current school-based interventions may have little or no long-term impact on parasite transmission. Here, we adopt a Darwinian approach to understand the impact of MDA on the neutral evolution of Schistosoma parasites and assess its potential to eliminate schistosomiasis. We develop a finite island model to simulate the impact of repeated treatments on the genetic diversity of schistosome populations locally (within each host, i.e. infrapopulation) and regionally (within all hosts combined, i.e. component population). We show that repeated treatments induced strong and lasting declines in parasite infrapopulation sizes, resulting in concomitant genetic bottlenecks within the treated individuals. However, parasite genetic diversity recovered quickly in a few generations due to re-infection, and there was little or no impact of treatment on the genetic diversity of the component population when treatment coverage was 95% or lower. This was mainly due to parasite infrapopulations of the untreated host individuals that acted as reservoirs of genetic diversity, sustaining the diversity of the component population. Hence, lasting declines in parasite genetic diversity were only observed when coverage of treatment was 100%, resulting in population crashes after a minimum of six treatment rounds. We argue that achieving a full coverage of treatment is highly challenging for most endemic regions in sub-Saharan Africa, and conclude that MDA alone has little potential to achieve elimination within a conceivable time frame. Our results raise skepticism about the current WHO goals of elimination of schistosomiasis by 2025.

Population genetics of African Schistosoma species

“…Also, Lelo et al (2014) concluded that MDA programs targetingschool-aged children only may have limited impact on parasite transmission at the community level. This was also the main finding of a simulation study that used an island model to investigate the impact of MDA on long-term parasite population dynamics (Van den Broeck et al, 2020). The study revealed that repeated treatments induced strong and lasting declines in parasite infrapopulation sizes, resulting in concomitant genetic bottlenecks.…”

“…Studies focusing on the genetic structure of Schistosoma populations and their response to MDA suggest that rapid re-infection of parasites from genetically differentiated source populations occurs and that MDA alone is not sufficient to control the disease transmission (Van den Broeck et al, 2020). High levels of gene flow between parasite populations before and after treatment together with refugia may facilitate a rapid recovery of population genetic diversity with treatment having only a limited impact on parasite transmission at the community level.…”

“…The study revealed that repeated treatments induced strong and lasting declines in parasite infrapopulation sizes, resulting in concomitant genetic bottlenecks. However, parasite genetic diversity recovered quickly in a few generations due to re-infection, and there was little or no impact of treatment on the genetic diversity of the component population when treatment coverage was 95% or lower (Van den Broeck et al, 2020). The authors concluded that community-wide distribution of praziquantel is essential to induce long-term effects on parasite population dynamics (Van den Broeck et al, 2020).…”

Prospects for genomic surveillance for selection in schistosome parasites

“…For example, in a small population we expect many loci to have maximal F ST value ( Figure 2B ), even in the absence of selection. Simulations can also be beneficial to understand how rapidly adaptation may have occurred in response to control measures ( 55 ) and to predict the conditions under which drug resistance may be expected to lead to parasite elimination or to lead to the evolution of drug resistance ( 56 ).…”