Study detects early warning signs of schistosomiasis drug resistance

Scientists have identified genetic changes in wild populations of the parasitic worm that causes schistosomiasis which may reduce its response to praziquantel, the only available treatment. The study provides an early warning for disease control and elimination programs.

Researchers from the Wellcome Sanger Institute, the Royal Veterinary College (RVC) and Medical College of Wisconsin (MCW) led a large-scale international collaboration analysing hundreds of Schistosoma mansoni genomes collected from people in several African and Caribbean countries. The study is the largest genomic analysis of the parasite from human infections to date.

Published today (17 July) in Science Advances, the findings highlight the need for ongoing genomic surveillance to help protect the long-term effectiveness of praziquantel.

Schistosomiasis is one of the world's most widespread neglected tropical diseases, affecting more than 250 million people across 79 countries, and is particularly common among children and vulnerable communities. People become infected when the larval stage of tiny parasitic worms, known as schistosomes or blood flukes, penetrate the skin during contact with infested water.

Praziquantel is the only currently available treatment for schistosomiasis. It is a tablet that works by causing severe spasms and paralysis of the worms' muscles. Large-scale mass drug administration programs for schistosomiasis began in Uganda in 2003 and have since expanded across sub-Saharan Africa and beyond. However, as its use has expanded over the past two decades, concerns have grown about the potential of emerging resistance to praziquantel.

In a new study, researchers analysed whole-genome sequencing data from 570 Schistosoma mansoni parasites, the major causative agent of human intestinal schistosomiasis, and the closely related rodent-borne species Schistosoma rodhaini. Samples were collected from across Africa and the Caribbean, including Senegal, Cameroon, Kenya, Uganda, Tanzania, Puerto Rico and Guadeloupe. The team combined this newly generated genomic data with publicly available datasets to investigate how the genetic makeup of parasite populations is changing under long-term treatment.

The researchers found clear genetic differences between parasite populations in different countries, alongside evidence that parasites can spread over large geographic distances. They also identified four naturally occurring genetic changes in the gene Sm.TRPM_PZQ that were associated with reduced sensitivity to praziquantel in laboratory testing.

The team also analysed parasites collected from infected individuals before and after treatment with praziquantel. In some cases, parasites persisted following treatment, providing further evidence that reduced drug effectiveness may already exist at low levels in endemic populations.

These findings are significant because genetic changes linked to drug resistance may allow resistance to emerge and spread over time, allowing infections to persist. The findings also provide an important baseline for monitoring parasite populations as countries intensify efforts to eliminate schistosomiasis.

The genomes of parasites offer fascinating insights into their past and can reveal hints about their future. Whole-genome sequencing gives us an unprecedented window into how schistosome populations are structured and evolving across Africa, and by characterising variation in the drug's molecular target at scale, we can move from reactive surveillance to proactive monitoring. Understanding this genetic variation has significant potential to support control efforts, identifying the warning signs of resistance before it takes hold and threatens the progress made through decades of treatment programmes that affect hundreds of millions of people worldwide."

Dr Stephen Doyle, co-senior author, Wellcome Sanger Institute

Professor Joanne Webster, co-senior author at the RVC and Director of the Global Centre for Neglected Tropical Disease Research (GCNTDR), said: "Since mass drug administration programmes began across sub-Saharan Africa in 2003, praziquantel has been used to treat millions of people and has become the foundation of schistosomiasis control efforts. This widespread use places increasing evolutionary pressure on parasite populations. While praziquantel remains largely highly effective, our findings provide a sobering warning about the reliance on a single drug for schistosomiasis control and highlight the need for comprehensive surveillance to monitor the potential emergence of drug resistance."