New RVC-Sanger research examines the impact of mass drug administration on the genome of a major parasitic disease

A new study, produced in partnership between the Royal Veterinary College (RVC), the Wellcome Sanger Institute, Imperial College and the Vector Borne and Neglected Tropical Disease Control Division of the Ministry of Health, Uganda, has been published in Nature Communications. This research paves the way for a more effective genomic surveillance of schistosomiasis, a major human parasite. The study represents the largest fine-scale genomic investigation into the impact of repeated, long-term mass drug administration (MDA) of children and at-risk adults on populations of schistosome parasites.

Schistosomiasis is one of the most prevalent neglected tropical diseases (NTDs), infecting more than 240 million people across 78 countries, primarily in sub-Saharan Africa. In 2001, the World Health Organization (WHO) endorsed preventive chemotherapy, in the form of mass drug administration (MDA) of praziquantel, as the primary strategy for schistosomiasis control. This is the only available drug for this disease in humans and animals worldwide. Praziquantel MDA aims to provide periodic treatment of large populations at risk of disease, focusing primarily on school-aged children, a group shown to have the highest infection prevalence, intensity and future morbidity risks. 

MDA in sub-Saharan Africa began in 2003, starting in Uganda.  In 2019 alone, MDA programmes delivered praziquantel to 105.4 million people. These programmes have generally been effective at reducing the prevalence and intensities of infections in targeted regions. Following these early successes, in 2012, the WHO set goals of controlling schistosomiasis morbidity. Most recently, the revised WHO 2021–2030 NTD roadmap was launched, with its ambitious goal of achieving elimination as a public health problem in all 78 endemic countries, and the interruption of transmission in selected regions by 2030. However, despite the many successes to date, numerous persistent schistosomiasis hotspots remain, presenting substantial challenges towards reaching these 2030 targets. Accurately measuring changes in parasite populations will be a key part of understanding the current and future impact of MDA.
In this study, selected as a Nature Editors’ Highlights Featured article, the genomic impact of repeated MDA on Schistosoma mansoni populations from infected children with contrasting treatment histories and documented reduced drug efficacy within Uganda was assessed. Parasites were found to be highly diverse, with shared gene flow, and did not reduce in this diversity after a single round of drug treatment. The authors did, however, find evidence of positive selection acting on members of gene families previously implicated in praziquantel drug action. As efforts to eliminate schistosomiasis intensify, this study will thereby provide a valuable foundation for genomic surveillance of this major human parasite.
Duncan Berger, joint first author and final year PhD student at the Wellcome Sanger Institute and the RVC (supervised by Professor Joanne P Webster, Dr James Cotton and Dr Matt Berriman), said:
“Our study found that even after nearly a decade of mass-drug administration (MDA) parasite populations remained diverse and unstructured suggesting that these MDA programmes are struggling to produce large-scale impacts on schistosome populations. Concerningly, we also found early indications of gradual adaptation to MDA which merits further investigation. 
“This demonstrates that genome sequencing of these parasites can now be conducted on a large enough scale that genomic data can and should be used to inform schistosomiasis control programmes. I hope this study represents a first step in establishing genomic surveillance to characterise and monitor these parasites in full. 

“It has been fantastic to be able to combine the epidemiological expertise and field experience of my supervisor and her team at the Royal Veterinary College with that of my supervisory team at the genome sequencing capacity of the Wellcome Sanger Institute. It also really highlights how beneficial multidisciplinary approaches can be to the study of these devastating neglected tropical diseases.”

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