Anthelmintic resistance in Southeast Asia (AHR-SEA): implications for control and elimination of intestinal helminths

Soil-transmitted helminth or intestinal worm infections, are a major health burden worldwide, particularly in rural and poor urban areas of low- and middle-income countries, including in Southeast Asia. They infect over 1 billion people worldwide, causing considerable disease including anaemia and stunting and wasting in children. They can also significantly exacerbate poverty, particularly in marginalised communities. In the Philippines nearly 30% of school-aged children are infected with intestinal worms, whereas in Malaysia and Thailand infections are particularly common in indigenous communities, refugees and migrants. The diseases caused by intestinal worms are classified as Neglected Tropical Diseases by the World Health Organization (WHO). In its Roadmap for Neglected Tropical Diseases, WHO targets intestinal worm diseases for elimination as a public health problem by 2030. The main approach for intestinal worm control is regular distribution of deworming drugs to individuals living in endemic areas. However, there are concerns that resistance will arise to deworming drugs in human intestinal worms, as is common in similar worm infections in animals, thus jeopardising control programmes. Therefore, there is an urgent need to understand how effective deworming drugs are in treating intestinal worms, what the impacts would be on WHO elimination targets if resistance does emerge and to explore alternative control approaches.

Our project brings together an interdisciplinary team of expert researchers from Malaysia, the Philippines, Thailand and the United Kingdom and aims to address current knowledge gaps in relation to performance of deworming drugs in treatment of Intestinal worms and to identify alternative control strategies for Intestinal worms which are acceptable to communities. We will do this by undertaking field studies to assess performance of deworming drugs in treatment of intestinal worms in areas of the three countries where high levels of intestinal worms persist despite deworming treatment. We will use cutting-edge genomics approaches to determine whether there are genetic variations associated with resistance to deworming treatment in the intestinal worms circulating in the study sites. We will also investigate interactions between intestinal worms, deworming treatment and people’s gut microbial community (microbiome) to propose alternative intestinal worm treatment options and to explore whether gut microbes might influence treatment responses. Furthermore, we will employ machine learning methods to predict emergence of resistance to deworming drugs and use mathematical modelling and health economics approaches, informed by preference, symptoms and health-related quality-of-life data collected during the field studies, to determine what impact emergence of resistance will have on intestinal worm control and identify alternative control approaches which are acceptable to communities. Finally, we will design a strategy to monitor for emergence of deworming resistance. Integrated into the project will be a programme of knowledge exchange and research capacity building activities including training courses, researcher exchanges and field-based training.

By embracing a collaborative interdisciplinary approach, this project will shed new light on the issue of intestinal worm resistance to deworming drugs and the effect that emergence of resistance will have on intestinal worm control and elimination. Ultimately, the project will deliver evidence-based strategies to monitor for resistance emergence and minimise the impact of resistance emergence on achieving the WHO 2030 targets—crucial information for public health policy makers.

The project has three main objectives:

1. Assess the efficacy of current deworming drugs
   • Evaluate how effective deworming drugs are against intestinal worm infections in Malaysia, the Philippines and Thailand.
   • Use advanced genetic (genotyping) methods to detect potential markers of drug resistance in intestinal worm populations.
2. Understand interactions between intestinal worms, deworming treatment and the gut microbiome
   • Investigate how intestinal worm infections and deworming treatment affect the gut microbiome.
   • Use metagenomic sequencing to explore whether microbiome composition influences treatment response and public health outcomes.
3. Evaluate the impact of resistance and identify sustainable control strategies
   • Model the potential impact of emerging anthelmintic resistance on intestinal worm control and progress toward WHO elimination goals.
   • Use machine learning, epidemiological modelling, and health economic evaluation to:
     • Predict resistance emergence,
     • Assess cost-effectiveness of alternative interventions,
     • Design a practical surveillance strategy for monitoring anthelmintic resistance that is acceptable to affected communities.