Unravelling how parasitic worms respond to drug treatment

Parasitic worms, or helminths, pose a significant global health problem . A group of intestinal worms, called soil-transmitted helminths, currently cause disease in over 24% of people worldwide and play a central role in maintaining poverty in affected countries. The World Health Organization has called for drugs to be delivered to all populations most at risk from the impact of these diseases.

However, relatively few treatment options are available, and the current drugs do not work equally well against all worm species. Scientists are also concerned that the worms may be developing drug resistance after years of extensive drug use. But there is renewed hope. The STOP2030 consortium is developing a new fixed-dose combination drug to combat these diseases. The drug could then be used in large-scale public health interventions, with scientists at the Sanger Institute testing the impact of the new treatment. If successful, this will help alleviate poverty and potentially influence global health policy.

Neglected parasites

Diseases caused by soil-transmitted helminths disproportionately affect children in sub-Saharan Africa, South America, and Asia. These illnesses cause various health problems such as malnutrition and developmental conditions. Unlike more deadly infections such as malaria, they attract less scientific attention and are considered Neglected Tropical Diseases. Yet despite these infections not being lethal, the serious impact of these helminth-related diseases on people’s quality of life, early childhood development, and ability to work and attend school is a key factor sustaining poverty in these affected countries.

Soil-transmitted helminths are made up of five groups of worms, known as roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), threadworm (Strongyloides stercoralis) and two species of hookworm (Ancylostoma duodenale and Necator americanus). As a soil-transmitted pathogen, their lives are split between being buried in the soil and living inside humans. These worms are transmitted to humans through either contaminated food or water, or via contact with the soil, which enables them to burrow into skin. With their widespread distribution and complex lifecycles, it is difficult for scientists to treat and control these infections effectively.

Clockwise from top left: Necator americanus (hookworm), Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), Ancylostoma duodenale (hookworm) and Strongyloides stercoralis (threadworm). Image credits in image descriptions

Whilst a limited number of drugs are available, some are very effective in treating certain worm species but not as effective in others. Moreover, the current reliance on a single drug means that drug resistance is a serious threat, and some health experts are concerned that some species of worms are showing signs they may already be developing resistance.

The promise of new treatments

In recent years, the STOP Consortium has developed a promising new treatment that combines two established drugs - albendazole and ivermectin - into a single pill. With over five years of clinical trials in three African countries, this drug seems to be a safe and effective treatment against almost all of these five groups of helminths.

The Sanger Institute joined the EU-funded STOP2030 project last year. Sanger Group Leader, Steve Doyle, and his team will use the Institute’s leading genomic capabilities to unravel the complex helminth biology. This may help scientists determine why current treatments are not working to stop the helminths and possibly identify genetic variants that control their drug susceptibility.

Using genomics to fight worm infections

Most previous genomic studies of these helminths worked with a limited number of pre-existing stored samples, narrowing the research scope.

“A real challenge in parasitology, especially working with human-infective parasites from places like sub-Saharan Africa, is getting access to quality samples. With STOP2030 using very dense and methodically robust sampling, we now have a huge advantage in exploring the genetics of how parasites respond to drugs."

Dr Steve Doyle,
Group Leader, Parasite Genomics, Wellcome Sanger Institute

Sanger Institute researchers will apply genomic epidemiology to understand how helminths are related to each other in different groups of people and how parasite populations change over time. This will start to reveal how different subpopulations of worms are responding to treatment and identify genetic changes that link to drug resistance.

“Understanding the relationship between parasite response to drugs and their genetics is very important from a disease control perspective. If there are genetic variants that could cause drug resistance and we keep applying this drug, it will result in widespread drug resistance."

Dr Steve Doyle,
Group Leader, Parasite Genomics, Wellcome Sanger Institute

The combined samples from STOP2030 and previous projects cover a region of four different African countries: Kenya, Ghana, Ethiopia and Mozambique. The results from the STOP2030 project will be made publicly available to benefit the research community studying these parasites.

Climate change and parasitic disease

Scientists believe climate change, especially an increase in warm and moist environments, will significantly affect the distribution, prevalence and transmission of these parasites. Soil-transmitted helminths are already appearing in new locations, and re-emerging from places they had previously disappeared from, including some of the southern states in the US.

Sanger Institute researchers will continue to study the inter-relationships between climate change, drug effectiveness, the movement of people, and the genetics of these parasites.

Global partnership against parasitic infections

International collaboration is vital for combatting Neglected Tropical Diseases at a global scale. The Sanger Institute and STOP2030 work closely with researchers, health organisations and pharmaceutical companies in affected countries and beyond. This will ensure that new drugs are available for those who need them, and help overcome any challenges in delivery. The consortium is already working with the World Health Organization to discuss the rollout of the new drug.

As Sanger Institute researchers accelerate our understanding of helminth genetics, new treatment strategies may lead to improved control of parasitic worm infections in affected countries, helping to alleviate poverty and improve the quality of life for billions of people. This work highlights the importance of publicly available genomic data in the fight against Neglected Tropical Diseases.

The work was co-funded by the European Union, UKRI, and Wellcome.