Parasitic Nematodes

Parasitic nematodes are some of the most common parasites on the planet, infecting both people and animals. Globally, approximately 1.5 billion people are infected. These parasites are responsible for the four of the World Health Organisation’s 20 Neglected Tropical Diseases, highlighting their major impact on public health.

One important group of these parasitic nematodes infecting people are the soil-transmitted helminths (STHs). The main STHs include:

• roundworms (Ascaris lumbricoides),
• hookworms (Necator americanus and Ancylostoma duodenale),
• whipworms (Trichuris trichiura),
• and threadworms (Strongyloides stercoralis).

These parasites live in human guts and their eggs are released in faeces, contaminating the soil. New infections happen in two main ways: skin penetration – for hookworm and Strongyloides, where larvae in soil penetrate bare skin; accidental swallowing – for Ascaris and Trichuris, where eggs are eaten, often from contaminated food, water, or unwashed hands.

STHs are most common in low- and middle-income countries (LMICs), where poor sanitation and limited access to clean water allow them to spread easily. Despite their widespread impact, they are often overlooked as a global health priority.

It's not just people that are infected with these parasites – similar ones also infect many animals, including livestock, which can affect food security and livelihoods.

Mass Drug Administration (MDA)

STHs don’t usually kill people, but they still cause serious health problems. In fact, the WHO estimates that these infections are responsible for more years of disability worldwide than malaria, tuberculosis, or HIV/AIDS. 

Because STH parasites are common and widespread in LIMCs, many have implemented MDA programmes at least annually. In these programmes, children are treated at least annually with anthelmintic drugs that kill the nematodes. The impact of these drugs improves children’s health and school performance, and it benefits the wider community by reducing the spread of infection.

However, there is a challenge ahead. While these drugs may still be effective today, their prolonged use in MDA programmes may lead to drug resistance – a problem already seen in livestock, where parasites no longer respond to the drugs.

The continued success of anti-STH MDAs depends on the anthelmintics continuing to work. MDA programmes are at risk of failure if there are widespread reductions in anthelmintic efficacy. The nature and extent of anthelmintic efficacy against STHs is not well known and is a major evidence gap that our work seeks to fill, generating information which is directly relevant to stakeholders, policymakers and users.

Our study

We aim to investigate how MDA in Southeast Asia is contributing to reductions in anthelmintic efficacy against STHs, altering the population genetic structure of STHs, and selecting STH genomes that cause anthelmintic resistance. We will leverage a “natural experiment” that is occurring in Southeast Asia, comparing STHs where MDA is present (Indonesia and the Philippines) with those where it is absent (Malaysia).

Our idea is that the use of anthelmintics in MDA programmes is selecting STHs and driving the evolution of anthelmintic resistance. From this, we predict that:

1. Repeated use of anthelmintics will lead to lower anthelmintic efficacy. We will test this by measuring anthelmintic drug efficacy in areas with (Indonesia and the Philippines) and without (Malaysia) MDA programmes.
2. Repeated anthelmintic use will change the STH population structure by repeatedly bottlenecking their populations. We will investigate this by whole-genome analysis of STH genetic diversity in MDA and non-MDA regions.
3. STH genomes are being selected by the repeated use of anthelmintics. We will investigate this by doing genome scans for sites of selection.

The outputs and benefits of this work are: (a) measuring anthelmintic efficacy against STHs, which will feed into policy and practice in Southeast Asia; (b) determining the genetic effect of anthelmintic selection on STHs; (c) building a sustainable Southeast Asia - UK research network; (d) capacity strengthening a generation of researchers in state-of-the-art bioinformatics analyses of genomic data applied to improving human health and wellbeing.