Determining the Role of Mass Drug Administration in the Emergence of Anthelminthic Resistance of Soil-Transmitted Helminths in Southeast Asia

Our aim is to discover how the mass administration of anthelminthic drugs to children in Southeast Asia is causing reductions in anthelminthic efficacy against soil-transmitted helminths (STHs), altering the population genetic structure of STHs, and selecting STH genomes for anthelminthic resistance. This work will leverage a “natural experiment” that is happening in Southeast Asia, comparing STHs where there is mass drug administration (Indonesia and the Philippines) with STHs where there is not (Malaysia). STHs are one of the World Health Organization’s-defined 20 Neglected Tropical Diseases, infect 1.5 billion people globally, and cause more Years Lost Due to Disability than malaria, TB or HIV/AIDS. Because of the harm caused by STHs, many countries have national programmes of Mass Drug Administration (MDA) where children in high-risk populations are treated at least annually with anthelminthic drugs. These MDA programmes bring health and wider benefits to infected children and to their families. The continued success of anti-STH MDAs depends on the sustained efficacy of anthelminthics, However, there is already evidence of reduced anthelminthic efficacy against STHs. The long-term and widespread use of anthelminthics is predicted to lead to STHs developing anthelminthic resistance. There is extensive evidence of widespread, anthelminthic resistance in nematodes infecting livestock to the same drug classes used to treat STHs, a portent of the future for human STHs. MDA programmes are at a major risk of failure if there are widespread reductions in anthelminthic efficacy. The nature and extent of anthelminthic efficacy in STHs in Southeast Asia is unknown and a major evidence gap that our work will fill, generating information which is directly relevant to stakeholders, policymakers and users. Our central hypothesis is that the use of anthelminthics in MDA programmes is selecting STHs and driving the evolution of anthelminthic resistance. From this we predict that: (1) Repeated use of anthelminthics will lead to lower anthelminthic efficacy. We will test this by measuring anthelminthic drug efficacy in areas with (Indonesia and the Philippines) and without (Malaysia) MDA programmes, our Work Package 1. (2) Repeated anthelminthic 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, our Work Package 2. (3) STH genomes are being selected by the repeated use of anthelminthics. We will investigate this by doing genome scans for sites of selection, our Work Package 3. The outputs and benefits of this work are: (a) ascertaining anthelminthic efficacy against STHs, which will feed into policy and practice in Southeast Asia; (b) determining the genetic effect of anthelminthic 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.