Title: Profiling the dynamics of nucleic acid secretion by neglected tropical disease parasites - a route to improved diagnostics?
Funder: The Academy of Medical Sciences

Abstract: OBJECTIVES: (1) Understand the fundamental biology and dynamics of extracellular nucleic acid (exNA) secretion by soil transmitted helminth (STH) parasites; (2) Apply those data to biomarker discovery for human STH diagnostics. STH are neglected tropical disease (NTD) parasites that cause significant morbidity across the developing world. Ongoing WHO-sponsored elimination programmes are hindered by the lack of appropriately sensitive diagnostic tools, preventing disease tracking in the low-prevalence settings that follow drug treatment of at-risk populations. Helminths secrete exNAs, which are detectable in host blood and other fluids, and are considered potential diagnostic biomarkers which could underpin improved diagnostic tools. However, exNAs have not yet been profiled for STH species, and indeed we do not know how exNA profiles change between individuals, or in response to parasite burden, development or anthelmintic treatment for any parasite. We will study Strongyloides stercoralis, which is the only native human STH species which can be maintained in a non-immunocompromised rodent host (the gerbil). This flexible system will allow us to study the effects of parasite burden, parasite migration and in-host development, and anthelmintic drug treatment, on exNA profiles in gerbil plasma. We hypothesise that this will identify a set of exNA markers capable of detecting pre-patent infections, quantifying worm burden, and identifying successful anthelmintic clearance of parasite infection. We will then test these markers for conservation in plasma from human STH patients from SE Asia. These outcomes will address UN Sustainable Development Goals by catalysing development of essential diagnostic tools for STH elimination programmes.

Lay abstract: More than 1.5 billion people in the poorest parts of the developing world carry worm parasites in their gut, spread through poor hygiene. These infections don’t kill many people, but cause illnesses that slow childhood development, and make it difficult for adults to work, condemning the world’s poorest communities to continued poverty. Charities treat infections by giving anti-parasite drugs to millions of people at-risk. Diagnostic tools identify infections and help us to decide when and where those drugs need to be given. The diagnostics that we currently have can only detect high levels of infection, meaning that we cannot detect low level infections that can still be transmitted and make people sick. To help them survive, parasites “spit out” lots of different molecules into their hosts. Since these molecules are not found in uninfected hosts, they can be used to diagnose parasite infections. To find these molecules, we need to infect gerbils with known numbers of parasites, taking blood samples as infections develop. Comparing the parasite molecules that we find with the number of parasites in the gerbils will identify markers that help us to measure parasite infections. We will then test whether we can also find these markers in samples from STH infected people from Thailand. This work will help us to develop improved STH diagnostics for the developing world. This outcome will improve the diagnostic guidance of drug treatment, hastening efforts to eliminate these poverty producing diseases from the world’s poorest countries.

Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION