Turner, Louise and Worthington, John (2026) Utilizing Volatile Organic Compound Detection for Whipworm Diagnosis. Masters thesis, Lancaster University.
Abstract
Soil-transmitted helminth (STH) infections afflict approximately 1/4 of the world’s population. Trichuris trichiura ‘whipworm’ accounts for about 40% of this statistic, reducing quality of life and causing significant morbidity in mainly children through stunting nutrition, cognition, and growth. Currently available diagnostic methods are often limited by specificity and sensitivity, with cost, time, and training often inaccessible to the low income/resource areas where STH infections are most prevalent. Appropriate, accurate, and obtainable diagnostic tools would aid successful intervention and parasite control. Infection status alters volatile organic compound (VOC) emissions and immune responses with distinct, complex interactions between multiple different cells and cytokines may cause such modifications. Currently research is sparse concerning trichuriasis-induced odour changes, and the identification, recognition, and understanding of disease-specific VOCs could progress investigation into the pathophysiological mechanisms of trichuriasis and provide alternative diagnostic routes. Mouse urine is an intraspecific olfactory communication method, abundant with notable VOC contributors, such as major urinary proteins (MUPs), that relay health/social status and so may exhibit detectable odour changes specific to Trichuris muris infection. To scrutinize the influence T. muris-induced immune response has on urine odour, we used a well-studied C57BL/6 mouse model to determine if infected odour profiles were distinct, utilising qPCR analysis of MUP expression, flow cytometry, and portable VOC analysis. As biological detectors of immune response, sandfly attraction choice experiments were conducted, aligning with unpublished research suggesting sandflies can distinguish T. muris-induced odour changes from mouse hair. We found infection-induced changes in MUP expression, with VOC analysis confirming the presence of detectable T. muris-induced differences, with discriminable differences between acute and chronic infections. Whilst acute T. muris infection induced changes in bladder monocytes, other immune cell subsets had no clear involvement within the liver and bladder, and sandflies did not exhibit significant attraction to infected urine groups nor towards isolated specific Th1 and Th2-related cytokines. Interestingly, preliminary VOC analysis could distinguish between infected and uninfected faecal samples with 100% accuracy, with moderate distinguishment between acute and chronic infections. These data suggest further examination into T. muris-induced faecal odour changes could reveal a potential diagnostic source and clarify the potential mechanistic involvement of the microbiome in infection-induced odour changes.