Population Histamine Burden Assessed Using Wastewater-based Epidemiology: The Association of 1,4‑methylimidazole Acetic Acid and Fexofenadine

Systematic sampling and analysis of wastewater has become an important tool for monitoring consumption of drugs and other substances, and has been proposed as a method to evaluate aspects of population health using endogenous biomarkers. 1,4‑methylimidazoleacetic acid (MIAA) is an endogenous biomarker and metabolite of histamine turnover. Its urinary excretion is elevated in conditions such as mastocytosis, hay fever, hives, food allergies and anaphylaxis. The aim of this study was to develop and apply methods for MIAA in wastewater and compare its occurrence with antihistamine use in wastewater. Consecutive daily samples were collected from seven catchments serving populations from 3000 to 2 million and covering rural and urban communities during the 2016 Census in Australia. MIAA and the antihistamines (ranitidine, fexofenadine, cetirizine) were quantified consistently. Per capita excretion of MIAA (mg/d/capita) estimated from the WW concentrations were consistent with findings from previous clinical studies. We found significant positive correlations between loads of MIAA and fexofenadine (R = 0.68, p < 0.0001) and cetirizine (R = 0.25, p = 0.03) across the various catchments. Sewer reactor experiments on the degradation of MIAA and the antihistamines found that fexofenadine is stable for at least 24 h while MIAA, ranitidine and cetirizine are subject to degradation, and this should be considered in interpretations. To the best of our knowledge, this study is the first wastewater study to introduce and monitor an endogenous metabolite of histamine, and the first study to monitor and relate proxies of disease and treatment of disease.