Development of diagnostic tools to measure indicators of disease and antimicrobial resistance via urban water profiling
: (Alternative Format Thesis)

  • Elizabeth Holton

Student thesis: Doctoral ThesisPhD


Outbreaks of infectious disease are difficult to predict. Infection control relies on both preventive and reactive measures. Reactive actions are easier to implement, but less favourable in the long-term. Treatment of infectious outbreaks is dependent on the efficacy of the pharmaceuticals available. Discovery and development of new antimicrobials is surpassed by an increasing occurrence of pathogenic drug tolerance. This phenomenon is typically referenced via antibiotic resistance; however, antifungals and antivirals are also susceptible, i.e., antimicrobial resistance (AMR). Advancing our understanding of the AMR emergence and dissemination in urban waters may be used to enhance the measures of prevention control.
The aim to develop early-warning systems for infectious disease was broken down into the construction of several diagnostic tools. The purpose of the thesis is to introduce new monitoring techniques for the presence of antimicrobials in urban waterways; and the subsequent evaluation of community-wide human drug consumption, over time. The objectives included the development of analytical methods for the quantitation of antimicrobials and their human metabolites; longitudinal monitoring of an urban catchment in South Africa; and design and application of correction factors for drug excretion into sewage systems.
Novel analytical methods and wastewater-based epidemiology (WBE) approaches were required for the determination of drug concentration in samples from wastewater treatment plant and river systems. Longitudinal monitoring of a case study catchment area is used to establish spatiotemporal trends of antimicrobial usage, in both formal and informal settlements. Coordination and statistical review of multiple datasets are used to add context to the results, such as system flow rates; population estimates; prescription records; and pharmacokinetic data from published literature.
Analytical methods were developed for the quantitation of broad- and narrow-spectrum antibiotics; one antifungal; two antiretrovirals; and several drug metabolites, via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation studies were conducted for multiple solid and aqueous matrices associated with urban waterways; enabling comprehensive analyses throughout any urban catchment. The case study location, (Eerste River catchment, South Africa) was selected due to broad socioeconomic diversity and infrastructure. The health of both formal and informal settlements could be observed over time via the community-wide monitoring technique, WBE. Spatiotemporal patterns were identified for individual antimicrobials and per drug class, including distinctions between climatic and behavioural trends.
Analyte concentrations and mass loads can be used to characterise pollution and the removal efficacy of wastewater treatment plants, respectively; but correction factors for metabolism and excretion must be applied in order to accurately calculate drug consumption in a community. A systematic literature review of pharmacokinetic metabolite excretion research was conducted to determine correction factors for seventeen antimicrobials. Selection of the most favourable metabolite (unchanged/parent or structural analogue) was conducted using a UK WBE dataset against corresponding National Health Service (NHS) prescription records. Metabolite excretion percentage, stability, recovery, and biotransformation were the major variables effecting the calculation of daily intake. The efficacy of each metabolite was correlated against the catchment prescription data. These correction factors were then able to be applied to catchments without/with only partial prescription records, with a better understanding of the specific strengths and limitations. Partial records were obtained for the Eerste River catchment. Comparisons of municipal and informal settlement waste demonstrated the difference in antimicrobial consumption between communities. Population estimates for the number of individuals contributing waste to the settlement runoff were approximated from multiple sources. However, even upper estimates suggest that the antimicrobial consumption patterns vary significantly from those observed in municipal waste.
Further work should include utilisation of the high-resolution semi-targeted mass spectrometry dataset to priortise the analysis of additional metabolites and transformation products. In order to develop early- warning systems for infectious disease outbreak, continuous, regular monitoring is required. A baseline for average spatiotemporal variance has been established for one region. Additional catchments and further monitoring will contribute towards the development of these systems. Newer, collaborative pharmacokinetic research would be required to improve current metabolite excretion correction factors, as well as the application of the systematic literature review methodology for other drug metabolites. Finally, the combination of chemical and biological approaches will further our understanding of the emergence and dissemination of AMR.
Date of Award16 Nov 2022
Original languageEnglish
Awarding Institution
  • University of Bath
SupervisorBarbara Kasprzyk-Hordern (Supervisor), Edward Feil (Supervisor) & Christopher Frost (Supervisor)


  • Antimicrobial agents
  • antimicrobial resistance
  • early warning system
  • pharmacokinetics
  • urban water fingerprinting
  • Wastewater-Based Epidemiology

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