WAAW Blog: What can wastewater-based epidemiology tell us about antimicrobial resistance?

Sophie Gullino

Early Career Researcher

Environmental Monitoring for Health Protection

UK Health Security Agency

What can wastewater-based epidemiology tell us about antimicrobial resistance?

Antimicrobial medicines, such as antibiotics or antivirals, are heavily used to tackle a plethora of diseases—from extremely common urinary tract infections, to pneumonia and life-threatening conditions, such as tuberculosis and malaria. For this reason, antimicrobial resistance (AMR)—the ability of microorganisms to become resistant to antimicrobial medicines—is a growing global health threat. In fact, it reduces the effectiveness of current medical interventions, rendering therapy more precarious and costly, and contributing to decreasing the patients’ quality of life (Hay et al., 2018; Levy and Bonnie, 2004).

Because of the breadth of its clinical impact, AMR has been primarily addressed at the healthcare level, aiming to minimize infections and provide safe care to patients. One of the cornerstones of AMR management, is patients-based surveillance, which involves identifying and quantifying AMR from samples collected for clinical purposes. Nonetheless, microorganisms and their genes can move freely between humans, animals, and the environment, hence surveillance and control measures can benefit from an integrated interdisciplinary approach. This is the idea behind the ‘One-Health’ approach, aiming to mobilise multiple sectors and departments to work together towards a common goal (McEwen and Collignon, 2018; Miłobedzka et al., 2022). Here, we want to stress the importance of environmental surveillance, within a joint effort to address the AMR crisis.

Emergence of resistance is a natural phenomenon that occurs through the process of natural selection. In fact, when microorganisms are faced with an environmental pressure—in this case antimicrobial medicines—they enhance their fitness and resilience by acquiring relevant genes that can be subsequently shared with other organisms. Hence, antimicrobial use, overuse or improper disposal, are important drivers of antimicrobial resistance. Other factors promoting the spread of resistant organisms and their genes are poor infection control or sanitation, reduced access to clean water, environmental contamination, and movement of infected humans and animals (Holmes et al., 2016; McEwen and Collignon, 2018). This highlights the importance of the environment as a reservoir of resistance that can be employed to monitor AMR prevalence and estimate the risk of further infections.

Wastewater-based epidemiology provides an ethically acceptable and relatively cost-effective option to achieve large-scale environmental AMR surveillance, avoiding patient-by-patient sampling (Hendriksen et al., 2019). Wastewater monitoring has been employed for decades, but it has recently gained popularity due to its successes during the COVID-19 pandemic, where it was employed for rapid and inexpensive mass surveys. There are countless examples of COVID-19 being detected in wastewater, even prior to cases being identified in a healthcare setting, allowing for timely intervention (Daughton, 2020). Within UKHSA, Environmental Monitoring for Health Protection (EMHP) was first established as the Covid-19 Wastewater Epidemiology Programme, and is now aiming to continue employing its extensive expertise in wastewater surveillance beyond COVID-19.

Wastewater-based surveillance of AMR prevalence is particularly advantageous, as it allows to collect data from both community-based populations (e.g. sampling outside a major city) and vulnerable populations (e.g. sampling in proximity to hospitals or nursing homes). Moreover, AMR can be monitored in wastewater discharges from relevant locations, such as animal abattoirs or pharmaceutical companies. Through wastewater-based epidemiology, AMR prevalence in different populations can be compared, or tracked over time, allowing for rapid identifications of hotspots, new outbreaks of known resistant pathogens or new kinds of resistance. As a result, early detection of AMR can be used as an early warning tool to inform policy, set up interventions and prevent hospital outbreaks. Additionally, data on AMR spread can be critical for informing clinicians on which antibiotics are likely to be most effective within a given population (Flach et al., 2021; Liguori et al., 2022; Robins et al., 2022).

Lastly, wastewater surveillance is paramount for identifying wastewater treatment technologies that are successful for mitigating environmental spread of AMR, both in the UK and globally (Pazda et al., 2019). In their action plan to tackle AMR spread, the UK proposes to incorporate AMR thinking into their work on nutrition, as well as WASH (water, sanitation and hygiene) in low- and middle-income countries (DHSC, 2019). This is vital as universal access to clean water is at the heart of limiting AMR spread. Thus, investing in AMR wastewater-based epidemiology can also aid the UK in continuing to be a good global partner, and driving innovation. Furthermore, large-scale AMR surveillance would allow the collection of essential information for setting national and global priorities, assessing the impact of interventions and informing treatment guidelines (Pruden et al., 2021; Robins et al., 2022). Overall, wastewater-based epidemiology can significantly contribute to addressing the challenges posed by AMR, and thus should warrant further exploration.

References

DHSC.  (2019b) ‘UK 5-year action plan for antimicrobial resistance 2019 to 2024’.

Daughton, C. G. (2020) Wastewater surveillance for population-wide Covid-19: The present and future. Science of The Total Environment 736: 139631.

Flach, C.-F., Hutinel, M., Razavi, M., Åhrén, C., and Larsson, D. G. J. (2021) Monitoring of hospital sewage shows both promise and limitations as an early-warning system for carbapenemase-producing Enterobacterales in a low-prevalence setting. Water research 200: 117261.

Hay, S. I., Rao, P. C., Dolecek, C., Day, N. P. J., Stergachis, A., Lopez, A. D., and Murray, C. J. L. (2018) Measuring and mapping the global burden of antimicrobial resistance. BMC medicine 16(1): 1–3.

Hendriksen, R. S., Munk, P., Njage, P., van Bunnik, B., McNally, L., Lukjancenko, O., et al. (2019) Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage. Nature Communications 10(1).

Holmes, A. H., Moore, L. S. P., Sundsfjord, A., Steinbakk, M., Regmi, S., Karkey, A., Guerin, P. J., and Piddock, L. J. v (2016) Understanding the mechanisms and drivers of antimicrobial resistance. The Lancet 387(10014): 176–187.

Levy, S. B., and Bonnie, M. (2004) Antibacterial resistance worldwide: Causes, challenges and responses. Nature Medicine.

Liguori, K., Keenum, I., Davis, B. C., Calarco, J., Milligan, E., Harwood, V. J., and Pruden, A. (2022) Antimicrobial Resistance monitoring of water environments: A framework for standardized methods and quality control. Environmental science & technology 56(13): 9149–9160.

McEwen, S. A., and Collignon, P. J. (2018) Antimicrobial Resistance: a One Health Perspective. Microbiology Spectrum 6(2).

Miłobedzka, A., Ferreira, C., Vaz-Moreira, I., Calderón-Franco, D., Gorecki, A., Purkrtova, S., Jan Bartacek, Dziewit, L., Singleton, C. M., Nielsen, P. H., Weissbrodt, D. G., and Manaia, C. M. (2022/15/February) Monitoring antibiotic resistance genes in wastewater environments: The challenges of filling a gap in the One-Health cycle. Journal of Hazardous Materials. Elsevier B.V.

Pazda, M., Kumirska, J., Stepnowski, P., and Mulkiewicz, E. (2019/20/December) Antibiotic resistance genes identified in wastewater treatment plant systems – A review. Science of the Total Environment. Elsevier B.V.

Pruden, A., Vikesland, P. J., Davis, B. C., and de Roda Husman, A. M. (2021/1/December) Seizing the moment: now is the time for integrated global surveillance of antimicrobial resistance in wastewater environments. Current Opinion in Microbiology. Elsevier Ltd.

Robins, K., Leonard, A. F. C., Farkas, K., Graham, D. W., Jones, D. L., Kasprzyk-Hordern, B., Bunce, J. T., Grimsley, J. M. S., Wade, M. J., Zealand, A. M., and McIntyre-Nolan, S. (2022) Research needs for optimising wastewater-based epidemiology monitoring for public health protection. Journal of Water and Health 20(9): 1284–1313.