“Without surveillance, we have no clue,” says Professor Frank Møller Aarestrup from DTU Food, who for more than 20 years has conducted antimicrobial resistance research.
For the past four years, he and his colleagues in the Research Group for Genetic Epidemiology at DTU Food have led an international team of researchers who have shown that genome sequencing of wastewater samples from around the world can provide important knowledge about exactly which resistant bacteria flourish in certain areas. Wastewater analyses thus hold out great potential as a tool for monitoring antimicrobial resistance.
And it is crucial that we monitor, says Frank Møller Aarestrup:
“It’s really quite simple: If you’ve no idea where you are, you’ve no idea where you’re going. We need to know the extent of the problem in order to determine whether resistance is increasing or decreasing. By carrying out wastewater analyses, we get data that gives us a baseline for assessing whether the interventions that are being put in place to reduce resistance are working. Monitoring gives us an opportunity to follow developments.”
Wastewater from many countries
"We need to know the extent of the problem in order to determine whether resistance is increasing or decreasing"
Professor Frank Møller Aarestrup, DTU Food
The research team has analysed wastewater from 258 cities in 103 countries by mapping all bacterial DNA in the samples, enabling them to generate the first comparable global data for the amount and type of resistant bacteria that mainly healthy people carry around in all these countries. The analyses show that the incidence of resistance is generally lowest in North America, Western Europe, Australia, and New Zealand—while it is highest in Asia, Africa, and South America.
According to the researchers, the use of antimicrobial agents explains only a small proportion of the incidence of resistance in countries. They have therefore looked for other factors that either affect the development of resistance or are indicators of the presence of resistant bacteria. In this work, they have used several comprehensive World Bank data sets which have, among other things, measured the health and development of countries.
The work shows that most of the variables associated with the prevalence of resistance in a country relate to the sanitation conditions in the country and the general health of the population, suggesting that resistance spreads more in poor sanitation conditions.
In the fight against antimicrobial resistance, it can therefore be a very effective strategy to take much more ambitious action to improve sanitation in countries with a high level of resistance,” says Frank Møller Aarestrup.
Monitoring antimicrobial resistance through wastewater analysis has several benefits. First, it is a quick and relatively inexpensive method. It does not require ethical approval, as the test material cannot be linked to individuals. It also gives a representative picture of the state of a population, as the wastewater comes from all social classes. This is particularly important in those countries where data otherwise comes only from the most privileged social classes with access to tests by a doctor or a hospital. And in the future, as new resistance genes are discovered, researchers will also be able to reuse the publicly available raw data from the wastewater studies to rapidly determine how the new resistance has emerged and spread.
New technology, old idea
The method of sequencing wastewater can also be used to monitor disease outbreaks caused by completely different microorganisms, says Frank Møller Aarestrup:
“The idea of using wastewater for disease surveillance is several decades old and was used, among other things, for monitoring polio. What’s new is that we can find and genome sequence bacterial DNA in wastewater. But we can also search for viruses. In the spring, when SARS-CoV-2 arrived, we started looking for the virus in the wastewater samples from Copenhagen.”
The analyses may not say exactly how many people are infected with SARS-CoV-2, but they can reveal whether the reproduction rate is rising or falling. Wastewater monitoring could thus give early warning if a new wave of disease is on the way. Similar analyses are carried out by colleagues from the global wastewater project, which is located in Italy, the Netherlands, Spain, the United States, and New Zealand.
System ready for roll-out
The research group has an ambition to develop a system that allows information to be exchanged and interpreted in ‘real time’ across national borders. In this way, it is possible to use global surveillance data to tackle diseases when they threaten to spread from one country and develop into pandemics.
The development of the global monitoring of antimicrobial resistance is being implemented with funding from the Novo Nordisk Foundation in a six-year project ending in 2023. However, efforts are already under way to ensure that responsibility for global wastewater monitoring is handed over to the right body. Professor Frank Møller Aarestrup suggests that the World Health Organization (WHO) or the European Centre for Disease Prevention and Control (ECDC) takes over the technology and continues monitoring.
“Monitoring is a core discipline and now we have a system that can monitor antimicrobial resistance and which can be rolled out, so it’s just a question of doing it. At the same time, the system can include everything from SARS-CoV-2 to foodborne disease outbreaks, so it has some great prospects that we should exploit,” concludes Frank Møller Aarestrup.