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Disease and treatment

Who will monitor our sewage for global antimicrobial resistance after 2023?

A Danish professor seeks a successor to manage a global antimicrobial surveillance system based on sewage that he has developed since 2016. He hopes that the World Health Organization (WHO) will take over the project and continue it in parallel with WHO’s existing clinical monitoring of antimicrobial resistance before the current Novo Nordisk Foundation grant expires in 2023.

In 2016, the Novo Nordisk Foundation awarded a grant of DKK 60 million to Frank Møller Aarestrup from the Technical University of Denmark (DTU) to develop and test a global antimicrobial surveillance system based on sewage. These efforts have resulted in a tried-and-tested surveillance system that is ready to implement.

But who will continue the surveillance when the current grant ends in 2023? Although it is only 2020, Frank Møller Aarestrup is already grappling with this issue for good reasons.

“It may seem unusual to talk about finding a successor for a project three and a half years before the grant ends. Nevertheless, the reason is that surveillance projects must run continuously for years so that the data sets have no gaps. We are therefore very interested in finding a home for the project in an organization that has a mandate to carry out global surveillance before the project period ends,” explains Frank Møller Aarestrup.

WHO has the mandate

Together with a colleague from the University of Edinburgh, Frank Møller Aarestrup recently had a peer-reviewed comment published in Science describing the need to have global surveillance based on sewage located at an organization that has a mandate to carry out global surveillance.

Frank Møller Aarestrup is certain who the best host for the project would be.

“If surveillance is to be global, it must be based on an organization that has a global mandate, and naturally this points to WHO. WHO has many research institutes as collaborating centres that would be asked to carry out the surveillance,” he says.

If the project ends up being based at WHO, Frank Møller Aarestrup might have the opportunity to continue being involved with the surveillance system after 2023. He and his research group are already carrying out work for WHO through the WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and Genomics that he leads, located at the National Food Institute at the Technical University of Denmark.

However, he emphasizes the importance of basing the project at an international organization with the appropriate mandate, such as WHO, rather than continuing it under the umbrella of a single university, such as the Technical University of Denmark, even if funding is available.

“At present, a centre at DTU happens to be working with WHO on antimicrobial resistance. However, to ensure that the project is sustainable in the long term, it must generally be based at an organization that has the appropriate international mandate to continue the project, even if at some point the implementation role ends up being located somewhere other than our University,” says Frank Møller Aarestrup.

Could operate in parallel with clinical surveillance

WHO already has a surveillance programme focusing on antimicrobial resistance. WHO launched its Global Antimicrobial Resistance Surveillance System (GLASS) in 2015. GLASS supports global surveillance and research to strengthen the evidence base on antimicrobial resistance.

GLASS is based on clinical surveillance and obtains its data from hospital inpatients. GLASS focuses on patients who are hospitalized with antimicrobial-resistant infections. They mostly received treatment with several types of antibiotics that were not effective before being hospitalized and thus are taking last-resort antibiotics, which are used when all other options are exhausted.

Surveillance based on sewage can be an effective tool to monitor the spread of resistance to first-line antibiotics: the initial treatment for suppressing bacterial infections. This is because the sewage samples provide information on the bacteria circulating in the general population not in hospitals.

“Sewage samples focus on the entire resistome – all antibiotic-resistance genes and their precursors in both pathogenic and non-pathogenic bacteria – and therefore indicate the bacteria present in the general population. Healthy people get infected before they get sick, so sewage provides much valuable information,” explains Frank Møller Aarestrup.

GLASS naturally focuses on clinical surveillance, since data are collected from people hospitalized around the world. In contrast, surveillance using sewage focuses more on the healthy population – or at least the people not hospitalized for antimicrobial-resistant infections. This provides completely new opportunities to gather knowledge about the bacteria circulating in the general population. According to Frank Møller Aarestrup, these two types of surveillance complement each other well.

Technological development has paved the way for effective surveillance based on sewage

Researchers use next-generation sequencing to purify DNA from sewage samples. The development of this technology is crucial if surveillance is to be effectively based on sewage. Next-generation sequencing is many times faster than traditional methods such as Sanger sequencing because it can process a much larger volume of samples, with more being sequenced in parallel.

“Ten years ago, this type of sequencing was impossible, and five years ago it would have been a challenge. Next-generation sequencing can purify all DNA from the wastewater and compare the samples with a large database containing all the known resistance genes. This provides knowledge about the prevalence of antimicrobial resistance in the areas in which the sewage samples are collected,” explains Frank Møller Aarestrup.

The data on the DNA sequences from the sewage samples can be used to map a metagenome that can inform about the prevalence of antimicrobial resistance in parallel with the clinical samples from hospitals traditionally used for monitoring antimicrobial resistance.

“The metagenome has the advantage that we can save the strings of data and retrieve them again and screen them for historical data when a new trend is discovered in the population. We can then use surveillance of sewage to develop forecasts for the types of antimicrobial resistance that might become relevant in a specific region,” says Frank Møller Aarestrup.

Full circle

If the surveillance of sewage is successfully transferred to WHO, this will bring the project full circle. The idea of implementing a global surveillance system started as early as 2012, when Frank Møller Aarestrup first heard about using sewage to monitor polio globally in a conversation with David Heymann, then WHO’s Assistant Director-General for Health Security and Environment.

“Using sewage to monitor diseases such as polio, in which few people are clinically ill and thus hospitalized, is sensible. This made me think about whether anything else can be monitored in sewage,” explains Frank Møller Aarestrup about the discussion that initiated what is now a fully functioning surveillance system.

Frank Møller Aarestrup can easily imagine that surveillance of sewage will be added to the existing GLASS tasks. The research group behind the sewage surveillance system already has good dialogue with WHO, which so far has been positive about incorporating the surveillance of sewage in parallel with its clinical surveillance.

“We already collaborate well with WHO. For example, WHO has organized webinars on the surveillance of sewage under the auspices of GLASS, and I can envisage the two types of global surveillance operating in parallel under the guidance of WHO,” concludes Frank Møller Aarestrup.

Using sewage for surveillance of antimicrobial resistance by Frank Møller Aarestrup and Mark E.J. Woolhouse was published in Science in February 2020. In 2016, the Novo Nordisk Foundation awarded a Challenge Programme grant of DKK 60 million to Frank Møller Aarestrup for the project Global Monitoring of Antimicrobial Resistance.

Frank Møller Aarestrup
Professor, Head of Research Group
Global monitoring of antibiotic resistance Effectively reducing the prevalence of antibiotic resistance and using the best antibiotics requires knowledge based on continually monitoring the prevalence and spread of different types of antibiotic resistance globally. To increase this knowledge, the project will collect and analyse wastewater from cities throughout the world and make the results universally available, including for the public authorities, researchers and citizens. The project will use whole-genome sequencing, a technique that reveals the full DNA profile of bacteria. This will enable the prevalence of all known genes that produce antibiotic resistance to be determined in one operation.