TEXT Emanuel Wyler, Markus Landthaler
The water in our sewage system is as murky as it is rich in information. Among other things, it can help us contain infectious diseases in good time, or to detect antibiotic resistance. We should exploit its potential as an early warning system.
There are countless bacteria, viruses, parasites and fungi - known and unknown that can infect people and animals. Some of these microbes are under permanent surveillance. We monitor their quantity, spread and genetic evolution. For poliovirus, for example, wastewater testing is routine. The past three pandemic years have spurred this research and demonstrated the enormous potential of such approaches. The question now is what long-term benefits we as a society want to derive from them. One conceivable use case could be a kind of “weather forecast for viruses.“
For us, observing microbes in wastewater means detecting genetic information in the form of nucleic acids, i.e., DNA or RNA, that humans or animals have excreted. Sometimes it is present in whole, infectious particles, as is the case for polio virus. Sometimes, only fragments remain, probably bound to solids, e.g., for SARS-CoV-2.
When a person is tested for a pathogen, it is a clean affair. The swab used for sampling is sterile, and the sample is subsequently analyzed in the laboratory by PCR. Wastewater is a completely different matter: excretions and waste flow through dirty pipes, mixing with drain from roads or businesses, with silt and sand. Accordingly, it is quite difficult to derive meaningful data from the mixture. During the pandemic, hundreds of scientific publications refining the existing methods have been published - including ours. Such basic research makes wastewater measurements more reliable.
Once the nucleic acids have been extracted from the water, two aspects are of interest. How often does a particular microbe or subgroup - occur? The more people are infected, the more nucleic acids of the same virus the PCR detects in the wastewater samples. It's effectively a “PCR test for the whole city.“ Dozens of countries use wastewater to monitor coronaviruses and make their data publicly available. In Germany, we have the Federal Ministry of Health's Pandemic Radar for this, as well as websites of various states and cities.
The second aspect is the sequence, the order of the four building blocks in nucleic acids. Based on the nucleic acid fragments in the wastewater, the 30,000 “letters“ of the coronavirus genome are read and assembled. This allows us to determine the variant that is circulating in the catchment area of the wastewater treatment plant, and to observe the evolution of the virus over time with repeated testing. Such monitoring is feasible because high-throughput sequencing has become much cheaper and easier in recent years.
Why should we measure microbes in wastewater?
We can detect a broad spectrum of clinically relevant pathogens in wastewater. In addition to respiratory viruses such as SARS-CoV-2, influenza and respiratory syncytial virus (RSV), these include Mpox (monkeypox), enteroviruses, noroviruses or rotaviruses, and yeasts - as well as genes that help bacteria develop antibiotic resistance.
During the pandemic, we were able to prove that wastewater monitoring indicates the rise of an infection wave with about a week's lead time. Thus, it can act as an “early warning system.“ In the case of influenza, wastewater monitoring could help to intensify vaccination campaigns in a targeted manner. In Germany, only just under half of all people over the age of 60 get vaccinated against influenza every year. Perhaps they would be more motivated if they could see from wastewater data that an outbreak is approaching. In the case of RSV, wastewater data could provide advance warning to pediatric clinics that are particularly burdened, and facilitate planning of treatment capacities.
Samples from wastewater treatment plants can provide a representative picture of the microbes circulating in a population. However, wastewater can also be sampled with a local focus. On the premises of large companies, viral signals from wastewater could serve as a forecast of sick leave; they could then react with home office assignments. In the wastewater of hospitals or nursing homes, one could search for antibiotic resistance genes. In diagnostics, wastewater can be used to narrow down which microbes a patient should be tested for - while the symptoms of infectious diseases are often not very specific.
Institutions in the healthcare sector, companies, government agencies and private individuals alike could draw conclusions from a “weather forecast for viruses.“ A doctor's office might reintroduce mandatory masking. A new awareness for the need for preventive measures could arise in the general population. However, this requires clear data preparation to explain the significance and meaning of the numbers and figures.
Beyond wastewater
Wastewater is not the only source for observing pathogens. Swabs from surfaces in public transportation, nucleic acids from captured mosquitoes, or water samples from lakes and rivers - comprehensive monitoring can help us understand the entirety of microbes around us and their evolution over time.
Human, animal, and environmental health are intricately intertwined, and significant changes are ahead of us due to global warming. Data collected from high-throughput sequencing of environmental samples can contribute to the understanding of ecological relationships in the spirit of the One Health approach. To analyze these gigantic data collections, we need artificial intelligence algorithms. They can identify relevant patterns in the vast noise of the data. Ultimately, all this data can unearth untold treasures: enzymes from bacteria, phages or fungi, or their products, can become valuable tools in medicine or biotechnology.
Of course, we should also be prepared for the next pandemic. The pathogen in question will probably be found in our wastewater - as was the case in the summer of 2022 after the first Mpox cases. Expertise and experience will help to quickly contain the spread of the virus next time. Not least thanks to a functioning wastewater monitoring.
Prof. Markus Landthaler “RNA Biology and Posttranscriptional Gene Regulation“ Lab at the Berlin Institute for Medical Systems Biology of the Max-Delbrück-Center (MDC-BIMSB).
Dr. Emanuel Wyler “RNA Biology and Posttranscriptional Gene Regulation“ Lab at the Berlin Institute for Medical Systems Biology of the Max-Delbrück-Center (MDC-BIMSB).
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