To make it clear

The art of drawing conclusions from experiments and observations consists in evaluating probabilities and in estimating whether they are sufficiently great or numerous enough to constitute proofs.

Antoine Lavoisier (1743–1794)

Wastewater-based epidemiology has been established for about two decades. It was conceived in the 1950s but it was not until the year 2000 that it was formally proposed as a discipline. This approach is based on the premise that any substance excreted by humans, and stable enough in wastewater, can be used to estimate the original concentration excreted by the represented population. The aim of these studies is to establish trends in consumption or exposure to chemical agents such as drugs, medicines, toxins, food additives, or caffeine. In fact, one of the first notable wastewater-based studies, around 2005, involved detecting traces of cocaine in the Po river in northern Italy. This ability to estimate concentrations of excreted substances is what extended wastewater-based epidemiology to virus surveillance.

Why viruses and not other micro-organisms such as bacteria? Because viruses cannot multiply outside the organism they infect. Therefore, the concentration of viruses in wastewater can represent the concentrations excreted by the human population under study, taking into account their persistence at the time of sampling.

The design of studies based on wastewater sampling can cover both temporal comparisons, with samples taken at different times, and spatial comparisons, with samples taken at different locations. What makes these studies so different is that they can potentially collect massive amounts of data that are representative at a community scale. This tool therefore complements and contrasts other types of studies based on individual clinical samples.

Wastewater-based epidemiological surveillance of viruses has achieved extraordinary relevance during the SARS-CoV-2 pandemic. It had already been used to monitor some orophecally transmitted viruses that do not have the membranous envelope that we call a sheath. In particular, it has been applied in poliovirus eradication programmes or to predict outbreaks of hepatitis A virus, rotavirus, or norovirus. These viruses without a membranous envelope have a capsid that is difficult to destroy. Imagine them as solid as a Rubik’s cube made of perfectly fitted proteins. They can withstand a very wide range of adverse temperature, pH, or humidity conditions, which allows them to survive for long periods of time.

The wonderful idea was to apply this knowledge previously acquired with enteroviruses, intestinal viruses, to SARS-CoV-2, a respiratory virus with a membranous envelope that is not exactly a good protection against the environment outside the human body. Fortunately, unlike other respiratory viruses, SARS-CoV-2 RNA has been proved to be detectable in faecal or sewage water.

What are the current challenges for epidemiological surveillance of SARS-CoV-2 in wastewater? First, to develop an adapted standard methodology that allows comparisons between virus concentrations from different types of samples. And secondly, as Lavoisier would say, to determine what is statistically significant and what is not. In other words, to establish threshold values for SARS-CoV-2 concentrations in wastewater that unequivocally advise public health action by the authorities.

In December 2021, an excessive increase of SARS-CoV-2 in wastewater in South Africa alerted experts to the potential for high transmission of a new variant, omicron. And they got it right.

 

© Mètode 2022 - 113. Assembled life - Volume 2 (2022)
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Professor of the Department of Genetics at the University of Valencia.