Wastewater-based Epidemiology
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Wastewater-based epidemiology (or wastewater-based surveillance or sewage chemical-information mining) analyzes
wastewater Wastewater (or waste water) is water generated after the use of freshwater, raw water, drinking water or saline water in a variety of deliberate applications or processes. Another definition of wastewater is "Used water from any combination of do ...
to determine the consumption of, or exposure to, chemicals or
pathogens In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ. The term ...
in a population. This is achieved by measuring chemical or
biomarkers In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
in wastewater generated by the people contributing to a
sewage treatment plant Sewage treatment is a type of wastewater treatment which aims to remove contaminants from sewage to produce an effluent that is suitable to discharge to the surrounding environment or an intended reuse application, thereby preventing water p ...
catchment. Wastewater-based epidemiology has been used to estimate illicit drug use in communities or populations, but can be used to measure the consumption of alcohol, caffeine, various pharmaceuticals and other compounds. Wastewater-based
epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...
has also been adapted to measure the load of pathogens such as
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
in a community. It differs from traditional drug testing,
urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
or stool testing in that results are population-level rather than individual level. Wastewater-based epidemiology is an interdisciplinary endeavour that draws on input from specialists such as wastewater treatment plant operators, analytical chemists, molecular biologists and epidemiologists.


History

Wastewater-based epidemiology (WBE) can be applied in the field of research that uses the analysis of sewage and wastewater to monitor the presence, distribution, and prevalence of a disease or chemicals in communities. The technique has been used for several decades, and an example of its early application is in the 1940s when WBE was applied for the detection and distribution of poliovirus in the sewage of New York, Chicago, and other cities. Another early application came in 1954, in a study of schistosome of snails. Wastewater-based epidemiology thereafter spread to multiple countries. By the turn of the 21st century, numerous studies had adopted the technique. A 2005 study measured
cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
and its metabolite benzoylecgonine in water samples from the
River Po The Po ( , ) is the longest river in Italy. It flows eastward across northern Italy, starting from the Cottian Alps. The river's length is , or if the Maira, a right bank tributary, is included. The headwaters of the Po are formed by a spring ...
in
Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...
. Wastewater-based epidemiology is supported by government bodies such as the
European Union Drugs Agency The European Union Drugs Agency (EUDA), known until 2024 as the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), is an agency of the European Union headquartered in Lisbon, Portugal, and established in 1993. In June 2022, the ...
in Europe. Similar counterparts in other countries, such as the Australian Criminal Intelligence Commission in Australia and authorities in China use wastewater-based epidemiology to monitor drug use in their populations. As of 2022, WBE had reached 3,000 sites in 58 countries.


Technique

Wastewater-based epidemiology is analogous to
urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a Test panel, panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and #Microscopic examination, m ...
on a community scale. Small molecule compounds consumed by an individual can be excreted in the urine and/or feces in the form of the unchanged parent compound or a metabolite. In communities with
sewerage Sewerage (or sewage system) is the infrastructure that conveys sewage or surface runoff ( stormwater, meltwater, rainwater) using sewers. It encompasses components such as receiving drains, manholes, pumping stations, storm overflows, and scr ...
, this urine combines with other wastes including other individuals' urine as they travel to a municipal wastewater treatment plant. The wastewater is sampled at the plant's inlet, prior to treatment. This is typically done with autosampler devices that collect 24-hour flow or temporally composite samples. These samples contain biomarkers from all the people contributing to a catchment. Collected samples are sent to a laboratory, where
analytical chemistry Analytical skill, Analytical chemistry studies and uses instruments and methods to Separation process, separate, identify, and Quantification (science), quantify matter. In practice, separation, identification or quantification may constitute t ...
techniques (such as liquid chromatography-mass spectrometry) are used to quantify compounds of interest. These results can be expressed in per capita loads based on the volume of wastewater. Per capita daily consumption of a chemical of interest (e.g. a drug) is determined as where ''R'' is the concentration of a residue in a wastewater sample, ''F'' is the volume of wastewater that the sample represents, ''C'' is a correction factor which reflects the average mass and molar excretion fraction of a parent drug or a metabolite, and ''P'' is the number of people in a wastewater catchment. Variations or modifications may be made to C to account for other factors such as the degradation of a chemical during its transport in the sewer system. For microbial surveillance, methods from molecular biology like PCR ( qPCR and dPCR) and genetic sequencing are used. These methods are often highly susceptible to inhibition by various chemical substances commonly found in wastewater. Monitoring of inhibition or removal of these inhibitors is therefore recommended.


Applications

Commonly detected chemicals include, but are not limited to the following; *
Cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...
*
Amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...
*
Methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...
*
Methylone Methylone, also known as 3,4-methylenedioxy-''N''-methylcathinone (MDMC), is an entactogen and stimulant drug of the amphetamine, cathinone, and benzodioxole families related to 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy"). It is th ...
* Ecstasy *
Heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...
*
Alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...
*
Nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...
*
Caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...
*
Ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...
*
Opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
s *
Antidepressants Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexu ...
*
Antipsychotics Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizo ...
* Antimicrobials *
Antihistamines Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides r ...
* Aritificial sweeteners


Temporal comparisons

By analyzing samples taken across different time points, day-to-day or longer-term trends can be assessed. This approach has illustrated trends such as increased consumption of alcohol and recreational drugs on weekends compared to weekdays. A temporal wastewater-based epidemiology study in Washington measured wastewater samples in Washington before, during and after cannabis legalisation. By comparing cannabis consumption in wastewater with sales of cannabis through legal outlets, the study showed that the opening of legal outlets led to a decrease in the market share of the illegal market.


Spatial comparisons

Differences in chemical consumption amongst different locations can be established when comparable methods are used to analyse wastewater samples from different locations. The
European Monitoring Centre for Drugs and Drug Addiction The European Union Drugs Agency (EUDA), known until 2024 as the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), is an agency of the European Union headquartered in Lisbon, Portugal, and established in 1993. In June 2022, the ...
conducts regular multi-city tests in Europe to estimate the consumption of illegal drugs. Data from these monitoring efforts are used alongside more traditional monitoring methods to understand geographical changes in drug consumption trends.


Microbial surveillance


Virus surveillance

Sewage can also be tested for signatures of
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
es excreted via feces, such as the
enterovirus ''Enterovirus'' is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal). Serologic ...
es poliovirus, aichivirus and coronavirus. Systematic wastewater surveillance programs for monitoring enteroviruses, namely poliovirus, were instituted as early as 1996 in Russia. Wastewater testing is recognised as an important tool for poliovirus surveillance by the WHO, especially in situations where mainstream surveillance methods are lacking, or where viral circulation or introduction is suspected. Wastewater-based epidemiology of viruses has the potential to inform on the presence of viral outbreaks when or where it is not suspected. A 2013 study of archived wastewater samples from the Netherlands found viral RNA of Aichivirus A in Dutch sewage samples dating back to 1987, two years prior to the first identification of Aichivirus A in Japan. During the
COVID-19 pandemic The COVID-19 pandemic (also known as the coronavirus pandemic and COVID pandemic), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began with an disease outbreak, outbreak of COVID-19 in Wuhan, China, in December ...
, wastewater-based epidemiology using qPCR and/or
RNA-Seq RNA-Seq (named as an abbreviation of RNA sequencing) is a technique that uses next-generation sequencing to reveal the presence and quantity of RNA molecules in a biological sample, providing a snapshot of gene expression in the sample, also k ...
was used in various countries as a complementary method for assessing the load of
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by the coronavirus SARS-CoV-2. In January 2020, the disease spread worldwide, resulting in the COVID-19 pandemic. The symptoms of COVID‑19 can vary but often include fever ...
and its variants in populations. Regular surveillance programs for monitoring SARS-Cov-2 in wastewater has been instituted in populations within countries such as
Canada Canada is a country in North America. Its Provinces and territories of Canada, ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, making it the world's List of coun ...
,
UAE The United Arab Emirates (UAE), or simply the Emirates, is a country in West Asia, in the Middle East, at the eastern end of the Arabian Peninsula. It is a federal elective monarchy made up of seven emirates, with Abu Dhabi serving as i ...
,
China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...
,
Singapore Singapore, officially the Republic of Singapore, is an island country and city-state in Southeast Asia. The country's territory comprises one main island, 63 satellite islands and islets, and one outlying islet. It is about one degree ...
, the
Netherlands , Terminology of the Low Countries, informally Holland, is a country in Northwestern Europe, with Caribbean Netherlands, overseas territories in the Caribbean. It is the largest of the four constituent countries of the Kingdom of the Nether ...
,
Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...
,
Austria Austria, formally the Republic of Austria, is a landlocked country in Central Europe, lying in the Eastern Alps. It is a federation of nine Federal states of Austria, states, of which the capital Vienna is the List of largest cities in Aust ...
,
Germany Germany, officially the Federal Republic of Germany, is a country in Central Europe. It lies between the Baltic Sea and the North Sea to the north and the Alps to the south. Its sixteen States of Germany, constituent states have a total popu ...
and the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
. In addition to surveillance of human wastewater, studies have also been conducted on livestock wastewater. A 2011 article reported findings of 11.8% of collected human wastewater samples and 8.6% of swine wastewater samples as positive of the pathogen Clostridioides difficile.


Applications against major outbreaks

Wastewater surveillance, which substantially expanded during the earlier
COVID-19 pandemic The COVID-19 pandemic (also known as the coronavirus pandemic and COVID pandemic), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), began with an disease outbreak, outbreak of COVID-19 in Wuhan, China, in December ...
was used to detect monkeypox in the 2022 monkeypox outbreak. It is unclear how cost-effective wastewater surveillance is, but national coordination and standardized methods could be useful. Less common infections may be difficult to detect, including, such as those that cause hepatitis or foodborne illness. A warning of increased cases from wastewater surveillance can "provide health departments with critical lead time for making decisions about resource allocation and preventive measures" and "unlike testing of individual people, wastewater testing provides insights into the entire population within a catchment area". A 2023 report by the National Academies of Sciences, Engineering and Medicine called for moving from the grass roots system that "sprung up in an ad hoc way, fueled by volunteerism and emergency pandemic-related funding" to a more standardized national system and suggested such a system "should be able to track a variety of potential threats, which could include future coronavirus variants, flu viruses, antibiotic resistant bacteria and entirely new pathogens".


Antimicrobial resistance

In 2022, genomic epidemiologists reported results from a
global Global may refer to: General *Globe, a spherical model of celestial bodies *Earth, the third planet from the Sun Entertainment * ''Global'' (Paul van Dyk album), 2003 * ''Global'' (Bunji Garlin album), 2007 * ''Global'' (Humanoid album), 198 ...
survey of
antimicrobial resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resista ...
(AMR) via genomic wastewater-based epidemiology, finding large regional variations, providing maps, and suggesting resistance genes are also passed on between microbial species that are not closely related. A 2023 review on wastewater-based epidemiology opined the necessity of surveillance wastewater from farms with livestock, wet markets and surrounding areas given the greater risk of pathogen spillover to humans.


References

{{Reflist, 2 Epidemiology Public health Water management