Passive sampling of wastewater as a tool for the long-term monitoring of community exposure: Illicit and prescription drug trends as a proof of concept

Embargo until 20 May 2019.A passive sampling device, the Polar Organic Chemical Integrative Sampler (POCIS), was calibrated in-situ over a 4-week period in Oslo (Norway) for 10 illicit drugs and pharmaceuticals with the goal of developing an approach for monitoring long-term wastewater drug loads. The calibrations were performed in triplicate using three different overlapping calibration sets under changing environmental conditions that allowed the uncertainty of the sampling rates to be evaluated. All 10 compounds exhibited linear uptake kinetics and provided sampling rates of between 0.023 and 0.192 L d−1. POCIS were deployed for consecutive 2-week periods during 2012 and 2013 and the calculated time-weighted average (TWA) concentrations used to define different drug use trends. The relative uncertainty related to the POCIS data was approximately 40% and, except for citalopram, 85% of all the long-term measurements of pharmaceuticals were within the confidence interval levels calculated to evaluate the effects of changing environmental conditions on the TWA estimations. POCIS was demonstrated to be sufficiently robust to provide reliable annual drug use estimates with a smaller number of samplers (n = 24) than recommended for active sampling (n = 56) within an acceptable level of sample size related uncertainty < 10%. POCIS is demonstrated to be a valuable and reliable tool for the long-term monitoring of certain drugs and pharmaceuticals within a defined population.acceptedVersio

Effectiveness of environmental surveillance of SARS-CoV-2 as an early warning system during the first year of the COVID-19 pandemic: a systematic review

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Analysis of stimulant drugs in the wastewater of five Nordic capitals

Publisher's version (útgefin grein)Wastewater-based epidemiology is an efficient way to assess illicit drug use, complementing currently used methods retrieved from different data sources. The aim of this study is to compare stimulant drug use in five Nordic capital cities that include for the first time wastewater samples from Torshavn in the Faroe Islands. Currently there are no published reports that compare stimulant drug use in these Nordic capitals. All wastewater samples were analyzed using solid phase extraction and ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The results were compared with data published by the European Monitoring Centre for Drugs and Drug Addiction based on illicit drugs in wastewater from over 50 European cities. Confirming previous reports, the results showed high amphetamine loads compared with other European countries. Very little apparent abuse of stimulant drugs was detected in Torshavn. Methamphetamine loads were the highest from Helsinki of the Nordic countries, indicating substantial fluctuations in the availability of the drug compared with previous studies. Methamphetamine loads from Oslo confirmed that the use continues to be high. Estimated cocaine use was found to be in the lower range compared with other cities in the southern and western part of Europe. Ecstasy and cocaine showed clear variations between weekdays and weekends, indicating recreational use. This study further demonstrates geographical trends in the stimulant drug market in five Nordic capitals, which enables a better comparison with other areas of the continent.We wish to acknowledgesupport by COST (EuropeanCooperation inScience and Technology) [Grant number ES1307], as well as the Icelan-dic Research Fund [Grant number 163049-051] and the University ofIceland Research Fund [Grant number HI17060092].Peer Reviewe

Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities

Background: Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE) has been shown to be a reliable approach complementing such surveys. Method: This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison. Results: High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4- methylenedioxymethamphetamine (MDMA) and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data. Conclusions: This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.Jose Antonio Baz Lomba, Stefania Salvatore, Richard Bade, Erika Castrignanò, Ana Causanilles, Juliet Kinyua, Ann-Kathrin McCall, Pedram Ramin, Nikolaos I. Rousis, and Yeonsuk Ryu acknowledge the EU Marie-Skłodowska Curie Initial Training Network SEWPROF (Marie Curie-FP7-PEOPLE, grant number 317205) for their Early Stage Researcher grant and Emma Gracia-Lor for her Experienced Researcher grant. We thank the people and agencies who assisted in the collection of the wastewater samples, in particular Pia Ryrfors and colleagues at Vestfjorden Avløpselskap (VEAS, Oslo, Norway)

Estimation of caffeine intake from analysis of caffeine metabolites in wastewater

Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further information is needed to standardize this approach. Wastewater analysis proved useful to providing additional local information on caffeine use

Wastewater-based epidemiology to assess pan-European pesticide exposure

Human biomonitoring, i.e. the determination of chemicals and/or their metabolites in human specimens, is the most common and potent tool for assessing human exposure to pesticides, but it suffers from limitations such as high costs and biases in sampling. Wastewater-based epidemiology (WBE) is an innovative approach based on the chemical analysis of specific human metabolic excretion products (biomarkers) in wastewater, and provides objective and real-time information on xenobiotics directly or indirectly ingested by a population. This study applied the WBE approach for the first time to evaluate human exposure to pesticides in eight cities across Europe. 24 h-composite wastewater samples were collected from the main wastewater treatment plants and analyzed for urinary metabolites of three classes of pesticides, namely triazines, organophosphates and pyrethroids, by liquid chromatography-tandem mass spectrometry. The mass loads (mg/day/1000 inhabitants) were highest for organophosphates and lowest for triazines. Different patterns were observed among the cities and for the various classes of pesticides. Population weighted loads of specific biomarkers indicated higher exposure in Castellon, Milan, Copenhagen and Bristol for pyrethroids, and in Castellon, Bristol and Zurich for organophosphates. The lowest mass loads (mg/day/1000 inhabitants) were found in Utrecht and Oslo. These results were in agreement with several national statistics related to pesticides exposure such as pesticides sales. The daily intake of pyrethroids was estimated in each city and it was found to exceed the acceptable daily intake (ADI) only in one city (Castellon, Spain). This was the first large-scale application of WBE to monitor population exposure to pesticides. The results indicated that WBE can give new information about the “average exposure” of the population to pesticides, and is a useful complementary biomonitoring tool to study population-wide exposure to pesticides

Comparison of phosphodiesterase type V inhibitors use in eight European cities through analysis of urban wastewater

In this work a step forward in investigating the use of prescription drugs, namely erectile dysfunction products, at European level was taken by applying the wastewater-based epidemiology approach. 24-h composite samples of untreated wastewater were collected at the entrance of eight wastewater treatment plants serving the catchment within the cities of Bristol, Brussels, Castellón, Copenhagen, Milan, Oslo, Utrecht and Zurich. A validated analytical procedure with direct injection of filtered aliquots by liquid chromatography-tandem mass spectrometry was applied. The target list included the three active pharmaceutical ingredients (sildenafil, tadalafil and vardenafil) together with (bio)transformation products and other analogues. Only sildenafil and its two human urinary metabolites desmethyl- and desethylsildenafil were detected in the samples with concentrations reaching 60 ng L. The concentrations were transformed into normalized measured loads and the estimated actual consumption of sildenafil was back-calculated from these loads. In addition, national prescription data from five countries was gathered in the form of the number of prescribed daily doses and transformed into predicted loads for comparison. This comparison resulted in the evidence of a different spatial trend across Europe. In Utrecht and Brussels, prescription data could only partly explain the total amount found in wastewater; whereas in Bristol, the comparison was in agreement; and in Milan and Oslo a lower amount was found in wastewater than expected from the prescription data. This study illustrates the potential of wastewater-based epidemiology to investigate the use of counterfeit medication and rogue online pharmacy sales

Making Waves : Collaboration in the time of SARS-CoV-2-rapid development of an international co-operation and wastewater surveillance database to support public health decision-making

The presence of SARS-CoV-2 RNA in wastewater was first reported in March 2020. Over the subsequent months, the potential for wastewater surveillance to contribute to COVID-19 mitigation programmes has been the focus of intense national and international research activities, gaining the attention of policy makers and the public. As a new application of an established methodology, focused collaboration between public health practitioners and wastewater researchers is essential to developing a common understanding on how, when and where the outputs of this non-invasive community-level approach can deliver actionable outcomes for public health authorities. Within this context, the NORMAN SCORE "SARS-CoV-2 in sewage" database provides a platform for rapid, open access data sharing, validated by the uploading of 276 data sets from nine countries to-date. Through offering direct access to underpinning meta-data sets (and describing its use in data interpretation), the NORMAN SCORE database is a resource for the development of recommendations on minimum data requirements for wastewater pathogen surveillance. It is also a tool to engage public health practitioners in discussions on use of the approach, providing an opportunity to build mutual understanding of the demand and supply for data and facilitate the translation of this promising research application into public health practice. (C) 2021 Elsevier Ltd. All rights reserved.Peer reviewe

Making Waves:Collaboration in the time of SARS-CoV-2 - rapid development of an international co-operation and wastewater surveillance database to support public health decision-making

The presence of SARS-CoV-2 RNA in wastewater was first reported in March 2020. Over the subsequent months, the potential for wastewater surveillance to contribute to COVID-19 mitigation programmes has been the focus of intense national and international research activities, gaining the attention of policy makers and the public. As a new application of an established methodology, focused collaboration between public health practitioners and wastewater researchers is essential to developing a common understanding on how, when and where the outputs of this non-invasive community-level approach can deliver actionable outcomes for public health authorities. Within this context, the NORMAN SCORE “SARS-CoV-2 in sewage” database provides a platform for rapid, open access data sharing, validated by the uploading of 276 data sets from nine countries to-date. Through offering direct access to underpinning meta-data sets (and describing its use in data interpretation), the NORMAN SCORE database is a resource for the development of recommendations on minimum data requirements for wastewater pathogen surveillance. It is also a tool to engage public health practitioners in discussions on use of the approach, providing an opportunity to build mutual understanding of the demand and supply for data and facilitate the translation of this promising research application into public health practice.</p

Specific toxicity of azithromycin to the freshwater microalga Raphidocelis subcapitata

Pharmaceuticals are produced to inflict a specific physiological response in organisms. However, as only partially metabolized after administration, these types of compounds can also originate harmful side effects to non-target organisms. Additionally, there is still a lack of knowledge on the toxicological effects of legacy pharmaceuticals such as the antibiotic azithromycin. This macrolide occurs at high concentrations in the aquatic environment and can constitute a threat to aquatic organisms that are at the basis of the aquatic food chain, namely microalgae. This study established a high‐throughput methodology to study the toxicity of azithromycin to the freshwater microalga Raphidocelis subcapitata. Flow cytometry and pulse amplitude modulated (PAM) fluorometry were used as screening tools. General toxicity was shown by effects in growth rate, cell size, cell complexity, cell viability and cell cycle. More specific outcomes were indicated by the analysis of mitochondrial and cytoplasmatic membrane potentials, DNA content, formation of ROS and LPO, natural pigments content and photosystem II performance. The specific mode of action (MoA) of azithromycin to crucial components of microalgae cells was revealed. Azithromycin had a negative impact on the regulation of energy dissipation at the PSII centers, along with an insufficient protection by the regulatory mechanisms leading to photodamage. The blockage of photosynthetic electrons led to ROS formation and consequent oxidative damage, affecting membranes and DNA. Overall, the used methodology exhibited its high potential for detecting the toxic MoA of compounds in microalgae and should be considered for future risk assessment of pharmaceuticals.publishedVersio