Making waves: The NORMAN antibiotic resistant bacteria and resistance genes database (NORMAN ARB&ARG)-An invitation for collaboration to tackle antibiotic resistance.

With the global concerns on antibiotic resistance (AR) as a public health issue, it is pivotal to have data exchange platforms for studies on antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the environment. For this purpose, the NORMAN Association is hosting the NORMAN ARB&ARG database, which was developed within the European project ANSWER. The present article provides an overview on the database functionalities, the extraction and the contribution of data to the database. In this study, AR data from three studies from China and Nepal were extracted and imported into the NORMAN ARB&ARG in addition to the existing AR data from 11 studies (mainly European studies) on the database. This feasibility study demonstrates how the scientific community can share their data on AR to generate an international evidence base to inform AR mitigation strategies. The open and FAIR data are of high potential relevance for regulatory applications, including the development of emission limit values / environmental quality standards in relation to AR. The growth in sharing of data and analytical methods will foster collaboration on risk management of AR worldwide, and facilitate the harmonization in the effort for identification and surveillance of critical hotspots of AR. The NORMAN ARB&ARG database is publicly available at: https://www.norman-network.com/nds/bacteria/.

Workflow to facilitate the detection of new psychoactive substances and drugs of abuse in influent urban wastewater.

The complexity around the dynamic markets for new psychoactive substances (NPS) forces researchers to develop and apply innovative analytical strategies to detect and identify them in influent urban wastewater. In this work a comprehensive suspect screening workflow following liquid chromatography - high resolution mass spectrometry analysis was established utilising the open-source InSpectra data processing platform and the HighResNPS library. In total, 278 urban influent wastewater samples from 47 sites in 16 countries were collected to investigate the presence of NPS and other drugs of abuse. A total of 50 compounds were detected in samples from at least one site. Most compounds found were prescription drugs such as gabapentin (detection frequency 79%), codeine (40%) and pregabalin (15%). However, cocaine was the most found illicit drug (83%), in all countries where samples were collected apart from the Republic of Korea and China. Eight NPS were also identified with this protocol: 3-methylmethcathinone 11%), eutylone (6%), etizolam (2%), 3-chloromethcathinone (4%), mitragynine (6%), phenibut (2%), 25I-NBOH (2%) and trimethoxyamphetamine (2%). The latter three have not previously been reported in municipal wastewater samples. The workflow employed allowed the prioritisation of features to be further investigated, reducing processing time and gaining in confidence in their identification.

Phytoextraction of per- and polyfluoroalkyl substances (PFAS) and the influence of supplements on the performance of short-rotation crops.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic compounds threatening water quality and food safety worldwide. Phytoremediation is a nature-based, cost-effective, and scalable solution with high potential for treating PFAS-contaminated sites. However, there is a large knowledge gap regarding choice of plant species and methods to enhance performance. This study assessed the PFAS phytoextraction potential of sunflower (Helianthus annuus), mustard (Brassica juncea), and industrial hemp (Cannabis sativa) in a greenhouse experiment, using inorganic fertilizer and a microbial mixture as supplements. PFAS concentrations were measured using UPLC-MS/MS, and bioconcentration factors for different plant tissues and removal efficiency were determined. Perfluoroalkyl carboxylic acid (PFCA) accumulation was 0.4-360 times higher than that of perfluoroalkyl sulfonic acid (PFSA) homologues of similar perfluorocarbon chain length. Inorganic fertilizer significantly (p < 0.001) reduced PFAS concentration in all plant tissues, whereas the microbial mixture tested did not affect PFAS concentration. PFAS uptake ranged from 0.2 to 33% per crop cycle. Overall, the potential number of crop cycles required for removal of 90% of individual PFAS ranged from six (PFPeA) to 232 (PFOA) using sunflower, 15 (PFPeA) to 466 (PFOS) using mustard and nine (PFPeA) to 420 (PFOS) using Hemp. In this study, the percentage of PFAS removal by plants was determined, and an estimation of the time required for PFAS phytoextraction was determined for the first time. This information is important for practical phytoremediation applications.

Antimicrobial Transformation Products in the Aquatic Environment: Global Occurrence, Ecotoxicological Risks, and Potential of Antibiotic Resistance.

The global spread of antimicrobial resistance (AMR) is concerning for the health of humans, animals, and the environment in a One Health perspective. Assessments of AMR and associated environmental hazards mostly focus on antimicrobial parent compounds, while largely overlooking their transformation products (TPs). This review lists antimicrobial TPs identified in surface water environments and examines their potential for AMR promotion, ecological risk, as well as human health and environmental hazards using in silico models. Our review also summarizes the key transformation compartments of TPs, related pathways for TPs reaching surface waters and methodologies for studying the fate of TPs. The 56 antimicrobial TPs covered by the review were prioritized via scoring and ranking of various risk and hazard parameters. Most data on occurrences to date have been reported in Europe, while little is known about antibiotic TPs in Africa, Central and South America, Asia, and Oceania. Occurrence data on antiviral TPs and other antibacterial TPs are even scarcer. We propose evaluation of structural similarity between parent compounds and TPs for TP risk assessment. We predicted a risk of AMR for 13 TPs, especially TPs of tetracyclines and macrolides. We estimated the ecotoxicological effect concentrations of TPs from the experimental effect data of the parent chemical for bacteria, algae and water fleas, scaled by potency differences predicted by quantitative structure-activity relationships (QSARs) for baseline toxicity and a scaling factor for structural similarity. Inclusion of TPs in mixtures with their parent increased the ecological risk quotient over the threshold of one for 7 of the 24 antimicrobials included in this analysis, while only one parent had a risk quotient above one. Thirteen TPs, from which 6 were macrolide TPs, posed a risk to at least one of the three tested species. There were 12/21 TPs identified that are likely to exhibit a similar or higher level of mutagenicity/carcinogenicity, respectively, than their parent compound, with tetracycline TPs often showing increased mutagenicity. Most TPs with increased carcinogenicity belonged to sulfonamides. Most of the TPs were predicted to be mobile but not bioaccumulative, and 14 were predicted to be persistent. The six highest-priority TPs originated from the tetracycline antibiotic family and antivirals. This review, and in particular our ranking of antimicrobial TPs of concern, can support authorities in planning related intervention strategies and source mitigation of antimicrobials toward a sustainable future.

Degradation of 75 organic micropollutants in fresh human urine and water by UV advanced oxidation process.

In household wastewater, a large proportion of organic micropollutants (OMPs) load is attributed to human urine. OMPs could pose a risk to human and environmental health when urine collected in source-separating sanitation systems is recycled as crop fertiliser. This study evaluated degradation of 75 OMPs in human urine treated by a UV-based advanced oxidation process. Fresh urine and water samples were spiked with a broad range of OMPs and fed into a photoreactor equipped with a UV lamp (185 and 254 nm) that generated free radicals in situ. Degradation rate constant and the energy required to degrade 90% of all the OMPs in both matrices were determined. At a UV dose of 2060 J m-2, average ΣOMP degradation of 99% (±4%) in water and 55% (±36%) in fresh urine was achieved. The energy demand for removal of OMPs in water was <1500 J m-2, but for removal of OMPs in urine at least 10-fold more energy was needed. A combination of photolysis and photo-oxidation can explain the degradation of OMPs during UV treatment. Organic substances (e.g. urea, creatinine) likely inhibited degradation of OMPs in urine by competitively absorbing UV-light and scavenging free radicals. There was no reduction in the nitrogen content of urine during treatment. In summary, UV treatment can reduce the load of OMPs to urine recycling sanitation systems.

Three years of wastewater surveillance for new psychoactive substances from 16 countries.

The proliferation of new psychoactive substances (NPS) over recent years has made their surveillance complex. The analysis of raw municipal influent wastewater can allow a broader insight into community consumption patterns of NPS. This study examines data from an international wastewater surveillance program that collected and analysed influent wastewater samples from up to 47 sites in 16 countries between 2019 and 2022. Influent wastewater samples were collected over the New Year period and analysed using validated liquid chromatography - mass spectrometry methods. Over the three years, a total of 18 NPS were found in at least one site. Synthetic cathinones were the most found class followed by phenethylamines and designer benzodiazepines. Furthermore, two ketamine analogues, one plant based NPS (mitragynine) and methiopropamine were also quantified across the three years. This work demonstrates that NPS are used across different continents and countries with the use of some more evident in particular regions. For example, mitragynine has highest mass loads in sites in the United States, while eutylone and 3-methylmethcathinone increased considerably in New Zealand and in several European countries, respectively. Moreover, 2F-deschloroketamine, an analogue of ketamine, has emerged more recently and could be quantified in several sites, including one in China, where it is considered as one of the drugs of most concern. Finally, some NPS were detected in specific regions during the initial sampling campaigns and spread to additional sites by the third campaign. Hence, wastewater surveillance can provide an insight into temporal and spatial trends of NPS use.

Impact of a megacity on the water quality of a tropical estuary assessed by a combination of chemical analysis and in-vitro bioassays.

Tropical estuaries are threatened by rapid urbanization, which leads to the spread of thousands of micropollutants and poses an environmental risk to such sensitive aqueous ecosystems. In the present study, a combination of chemical and bioanalytical water characterization was applied to investigate the impact of Ho Chi Minh megacity (HCMC, 9.2 million inhabitants in 2021) on the Saigon River and its estuary and provide a comprehensive water quality assessment. Water samples were collected along a 140-km stretch integrating the river-estuary continuum from upstream HCMC down to the estuary mouth in the East Sea. Additional water samples were collected at the mouth of the four main canals of the city center. Chemical analysis was performed targeting up to 217 micropollutants (pharmaceuticals, plasticizers, PFASs, flame retardants, hormones, pesticides). Bioanalysis was performed using six in-vitro bioassays for hormone receptor-mediated effects, xenobiotic metabolism pathways and oxidative stress response, respectively, all accompanied by cytotoxicity measurement. A total of 120 micropollutants were detected and displayed high variability along the river continuum with total concentration ranging from 0.25 to 78 µg L-1. Among them, 59 micropollutants were ubiquitous (detection frequency ≥ 80 %). An attenuation was observed in concentration and effect profiles towards the estuary. The urban canals were identified as major sources of micropollutants and bioactivity to the river, and one canal (Ben Nghé) exceeded the effect-based trigger values derived for estrogenicity and xenobiotic metabolism. Iceberg modelling apportioned the contribution of the quantified and the unknown chemicals to the measured effects. Diuron, metolachlor, chlorpyrifos, daidzein, genistein, climbazole, mebendazole and telmisartan were identified as main risk drivers of the oxidative stress response and xenobiotic metabolism pathway activation. Our study reinforced the need for improved wastewater management and deeper evaluations of the occurrence and fate of micropollutants in urbanized tropical estuarine environments.

A novel method for extraction, clean-up and analysis of per- and polyfluoroalkyl substances (PFAS) in different plant matrices using LC-MS/MS.

Per- and polyfluoroalkyl substances (PFAS) are chemicals of concern due to their persistence, bioaccumulation, and toxic properties. PFAS accumulation in plants poses a risk of human and animal exposure due to consumption of the affected plants, but also allows plants to be used in remediation of PFAS-contaminated soils and groundwater. Therefore, effective extraction, cleanup, and analytical methods for measuring PFAS concentrations in plants are fundamental for research on animal and environmental health. PFAS analysis in plant matrices is complex, due to high matrix interference, and scarcity of methods for analyzing different classes of PFAS. In this study, a simple sample preparation method for PFAS analysis in various plant tissues (leaves, needles, twigs, stems, roots from 10 different species) was developed and validated. Instrumental analysis was performed using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method was optimized considering six different extraction conditions and three different cleanup techniques. Methanol as extraction solvent, combined with 1 g ENVI carb cartridges, showed best performance among all extraction conditions and cleanup techniques tested. Method validation showed good recovery (90-120%), high within-day and between-day precision (<20% relative standard deviation), and low method detection limit (0.04-4.8 ng g-1 dry weight (dw)) for different plant matrices. In tests of the method on soil and different plant tissues of silver birch (Betula pendula) and Norway spruce (Picea abies) at a PFAS-contaminated site, 16 of 24 target PFAS were detected in plants and 17 in soil. Æ©PFAS concentration in soil was 43 ng g-1 dw. PFAS distribution in silver birch tissues ranged from 7.1 ng g-1 dw in roots to 64 ng g-1 dw in leaves, and in Norway spruce from 14 ng g-1 dw in roots to 16 ng g-1 dw in needles. This novel method for PFAS analysis in plants can be valuable in future monitoring, process understanding, remediation, and risk assessments.

Refining the estimation of amphetamine consumption by wastewater-based epidemiology.

Consumption of amphetamine and methamphetamine, two common illicit drugs, has been monitored by wastewater-based epidemiology (WBE) in many countries over the past decade. There is potential for the estimated amount of amphetamine used to be skewed at locations where methamphetamine is also consumed, because amphetamine is also excreted to wastewater following methamphetamine consumption. The present study aims to review the available data in the literature to identify an average ratio of amphetamine/methamphetamine (AMP/METH) that is excreted to wastewater after methamphetamine consumption. This ratio could then be used to refine the estimation of amphetamine consumption in catchments where there is both amphetamine and methamphetamine use. Using data from more than 6000 wastewater samples from Australia where methamphetamine is the dominant illicit amphetamine-type substance on the market, we were able to subtract the contribution of legal sources of amphetamine contribution and obtain the median AMP/METH ratio in wastewater of 0.09. Using this value, the amphetamine derived from methamphetamine consumption can be calculated and subtracted from the total amphetamine mass loads in wastewater samples. Without considering the contribution of amphetamine from methamphetamine use, selected European catchments with comparable consumption of amphetamine and methamphetamine showed up to 83% overestimation of amphetamine use. For catchments with AMP/METH ratio greater than 1.00, the impact of amphetamine from methamphetamine would be negligible; for catchments with AMP/METH ratio in the range of 0.04-0.19, it will be difficult to accurately estimate amphetamine consumption.

Enhancing spectral quality in complex environmental matrices: Supporting suspect and non-target screening in zebra mussels with ion mobility.

Identification of bioaccumulating contaminants of emerging concern (CECs) via suspect and non-target screening remains a challenging task. In this study, ion mobility separation with high-resolution mass spectrometry (IM-HRMS) was used to investigate the effects of drift time (DT) alignment on spectrum quality and peak annotation for screening of CECs in complex sample matrices using data independent acquisition (DIA). Data treatment approaches (Binary Sample Comparison) and prioritisation strategies (Halogen Match, co-occurrence of features in biota and the water phase) were explored in a case study on zebra mussel (Dreissena polymorpha) in Lake Mälaren, Sweden's largest drinking water reservoir. DT alignment evidently improved the fragment spectrum quality by increasing the similarity score to reference spectra from on average (±standard deviation) 0.33 ± 0.31 to 0.64 ± 0.30 points, thus positively influencing structure elucidation efforts. Thirty-two features were tentatively identified at confidence level 3 or higher using MetFrag coupled with the new PubChemLite database, which included predicted collision cross-section values from CCSbase. The implementation of predicted mobility data was found to support compound annotation. This study illustrates a quantitative assessment of the benefits of IM-HRMS on spectral quality, which will enhance the performance of future screening studies of CECs in complex environmental matrices.

Are preserved coastal water bodies in Spanish Mediterranean basin impacted by human activity? Water quality evaluation using chemical and biological analyses.

The Spanish Mediterranean basin is particularly susceptible to climate change and human activities, making it vulnerable to the influence of anthropogenic contaminants. Therefore, conducting comprehensive and exhaustive water quality assessment in relevant water bodies of this basin is pivotal. In this work, surface water samples from coastal lagoons or estuaries were collected across the Spanish Mediterranean coastline and subjected to target and suspect screening of 1,585 organic micropollutants by liquid chromatography coupled to ion mobility separation and high resolution mass spectrometry. In total, 91 organic micropollutants could be confirmed and 5 were tentatively identified, with pharmaceuticals and pesticides being the most prevalent groups of chemicals. Chemical analysis data was compared with data on bioanalysis of those samples (recurrent aryl hydrocarbon receptor (AhR) activation, and estrogenic receptor (ER) inhibition in wetland samples affected by wastewater streams). The number of identified organic contaminants containing aromatic rings could explain the AhR activation observed. For the ER antagonistic effects, predictions on estrogenic inhibition potency for the detected compounds were used to explain the activities observed. The integration of chemical analysis with bioanalytical observations allowed a comprehensive overview of the quality of the water bodies under study.

Exploring antibiotic consumption between urban and sub-urban catchments using both parent drugs and related metabolites in wastewater-based epidemiology.

Consumption of antibiotics leads to the dissemination of antimicrobial resistance worldwide. Better knowledge of temporal and spatial consumption of antibiotics helps public health authorities to control their usage and combat antimicrobial resistance. However, measuring antibiotic consumption with population surveys, sales data, and production statistics remains challenging due to the complexity of prescription preference, patient compliance, and direct disposal of unused drugs. With the approach of wastewater-based epidemiology (WBE), this study aims to evaluate the consumption of eight commonly-used antibiotics between developed urban and developing sub-urban catchments in China and to characterise the ratios of parent drugs to metabolites in studying the consumption. Seven parent antibiotics were detected in all the wastewater samples (n = 56), whereas some metabolites were detected sporadically. The ratios of parent chemicals to metabolites varied among locations and were often higher than the ratios in pharmacokinetic studies. Estimated consumption of antibiotics ranged from 3.2 ± 2.0 mg/day/1000 inhabitants for trimethoprim to 28,400 ± 7800 mg/day/1000 inhabitants for roxithromycin in the studied catchments. Higher consumption of sulfapyridine, sulfadiazine and roxithromycin was observed in urban than suburban catchments, while consumption of sulfamethoxazole, norfloxacin, and trimethoprim was higher in suburban than in urban catchments. Using the literature data, we found more than 95% reduction of antibiotic use in an urban catchment. Our study revealed the geographical pattern in antibiotic use across different urban and suburban catchments via WBE, and the potential of monitoring parent-to-metabolite ratios for WBE in estimating antibiotic use. These results provide a basis for health authorities to plan different drug-specific control policies between urban and suburban catchments, and for future WBE studies to be aware of other sources, such as animal husbandry and disposals of unused drugs, that can influence the estimated consumption.

Profiles of environmental antibiotic resistomes in the urban aquatic recipients of Sweden using high-throughput quantitative PCR analysis.

Antibiotic resistance in aquatic ecosystems presents an environmental health issue worldwide. Urban recipient water quality is susceptible to effluent discharges with antibiotic resistance contaminants and needs to be protected, particularly for those as sources of drinking water production. Knowledge on aquatic resistome profiles in downstream of wastewater treatment plants allows a better understanding of the extent to which antibiotic resistance contaminants emerge and spread in recipient waters, but such information remains very limited in Sweden. The key objective of this study was to determine the resistome profiles of numerous antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and other genes in urban recipient water systems connected to Sweden's major drinking water reservoir. This was achieved through analysis of surface water samples for 296 genes using high-throughput quantitative PCR arrays. A total of 167 genes were detected in at least one of the samples, including 150 ARGs conferring resistance to 11 classes of antibiotics, 7 integrase MGEs and 9 other genes. There was a spatial difference in the resistome profiles with the greatest average relative abundance of resistance genes observed in the water body of Västerås followed by Uppsala, Stockholm and Eskilstuna, as similar to the general pattern of the antibiotic sales for these regions. ARGs against ß-lactams and sulfonamides showed the highest average relative abundance in the studied water bodies, while vancomycin resistance genes were only found in the Uppsala water environment. Generally, the recipient water bodies were detected with higher numbers of genes and greater relative abundances as compared to the upstream sites. Anthropogenic pollution, i.e., wastewater discharge, in the recipient water was also reflected by the finding of intI, sul1 and crAssphage. Overall, this study provided the first quantitative assessment of aquatic environmental resistomes in Sweden, highlighting the widespread of antibiotic resistance contaminants in urban recipient waters.

Mining chemical information in Swedish wastewaters for simultaneous assessment of population consumption, treatment efficiency and environmental discharge of illicit drugs.

Consumption of illicit drugs poses health risks to the public and environment. Knowledge on their usage helps better implementations of intervention strategies to reduce drug-related harms in the society and also policies to limit their releases as emerging contaminants to recipient environments. This study aimed to investigate from the daily consumption to treatment efficiency and subsequent discharge of illicit drugs by the Swedish urban populations based on simultaneous collection and analysis of influent and effluent wastewater. Two different weekly monitoring campaigns showed similar drug prevalence in Stockholm and Uppsala, with amphetamine as the most popular drug. Almost all target drug residues were still measurable in effluent wastewater. High removal efficiencies (> 94%) were observed for amphetamine, cocaine and benzoylecgonine, whereas ketamine, 3,4-methylenedioxymethamphetamine (MDMA), mephedrone and methamphetamine were the least removed substances (< 64%), with the highest discharge observed for MDMA in both catchments (~ 3.0 g/day in Uppsala; ~ 18 g/day in Stockholm). Our study provides new insights into short-term changes in the use and related discharge of illicit drugs by urban populations. Such wastewater monitoring can provide useful information to public health, forensic and environmental authorities in planning future intervention and regulation policies.

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.

Occurrence and removal of chemicals of emerging concern in wastewater treatment plants and their impact on receiving water systems.

Wastewater treatment plants (WWTPs) are considered the main sources of chemicals of emerging concern (CECs) in aquatic environments, and can negatively impact aquatic ecosystems. In this study, WWTP influent, effluent, and sludge, and upstream and downstream waters from the WWTP recipient were investigated at 15 locations for a total of 164 CECs, including pharmaceuticals, personal care products, industrial chemicals, per- and polyfluoroalkyl substances (PFASs), and pesticides. In addition, zebrafish (Danio rerio) embryo toxicity tests (ZFET) were applied to WWTP influent and effluent, and upstream and downstream waters from WWTP recipients. A total of 119 CECs were detected in at least one sample, mean concentrations ranging from 0.11 ng/L (propylparaben) to 64,000 ng/L (caffeine), in wastewater samples and from 0.44 ng/L (ciprofloxacin) to 19,000 ng/L (metformin) in surface water samples. Large variations of CEC concentrations were found between the selected WWTPs, which can be explained by differences in CEC composition in influent water and WWTP treatment process. The sludge-water partitioning coefficient (Kd) of CECs showed a significant linear correlation to octanol/water partition coefficient (KOW) (p < 0.001), and thus could be used for predicting their fate in the aqueous and solid phase. The ΣCEC concentrations in WWTPs declined by on average 60%, based on comparisons of WWTP influent and effluent concentrations. The high concentrations of CECs in WWTP effluent resulted in, on average, 50% higher concentrations of CECs in water downstream of WWTPs compared with upstream. Some WWTP samples showed toxicity in ZFET compared with the respective control group, but no individual CECs or groups of CECs could explain this toxicity. These results could provide a theoretical basis for optimization of existing treatment systems of different designs, and could significantly contribute to protecting recipient waters.

Testing wastewater from a music festival in Switzerland to assess illicit drug use.

This article describes the application of a recently proposed framework for deploying wastewater-based epidemiology (WBE) to monitor illicit drug use within festivals (Benaglia et al., 2019). The festival under study was a week-long music festival in Switzerland (Swiss Festival) which attracted around 50,000 people daily. Wastewater sampling was performed during its 2014 and 2015 editions. As the Swiss Festival's wastewater is conveyed to the sewage treatment plant (STP) of the nearby city, to assess illicit drug use when there is no festival (i.e. the background consumption) wastewater sampling was also carried out during an off-festival week in 2015. During the 2014 and 2015 editions of the Swiss Festival, WBE highlighted that the most consumed illicit drugs were cannabis, MDMA, cocaine and amphetamine. Excluding cannabis, the means per capita loads of all illicit drugs were not statistically different between both editions of the Swiss Festival. The results were then compared to those of an Australian festival which had also been subject of a quantitatively assessed illicit drug use study (Lai et al., 2013). This comparison confirmed that MDMA is highly prevalent, as well as amphetamine, although to a lesser extent. Consumption of cocaine (in Switzerland) and methamphetamine (in Australia) is also high, but their use seems to be related to their availability (i.e. to the country where the festival takes place). Furthermore, it was observed that MDMA and amphetamine are more consumed during the festival compared to normal times, when there is no festival. This might suggest that their availability is increased and therefore, that a market for these substances potentially exists during the festival. This last hypothesis was assessed by consulting drug seizures made by the police during the 2015 Swiss Festival. Despite very limited data, police records suggested that most of the drugs were purchased at the festival, which supports the previous hypothesis. Results validate, on the one hand, WBE as a useful indicator to monitor illicit drug use within festivals and on the other hand, the suggested framework for deploying WBE in such environment. In addition, this study suggests the need for prevention and harm reduction measures targeted on MDMA and amphetamine during the Swiss Festival, such as drug checking laboratories.

Using wastewater-based epidemiology to estimate consumption of alcohol and nicotine in major cities of China in 2014 and 2016.

Monitoring the use of alcohol and tobacco in the population is important for public health planning and evaluating the efficacy of intervention strategies. The aim of this study was to use wastewater-based epidemiology (WBE) to estimate alcohol and tobacco consumption in a number of major cities across China and compare WBE estimates with other data sources. Daily composite influent wastewater samples were collected from wastewater treatment plants (WWTPs) across China in 2014 (n = 53) and 2016 (n = 45). The population-normalized daily consumption estimated by WBE were compared with other data sources where available. The average consumption of alcohol was 8.1 ± 7.0 mL ethanol/person aged 15+/day (EPD) in the investigated cities of 2016 while those involved in 2014 had an average consumption of 4.7 ± 3.0 EPD. The average tobacco consumption was estimated to be 3.7 ± 2.2 cigarettes/person aged 15+/day (CPD) in 2016 and 3.1 ± 1.9 CPD in 2014. The changes in the average consumption in those cities from 2014 to 2016 were supported by the results from a limited number of WWTPs where samples were collected in both years. Consumption of alcohol and tobacco in urban China is at a medium level compared with other countries on a per capita basis. WBE estimates of tobacco consumption were relatively comparable with results of traditional surveys and sales statistics. WBE estimates of alcohol consumption were lower than WHO survey results, probably due to EtS degradation and uncertainty in the EtS excretion factor.

A mood state-specific interaction between kynurenine metabolism and inflammation is present in bipolar disorder.

OBJECTIVES: Cytokines are thought to contribute to the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) and studied their relation to kynurenine metabolites and mood. METHODS: Patients with BD suffering from an acute mood episode were assigned to the depressive (n = 35) or (hypo)manic (n = 32) subgroup. Plasma levels of inflammatory markers [cytokines, C-reactive protein] and kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KYNA)] were measured on 6 time points during 8 months follow-up. Biological marker levels in patients were compared to controls (n = 35) and correlated to scores on mood scales. Spearman correlations and linear mixed models were used for statistical analysis. RESULTS: Twenty patients of the manic subgroup, 29 of the depressive subgroup, and 30 controls completed the study. The manic subgroup had a rapid remission of mood symptoms, but in the depressive subgroup subsyndromal symptoms persisted. No differences in inflammation were found between groups. A strong correlation between tumor necrosis factor-α and KYN, KYN/TRP, 3-HK and QA (ρ > 0.60) was specific for the manic group, but only at baseline (during mania). The depressive subgroup had a lower neuroprotective ratio (KYNA/3-HK, P = .0004) and a strong association between interferon-y and kynurenine pathway activation (P < .0001). KYNA was low in both patient groups versus controls throughout the whole follow-up (P = .0008). CONCLUSIONS: Mania and chronic depressive symptoms in BD are accompanied by a strong interaction between inflammation and a potentially neurotoxic kynurenine metabolism.

Spatio-temporal assessment of illicit drug use at large scale: evidence from 7 years of international wastewater monitoring.

BACKGROUND AND AIMS: Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population-normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011-17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data. DESIGN: Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017. SETTING AND PARTICIPANTS: Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries. MEASUREMENTS: Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of Δ9 -tetrahydrocannabinol (11-nor-9-carboxy-Δ9 -tetrahydrocannabinol) were measured in wastewater using liquid chromatography-tandem mass spectrometry. Daily mass loads (mg/day) were normalized to catchment population (mg/1000 people/day) and converted to the number of combined doses consumed per day. Spatial differences were assessed world-wide, and temporal trends were discerned at European level by comparing 2011-13 drug loads versus 2014-17 loads. FINDINGS: Benzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North-Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge. CONCLUSIONS: The analysis of wastewater to quantify drug loads provides near real-time drug use estimates that globally correspond to prevalence and seizure data.