The \'recreational use\' of selected over-the-counter (OTC) medicines is an unofficial activity. The traditional surveys assessing the use of drugs are affected by the bias of underreporting and are thus unreliable. The development of analytical techniques helps to monitor the substances at trace levels, such as in wastewater, and might be applied to estimate the consumption of an analyte of interest and ensure additional, evidence-based information complementary to population surveys. We reviewed studies focused on evaluating the estimated consumption of drugs as a reliable and unbiased source of evidence-based information (called wastewater-based epidemiology, WBE) to monitor the scale of this phenomenon. We found there is a need to test not only narcotics in the environment but also medicines that may be abused or recreationally used. The reviewed studies show methods that might provide reliable information about consumption of drugs, narcotics, and OTC medications for proposing targeted, preventive actions. Moreover, as all the selected studies were based on mass spectrometry, there is a potential to include the dextromethorphan and/or related compounds as part of the screening for narcotics and OTC drugs that can be socially harmful, overused, or misused. This article reviews the analytical methods for detecting dextromethorphan and/or its transformation products in environmental water samples.

Wastewater-based epidemiology (WBE) and wastewater surveillance have become a valuable complementary data source to collect information on community-wide exposure through the measurement of human biomarkers in influent wastewater (IWW). In WBE, normalization of data with the de facto population that corresponds to a wastewater sample is crucial for a correct interpretation of spatio-temporal trends in exposure and consumption patterns. However, knowledge gaps remain in identifying and validating suitable de facto population biomarkers (PBs) for refinement of WBE back-estimations. WBE studies that apply de facto PBs (including hydrochemical parameters, utility consumption data sources, endo- and exogenous chemicals, biological biomarkers and signalling records) for relative trend analysis and absolute population size estimation were systematically reviewed from three databases (PubMed, Web of Science, SCOPUS) according to the PRISMA guidelines. We included in this review 81 publications that accounted for daily variations in population sizes by applying de facto population normalization. To date, a wide range of PBs have been proposed for de facto population normalization, complicating the comparability of normalized measurements across WBE studies. Additionally, the validation of potential PBs is complicated by the absence of an ideal external validator, magnifying the overall uncertainty for population normalization in WBE. Therefore, this review proposes a conceptual tier-based cross-validation approach for identifying and validating de facto PBs to guide their integration for i) relative trend analysis, and ii) absolute population size estimation. Furthermore, this review also provides a detailed evaluation of the uncertainty observed when comparing different de jure and de facto population estimation approaches. This study shows that their percentual differences can range up to ±200 %, with some exceptions showing even larger variations. This review underscores the need for collaboration among WBE researchers to further streamline the application of de facto population normalization and to evaluate the robustness of different PBs in different socio-demographic communities.

Wastewater analysis can serve as a source of public health information. In recent years, wastewater-based epidemiology (WBE) has emerged and proven useful for the detection of infectious diseases. However, insights from the wastewater treatment plant do not allow for the small-scale differentiation within the sewer system that is needed to analyze the target population under study in more detail. Small-scale WBE offers several advantages, but there has been no systematic overview of its application. The aim of this scoping review is to provide a comprehensive overview of the current state of knowledge on small-scale WBE for infectious diseases, including methodological considerations for its application. A systematic database search was conducted, considering only peer-reviewed articles. Data analyses included quantitative summary and qualitative narrative synthesis. Of 2130 articles, we included 278, most of which were published since 2020. The studies analyzed wastewater at the building level (n = 203), especially healthcare (n = 110) and educational facilities (n = 80), and at the neighborhood scale (n = 86). The main analytical parameters were viruses (n = 178), notably SARS-CoV-2 (n = 161), and antibiotic resistance (ABR) biomarkers (n = 99), often analyzed by polymerase chain reaction (PCR), with DNA sequencing techniques being less common. In terms of sampling techniques, active sampling dominated. The frequent lack of detailed information on the specification of selection criteria and the characterization of the small-scale sampling sites was identified as a concern. In conclusion, based on the large number of studies, we identified several methodological considerations and overarching strategic aspects for small-scale WBE. An enabling environment for small-scale WBE requires inter- and transdisciplinary knowledge sharing across countries. Promoting the adoption of small-scale WBE will benefit from a common international conceptualization of the approach, including standardized and internationally accepted terminology. In particular, the development of good WBE practices for different aspects of small-scale WBE is warranted. This includes the establishment of guidelines for a comprehensive characterization of the local sewer system and its sub-sewersheds, and transparent reporting to ensure comparability of small-scale WBE results.

BACKGROUND: Public health surveillance plays a vital role in informing public health decision-making. The onset of the COVID-19 pandemic in early 2020 caused a widespread shift in public health priorities. Global efforts focused on COVID-19 monitoring and contact tracing. Existing public health programs were interrupted due to physical distancing measures and reallocation of resources. The onset of the COVID-19 pandemic intersected with advancements in technologies that have the potential to support public health surveillance efforts.
OBJECTIVE: This scoping review aims to explore emergent public health surveillance methods during the early COVID-19 pandemic to characterize the impact of the pandemic on surveillance methods.
METHODS: A scoping search was conducted in multiple databases and by scanning key government and public health organization websites from March 2020 to January 2022. Published papers and gray literature that described the application of new or revised approaches to public health surveillance were included. Papers that discussed the implications of novel public health surveillance approaches from ethical, legal, security, and equity perspectives were also included. The surveillance subject, method, location, and setting were extracted from each paper to identify trends in surveillance practices. Two public health epidemiologists were invited to provide their perspectives as peer reviewers.
RESULTS: Of the 14,238 unique papers, a total of 241 papers describing novel surveillance methods and changes to surveillance methods are included. Eighty papers were review papers and 161 were single studies. Overall, the literature heavily featured papers detailing surveillance of COVID-19 transmission (n=187). Surveillance of other infectious diseases was also described, including other pathogens (n=12). Other public health topics included vaccines (n=9), mental health (n=11), substance use (n=4), healthy nutrition (n=1), maternal and child health (n=3), antimicrobial resistance (n=2), and misinformation (n=6). The literature was dominated by applications of digital surveillance, for example, by using big data through mobility tracking and infodemiology (n=163). Wastewater surveillance was also heavily represented (n=48). Other papers described adaptations to programs or methods that existed prior to the COVID-19 pandemic (n=9). The scoping search also found 109 papers that discuss the ethical, legal, security, and equity implications of emerging surveillance methods. The peer reviewer public health epidemiologists noted that additional changes likely exist, beyond what has been reported and available for evidence syntheses.
CONCLUSIONS: The COVID-19 pandemic accelerated advancements in surveillance and the adoption of new technologies, especially for digital and wastewater surveillance methods. Given the investments in these systems, further applications for public health surveillance are likely. The literature for surveillance methods was dominated by surveillance of infectious diseases, particularly COVID-19. A substantial amount of literature on the ethical, legal, security, and equity implications of these emerging surveillance methods also points to a need for cautious consideration of potential harm.

For effective implementation of the wastewater-based epidemiology (WBE) approach, real-time quantification of markers in wastewater is critical for data acquisition before data interpretation, dissemination, and decision-making. This can be achieved by using biosensor technology, but whether the quantification/detection limits of different types of biosensors comply with the concentration of WBE markers in wastewater is unclear. In the present study, we identified promising protein markers with relatively high concentrations in wastewater samples and analyzed biosensor technologies that are potentially available for real-time WBE. The concentrations of potential protein markers in stool and urine samples were obtained through systematic review and meta-analysis. We examined 231 peer-review papers to collect information regarding potential protein markers that can enable us to achieve real-time monitoring using biosensor technology. Fourteen markers in stool samples were identified at the ng/g level, presumably equivalent to ng/L of wastewater after dilution. Moreover, relatively high average concentrations of fecal inflammatory proteins were observed, e.g., fecal calprotectin, clusterin, and lactoferrin. Fecal calprotectin exhibited the highest average log concentration among the markers identified in stool samples with its mean value being 5.24 [95 % CI: 5.05, 5.42] ng/g. We identified 50 protein markers in urine samples at the ng/mL level. Uromodulin (4.48 [95 % CI: 4.20, 4.76] ng/mL) and plasmin (4.18 [95 % CI: 3.15, 5.21] ng/mL) had the top two highest log concentrations in urine samples. Furthermore, the quantification limit of some electrochemical- and optical-based biosensors was found to be around the femtogram/mL level, which is sufficiently low to detect protein markers in wastewater even after dilution in sewer pipes.

The novel coronavirus SARS-CoV-2 has spread at an unprecedented rate since late 2019, leading to the global COVID-19 pandemic. During the pandemic, being able to detect SARS-CoV-2 in human populations with high coverage quickly is a huge challenge. As SARS-CoV-2 is excreted in human excreta and thus exposed to the aqueous environment through sewers, the goal is to develop an ideal, non-invasive, cost-effective epidemiological method for detecting SARS-CoV-2. Wastewater surveillance has gained widespread interest and is increasingly being investigated as an effective early warning tool for monitoring the spread and evolution of the virus. This review emphasizes important findings on SARS-CoV-2 wastewater-based epidemiology (WBE) in different continents and techniques used to detect SARS-CoV-2 in wastewater during the period 2020-2022. The results show that WBE is a valuable population-level method for monitoring SARS-CoV-2 and is a valuable early warning alert. It can assist policymakers in formulating relevant policies to avoid the negative impacts of early or delayed action. Such strategy can also help avoid unnecessary wastage of medical resources, rationalize vaccine distribution, assist early detection, and contain large-scale outbreaks.

On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19), whose causative agent is the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pandemic. This virus is predominantly transmitted via respiratory droplets and shed via sputum, saliva, urine, and stool. Wastewater-based epidemiology (WBE) has been able to monitor the circulation of viral pathogens in the population. This tool demands both in-lab and computational work to be meaningful for, among other purposes, the prediction of outbreaks. In this context, we present a systematic review that organizes and discusses laboratory procedures for SARS-CoV-2 RNA quantification from a wastewater matrix, along with modeling techniques applied to the development of WBE for COVID-19 surveillance. The goal of this review is to present the current panorama of WBE operational aspects as well as to identify current challenges related to it. Our review was conducted in a reproducible manner by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We identified a lack of standardization in wastewater analytical procedures. Regardless, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) approach was the most reported technique employed to detect and quantify viral RNA in wastewater samples. As a more convenient sample matrix, we suggest the solid portion of wastewater to be considered in future investigations due to its higher viral load compared to the liquid fraction. Regarding the epidemiological modeling, the data-driven approach was consistently used for the prediction of variables associated with outbreaks. Future efforts should also be directed toward the development of rapid, more economical, portable, and accurate detection devices.

Cardiovascular disease (CVD) and cancer are collectively responsible for tens of millions of global deaths each year. These rates are projected to intensify as the COVID-19 pandemic has caused delays in individualized diagnostics, or exacerbated prevalence due to Post Acute Coronavirus (COVID-19) Syndrome. Wastewater-based epidemiology (WBE) has successfully been employed as a useful tool for generating population-level health assessments, and was examined here in this systematic scoping literature review to (i) identify endogenous human biomarkers reported to indicate CVD or cancer in clinical practice, (ii) assess specificity to the indicated diseases, (iii) evaluate the utility for estimating population-level disease prevalence in community wastewater, and (iv) contextualize the obtained information for monitoring CVD and cancer presence via WBE. A total of 48 peer-reviewed papers were critically examined identifying five urinary protein biomarkers: cardiac troponin I (cTnI) (heart attack/heart failure), cystatin C (atherosclerosis), normetanephrine (tumor presence), α-fetoprotein (prostate and liver cancer), and microtubule assisted serine/threonine kinase 4 (MAST4) (breast cancer). Next, urinary excretion information was utilized to predict biomarker concentrations extant in community wastewater, resulting in average healthy concentrations ranging from 0.02 to 1159 ng/L, and disease-indicating thresholds from 0.16 to 3041 ng/L. Finally, estimating prevalence-adjusted wastewater measurements was explored in order to assess community-level CVD and cancer presence utilizing U.S. reported prevalence rates. Results obtained suggest that WBE can serve as a viable tool in support of current methods for CVD and cancer assessment to reduce morbidities and mortalities worldwide.

Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to be a valuable source of information regarding SARS-CoV-2 transmission and coronavirus disease 2019 (COVID-19) cases. Although the method has been used for several decades to track other infectious diseases, there has not been a comprehensive review outlining all of the pathogens that have been surveilled through wastewater. Herein we identify the infectious diseases that have been previously studied via wastewater surveillance prior to the COVID-19 pandemic. Infectious diseases and pathogens were identified in 100 studies of wastewater surveillance across 38 countries, as were themes of how wastewater surveillance and other measures of disease transmission were linked. Twenty-five separate pathogen families were identified in the included studies, with the majority of studies examining pathogens from the family Picornaviridae, including polio and nonpolio enteroviruses. Most studies of wastewater surveillance did not link what was found in the wastewater to other measures of disease transmission. Among those studies that did, the value reported varied by study. Wastewater surveillance should be considered as a potential public health tool for many infectious diseases. Wastewater surveillance studies can be improved by incorporating other measures of disease transmission at the population-level including disease incidence and hospitalizations.

Wastewater-based epidemiology (WBE) has been employed by many countries globally since the beginning of the COVID-19 pandemic in order to assess the benefits of this surveillance tool in the context of informing public health measures. WBE has been successfully employed to detect SARS-CoV-2 at wastewater treatment plants for community-wide surveillance, as well as in smaller catchments and institutions for targeted surveillance of COVID-19. In addition, WBE has been successfully used to detect new variants, identify areas of high infection levels, as well as to detect new infection outbreaks. However, due to to the large number of inherent uncertainties in the WBE process, including the inherent intricacies of the sewer network, decay of the virus en route to a monitoring point, levels of recovery from sampling and quantification methods, levels of faecal shedding among the infected population, as well as population normalisation methods, the usefulness of wastewater samples as a means of accurately quantifying SARS-CoV-2 infection levels among a population remains less clear. The current WBE programmes in place globally will help to identify new areas of research aimed at reducing the levels of uncertainty in the WBE process, thus improving WBE as a public health monitoring tool for future pandemics. In the meantime, such programmes can provide valuable comparisons to clinical testing data and other public health metrics, as well being an effective early warning tool for new variants and new infection outbreaks. This review includes a case study of sampled wastewater from the sewer network in Dublin, Ireland, during a peak infection period of COVID-19 in the city, which evaluates the different uncertainties in the WBE process.