Wastewater-based epidemiology (WBE) is an unobtrusive method used to observe patterns in illicit drug use, poliovirus, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The pandemic ...and need for surveillance measures have led to the rapid acceleration of WBE research and development globally. With the infrastructure available to monitor SARS-CoV-2 from wastewater in 58 countries globally, there is potential to expand targets and applications for public health protection, such as other viral pathogens, antimicrobial resistance (AMR), pharmaceutical consumption, or exposure to chemical pollutants. Some applications have been explored in academic research but are not used to inform public health decision-making. We reflect on the current knowledge of WBE for these applications and identify barriers and opportunities for expanding beyond SARS-CoV-2. This paper critically reviews the applications of WBE for public health and identifies the important research gaps for WBE to be a useful tool in public health. It considers possible uses for pathogenic viruses, AMR, and chemicals. It summarises the current evidence on the following: (1) the presence of markers in stool and urine; (2) environmental factors influencing persistence of markers in wastewater; (3) methods for sample collection and storage; (4) prospective methods for detection and quantification; (5) reducing uncertainties; and (6) further considerations for public health use.
Many studies have characterised resistomes in river microbial communities. However, few have compared resistomes in parallel rural catchments that have few point-source inputs of antimicrobial genes ...(ARGs) and organisms (i.e., AMR) – catchments where one can contrast more nebulous drivers of AMR in rural rivers. Here, we used quantitative microbial profiling (QMP) to compare resistomes and microbiomes in two rural river catchments in Northern England, the Coquet and Eden in Northumberland and Cumbria, respectively, with different hydrological and geographical conditions. The Eden has higher flow rates, higher annual surface runoff, and longer periods of soil saturation, whereas the Coquet is drier and has lower flowrates. QMP analysis showed the Eden contained significantly more abundant microbes associated with soil sources, animal faeces, and wastewater than the Coquet, which had microbiomes like less polluted rivers (Wilcoxon test, p < 0.01). The Eden also had greater ARG abundances and resistome diversity (Kruskal Wallis, p < 0.05), and higher levels of potentially clinically relevant ARGs. The Eden catchment had greater and flashier runoff and more extensive agricultural land use in its middle reach, which explains higher levels of AMR in the river. Hydrological and geographic factors drive AMR in rural rivers, which must be considered in environmental monitoring programmes.
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•Resistomes and microbiomes were quantified in two rural UK river catchments.•Differences in resistance were contrasted between the rivers vs local hydrology.•Microbiomes were assessed through Quantitative Microbial Profiling.•The wetter Eden River had higher levels of resistance than the drier Coquet River.•Local hydrology impacts levels of resistance in rivers with diffuse pollution.
Antibiotic resistance genes (ARGs) that can encode resistance traits in bacteria are found across the environment. While it is often difficult to discern their origin, their prevalence and diversity ...depends on many factors, one of which is their exposure to potentially toxic elements (PTE, i.e., metals and metalloids) in soils. Here, we investigated how ambient ARGs and mobile genetic elements (MGEs) relate to the relative bioavailability of different PTEs (total versus exchangeable and carbonate-bound PTE) in rural and urban soils in northeast England. The average relative abundances of ARGs in rural sites varied over a 3-log range (7.24 × 10−7 to 1.0 × 10−4 genes/16S rRNA), and relative ARG abundances in urban sites varied by four orders of magnitude (1.75 × 10−6 to 2.85 × 10−2 genes/16S rRNA). While beta-lactam and aminoglycoside resistance genes dominated rural and urban sites, respectively, non-specific ARGs, also called multidrug-resistance genes, were significantly more abundant in urban sites (p < 0.05). Urban sites also had higher concentrations of total and exchangeable forms of PTE than rural sites, whereas rural sites were higher in carbonate-bound forms. Significant positive Spearman correlations between PTEs, ARGs and MGEs were apparent, especially with bioavailable PTE fractions and at urban sites. This study found significant positive correlations between ARGs and beryllium (Be), which has not previously been reported. Overall, our results show that PTE bioavailability is important in explaining the relative selection of ARGs in soil settings and must be considered in future co-selection and ARG exposure studies.
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•Patterns of antibiotic resistance genes differ between urban and rural landscapes.•In rural settings, antibiotic resistance is directly associated with mobile genetic elements.•In urban sites, antibiotic resistance is more directly linked with potentially toxic elements.•The presence of antibiotic resistance genes and mobile genetic elements correlate better with bioavailable elements (metals).
The chemical and isotopic analysis of archaeological materials at a microscopic scale involves sampling by largely non-destructive methods using “microbeam” techniques that remove tiny amounts of the ...artifact for chemical compositional analysis. Such methods can provide significant insight into the provenance (i.e., geographic or geological origin of artifact raw materials) of objects that are of cultural or archaeological significance. For metallic artifacts in particular, surface corrosion (i.e., oxidation and hydration of the metal to produce a patina) can change the original composition of the metal, requiring methods to sample the fresh material under this corrosion layer. Traditionally, chemical analysis of
Abstract
Background
BCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth ...alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization.
Methods
A whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands.
Results
Compared to BCG-naive infants, BCG-vaccinated infants had increased production of interferon gamma (IFN-γ) and monokine induced by gamma interferon (MIG) (CXCL9) in response to mycobacterial stimulation and decreased production of IFN-γ in response to heterologous stimulation and TLR ligands. Reduced IFN-γ responses were attributable to a decrease in the proportion of infants who mounted a detectable IFN-γ response. BCG-vaccinated infants also had increased production of MIG (CXCL9) and interleukin-8 (IL-8), and decreased production of IL-10, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination.
Conclusions
BCG vaccination leads to changes in IFN-γ responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation vary by pathogen.
Neonatal BCG vaccination results in a decreased proportion of infants mounting an IFN-γ response to heterologous stimulation at 7 months of age. Both sex and maternal BCG vaccination status influenced the effect of BCG vaccination on heterologous cytokine responses.
Neonatal BCG vaccination is associated with a reduction in all-cause mortality. This study reports altered cytokine responses to heterologous pathogens and TLR ligands in BCG-vaccinated neonates ...compared to non-BCG-vaccinated controls, consistent with modulation of innate immunity.
Abstract
Background
BCG vaccination is associated with a reduction in all-cause infant mortality in high-mortality settings. The underlying mechanisms remain uncertain, but long-term modulation of the innate immune response (trained immunity) may be involved.
Methods
Whole-blood specimens, collected 7 days after randomization from 212 neonates enrolled in a randomized trial of neonatal BCG vaccination, were stimulated with killed pathogens and Toll-like receptor (TLR) ligands to interrogate cytokine responses.
Results
BCG-vaccinated infants had increased production of interleukin 6 (IL-6) in unstimulated samples and decreased production of interleukin 1 receptor antagonist, IL-6, and IL-10 and the chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and monocyte chemoattractant protein 1 (MCP-1) following stimulation with peptidoglycan (TLR2) and R848 (TLR7/8). BCG-vaccinated infants also had decreased MCP-1 responses following stimulation with heterologous pathogens. Sex and maternal BCG vaccination status interacted with neonatal BCG vaccination.
Conclusions
Neonatal BCG vaccination influences cytokine responses to TLR ligands and heterologous pathogens. This effect is characterized by decreased antiinflammatory cytokine and chemokine responses in the context of higher levels of IL-6 in unstimulated samples. This supports the hypothesis that BCG vaccination modulates the innate immune system. Further research is warranted to determine whether there is an association between these findings and the beneficial nonspecific (heterologous) effects of BCG vaccine on all-cause mortality.
Aim
We investigated the effect of early‐life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first ...year of life.
Methods
One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured in 398 healthy infants. The geometric mean concentration (GMC) of antibodies (adjusted for effect modifiers with multiple linear regression) and the seroprotection rate for each vaccine were compared for each early‐life factor.
Results
Sex had an influence on GMCs. Antibody concentrations were significantly lower at 7 months of age in females for tetanus and filamentous haemagglutinin and at 13 months of age for pertactin. In contrast, at 13 months of age, antibody concentrations were significantly higher in females for polio type 3, pneumococcal serotype 6A and measles. Sex did not have an influence on seroprotection rates. Delivery mode, feeding method and antibiotic exposure did not exert a substantial influence on vaccine antibody concentrations.
Conclusion
There is a difference between males and females in the humoral response to routine vaccinations in the first year of life.
Background
Bacille Calmette‐Guérin (BCG) vaccine could play a role in counteracting the rising prevalence of atopic diseases, through its beneficial off‐target effects. We aimed to determine whether ...neonatal BCG vaccination reduces the incidence of eczema in infants.
Methods
Randomized controlled trial with 1272 infants allocated to receive BCG‐Denmark or no BCG at birth. The primary outcome was the 12‐month incidence of eczema based on 3‐monthly questionnaires. Eczema was also assessed at a 12‐month clinic visit. ClinicalTrial.gov: NCT01906853.
Results
The 12‐month eczema incidence was 32.2% in the BCG group compared with 36.6% in the control group (adjusted risk difference (aRD) −4.3%, 95% CI −9.9% to 1.3%, multiple imputation model). In addition, comparing infants in the BCG group with the control group, 15.7% vs. 19.2% had eczema lesions at the 12‐month visit (aRD −3.5%, 95% CI −8.0% to 1.0%); 35.7% vs. 39.0% reported using topical steroids (aRD −3.3, 95% CI −9.2 to 2.7); and 7.3% vs. 10.2% had severe eczema scores (aRD −3.0%, 95% CI −8.8% to 2.7%). In 344 high‐risk infants (two atopic parents), the 12‐month eczema incidence was 35.3% in the BCG group compared with 46.8% in the control group (aRD −11.5%, 95% CI −21.9% to −1.2%; number needed to treat 8.7, 95% CI 4.6 to 83.3).
Conclusion
There is insufficient evidence to recommend neonatal BCG vaccination in all infants for the prevention of eczema in the first year of life; however, a modest beneficial effect was observed among high‐risk infants. A single dose of BCG‐Denmark soon after birth could reduce the incidence of eczema in infants with two atopic parents.
Prevention of infant eczema by neonatal bacille Calmette‐Guérin vaccination: the MIS BAIR randomised controlled trial. In this RCT, a modest reduction in the 12‐month cumulative incidence of eczema was observed in infants vaccinated with BCG‐Denmark at birth compared with non‐BCG‐vaccinated infants in the control group. This reduction was greater in high‐risk infants (two atopic parents). The risk difference in high‐risk infants was ‐11.5% (95% CI −21.9% to −1.2%) with a NNT of 8.7 (95% CI 4.6 to 83.3).
Abbreviations: BCG, bacille Calmette‐Guérin; CI, confidence interval; NNT, number needed to treat; RCT, randomised controlled trial.
Abstract
Background
Bacille Calmette-Guérin (BCG) vaccination has beneficial off-target effects that may include protecting against non-mycobacterial infectious diseases. We aimed to determine ...whether neonatal BCG vaccination reduces lower respiratory tract infections (LRTI) in infants in the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) trial.
Methods
In this investigator-blinded trial, neonates in Australia were randomized to receive BCG-Denmark vaccination or no BCG at birth. Episodes of LRTI were determined by symptoms reported in parent-completed, 3-month questionnaires over the first year of life. Data were analyzed by intention-to-treat using binary regression.
Results
A total of 1272 neonates were randomized to the BCG vaccination (n = 637) or control (n = 635) group. The proportion of participants with an episode of LRTI in the first year of life among BCG-vaccinated infants was 54.8% compared to 58.0% in the control group, resulting in a risk difference of −3.2 (95% confidence interval, −9.0 to 2.6) after multiple imputation. There was no interaction observed between the primary outcome and sex, maternal BCG, or the other prespecified effect modifiers.
Conclusions
Based on the findings of this trial, there is insufficient evidence to support the use of neonatal BCG vaccination to prevent LRTI in the first year of life in high-income settings.
In an RCT in a high-income setting (with neonatal HepB vaccination), infants randomized to neonatal BCG vaccination had a small, −3.2 (95% CI, −9.0 to 2.6), reduction in the risk of respiratory tract infection in the first year of life.
Aberrant global DNA methylation status is a known biomarker for increased disease risk, especially cancer. There is little published data on the association between toxic and essential metal mixtures ...and global DNA methylation in electronic waste (e-waste) workers. We aimed to establish the association between toxic and essential metals in blood and the effect of their interactions on global DNA methylation among e-waste recyclers and a reference group in Ghana. We used ICP-MS to measure the level of five metals (Se, Zn, Mn, Cd, and Pb) in the blood of 100 e-waste workers and 51 controls. We quantified blood DNA methylation levels of LINE-1 as an indicator of global DNA methylation. Cd, Mn, and Se levels were significantly higher in the reference group than in e-waste workers. Only Pb was significantly higher in the e-waste workers compared to the controls. Our linear regression analysis results showed a significant inverse association between Zn and LINE-1 DNA methylation (
β
Zn
= − 0.912; 95% CI, − 1.512, − 0.306;
p
= 0.003) which corresponds to a 0.009 decrease in %LINE-1 methylation (95% CI, − 0.015, − 0.003;
p
= 0.003) for a 1% increase in Zn concentration. Potential interactions between Cd and Zn on global DNA methylation were observed. In summary, co-exposure to toxic and essential metals is associated with global (LINE-1) DNA methylation.
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