Persistence of 'wet wipes' in beach sand: An unrecognised reservoir for localised E. coli contamination.

The flushing of wet wipes down toilets leads to blockages of sewerage systems. This, together with unregulated sewage discharge, often results in increasing numbers of wet wipes washing up onto beaches. However, it is unclear how long wet wipes can persist on the beach and whether they pose a prolonged public health risk if contaminated by E. coli. In this mesocosm study, three types of wet wipes (plastic containing, and home and commercially compostable) colonised with E. coli were buried in beach sand and their degradation, tensile strength, and concentration of E. coli was quantified over 15 weeks. Wet wipes containing plastic remained largely intact for 15 weeks, whilst both compostable wet wipes fragmented and degraded. Importantly, E. coli persisted on all three wet wipe types, representing localised reservoirs of E. coli in the sand, which could present a human health risk at the beach.

A Multisite Investigation of Areas for Improvement in COVID-19 Surge Capacity Management.

The congressionally authorized National Disaster Medical System Pilot Program was created in December 2019 to strengthen the medical surge capability, capacity, and interoperability of affiliated healthcare facilities in 5 regions across the United States. The COVID-19 pandemic provided an unprecedented opportunity to learn how participating healthcare facilities handled medical surge events during an active public health emergency. We applied a modified version of the Barbisch and Koenig 4-S framework (staff, stuff, space, systems) to analyze COVID-19 surge management practices implemented by healthcare stakeholders at 5 pilot sites. In total, 32 notable practices were identified to increase surge capacity during the COVID-19 pandemic that have potential applications for other healthcare facilities. We found that systems was the most prevalent domain of surge capacity among the identified practices. Systems and staff were discussed across all 5 pilot sites and were the 2 domains co-occurring most often within each surge management practice. These results can inform strategies for scaling up and optimizing medical surge capability, capacity, and interoperability of healthcare facilities nationwide. This study also specifies areas of surge capacity worthy of strategic focus in the pilot's planning and implementation efforts while more broadly informing the US healthcare system's response to future large-scale, medical surge events.

Clinically important E. coli strains can persist, and retain their pathogenicity, on environmental plastic and fabric waste.

Plastic waste is ubiquitous in the environment and there are increasing reports of such waste being colonised by human pathogens. However, the ability of pathogens to persist on plastics for long periods, and the risk that they pose to human health, is unknown. Here, under simulated environmental conditions, we aimed to determine if pathogenic bacteria can retain their virulence following a prolonged period on plastic. Using antibiotic selection and luciferase expression for quantification, we show that clinically important strains of E. coli can survive on plastic for at least 28-days. Importantly, these pathogens also retained their virulence (determined by using a Galleria mellonella model as a surrogate for human infection) and in some cases, had enhanced virulence following their recovery from the plastisphere. This indicates that plastics in the environment can act as reservoirs for human pathogens and could facilitate their persistence for extended periods of time. Most importantly human pathogens in the plastisphere are capable of retaining their pathogenicity. Pathogens colonising environmental plastic waste therefore pose a heightened public health risk, particularly in areas where people are exposed to pollution.

From wastewater discharge to the beach: Survival of human pathogens bound to microplastics during transfer through the freshwater-marine continuum.

Large quantities of microplastics are regularly discharged from wastewater treatment plants (WWTPs) into the aquatic environment. Once released, these plastics can rapidly become colonised by microbial biofilm, forming distinct plastisphere communities which may include potential pathogens. We hypothesised that the protective environment afforded by the plastisphere would facilitate the survival of potential pathogens during transitions between downstream environmental matrices and thus increase persistence and the potential for environmental dissemination of pathogens. The survival of Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa colonising polyethylene or glass particles has been quantified in mesocosm incubation experiments designed to simulate, (1) the direct release of microplastics from WWTPs into freshwater and seawater environments; and (2) the movement of microplastics downstream following discharge from the WWTP through the river-estuary-marine-beach continuum. Culturable E. coli, E. faecalis and P. aeruginosa were successfully able to survive and persist on particles whether they remained in one environmental matrix or transitioned between different environmental matrices. All three bacteria were still detectable on both microplastic and glass particles after 25 days, with higher concentrations on microplastic compared to glass particles; however, there were no differences in bacterial die-off rates between the two materials. This potential for environmental survival of pathogens in the plastisphere could facilitate their transition into places where human exposure is greater (e.g., bathing waters and beach environments). Therefore, risks associated with pathogen-microplastic co-pollutants in the environment, emphasises the urgency for updated regulations on wastewater discharge and the management of microplastic generation and release.

Sewage-associated plastic waste washed up on beaches can act as a reservoir for faecal bacteria, potential human pathogens, and genes for antimicrobial resistance.

Sewage-associated plastic wastes, such as wet wipes and cotton bud sticks, commonly wash up on beaches; however, it is unclear whether this represents a public health risk. In this study, sewage-associated plastic waste, and naturally occurring substrates (seaweed and sand), were collected from ten beaches along the Firth of Forth estuary (Scotland, UK) and analysed using selective media for the faecal indicator organisms (FIOs) E. coli and intestinal enterococci (IE), and potential human pathogens (Vibrio spp.). Minimum inhibitory concentration (MIC) analysis was used to determine antibiotic resistance in selected strains. FIOs and Vibrio were more often associated with wet wipes and cotton bud sticks than with seaweed, and there was evidence of resistance to several antibiotics. This work demonstrates that plastics associated with sewage pollution can facilitate the survival and dissemination of FIOs and Vibrio and thus, could present an as yet unquantified potential risk to human health at the beach.

Quantifying the importance of plastic pollution for the dissemination of human pathogens: The challenges of choosing an appropriate 'control' material.

Discarded plastic wastes in the environment are serious challenges for sustainable waste management and for the delivery of environmental and public health. Plastics in the environment become rapidly colonised by microbial biofilm, and importantly this so-called 'plastisphere' can also support, or even enrich human pathogens. The plastisphere provides a protective environment and could facilitate the increased survival, transport and dissemination of human pathogens and thus increase the likelihood of pathogens coming into contact with humans, e.g., through direct exposure at beaches or bathing waters. However, much of our understanding about the relative risks associated with human pathogens colonising environmental plastic pollution has been inferred from taxonomic identification of pathogens in the plastisphere, or laboratory experiments on the relative behaviour of plastics colonised by human pathogens. There is, therefore, a pressing need to understand whether plastics play a greater role in promoting the survival and dispersal of human pathogens within the environment compared to other substrates (either natural materials or other pollutants). In this paper, we consider all published studies that have detected human pathogenic bacteria on the surfaces of environmental plastic pollution and critically discuss the challenges of selecting an appropriate control material for plastisphere experiments. Whilst it is clear there is no 'perfect' control material for all plastisphere studies, understanding the context-specific role plastics play compared to other substrates for transferring human pathogens through the environment is important for quantifying the potential risk that colonised plastic pollution may have for environmental and public health.

Loss of Th22 cells is associated with increased immune activation and IDO-1 activity in HIV-1 infection.

BACKGROUND: Immune activation plays a key role in the immunopathogenesis of HIV-1 infection. Microbial translocation, secondary to loss of epithelial integrity and mucosal immune deficiency, is believed to contribute to systemic immune activation. Interleukin 22 maintains intestinal epithelial barrier integrity and stimulates the secretion of antimicrobial peptides that limit bacterial dissemination and intestinal inflammation. Interleukin 22 is secreted by CD4 T-helper (Th)22 cells independently of interleukin 17A and interferon γ. Th22 cells are characterized by the expression of chemokine receptors (CCR)4, CCR6, and CCR10. METHODS: We analyzed the frequency of Th22, Th17, Th1, and CD4 T regulatory (Treg) cells, markers of immune activation (expression of CD38 on CD8 T cells, neopterin, soluble CD14), microbial translocation (lipopolysaccharide-binding protein and 16s ribosomal DNA), and indoleamine 2,3-dioxygenase 1 activity in peripheral blood of antiretroviral therapy (ART)-experienced and ART-naive HIV-1-infected patients and healthy controls. RESULTS: We showed a significant reduction in the frequency of Th22 cells in HIV ART-naive patients compared with the healthy controls and HIV ART-experienced patients. We observed a shift away from Th22 and Th17 to Treg cells, which was partially reversed by effective ART. Markers of immune activation negatively correlated with Th22 and Th17 proportions, and with Th22:Treg and Th17:Treg ratios in ART-naive patients. Increased indoleamine 2,3-dioxygenase 1 activity negatively correlated with Th22:Treg and Th17:Treg ratios in the ART-naive group. CONCLUSIONS: Loss of Th22 cells and disruption in the balance of Th22 and Treg cells may contribute toward systemic immune activation and mucosal immune deficiency during HIV-1 infection.

CD8+/CD161++ mucosal-associated invariant T-cell levels in the colon are restored on long-term antiretroviral therapy and correlate with CD8+ T-cell immune activation.

Mucosal-associated invariant T (MAIT) cells are tissue-homing T cells recently implicated in HIV pathogenesis. We found that the proportion of MAIT cell in blood and colon of HIV+ patients are reduced in untreated infection. Antiretroviral therapy restored colonic but not blood MAIT cell percentages. We observed a negative correlation between colonic MAIT cells and T-cell activation in blood and suggest mucosal MAIT cell depletion may contribute to systemic immune activation in HIV infection.

Reduced T(H)1/T(H)17 CD4 T-cell numbers are associated with impaired purified protein derivative-specific cytokine responses in patients with HIV-1 infection.

BACKGROUND: In HIV-1-infected patients impaired IFN-γ responses to purified protein derivative (PPD) are associated with an increased risk of active tuberculosis. Tuberculosis antigen-specific cells are found in the T(H)1/T(H)17 subset of CD4 T cells, which support HIV-1 replication. Selective loss of T(H)1/T(H)17 cells in patients with HIV-1 infection might contribute to reduced tuberculosis-induced immune responses and an increased susceptibility to active tuberculosis. OBJECTIVES: We sought to investigate the association between T(H)1/T(H)17 cells and PPD-specific cytokine responses in HIV-1-infected patients. METHODS: A cross-sectional study was performed on healthy control subjects, HIV-1-infected patients receiving successful antiretroviral therapy (ART(+)), and ART-naive HIV-1-infected patients (ART(-)). All patients studied had evidence of BCG vaccination. Four discrete CD4 T-cell subsets were assessed by flow cytometry: T(H)1/T(H)17 cells (CXCR3(+)CCR6(+)CCR4(-)), T(H)1 cells (CXCR3(+)CCR6(-)CCR4(-)), T(H)17 cells (CXCR3(-)CCR6(+)CCR4(+)), and T(H)2 cells (CXCR3(-)CCR6(-)CCR4(+)). IFN-γ and IL-2 PPD-specific cytokine responses were assessed in PBMCs by using the enzyme-linked immunospot assay. RESULTS: Twenty-nine healthy control subjects, 34 ART(+) patients, and 26 ART(-) patients were recruited. The number and frequency of T(H)1/T(H)17 and T(H)1/T(H)17 CCR5(+) CD4 T cells were significantly reduced in HIV-1-infected patients. IFN-γ and IL-2 PPD responses were significantly lower in ART(-) patients and were partially reconstituted with successful ART. Loss of T(H)1/T(H)17 CCR5(+) cells was associated with reduced IFN-γ and IL-2 PPD responses. CONCLUSIONS: Selective loss of T(H)1/T(H)17 cells may be a risk factor for the development of active tuberculosis in patients with HIV-1 infection and might be a useful biomarker in the development of tuberculosis vaccines.

Quantitative validation and comparison of multiplex cytokine kits.

The focus of biomarker studies is shifting toward deciphering patterns of biomolecules as they provide a more comprehensive depiction of disease than individual biomarkers. Multiplexing technologies are crucial in deciphering such patterns, but it is essential that they are validated for reproducibility and precision to ensure accurate protein identification. Here the authors examine such properties in Cytokine Bead Array (CBA) and Luminex kits and compare concentration measurements to those obtained using enzyme-linked immunosorbent assay (ELISA). Luminex kits were found to be highly reproducible and reliable; however, CBA kits were not due to aberrant standards. Absolute cytokine concentrations were dependent on the detection kit, but correlations with ELISA were good for all technologies.

Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease state, characterised by progressive airflow limitation that is not fully reversible. Although COPD is primarily a disease of the lungs there is now an appreciation that many of the manifestations of disease are outside the lung, leading to the notion that COPD is a systemic disease. Currently, diagnosis of COPD relies on largely descriptive measures to enable classification, such as symptoms and lung function. Here the limitations of existing diagnostic strategies of COPD are discussed and systems biology approaches to diagnosis that build upon current molecular knowledge of the disease are described. These approaches rely on new 'label-free' sensing technologies, such as high-throughput surface plasmon resonance (SPR), that we also describe.