RESUMEN
Cerebrospinal fluid (CSF) is an aqueous solution responsible for nutrient delivery and waste removal for the central nervous system (CNS). The three-layer meningeal coverings of the CNS support CSF flow. Peripheral nerves have an analogous three-layer covering consisting of the epineurium, perineurium, and endoneurium. Peripheral axons, located in the inner endoneurium, are bathed in "endoneurial fluid" similar to CSF but of undefined origin. CSF flow in the peripheral nervous system has not been demonstrated. Here we show CSF flow extends beyond the CNS to peripheral nerves in a contiguous flowing system. Utilizing gold nanoparticles, we identified that CSF is continuous with the endoneurial fluid and reveal the endoneurial space as the likely site of CSF flow in the periphery. Nanogold distribution along entire peripheral nerves and within their axoplasm suggests CSF plays a role in nutrient delivery and waste clearance, fundamental aspects of peripheral nerve health and disease. One Sentence Summary: Cerebrospinal fluid unites the nervous system by extending beyond the central nervous system into peripheral nerves.
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AIMS: Contaminated laundry can spread infections. However, current directives for safe laundering are limited to healthcare settings and not reflective of domestic conditions. We aimed to use quantitative microbial risk assessment to evaluate household laundering practices (e.g., detergent selection, washing and drying temperatures, and sanitizer use) relative to log10 reductions in pathogens and infection risks during the clothes sorting, washer/dryer loading, folding and storing steps. METHODS AND RESULTS: Using published data, we characterized laundry infection risks for respiratory and enteric pathogens relative to a single user contact scenario and a 1.0 × 10-6 acceptable risk threshold. For respiratory pathogens, risks following cold water wash temperatures (e.g. median 14.4â) and standard detergents ranged from 2.2 × 10-5 to 2.2 × 10-7 . Use of advanced, enzymatic detergents reduced risks to 8.6 × 10-8 and 2.2 × 10-11 respectively. For enteric pathogens, however, hot water, advanced detergents, sanitizing agents and drying are needed to reach risk targets. SIGNIFICANCE AND IMPACT OF THE STUDY: Conclusions provide guidance for household laundry practices to achieve targeted risk reductions, given a single user contact scenario. A key finding was that hand hygiene implemented at critical control points in the laundering process was the most significant driver of infection prevention, additionally reducing infection risks by up to 6 log10 .
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Lavandería , Textiles , DetergentesRESUMEN
We used a quantitative microbial risk assessment approach to relate log10 disinfection reductions of SARS-CoV-2 bioburden to COVID-19 infection risks. Under low viral bioburden, minimal log10 reductions may be needed to reduce infection risks for a single hand-to-fomite touch to levels lower than 1:1,000,000, as a risk comparison point. For higher viral bioburden conditions, log10 reductions of more than 2 may be needed to achieve median infection risks of less than 1:1,000,000.
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COVID-19 , Fómites , Desinfección , Humanos , Conducta de Reducción del Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: The growing understanding of the importance of a healthy microbiome is challenging traditional thinking that resulted in the general acceptance of the Germ Theory of Disease. We propose a more encompassing Microbial Theory of Health that will have implications for the way that we address our relationship with microbes, including hygiene policy and community-based infection control practices. METHODS: This paper considers theories over the last 30 years that have impacted hygiene policy and consumer practice, from the Germ Theory of Disease and the Hygiene Hypothesis, to the Microbial Theory of Health, including the concept of Bidirectional Hygiene. Here we present a high-level review of the literature on pathogen transmission and the cycle of infection in the home and everyday settings. RESULTS: Targeted hygiene is an evidence-based hygiene policy that is employed to prevent transmission of pathogens and the transmission of infectious diseases through targeting only sites, surfaces, and practices that are considered high risk for pathogen transmission. Targeted hygiene also discourages the indiscriminate use of broad-spectrum microbicides for lower-risk activities and surfaces. CONCLUSIONS: The Microbial Theory of Health, including age-appropriate and health-appropriate hygiene practices for home and everyday life, should usher in a new era in which pathogen reduction can be accomplished without indiscriminate elimination of potentially beneficial microbes from the human and environmental microbiomes.
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Teoría del Gérmen de la Enfermedad , Microbiota , Humanos , Higiene , Control de InfeccionesRESUMEN
Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of health care facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country's Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in health care settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies, and health care professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR.
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Antibacterianos/efectos adversos , Farmacorresistencia Bacteriana , Salud Global/normas , Higiene/normas , Uso Excesivo de Medicamentos Recetados/prevención & control , Infecciones Bacterianas/tratamiento farmacológico , Humanos , Saneamiento/normasRESUMEN
AIMS: To review the burden of allergic and infectious diseases and the evidence for a link to microbial exposure, the human microbiome and immune system, and to assess whether we could develop lifestyles which reconnect us with exposures which could reduce the risk of allergic disease while also protecting against infectious disease. METHODS: Using methodology based on the Delphi technique, six experts in infectious and allergic disease were surveyed to allow for elicitation of group judgement and consensus view on issues pertinent to the aim. RESULTS: Key themes emerged where evidence shows that interaction with microbes that inhabit the natural environment and human microbiome plays an essential role in immune regulation. Changes in lifestyle and environmental exposure, rapid urbanisation, altered diet and antibiotic use have had profound effects on the human microbiome, leading to failure of immunotolerance and increased risk of allergic disease. Although evidence supports the concept of immune regulation driven by microbe-host interactions, the term 'hygiene hypothesis' is a misleading misnomer. There is no good evidence that hygiene, as the public understands, is responsible for the clinically relevant changes to microbial exposures. CONCLUSION: Evidence suggests a combination of strategies, including natural childbirth, breast feeding, increased social exposure through sport, other outdoor activities, less time spent indoors, diet and appropriate antibiotic use, may help restore the microbiome and perhaps reduce risks of allergic disease. Preventive efforts must focus on early life. The term 'hygiene hypothesis' must be abandoned. Promotion of a risk assessment approach (targeted hygiene) provides a framework for maximising protection against pathogen exposure while allowing spread of essential microbes between family members. To build on these findings, we must change public, public health and professional perceptions about the microbiome and about hygiene. We need to restore public understanding of hygiene as a means to prevent infectious disease.
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Exposición a Riesgos Ambientales , Hipótesis de la Higiene , Hipersensibilidad , Microbiota , Técnica Delphi , Femenino , Humanos , Higiene , MasculinoRESUMEN
Many PCR-based methods for microbial source tracking (MST) have been developed and validated within individual research laboratories. Inter-laboratory validation of these methods, however, has been minimal, and the effects of protocol standardization regimes have not been thoroughly evaluated. Knowledge of factors influencing PCR in different laboratories is vital to future technology transfer for use of MST methods as a tool for water quality management. In this study, a blinded set of 64 filters (containing 32 duplicate samples generated from 12 composite fecal sources) were analyzed by three to five core laboratories with a suite of PCR-based methods utilizing standardized reagents and protocols. Repeatability (intra-laboratory variability) and reproducibility (inter-laboratory variability) of observed results were assessed. When standardized methodologies were used, intra- and inter-laboratory %CVs were generally low (median %CV 0.1-3.3% and 1.9-7.1%, respectively) and comparable to those observed in similar inter-laboratory validation studies performed on other methods of quantifying fecal indicator bacteria (FIB) in environmental samples. ANOVA of %CV values found three human-associated methods (BsteriF1, BacHum, and HF183Taqman) to be similarly reproducible (p > 0.05) and significantly more reproducible (p < 0.05) than HumM2. This was attributed to the increased variability associated with low target concentrations detected by HumM2 (approximately 1-2 log10copies/filter lower) compared to other human-associated methods. Cow-associated methods (BacCow and CowM2) were similarly reproducible (p > 0.05). When using standardized protocols, variance component analysis indicated sample type (fecal source and concentration) to be the major contributor to total variability with that from replicate filters and inter-laboratory analysis to be within the same order of magnitude but larger than inherent intra-laboratory variability. However, when reagents and protocols were not standardized, inter-laboratory %CV generally increased with a corresponding decline in reproducibility. Overall, these findings verify the repeatability and reproducibility of these MST methods and highlight the need for standardization of protocols and consumables prior to implementation of larger scale MST studies involving multiple laboratories.
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Bacterias/clasificación , Monitoreo del Ambiente/métodos , Heces/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Microbiología del Agua/normas , Contaminación del Agua/análisis , Bacterias/genética , Bacterias/metabolismo , California , Reproducibilidad de los ResultadosRESUMEN
Terminal restriction fragment length polymorphism (TRFLP) is an attractive community analysis method for microbial source tracking (MST) because it is accessible, relatively inexpensive, and can discern multiple fecal sources simultaneously. A new Bacteroidales TRFLP (Bac-TRFLP) method was developed and its source identification performance was evaluated by itself, in comparison to, and in combination with an existing universal bacterial TRFLP method in two laboratories. Sixty-four blind samples from 12 fecal sources (sewage, septage, human, dog, horse, cow, deer, pig, chicken, goose, pigeon, and gull) were used for evaluation. Bac- and Univ-TRFLP exhibited similarly high overall correct identification (>88% and >89%, respectively), excellent specificity regardless of fecal sources, variable sensitivity depending on the source, and stable performance across two laboratories. Compared to Univ-TRFLP, Bac-TRFLP had better sensitivity and specificity with horse, cow, and pig fecal sources but was not suited for certain avian sources such as goose, gull, and pigeon. Combining the general and more targeted TRFLP methods (Univ&Bac-TRFLP) achieved higher overall correct identification (>92%), higher sensitivity and specificity metrics, and higher reproducibility between laboratories. Our results suggest that the Bac-TRFLP and Univ&Bac-TRFLP methods are promising additions to the MST toolbox and warrant further evaluation and utilization in field MST applications.
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Bacteroidetes/clasificación , Bacteroidetes/genética , Monitoreo del Ambiente/métodos , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Aguas Residuales/microbiología , Animales , Bacteroidetes/aislamiento & purificación , Bacteroidetes/metabolismo , Aves/microbiología , ADN Bacteriano/clasificación , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Heces/microbiología , Humanos , Mamíferos/microbiología , ARN Ribosómico 16S/clasificación , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Sensibilidad y EspecificidadRESUMEN
Home and everyday life hygiene is a key part of the public health strategy to reduce infectious disease, but an effective code of practice is required. This short review summarizes the basic scientific principles of a risk-based approach to home hygiene where hygiene procedures are applied at critical points at appropriate times. It suggests that, although detergent-based cleaning can be used to break the chain of infection, in some cases an antimicrobial agent is required.
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Antiinfecciosos/farmacología , Detergentes/farmacología , Higiene de las Manos/métodos , Control de Infecciones/métodos , Artículos Domésticos , Humanos , Control de Infecciones/normas , Medición de RiesgoRESUMEN
Inhalational anthrax is a rare but potentially fatal infection in man. The common marmoset (Callithrix jacchus) was evaluated as a small non-human primate (NHP) model of inhalational anthrax infection, as an alternative to larger NHP species. The marmoset was found to be susceptible to inhalational exposure to Bacillus anthracis Ames strain. The pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. The calculated LD(50) for B. anthracis Ames strain in the marmoset was 1.47 x 10(3) colony-forming units, compared with a published LD(50) of 5.5 x 10(4) spores in the rhesus macaque and 4.13 x 10(3) spores in the cynomolgus macaque. This suggests that the common marmoset is an appropriate alternative NHP and will be used for the evaluation of medical countermeasures against respiratory anthrax infection.
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Carbunco/patología , Bacillus anthracis/patogenicidad , Modelos Animales de Enfermedad , Infecciones del Sistema Respiratorio/patología , Aerosoles , Animales , Carbunco/microbiología , Bacillus anthracis/aislamiento & purificación , Peso Corporal , Callithrix , Recuento de Colonia Microbiana , Femenino , Exposición por Inhalación , Dosificación Letal Mediana , Masculino , Infecciones del Sistema Respiratorio/microbiología , VirulenciaRESUMEN
Foodborne illnesses impose a substantial economic and quality-of-life burden on society by way of acute morbidity and chronic sequelae. We developed an economic model to evaluate the potential cost-effectiveness of a disinfection program that targets high-risk food preparation activities in household kitchens. For the United States, Canada, and the United Kingdom, we used published literature and expert opinion to estimate the cost of the program (excluding the educational component); the number of cases of Salmonella, Campylobacter, and Escherichia coli O157:H7 infections prevented; and the economic and quality-of-life outcomes. In our primary analysis, the model estimated that approximately 80,000 infections could be prevented annually in U.S. households, resulting in 138 million dollars in direct medical cost savings (e.g., physician office visits and hospitalizations avoided), 15,845 quality-adjusted life-years (QALYs) gained, 788 million dollars in program costs, and a favorable cost-effectiveness ratio of 41,021 dollars/QALY gained. Results were similar for households in Canada and the United Kingdom (21,950 dollars Can/QALY gained and 86,341 pounds sterling/QALY gained, respectively). When we evaluated implementing the program only in U.S. households with high-risk members (those less than 5 years of age, greater than 65 years of age, or immunocompromised), the cost-effectiveness ratio was more favorable (10,163 dollars/QALY gained). Results were similar for high-risk households in Canada and the United Kingdom (1,915 dollars Can/QALY gained and 28,158 pounds sterling/QALY gained, respectively). Implementing a targeted disinfection program in household kitchens in the United States, Canada, and the United Kingdom appears to be a cost-effective strategy, falling within the range generally considered to warrant adoption and diffusion (<100,000 dollars/QALY gained).