Pathogens and Immunity最新文献

Background: Murine experimental cerebral malaria studies suggest both protective and deleterious central nervous system effects from alterations in the interleukin-33 (IL-33)/ST2 pathway.

Methods: We assessed whether soluble ST2 (sST2) was associated with neuronal injury or cognitive impairment in a cohort of Ugandan children with cerebral malaria (CM, n=224) or severe malarial anemia (SMA, n=193).

Results: Plasma concentrations of sST2 were higher in children with CM than in children with SMA or in asymptomatic community children. Cerebrospinal fluid (CSF) sST2 levels were elevated in children with CM compared with North American children. Elevated plasma and CSF ST2 levels in children with CM correlated with increased endothelial activation and increased plasma and CSF levels of tau, a marker of neuronal injury. In children with CM who were ≥5 years of age at the time of their malaria episode, but not in children <5 years of age, elevated risk factor-adjusted plasma levels of sST2 were associated with worse scores for overall cognitive ability and attention over a 2-year follow-up.

Conclusions: The study findings suggest that sST2 may contribute to neuronal injury and long-term neurocognitive impairment in older children with CM.

Background: Clinical studies suggest that doxycycline poses a low risk for promotion of Clostridioides difficile infection, but the microbiologic explanation for this finding is unclear.

Methods: Mice treated with oral doxycycline, oral azithromycin, subcutaneous ceftriaxone, doxycycline plus ceftriaxone, or azithromycin plus ceftriaxone were challenged with 10⁴ colony-forming units of 2 different C. difficile strains on day 2 of 5 of treatment. The concentration of C. difficile was measured in stool 2 and 5 days after challenge. The impact of the treatments on the microbiota was assessed by sequencing.

Results: Doxycycline and azithromycin treatment did not promote colonization by either C. difficile strain in comparison to saline controls. Doxycycline treatment significantly reduced ceftriaxone-induced overgrowth of a C. difficile strain with doxycycline minimum-inhibitory concentration (MIC) of 0.06 µg/mL (P<0.01) but not a strain with doxycycline MIC of 48 µg/mL (P>0.05); azithromycin treatment did not reduce ceftriaxone-induced overgrowth of either strain. 16S rRNA amplicon sequencing revealed significantly lower bacterial diversity in the stool of ceftriaxone-treated mice, in comparison to doxycycline-treated and azithromycin-treated mice.

Conclusions: These findings suggest that doxycycline may have a low propensity to promote C. difficile colonization because it causes relatively limited alteration of the indigenous microbiota that provide colonization resistance and because it provides inhibitory activity against some C. difficile strains.

Background: Ultraviolet light in the UV-C band is also known as germicidal radiation, and it is widely used for decontamination and disinfection of environments, water, and food. The ultraviolet source transfers electromagnetic energy from a mercury arc lamp to an organism's genetic material. When UV radiation penetrates the cell wall of an organism, it destroys the cell's ability to reproduce, through a physical and not chemical process. Thus, the objective of this study was to evaluate the antimicrobial potential of a new UV-C generating device (Asepsis) against clinically important microorganisms that may be present in beauty centers.

Methods: We present here a set of tests performed on tools easy to find in beauty salons (hair-brushes, nail pliers, makeup brushes, and, due to the recent COVID-19 pandemic, face mask samples). They were individually contaminated with bacteria (Pseudomonas aeruginosa, Staphylococcus aureus), fungi (Microsporum canis, Trichophyton rubrum, Candida albicans, Malassezia furfur), and the Chikungunya virus. Different times of exposure were evaluated (1, 3, and 5 minutes).

Results: There was notable reduction in the microbial load in every test, in comparison with control groups. Best results were observed on face mask samples, while the makeup brush showed less reduction, even with longer periods of exposure.

Conclusions: Beauty salons present a risk of infections due to microbial exposure. The device tested can efficiently inactivate, in a short time, microorganisms contaminating most tools found in this setting. The device also showed promising results against enveloped virus.

Background: Travel poses a risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. Poorly ventilated indoor settings pose a particularly high risk for transmission.

Methods: We used carbon dioxide measurements to assess adequacy of ventilation during 5 trips that included air travel. During selected parts of each trip that involved indoor settings, we monitored carbon dioxide levels every 1 minute and recorded peak levels and the number of people present. Carbon dioxide readings above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation.

Results: Carbon dioxide levels remained below 800 ppm during train rides to and from the airport and inside airports except in a crowded boarding area with ~300 people present. Carbon dioxide levels exceeded 800 ppm inside the airplanes, but the air was filtered with high efficiency particulate air filters. Carbon dioxide levels remained below 800 ppm in common areas of a hotel but exceeded 800 ppm in a hotel room with 2 to 3 occupants and in a fitness center with 3 people exercising. In restaurants, carbon dioxide levels increased above 800 ppm during crowded conditions with 24 or more people present and 75% or more seat occupancy.

Conclusion: Our results suggest that ventilation may be sufficient to minimize the risk for airborne transmission in many situations during travel. However, ventilation may be suboptimal in some areas or under certain conditions such as in hotel rooms or when restaurants, fitness centers, or airplane boarding areas are crowded. There is a need for larger scale studies to assess the quality of ventilation in a wide range of community settings.

Background: Uropathogenic Escherichia coli (UPEC) infections are common and when they disseminate can be of high morbidity.

Methods: We studied the effects of UPEC infection using single cell RNA sequencing (scRNAseq) in zebrafish. Bulk RNA sequencing has historically been used to evaluate gene expression patterns, but scRNAseq allows gene expression to be evaluated at the single cell level and is optimal for evaluating heterogeneity within cell types and rare cell types. Zebrafish cohorts were injected with either saline or UPEC, and scRNAseq and canonical pathway analyses were performed.

Results: Canonical pathway analysis of scRNAseq data provided key information regarding innate immune pathways in the cells determined to be thymus cells, ionocytes, macrophages/monocytes, and pronephros cells. Pathways activated in thymus cells included interleukin 6 (IL-6) signaling and production of reactive oxygen species. Fc receptor-mediated phagocytosis was a leading canonical pathway in the pronephros and macrophages. Genes that were downregulated in UPEC vs saline exposed embryos involved the cellular response to the Gram-negative endotoxin lipopolysaccharide (LPS) and included Forkhead Box O1a (Foxo1a), Tribbles Pseudokinase 3 (Trib3), Arginase 2 (Arg2) and Polo Like Kinase 3 (Plk3).

Conclusions: Because 4-day post fertilization zebrafish embryos only have innate immune systems, the scRNAseq provides insights into pathways and genes that cell types utilize in the bacterial response. Based on our analysis, we have identified genes and pathways that might serve as genetic targets for treatment and further investigation in UPEC infections at the single cell level.

Background: Poorly ventilated enclosed spaces pose a risk for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. Limited information is available on ventilation in motor vehicles under differing driving conditions.

Methods: We conducted carbon dioxide measurements to assess ventilation in motor vehicles under varying driving conditions with 2 to 3 vehicle occupants. During routine driving, carbon dioxide produced by the breathing of vehicle occupants was measured inside 5 cars and a van under a variety of driving conditions with or without the ventilation fan on and with windows open or closed. Carbon dioxide readings above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation.

Results: Carbon dioxide levels remained below 800 ppm in all vehicles if the ventilation fan was on and/or the windows were open while parked or during city or highway driving. With the ventilation system set on non-recirculation mode, carbon dioxide levels rose above 800 ppm in all vehicles when the fan was off and the windows were closed while parked and during city driving, and in 2 of the 6 vehicles during highway driving. With the ventilation system set on recirculation mode, carbon dioxide rose above 800 ppm within 10 minutes in all vehicles tested.

Conclusion: Carbon dioxide measurements could provide a practical and rapid method to assess ventilation in motor vehicles. Simple measures such as opening windows, turning on the fan, and avoiding the recirculation mode greatly improve ventilation.

Background: In this work, we carried out a cross-sectional study examining HIV-1 and HCV free virus concentrations in blood and cerebrospinal fluid (CSF) to determine whether HIV-1 enters the central nervous system (CNS) passively as virus particles or in the context of migrating infected cells. If virions migrate freely across the blood-cerebrospinal fluid barrier (BCSFB) or the blood-brain barrier (BBB) then HCV and HIV-1 would be detectable in the CSF at proportions similar to that in the blood. Alternatively, virus entry as an infected cell would favor selective entry of HIV-1.

Methods: We measured HIV-1 and HCV viral loads in the CSF and blood plasma of 4 co-infected participants who were not on antiviral regimens for either infection. We also generated HIV-1 env sequences and performed phylogenetic analyses to determine whether HIV-1 populations in the CSF of these participants were being maintained by local replication.

Results: While CSF samples taken from all participants had detectable levels of HIV-1, HCV was not detectable in any of the CSF samples despite participants having HCV concentrations in their blood plasma, which exceeded that of HIV-1. Further, there was no evidence of compartmentalized HIV-1 replication in the CNS (Supplementary Figure 1). These results are consistent with a model where HIV-1 particles cross the BBB or the BCSFB within infected cells. In this scenario, we would expect HIV-1 to reach the CSF more readily because the blood contains a much greater number of HIV-infected cells than HCV-infected cells.

Conclusions: HCV entry into the CSF is restricted, indicating that virions do not freely migrate across these barriers and supporting the concept that HIV-1 is transported across the BCSFB and/or BBB by the migration of HIV-infected cells as part of an inflammatory response or normal surveillance.

Background: Inadequate ventilation may contribute to the high risk for household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: We evaluated the effectiveness of several interventions recommended to improve ventilation in households. In 7 residential homes, carbon dioxide monitoring was conducted to assess ventilation in occupied open areas such as family rooms and in bedrooms and/or offices. Carbon dioxide levels above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation for the number of people present. In 1 of the 7 homes, various interventions to improve ventilation or to filter air were assessed in a kitchen area by measuring clearance of aerosol particles produced using an aerosol-based spray system and carbon dioxide generated by cooking with a gas stove.

Results: Carbon dioxide levels rose above 800 ppm in bedrooms and offices with 2 occupants when windows and doors were closed and in open areas during gatherings of 5 to 10 people; carbon dioxide levels decreased when windows or doors were opened. Clearance of carbon dioxide and aerosol particles significantly increased with interventions including running fans, operating portable air cleaners, and opening windows, particularly when there was a noticeable breeze or when a window fan was used to blow contaminated air outside.

Conclusion: In households, several measures to improve ventilation or air filtration were effective in reducing carbon dioxide accumulation or enhancing clearance of carbon dioxide and aerosol particles. Studies are needed to determine if interventions to improve ventilation can reduce the risk for airborne transmission of SARS-CoV-2 in households.