Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

Energy Dependent Tunneling in a Quantum Dot

We present measurements of the rates for an electron to tunnel on and off a quantum dot, obtained using a quantum point contact charge sensor. The tunnel rates show exponential dependence on drain-source bias and plunger gate voltages. The tunneling process is shown to be elastic, and a model describing tunneling in terms of the dot energy relative to the height of the tunnel barrier quantitatively describes the measurements.Comment: 4 pages, 4 figure

Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice

Peer reviewedPublisher PD

Efficacy of antimicrobial 405 nm blue-light for inactivation of airborne bacteria

Airborne transmission of infectious organisms is a considerable concern within the healthcare environment. A number of novel methods for ‘whole room’ decontamination, including antimicrobial 405 nm blue light, are being developed. To date, research has focused on its effects against surface-deposited contamination; however it is important to also establish its efficacy against airborne bacteria. This study demonstrates evidence of the dose-response kinetics of airborne bacterial contamination when exposed to 405 nm light.Bacterial aerosols of Staphylococcus epidermidis, generated using a 6-Jet Collison nebuliser, were introduced into an aerosol chamber designed to maintain prolonged airborne suspension and circulation. Aerosolized bacteria were exposed to increasing doses of 405 nm light, and air samples were extracted from the chamber using a BioSampler liquid impinger, with viability analysed using pour-plate culture. Initial results have demonstrated successful aerosol inactivation, with a 98.4% reduction achieved with 1-hour exposure to low irradiance (11.9 mWcm-2) 405 nm light (P=<0.001). Natural decay of the suspended aerosol was observed, however this was significantly less than achieved with light treatment (P=0.004). Overall, results have provided early evidence of the susceptibility of bacterial aerosols to 405 nm light. Although less germicidally efficient than UV-light, 405 nm light treatment offers benefits in terms of increased safety for human exposure, and eradication of microbes regardless of antibiotic resistance. Such benefits provide advantages for a number of applications including ‘whole room’ environmental decontamination, in which reducing levels of airborne bacteria should reduce the number of infections arising from airborne contamination

AGB subpopulations in the nearby globular cluster NGC 6397

It has been well established that Galactic Globular clusters (GCs) harbour more than one stellar population, distinguishable by the anti-correlations of light element abundances (C-N, Na-O, and Mg-Al). These studies have been extended recently to the asymptotic giant branch (AGB). Here we investigate the AGB of NGC 6397 for the first time. We have performed an abundance analysis of high-resolution spectra of 47 RGB and 8 AGB stars, deriving Fe, Na, O, Mg and Al abundances. We find that NGC 6397 shows no evidence of a deficit in Na-rich AGB stars, as reported for some other GCs - the subpopulation ratios of the AGB and RGB in NGC 6397 are identical, within uncertainties. This agrees with expectations from stellar theory. This GC acts as a control for our earlier work on the AGB of M 4 (with contrasting results), since the same tools and methods were used.Comment: 10 pages, 7 figures, 8 tables (2 online-only). Accepted for publication in MNRA

Assessment of the variability of airborne contamination levels in an intensive care unit over a 24 hour period

Introduction: The objective of this study was to evaluate the variability in the dynamics and levels of airborne contamination within a hospital ICU in order to establish an improved understanding of the extent to which airborne bioburden contributes to cross-infection of patients. Microorganisms from the respiratory tract or skin can become airborne by coughing, sneezing and periods of increased activity such as bed changes and staff rounds. Current knowledge of the clinical microflora is limited however it is estimated that 10-33% of nosocomial infections are transmitted via air. Methods: Environmental air monitoring was conducted in Glasgow Royal Infirmary ICU, in the open ward and in patient isolation rooms. A sieve impactor air sampler was used to collect 500 L air samples every 15 minutes over 10 hour (08:00-18:00 h) and 24 hour (08:00-08:00 h) periods. Samples were collected, room activity logged and the bacterial contamination levels were recorded as CFU/m3 of air. Results: A high degree of variability in levels of airborne contamination was observed over the course of a 10 hour day and a 24 period in a hospital ICU. Counts ranged from 12-510 CFU/m3 over 24 hours in an isolation room occupied for 10 days by a patient with C. difficile infection. Contamination levels were found to be lowest during the night and in unoccupied rooms, with an average value of 20 CFU/m3. Peaks in airborne contamination showed a direct relation to an increase in room activity. Conclusions: This study demonstrates the degree of airborne contamination that can occur in an ICU over a 24 hour period. Numerous factors were found to contribute to microbial air contamination and consideration should be given to potential improved infection control strategies and decontamination technologies which could be deployed within the clinical environment to reduce the airborne contamination levels, with the ultimate aim of reducing healthcare-associated infections from environmental sources

Evaluation of the airborne contamination levels in an intensive care unit over a 24 hour period

Airborne transmission of infectious microorganisms poses a critical threat to human health, particularly in the clinical setting where it is estimated that 10-33% of nosocomial infections are spread via the air. Within the clinical environment, microorganisms originating from the human respiratory tract or skin can become airborne by coughing and sneezing, and periods of increased activity such as bed and dressing changes, movement, staff rounds and visiting hours. Current knowledge of the clinical airborne microflora is limited and there is uncertainty surrounding the contribution of airborne microorganisms to the transmission of nosocomial infection. This study aims to establish an improved understanding of the variability in the dynamics and levels of airborne microbial contamination within an operational intensive care unit (ICU). Methods Environmental monitoring of airborne contamination levels was conducted in Glasgow Royal Infirmary ICU, in the open ward and in both occupied and unoccupied patient isolation rooms. Monitoring was performed using a sieve impactor air sampler, with 500 L air samples collected every 15 minutes over 10 hour (08:00-18:00 h) and 24 hour (08:00-08:00 h) periods. Samples were collected on tryptone soya agar (TSA) plates, and the bacterial contamination levels were recorded as CFU/m3 of air. An activity log was also collated over the 10 hour and 24 hour sampling periods in order to record any activity occurring in the ward/room that might contribute to spikes in airborne contamination levels. Results Results highlight the degree of variability in levels of airborne contamination over the course of both a working day and a 24 hour period in a hospital ICU. A high degree of variability was observed across the 24 hour period, with counts ranging from 12-510 CFU/m3 in one study in an occupied patient room. Peaks in airborne contamination showed a direct relation to an increase in room activity. Monitoring found contamination levels to be lower overall during the night, and in unoccupied isolation rooms, with an average value of 20 CFU/m3. The highest counts were observed in an isolation room occupied for 10 days by a patient with C. difficile infection which generated an average microbial load of 104 CFU/m3 and a peak value of 510 CFU/m3. Discussion This study has demonstrated the degree of airborne contamination that can occur in the ICU environment over a 24 hour period. Numerous factors were found to contribute to the microbial air contamination levels, including patient status, length of room occupation, time of day and room activity, and further work is required to establish the extent to which this airborne bioburden contributes to cross-infection of patients