The challenging problem of disease staging in human African trypanosomiasis (sleeping sickness): a new approach to a circular question

Human African trypanosomiasis (HAT), also known as sleeping sickness, puts millions of people at risk in sub-Saharan Africa and is a neglected parasitic disease that is almost always fatal if untreated or inadequately treated. HAT manifests itself in two stages that are difficult to distinguish clinically. The problem of staging in HAT is extremely important since treatment options, some of which are highly toxic, are directly linked to the disease stage. Several suggested investigations for disease staging have been problematic because of the lack of an existing gold standard with which to compare new clinical staging markers. The somewhat arbitrary current criteria based on the cerebrospinal fluid (CSF) white blood cell (WBC) count have been widely used, but the new potential biomarkers are generally compared with these, thereby making the problem somewhat circular in nature. We propose an alternative ‘reverse’ approach to address this problem, conceptualised as using appropriate statistical methods to test the performance of combinations of established laboratory variables as staging biomarkers to correlate with the CSF WBC/trypanosomes and clinical features of HAT. This approach could lead to the use of established laboratory staging markers, potentially leading to a gold standard for staging and clinical follow-up of HAT

Confidence in assessing the effectiveness of bath treatments for the control of sea lice on Norwegian salmon farms

The salmon louse Lepeophtheirus salmonis is the most important ectoparasite of farmed salmonids in the Northern hemisphere, having a major economic and ecological impact on the sustainability of this sector of the aquaculture industry. To a large extent, control of L. salmonis relies on the use of topical delousing chemical treatments in the form of baths. Improvements in methods for the administration and assessment of bathtreatments have not kept pace with the rapid modernization and intensification of the salmon industry. Bathtreatments present technical and biological challenges, including best practice methods for the estimation of the effect of licetreatment interventions. In this communication, we compare and contrast methods to calculate and interpret treatmenteffectiveness at pen and site level. The methods are illustrated for the calculation of the percentage reduction in mean abundance of mobile lice with a measure of confidence. Six different methods for the calculation of confidence intervals across different probability levels were compared. We found the quasi-Poisson method with a 90% confidence interval to be informative and robust for the measurement of bathtreatment performance

Quantifying bacterial transfer from patients to staff during burns dressing and bed changes : implications for infection control

Routine nursing activities such as dressing/bed changes increase bacterial dispersal from burns patients, potentially contaminating healthcare workers (HCW) carrying out these tasks. HCW thus become vectors for transmission of nosocomial infection between patients. The suspected relationship between %total body surface area (%TBSA) of burn and levels of bacterial release has never been fully established. Bacterial contamination of HCW was assessed by contact plate samples (n = 20) from initially sterile gowns worn by the HCW during burns patient dressing/bed changes. Analysis of 24 gowns was undertaken and examined for relationships between %TBSA, time taken for activity, and contamination received by the HCW. Relationships between size of burn and levels of HCW contamination, and time taken for the dressing/bed change and levels of HCW contamination were best described by exponential models. Burn size correlated more strongly (R2 = 0.82, p < 0.001) than time taken (R2 = 0.52, p < 0.001), with levels of contamination received by the HCW. Contamination doubled with every 6–9% TBSA increase in burn size. Burn size was used to create a model to predict bacterial contamination received by a HCW carrying out bed/dressing changes. This may help with the creation of burn-specific guidelines on protective clothing worn by HCW caring for burns patients

Clinical observations associated with proven and unproven cases in the ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery

Aims to describe cases of postoperative endophthalmitis in the European Society of Cataract and Refractive Surgeons (ESCRS) study of the prophylaxis of endophthalmitis, compare characteristics of unproven cases and cases proven by culture or polymerase chain reaction, and compare the characteristics with those in other reported series. Twenty-four ophthalmology units in Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and the United Kingdom. Univariable and multivariable logistic regression models were used to analyze data forstatistical association of signs and symptoms in cases with proven or unproven endophthalmitis. Specific data describing characteristics of the cases were compared between the 2 types of cases. Data from 29 endophthalmitis cases were analyzed. Swollen lids and pain were statistically associated with proven cases of endophthalmitis on univariable regression analysis. Multivariable analysis indicated that swollen lids and an opaque vitreous were associated with proven cases. Five cases of endophthalmitis occurred in the cefuroxime-treated groups. No case of streptococcal infection occurred in the cefuroxime-treated groups. However, cases of infection due to streptococci showed striking differences in visual acuity and were associated with earlier onset. Characteristics in the 29 cases parallel results in previous studies, such as the Endophthalmitis Vitrectomy Study, although the addition of a control group in the ESCRS study elicited additional findings. Swollen lids, pain, and an opaque vitreous were statistically associated with proven endophthalmitis cases in the ESCRS study

Clinical studies of the high-intensity narrow-spectrum light environmental decontamination system (HINS-light EDS), for continuous disinfection in the burn unit inpatient and outpatient settings

Infections are the leading cause of morbidity and mortality in burn patients and prevention of contamination from exogenous sources including the hospital environment is becoming increasingly emphasised. The High-Intensity Narrow-Spectrum light Environmental Decontamination System (HINS-light EDS) is bactericidal yet safe for humans, allowing continuous disinfection of the environment surrounding burn patients. Environmental samples were collected from inpatient isolation rooms and the outpatient clinic in the burn unit, and comparisons were then made between the bacterial contamination levels observed with and without use of the HINS-light EDS. Over 1000 samples were taken. Inpatient studies, with sampling carried out at 0800 h, demonstrated a significant reduction in the average number of bacterial colonies following HINS-light EDS use of between 27% and 75%, (p<0.05). There was more variation when samples were taken at times of increased activity in the room. Outpatient studies during clinics demonstrated a 61% efficacy in the reduction of bacterial contamination on surfaces throughout the room during the course of a clinic (p=0.02). The results demonstrate that use of the HINS-light EDS allows efficacious bacterial reductions over and above that achieved by standard cleaning and infection control measures in both inpatient and outpatient settings in the burn unit

Using agent-based modelling to predict the role of wild refugia in the evolution of resistance of sea lice to chemotherapeutants

A major challenge for Atlantic salmon farming in the northern hemisphere is infestation by the sea louse parasite Lepeophtheirus salmonis. The most frequent method of controlling these sea louse infestations is through the use of chemical treatments. However, most major salmon farming areas have observed resistance to common chemotherapeutants. In terrestrial environments, many strategies employed to manage the evolution of resistance involve the use of refugia, where a portion of the population is left untreated to maintain susceptibility. While refugia have not been deliberately used in Atlantic salmon farming, wild salmon populations that migrate close to salmon farms may act as natural refugia. In this paper we describe an agent-based model that explores the influence of different sizes of wild salmon populations on resistance evolution in sea lice on a salmon farm. Using the model, we demonstrate that wild salmon populations can act as refugia that limit the evolution of resistance in the sea louse populations. Additionally, we demonstrate that an increase in the size of the population of wild salmon results in an increased effect in slowing the evolution of resistance. We explore the effect of a population fitness cost associated with resistance, finding that in some cases it substantially reduces the speed of evolution to chemical treatments

Multivariate evaluation of the effectiveness of treatment efficacy of cypermethrin against sea lice (Lepeophtheirus salmonis) in Atlantic salmon (Salmo salar)

Background: The sea louse Lepeophtheirus salmonis is the most important ectoparasite of farmed Atlantic salmon (Salmo salar) in Norwegian aquaculture. Control of sea lice is primarily dependent on the use of delousing chemotherapeutants, which are both expensive and toxic to other wildlife. The method most commonly used for monitoring treatment effectiveness relies on measuring the percentage reduction in the mobile stages of Lepeophtheirus salmonis only. However, this does not account for changes in the other sea lice stages and may result in misleading or incomplete interpretation regarding the effectiveness of treatment. With the aim of improving the evaluation of delousing treatments, we explored multivariate analyses of bath treatments using the topical pyrethroid, cypermethrin, in salmon pens at five Norwegian production sites.Results: Conventional univariate analysis indicated reductions of over 90% in mobile stages at all sites. In contrast, multivariate analyses indicated differing treatment effectiveness between sites (p-value < 0.01) based on changes in the proportion and abundance of the chalimus and PAAM (pre-adult and adult males) stages. Low water temperatures and shortened intervals between sampling after treatment may account for the differences in the composition of chalimus and PAAM stage groups following treatment. Using multivariate analysis, such factors could be separated from those which were attributable to inadequate treatment or chemotherapeutant failure.Conclusions: Multivariate analyses for evaluation of treatment effectiveness against multiple life cycle stages of L. salmonis yield additional information beyond that derivable from univariate methods. This can aid in the identification of causes of apparent treatment failure in salmon aquaculture

Airborne bacterial dispersal during and after dressing and bed changes on burns patients

It is acknowledged that activities such as dressing changes and bed sheet changes are high-risk events; creating surges in levels of airborne bacteria. Burns patients are particularly high dispersers of pathogens; due to their large, often contaminated, wound areas. Prevention of nosocomial cross-contamination is therefore one of the major challenges faced by the burns team. In order to assess the contribution of airborne spread of bacteria, air samples were taken repeatedly throughout and following these events, to quantify levels of airborne bacteria. Air samples were taken at 3-min intervals before, during and after a dressing and bed change on a burns patient using a sieve impaction method. Following incubation, bacterial colonies were enumerated to calculate bacterial colony forming units per m3 (cfu/m3) at each time point. Statistical analysis was performed, whereby the period before the high-risk event took place acted as a control period. The periods during and after the dressing and bed sheet changes were examined for significant differences in airborne bacterial levels relative to the control period. The study was carried out four times, on three patients with burns between 35% total burn surface area (TBSA) and 51% TBSA. There were significant increases in airborne bacteria levels, regardless of whether the dressing change or bed sheet change took place first. Of particular note, is the finding that significantly high levels (up to 2614 cfu/m3) of airborne bacteria were shown to persist for up to approximately 1 h after these activities ended. This is the most accurate picture to date of the rapidly changing levels of airborne bacteria within the room of a burns patient undergoing a dressing change and bed change. The novel demonstration of a significant increase in the airborne bacterial load during these events has implications for infection control on burns units. Furthermore, as these increased levels remained for approximately 1 h afterwards, persons entering the room both during and after such events may act as vectors of transmission of infection. It is suggested that appropriate personal protective equipment should be worn by anyone entering the room, and that rooms should be quarantined for a period of time following these events

Simple model for tuberculosis in cattle and badgers

As an aid to the study of bovine tuberculosis (TB), a simple model has been developed of an epidemic involving two species, cattle and badgers. Each species may infect the other. The proportion of animals affected is assumed relatively small so that the usual nonlinear aspects of epidemic theory are avoided. The model is used to study the long-run and transient effect on cattle of culling badgers and the effect of a period without routine testing for TB, such as occurred during the 2001 epidemic of foot-and-mouth disease in Great Britain. Finally, by examining the changes in cattle TB over the last 15 years, and with some other working assumptions, it is estimated that the net reproduction number of the epidemic is 1.1. The implications for controlling the disease are discussed

Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites &lt;i&gt;Trypanosoma brucei&lt;/i&gt; (&lt;i&gt;T.b.&lt;/i&gt;) &lt;i&gt;gambiense&lt;/i&gt; or &lt;i&gt;T.b.rhodesiense&lt;/i&gt; and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage &lt;i&gt;T.b.rhodesiense&lt;/i&gt; infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-&#846;-cyclodextrin and melarsoprol randomly-methylated-&#946;-cyclodextrin. We found that these compounds retain trypanocidal properties &lt;i&gt;in vitro&lt;/i&gt; and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy