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.

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.

Evaluation of 'best practice' (SCOPS) guidelines for nematode control on commercial sheep farms in England and Wales.

Parasitic diseases are a major constraint to optimum livestock production and are the major cause of economic loss in UK sheep flocks, with farmers remaining dependant on anthelmintics for control. In the UK, research and evidence based, "best practice" guidelines for sustainable control of parasites in sheep (SCOPS) were first produced in 2004 and have been regularly updated since. This study was designed to evaluate the effect of these best practice guidelines for worm control on lamb production and infection levels, compared with more traditional management. Sixteen farms were selected based on a 2 cube factorial design with 3 factors known to affect worm epidemiology: control regimen; farm type; and climatic region. A formalised plan for worm control using 7 potential resistance-delaying practices was prepared for each of the 8 best practice (SCOPS) farms, in conjunction with the farms veterinarians. The 8 farms in the traditional management group (CONTROL farms) were selected based on ongoing evidence of them using worm control strategies deemed to be "higher-risk". A cohort of 40-50 study lambs at each farm was monitored from birth to finishing, allowing evaluation of lamb productivity, worm infection levels and for comparison of numbers of anthelmintic treatments. Birth and mid-season weights were used to calculate daily live-weight gain. Birth and finish dates were used to calculate time to finish and finish weights were also compared. Faecal egg counts, larval culture and species differentiation were undertaken throughout the year to assess the impact of the control strategies on worm burdens. There was no significant difference in results for any of the 3 production responses when comparing predicted means accounting for the differences in birth weight. In fact SCOPS farms had, on average, a higher daily weight gain and finish weight than CONTROL farms when comparing observed means. Statistical analysis of infection levels clearly showed no significant effect according to farm type (p=0.71) or treatment (p=0.81). In contrast the effect of region (p=0.08), although not significant, had a much larger effect size (standardised mean difference) with lower parasite burdens based on faecal egg counts on Northern farms compared to Southern farms. For both ewes and lambs, significantly fewer treatments were carried out on the SCOPS farms. The data collected from this study suggests that farms implementing SCOPS principles use less anthelmintic than other farms, without loss of animal performance or increased worm burden.

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

BACKGROUND: 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. METHODS: 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 m(3) (cfu/m(3)) 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. RESULTS: 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 2614cfu/m(3)) of airborne bacteria were shown to persist for up to approximately 1h after these activities ended. DISCUSSION: 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 1h 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. CONCLUSION: Airborne bacteria significantly increase during dressing and sheet changes on moderate size burns, and remain elevated for up to an hour following their cessation.

Modelling the impact of temperature-induced life history plasticity and mate limitation on the epidemic potential of a marine ectoparasite.

Temperature is hypothesized to contribute to increased pathogenicity and virulence of many marine diseases. The sea louse (Lepeophtheirus salmonis) is an ectoparasite of salmonids that exhibits strong life-history plasticity in response to temperature; however, the effect of temperature on the epidemiology of this parasite has not been rigorously examined. We used matrix population modelling to examine the influence of temperature on demographic parameters of sea lice parasitizing farmed salmon. Demographically-stochastic population projection matrices were created using parameters from the existing literature on vital rates of sea lice at different fixed temperatures and yearly temperature profiles. In addition, we quantified the effectiveness of a single stage-specific control applied at different times during a year with seasonal temperature changes. We found that the epidemic potential of sea lice increased with temperature due to a decrease in generation time and an increase in the net reproductive rate. In addition, mate limitation constrained population growth more at low temperatures than at high temperatures. Our model predicts that control measures targeting preadults and chalimus are most effective regardless of the temperature. The predictions from this model suggest that temperature can dramatically change vital rates of sea lice and can increase population growth. The results of this study suggest that sea surface temperatures should be considered when choosing salmon farm sites and designing management plans to control sea louse infestations. More broadly, this study demonstrates the utility of matrix population modelling for epidemiological studies.

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.

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 (R(2)=0.82, p<0.001) than time taken (R(2)=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.

BCG vaccination reduces risk of tuberculosis infection in vaccinated badgers and unvaccinated badger cubs.

Wildlife is a global source of endemic and emerging infectious diseases. The control of tuberculosis (TB) in cattle in Britain and Ireland is hindered by persistent infection in wild badgers (Meles meles). Vaccination with Bacillus Calmette-Guérin (BCG) has been shown to reduce the severity and progression of experimentally induced TB in captive badgers. Analysis of data from a four-year clinical field study, conducted at the social group level, suggested a similar, direct protective effect of BCG in a wild badger population. Here we present new evidence from the same study identifying both a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs. We show that intramuscular injection of BCG reduced by 76% (Odds ratio = 0.24, 95% confidence interval (CI) 0.11-0.52) the risk of free-living vaccinated individuals testing positive to a diagnostic test combination to detect progressive infection. A more sensitive panel of tests for the detection of infection per se identified a reduction of 54% (Odds ratio = 0.46, 95% CI 0.26-0.88) in the risk of a positive result following vaccination. In addition, we show the risk of unvaccinated badger cubs, but not adults, testing positive to an even more sensitive panel of diagnostic tests decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08, 95% CI 0.01-0.76; P = 0.03). When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21, 95% CI 0.05-0.81; P = 0.02).

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.

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 Trypanosoma brucei (T. b.) gambiense or T. b. rhodesiense 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 T. b. rhodesiense 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-ß-cyclodextrin and melarsoprol randomly-methylated-ß-cyclodextrin. We found that these compounds retain trypanocidal properties in vitro 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.

Magnetic resonance imaging to assess blood-brain barrier damage in murine trypanosomiasis.

The ability of trypanosomes to invade the brain and induce an inflammatory reaction is well-recognized. This study uses magnetic resonance imaging (MRI) in conjunction with a murine model of central nervous system (CNS) stage trypanosomiasis to investigate this phenomenon at the level of the blood-brain barrier (BBB). Mice were scanned before and after administration of the contrast agent. Signal enhancement maps were generated, and the percentage signal change was calculated. The severity of the neuroinflammation was also assessed. Statistical analysis of the signal change data revealed a significantly (P = 0.028) higher signal enhancement in mice at 28 days post-infection (least squares mean = 26.709) compared with uninfected animals (6.298), indicating the presence of BBB impairment. Leukocytes were found in the meninges and perivascular space of some blood vessels in the infected mice. This study shows that the integrity of the BBB is compromised during CNS stage trypanosomiasis and that the impairment does not correlate with inflammatory cell infiltration.

Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers.

Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (Meles meles). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of Mycobacterium bovis infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle.

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

PURPOSE: To describe cases of postoperative endophthalmitis in the European Society of Cataract & 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. SETTING: Twenty-four ophthalmology units in Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and the United Kingdom. METHODS: Univariable and multivariable logistic regression models were used to analyze data for statistical 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. RESULTS: 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. CONCLUSION: Swollen lids, pain, and an opaque vitreous were statistically associated with proven endophthalmitis cases in the ESCRS study.

Social group size affects Mycobacterium bovis infection in European badgers (Meles meles).

1. In most social animals, the prevalence of directly transmitted pathogens increases in larger groups and at higher population densities. Such patterns are predicted by models of Mycobacterium bovis infection in European badgers (Meles meles). 2. We investigated the relationship between badger abundance and M. bovis prevalence, using data on 2696 adult badgers in 10 populations sampled at the start of the Randomized Badger Culling Trial. 3. M. bovis prevalence was consistently higher at low badger densities and in small social groups. M. bovis prevalence was also higher among badgers whose genetic profiles suggested that they had immigrated into their assigned social groups. 4. The association between high M. bovis prevalence and small badger group size appeared not to have been caused by previous small-scale culling in study areas, which had been suspended, on average, 5 years before the start of the current study. 5. The observed pattern of prevalence might occur through badgers in smaller groups interacting more frequently with members of neighbouring groups; detailed behavioural data are needed to test this hypothesis. Likewise, longitudinal data are needed to determine whether the size of infected groups might be suppressed by disease-related mortality. 6. Although M. bovis prevalence was lower at high population densities, the absolute number of infected badgers was higher. However, this does not necessarily mean that the risk of M. bovis transmission to cattle is highest at high badger densities, since transmission risk depends on badger behaviour as well as on badger density.

Bovine tuberculosis in cattle and badgers in localized culling areas.

Bovine tuberculosis (TB) is a zoonotic disease that can have serious consequences for cattle farming and, potentially, for public health. In Britain, failure to control bovine TB has been linked to persistent infection of European badger (Meles meles) populations. However, culling of badgers in the vicinity of recent TB outbreaks in cattle has failed to reduce the overall incidence of cattle TB. Using data from a large-scale study conducted in 1998-2005, we show that badgers collected on such localized culls had elevated prevalence of Mycobacterium bovis, the causative agent of bovine TB, suggesting that infections in cattle and badgers were indeed associated. Moreover, there was a high degree of similarity in the M. bovis strain types isolated from cattle and associated badgers. This similarity between strain types appeared to be unaffected by time lags between the detection of infection in cattle and culling of badgers, or by the presence of purchased cattle that might have acquired infection elsewhere. However, localized culling appeared to prompt an increase in the prevalence of M. bovis infection in badgers, probably by disrupting ranging and territorial behavior and hence increasing intraspecific transmission rates. This elevated prevalence among badgers could offset the benefits, for cattle, of reduced badger densities and may help to explain the failure of localized culling to reduce cattle TB incidence.

The efficacy of emamectin benzoate against infestations of Lepeophtheirus salmonis on farmed Atlantic salmon (Salmo salar L) in Scotland, 2002-2006.

BACKGROUND: Infestations of the parasitic copepod Lepeophtheirus salmonis, commonly referred to as sea lice, represent a major challenge to commercial salmon aquaculture. Dependence on a limited number of theraputants to control such infestations has led to concerns of reduced sensitivity in some sea lice populations. This study investigates trends in the efficacy of the in-feed treatment emamectin benzoate in Scotland, the active ingredient most widely used across all salmon producing regions. METHODOLOGY/PRINCIPAL FINDINGS: Study data were drawn from over 50 commercial Atlantic salmon farms on the west coast of Scotland between 2002 and 2006. An epi-informatics approach was adopted whereby available farm records, descriptive epidemiological summaries and statistical linear modelling methods were used to identify factors that significantly affect sea lice abundance following treatment with emamectin benzoate (SLICE(R), Schering Plough Animal Health). The results show that although sea lice infestations are reduced following the application of emamectin benzoate, not all treatments are effective. Specifically there is evidence of variation across geographical regions and a reduction in efficacy over time. CONCLUSIONS/SIGNIFICANCE: Reduced sensitivity and potential resistance to currently available medicines are constant threats to maintaining control of sea lice populations on Atlantic salmon farms. There is a need for on-going monitoring of emamectin benzoate treatment efficacy together with reasons for any apparent reduction in performance. In addition, strategic rotation of medicines should be encouraged and empirical evidence for the benefit of such strategies more fully evaluated.

Impacts of widespread badger culling on cattle tuberculosis: concluding analyses from a large-scale field trial.

BACKGROUND: Bovine tuberculosis (TB) has re-emerged as a major problem for British cattle farmers. Failure to control the infection has been linked to transmission from European badgers; badger culling has therefore formed a component of British TB control policy since 1973. OBJECTIVES AND DESIGN: To investigate the impact of repeated widespread badger culling on cattle TB, the Randomised Badger Culling Trial compared TB incidence in cattle herds in and around ten culling areas (each 100 km2) with those in and around ten matched unculled areas. RESULTS: Overall, cattle TB incidence was 23.2% lower (95% confidence interval (CI) 12.4-32.7% lower) inside culled areas, but 24.5% (95% CI 0.6% lower-56.0% higher) higher on land

Assessing the convergence of Markov Chain Monte Carlo methods: an example from evaluation of diagnostic tests in absence of a gold standard.

The accessibility of Markov Chain Monte Carlo (MCMC) methods for statistical inference have improved with the advent of general purpose software. This enables researchers with limited statistical skills to perform Bayesian analysis. Using MCMC sampling to do statistical inference requires convergence of the MCMC chain to its stationary distribution. There is no certain way to prove convergence; it is only possible to ascertain when convergence definitely has not been achieved. These methods are rather subjective and not implemented as automatic safeguards in general MCMC software. This paper considers a pragmatic approach towards assessing the convergence of MCMC methods illustrated by a Bayesian analysis of the Hui-Walter model for evaluating diagnostic tests in the absence of a gold standard. The Hui-Walter model has two optimal solutions, a property which causes problems with convergence when the solutions are sufficiently close in the parameter space. Using simulated data we demonstrate tools to assess the convergence and mixing of MCMC chains using examples with and without convergence. Suggestions to remedy the situation when the MCMC sampler fails to converge are given. The epidemiological implications of the two solutions of the Hui-Walter model are discussed.

Culling and cattle controls influence tuberculosis risk for badgers.

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. In Britain, European badgers (Meles meles) are implicated in transmitting Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Badger culling has therefore been a component of British TB control policy for many years. However, large-scale field trials have recently shown that badger culling has the capacity to cause both increases and decreases in cattle TB incidence. Here, we show that repeated badger culling in the same area is associated with increasing prevalence of M. bovis infection in badgers, especially where landscape features allow badgers from neighboring land to recolonize culled areas. This impact on prevalence in badgers might reduce the beneficial effects of culling on cattle TB incidence, and could contribute to the detrimental effects that have been observed. Additionally, we show that suspension of cattle TB controls during a nationwide epidemic of foot and mouth disease, which substantially delayed removal of TB-affected cattle, was associated with a widespread increase in the prevalence of M. bovis infection in badgers. This pattern suggests that infection may be transmitted from cattle to badgers, as well as vice versa. Clearly, disease control measures aimed at either host species may have unintended consequences for transmission, both within and between species. Our findings highlight the need for policymakers to consider multiple transmission routes when managing multihost pathogens.

ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: Case for a European multicenter study.

PURPOSE: To present the development and design of the European Society of Cataract & Refractive Surgeons multicenter study of the prevention of postsurgical infective endophthalmitis after phacoemulsification and to describe the process for its successful implementation and conduct. SETTING: Twenty-four ophthalmology units and eye clinics in Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and the United Kingdom, with an administrative office in Ireland, coordinating center in England, and data management and statistical unit in Scotland. METHODS: This partially masked randomized placebo-controlled multinational clinical study was designed to evaluate prospectively the prophylactic effect of intracameral cefuroxime and/or perioperative topical levofloxacin on postoperative endophthalmitis after cataract surgery. Random allocation was based on a 2 x 2 factorial design that included participating centers as a class variable. Real-time electronic data collection monitored study progress and provided weekly outcome tables, monthly recruitment summaries, and quarterly analytical reports for the study's Data Monitoring Committee, which evaluated the safety and efficacy by Internet-based conferences. RESULTS: A 2-year lead time was required to meet harmonized standards of clinical research in the European Union, obtain ministerial authorization in 3 countries, gain institutional approvals at 24 hospitals, and procure indemnity insurance for surgical centers. Informed consent instruments, designed to comply with national health policies, were translated into 8 languages. The use of information technology to collect study data enabled the organizers to evaluate individual eligibility at enrollment, adherence with study medications during and after surgery, and postoperative status during follow-up. CONCLUSION: This international cooperative study provided the opportunity to estimate the current incidence of endophthalmitis after cataract surgery in Europe and determine whether 1 or both of 2 antimicrobial regimens reduces the risk for postsurgical intraocular infection.