BackgroundScabies is a parasitic skin infestation caused by the burrowing mite Sarcoptes scabiei. It is common worldwide and spreads rapidly under crowded conditions, such as those found in socially disadvantaged communities of Indigenous populations and in developing countries. Pruritic scabies lesions facilitate opportunistic bacterial infections, particularly Group A streptococci. Streptococcal infections cause significant sequelae and the increased community streptococcal burden has led to extreme levels of acute rheumatic fever and rheumatic heart disease in Australia's Indigenous communities. In addition, emerging resistance to currently available therapeutics emphasizes the need to identify potential targets for novel chemotherapeutic and/or immunological intervention. Scabies research has been severely limited by the availability of parasites, and scabies remains a truly neglected infectious disease. We report development of a tractable model for scabies in the pig, Sus domestica.Methodology/Principal FindingsOver five years and involving ten independent cohorts, we have developed a protocol for continuous passage of Sarcoptes scabiei var. suis. To increase intensity and duration of infestation without generating animal welfare issues we have optimised an immunosuppression regimen utilising daily oral treatment with 0.2mg/kg dexamethasone. Only mild, controlled side effects are observed, and mange infection can be maintained indefinitely providing large mite numbers (>6000 mites/g skin) for molecular-based research on scabies. In pilot experiments we explore whether any adaptation of the mite population is reflected in genetic changes. Phylogenetic analysis was performed comparing sets of genetic data obtained from pig mites collected from naturally infected pigs with data from pig mites collected from the most recent cohort.Conclusions/SignificanceA reliable pig/scabies animal model will facilitate in vivo studies on host immune responses to scabies including the relations to the associated bacterial pathogenesis and more detailed studies of molecular evolution and host adaption. It is a most needed tool for the further investigation of this important and widespread parasitic disease.

In order to eliminate potential selection bias, more RCTs need to be conducted in this area so that effectiveness, as well as efficacy, can be ascertained. The interlock programme appears to be effective while the device is installed in the vehicle of the offender. Studies need to address ways of improving recidivism rates in the long term, as the major challenges are participation rates, compliance and durability.

T acrolimus, a potent immunosuppressive agent, has emerged as a valuable therapeutic alternative to cyclosporine after adult liver transplantation. 1 Similar to cyclosporine, tacrolimus has a narrow therapeutic window. 2 Continuous adequate immunosuppression is imperative for maintenance of the graft, whereas overimmunosuppression can lead to serious toxicities, infections, and increased risk for lymphoproliferative disease. It is not possible to give a standard dosing regimen to all adults and achieve concentrations within this narrow therapeutic range. Tacrolimus shows considerable interindividual and intraindividual variability in its pharmacokinetics, with poor correlation between drug dosage and blood concentrations. 2 These factors make defining an optimal dosing schedule for this agent difficult. 3 A number of studies have evaluated the pharmacokinetic properties of tacrolimus. 2 Oral bioavailability of this agent is generally low (ϳ25%), but can vary from 4% to 93%. Tacrolimus binds extensively to erythrocytes and, in plasma, to ␣1-acid glycoprotein and albumin. It is extensively metabolized by the cytochrome P-450 system and subject to P-glycoprotein countertransport. 4 Greater than 95% of tacrolimus is eliminated by the biliary route; renal excretion of the parent drug accounts for less than 1% of total body clearance.To date, the majority of pharmacokinetic studies in adult liver transplant recipients have used a classic approach to data generation. [5][6][7][8][9][10][11][12] Kinetic information has been obtained through multiple blood sampling in small relatively homogenous patient groups during a single dosing interval or during a short time span in the immediate posttransplantation period. Different factors that may alter drug pharmacokinetics have not been investigated simultaneously. Such studies provide little information on interindividual and intraindividual pharmacokinetic variability. Furthermore, kinetic information has been based on immunoassay analysis of tacrolimus blood samples. Such assays are not specific for the parent drug, with reports of significant and variable cross-reactivity of assay antibody with some tacrolimus metabolites. 3 Such assay techniques as liquid chromatography-tandem mass spectrometry