A Tractable Experimental Model for Study of Human and Animal Scabies

Abstract

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.

The immunology of the porcine skin and its value as a model for human skin

“…This includes studies on wound healing (Ansell et al, 2012;Jung et al, 2013;Sullivan et al, 2001), burns (Abdullahi et al, 2014;Sheu et al, 2014), transdermal penetration, delivery and toxicology (Barbero and Frasch, 2009;Godin and Touitou, 2007;Mahl et al, 2006;Simon and Maibach, 2000;Yu et al, 2013), infectious diseases (Mounsey et al, 2010;Rampton et al, 2013;San Mateo et al, 1999), radiation and UVB impact (Agay et al, 2010;Brozyna et al, 2009;Smirnova et al, 2014), snake venom (Imkhieo et al, 2009) and taser (Jenkins et al, 2013) assessments, as well as stem cell research (Hao et al, 2009;Zhao et al, 2012). The pig was also employed as a model for experimentally induced allergic contact dermatitis, revealing similarities to human with respect to clinical, histological and immunohistological features (Vana and Meingassner, 2000).…”

Crusted scabies is associated with increased IL‐17 secretion by skin T cells

“…Animal models provide the opportunity to investigate the immunopathologic mechanisms of scabies development, and a tractable porcine model of scabies has been recently developed (11,16). When infested with S. scabiei var.…”

“…Peripheral blood responses were compared at early (1 week) and late (15 weeks) stages of scabies mite infestation, with local skin responses also examined at 15 weeks post-infestation. It has been suggested that IL-17 secretion by CD3 + cd + T cells plays a critical role in the pathogenesis of skin chronic inflammation, such as psoriasis (16)(17)(18). As some of the clinical manifestations of crusted scabies, such as epidermal hyperproliferation, are similar to psoriasis, we also investigated whether the levels of IL-17 were increased in mite-infested pigs, especially those with crusted scabies.…”

In Vitro Efficacy of Moxidectin versus Ivermectin against Sarcoptes scabiei

“…Scabies mites in this colony were originally obtained from naturally infested pigs and have had no known acaricide exposure. Establishment of this model and protocols for mite collection have been described in detail previously (23). Briefly, skin scrapings were obtained from the ears of infested pigs and transported to the laboratory.…”