Quantitative PCR-based genome size estimation of the astigmatid mites Sarcoptes scabiei, Psoroptes ovis and Dermatophagoides pteronyssinus

Background: The lack of genomic data available for mites limits our understanding of their biology. Evolving high-throughput sequencing technologies promise to deliver rapid advances in this area, however, estimates of genome size are initially required to ensure sufficient coverage. Methods. Quantitative real-time PCR was used to estimate the genome sizes of the burrowing ectoparasitic mite Sarcoptes scabiei, the non-burrowing ectoparasitic mite Psoroptes ovis, and the free-living house dust mite Dermatophagoides pteronyssinus. Additionally, the chromosome number of S. scabiei was determined by chromosomal spreads of embryonic cells derived from single eggs. Results: S. scabiei cells were shown to contain 17 or 18 small (< 2 M) chromosomes, suggesting an XO sex-determination mechanism. The average estimated genome sizes of S. scabiei and P. ovis were 96 ( 7) Mb and 86 ( 2) Mb respectively, among the smallest arthropod genomes reported to date. The D. pteronyssinus genome was estimated to be larger than its parasitic counterparts, at 151 Mb in female mites and 218 Mb in male mites. Conclusions: This data provides a starting point for understanding the genetic organisation and evolution of these astigmatid mites, informing future sequencing projects. A comparitive genomic approach including these three closely related mites is likely to reveal key insights on mite biology, parasitic adaptations and immune evasion

In vitro efficacy of moxidectin versus ivermectin against Sarcoptes scabiei

Moxidectin is under consideration for development as a treatment for human scabies. As some arthropods show decreased sensitivity to moxidectin relative to ivermectin, it was important to assess this for Sarcoptes scabiei. In vitro assays showed that the concentration of moxidectin required to kill 50% of mites was lower than that of ivermectin (0.5 μM versus 1.8 μM at 24 h; P < 0.0001). This finding provides further support for moxidectin as a candidate for the treatment of human scabies

Prospective Study in a Porcine Model of Sarcoptes scabiei Indicates the Association of Th2 and Th17 Pathways with the Clinical Severity of Scabies

BackgroundUnderstanding of scabies immunopathology has been hampered by the inability to undertake longitudinal studies in humans. Pigs are a useful animal model for scabies, and show clinical and immunologic changes similar to those in humans. Crusted scabies can be readily established in pigs by treatment with the glucocorticoid dexamethasone (Dex).Methodology/ Principal FindingsProspective study of 24 pigs in four groups: a) Scabies+/Dex+, b) Scabies+/Dex-, c) Scabies-/Dex+ and d) Scabies-/Dex-. Clinical symptoms were monitored. Histological profiling and transcriptional analysis of skin biopsies was undertaken to compare changes in cell infiltrates and representative cytokines. A range of clinical responses to Sarcoptes scabiei were observed in Dex treated and non-immunosuppressed pigs. An association was confirmed between disease severity and transcription of the Th2 cytokines IL-4 and IL-13, and up-regulation of the Th17 cytokines IL-17 and IL-23 in pigs with crusted scabies. Immunohistochemistry revealed marked infiltration of lymphocytes and mast cells, and strong staining for IL-17.Conclusions/ SignificanceWhile an allergic Th2 type response to scabies has been previously described, these results suggest that IL-17 related pathways may also contribute to immunopathology of crusted scabies. This may lead to new strategies to protect vulnerable subjects from contracting recurrent crusted scabies

Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies

peer-reviewedScabies is a neglected tropical disease of global significance. Our understanding of hostparasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating diseaseNational Health and Medical Research Counci

Treatment and control of scabies

PURPOSE OF REVIEW: The treatment of individual patients with scabies and its control in institutional and community settings remains challenging, with relatively few treatment choices available. In this review, evidence of the efficacy of available treatments will be discussed, and possible emerging drug resistance and new therapeutic directions outlined. RECENT FINDINGS: Although there has been attention on the use of ivermectin for the treatment of ordinary scabies and for mass drug administration, evidence supporting its superiority for both indications over alternative treatment is inconclusive. This is particularly true in light of several case reports of drug resistance in human and veterinary settings when the drug has been intensively used. When used correctly, topical agents such as permethrin and benzyl benzoate are effective. Little research on the development of new and more effective acaricides suitable for human use is underway. While the in-vitro acaricidal properties of several natural products have been documented, these are yet to be evaluated in animal studies or clinical trials. SUMMARY: When properly administered, chemotherapy for scabies remains effective in most situations. However, with reports of drug resistance increasing and with the need for therapies suitable for use in interventions to control community outbreaks, there is a need to develop new therapies

Host immune responses to the itch mite, Sarcoptes scabiei, in humans

Abstract Scabies is a parasitic disease due to infestation of skin by the burrowing mite Sarcoptes scabiei. Scabies is a major public health problem and endemic in resource poor communities worldwide affecting over 100 million people. Associated bacterial infections cause substantial morbidity, and in severe cases can lead to renal and cardiac diseases. Mite infestation of the skin causes localised cutaneous inflammation, pruritus, skin lesions, and allergic and inflammatory responses are mounted by the host against the mite and its products. Our current understanding of the immune and inflammatory responses associated with the clinical manifestations in scabies is far outweighed by the significant global impact of the disease. This review aims to provide a better understanding of human immune responses to S. scabiei in ordinary and crusted scabies phenotypes