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The disease scabies is one of the earliest diseases of humans for which the cause was known. It is caused by the mite, Sarcoptes scabiei, that burrows in the epidermis of the skin of humans and many other mammals. This mite was previously known as Acarus scabiei DeGeer, 1778 before the genus Sarcoptes was established (Latreille 1802) and it became S. scabiei. Research during the last 40 years has tremendously increased insight into the mite's biology, parasite-host interactions, and the mechanisms it uses to evade the host's defenses. This review highlights some of the major advancements of our knowledge of the mite's biology, genome, proteome, and immunomodulating abilities all of which provide a basis for control of the disease. Advances toward the development of a diagnostic blood test to detect a scabies infection and a vaccine to protect susceptible populations from becoming infected, or at least limiting the transmission of the disease, are also presented.

Background: Scabies, caused by the mite, Sarcoptes scabiei, infects millions of humans, and many wild and domestic mammals. Scabies mites burrow in the lower stratum corneum of the epidermis of the skin and are the source of substances that are antigenic or modulate aspects of the protective response of the host. Ordinary scabies is a difficult disease to diagnose., Objective: The goal of this project was to identify S. scabiei proteins that may be candidate antigens for use in a diagnostic test or may be used by the mite to modulate the host's protective response., Methods: An aqueous extract of S. scabiei was separated by 2-dimensional electrophoresis and proteins were identified by mass spectrometry. A parallel immunoblot was probed with serum from patients with ordinary scabies to identify IgM and/or IgG-binding antigens. The genes coding for 23 selected proteins were cloned into E. coli and the expressed recombinant proteins were screened with serum from patients with confirmed ordinary scabies., Results: We identified 50 different proteins produced by S. scabiei, 34 of which were not previously identified, and determined that 66% were recognized by patient IgM and/or IgG. Fourteen proteins were screened for use in a diagnostic test but none possessed enough sensitivity and specificity to be useful. Six of the 9 proteins selected for the possibility that they may be immunomodulatory were not recognized by antibodies in patient serum., Conclusions: Thirty-three proteins that bound IgM and/or IgG from the serum of patients with ordinary scabies were identified. None of the 14 tested were useful for inclusion in a diagnostic test. The identities of 16 proteins that are not recognized as antigens by infected patients were also determined. These could be among the molecules that are responsible for this mite's ability to modulate its host's innate and adaptive immune responses.

Background: The common scabies mite, Sarcoptes scabiei is a cosmopolitan parasite of humans and other mammals. An annotated genome of Sarcoptes scabiei var. canis has been deposited in the National Center for Biotechnology Information (NCBI) and VectorBase and a proteomic analysis of proteins in extracts of mite bodies and eggs from this strain has been reported. Here we mined the data to identify predicted proteins that are known to be involved in specific biological processes in other animals., Results: We identified predicted proteins that are associated with immunomodulation of the host defense system, and biological processes of the mite including oxygen procurement and aerobic respiration, oxidative metabolism, sensory reception and locating a host, neuronal transmission, stressors (heat shock proteins), molting, movement, nutrient procurement and digestion, and excretion and water balance. We used these data to speculate that certain biological processes may occur in scabies mites., Conclusion: This analysis helps understand the biology of Sarcoptes scabiei var. canis and adds to the data already available in NCBI and VectorBase.

The pruritic skin disease scabies is caused by the burrowing of the itch mite Sarcoptes scabiei (De Geer). It is difficult to diagnose this disease because its symptoms often resemble those of other skin diseases. No reliable blood or molecular diagnostic test is available. The aim of this project was to begin to characterize the scabies proteome to identify scabies mite proteins, including those that may be useful in the development of a diagnostic test or vaccine. Various scabies mite extracts were separated by two-dimensional electrophoresis, and 844 Coomassie Blue-stained protein spots were excised, subjected to trypsin digestion, and analyzed by Matrix Assisted Laser Desorption/Ionization Time-Of-Flight/Time-Of-Flight (MALDI-TOF/TOF) mass spectrometry (MS). Tryptic fragment sequences determined by MS were searched against the recently completed S. scabiei annotated genome, leading to the identification of >150 proteins. Only 10 proteins hit to previously identified scabies proteins including actin, tropomyosin, and several ABC transporters. Thirteen proteins had homology to dust mite allergens (members of groups 8, 10, 13, 17, 20, 25, and 28). Most other sequences showed some homology to proteins in other mites and ticks including homologs of calmodulin, calreticulin, lipocalin, and glutathione-S-transferase. These data will now allow the identification of the proteins to which scabies patients produce antibodies, including those that may be good candidates for inclusion in a diagnostic test and vaccine., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Scabies afflicts millions of people worldwide, but it is very difficult to diagnose by the usual skin scrape test, and a presumptive diagnosis is often made based on clinical signs such as rash and intense itch. A sensitive and specific blood test to detect scabies would allow a physician to quickly make a correct diagnosis., Objective: Our objective was to profile the mite-specific antibodies present in the sera of patients with ordinary scabies., Methods: Sera of 91 patients were screened for Ig, IgD, IgE, IgG and IgM antibodies to S. scabiei, as well as to the house dust mites Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei., Results: 45%, 27% and 2.2% of the patients had measurable amounts of mixed Ig, IgG and IgE that recognized scabies mite antigens. However, 73.6% of the scabies patients had serum IgM that recognized scabies proteins, and all except two of them also had IgM that recognized all of the three species of dust mites. No patient had serum antibody exclusively reactive to scabies mite antigens., Conclusions: Co-sensitization or cross-reactivity between antigens from scabies and house dust mites confounds developing a blood test for scabies.

The ectoparasitic mite, Sarcoptes scabiei that burrows in the epidermis of mammalian skin has a long co-evolution with its hosts. Phenotypic studies show that the mites have the ability to modulate cytokine secretion and expression of cell adhesion molecules in cells of the skin and other cells of the innate and adaptive immune systems that may assist the mites to survive in the skin. The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents (HSEs) that changed expression in response to the burrowing of live scabies mites. Overall, of the more than 25,800 genes measured, 189 genes were up-regulated >2-fold in response to scabies mite burrowing while 152 genes were down-regulated to the same degree. HSEs differentially expressed large numbers of genes that were related to host protective responses including those involved in immune response, defense response, cytokine activity, taxis, response to other organisms, and cell adhesion. Genes for the expression of interleukin-1α (IL-1α) precursor, IL-1β, granulocyte/macrophage-colony stimulating factor (GM-CSF) precursor, and G-CSF precursor were up-regulated 2.8- to 7.4-fold, paralleling cytokine secretion profiles. A large number of genes involved in epithelium development and keratinization were also differentially expressed in response to live scabies mites. Thus, these skin cells are directly responding as expected in an inflammatory response to products of the mites and the disruption of the skin's protective barrier caused by burrowing. This suggests that in vivo the interplay among these skin cells and other cell types, including Langerhans cells, dendritic cells, lymphocytes and endothelial cells, is responsible for depressing the host's protective response allowing these mites to survive in the skin.

Scabies is a contagious skin disease of humans and many other species of mammals. Previous studies suggested that the balance between the Th1 and Th2 immune responses may influence the outcome of a scabies infestation in a sensitized host. Therefore, in this study, we examined the T-helper cell cytokine profiles of splenocytes and lymph node cells in BALB/c mice that were immunized with scabies extract (primary response), infested with scabies mites (primary response), or immunized and then infested (secondary response). Lymphocyte cytokine expression was analyzed by flow cytometry after staining for intracellular cytokines. Immunization with scabies extract induced production of interferon-gamma (IFNgamma) (Th1 response) by both spleen and lymph node cells. Mice that were infested with scabies increased production of interleukin-4 by lymph node cells and of IFNgamma by splenocytes. Mice that were first immunized and then infested with mites increased production of IFNgamma by both spleen and lymph node cells. However, this increased level of IFNgamma was only about half of that induced by immunization alone. These results suggest that live scabies mites produced something that inhibited IFNgamma production in the lymph nodes of scabies-immunized mice. Our data also indicate that lymphocytes in the spleen and lymph nodes can present different cytokine response profiles.

Serum from seven patients with ordinary scabies and six with crusted scabies were screened by immunoblotting for IgE- and IgG-specific proteins in an extract of the mite, Sarcoptes scabiei variety canis. Sera from atopic individuals without sensitivity to house dust mites were used as controls. Serum from all of the patients with crusted scabies showed strong IgE binding to 11-21 and IgG binding to 1-7 scabies proteins. In contrast, three of the seven patients with ordinary scabies showed IgE binding to one to six scabies proteins, and their antibody binding was much weaker. Patients with crusted scabies had serum antibody that reacted with larger molecular weight proteins compared with patients with ordinary scabies. The results of this study indicate that patients with crusted scabies showed a pronounced IgE response to scabies mites, whereas patients with ordinary scabies did not.

Sarcoptes scabiei ("itch mite") causes scabies, a disease of considerable human and veterinary significance. Little work has been done at the molecular level because of the difficulty of obtaining mites. We have used mites in skin from the bedding of crusted scabies patients for the construction of a library of 10(5) cDNAs from S. scabiei var. hominis cloned in the vector pGEX4T-2. We describe the isolation by immunoscreening of 2 clones, one of which (Ssagl) is homologous to and cross-reactive with the house dust mite Euroglyphus maynei allergen M-177, an apolipoprotein from hemolymph. Immunohistochemistry revealed that it is located around the internal organs and cuticle of the mite and in eggs. Although it was not found to be protective in a challenge trial, the rabbits did not exhibit typical crust characteristics. This work shows that it is now possible to conduct such challenge trials with cloned scabies antigens.

The ectoparasitic mite, Sarcoptes scabiei that burrows in the epidermis of mammalian skin has a long co-evolution with its hosts. Phenotypic studies show that the mites have the ability to modulate cytokine secretion and expression of cell adhesion molecules in cells of the skin and other cells of the innate and adaptive immune systems that may assist the mites to survive in the skin. The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents (HSEs) that changed expression in response to the burrowing of live scabies mites. Overall, of the more than 25,800 genes measured, 189 genes were up-regulated >2-fold in response to scabies mite burrowing while 152 genes were down-regulated to the same degree. HSEs differentially expressed large numbers of genes that were related to host protective responses including those involved in immune response, defense response, cytokine activity, taxis, response to other organisms, and cell adhesion. Genes for the expression of interleukin-1α (IL-1α) precursor, IL-1β, granulocyte/macrophage-colony stimulating factor (GM-CSF) precursor, and G-CSF precursor were up-regulated 2.8- to 7.4-fold, paralleling cytokine secretion profiles. A large number of genes involved in epithelium development and keratinization were also differentially expressed in response to live scabies mites. Thus, these skin cells are directly responding as expected in an inflammatory response to products of the mites and the disruption of the skin’s protective barrier caused by burrowing. This suggests that in vivo the interplay among these skin cells and other cell types, including Langerhans cells, dendritic cells, lymphocytes and endothelial cells, is responsible for depressing the host’s protective response allowing these mites to survive in the skin. [ABSTRACT FROM AUTHOR]

Reports on a study which examine the T-helper cell cytokine profiles of splenocytes and lymph node cells in BALB/c mice that were immunized with scabies extract, infested with scabies mites, or immunized and then infested. Identification of scabies as a contagious disease of humans and many other species of mammals; Influence of balance between Th1 and Th2 immune responses on the outcome of scabies infestation in a synthesized host; Indication on the potential of lymphocytes in the spleen and lymph nodes to present different cytokine response profiles.