Transcriptome Analysis of Host Inflammatory Responses to the Ectoparasitic Mite Sarcoptes scabiei var. hominis.

Scabies, a human skin infestation caused by the ectoparasitic mite Sarcoptes scabiei var. hominis, affects more than 200 million people globally. The prevailing knowledge of the disease process and host immune response mechanisms is limited. A better understanding of the host-parasite relationship is essential for the identification of novel vaccine and drug targets. Here we aimed to interrogate the transcriptomic profiles of mite-infested human skin biopsies with clinical manifestations of ordinary scabies subjects ("OS"; n = 05) and subjects naive to scabies ("control"; n = 03) using RNASeq data analysis. A combined clustering, network, and pathway mapping approach enabled us to identify key signaling events in the host immune and pro-inflammatory responses to S. scabiei infestation. The clustering patterns showed various differentially expressed genes including inflammatory responses and innate immunity genes (DEFB4A, IL-19, CXCL8, CSF3, SERPINB4, S100A7A, HRNR) and notably upregulation of the JAK-STAT pathway in scabies-infested samples. Mite-infested human skin biopsies (GSE178563) were compared with an ex-vivo porcine infested model (E-MTAB-6433) and human skin equivalents (GSE48459). Marked enrichment of immune response pathways (JAK-STAT signaling, IL-4 and IL-13 pathway, and Toll receptor cascade), chemokine ligands and receptors (CCL17, CCL18, CCL3L1, CCL3L3, CCR7), and cytokines (IL-13 and IL-20) were observed. Additionally, genes known for their role in psoriasis and atopic dermatitis were upregulated, e.g., IL-19. The detailed transcriptomic profile has provided an insight into molecular functions, biological processes, and immunological responses and increased our understanding about transcriptomic regulation of scabies in human.

Comparative analysis of the allergenic characteristics and serodiagnostic potential of recombinant chitinase-like protein-5 and -12 from Sarcoptes scabiei.

BACKGROUND: Scabies is caused by burrowing of the mite Sarcoptes scabiei into the stratum corneum. Currently, diagnosis via routine skin scraping is very difficult, and information on the allergenic identification of S. scabiei remains limited. METHODS: We performed comparative analysis of the serological diagnostic potential of recombinant S. scabiei chitinase-like protein-5 (rSsCLP5) and recombinant S. scabiei chitinase-like protein-12 (rSsCLP12) by measuring the levels of serum-specific IgG and IgE antibodies (Abs) as diagnostic markers. In addition, the allergenic characteristics of rSsCLP5 and rSsCLP12 were evaluated using IgE-binding experiments and skin tests. RESULTS: The IgE Abs-based indirect enzyme-linked immunosorbent assay (ELISA) methods showed high sensitivity and specificity: the rSsCLP5-based assay had 93.5% sensitivity and 94.4% specificity; the rSsCLP12-based assay had 100% sensitivity and 98.1% specificity. The specific IgE Abs in infested mouse sera could bind rSsCLP5 and rSsCLP12. In skin tests, rabbits in the rSsCLP5 and rSsCLP12 groups and positive control (histamine) groups exhibited allergic reactions. Most test sites in the rSsCLP12 group had edema, bleeding spots, and even ulcers or scabs, but such allergy symptoms were rare in the rSsCLP5 group. Moreover, the allergic history rabbit group had more severe allergic reactions and lower levels of IgE Abs compared to the healthy rabbit group in the same protein group. CONCLUSIONS: These findings validate the use of IgE Abs to rSsCLP5 and rSsCLP12 as potentially useful markers for diagnosing scabies. Moreover, both rSsCLP5 and rSsCLP12 have allergenic properties, and the potential allergen rSsCLP12 is a stronger allergen than rSsCLP5.

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

Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite 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 disease.

Sequential Histopathological Changes and Cytokine Expressions in Dogs Naturally Infested with Sarcoptes scabiei Mites.

BACKGROUND: The diagnosis and treatment of canine scabies remain quite challenging as a result of the meddling of the invertebrate mite Sarcoptes scabiei var canis with the immunologic activity of its host. PURPOSE: This study aims to evaluate and better understand the immunologic, histomorphometric, histopathologic changes as well as their relationship in scabies infestation. METHOD: Ten healthy dogs were housed with five sarcoptes-ridden dogs. Skin biopsies were then obtained afterwards for 7 weeks into buffered formalin. Sections of obtained biopsies were processed and incubated in IL-4, IL-13, IL-17A and IL-23A antibodies, while the other sections were stained for cellular alterations, quantifications and measurement of tunnel height and diameters. Pearson's product-moment correlation was used to establish the association between the cytokines and the measured tunnel heights and diameters, while Student's t test and one-way analysis of variance were used to test for weekly significant differences in cytokine expressions. RESULTS: Histopathologic changes and early expression of all studied cytokines, eosinophils and mast cells were pronounced from the second week of infestation. Quite notable was the consistent amount of IL-13 and IL-23A all through the study duration. A dissimilar association was also observed between anti-inflammatory cytokines (IL-4 and IL-13) and pro-inflammatory cytokines (IL-17A and IL-23A). Also observed was the negative relationship between IL-13 and IL-23A as an increase in IL-13 was associated with a decrease in IL-23A. Tunnel height increase was also positively associated with pro-inflammation. CONCLUSION: Immunodiagnosis can possibly be achieved with IL-13 and IL-23A expressions, while immunotherapy seems possible with IL-13 cytokine therapy.

Comparative analysis of host resistance to Sarcoptes scabiei var. cuniculi in two different rabbit breeds.

BACKGROUND: Scabies, caused by infestation of the mite Sarcoptes scabiei, is one of the most severe ectoparasitic diseases in rabbits. Scabies seriously affects the commercial rabbit breeding, causing severe economic losses. Host resistance to S. scabiei is an important factor in further development of the rabbit industry. In the present study, we compared the host resistance to S. scabiei var. cuniculi of a new breed of domestic rabbit propagated by the Sichuan Animal Sciences Academy (QiXing rabbit, QX) compared with that of a traditional rabbit breed in the domestic rabbit industry (IRA rabbit, IRA). METHODS: Both QX and IRA rabbits were experimentally infested with live S. scabiei var. cuniculi mites for 48 h. Then, during the course of four-week experimental infestation period, the body weight of rabbits was recorded every two weeks for calculating body-weight variations in comparison to the non-infested control rabbits. Skin lesions in the foot area were assessed on weekly basis and serum samples were tested weekly for the estimation of changes in the total antibody levels (IgG, IgE and IgM). Moreover, DNA extracted from the blood samples was amplified for analysis of the genetic diversity in the major histocompatibility complex, class II, DQ Alpha (MHC-DQA) gene. RESULTS: Compared to the IRA rabbits, the QX rabbits showed a significantly higher (P < 0.05) relative body weight gain compared to the non-infested control rabbits and significantly lower (P < 0.05) scores for foot skin lesions and higher levels of IgG, IgE and IgM at weeks 1 to 4, week 2 and week 1 post-infestation, respectively. Furthermore, a polymorphism site at position 103 bp of exon two of MHC-DQA gene and a different gene frequency were found between two rabbit breeds, suggesting the genetic basis for the differential host resistance to the S. scabiei var. cuniculi between two rabbit breeds. CONCLUSIONS: The QX rabbits showed higher host resistance to S. scabiei var. cuniculi compared to the IRA rabbits at the clinical, immunological and genetic levels. These results provide a reference for the breeding of rabbits with adequately improved and sustained host resistance to scabies in the domestic rabbit industry.

The seroprevalence of Sarcoptes scabiei var. canis and its associated risk factors in dogs in Ibadan, Southwest Nigeria.

This study investigated the use of SARCOPTES-ELISA DOG KIT as a diagnostic tool in detecting anti-mite antibodies, establishing the prevalence of scabies in dogs and the associated risk factors of canine mange occurrence. A total of 384 dogs (149 males and 235 females) were randomly sampled from eight local government areas. The prevalence of canine sarcopticosis was found to be 67.45% (259/384) using the ELISA kit. ELISA test had a 96.4% sensitivity against microscopy test (21.42%) as skin scrapping with microscopy demonstrated mites in 12 out of 56 dogs, while ELISA detected antibodies in 54 out of the 56 dogs presented to treatment facilities. A significantly higher seroprevalence was found in the female dogs (P = .019), indigenous dog breeds (P = .01), dogs presented to government facilities for treatment (P = .000), and dogs with active lesions less than the palm of the hand (P = .000). There was no association between the age of dogs and scabies seroprevalence. Skin scrapping still remains ideal and unique in specific mite detection, but its deficiency in sensitivity can best be complimented with the use of a more sensitive ELISA diagnostic kit.

A chitinase-like protein from Sarcoptes scabiei as a candidate anti-mite vaccine that contributes to immune protection in rabbits.

BACKGROUND: Scabies is caused by Sarcoptes scabiei burrowing into the stratum corneum of the host's skin and is detrimental to the health of humans and animals. Vaccines are an attractive alternative to replace the acaricides currently used in their control. METHODS: In the present study, the S. scabiei chitinase-like protein 5 (SsCLP5) was characterized and recombinant SsCLP5 (rSsCLP5) was evaluated as a candidate vaccine protein for anti-mite protection in rabbits. The expression, characterization and immunolocalization of SsCLP5 were examined. Vaccination experiments were performed on three test groups (n = 12 per group) immunized with purified rSsCLP5. Control groups (n = 12 per group) were immunized with PBS, QuilA saponin or empty vector protein. After challenge, the inflammatory reaction and skin lesions were graded and rSsCLP5 indirect ELISA was used to detect antibody IgG levels in serum samples at the time of vaccination and post-challenge. RESULTS: The results showed that rSsCLP5 had high immunoreactivity and immunogenicity. In S. scabiei, SsCLP5 had a wide distribution in the chewing mouthpart, legs and exoskeleton, especially the outer layer of the exoskeleton. Vaccination with rSsCLP5 resulted in 74.3% (26/35) of rabbits showing no detectable lesions after challenge with S. scabiei. CONCLUSIONS: Our data demonstrate that rSsCLP5 is a promising candidate for a recombinant protein-based vaccine against S. scabiei. This study also provides a method for studying scabies vaccine using rabbit as an animal model and a basis for screening more effective candidate proteins.

Molecular characterization and allergenicity potential of triosephosphate isomerase from Sarcoptes scabiei.

Scabies is an allergic skin disease that affects millions of mammals worldwide, including humans. It is a neglected tropical disease that represents a significant public health threat, particularly in economically disadvantaged populations. An effective vaccine is not currently available, and the exact mode of pathogenesis remains unclear. Herein, we identified, cloned and recombinantly expressed triosephosphate isomerase from Sarcoptes scabiei (S. scabiei). Immunohistochemical analyses showed that S. scabiei triosephosphate isomerase (Ss-TIM) is localized in the legs and chewing mouthparts of mites, and in infected rabbit skin (keratinized skin and embedded mites). Intradermal skin tests of rabbits injected with recombinant S. scabiei triosephosphate isomerase (rSs-TIM) revealed a flare, erythema and wheal reaction. These findings suggest that Ss-TIM may contribute to host invasion and induce an allergic response in the host.

Atypical crusted scabies in a patient with chronic liver disease caused by hepatitis B and D viruses.

Crusted scabies is a less common variant of scabies that is highly contagious, difficult to treat and involves infestation by Sarcoptes scabiei var. hominis. The classical clinical presentation includes crusted, scaly and generally non-pruritic lesions usually located on the head, neck, palmar, plantar and periungual region. It was first described in Norway in 1848 in patients with leprosy who presented with crusted lesions. In this study, we report the case of a patient with crusted scabies with florid clinical manifestations and chronic liver disease due to hepatitis B and delta virus infection.

Atypical crusted scabies in a patient with chronic liver disease caused by hepatitis B and D viruses

Abstract: Crusted scabies is a less common variant of scabies that is highly contagious, difficult to treat and involves infestation by Sarcoptes scabiei var. hominis. The classical clinical presentation includes crusted, scaly and generally non-pruritic lesions usually located on the head, neck, palmar, plantar and periungual region. It was first described in Norway in 1848 in patients with leprosy who presented with crusted lesions. In this study, we report the case of a patient with crusted scabies with florid clinical manifestations and chronic liver disease due to hepatitis B and delta virus infection.

Increased risk of psoriasis following scabies infection: A nationwide population-based matched-cohort study.

Both scabies and psoriasis are pruritic inflammatory skin diseases. The clinical manifestations are similar and provocation of psoriasis by mite bite was reported. The association between scabies and psoriasis was not investigated before. We conducted this nationwide population-based matched-cohort study to describe if patients with a diagnosis of scabies have a different risk of developing new psoriasis. From the National Health Insurance Research Database of Taiwan, patients with scabies (n = 5137) were identified and matched for age and sex with non-scabies controls (n = 19 142). We tracked them for a 7-year period to identify the incidence of psoriasis. One hundred and ninety (0.8%) patients with newly diagnosed psoriasis were identified; 91 (1.8%) from the scabies group and 99 (0.5%) from the control group. Patients with scabies had a higher risk of subsequent psoriasis, with a crude hazard ratio of 3.45 and an adjusted hazard ratio (aHR) of 3.03 (95% confidence interval, 2.24-4.11). An increased risk for psoriasis among patients with scabies was observed (aHR, 3.03). Immunopathology involving the T-helper 17 cell-mediated inflammatory pathway may contribute to this association. Physicians may consider implementing assessments of psoriatic symptoms in patients with scabies.

Scabies, crusted (Norwegian) scabies and the diagnosis of mite sensitisation.

Scabies is observed with relatively high frequency in Allergy and Dermatology clinics in developing countries where poor sanitary conditions are prevalent and increasingly in some areas of the world with increased immigrant populations. Since the immunological response to scabies mites includes the production of IgE class antibodies to Sarcoptes scabiei allergens which cross-react with Dermatophagoides major allergens Der p 1 and Der p 2, positive immediate-type skin tests to house dust mite extracts should be interpreted cautiously. Additionally, scabies should be included routinely in the differential diagnosis of itchy rashes in patients living in those areas.

Identification of a novel PYP-1 gene in Sarcoptes scabiei and its potential as a serodiagnostic candidate by indirect-ELISA.

Scabies is a parasitic disease caused by the ectoparasite Sarcoptes scabiei, affecting different mammalian species, including rabbits, worldwide. In the present study, we cloned and expressed a novel inorganic pyrophosphatase, Ssc-PYP-1, from S. scabiei var. cuniculi. Immunofluorescence staining showed that native Ssc-PYP-1 was localized in the tegument around the mouthparts and the entire legs, as well as in the cuticle of the mites. Interestingly, obvious staining was also observed on the fecal pellets of mites and in the integument of the mites. Based on its good immunoreactivity, an indirect enzyme-linked immunosorbent assay (ELISA) using recombinant Ssc-PYP-1 (rSsc-PYP-1) as the capture antigen was developed to diagnose sarcoptic mange in naturally infected rabbits; the assay had a sensitivity of 92·0% and specificity of 93·6%. Finally, using the rSsc-PYP-1-ELISA, the Ssc-PYP-1 antibody from 10 experimentally infected rabbits could be detected from 1 week post-infection. This is the first report of S. scabiei inorganic pyrophosphatase and the protein could serve as a potential serodiagnostic candidate for sarcoptic mange in rabbits.

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

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.

Increase the risk of intellectual disability in children with scabies: A nationwide population-based cohort study.

Scabies is a common and distressing disease caused by the mite Sarcoptes scabiei var. hominis. Psychiatric disorder in childhood is an important disease and easily neglected. There are several similarities in scabies and psychiatric disorders in childhood (PDC). Both of them may present with pruritus. They are relatively common in patients with lower socioeconomic status and crowded environment. Furthermore, immune-mediated inflammatory processes play a role in the pathophysiology in both diseases. An association between scabies and psychiatric disorders may exist. This nationwide population-based cohort study utilized data from the National Health Insurance Research Database to investigate the relationship between scabies and PDC. A total of 2137 children with scabies were identified as the study group and 8548 age- and sex-matched children were selected as the control group. A total of 607 (5.68%) children developed PDC during the 7-year follow-up period. The overall incidences of PDC are similar but patients with scabies had a higher risk of developing intellectual disability (ID) (scabies group vs control group: 1.3% vs 0.6%, adjusted hazard ratio: 2.04 and 95% confidence interval: 1.25-3.32). The immune-mediated inflammatory processes of both diseases were reviewed and may contribute to the 104% increased risk of interleukin in patients with scabies. We suggest a more comprehensive management in treating patients with scabies or ID. Early and comprehensive treatment of scabies and other risk factors may decrease the risk of subsequent ID. When we approach patients with ID, concurrent evaluation of scabies and other risk factors may contribute to successful management.

Transcriptome-microRNA analysis of Sarcoptes scabiei and host immune response.

Scabies is a parasitic disease, caused by the mite Sarcoptes scabiei, and is considered one of the top 50 epidemic diseases and one the most common human skin disease, worldwide. Allergic dermatitis, including an intense itch, is a common symptom, however diagnosis is difficult and there is currently no effective vaccine. The goal of this study was to examine the immune interaction mechanism of both S. scabiei and infected hosts. mRNA-seq and microRNA-seq were conducted on the S. scabiei mite and on infected and uninfected hosts. We focused on differential expression of unigenes and microRNAs, as well as the real targets of unigenes in enriched immune signaling pathways. S. scabiei enhanced host immune function and decreased metabolism after infection, while the immune response of the host inhibited S. scabiei proliferation and metabolism signaling pathways. Differentially expressed unigenes of S. scabiei were enriched in the JAK-STAT signaling pathway and the Toll-like receptor signaling pathway. The differential expression analysis indicated that microRNAs of S. scabiei and hosts have major roles in regulating immune interactions between parasites and hosts.

Incidence of autoimmune diseases in patients with scabies: a nationwide population-based study in Taiwan.

Scabies is a commonly occurring infectious immune-mediated inflammatory skin disease. Immune-mediated inflammatory processes are also observed in autoimmune diseases. There have been very few previous studies; however, that have investigated the possible association between scabies and autoimmune diseases. To address this research gap, we conducted a nationwide population-based cohort study that included a total of 4481 scabies patients and 16,559 control subjects matched by gender, age, insured region, urbanization and income. We tracked both cohorts for a 7-year period to identify the incidence of autoimmune diseases in both groups during that follow-up period. Relatedly, a Cox regression analysis was performed to calculate and compare the hazard ratio (HR) for autoimmune diseases of both groups. An overall increased risk for 19 autoimmune diseases was observed in the scabies patients, with an adjusted HR (aHR) of 1.14 (95% CI 1.04-1.25). Compared with the control group, the scabies patients exhibited increased risks of hypersensitivity vasculitis (aHR 5.44, 95% CI 1.64-18.07), dermatomyositis (aHR 4.91, 95% CI 1.80-13.38), polyarteritis nodosa (aHR 2.89, 95% CI 1.46-5.73), systemic lupus erythematosus (aHR 2.73, 95% CI 1.33-5.64), psoriasis (aHR 2.31, 95% CI 1.85-2.88), myasthenia gravis (aHR 2.01, 95% CI 1.31-3.12), type 1 diabetes mellitus (aHR 1.93, 95% CI 1.53-2.44), pernicious anemia (aHR 1.92, 95% CI 1.42-2.61), and rheumatoid arthritis (aHR 1.43, 95% CI 1.12-1.83). In conclusion, the associations between scabies and a variety of autoimmune diseases may exist. Further studies are needed to clarify the shared etiologies and relationships between scabies and autoimmune diseases.