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Biomedical subjects

Shelley F Walton

Publications and source records attributed to Shelley F Walton.

12 recordsLinked to original sources
PubMed2006

Scabies mite inactivated serine protease paralogues are present both internally in the mite gut and externally in feces.

The scabies mite, Sarcoptes scabiei, is the causative agent of scabies, a disease that is common among disadvantaged populations and facilitates streptococcal infections with serious sequelae. Previously, we encountered large families of genes encoding paralogues of house dust mite protease allergens with their catalytic sites inactivated by mutation (scabies mite inactivated protease paralogues [SMIPPs]). We postulated that SMIPPs have evolved as an adaptation to the parasitic lifestyle of the scabies mite, functioning as competitive inhibitors of proteases involved in the host-parasite interaction. To propose testable hypotheses for their functions, it is essential to know their locations in the mite. Here we show by immunohistochemistry that SMIPPs exist in two compartments: 1) internal to the mite in the gut and 2) external to the mite after excretion from the gut in scybala (fecal pellets). SMIPPs may well function in both of these compartments to evade host proteases.

Animals↗
PubMed2005

Ectoparasitic infestations.

Ectoparasitic infestations are highly prevalent in resource-poor populations throughout the world and are associated with considerable morbidity. Reliable data on the epidemiology, immunology, and therapy of ectoparasitic infestations and on the biology of the parasites remain scarce. The control of parasitic skin diseases, such as scabies, pediculosis, tungiasis, myiasis, and cutaneous larva migrans in endemic areas remains a challenge. Using appropriate study designs, it is imperative to increase further the knowledge on the various aspects of the parasites and the infestations they cause.

Journal Article↗
PubMed2005

Identification and characterization of Sarcoptes scabiei and Dermatophagoides pteronyssinus glutathione S-transferases: implication as a potential major allergen in crusted scabies.

The astigmatid mite Sarcoptes scabiei is the causative agent of scabies, a highly infectious parasitic disease of the skin. Although the mite causes marked hypersensitivity reactions, particularly in crusted (severe) scabies, little is known about the specific scabies mite molecules involved in such immunologic responses. We have identified six genes encoding scabies mite homologues of mu and delta-like glutathione S-transferases (GSTs) as well as novel house dust mite GSTs. A mu class S. scabiei GST was subcloned into a prokaryotic expression system. The purified recombinant protein rSsGST01 reacted strongly with IgE and IgG4 in sera from crusted scabies patients. This response was not observed with control antigens or with ordinary scabies and uninfested patient sera. In addition, the specific IgE response to rSsGST01 did not correlate with the total IgE level of the patient. These results suggest that GST may play a role in the pathophysiology associated with crusted scabies.

Allergens↗
PubMed2004

First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei.

Ivermectin is increasingly being used to treat scabies, especially crusted (Norwegian) scabies. However, treatment failures, recrudescence, and reinfection can occur, even after multiple doses. Ivermectin resistance has been documented for some intestinal helminths in animals with intensive ivermectin exposure. Ivermectin resistance has also been induced in arthropods in laboratory experiments but, to date, has not been documented among arthropods in nature. We report clinical and in vitro evidence of ivermectin resistance in 2 patients with multiple recurrences of crusted scabies who had previously received 30 and 58 doses of ivermectin over 4 and 4.5 years, respectively. As predicted, ivermectin resistance in scabies mites can develop after intensive ivermectin use.

Adult↗
PubMed2004

Acaricidal activity of Melaleuca alternifolia (tea tree) oil: in vitro sensitivity of sarcoptes scabiei var hominis to terpinen-4-ol.

OBJECTIVE: To compare the acaricidal activity of Melaleuca alternifolia (tea tree) oil (TTO) and some of its individual active components on the itch mite Sarcoptes scabiei var hominis. DESIGN: In vitro acaricide sensitivity assessment. SETTING: The Menzies School of Health Research laboratory, located near the Infectious Diseases Ward of the Royal Darwin Hospital, Australia, where patients are admitted and treated for crusted scabies. PARTICIPANTS: Scabies mites (S scabiei var hominis) were collected from a 20-year-old Aboriginal woman admitted to the Royal Darwin Hospital with crusted scabies. Interventions Within 3 hours of collection, scabies mites were placed in continuous direct contact with the TTO products and control acaricides and were observed at regular intervals. MAIN OUTCOME MEASURES: Percentage of mites dead at regular observation intervals between 5 minutes and 24 hours during continuous exposure to the TTO products and acaricides. RESULTS: The 5% TTO and active component terpinen-4-ol were highly effective in reducing mite survival times. Statistically significant differences in mite survival curves were observed for 5% TTO, 2.1% terpinen-4-ol, 5% permethrin, and ivermectin (100 microg/g of Emulsifying Ointment British Pharmacopoeia 88). In vivo effectiveness was also observed. CONCLUSIONS: Documentation of resistance against antiectoparasitic compounds is increasing. Reported S scabiei treatment failures with lindane, crotamiton, and benzyl benzoate, as well as likely emerging resistance to 5% permethrin and oral ivermectin, are of concern and advocate for the identification and development of novel acaricidal drugs. Tea tree oil is a membrane-active biocide extracted from the tree M alternifolia. It is a principal antimicrobial in a wide range of pharmaceuticals sold in Australia, with the main active component being oxygenated terpenoids. The results suggest that TTO has a potential role as a new topical acaricide and confirm terpinen-4-ol as the primary active component.

Adult↗
PubMed2004

Scabies: new future for a neglected disease.

Scabies is a disease of global proportions in both human and animal populations, resulting from infestation of the skin with the "itch" mite Sarcoptes scabiei. Despite the availability of effective chemotherapy the intensely itching lesions engender significant morbidity primarily due to secondary sepsis and post-infective complications. Some patients experience an extreme form of the disease, crusted scabies, in which many hundreds of mites may infest the skin causin severe crusting and hyperkeratosis. Overcrowded living conditions and poverty have been identified as significant confounding factors in transmission of the mite in humans. Control is hindered by difficulties with diagnosis, the cost of treatment, evidence for emerging resistance and lack of effective vaccines. Historically research on scabies has been extremely limited because of the difficulty in obtaining sufficient quantities of the organism. Recent molecular approaches have enabled considerable advances in the study of population genetics and transmission dynamics of S. scabiei. However, the most exciting and promising development is the potential exploitation of newly available data from S. scabiei cDNA libraries and EST projects. Ultimately this knowledge may aid early identification of disease, novel forms of chemotherapy, vaccine development and new treatment possibilities for this important but neglected parasite.

Animals↗
PubMed2004

Circulating IgE in patients with ordinary and crusted scabies.

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.

Animals↗
PubMed2003

Mechanisms for a novel immune evasion strategy in the scabies mite sarcoptes scabiei: a multigene family of inactivated serine proteases.

Parasitic infestation of the skin by the mite Sarcoptes scabiei is a significant problem worldwide, particularly in socially disadvantaged communities. A multigene family of at least 24 homologs of a serine protease allergen have been identified in S. scabiei. Surprisingly, the products of all but one of these genes are predicted to be catalytically inactive, due to mutations at a critical triad of amino acids at the active site. We discuss the possibility that these genes for inactivated proteases have been conserved because they mediate a novel host defense evasion strategy that the mite has evolved as an adaptation to parasitism of the epidermis. The identification of this family, and elucidation of its value to the parasite, may present an unanticipated approach to protective vaccination.

Allergens↗
PubMed2003

Identification of a homologue of a house dust mite allergen in a cDNA library from Sarcoptes scabiei var hominis and evaluation of its vaccine potential in a rabbit/S. scabiei var. canis model.

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.

Allergens↗
PubMed2003

Generation and characterization of cDNA clones from Sarcoptes scabiei var. hominis for an expressed sequence tag library: identification of homologues of house dust mite allergens.

Molecular studies on scabies, a disease of considerable human and veterinary significance, have been limited because of the difficulty of obtaining the causative organism Sarcoptes scabiei, the "itch mite." We have used skin from the bedding of crusted scabies patients as a source of mites for the construction of libraries of cDNAs from S. scabiei var. hominis in the bacteriophage lambda vector lambdaZAP express. Sequences of 145 clones established that the libraries predominantly contain sequences from S. scabiei, enabling a major sequencing program to begin. Among those sequenced to date, cDNAs encoding S. scabiei homologues of 3 house dust mite allergens-the M-177 apolipoprotein, glutathione S-transferase, and paramyosin--were identified. The availability of cDNA libraries from S. scabiei var. hominis and S. scabiei var. vulpes and the emerging public sequence databases from both opens up new possibilities in scabies research.

Allergens↗
PubMed2002

The scourge of scabies.

Scabies ('Itch Mite') is truly a Great Neglected Disease that inflicts misery on millions. Molecular approaches, while still in their infancy, are providing a better understanding of the parasite and will have important implications for control and prevention. It has long been thought that dogs may act as a reservoir for human infections. However, genetic studies cast doubt over this supposition.

Animals↗