Scabies Mite Proteins As Targets For The Development Of New Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$299,564.00
Summary
Scabies and associated bacteria disease (pyoderma) are a significant health burden, with pyoderma implicated in rheumatic fever and heart disease. Investigations of the mechanism underlying scabies and bacteria disease links, identified scabies proteins inhibiting the human complement system. The inhibition prevents mite damage and promotes growth of bacteria. This proposal aims to elucidate the interaction between scabies, bacteria and the human host, in order to design new therapeutics.
Genetic Variation And Host-parasite Interactions Of Sarcoptes Scabiei
Funder
National Health and Medical Research Council
Funding Amount
$294,536.00
Summary
Scabies is a disease of skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. Although up to 45 different host species can be infested by this mite, this organism is currently classified as a single species existing as multiple strains or varieties. Previous studies have failed to identify any structural differences between host-associated populations, suggesting a single gene pool. Our recent molecular study of scabies in people and dogs, from Aboriginal communities in the Northern ....Scabies is a disease of skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. Although up to 45 different host species can be infested by this mite, this organism is currently classified as a single species existing as multiple strains or varieties. Previous studies have failed to identify any structural differences between host-associated populations, suggesting a single gene pool. Our recent molecular study of scabies in people and dogs, from Aboriginal communities in the Northern Territory and the North and South Americas, using DNA fingerprinting techniques, suggested mites cluster by host species with no evidence of cross-transmission. However although this data seems to suggest that these sub-species deserve species status, another molecular study suggests Sarcoptes is a single species, presumably a result of interbreeding. Understanding interbreeding between populations is important in the control of the disease and in controlling resistance to acaricides. We wish to further characterise the genetic separation of different 'strains' or populations of mites by studying the evolutionary gene flow between host-associated populations. We will use a mitochondrial DNA marker that will clarify fine scale transmission processes and more clearly delineate the biological species status of S. scabiei. Recent in vitro data and clinical evidence in a patient with severe crusted scabies indicated resistance to ivermectin, the treatment of choice for these patients. We will investigate the role and genetic mechanisms of ivermectin resistance. This is important for future control programs, as acaricide resistance can spread rapidly in parasite populations.Read moreRead less
Investigating The Molecular Basis Of Emerging Drug Resistance In Scabies Mites
Funder
National Health and Medical Research Council
Funding Amount
$516,000.00
Summary
Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location ....Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location of the Menzies School of Health Research in this region where scabies is endemic has enabled us to undertake a number of studies on the disease. Our world first molecular study using microsatellite markers demonstrated that scabies mites on people were genetically distinct from those on dogs. This had important implications in control programs in the communities. Additional work has focused on laboratory studies to monitor the sensitivity of mites to current treatments used in community control programs and for the treatment of crusted scabies, a very severe and debilitating form of the disease. We have reported evidence of increasing resistance of scabies mites to topical 5%permethrin and documented both in vitro and clinical evidence of resistance to oral ivermectin. We now seek support to extend this work to identify at the molecular level the mechanisms of resistance and use this knowledge to design a diagnostic test. This work has both local and global implications. Scabies is a significant disease of children primarily in many indigenous and third world communities, as well as associated with nursing homes and HIV infection. The tools developed in this project will enable the assessment of drug treatment failures and assist in the development of more sensitive methods for monitoring resistance in the community, including the potential for reversing it. This will avoid the current global problems of resistance observed in other organisms such as headlice.Read moreRead less
Scabies is a significant disease of children particularly in indigenous communities. This project is aimed at working out how scabies mites resist medications used to treat them and to design a test for drug resistance. The tools developed in this project will enable the assessment of treatment failures and assist in the development of more sensitive methods for monitoring resistance in the community, including the potential for reversing it.