Molecular Mechanisms Of Ivermectin Resistance In The Ectoparasitic Mite, Sarcoptes Scabiei
Funder
National Health and Medical Research Council
Funding Amount
$289,561.00
Summary
A largely neglected parasitic disease, scabies is a significant disease of children, particularly in remote Aboriginal communities in northern Australia. The recent emergence of ivermectin resistance threatens future control of scabies. This research explores the genetic basis of ivermectin resistance in the scabies mite, developing molecular markers to identify the emergence of resistance in the community, leading to improved tools for resistance management and sustainable treatment strategies.
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.
Antigens, Allergens And Immune Responses In Normal And Crusted Scabies
Funder
National Health and Medical Research Council
Funding Amount
$302,036.00
Summary
Scabies (itch mite), a parasitic skin infestation of the mite Sarcoptes scabiei, is a major problem among most children in many Aboriginal communities in Australia, often accompanied by streptococcal infections which cause serious diseases. Our world-first molecular studies utilised variable microsatellite markers to demonstrate that scabies mites on people are genetically distinct from those on dogs. This has important implications in control programs in Aboriginal communities. In our current N ....Scabies (itch mite), a parasitic skin infestation of the mite Sarcoptes scabiei, is a major problem among most children in many Aboriginal communities in Australia, often accompanied by streptococcal infections which cause serious diseases. Our world-first molecular studies utilised variable microsatellite markers to demonstrate that scabies mites on people are genetically distinct from those on dogs. This has important implications in control programs in Aboriginal communities. In our current NHMRC program we have cloned scabies antigens, with the aim of understanding more about immunity, which normally limits infestation from developing to the extreme levels seen in the debilitating disease crusted scabies. Our hypothesis is that crusted scabies is the consequence of an immune deficit in these patients. The first such cloned antigen is the equivalent of a known asthma-inducing allergen from a closely related housedust mite. We seek support to continue this successful program and to extend it to search for candidate vaccine antigens.The development of a vaccine would be a step of major importance in prevention. Recent reports estimate up to 300 million scabies cases worldwide, commonly associated with overcrowding and poverty. We are the first laboratory worldwide to have successfully initiated molecular studies on scabies. We have formed close collaborations with the only laboratory with an animal model (Arlian, USA), and the best group working on epidemiology and control of human scabies (Taplin, USA) and co-published with these groups. It is imperative that our NHMRC support be continued and increased to a level compatible with the importance, potential and achievements so far of this unique program.Read moreRead less
Immunity And Pathogenesis In Tropical And Infectious Diseases: Implications For Vaccines And
Funder
National Health and Medical Research Council
Funding Amount
$15,794,553.00
Summary
Malaria, streptococcal diseases, helminthiases and scabies are diseases of indigenous people on a massive scale, which lack vaccines. We aim to understand the pathogenesis of these diseases and develop vaccines and other treatments to combat them. Team includes senior experts on infectious diseases with long collaborative histories and younger members with impressive credentials. The work proposed also concerns inventive new ways of making such vaccines by novel chemical methods and aspects of d ....Malaria, streptococcal diseases, helminthiases and scabies are diseases of indigenous people on a massive scale, which lack vaccines. We aim to understand the pathogenesis of these diseases and develop vaccines and other treatments to combat them. Team includes senior experts on infectious diseases with long collaborative histories and younger members with impressive credentials. The work proposed also concerns inventive new ways of making such vaccines by novel chemical methods and aspects of delivery.Read moreRead less
Skin Disease Control In Remote Aboriginal Children: Translating Evidence Into Practice With A Cluster Randomised, Stepped Wedge Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,818,581.00
Summary
At any one time, almost one in two children living in remote Indigenous Australian communities have skin sores and one in three have scabies . Despite this high burden, skin infections are under-recognised. Increasing community and health care provider knowledge and access to the best available treatments will be evaluated with the goal of halving the burden of skin infection over five years and implementing the strategies, resources and knowledge to sustain this.
Scabies is a global disease and a major health problem in many developing countries, related primarily to poverty and overcrowding. In remote Aboriginal communities in northern Australia prevalences of up to 50% in children have been described, despite the availability of effective chemotherapy. Scabies is caused by a tiny mite burrowing under the skin and symptoms include intensely itching lesions that can be very distressing, and often become secondarily infected with Group A Streptococcus. Th ....Scabies is a global disease and a major health problem in many developing countries, related primarily to poverty and overcrowding. In remote Aboriginal communities in northern Australia prevalences of up to 50% in children have been described, despite the availability of effective chemotherapy. Scabies is caused by a tiny mite burrowing under the skin and symptoms include intensely itching lesions that can be very distressing, and often become secondarily infected with Group A Streptococcus. These skin sores can result in serious complications, including blood poisoning and kidney damage. Control of scabies is hindered by difficulties with diagnosis, the cost of treatment, evidence for emerging resistance, and lack of effective vaccines. The symptoms of scabies infestations can mimic many other skin diseases such as dermatitis, eczema, impetigo, and allergic reactions, and traditional tests to diagnose scabies are often less than 50% accurate. Control measures in endemic regions include community-based scabies intervention programs and although successful at reducing levels of scabies in the short term, have proved difficult to sustain due to low levels of scabies persisting within communities. Recent developments leading to expression and purification of scabies mite recombinant antigens have identified a number of molecules with diagnostic potential and this study aims to investigate the accuracy of these recombinant proteins to identify scabies specific antibodies in people with active scabies. An effective simple, cheap, rapid, sensitive and specific diagnostic test for scabies will aid in the early identification of disease and thus treatment. Furthermore it will enable the selective treatment of affected children and their families, reducing the requirement for mass treatment and associated costs, decrease the potential for escalating mite resistance, and provide another means of controlling scabies in highly affected areas.Read moreRead less