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Scabies: Emerging Ivermectin Resistance in a Neglected Ectoparasitic Disease
Abstract

Scabies: Emerging Ivermectin Resistance in a Neglected Ectoparasitic Disease

Kate E Mounsey, J S McCarthy, D C Holt, C Pasay, B J Currie and Shelley F Walton
57th American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting: Abstract Book, pp.16-17
American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting, 57th (New Orleans, United States, 07-Dec-2008–11-Dec-2008)
2008
url
http://www.astmh.org/AM/Template.cfm?Section=Meeting_Archives&Template=/CM/ContentDisplay.cfm&ContentID=1764View
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Abstract

Medical Microbiology
Scabies, an infectious skin disease caused by infestation of the mite Sarcoptes scabiei, is particularly problematic in socially disadvantaged communities and institutional settings. Of the few treatment options for scabies, ivermectin is the only available oral agent. It is the treatment of choice for hyper-infested (crusted) scabies, is used increasingly for ordinary scabies, and has been identified as a promising acaricide for mass treatment in scabies endemic communities. However, reports of ivermectin resistance in S. scabiei raise concerns regarding the sustainability of such programs. It is therefore critical to define the molecular mechanisms of emerging ivermectin resistance. Candidate mechanisms include 1) Drug efflux, mediated by ATP-binding-cassette (ABC) transporters such as P-glycoprotein; 2) Alteration to drug targets, such as ligand gated chloride channels and 3) Metabolic detoxification, mediated by enzymes such as glutathione S-transferases (GSTs). A survey of a S. scabiei expressed sequence tag dataset resulted in the identification of several ABC transporter and GST genes of interest. To evaluate transcription levels of these genes, mites were obtained from crusted scabies patients and separated according to life stage and ivermectin exposure. qRT-PCR was performed using SYBR green for seven target genes, amplified in parallel with β-actin, allowing for normalisation. GSTs were highly expressed at all life stages of S. scabiei, with expression of ABC transporter genes comparatively low. Of note, P-glycoprotein and GSTs were significantly up-regulated in ivermectin exposed adult female S. scabiei, suggesting these molecules may be associated with the development of ivermectin resistance in scabies mites. These advances should assist the development of molecular based diagnostics for the rapid detection of ivermectin resistance in S. scabiei. Such tools will become increasingly important to avert the scenario of widespread emergence of ivermectin resistance, particularly in light of proposed mass-treatment programs.

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