Shelley F. Walton

Problems in Diagnosing Scabies, a Global Disease in Human and Animal Populations

SUMMARY Scabies is a worldwide disease and a major public health problem in many developing countries, related primarily to poverty and overcrowding. In remote Aboriginal communities in northern Australia, prevalences of up to 50% among children have been described, despite the availability of effective chemotherapy. Sarcoptic mange is also an important veterinary disease engendering significant morbidity and mortality in wild, domestic, and farmed animals. Scabies is caused by the ectoparasitic mite Sarcoptes scabiei burrowing into the host epidermis. Clinical symptoms include intensely itchy lesions that often are a precursor to secondary bacterial pyoderma, septicemia, and, in humans, poststreptococcal glomerulonephritis. Although diagnosed scabies cases can be successfully treated, the rash of the primary infestation takes 4 to 6 weeks to develop, and thus, transmission to others often occurs prior to therapy. In humans, the symptoms of scabies infestations can mimic other dermatological skin diseases, and traditional tests to diagnose scabies are less than 50% accurate. To aid early identification of disease and thus treatment, a simple, cheap, sensitive, and specific test for routine diagnosis of active scabies is essential. Recent developments leading to the expression and purification of S. scabiei recombinant antigens have identified a number of molecules with diagnostic potential, and current studies include the investigation and assessment of the accuracy of these recombinant proteins in identifying antibodies in individuals with active scabies and in differentiating those with past exposure. Early identification of disease will enable selective treatment of those affected, reduce transmission and the requirement for mass treatment, limit the potential for escalating mite resistance, and provide another means of controlling scabies in populations in areas of endemicity.

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.

Scabies: more than just an irritation

Human scabies, caused by skin infestation with the arthropod mite, Sarcoptes scabiei, typically results in a papular, intensely pruritic eruption involving the interdigital spaces, and flexure creases. Recent research has led to a reassessment of the morbidity attributable to this parasite in endemic communities, particularly resulting from secondary skin sepsis and postinfective complications including glomerulonephritis. This has led to studies of the benefits of community based control programmes, and to concerns regarding the emergence of drug resistance when such strategies are employed. The renewed research interest into the biology of this infection has resulted in the application of molecular tools. This has established that canine and human scabies populations are genetically distinct, a finding with major implications for the formulation of public health control policies. Further research is needed to increase understanding of drug resistance, and to identify new drug targets and potential vaccine candidates.

Scabies in the developing world—its prevalence, complications, and management

Scabies remains one of the commonest of skin diseases seen in developing countries. Although its distribution is subject to a cycle of infection, with peaks and troughs of disease prevalence, this periodicity is often less obvious in poor communities. Scabies is a condition that affects families, particularly the most vulnerable; it also has the greatest impact on young children. Largely through the association with secondary bacterial infection caused by group A streptococci and Staphylococcus aureus, the burden of disease is compounded by nephritis, rheumatic fever and sepsis in developing countries. However, with a few notable exceptions, it remains largely neglected as an important public health problem. The purpose of this review is to provide an update on the current position of scabies with regard to its complications and control in resource-poor countries.

Studies in vitro on the relative efficacy of current acaricides for Sarcoptes scabiei var. hominis

Resistance of Sarcoptes scabiei to various topical therapies has been described, but clinical assessment of treatment failure is problematic and in-vitro assays are generally not available. We describe a simple in-vitro analysis used to evaluate the relative efficacy of a range of topical, oral, and herbal treatments available in Australia for the treatment of scabies. S. scabiei var. hominis mites were collected from skin scrapings obtained from 7 crusted scabies patients over a period of 2 years (1997 and 1998). Larvae, nymphal instars, and adult mites were tested within 3 h of collection and continuously exposed to selected commercially available treatment products until death, with the elapsed time recorded. Neem was the only product to show little acaricidal activity. Survival curves indicated that, of the other agents, 5% permethrin (Lyclear) had the slowest killing time, with 35% of mites still alive after 3 h, and 4% still alive after 18-22 h of constant exposure. In contrast, no mites were alive after 3 h exposure to 25% benzyl benzoate (Ascabiol), 1% lindane (Quellada), 5% tea tree oil and 100-8000 ng/g of ivermectin (Equimec). Despite the slower killing time with 5% permethrin, there was no evidence of any mite tolerance in vivo or treatment failure in any patients or contact cases.

The mitochondrial 12S gene is a suitable marker of populations of Sarcoptes scabiei from wombats, dogs and humans in Australia

Abstract. We sequenced part of the mitochondrial 12S ribosomal RNA gene of 23 specimens of Sarcoptes scabiei from eight wombats, one dog and three humans. Twelve of the 326 nucleotide positions varied among these mites and there were nine haplotypes (sequences) that differed by 1–8 nucleotides. Phylogenetic analyses indicated that these mites were from two lineages: (1) mites from wombats from Victoria, Australia, and mites from the humans and dog from the Northern Territory, Australia (haplotypes 1–4, 9); and (2) mites from the humans and dog from the Northern Territory (haplotypes 5–8). Mites from the three different hosts (wombats, a dog and humans) had not diverged phylogenetically; rather, these mites had similar 12S sequences. Thus, we conclude that these mites from wombats, humans and a dog are closely related, and that they diverged from a common ancestor relatively recently. This conclusion is consistent with the argument that people and/or their dogs introduced to Australia the S. scabiei mites that infect wombats in Australia . So, S. scabiei, which has been blamed for the extinction of populations of wombats in Australia, may be a parasitic mite that was introduced to Australia with people and/or their dogs. These data show that the mitochondrial 12S rRNA gene may be a suitable population marker of S. scabiei from wombats, dogs and humans in Australia.

Scabies: molecular perspectives and therapeutic implications in the face of emerging drug resistance.

Limited effective treatments, coupled with recent observations of emerging drug resistance to oral ivermectin and 5% permethrin, raise concerns regarding the future control of scabies, especially in severe cases and in endemic areas where repeated community treatment programs are in place. There is consequently an urgent need to define molecular mechanisms of drug resistance in scabies mites and to develop and assess alternative therapeutic options, such as tea tree oil, in the event of increasing treatment failure. Molecular studies on scabies mites have, until recently, been restricted; however, recent advances are providing new insights into scabies mite biology and genetic mechanisms underlying drug resistance. These may assist in overcoming many of the current difficulties in monitoring treatment efficacy and allow the development of more sensitive tools for monitoring emerging resistance.

Evidence incriminating midges (Diptera: Ceratopogonidae) as potential vectors of Leishmania in Australia.

The first autochthonous Leishmania infection in Australia was reported by Rose et al. (2004) and the parasite was characterised as a unique species. The host was the red kangaroo (Macropus rufus) but the transmitting vector was unknown. To incriminate the biological vector, insect trapping by a variety of methods was undertaken at two field sites of known Leishmania transmission. Collected sand flies were identified to species level and were screened for Leishmania DNA using a semi-quantitative real-time PCR. Collections revealed four species of sand fly, with a predominance of the reptile biter Sergentomyia queenslandi (Hill). However, no Leishmania-positive flies were detected. Therefore, alternative vectors were investigated for infection, giving startling results. Screening revealed that an undescribed species of day-feeding midge, subgenus Forcipomyia (Lasiohelea) Kieffer, had a prevalence of up to 15% for Leishmania DNA, with high parasitemia in some individuals. Manual gut dissections confirmed the presence of promastigotes and in some midges material similar to promastigote secretory gel, including parasites with metacyclic-like morphology. Parasites were cultured from infected midges and sequence analysis of the Leishmania RNA polymerase subunit II gene confirmed infections were identical to the original isolated Leishmania sp. Phylogenetic analysis revealed the closest known species to be Leishmania enriettii, with this and the Australian species confirmed as members of Leishmania sensu stricto. Collectively the results strongly suggest that the day-feeding midge (F. (Lasiohelea) sp. 1) is a potential biological vector of Leishmania in northern Australia, which is to our knowledge the first evidence of a vector other than a phlebotomine sand fly anywhere in the world. These findings have considerable implications in the understanding of the Leishmania life cycle worldwide.

New insights into disease pathogenesis in crusted (Norwegian) scabies: the skin immune response in crusted scabies

Background  Crusted scabies is a rare and severely debilitating disease characterized by infestation of the skin with up to millions of Sarcoptes scabiei mites, high total IgG levels, extremely high total IgE levels, and the development of hyperkeratotic skin crusts that may be loose, scaly and flaky or thick and adherent.

The immunology of susceptibility and resistance to scabies

The transmission of scabies occurs with the burrowing of Sarcoptes scabiei var. hominis mites into the skin. Infestation invariably leads to the development of localized cutaneous inflammation, pruritis and skin lesions. Classical transmission studies document an initial increase in S. scabiei numbers subsequent to primary infestation with a gradual reduction as host immunity develops. However, certain individuals fail to control infection and develop severe crusting of the skin, accompanied with extremely high mite burdens, elevated antibody levels and eosinophilia. These individuals have the nonhealing form of the human disease known as crusted scabies. The genetic predisposition for susceptibility or resistance to S. scabiei infection in humans is hypothesized to correlate with the dominance of an IgE‐driven Th2 response in severe disease or an interferon‐γ‐dominated Th1 response that promotes parasite control. However, recent data reveals complexities in cytokine regulation in the skin and the mechanisms of acquired resistance and immune escape. In this review, we consider the recent immunological and biomolecular advances in understanding the human host immune response to S. scabiei infestations in the context of earlier studies and attempt to reconcile apparent differences and emphasize those aspects of the Th1/Th2 model that are supported or refined.