Dermatology Online Journal

Recent immunologic considerations regarding the itch and treatment of scabies
Craig G Burkhart MD MPH
Dermatology Online Journal 12 (7): 7

Medical University of Ohio at Toledo, and Ohio University College of Osteopathic Medicine, Sylvania, Ohio. cgbakb@aol.com

---

Abstract

Scabies continues to be a major public health problem. Recent findings reveal that these mites produce substances that modulate the host's immune response resulting in the latency period prior to symptoms. In terms of treatment, two cases of ivermectin resistance have become apparent in Australia in patients treated over fifty times with the agent. Additionally, work in the development of vaccination of hosts with antigenic midgut proteins of mites to control ectoparasitic infestations continues.

---

Human scabies is a common public health problem worldwide with an estimated 300 million infected individuals. The associated mite, Sarcoptes scabiei var humanus, lives its entire lifespan in the stratum corneum of the human host. The adult female mite, which measures 0.4 by 0.3 mm and is too small to be seen by the naked eye, burrows a 1-cm long tunnel in the stratum corneum to the boundaries of the stratum granulosum of the epidermis. She lays her eggs within this burrow, where the emerging larvae complete their maturation. This organism has no protective mechanisms against enemies, because it has none.

Classic scabies is manifested as nocturnal pruritus. The pruritus associated with scabies results from a type-IV immunologic reaction to the mite, its secretions, or its fecal pellets. The incubation period prior to symptoms formerly was considered to be as little as 3 days to 6 weeks, but prolonged latency periods of 7 months or more are now acknowledged. Moreover, asymptomatic scabies-infested people are not uncommon and can be considered to be carriers [1]. Similar to the human response to other insects such as fleas, yellow jackets, and mosquitoes, there is a wide range of clinical responses to an infestation with scabies. There are numerous atypical presentations of this entity. Thus, within the same household, some of the occupants may be totally asymptomatic, while others demonstrate skin lesions and considerable itching.

Mites produce substances that modulate normal itch symptoms

The mites produce substances that modulate the host's immune response [2, 3, 4, 5]. Some of these substances stimulate keratinocytes to produce interleukin (IL)-1α and IL-1β [3]. In vitro studies of whole body extracts of the scabies mites reveal additional substances that modulate cytokine secretion by fibroblasts, keratinocytes, and monocytes [4, 5]. Additionally, the mites emit substances that stimulate the proliferation of T-regulatory cells and their secretion of IL-10, which would inhibit the inflammatory and immune responses in humans to the mites [2]. Thus, the arthropod itself is genetically endowed with immunologic material to thwart the host from responding to its presence in the skin, at least initially.

First case of ivermectin resistance in humans

Scabies is endemic in many remote Aboriginal communities in northern Australia. Some of the inhabitants have been treated with over 50 oral doses of ivermectin over the last 5 years [6]. Clinical and in vitro evidence of ivermectin resistance has developed in two individuals [6]. No ivermectin-resistant arthropod has previously been reported to cause human infestation, however, such resistance has been induced in the laboratory under intense drug exposure with the horn fly [7], fruit fly [8], and a species of tick [9].

From their experience in this endemic population, Currie et al. now recommend a weekly dosing interval for ivermectin rather than their previous use of a fortnight between treatments [6]. Additionally, they note that higher doses have been suggested by some authors [1].

Summary of available treatments for scabies

The standard treatment of scabies has been the application of a prescription scabicide overnight to the entire body surface. The scalp is normally excluded with adults, but treatment of this body region is important in infants. Inasmuch as the mite prefers warm, moist areas, the finger and toe creases, intergluteal cleft, umbilicus, and skin beneath finger and toe nails must be treated thoroughly. To reduce the incidence of reinfestation and fomite transmission, clothing, linens, and towels used within the previous week should be washed in hot water and dried on high heat. All family members and close contacts must be treated simultaneously, even if they have not developed pruritus or other clinical signs of scabies. The relatively common occurrence of asymptomatic mite carriers is greatly underappreciated.

The antiparasitic agent, ivermectin, has been used for 10 years in humans for this disease and is slowly gaining prominence because of its high efficacy, ease of treatment, and low risk of side effects. A summary of the standard topical therapies with comments are listed in Table 1.

Future treatment of scabies—vaccination

The immunization of a host with antigenic material, usually midgut proteins, from blood-feeding arthropods to control ectoparasitic infestations has gained recent interest. Insects fed on immunized hosts containing these antibodies are damaged by specific antibodies or immune complexes from the hosts' blood, resulting in rupture of the parasites' midgut. For example, cattle have been vaccinated successfully against both the blood-sucking tick, Boophilus microplus, and the louse, Linognathus vituli, by means of antigenic proteins from the tick gut. Initial work with scabies with similar midgut antibodies has been auspicious. Specifically, scabies mites ingest host immunoglobulin directed against the mites as identified by the localization of fluorescent-labeled antibody to host immunoglobulin in the anterior midgut and esophagus of fresh mites removed from the host [10]. This is significant in that scabies is a non-blood-feeding ectoparasite that ingests host antibody only while feeding on tissue fluid that seeps into the stratum corneum. Further immunization studies for scabies are warranted.

References

1. Burkhart CG, Burkhart CN. An epidemiologic and therapeutic reassessment of scabies. Cutis 2000;65:233-40. PubMed

2. Arlian LG, Morgan MS, Paul CC. Evidence that scabies mites (Acari: Sarcoptidae) influence production of interleukin-10 and function of T-regulatory cells (Tr1) in humans. J Med Entomol 2006:43:283-7. PubMed

3. Arlian LG, Vyszenski-Moher DL, Rapp M, Hull BE. Production of IL-1α and IL-1β by human skin equivalents parasitized by Sarcoptes scabiei. J Parasitol 1996;82:719-23. PubMed

4. Arlian LG, Morgan MS, Neal JS. Modulation of cytokine expression in human keratinocytes and fibroblasts by extracts of scabies mites. AM J Trop Med Hyg 2003;69:652-6. PubMed

5. Arlian LG, Morgan MS, Neal JS. Extracts of scabies mites (Sarcoptidae: Sarcoptes scabiei) modulate cytokine expression by human peripheral blood mononuclear cells and dendritic cells. J Med Entomol 2004;41:69-73. PubMed

6. Currie BJ, Harumal P, McKinnon M, Walton SF. First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei. Clin Infect Dis 2004:39:e8-e12. PubMed

7. Byford RL, Craig ME, DeRouen SM. Influence of permethrin, diazinon, and ivermectin treatments on insecticide resistance in the horn fly (Diptera: Muscidae). Int J Parasitol 1999;29:125-35. PubMed

8. Kane NS, Hirschberg B, Qian S. Drug-resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. Proc Natl Acad Sci USA 2000;97:13949-54. PubMed

9. Benavides E, Romero A. Preliminary results of a larval resistance test to ivermectins using Boophilus microplus reference strains. Ann NY Acad Sci 2000;916:610-2. PubMed

10. Rapp CM, Morgan MS, Arlian LG. Presence of host immunoglobulin in the gut of Sarcoptes scabiei (Acari: Sarcoptidae). J Med Entomol 2006;43:539-42. PubMed

© 2006 Dermatology Online Journal