66 Scabies and other mite infections

Acariasis in humans and animals is caused by a diversity of parasitic mites taxonomically grouped into the class Arachnida, subclass Acari. The zoonotic species that can transfer from birds and animals to man (e.g. Cheyletiella spp.; Dermanyssus spp. and Ornithonyssus spp.) are important in that they often cause major skin irritation or a hypersensitivity reactions or alternatively act as vectors of diseases such as scrub typhus. Like ticks the life cycle of mites involves four life stages of development. The female mite lays eggs on the host or in the environment; the eggs hatch into larvae and pass through two nymphal stages. All stages have eight legs except the six-legged larva. Transmission is predominantly via direct contact between hosts; however fomites have been recognized as a potential source of infestation although the importance of this is variable and dependent on the ability of the mite to survive in the environment. The geographic range of most zoonotic species is worldwide although some varieties may be rare or non-existent in some countries. No developmental change or propagation of the organism occurs during the transmission.

While mites rarely transmit disease to humans, they definitely impact health in ways that range from simply being a nuisance, to inflicting severe skin irritation that can cause intense itching. The most commonly encountered mites, including those that can adversely affect human health, are listed below.

Scabies is one of the oldest diseases known to man, and was recognized from as early as 1,000 BC, with references to disease symptoms in the Old Testament of the Bible, and by Aristotle (384–322 BC). Several writers describe the condition of human scabies, including Tabarii (970AD), Saint Hillegard (1098–1179) and Avenzoar (1091–1162). However, until the early seventeenth century scabies was described as a ‘corruption of flesh and blood’, thought to originate from an internal illness rather than the presence of mites in the skin. In 1687, Bonomo and Cestoni first described the ectoparasitic association of scabies, making it one of the first diseases of man with a known causative agent. However, their revelation was largely ignored for nearly 200 years. In 1778, de Geer gave the first accurate description of the scabies mite, and to his credit the parasite was commonly referred to as Sarcoptes scabiei de Geer (Buxton 1941). In 1868, Hebra published a well received treatise on scabies, and acceptance of the origin of this disease was finally established. Alternative names for the mite through history include Acarus siro var. scabiei, Acarus scabiei, Sarcoptes hominis, Sarcoptes communis, and its present designation as Sarcoptes scabiei.

Sarcoptes scabiei belongs to the phylum Arthropoda, class Acari, order Astigmata and family Sarcoptidae. The family Sarcoptidae includes Sarcoptes scabiei, Notoedres cati and Trixacarus caviae. The mite infests up to 40 different mammalian hosts across 17 families (Elgart 1990). Common hosts include humans, dogs, pigs and foxes. It has been widely debated whether these variants represent separate species, or if one highly variable species exist. Although S. scabiei mites isolated from different hosts are morphologically similar, cross infectivity studies have demonstrated they are physiologically different and largely host specific. This is supported by genetic studies showing substantial genetic variation between human-derived and canine-derived S. scabiei, even in mites collected from the same household (Walton et al. 2004a). Limited gene flow and apparent lack of interbreeding between these populations supports designation of separate species, but current convention still involves sub-typing mites according to their host species, for example, S. scabiei var. hominis (human), canis (dog), suis (pig) etc.

S. scabiei is a tiny mite, its ovoid body measuring 0.2–0.5mm long and 0.16–0.42mm wide. Adult female mites are 0.3–0.5mm, just visible to the naked eye and easily observed with microscopy. The mite is an opaque, creamy white colour with brown legs and mouthparts. The convex dorsal surface of the body is covered with numerous spines, setae and striations, and the ventral surface is flattened. Adult and nymph S. scabiei have four pairs of legs, while larvae have three pairs. Male mites are smaller (0.2–0.3mm) and appear darker and than females. They also differ from females on leg IV (males have short stalked pulvilli whereas females have long setae).

Historically, it has been difficult to study the passage of the mite through various life stages in detail, due the difficulty in locating mites on the host. As a result, much of the information on the scabies life cycle has been largely anecdotal and sometimes contradictory. Much of this uncertainty was resolved by Arlian and colleagues in 1988, using a model of New Zealand white rabbits experimentally infested with Sarcoptes scabiei var. canis (Arlian and Vyszenski-Moher 1988). The fertilized adult female penetrates the horny layer of the skin to form a burrow. It is thought they achieve this by secreting a proteolytic saliva like substance which dissolves the host keratinocytes. The female begins to lay her eggs just hours after starting the burrow, and continues to lay 2–3 eggs per day for the rest of her life (around 4–6 weeks). It appears that very few of these eggs actually develop into adult mites. The eggs hatch after about 50 hours of incubation. The larvae find their way to the skin surface to seek food and shelter in the hair follicles, where they remain for 3–4 days. They then moult into protonymphs, then tritonymphs, from which an adult male or female emerges. Following fertilization of the female the cycle begins again. The development from egg to adult requires 10–13 days.

Mites are extremely sensitive to desiccation; therefore survival off the host is highly dependent on relative humidity and temperature. In general, mite survival is favoured by low temperature and high relative humidity. The ability of mites to survive off the host has important implications for disease transmission. Arlian found that mites held for 24–36 hours at room temperature were still capable of host penetration, although these experiments involved artificial transmission (Arlian et al. 1984). The experiments of Kenneth Mellanby in the 1940s provided fascinating insights into many aspects of the disease, using conscientious objectors to World War II as human subjects. Exchanging clothes and sleeping in beds previously occupied by infested patients failed to transmit scabies, despite intensive efforts. He found that the disease was most commonly transmitted by skin to skin contact, and that individuals with higher mite numbers were more likely to transmit the disease (Mellanby 1944). From this it appears that fomites are an insignificant source of transmission, except in cases of crusted scabies, where shed skin may contain enormous numbers of live mites.

Previous attempts to transfer canine mites to mice, rats, guinea pigs, pigs, cattle, goats or sheep were unsuccessful; likewise human or pig mites could not be transferred to New Zealand white rabbits. Human infestations of scabies derived from other animal hosts are commonly reported; however are almost always self limiting. Host immunity appears to play a role in this process, since sensitization to animal transmitted scabies is very different to a human infestation.

Scabies infestation in animals is referred to as sarcoptic mange. It affects many companion animals and livestock such as dogs, horses, pigs and camels. It is a particularly serious disease and cause of mortality in wild red foxes, wombats, rabbits, agile wallabies and alpacas. Sarcoptic mange causes significant losses to primary industries; especially in pig herds (Davies 1995), and in the UK, mange is increasingly reported as a cause of production losses in imported Camelid species.

This initial penetration of host skin takes less than 30 minutes (Arlian et al. 1984). In a primary mange infestation symptoms generally take 2–6 weeks to develop, consistent with a delayed hypersensitivity immune response. In subsequent infestations sensitization is rapid, generally less than 48 hours (Mellanby 1944).

Clinical manifestations may vary according to species, but generally involve raised, red papules and vesicles. If infestation progresses to chronic mange, skin proliferation occurs, and mite-infested hyperkeratotic plaques form. The skin becomes thickened and wrinkled, and extensive alopecia results from a reduced supply of blood to the hair follicles. As with humans, intense pruritus is experienced and secondary bacterial infections may occur concomitantly with infestation. Mites appear to have a predilection for areas of thin skin, and sparse hair. Hence, in pigs, sheep and horses, sites first infected are generally the face and ears. In dogs, areas affected may include the muzzle, ears and face, legs, thighs, trunk and tail. Transmission of mites among a group of animals is most likely through direct contact or via contaminated bedding.

While the presence of thickened skin crusts is distinctive of advanced or chronic mange, diagnosis is more difficult in earlier stages as symptoms may mimic other skin conditions such as eczema, insect bites, dermatitis, or other non-sarcoptic mange conditions. The obvious ‘gold standard’ for diagnosis is the identification of mites, their eggs, or faeces (Burgess 1996). Skin scrapings are performed by firmly scraping with a scalpel at right angles to the skin, to remove superficial layers. Paraffin or mineral oil may be used to assist collection. Scrapings can then be examined under low power microscopy. Treating the scraping with 10% potassium hydroxide is useful for dissolving skin and improving resolution of mites, however will also dissolve faecal pellets. This technique has poor sensitivity due to low numbers of mites present in many infections. Sensitivity of skin scrapings is also influenced by the scraping technique, number of sites sampled, size of the scraping and the type of lesion sampled. Mites may also be observed in histological sections of skin biopsies.

The ideal diagnostic test for scabies would involve serological tests where the identification of mites was not required. ELISAs using whole mite extract to detect sarcoptic mange in animal herds are commercially available, however a significant degree of variation exists in sensitivity between kits (Lowenstein et al. 2004). These tests are also only suitable for diagnosis of infected herds rather than individual animals. The use of whole mite extracts may be problematic due to the heterogeneous combination of both host and parasite antigens and potential for cross reactivity (Walton and Currie 2007).

The disease progression of mange in pigs is well documented. Clinical symptoms are evident after about 2 weeks, by which time mites have begun to make numerous burrows in the skin. By four weeks keratinized crusts begin to appear. Crusts thicken as mites proliferate, which peak infestation at around 8–10 weeks. After this peak, crusts will become detached and regress three to four weeks later (Cargill and Dobson 1979). This natural regression suggests host immune responses act to inhibit growth of the mite population. Chronic mange appears to occur due to a failure to mount this protective immune response.

The humoral immune response in swine mange is well documented. Morsy and Gaafar (1989) reported high numbers of IgG, IgM, and IgA secreting cells in the dermis of infected pigs, peaking at 3 weeks post infection. In another study, circulating antibody titres peaked at about 8 weeks (Wooten et al. 1986).

Histological sections of crusted mange lesions in swine showed tracts of necrotic material surrounded by eosinophils, neutrophils, lymphocytes and mast cells. Papular, erythmatous lesions also contained numerous eosinophils and lymphocytes. The eosiniophilla observed in infected pigs appeared to be related to the degree of pruritus (Cargill and Dobson 1979).

Although these early studies have given great insights into swine immune responses to mange, there is still little understood regarding the temporality of cellular immune responses to infestation, nor the specific immune deficits predisposing animals to severe or chronic mange. Such information would assist the development of new immunodiagnostics and vaccines, of value for both animal and human populations.

Traditional treatments for sarcoptic mange involved the application of topical agents such as sulphur, lindane, organophosphates and synthetic pyrethroids. Although many of these are effective, difficulties in application and potential side effects preclude their use in many settings.

Nowadays, treatment for mange largely relies on the macrocyclic lactone (ML) family of drugs. They offer flexibility of use as they can be administered both systemically and topically. Additionally, they offer broad spectrum coverage against a range of endo and ectoparasites. Commonly used MLs for sarcoptic mange include ivermectin, doramectin, selamectin, moxidectin and milbemycin. The pharmacokinetics of MLs vary substantially in animals according to species, sex, age, and physiological status (reviewed in Cerkvenik-Flajs and Grabnar 2002). Therefore the choice of drug is influenced by the animal. Caution is advised with use of ivermectin in certain breeds of dog, due to mutations in the mdr1 gene. This mutation is present in dogs of the collie lineage, and results in a deficient P-glycoprotein pump, allowing the drug to cross the blood brain barrier. Signs of ivermectin toxicity in dogs include ataxia, increased salivation, depression, coma, or even death. Alternatives such as selamectin are reported to have a wider margin of safety. The recommended dosage of most MLs for sarcoptic mange is 200–400 µg/kg weekly for 4–6 weeks, depending on the severity of the condition. Moxidectin and doramectin are reported to be highly effective against mange in dogs, pigs and cattle.

Amitraz has been used successfully in camelid species which appear to be poorly responsive to MLs (Lau et al. 2007). For sarcoptic mange, the recommended dose is 0.25–0.5%, fortnightly for 4–6 weeks. Maximum effectiveness was obtained when acaricide therapy was combined with keratolytic bathing or clipping of hair to increase absorption. However, amitraz is contraindicated in pregnant and nursing bitches, as well as puppies. Reported side effects include depression, sedation, bradycardia (Curtis 2004).

Topical alternatives to amitraz include spot on formulations of fipronil, which may be useful for earlier stages of the disease, or where other treatments are contraindicated. A recently developed spot-on combination of imidicloprid and moxidectin, applied monthly for two months, was highly effective against canine mange (Fourie et al. 2006).

Prognosis depends on the severity of mange, the degree of secondary infection, and the host species. If treated promptly, and if re-infestation does not occur, the outcome is excellent in most animals. However in certain species, such as wombats, angora rabbits, and camelids, distress is significant and death may occur. Angorra rabbits may be particularly difficult to treat, and euthanasia is recommended in severe cases. Fortunately however, the new generation macrocyclic lactones have dramatically improved outcomes.

The scabies mite infecting humans is referred to as Sarcoptes scabiei var. hominis. Animals infested with scabies can transmit infections to humans, but due to the host specificity of the mites, infestations are transient. People who work closely with farm animals may be affected, especially from cattle infected with Sarcoptes scabiei var. bovis (‘dairyman’s itch’) or pigs with S. scabiei var. suis (‘pig handlers itch’). In humans, animal transmitted scabies can be distinguished from other forms of scabies by rapid onset of sensitization (within 48 hours) and the absence of burrows. Furthermore, areas affected reflect where direct exposure to the animal occurred. The disease is self-limiting, and removal of the animal often leads to clearing of symptoms. The following section will focus solely on infection caused by the human mite variant.

In a primary infestation of scabies, symptoms usually take 4–6 weeks to develop. This is thought to be due to delayed immune recognition, as sensitization is very rapid in subsequent infestations, generally less than 48 hours (Mellanby 1944). This delayed onset of symptoms contributes heavily to the spread of scabies, as people do not seek treatment until infestation and transmission is well established.

Often referred to as ‘classical’ or ‘uncomplicated’ scabies, ordinary scabies is the most prevalent form of the disease. It is caused by infestation with surprisingly few parasites, with the average number of female mites per patient less than 15, reducing with repeat infestations. Infestation commonly involves the hands, particularly the wrists and interdigital spaces. Elbows, knees, feet and genitalia may also be affected. Symptoms may vary substantially in severity, but almost always include intense pruritus, often worsening at night. Visible symptoms may include papular or vesicular lesions related to the site of mite burrowing, in addition to a more generalized itchy rash assumed to be part of the allergic response to the mite products. Mite burrows, often regarded as the classical indicator of scabies, can be observed as a thin, greyish, line of 5–15mm (Buxton 1941). However, burrows can be very difficult see with the unaided eye, particularly on dark skin, and are not always present.

Scabies is easily transmitted to young infants and children, probably because of increased body contact during these years. Lesions reflect those of adults, but with a more widespread distribution over the body, commonly involving the palms, soles, midriff, face, neck and scalp. This is attributed to the mites’ predilection for soft, folded areas of skin (Gordon and Unsworth, 1945). Vesicular and papular lesions are very common. Mellanby et al. (1942) noted a higher average number of mites in children, which may reflect underdevelopment of the immune system.

In addition to the symptoms described above, atypical manifestations of scabies may be observed. Nodular scabies involves the formation of extremely pruritic, reddish-brown nodules, which may persist for months following treatment. Mites are not found in nodules, making diagnosis difficult. In the elderly, inflammation of lesions may not be observed, although itching is intense. The distribution of mites may also involve the back, scalp, or behind the ears. The itching is commonly misdiagnosed, incorrectly attributed to dry skin, anxiety or senility. Scabies outbreaks in nursing homes are very common.

Akin to chronic mange in animals, crusted scabies is the most severe clinical manifestation of scabies, characterized by a proliferation of mites and formation of hyperkeratotic skin crusts. The condition was first described in 1848 as a variant of leprosy in Norway; and in 1851 mites were correctly identified as the causative agent. Thus, the condition is still commonly described as ‘Norwegian scabies’ despite having no inherent connection with this country. Crusted scabies in caused by the same mite as ordinary scabies, although it was once thought to be caused by a different variant, S. scabiei var. crustosa (Green 1989). It is now understood that crusted scabies results from the inability of the host immune system to control the mite burden, resulting in thousands to millions of mites present on a single patient in extreme cases. Areas affected differ to ordinary scabies and may include the soles of the feet and palms, back and buttocks. Crusting may be widespread or localized, with severe cases involving greater than 30% total body surface area. Crusts can range in thickness from 1–2mm up to 2–3cm and vary in their appearance. They can be loose, soft and spongy, containing many vacant burrows, and may be easily shed. Conversely, crusts can be very hard and adherent, with punch biopsies needed to reveal mites residing in the deep crusts. In many cases pruritus can be completely absent, but in other patients it may be extreme.

Scabies has been referred to as one of the most difficult diagnoses in dermatology. As described previously, symptoms may closely resemble those of other skin conditions. For practical purposes, diagnosis relies largely on clinical presentation and the history of the patient and their contacts. Despite 100% specificity, skin scrapings have very poor sensitivity due to the low numbers of mites present in ordinary human scabies and the difficulty in identifying burrows in some cases. Even when performed by an expert, a negative skin scraping does not exclude scabies.

Epiluminesence microscopy and videodermatoscopy have been proposed as accurate and non-invasive techniques, however these require specialized equipment. Visibility of mite burrows may be improved by the use of India ink. The use of a PCR-ELISA method for detecting previously undiagnosed scabies has been reported, but due to the technical expertise required and hypothesized low levels of S. scabiei DNA present on the skin it is not currently a viable approach.

No immunodiagnostic tests are currently available for human scabies, with research in this area historically impeded due to the absence of an in vitro culture system and limited availability of purified recombinant mite antigens. However, through the establishment of S. scabiei expressed sequence tag libraries, several candidate S. scabiei antigens have been reported (Fischer et al. 2003). The ability to produce a constant supply of purified recombinant antigen, facilitating detailed in vitro studies, suggests a highly specific diagnostic test for scabies may be a real possibility in the near future (Walton and Currie 2007).

Crusted scabies usually results from an unknown underlying immunodeficiency. Predisposing conditions include substance abuse, HIV, HTLV-I, systemic lupus erythematosus, type 2 diabetes, previous leprosy and immunosuppression in transplant recipients. It also may be seen in patients with cognitive deficiency such as Down’s syndrome, or in the elderly or institutionalized who may be unable to interpret the itch. Importantly, crusted scabies also occurs in people with no known immunological deficit. A recent clinical review of 78 crusted scabies patients in northern Australia found that 42% had no known risk factor (Roberts et al. 2005). These patients appear to have a specific, as yet unknown immune deficit predisposing them to crusted scabies.

Scabies patients generally have elevated levels of circulating antibodies, particularly IgG and IgE. The elevation of IgE in crusted scabies is striking and may be over 1,000 times higher than normal (Roberts et al. 2005). This dramatic, non-protective humoral response is probably due to the extreme antigenic load presented by the high mite burden. Specific antigens responsible for immune reactions include components of mite saliva and secretions, egg cases or faecal products.

Histopathological features of ordinary scabies include inflammatory infiltrates of eosinophils, lymphocytes and histiocytes. Whereas CD4+ T-lymphocytes were predominant in lesions of ordinary scabies patients, those from crusted scabies lesions were primarily CD8+ (Walton et al. 2008). Blood CD4+ and CD8+ levels and ratios were within normal limits in crusted scabies (Roberts et al. 2005), suggesting selective recruitment of these cells into the skin. Interestingly, no B-cells are observed in lesions of either crusted scabies or chronic mange, which may partially explain the lack of protective immune responses. Crusted scabies patients also have increased levels of inflammatory cytokines such as IL-4 (Walton et al. 2008). It is hypothesized that crusted scabies results from a preferential, non-protective Th-2 immune response, and interestingly IL-4 has been shown to stimulate keratinocyte proliferation (Yang et al. 1996). Similar Th-2 skewed responses have also been observed in atopic dermatitis and psoriasis.

Sulphur compounds have been used as acaricides for centuries, and are still a relevant option in certain cases today. It is generally used as a 2–10% precipitate in a petrolatum base. It is considered safe for pregnant and lactating women, and for infants younger than two months. Although effective and inexpensive, sulphur compounds are messy, smelly and sometimes irritating. Furthermore, multiple applications are often required for successful treatment. Therefore, sulphur has largely been abandoned for more ‘user friendly’ alternatives.

Ten per cent crotamiton ointment has been used as an acaricide since 1946. It has antibacterial, antiparasitic and antipruritic activity, which coupled with low-toxicity, makes it a popular option for children. However, its clinical efficacy is questionable, with low cure rates reported. For successful treatment, multiple applications are required.

Benzyl benzoate has been employed for its acaricidal properties since 1900, and remains widely prescribed today. At a concentration of 25% it is highly effective in vivo and in vitro. Unfortunately this concentration can cause severe skin irritation, particularly in children and thus it is generally not recommended for infants and pregnant women due to its allergenic potential. Treatment guidelines for this drug vary, with some recommending three applications within 24 hours. Given its extreme potency in vitro, this may be excessive.

Until recently, lindane was one of the most commonly used medications for scabies worldwide. It is a potent lipophilic insecticide first used for scabies in 1948. Potential neurotoxicity associated with lindane use has been a lingering concern, leading to its withdrawal from the market in many countries. Adverse effects reported include numbness, cramps, dizziness, seizures and even death. Toxicity is believed to occur through increased subcutaneous absorption, with infants and the elderly at particular risk. To minimize absorption, it is advised that lindane be applied to cool, dry skin, and not immediately after taking a bath. It is important to note that most side effects have been attributed to inappropriate application. Despite these issues, lindane remains as a first or second line treatment choice in many countries.

Permethrin is a synthetic pyrethroid first marketed in 1977. Originally used in an agricultural setting, it has been available for scabies for about 20 years, over which time its use has steadily increased in popularity. For scabies, permethrin is applied topically at a concentration 5%. Permethrin has potent insecticidal activity, but low toxicity and is well tolerated by most. When applied correctly, cure rates of over 90% for ordinary scabies have been observed, reportedly more efficacious than lindane or crotamiton. Permethrin has now replaced lindane as the first line treatment for scabies in Australia, the UK and the USA. It has also been successfully implemented for community treatment of scabies, but concerns have been raised regarding the emergence of drug resistance as a result of these treatment protocols (Pasay et al. 2009).

Although used for the treatment of sarcoptic mange in animals for many years, ivermectin is a relatively new treatment for human scabies. Ivermectin is the only oral acaricide, which has obvious advantages with ease of application simplifying treatment. Several studies report the efficacy of ivermectin for ordinary scabies, and concentrations of around 200 µg/kg appear to be the most effective. Given its relatively low residual activity in humans, and lack of demonstrated ovicidal activity, multiple treatments may be required in severe cases and to kill newly hatched mites. Ivermectin is particularly useful for crusted scabies, where topical application may not adequately penetrate the thick crusts. Recommended treatment for severe crusted scabies involves multiple doses of ivermectin, combined with keratolytic and topical therapy. Despite these comprehensive measures, treatment failures have been reported and clinical and in-vitro resistance to ivermectin has been observed in mites isolated from patients residing in scabies endemic northern Australia (Currie et al. 2004, Mounsey et al. 2009).

It can be seen that there are few acaricides available today that are safe, simple and effective. Furthermore, with emerging drug resistance a very real consideration, development of novel acaricides would undoubtedly be of benefit. Several natural agents with acaricidal properties have been described, including lippia oil (Lippia multiflora), camphor oil (Eucalyptus globulus), and pastes of tumeric (Circuma longa) and neem (Azadirachta indica). Tea-tree oil (Melaleuca alternifolia) had excellent acaricidal properties in-vitro at a concentration of 5% and was primarily attributed to the active ingredient terpinen-4-ol (Walton et al. 2004b).

Given that treatments are applied correctly, prognosis for ordinary scabies is good. It is important to consider itching may persist for some time after treatment most likely due to immune responses to dead mite products, and therefore residual itching is not necessarily indicative of treatment failure. Outcomes for crusted scabies are less favourable, and left untreated, secondary bacterial infections often lead to fatal sepsis. Previously, five-year mortality rates for crusted scabies exceeded 50%, but this has dramatically reduced with improved therapeutic protocols. Recurrent crusted scabies patients may experience permanent skin thickening and considerable de-pigmentation. The disease is physically and psychologically distressing, and due to the highly contagious nature of their infection patients are often stigmatized within their communities.

There are several reports commenting on the cyclical epidemiology of scabies, with epidemics apparently occurring every 30 years. Peaks in the incidence of scabies occurred between 1919 and 1925, 1936 and 1949, and 1964 and 1979 (Green 1989). These peaks roughly coincided with the major wars, and the cyclical theory is an over-simplification, as scabies epidemics are probably more reflective of the change in social environment at the time.

Scabies affects people of all ages, races and socioeconomic levels. It is clear that poverty and overcrowding are the two most important epidemiological cofactors. Since poor hygiene occurs concomitantly with these, it is often incorrectly labelled as a cofactor, although washing may help remove mites by physical dislodgement. In remote Aboriginal communities of northern Australia overcrowding is common, with up to 30 individuals often occupying the same household. This is almost certainly contributing to the endemic levels of scabies, exacerbated by poor resources and inadequate medical facilities.

Regardless of the acaricide used, there are three important principles governing scabies control:

Recently, there has been an increase in efforts to reduce the prevalence of scabies in endemic areas, due to concerns that bacterial infections secondary to scabies are linked to more serious complications such as renal and rheumatic heart disease. Control programs based on mass treatment with 5% permethrin have been applied in Panama and northern Australia, with varied levels of success (Taplin et al. 1991; Carapetis et al. 1997; La Vincente et al. 2009). Sustainability of these measures relies on strict treatment compliance, which may be difficult with topical acaricides. In contrast, mass treatment with single dose oral ivermectin was used successfully in the Solomon Islands, with trials in Australia now proposed.

Demodex spp. are commensal mites of mammals, residing in hair follicles and sebaceous glands and utilizing sebum as nourishment. There are more than 65 known species. Hosts include dogs, cats, horses, bovines, sheep, pigs and humans. Although mites are generally ubiquitous and non-pathogenic, under some circumstances infestation can result in demodectic mange, or demodicidosis. This can occur through hyper-proliferation of mites, probably due to failure of cell mediated immunity to control the mite population.

Demodex belongs to the order prostigmata, and is the sole genus in the family Demodicidae. The human species, Demodex folliculorum was first identified in 1842. It appears that most hosts harbour two or more species of Demodex, for example D. folliculorum and D. brevis in human, D. cati and D. gatoi in cats, etc. These species differ in morphology and habitats. Residing in hair follicles, the ‘long’ species measure 0.3–0.4 mm in length, while the alternate mite is shorter (0.1–0.25mm), stubbier, and resides in sebaceous glands. Demodex are semi-transparent, with two fused body segments. Four short legs are attached to first body segment, and the abdomen is distinctly elongated, making Demodex easily distinguishable from other mites. The lifecycle consists of egg, larvae, protonymph, nymph and adult, with completion in 18–24 days.

Demodectic mange has been reported, but is relatively uncommon in cats, horses, sheep and pigs. The condition is more serious in cattle, goats, and dogs. Dogs are now known to harbour three species of mite- D. canis, D. injai, and a more recently discovered unnamed short-bodied form (Hillier and Desch 2002).

It has been asserted by many authors that Demodex is present in the skin of over 50% of normal dogs, and becomes pathogenic only when the immune system fails to control mite proliferation. However other reports suggest prevalence is actually much lower and that the presence of any Demodex mites should be further investigated (Fondati et al. 2009). Accurate estimates of prevalence are difficult because of the low diagnostic sensitivity of skin scrapings.

Transmission between animal hosts generally only occurs early in life, through suckling or other close personal contact. Susceptibility may be influenced by genetics, nutrition and stress. Certain breeds appear to be more prone to the condition. In adult dogs, demodectic mange is usually associated with underlying immunosuppression, or can be induced by corticosteroid use.

In dogs, demodectic mange can be classified as juvenile or adult onset, with localized or generalized infestation. In juveniles, infection may become apparent between 3 and 9 months of age, with localized infections self-resolving in 90% of cases. Symptoms include hair loss, scaling, wrinkling and a ‘bruised’ appearance. Pustular mange involves formation of pustules through accumulation of mites in the sebaceous glands. Affected areas include the muzzle, chest, abdomen flanks and feet. Itching and secondary bacterial infection, especially by Staphylococcus is common, and serious demodectic pyoderma may result. Cattle are also prone to this form of the disease.

Diagnosis of demodectic mange in animals is generally made by deep skin scrapings at several sites over the body and identification by microscopy. Like Sarcoptes, resolution may be improved by pre-treatment of the skin scraping with potassium hydroxide. If numerous Demodex mites are identified across multiple regions, the infestation is treated as generalized (Ghubash 2006). D. canis may also be identified plucked hair, but this method is probably less sensitive. In bovines, Demodex mites may be easily identified in pustular exudate.

Proliferation of mites causes distension of the hair follicles, and blockage with mites and debris. Hyperkeratosis and hyperpigmentation occur, giving the skin a red or bruised appearance. The pustular form of the disease involves infiltration by leucocytes and lymphocytes. Demodectic mange in dogs appears to be associated with a compromised cell mediated immune response. It is also possible that proliferation of mites themselves also further depress the immune system. It is not understood why demodectic mange is more severe in dogs compared to other host species.

Localized demodicidosis can be treated with topical application of agents such as rotenone or benzyl peroxide. Other topical agents include pyrethroids, benzyl benzoate, or amitraz. For severe cases of generalized demodicidosis, systemic therapy with macrocyclic lactones such as ivermectin has been successful. The recommended dose is 0.4–0.6 µg/kg of ivermectin daily. Due to toxicity concerns in certain breeds, it is advisable to commence treatment with low doses of ivermectin and gradually increase to the therapeutic dose, enabling monitoring for side effects (Ghubash 2006). Other macrocyclic lactones such as milbemycin and moxidectin may also be considered as safer alternatives to ivermectin. Weekly topical treatment with a moxidectin-imidacloprid combination has also been successful (Fourie et al. 2009).

Assessment of acaricidal efficacy in demodectic mange is difficult, due natural cyclical regression of the disease and changes in the mite population. This is particularly evident in bovine demodicidosis, with mite infested nodules often disappearing after 2–4 months before reappearing. Treatment should be continued for 4–6 months, or until three consecutive skin scrapings are clear of mites. Demodectic mange complicated by secondary bacterial infection requires adjunctive therapy with antibiotics.

Prognosis depends on the extent of infestation, time of diagnosis, and degree of secondary infection. In many hosts, localized infection, and juvenile dogs, mange lesions will self-resolve within six to eight weeks. Because of the difficulties in eradication, prognosis is poor unless the infections are treated early.

Demodex are the most common ectoparasites of man. Humans may harbour two species of Demodex- D. folliculorum, residing in hair follicles, and D. brevis, located deeper in sebaceous glands and ducts.

Clinical manifestations of heavy Demodex infestation include pityriasis folliculorum, involving faint redness, burning and the appearance of fine follicular ‘plugs’; and the more severe rosacea-like demodicidosis (Baima and Sticherling 2002). Symptoms of demodicidosis resemble rosacea, with redness, scaling, oedema, papules and papulopustules containing mites. Other conditions possibly associated with Demodex infestation include acne, impetigo and blepharitis. Areas affected are consistent with the sebum-producing sites of mite predilection, such as the cheeks, nose, temples and eyelids.

Diagnosis of D. folliculorum may be made by skin scrapings and treatment with 10–40% potassium hydroxide prior to examination by microscopy. Generally, greater than 5 mites observed per cm², is indicative of pathology (Baima and Sticherling 2002). Standardized skin surface biopsy is a non-invasive method described to identify mites in horny layers of skin and follicular contents (Forton and Seys 1993). There are few reliable diagnostic methods for D. brevis due to its depth in the skin.

The role of Demodex in skin pathogenesis has been debated for decades. Several studies show that rosacea patients have a higher number of mites compared to age–matched controls (Forton and Seys 1993; Georgala et al. 2001). This is further supported by cases of rosacea refractory to conventional treatment, but cleared by acaricides. Histological examination of Demodex associated papulopustular rosacea showed inflammation of follicles, with infiltrates of CD4+ T lymphocytes, macrophages, and Langerhans cells, indicative of a cell mediated, delayed hypersensitivity response to mite antigens (Georgala et al. 2001). While there is no direct evidence of causal association, most concede that the environment created by increased vascularization of rosacea is likely favourable to Demodex proliferation, which then further exacerbates the condition.

Studies have shown that conventional treatments for rosacea such as metronidazole do not reduce Demodex burden. Treatment with topical lindane and permethrin at concentrations of 1% is not sufficient to kill mites. In general, treatments which are effective for Sarcoptes should also be effective against Demodex. Successful treatment regimens include 10% benzyl benzoate, 10% crotamiton, 5% permethrin, and oral ivermectin. The irritation experienced with benzyl benzoate and sulphur may preclude use, especially on sensitive facial skin. In this case, crotamiton, ivermectin or permethrin are good choices. Tea-tree oil has also been reported to be effective against ocular demodicidosis, but at high concentrations (50%) which may cause irritation in some patients (Gao et al. 2005).

Demodex is considered to be part of normal skin flora. The prevalence of Demodex infestation increases with age, estimated to be around 30% in young adults, increasing to 100% in older age (Forton and Seys 1993). This is likely due to changes in sebum production. In most cases, mite density is low and progression to demodicidosis is rare. Women may be at an increased risk of developing clinically relevant infestation, together with patients with underlying immunosuppression, such as HIV or leukaemia.

Cheyletiella spp. are non-burrowing mites of the order prostigmata and family Cheyletoidea. Fur mites live on the keratin layer of skin in mammals, most commonly rabbits, cats and dogs. The first species to be identified by Megnin in 1878 was C. parasitivorax, the rabbit fur mite. It is now know that there are actually several closely related host specific species, as described by Smiley in 1965:

Cheyletiella are small, very motile mites with characteristic bristles and hooks which enable them to hold onto the hairs of the host. The life cycle progression is 21 days, and female mites lay eggs which attach to hairs 2–3 mm above the skin surface. Mites appear to stimulate keratin production, and infected animals develop a dandruff-like scale and scurfy appearance. This may be accompanied by pruritus, dermatitis and alopecia, particularly in cats. Infections in adult dogs are usually mild, although it appears that some breeds such as Spaniels are more susceptible. Mites and eggs are easily identified in infected animals by superficial skin scale scrapings and examination of hair under a dissecting microscope.

The high motility of the mite, combined with the fact that they can live off the host for up to 10 days, means that mites are very contagious and potential for zoonoses is high. Transient hypersensitivity reactions commonly occur in humans exposed to the mite through infected pets. Humans are likely an accidental host, and mites have been described as ‘biting and running’. Zoonotic infections with Cheyletiella were recognized as early as 1918. Irritation usually develops within 2–4 days of exposure, although if daily contact is maintained chronic irritation is observed. Symptoms involve pruitic, papular lesions directly linked to areas of contact with the animal, e.g. the chest, abdomen, and forearms.

In animals, infestation can be cleared by conventional acaricides. Effective treatments reported include spot-on fipronil, or host appropriate macrocyclic lactones such as ivermectin, milbemycin, or selamectin. Skin scrapings should be repeated after 4–6 weeks, and treatment continued for 2–4 weeks after infestation appears to have cleared. Due to the high potential for survival off the host, bedding and other environmental contacts should also be decontaminated. Affected humans require no specific treatment, although soothing agents such as calamine lotion can assist until the animal is cleared.

The diverse array of Trombiculid mites normally live in soil and vegetation, except for the parasitic larval stage, which feed off man or other mammals. Common species are Trombicula autumnalis (European harvest mite, berry bug, red itch mite) and Trombicula alfreddugesi (American chigger, red bug). The bite of chigger mites can cause intense irritation and dermatitis in man, but are relatively harmless. More insidious however is the capacity for the south east Asian Trombiculids Leptotrombium akamushi and L. deliense to transmit the bacteria Orientia tsutsugamushi—the causative agent of scrub typhus.

The rash (‘scrub itch’) associated with trombiculid mites has been acknowledged in China for hundreds of years, with references dating back to 500AD. Mites were first recognized in North America in 1733. Trombiculidae were first described as an independent family by Ewing in 1944. The association between scrub typhus and mites was not identified until 1899, and chiggers received renewed attention after the Second World War, due to the problems they caused to soldiers.

Trombiculid mites belong to the order prostigmata, and superfamily Trombidioidea. There are four sub families, and at least 35 genera/subgenera. The most medically important family are the Trombiculidae, with around 40 different species. Genera include Trombicula, Neotrombicula, Eutrotrombicula, Leptotrombidium, and Ascoschoengastia. The larval stage of the mite may feed off man and other mammals, birds and reptiles. The fact that man is an atypical host may explain the extreme irritation caused by the bite.

Trombiculid larvae are very small (0.1–0.2mm), covered with long setae, and motile. They are yellow to bright red, depending on their stage of engorgement. Adult females can live up to one year and can lay up to 15 eggs per day in damp soil. This is dependent on higher soil humidity and temperature, so chiggers are more problematic in summer months or in tropical regions. Larvae hatch from eggs and then migrate to grass or other vegetation to await passing hosts. These hosts are normally small rodents, but may be other mammals including humans, domestic and grazing animals. Larvae feed off digested skin, lymph and other fluids. They only take a single meal and drop off the host once engorged, returning to the soil to continue the lifecycle, which takes 50–70 days.

In the case of scrub typhus, rikettsia are transmitted by trombiculid mites of the genus Leptotrombidium. The bacteria are transmitted transovarially (through the ovary) so the female mite herself plays no active role in transmission. During its single feed on a mammalian host, the larvae is capable of both transmitting and becoming infected with the rickettsia.

Trombiculid mites feed on many warm-blooded animals and dogs, cats, horses, cattle and birds can all be affected. These mites have a predilection for soft, moist areas, and are commonly found in clusters. In dogs and cats, they attach to the feet and up the legs, abdomen, face and pinnae. Similarly, horses and cattle will be attacked on the lower eggs and face.

In animals, heavy trombiculid mite infestations may be seen with the naked eye, with the distinctive colour of the mites giving affected areas a ‘paprika’ like appearance. Host responses to mites can be variable, but generally will cause intense pruritus, eyrethema and scratching. Hypersensitivity reactions involving wheals, papules and severe excoriation may develop.

Diagnosis can often be made by visual inspection. However if excoriation and exudates are present, a skin scraping may be needed to identify the mites microscopically.

Mites attach to the host and secrete salivary enzymes to break down the skin. These digestive secretions also cause surrounding tissues to harden, forming a stylosome (feeding tube), where digested material, lymph and cell debris can be sucked up and ingested. Contrary to popular belief, mites do not burrow, feed on blood, or lay eggs on the host. Larvae may feed for up to ten days before becoming engorged and falling off the host. Irritation to the host occurs due to an allergic immune response to secretory products.

Conventional acaricides and insecticides such pyrethroid based dips will be effective at killing mites, and topical or injectable steroids can be used to help relieve irritation. As there is a high risk of re-infection, especially during warmer weather, the best control measure is to avoid areas where chiggers are found.

Sites of infestation are where skin is soft, moist and protected. Areas of predilection therefore include ankles, behind the knees, groin, armpits, and areas of constriction, for example beneath underwear and belt sites. Unlike animals, chigger bites develop after mite exposure, and may continue for a week or longer. Therefore it is unlikely that mites will be identified directly on the patient. Due to their delicate skin, infants may experience more severe reactions.

Itchy papules appear at the site of infestation, and may enlarge to form nodules. The bite of the mite in humans leaves a characteristic black spot in the centre, which may be a useful diagnostic aid. In heavy infestations lesions may be extensive. Delayed hypersensitivity reactions may manifest as red welts with a white, hard central area on the skin that itches severely.

Control centres on personal prophylaxis such as insect repellants, and reducing the mites opportunity to access the skin through adequate clothing protection. Laundering clothes at high temperatures will effectively kill any remaining mites. Temporary relief of itching may be achieved with agents such as hydrocortisone or calamine lotion. The application of heat soon after suspected exposure to chiggers may help eliminate mites before symptoms develop.

In areas where scrub typhus is a risk, insecticide treatment of vegetation will help to reduce mite populations. On a larger scale, burning or clearing of vegetation will confine mites to specific areas away from potential human contact.

Scrub typhus is commonly seen in the Asian-Pacific region, spreading from India and Pakistan in the East, Korea and Siberia in the North, and the Pacific Islands and northern Australia to the South. This region is sometimes referred to the ‘tsutsugamushi triangle’. This endemic region is host to around 1 billion people, and an estimated 1 million cases of scrub typhus occur annually. Mortality rates range from <1% to 50%, depending on the rickettsial strain involved and treatment (Chattopadhyay and Richards 2007). Transmission of scrub typhus is dependent on the presence of the Leptotrobium vector, which can be found anywhere suitable for rodent populations and where ground moisture is sufficient for mite survival. Most common sites are the vegetation areas between woods and clearings, as these become re-colonized by scrub, trombiculid mites and their rodent hosts. The main risk factors for contracting scrub typhus are therefore occupational— outdoor related agricultural activities including fruit picking, chestnut gathering, or taking rest breaks amongst mite-infested vegetation (Kim et al. 2007).

Dermanyssus and Ornithonyssus are members of the order mesostigmata and family Dermanyssoidea. D. gallinae is a haematogphagous mite commonly known as the chicken or poultry red mite. D. gallinae mites were first described in 1834 by Duges. The mites are up to 0.7mm with a grey to dark red appearance (depending on time since blood meal). Mites feed at night for 0.5–1.5 hours, but generally live away from their host, residing in wall cracks, crevices and nesting boxes. They can survive around 8 months without feeding and are resistant to desiccation but do not survive well in humid conditions. With a very short life cycle of seven days, mite populations can grow exponentially and result in heavy infestations.

Poultry red mites result in substantial morbidity and loss of productivity to the industry, causing anaemia, restlessness, decreased egg production and egg quality. Heavy infestations may even cause death. It is also known that D. gallinae are reservoirs of several bacterial pathogens, which may have more serious implications for zoonotic disease transmission. Studies on D. gallinae have identified pathogens such as St-Louis encephalitis, Pasturella multocida, Erysopelothrix rhusiopathiae, Coxiella burnetii and Listeria monocytogenes. However presence is not indicative of vectorial capacity, and few studies have been able to demonstrate transmission in the field. Recent evidence however has shown that D. gallinae was implicated in the transmission of salmonellosis on poultry farms (Valiente Moro et al. 2009). As this is one of the most commonly encountered zoonotic diseases in man, control of the poultry mite is of increasing importance.

Ornithonyssus sp. are similar to Dermanyssus in appearance, differing in the shape of anal plates (Dermnyssus is triangular, while Ornithonyssus is pear-shaped). The two predominant species are O. sylviarum (northern fowl mite) and O. bursa (tropical fowl mite). O. sylviarum was first identified by Canestrini and Fanzago in 1877. The taxonomic position of Ornithonyssus has been variable through the years, having being placed in the genera Macronyssus, Liponyssus and Bdellonyssusis. Ornithonyssus infestations of poultry are more common in the USA, with Dermanyssus playing a minor role in this region. As opposed to Dermanyssus, Ornithonyssus mites lay eggs on the host, and feed during both day and night, and thus are a constant source of irritation.

Poultry mites can induce irritation in humans, and heavily infested flocks are a source of itching dermatitis to poultry workers. Like most other mite zoonoses, infestation is transient. Inhalation of O. sylviarum allergens may be a source of occupational asthma in personnel working in poultry premises (Lutsky and Bar-Sela 1982).

Control of poultry mites is problematic due to prolonged survival time off the host and niche habitats. Traditional control methods involved spraying of pens with agents such as carbamates, organophosphates and pyrethroids. The choice of acaricide is limited due to environmental and food-safety issues. Additionally, resistance has been reported for pyrethroids and organophosphates. Systemic acaricides such as ivermectin have been tested, but are only effective at extremely high doses (2–5 mg/kg), precluding its use due to toxicity and cost-effectiveness concerns. There is now an increasing research focus on the use of alternative control methods, such as natural product extracts and immunological approaches to combat this problematic group of mites.

Closely related to poultry mites are the haematophagous Ornithnyssus bacoti. The mite infests rodents, most commonly rats, mice, gerbils and hamsters. O. bacoti are morphologically similar to other macronyssid mites, but can be distinguished by the location and shape of genital shields, and are hairier when viewed by microscopy. Contrary to their common name, O. bacoti mites are prevalent in all continents where rodents are present. Like D. gallinae, the tropical rat mite lays eggs and spends time predominantly away from the host. They have low host-specificity and subsequently, in the absence of a rodent host they will readily seek out humans as opportunistic blood meals. Dermatitis associated with tropical rat mites was first described by Hirst in 1913, and has been frequently reported worldwide. Symptoms of rat mite dermatitis in humans resemble that of flea bites, with flat to raised erythmatous lesions. Mild pain may be felt upon biting, followed by intense pruritus. Lesions normally appear in linear configurations or in groups. Symptoms have been described in workers from animal laboratory facilities, and also in people occupying rodent-infested premises. Mites are rarely found on hosts but may be readily located in the host environment. Eradication of the mites through conventional acaricides will resolve symptoms. O. bacoti has also been shown to harbor organisms such as Pastuerella tularensis, but there have been no reports on transmission of diseases to humans, with the exception of a 1931 report implicating mites in the spread of human typhus.

Trixacarus caviae is a burrowing Sacroptid mite closely related to Sarcoptes scabiei. It appears to be host specific for guinea pigs, causing intense pruritus, dermatitis, alopecia and crusting. Infestations may be associated with secondary bacterial infection, complications of which may lead to seizures and death of the animal. Trixacarus mites can be distinguished from the other Sarcoptid mites (S. scabiei and Notoedres cati) in their smaller size (females <200 µM) and differing appearance of dorsal setae and spines (Fuentealba and Hanna 1996). Guinea pigs with genetic resistance to infection with the nematode Trichostrongylus colubriformis are more susceptible to T. caviae, with higher mite numbers and increased hyperkeratosis (Rothwell et al. 1989). Pruritis and popular dermatitis has been reported in humans in contact with infested guinea pigs, but these are again transient and self limiting (Kummel et al. 1980).

House dust mites are free living, astigmatid mites belonging to the family Pyroglyphidae. These mites include Dermatophagoides farinae, D. pteronyssinus, and Euroglyphus maynei. Mites feed on shed human and animal skin and organic debris, and are a common household occupant, thriving wherever dead skin may accumulate, such as carpets and pillows. Mites flourish in areas of high relative humidity, however even in drier climates proximity to humans provides the mite with adequate moisture levels. Mite faecal pellets are allergenic and can induce a range of hypersensitivity reactions, including asthma. Signs of house dust mite allergy include sneezing, itchiness, watery eyes, runny nose, and eczema. House dust mite allergy is diagnosed by determining IgE reactivity to various Dermatophagoides antigens.

Grain and storage mites comprise over 10 genera, including Acarus, Glycyphagus, Tyrophagus, Chortoglycphus and Blomia. They are associated in grain and meal, stored products, and processed foods such as flour and cheese. They present an occupational hazard to humans exposed from straw, grain silos, bakeries, warehouses and other storage centres. Exposure can cause occupational asthma or various forms of allergic dermatitis, commonly known as ‘grain itch’, ‘straw itch’, ‘bakers itch’ etc.