Iran J Parasitol: Vol. 12, No. 1, Jan-Mar 2017, pp. 12-21 Iran J Parasitol Tehran University of Medical Open access Journal at Iranian Society of Parasitology Sciences Public a tion http:// ijpa.tums.ac.ir http:// isp.tums.ac.ir http:// tums.ac.ir Review Article Human Permanent Ectoparasites; Recent Advances on Biology and Clinical Significance of Demodex Mites: Narrative Review Article Dorota LITWIN 1, WenChieh CHEN 2, 3, Ewa DZIKA 1, Joanna KORYCIŃSKA 1 1. Dept. of Medical Biology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland 2. Dept. of Dermatology and Allergy, Ludwig-Maximilian-University of Munich, Munich, Germany 3. Women’s Health Center, Far Eastern Memorial Hospital, New Taipei, Taiwan Received 10 Feb 2016 Abstract Accepted 21 Jul 2016 Background: Demodex is a genus of mites living predominantly in mammalian pilosebaceous units. They are commonly detected in the skin of face, with in- creasing numbers in inflammatory lesions. Causation between Demodex mites Keywords: and inflammatory diseases, such as rosacea, blepharitis, perioral and seborrhoeic Demodex folliculorum, dermatitis or chalazion, is controversially discussed. Clinical observations indi- Demodex brevis, cate a primary form of human Demodex infection. The aim of this review was to Demodicosis, highlight the biological aspects of Demodex infestation and point out directions Ectoparasites for the future research. Methods: We conducted a broad review based on the electronic database sources such as MEDLINE, PubMed and Scopus with regard to the characte- ristics of the Demodex species, methods of examination and worldwide epidemi- *Correspondence Email: ology, molecular studies and its role in the complex human ecosystem. [email protected] Results: Demodex mites are organisms with a worldwide importance as they act in indicating several dermatoses, under certain conditions. However, correla- tions between Demodex and other parasites or microorganisms occupying one host, as well as interactions between these arachnids and its symbiotic bacteria should be considered. There are few methods of human mites' examination depending on purpose of the study. Nevertheless, paying attention must be needed as polymorphism of Demodex species has been reported. Conclusion: Overall, the present review will focus on different aspects of De- modex mites’ biology and significance of these arachnids in human’s health. 12 Available at: http://ijpa.tums.ac.ir Litwin et al.: Human Permanent Ectoparasites: Recent Advances on Biology and Clinical … Introduction here are three main groups of para- Therefore, it is really important to know bet- sites that can cause disease in hu- ter the biology of Demodex mites in order to T mans: protozoans, helminths and understand the complex relationship between ectoparasites. Parasitic mites of humans in- these mites and humans and most of all, to clude chiggers (i.e. Trombicula autumnalis), hu- apply the right treatment when needed. man scabies (Sarcoptes scabiei var. hominis) and Demodex mites. Among them, only Demodex Methods mites are permanent ectoparasites of human and other mammalian pilosebaceous unit. A We conducted a review based on the data- total of 140 species or subspecies have been base sources such as MEDLINE, PubMed, identified worldwide in 11 orders of mammals and Scopus. Keyword used for searching all including humans (1). Human Demodex have valuable information were: Demodex, Demodi- been found in nearly all age and racial groups cidae, human mites and its combinations with (2- 4). all words regarding to biological characteristic There are two species of parasitize humans: of the species and interactions among one D. folliculorum, and D. brevis. The first usually host organism, epidemiology and methods of lives in the follicular infundibulum, while D. examination or molecular studies. The search brevis is located in sebaceous and Meibomian included the articles published up to the 2015. glands (5). They infect mainly skin of the face No restrictions were placed on study design or and scalp, although both species were original- language of publication. ly found in the ear canal (6). D. folliculorum of- ten occupies follicles of the eyelashes (7-9). Results Identification of D. folliculorum in the nipple discharge (10) or in biopsy specimens of nevi Classification, morphology and life cycle (11) and skin cancers (12) has been reported. Mites are small arthropods belonging to the Every human being carries a colony of 1000 subclass Acari. They live in an enormous to 2000 Demodex mites (13). Although Demodex number of habitats; often spend their entire mites are considered to be highly host species- lives as parasites. Demodex mites belong to the specific, cross-infections between humans and superorder Acariformes, order Trombidi- animals have been documented (14, 15). formes, suborder Prostigmata, superfamily However, the reliability of these rare case re- Cheyletoidea, family Demodicidae and genus ports remains to be verified, particularly be- Demodex (1). In humans, parasitize two spe- cause of the polymorphism reported in D. ca- cies: D. folliculorum and D. brevis. Lately, the nis and D. folliculorum (16,17). Many studies phenotypic differentiation among the former have shown higher density of the parasites in has been found (16). Mites of the family De- diseased inflammatory skin than in normal modicidae are tiny organisms (usually 0, 2-0, 4 skin, but whether it is the cause or result of mm). Most of them have vermiform elonga- the inflammation remains unclear (18-20). tion of the body, which consists of three main When compared to well-known skin microor- parts: gnathosoma, podosoma and opistho- ganisms inhabiting the human microbiome, soma. Four pairs of legs are spaced along the such as Propionibacterium acnes, Staphylococcus epi- podosoma, each with a pair of claws (21). The dermidis and Malassezia, Demodex mites possess mouthparts include a round oral opening with a much higher hierarchy in the timeline of life a spindle hypostome and stylet-like chelicerae evolution. (21) as they feed on the contents of sebum Available at: http://ijpa.tums.ac.ir 13 Iran J Parasitol: Vol. 12, No. 1, Jan-Mar 2017, pp. 12-21 and epithelial cells. The limitations of these shortest (28). Survival of both species was mites to the dimensions of hair follicles have longest on human serum and resulted in a reduction of organ systems. They 1640/seroculture solution (28). do not have a tracheal system and their diges- In developing ex vivo culture model of De- tive system is highly modified, consisting of: modex mites' artificial skin can be helpful. The the chelicerae and a poorly formed midgets model of human skin tissue has been devel- lumen with no hindgut and anus (22). The lat- oped yet but the presence of hair follicles and ter helps to avoid triggering an immune re- blood vessels are crucial for cultivating human sponse from the host, but there are issues with mites. Preliminary studies of German scien- waste excretion that consequently leads to a tists on the combined skin are promising (29). time-limited life. Demodex spends its entire life cycle (14-18 d) Molecular studies on the host (8). The reproduction is sexual, The presence of hard chitinous exoskeleton involving adult males mating with adult fe- makes Demodex mites difficult to study at the males. Nymphs are probably ignored, as they molecular level. Therefore, searching for their are not sexually matured. The male genital ori- genotype has only started recently (17, 30). fice is placed dorsal, between a second pair of The first partial DNA sequence of D. canis legs, while the vulva extends ventrally at the chitin synthase (CHS) was submitted to Gen- level of the fourth pair of legs (23). Adults co- Bank (No. AB080667). The CHS gene frag- pulate in the opening of the hair follicle (8). ments of D. canis and D. brevis were cloned and There is no data on mating behavior, but we sequenced with results showing similarities at can suppose it goes similarly to other mites: a level of 99.1%-99.4% between these two male and female face in opposite directions, species (31). In the same year, genomic DNA the penis is inserted into the female opening extraction from individual Demodex mites was and sperm are transferred to the female (24). carried out successfully (1). Copulation may take up to 48h in house-dust The genetic relationship between D. folliculo- mites, during which time the female is mobile rum and D. canis is closer than that between D. (24). The eggs of Demodex mites are lying in- folliculorum and D. brevis (32). The prediction of side the hair follicles or sebaceous glands. The the secondary structure for the complete subsequent stages are larva, protonymph, deu- rDNA sequence of D. folliculorum was focused tonymph and adult (25). (33). In the effort to identify inter- and intras- pecies variation, the cytochrome oxidase I Demodex culture model (cox1) gene region is a useful tool in discrimi- The only way to obtain Demodex mites is col- nating between populations such as those of lect them from human beings, thus setting up D. folliculorum (17). Intraspecies variations culture model would greatly increase possibili- based on cox1 and mitochondrial 16S rDNA ties of research. Their maintenance in vitro (16S mtDNA) was evaluated (1, 34). There has not been achieved yet, because of their were no geographical differences existing ease of dying. However, the effect of tempera- among Demodex isolates from Spain and China. ture and medium on the viability in vitro of However, differences in the cox1 gene were Demodex mites has been studied (26). The ac- observed between populations of D. folliculo- tivity of the mites is related to the photoperiod rum from facial skin and eyelids, caused by and the temperature (27). Demodex mites are variations in the local environment (34). photonegative (27). The optimal temperature Cox1 gene encodes protein that is the com- in vitro for both: D.