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Demodex Update

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Image courtesy of Wikimedia Commons

There is a huge number of articles on demodex and rosacea (the RRDi started a list sometime back and abandoned this project so if you are interested here is the link). If a volunteer wants to take on this project and update it contact us. It would be better to use Google Sheets for this project and you need a lot of time to gather all the demodex articles onto one Google Sheet. This is not for the faint of heart. 

We have browsed some of the most interesting articles on demodex since our last investigation and here are some interesting thoughts on this subject that has been gleaned and the highlights are shown below: 

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Under the lash
"Because all adult mites have a limited life cycle, their ability to expand in numbers in a human host depends on successful copulation by adult male and female mites in the opening of the hair follicle (near the skin surface). Afterwards, the gravid female moves to the sebaceous gland to deposit eggs, each of which gives rise to a larva and then a protonymph in the sebaceous canal. A protonymph is brought to the opening of the hair follicle and matures into a deutonymph, which crawls on to the skin surface, then re-enters a hair follicle to become an adult. Therefore, during a life cycle, if adults can successfully copulate and produce the next generation, the extent of Demodex infestation will gradually increase in the host over time.

Scanning electron microscopy reveals the special piercing mouthparts of D. folliculorum as a sharp offensive weapon capable of destroying adipose tissue. Although it has also been proposed that mites feed on follicular and glandular epithelial cells, sebum is thought to be the mite’s main food source. As a result, both Demodex species often coexist at the same skin area and gather in the face, cheeks, forehead, nose and external ear tract, where active sebum excretion creates favourable habitats and breeding conditions. Because these mites are susceptible to desiccation, their lifespan is limited outside the living body, and direct contact is required for transmission of mites from one individual to another. Consequently, an effective regimen in eradicating Demodex infestation should include killing as well as prevention of their copulation and transmission.....

......To quantify the extent of Demodex infestation in the skin, a surface biopsy has been standardized as the main method4. After cleaning the patient’s skin and a glass slide with ether to improve adherence, a spot of cyanoacrylate adhesive (superglue) is applied on the skin surface of interest before being overlaid with a slide. After approximately 1 minute on the skin, the slide is gently removed and covered by one drop of immersion oil before being mounted with a coverslip. The density of D. folliculorum is measured by counting the number of mites on the slide in a pre-marked surface area of 1 cm2 at a magnification of ×40 and ×100 under a microscope......

......It has been proposed that the pathogenic potential increases if a mite density is higher than five per cm2 1. Several studies have shown a higher mite density on the faces of rosacea patients than on those of age- and sex-matched non-rosacea controls. It is intriguing that Demodex numbers increase when the outside temperature elevates in spring and summer, coinciding with the time when rosacea is exacerbated......

.....Contiguous to the skin, the eye can also be infested by Demodex mites....As a matter of fact, the first disorder that was associated with Demodex, dated as early as 1899, was blepharitis (inflammation of the lid), a disease that has continued to be a subject of investigation ever since....Hence, we believe that one way of determining the pathogenic potential of Demodex infestation in blepharitis and other ocular diseases is to identify a treatment that can kill Demodex with a good safety profile.....

.....Nevertheless, one cannot rule out the pathogenic role of microbial agents that may be associated with Demodex infestation. The notion that microbes are involved in pathogenesis of mite-infested diseases has long been suggested because the skin inflammation in rosacea can be markedly improved by topical metronidazole or oral antibiotics including tetracycline, i.e. treatments that do not kill mites......

.....In short, the co-morbidity based on a symbiotic relationship of B. oleronius in Demodex mites also justifies the consideration of a therapeutic strategy directed to killing the symbiotic bacterium via oral antibiotics such as tetracycline and to killing and preventing mating/reinfestation of Demodex mites, e.g. lid scrub with TTO and general hygiene at the same time...."

Biochem (Lond). 2009;31(4):2-6
Under the lash
Demodex mites in human diseases
Noreen Lacey, Kevin Kavanagh, and Scheffer C.G. Tseng

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The potential role of Demodex folliculorum mites and bacteria in the induction of rosacea.

".....Over a significant period of time, there have been numerous attempts to connect the etiopathogenesis of rosacea with the presence of some micro-organisms on or within the skin (Lazaridou et al., 2011), including Demodex mites and bacteria. It is well established that there is a higher density of Demodex mites in the skin of rosacea patients than control patients but the significance of this has been disputed (Vance, 1986; Bonnar et al., 1993; Erbağci & Ozgöztaşi, 1998). This review will explore the current understanding of the role of these organisms in the induction of rosacea....

.....Demodex mites use the chelicerae to cut the epithelial cells of the host skin, secrete lytic enzymes for pre-oral digestion and evacuate liquid cytoplasm components (Desch & Nutting, 1972). In the process of destroying the epithelial cells, the epithelial barrier is often disturbed and the mite penetrates into the dermis stimulating Toll-like receptors (TLR) (Schauber et al., 2007). Proteolytic enzymes (proteases) are among the digestive enzymes secreted by Demodex mites. Concrements of serum immunoglobulin IgD and two inhibitors of serum proteases (α-1-antitrypsin and α-1-antichymotrypsin), which might be a specific defensive reaction of the host against mites, have been detected on the surface of Demodex mites (Tsutsumi, 2004). In atopic dermatitis, proteases produced by house dust mites have been identified as the factor responsible for local skin irritation (Deleuran et al., 1998)......

....In all phases of their life cycle, Demodex mites avoid sunlight. They emerge from the pilosebaceous units at night and migrate across the surface of the skin to find a mating partner, travelling at a speed of about 16 mm h−1 (Lacey et al., 2011). The life cycle of Demodex mites consists of five phases of development and lasts from 14 to 18 days. The copulation takes place near the entry of the hair follicle. Afterwards, the gravid female moves to the inside of the sebaceous gland, where she deposits eggs, from which the larvae will emerge about 60 h later. Protonymphs and nymphs are the next phases of the Demodex life cycle (Lacey et al., 2009; Spickett, 1961)
Due to the fact that Demodex mites are obligate parasites of the pilosebaceous units and highly susceptible to desiccation, they are not capable of surviving for long periods outside the host. Routes of transmission are not fully known but it may occur by direct contact as well as through dust. While the skin of new-borns is free of Demodex folliculorum, colonization of the skin in humans takes place in childhood or early adulthood. Demodex mites are found in representatives of all human races and in all geographical areas (Lacey et al., 2009).....

....Demodex mites were originally perceived to be commensals, having a symbiotic relationship with the human host. However the opinion about the role of Demodex in pathogenesis of many diseases, including rosacea has been changing (Lacey et al., 2009). In some specific conditions in the host system, Demodex mites may become potential pathogens. This may happen when the immunological conditions of the host change and new environmental conditions on the skin facilitate the development of Demodex mites (Dahl et al., 2004; Whitfeld et al., 2011).....

.....The extent of Demodex colonization in the human population is high (20–80%), reaching 100% in elderly people (Elston, 2010). Mite density starts to rise in the sixth decade of life and stays at the same level until the eight decade of life. Mite density is very low in young adults, even though their levels of sebum production, a potential source of food for mites, are very high (Ozdemir et al., 2005; Aylesworth & Vance, 1982). Patients with papulopustular rosacea produce sebum with an altered fatty acid profile, suggesting that the nature of the sebum, rather than its quantity, may favour the development of Demodex mites (Ní Raghallaigh et al., 2012). This finding raises the possibility that non-antibiotic therapies to restore the normal fatty acid composition of sebum may improve skin integrity and inhibit the proliferation of Demodex mites

Due to the fact that Demodex mites are commonly found in healthy individuals and the density of mites is generally low, the presence of mites on the skin is not enough to determine pathogenicity. An increase in mite density on facial skin is observed in perioral dermatitis, caused by long-term use of local steroids or other immunomodulating drugs (Fujiwara et al., 2010). Higher numbers of Demodex mites have been noted in patients undergoing immunosuppressive therapy, for example children receiving chemotherapy for leukaemia (Ivy et al., 1995), patients with HIV-infection or AIDS (Aquilina et al., 2002; Dominey et al., 1989) and chronic dialysis patients (Karincaoglu et al., 2005).....

....Most probably, when Demodex mites breach the epithelial barrier, their antigens influence the immune system of the host and induce a type IV hypersensitivity reaction. Demodex mites may then be attacked by giant cells giving rise to dermal granulomas, which are most often observed in granulomatous acne rosacea. Granulomas are also found in skin biopsies of patients with papulopustular rosacea and even in patients with erythematous rosacea (Hsu et al., 2009).

The causal relationship of Demodex mites in skin lesions has been suspected to occur through several mechanisms. They may mechanically block the follicles, leading to distension and causing intra-follicular hyperkeratosis. The presence of mite’s chitinous external skeleton may act like a foreign body and contribute to the formation of granulomas. The waste products of Demodex mites and/or associated bacteria may activate the elements of innate immune system or stimulate the immune system through the mechanism of delayed hypersensitivity reaction (Bevins & Liu, 2007).....

....One hypothesis concerning the role of Demodex mites in the induction of rosacea assumes that Demodex are vectors for micro-organisms that causes and exacerbates skin lesions (Hsu et al., 2009). The theory has its roots in the fact that clinical improvement was noted in patients with rosacea who were administered tetracycline antibiotics, although these antibiotics neither demonstrate activity against D. folliculorum nor reduce their numbers on the skin. It has been suggested that the beneficial activity of antibiotics was due to their anti-inflammatory properties; however, other anti-inflammatory agents, such as steroids or tacrolimus, intensify the symptoms of rosacea or even induce its development (Antille et al., 2004). The fact that only some drugs proved to be effective in the treatment of rosacea suggested that that an unknown bacterium may have a role in the pathogenesis of the disease.....

.....Bacillus oleronius was isolated from a Demodex mite, obtained from a patient with papulopustular rosacea (Lacey et al., 2007)......

....Staphylococcus epidermidis has been isolated from the pustules of 9 out of 15 patients with papulopustular rosacea, whereas this bacterium was not detected on unaffected areas of the skin (Whitfeld et al., 2011). S. epidermidis was also isolated from the eyelid margins of 4 out of 15 patients with papulopustular rosacea, whereas no pure growth was isolated from the eyelids of age- and sex-matched control subjects. The same study also found that this bacterium was susceptible to antibiotics commonly used to treat rosacea.....

.....It is believed that B. oleronius forms a symbiotic relationship with Demodex, as it does in the termite (Kuhnigk et al., 1995). On the skin of humans, this bacterium may occur in the endospore form, which enters the digestive tract of Demodex mites when they consume epithelial cells. The dead mites then decompose inside the hair follicles, where they release significant numbers of bacterial antigens, which have the potential to stimulate a strong immune response (O’Reilly et al., 2012). Thus, the intensification of blepharitis and rosacea, especially the papulopustular variant, may not be induced so much by the presence of the mites alone but by the presence of Demodex mites that carry B. oleronius in their digestive tract. Empirically confirmed sensitivity of B. oleronius to different antibiotics, especially doxycycline, (Lacey et al., 2007) might explain the favourable therapeutic effect of the drug in diseases such as rosacea and blepharitis.....

....The pathogenic role of Demodex mites, as well as B. oleronius and S. epidermidis, in the induction and persistence of rosacea remains an unresolved issue.....

Journal of Medical Microbiology, 61 (11 ). pp. 1504-1510. ISSN 0022-2615
The potential role of Demodex folliculorum mites and bacteria in the induction of rosacea.  
Jarmuda, Stanislaw and O’Reilly, Niamh and Zaba, Ryszard and Jakubowicz, Oliwia and Szkaradkiewicz, Andrzej and Kavanagh, Kevin (2012) 

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Ubiquity and Diversity of Human-Associated Demodex Mites
"Here we use a new molecular method to assess the occurrence of Demodex mites on humans.....A phylogenetic analysis of 18S rDNA reveals intraspecific structure within one of the two named human-associated Demodex species, D. brevis....While these mites are well known to dermatologists, ophthalmologists, and veterinarians and have been the subject of study for 172 years, their ubiquity, diversity and evolution are poorly understood....

....Methods used to collect Demodex mites from humans include biopsy, the cellophane tape method (placing tape on the face to stick to the mites), scraping areas where mites are likely to reside, and plucking eyelash and eyebrow hairs. Based on the visual observation of mites collected from healthy individuals by these methods, it appears that approximately 3–55% of humans harbor Demodex, with most studies falling in the range of 10–20%. However, because these mites may occur in patches around the body, as in dogs, and all existing collection methods sample just small patches of skin (and even incompletely sample those patches), it is difficult to know to what extent the absence of mites in a sample equates to the absence of mites on the body. Intriguingly, in postmortem studies, mites appear to be present on all adult cadavers. The ubiquity of mites on cadavers might indicate they are universally present on living, adult humans but missed by current sampling methods. Alternately, conditions in which cadavers are found might facilitate colonization by mites and, in doing so, artificially inflate estimates of their incidence......

.....Only recently have molecular studies begun to consider Demodex mites. Existing phylogenies and estimates of molecular divergence include very limited sampling of Demodex species, are based on few genetic markers, and include only minimal geographic representation......

.....Here we test a new molecular approach to detect the presence of mites on human bodies and assess the proportion of individuals in one population colonized by mites. We then use phylogenetic reconstruction based on the nuclear 18S rRNA gene (18S rDNA) to better understand the diversity of these mites.....

....All sample collections were performed in Raleigh, NC at either the North Carolina Museum of Natural Sciences or North Carolina State University. Each participant was gently scraped with a metal laboratory spatula along the creases of the nose and over the surrounding cheek area. The facial habitats were chosen based on their high levels of sebum production and ease of pore expression. In addition, Bonnar et al. (1993) found the greatest abundance of mites in the cheek area among rosacea patients.....

....DNA was extracted from the sebum of individual participants, regardless of the presence or absence of an observed mite,...

....The 16S rDNA PCR products were separated on 2% agarose gels to assess presence or absence of mite DNA within a sample.....

....The 18S rDNA PCR products were sequenced from four individuals and used for phylogenetic analyses.....

....Phylogenetic analyses were conducted using maximum likelihood (ML) and Bayesian inference (BI). Under both methods, gaps in the alignment were treated as missing data.....

.....Molecular evidence suggests Demodex prevalence is much higher than recognized through visual observation alone. Our results are in line with postmortem studies that find Demodex mites present on all adult cadavers....

.....Here we tested 29 people for the presence of Demodex mites and found that mites were much more common than expected in comparison to methods that rely solely on the visual confirmation of whole mite specimens taken from living humans. When we sampled individuals using traditional approaches, our results were similar to those of the many previous morphologically based studies....

.....Little is known about the transmission of mites among humans. Recent studies find that many symbiotic microbes are passed directly from mother to offspring during breast-feeding or during birth (especially if birth is vaginal), and dogs acquire their Demodex mites as nursing pups. In light of this, the same means of mite transmission seems possible in humans, supported by the fact that in one study, Demodex mites were found in 77% of nipple tissue from mastectomies.....

.....Mites could be more ubiquitous on children than noted in postmortem studies or herein but at levels or in locations that make the mites difficult to detect even with the use of molecular approaches. One study of Demodex mites on Tokelau islanders found that mites were present on a greater number of children than on adults. These conflicting findings highlight our limited understanding of how and when mites move onto and among human bodies....

....The evolutionary history of the two human-associated Demodex species is, at best, poorly understood. D. folliculorum was described by Simon in 1842, and as late as 1933, all human Demodex were regarded as one, albeit variable, species. It was only in 1963 that D. brevis was distinguished from D. folliculorum and described as a separate, but closely related, species. Yet de Rojas et al. (2012) have demonstrated that interpreting variation in the morphology of the two human-associated Demodex mite species is problematic, even when interpreted in light of molecular (16S rDNA) sequence data. The closest relatives for both human-associated species, D. folliculorum and D. brevis, remain unknown and are likely to remain unknown until these mites are much better sampled from other primates and mammalian hosts in general. Of the described Demodex species, only 13 have been sampled for molecular data and included in phylogenetic analyses....

.....Demodex are generally considered to be species specific, which would suggest there might be as many as 10,000 Demodex species on living mammals if there are two host specific mites per mammal species.....

.....Our phylogeny indicates that the two human-associated mite lineages do not share a recent common ancestor and likely have separate evolutionary histories of transmission to humans. The 18S rDNA sequence does not resolve the sister group to D. folliculorum, but places a paraphyletic group of dog-associated mites as the closest relative to D. brevis.....

.....Phylogenetic estimates based on 16S rDNA also find that dog-hosted Demodex mites share a recent common ancestor with a human-associated species, though in this case D. folliculorum and D. brevis are both more closely related to goat-associated mites,....

Plos | One
Ubiquity and Diversity of Human-Associated Demodex Mites
Megan S. Thoemmes , Daniel J. Fergus, Julie Urban, Michelle Trautwein, Robert R. Dunn

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