Demodectic Mange in Dogs - A Scientific Look at Causes and Treatment

Demodectic mange in dogs is a very serious skin disorder that can be fatal if not treated in time. There are two known types of mange in dogs: demodectic and sarcoptic mange.

Demodectic mange is the most common and a more serious condition among the two, and it’s the primary focus of this evidence-based article.

Understanding the functions and development of demodectic mange mites is important, because it will affect how you diagnose your pet, treat and prevent future mange in dogs.

In this article, you’ll find literally everything you need to know about demodectic mange in dogs and dog mites in general. I will also give you a full breakdown of potential demodectic mange treatment, and point you in the direction of what works and what doesn’t when dealing with this scary canine skin disease.

What is Mange on Dogs?

Mange itself is a dog’s skin disease caused by microscopic mites. The first disorders associated with mange mites date back to 1899 (1). There are two different types of canine mange, caused by two types of dog mites (2, 3, 4).

Sarcoptic mange mites live just under the surface of the skin. This condition is also known as canine scabies, and is caused by a parasite called Sarcoptes scabiei.

Demodectic mange mites live deep in the dog’s hair follicles. These mites are known as Demodex canis, and the condition itself is sometimes called demodicosis, puppy mange, red mange, or follicular mange.

In order to best identify which mange your dog has, a skin scrape or biopsy is needed (5). Other methods can also be used for diagnosis, such as acetate tape impressions, skin samplings and skin biopsies, most of which are equally effective (6).

Studies have also found that acetate tape impressions may be slightly more effective in diagnosing demodectic mange in dogs than skin scraping or sampling (7).

Summary: There are two types of mange in dogs: demodectic and sarcoptic. Demodectic mange is more common and more dangerous to a dog’s health. To identify a type of mange, skin scrape or biopsy is needed.

Demodectic Mange in Dogs (Demodicosis)

Medically known as demodicosis and colloquially known as red mange, demodectic mange is a most common type of mange in dogs. It occurs when a dog suffers from a sensitivity to and over population of the Demodex canis mites.

It’s not true for most dogs that demodectic mange can be inherited. Only dogs with certain genes are more predisposed to this condition (8, 9, 10).

Mange is mostly caused due to a suppression of the immune system in puppies, which allows mange mites to infect them more easily (9, 11, 12, 13, 14).

D. canis can reproduce quickly when the dog’s immune system is “malfunctioning” (15).

Canines are usually immunocompromised from birth, and since Demodex canis is transferred to them almost after they are born, most immunodeficient puppies usually experience their first hair loss at a mere four months of age.

Only the sensitivity to mange mites can be passed onto to other dogs through genes. Therefore, dogs that are more susceptible to demodicosis should not be bred, which will eventually allow to eliminate this condition altogether.

Even though mange is mostly detected in young puppies, older dogs may also be susceptible to red mange as their immune system begins to decline. Certain illnesses or drugs affecting dog’s immune system may raise chances of occurrence.

Summary: Demodectic mange in dogs is not inherited but passed onto puppies after birth. Only dogs with poor immune response experience symptoms.

Symptoms of demodectic mange on dogs

Demodectic mange is a gradual process as the mites must first grow in numbers to do noticeable harm to the dog. However, the signs are unmistakable once they take hold.

Hair loss, lesions, red and inflamed skin, crusty or scaling skin and an oily looking skin are some of the most obvious signs of demodicosis.

As puppies grow and develop their own immunity, lesions will start to heal by themselves. Only very serious cases of lesions will need treatment.

Although rare, some dogs may lose their appetite, become lethargic and develop a fever.

Summary: Signs of demodicosis in dogs include hair loss, lesions, hot spots, scaling or oily skin. Fever and loss of appetite are rare.

Localized vs generalized red mange

Localized vs Generalized Red Mange in DogsRegarded as the most serious of canine dermatosis (skin disease), demodectic mange in dogs begins when D. canis proliferates in the hair follicle and sebaceous gland (16).

This will develop into localized or generalized red mange. Of the two types, generalized red mange poses the greatest threat to dog’s health.

Parasite’s unpredictable nature means that it can spread to various part of the canine’s body without warning, causing hair loss, pain and deep skin in dogs (17).

Puppy mange lesions develop at slightly later stages of demodicosis. Localized demodicosis is characterized by less than 5 isolated lesions. More than five lesions spread out all over the body is categorized as generalized demodicosis.

Dogs with generalized demodectic mange need immediate attention and treatment.

Summary: Localized mange is an easy to treat condition. Generalized mange is a serious condition that requires immediate attention.

What does demodectic mange do to dogs?

Not all dogs affected by demodectic mange will itch. Patchy hair loss may occur. Blood testing shows that canines afflicted with generalized demodicosis display low levels of zinc and copper but an unusually high iron count (18).

This slows down blood flow and makes it difficult for the dog’s body to fight off the mites.

Researchers have also noted that dogs with mange showed a great deal of inflammation throughout their bodies and were highly imbalanced in their oxidant/antioxidant levels (18). This further distresses the dog’s immunity and health, making it nearly impossible to stave off the disease.

Summary: Demodectic mange lowers levels of copper and zinc in dogs. It also suppresses the immune system, thus making it harder for the dog to fight the condition.

 

How to diagnose demodectic mange in dogs

How to diagnose demodectic mange in dogs

The most common two ways to diagnose mange in dogs is through biopsy or skin scraping. Since mites are much too small to see with a naked eye, a microscope is used for identification.

Presence of mange mites by itself does not mean that a dog needs treatment, since majority of canines carry mange mites with no clinical symptoms. Only when paired with lesions or other severe symptoms mentioned above can it be diagnosed that a dog needs treatment for mange.

A vet will inquire about medications and nutritional history of the dog. Senior canines will also be tested for several other diseases to rule them out first.

Summary: Skin scraping is the most common way to diagnose mange in dogs.

When are dogs most susceptible to demodicosis?

While observing mange lesion development, researchers have noticed that there is a significant increase in Demodex canis infection during winter months (19). Furthermore, the month of March seems to be the hottest month for mange infestation (20).

Explanations for this include an increase in susceptibility during their winter coat development and mass hatching of D. canis. However, research into the actual cause has been so far inconclusive.

Summary: Winter months, and particularly March, is when most dogs are affected by demodicosis.

Breeds that are more susceptible to mange mites

It has been observed that certain dog breeds are more susceptible to contracting red mange. Studies suggest that the Tibetan Apso and Spitz are at great vulnerability to the spread of the mite (20, 21).

In general, pure breeds have shown a greater disposition to demodectic mange (22).

This may be a result of the breed’s genetic weakening through the practice of inbreeding to achieve many lines of pure breeds.

Summary: Pure breeds are more susceptible to mange. Tibetan Apso and Spitz in particular are more likely to develop the condition.

Is demodectic mange contagious?

There is over 100 of Demodex mite species (23). Each species can only infest a specific host. For example, as the name suggests, Demodex canis mites (discussed below) can only infect dogs. Demodex folliculorum will infect people, and Demodex bovis will infect cattle (24).

Humans cannot be infected by Demodex canis found in dogs, nor can other animals (25).

Also, because mange mites are found on virtually all dogs, there is no risk of exposing a dog with demodectic mange to normal dogs. In fact, some dogs are even used to detect mange in other animals (26).

Summary: Mange mites are host-specific. Demodectic mange is not contagious. Humans cannot attract it from dogs or other animals.

How to prevent demodectic mange in dogs

Some may argue that demodicosis can be avoided as long as a clean kennel is maintained. While this sounds good in theory, unfortunately, that is not true.

Demodectic mange erupts when the dogs’ immune system is compromised. This leaves the mite population unchecked and their numbers grow (27).

General cleanliness of kennels has nothing to do with avoiding demodectic mange.

In theory, as a preventative measure, owners may wish to avoid high carbohydrate diets.

There are theories that nutritional yeast and sugars found in high-carb food sources may serve to feed mange mites and allow them to proliferate all the more. However, there’s no evidence that a low-carb canine diet will definitely help.

Summary: Since mange is developed close to puppy’s birth, there’s no way it can be prevented. Low-carb diets have been suggested, but there’s no evidence they work.

What is Demodex Canis?

Demodex canis is known as the more serious and deadly mite that causes demodectic mange in dogs. D. canis resides mainly in the dog’s hair follicles and is not deemed contagious. However, they may also become carriers of other skin related bacteria (28, 29).

Most people are surprised by the fact that this mite is a normal inhabitant in canine’s skin (16). In fact, since the 19th century, a multitude of methods have been tried and tested to eradicate mange mites both on humans and animals to no avail (30, 31).

Studies show that majority of dogs are mere carriers of the D. canis and do not exhibit any reactions whatsoever (27).

There is no need to worry if you notice that your dog may be carrying D. canis on its skin. This is perfectly normal, and studies have shown that anywhere from 46-85% of dogs are carriers of these mange mites (32, 33).

Life cycle of Demodex in dogs

Demodex mites will normally spend their entire life in the dog’s skin.

Similarly to a tick’s life cycle, a female Demodex canis mite will lay eggs, which later hatch and mature into nymphs and then into adult mites.

The numbers vary, but the life cycle of mange mites usually takes from 14 to 30 days (34).

How is Demodex canis transmitted to dogs?

Dog mange mites are usually transferred from the mother to the pup within three days of birth, but can take up to a week (17).

Studies have shown that almost every female dog has these mites and transfers them onto puppies. However, most canines are immune to mange mites and will not display any clinical symptoms. A few dogs may not have immunity to mange mites, and they are the ones who will get infected.

These parasites cannot survive in the environment without the animal, thus mange mites can be transferred through physical contact only. What this means is that crates, beds or kennels cannot be contaminated with mange mites, and it’s pointless to treat the environment with the goal to prevent puppy mange.

Once the puppy has been infected, lesions will start appearing on his head. Itching may occur.

SummaryDemodex canis is a canine-specific mite that causes demodectic mange in dogs. Its life cycle ranges from 14 to 30 days, and studies have shown that virtually all canines are carriers of these dog mites.

How to Treat Mange in Dogs

Fortunately, we can be proactive in the treatment of demodectic mange on dogs. This is especially true for localized demodicosis, which is more responsive to treatment and doesn’t require serious measures. In fact, most of the time treating localized demodicosis isn’t even necessary as it resolves itself as the puppy matures.

Generalized mange, on the other hand, must be treated using a more serious approach. Unfortunately, it usually means that this will be a much longer and more expensive treatment.

So far, the best treatment for mange in dogs are topical insecticides and oral parasite killing medicine (35, 36, 37, 38, 39, 40).

Topical demodectic mange treatment

Topical treatment of demodectic mange in dogs is the most popular option used today (41).

These insecticides must be used under vet’s supervision because side effects are possible, particularly with certain types of drugs (42, 43, 44, 45, 46).

Mitaban (Amitraz)

Amitraz is an insecticide and acaricide, the most popular treatment for red mange. It is available under the brand name Mitaban, and should be applied with care.

Multiple studies have demonstrated its relative safety and efficacy for treating demodectic mange in dogs (47, 48, 49, 50, 51, 52).

It’s sold only with prescription. Mitaban must always be carefully administered on the dog’s skin in a well-ventilated area using rubber gloves.

For best results, vets recommend bathing a dog using a benzoyl peroxide containing dog shampoo, and then cutting dog’s hair very short before using amitraz. It will take from 6 to 14 applications of amitraz at 1-2 week intervals for most canines.

After the first 2-4 dips, skin scraping has to be performed in order to see if the substance works and that mites have been eliminated.

Some dogs may be sensitive to amitraz, and a half-strong dosage should be used on them.

Summary: Topical application of Mitaban (Amitraz) is the most common way to treat demodectic mange in dogs. Careful administration and vet’s supervision is needed as side effects are possible.

Oral treatment of mange in dogs

There are several ways owners can address demodectic mange in dogs through oral treatment. Remember that all the below drugs are very strong and have potential side effects, including death. It’s important to consult with a veterinarian before using them.

1. Heartgard (Ivermectin)

Ivermictin is a well-known type of anti-parasite substance often used for demodectic mange. The most popular brand of ivermectic-based medication is Heartgard.

Multiple trials have shown ivermictin’s effectiveness for mange in dogs (4253, 54, 55, 56).

Vets recommend to avoid ivermectin for herding breeds (465758, 59, 60, 61, 62, 63, 64). More specifically, do not use ivermictin with these breeds:

  • Shetland Sheepdogs
  • Old English Sheepdogs
  • Border Collies
  • Australian Shepherds

Although other studies found that smaller doses are completely safe for some of these dogs, it’s still best to avoid the drug for the above breeds and move onto other methods (65).

More research has pointed to its effectiveness when used with antioxidants such as Vitamin E (66). It’s also effective and safe to use ivermectin alongside other drugs on this page (67).

2. Interceptor (Milbemycin oxime)

Another option for owners of dogs with mange is using antiparasitic Milbemycin oxime. This drug works well against dog mites, and is sold under a trade name Interceptor.

Studies have shown this to be an effective treatment against demodectic mange in dogs (3568). It was also demonstrated that 80% of dogs that did not respond to Mitaban responded to milbemycin oxime. In this case as well, Collies remain more susceptible to drug’s side effects but rarely (69, 70).

3. Moxidectin

Moxidectin is the last one of the possible treatments for demodectic mange in dogs. It can be used orally, topically or as an injection, and many different brands use this as active ingredient in their formulas.

Studies have shown this to be an effective anthelmintic drug against mange mites (71, 72, 73). However, it seems to be weaker than the above mention ivermectin (74, 75, 76).

Only when fighting other parasites has it been shown for moxidectin to be slightly more effective than ivermectin, but the difference wasn’t statistically significant (77).

Research has shown this drug to not only be effective but also safe for most dogs (78, 79).

4. Fluralaner

Fluralaner is a known drug often used in treatment of fleas and ticks on dogs (80, 81, 82). Researchers have found that administering fluralaner as a pesticide safe for consumption typically eradicates mange mite count in dogs within a two-month period (83, 84).

Moreover, after three months of use, a significant reduction in lesions and an increase in hair growth was observed (83).

Fluralaner essentially turns a dogs’ body into a toxic food source for the mange mites. Since fluralaner is technically a pesticide, owners need to exercise great care and consult with a veterinarian before administering it.

A study on the safety of fluralaner using a dose higher than recommended has demonstrated its efficacy and showed no major side effects in dogs (85). However, this study was funded by Merck, so we need to consider possible biases. Further research has shown that fluralaner and ivermectin can be used together safely (86).

Finally, fluralaner can also be used alongside topical applications for better results (87). Most likely, this also applies to other similar drugs on this list.

Summary: Studies show that oral antiparasitic medicine is very effective and can be used alongside topical treatments for better results. Side effects are possible, and certain breeds should not be given these drugs.

Nutrition and diet for treating dogs with mange

Specific diet changes may or may not help to deal with mange in dogs. While research is still lacking in this area, improving your canine’s diet is generally a good idea anyway.

1. Antioxidants

It’s been shown that increasing zinc and copper levels may provide some aid (88). Zinc and copper are necessary ingredients for skin formation and can help heal wounds faster.

Vitamin E used alongside ivermectin has been shown to kill mites in dogs (66).

2. Omega-3s

Apart from all the health benefits for dog’s general health (89, 90, 91), omega-3s also have positive effects for a dog’s general skin condition (92, 93).

Fish oil in particular containing a lot of omega-3s can be a good addition to the diet. Research shows that to relieve itching and improve skin conditions, other dog supplements with omega-3 fatty acids such as flax seed oil or  pumpkin oil may also be introduced (94).

3. Nutrition

Changing dog’s diet may help to strengthen the immune system’s response to red mange. Adding probiotics and prebiotics to a dog’s diet can help with overall health (95, 96).

It’s also been suggested that diet very low in carbohydrates will stave off mites.

To further increase antioxidant levels and help speed up the healing process, raw dark leafy greens such as broccoli and watercress can be regularly added to the infected dog’s food.

Overall, there’s absolutely no evidence that diet changes can affect demodectic mange in dogs. However, improving canine’s diet will never be the wrong way to go.

Summary: Supplements and proper nutrition may help in strengthening dog’s immune system and fighting red mange, but there’s no evidence to show this is true.

Holistic home remedies for mange in dogs

For some owners, the use of “poisons” such as fluralaner on their dog may not seem right. Many owners often turn to alternative or homeopathic remedies to treat demodectic mange in dogs, some of which can be effective.

1. Jatropha curcas and Withania somnifera

For example, a combination of Jatropha curcas oil and Withania somnifera root can be beneficial.

Jathropha is a plant native to the American tropics that possesses inherent pesticidal and fungicidal properties. Withania comnifera root is known as Indian ginseng and is used in Ayurvedic medicine

The combo of the two has shown some potential efficacy in dealing with demodicosis (97).

2. Tea tree oil

There is some evidence that using the right dose of tea tree oil may kill Demodex mites (98).

Tea tree oil is a natural essential oil that has been steam-distilled from the leaves of Melaleuca alternifolia. This method has been used as an aboriginal traditional medicine against infections for a long time, particularly in Australia.

Baby shampoos were shown to be slightly effective against mange mites, but they were especially effective when combined with tea tree oil, according to research (99, 100). Evidence shows that in most cases, it takes about 4 weeks of regular application.

3. Other homeopathic remedies

In addition, used as a topical salve, diluted garlic oil may aid in minimizing bacterial infection due to its innate antibacterial properties.

Sulphur, Psorinum and Silicea when used as a homeopathic remedy, and in conjunction with topically applied neem oil, can be considered as a treatment protocol for demodicosis (94).

Neem oil eliminates Demodex canis mites upon contact. The preparation containing sulphur, psorinum and silicea (among others) reduces the likelihood of recurrence.

Summary: Certain holistic methods to treat demodectic mange in dogs have been proven to be effective, particularly tea tree oil.

Post-treatment of mange in dogs and prognosis

In most cases, treatment of demodectic mange in dogs is successful, but in cases of generalized demodicosis it takes a long time to see results.

Some rare instances of defective immune system in dogs may prevent treatments from being effective. Relapses are possible, especially in dogs up to the age of 18 months.

Treating relapses is very important, and this should be addressed immediately.

Summary: Treatment for demodectic mange in dogs is usually successful, but could take a long time. Relapses are possible and treatment must be started again immediately once that occurs.

Summary of Demodectic Mange in Dogs

Generalized demodectic mange is the most common type of skin disease in dogs. D. canis dog mites are transferred from mother onto puppy within the first week after birth.

First sign of mange is usually hair loss. It may not occur until about 4 months of age.

Mange in dogs is not inherited, only sensitivity can be passed on through genes. All dogs carry these mites, and only those with suppressed immune system experience symptoms.

There are many treatments for mange in dogs. Most are effective but side effects are possible. Demodectic mange treatment can become a long, arduous and expensive process.

REFERENCES
  1. Norn MS. Demodex folliculorum. Incidence, regional distribution, pathogenicity. Dan Med Bull. 1971 Feb;18(1):14-7.
  2. Gerasimova GN, Zhidkov AE, Strel’chik VA, Gapon NM, Polienko VF. [Sarcoptidosis and demodectic mange in carnivores]. Veterinariia. 1979 Apr;(4):41-2.
  3. Schwartzman RM. Reflections on demodectic mange in dogs. Int J Dermatol. 1976 Mar;15(2):125.
  4. Bagnall BG. Demodectic mange. Australas J Dermatol. 1974 Apr;15(1):29-30.
  5. Forton F1, Seys B. Density of Demodex folliculorum in rosacea: a case-control study using standardized skin-surface biopsy. Br J Dermatol. 1993 Jun;128(6):650-9.
  6. Angelbeck-Schulze M1, Stahl J, Brodesser S, Rohn K, Naim H, Hewicker-Trautwein M, Kietzmann M, Bäumer W, Mischke R. Comparison of three different sampling methods for canine skin lipids. Vet Dermatol. 2013 Apr;24(2):233-e51. doi: 10.1111/vde.12015.
  7. Pereira AV1, Pereira SA, Gremião ID, Campos MP, Ferreira AM. Comparison of acetate tape impression with squeezing versus skin scraping for the diagnosis of canine demodicosis. Aust Vet J. 2012 Nov;90(11):448-50. doi: 10.1111/j.1751-0813.2012.00994.x. Epub 2012 Sep 19.
  8. It V1, Barrientos L, López Gappa J, Posik D, Díaz S, Golijow C, Giovambattista G. Association of canine juvenile generalized demodicosis with the dog leukocyte antigen system. Tissue Antigens. 2010 Jul;76(1):67-70. doi: 10.1111/j.1399-0039.2010.01463.x. Epub 2010 Mar 14.
  9. Gortel K1. Update on canine demodicosis. Vet Clin North Am Small Anim Pract. 2006 Jan;36(1):229-41, ix.
  10. Corbett R, Banks K, Hinrichs D, Bell T. Cellular immune responsiveness in dogs with demodectic mange. Transplant Proc. 1975 Dec;7(4):557-9.
  11. Medleau L, Hnilica KA. Small Animal Dermatology: A Color Atlas and Therapeutic Guide, 2nd ed. Saunders Elsevier, Philadelphia, Pennsylvania, USA. 2006. 526 pp. ISBN 9780-7216-2825-7. Can Vet J. 2007 Dec; 48(12): 1287.
  12. Singh SK1, Dimri U2. The immuno-pathological conversions of canine demodicosis. Vet Parasitol. 2014 Jun 16;203(1-2):1-5. doi: 10.1016/j.vetpar.2014.03.008. Epub 2014 Mar 13.
  13. Barriga OO1, al-Khalidi NW, Martin S, Wyman M. Evidence of immunosuppression by Demodex canis. Vet Immunol Immunopathol. 1992 Apr;32(1-2):37-46.
  14. Owen LN. Demodectic mange in dogs immunosuppressed with antilymphocyte serum. Transplantation. 1972 Jun;13(6):616-7.
  15. Gaafar SM. Immunology and allergy of demodectic mange. Vet Clin North Am. 1974 Feb;4(1):125-31.
  16. Scott DW, Miller MH, Griffin CE. Parasitic skin diseases. Muller and Kirk’s Small Animal Dermatoloy (6th edn.). 2001; 457-474.
  17. Horvath, C. and Neuber, A. (2007), Pathogenesis of canine demodicosis. Companion Animal, 12: 55–59. doi: 10.1111/j.2044-3862.2007.tb00131.x
  18. Beigh SA1, Soodan JS, Singh R, Khan AM. Trace minerals status and antioxidative enzyme activity in dogs with generalized demodecosis. Vet Parasitol. 2013 Nov 15;198(1-2):180-6. doi: 10.1016/j.vetpar.2013.08.001. Epub 2013 Aug 12.
  19. Yu-Jen Tsai, Wen-Cheng Chung, Lian-Chen Wang, Yu-Ten Ju, Chin-Lin Hong, Yu-Yang Tsai, Yi-Hung Li, Ying-Ling Wu. The Dog Mite, Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis. J Insect Sci. 2011; 11: 76. Published online 2011 Jun 29. doi: 10.1673/031.011.7601 
  20. Aujla, R. S.; Singla, L. D.; Juyal, P. D.; Gupta, P. P. Prevalence and pathology of mange-mite infestations in dogs. Journal of Veterinary Parasitology 2000 Vol. 14 No. 1 pp. 45-49
  21. Nayak DC1, Tripathy SB, Dey PC, Ray SK, Mohanty DN, Parida GS, Biswal S, Das M. Prevalence of canine demodicosis in Orissa (India). Vet Parasitol. 1997 Dec 31;73(3-4):347-52.
  22. Solanki JB, Hasnani JJ, Patel DM, Patel PV, Raval S.K. (2007). Canine demodicosis in Anand. J.Vet. Parasitol. 21(1): 79–80. 
  23. Noreen Lacey, Kevin Kavanagh, Scheffer C.G. Tseng. Under the lash – Demodex mites in human diseases. Biochem (Lond). Author manuscript; available in PMC 2010 Jul 20. Published in final edited form as: Biochem (Lond). 2009 Aug 1; 31(4): 2–6.
  24. Baima B1, Sticherling M. Demodicidosis revisited. Acta Derm Venereol. 2002;82(1):3-6.
  25. Pena GP1, Andrade Filho JS. Is demodex really non-pathogenic? Rev Inst Med Trop Sao Paulo. 2000 May-Jun;42(3):171-3.
  26. Samer Alasaad, Roberto Permunian,2 Francis Gakuya,3 Matthew Mutinda,3 Ramón C Soriguer, Luca Rossi. Sarcoptic-mange detector dogs used to identify infected animals during outbreaks in wildlife. BMC Vet Res. 2012; 8: 110. Published online 2012 Jul 9. doi: 10.1186/1746-6148-8-110
  27. Gothe R. [Demodicosis of dogs–a factorial disease?]. Berl Munch Tierarztl Wochenschr. 1989 Sep 1;102(9):293-7.
  28. Wolf R1, Ophir J, Avigad J, Lengy J, Krakowski A. The hair follicle mites (Demodex spp.). Could they be vectors of pathogenic microorganisms? Acta Derm Venereol. 1988;68(6):535-7.
  29. Bevins CL, Liu FT. Rosacea: skin innate immunity gone awry? Nat Med. 2007 Aug;13(8):904-6.
  30. Gao YY1, Di Pascuale MA, Li W, Liu DT, Baradaran-Rafii A, Elizondo A, Kawakita T, Raju VK, Tseng SC. High prevalence of Demodex in eyelashes with cylindrical dandruff. Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3089-94.
  31. Kheirkhah A1, Blanco G, Casas V, Tseng SC. Fluorescein dye improves microscopic evaluation and counting of demodex in blepharitis with cylindrical dandruff. Cornea. 2007 Jul;26(6):697-700.
  32. Izdebska JN, Fryderyk S. Diversity of three species of the genus Demodex (Acari, Demodecidae) parasitizing dogs in Poland. Pol J of Environ Stud. 2011;3:565–9.
  33. Stankiewicz W, Augustynowicz L, Florianczyk R, et al. Trials of treatment of dogs with demodecosis. Med Wet. 1970.
  34. Rufli T, Mumcuoglu Y. The hair follicle mites Demodex folliculorum and Demodex brevis: biology and medical importance. A review. Dermatologica. 1981;162(1):1-11.
  35. Mueller RS1. Treatment protocols for demodicosis: an evidence-based review. Vet Dermatol. 2004 Apr;15(2):75-89.
  36. Heine J1, Krieger K, Dumont P, Hellmann K. Evaluation of the efficacy and safety of imidacloprid 10% plus moxidectin 2.5% spot-on in the treatment of generalized demodicosis in dogs: results of a European field study. Parasitol Res. 2005 Oct;97 Suppl 1:S89-96.
  37. M Paradis, C de Jaham, N Pagé. Topical (pour-on) ivermectin in the treatment of canine scabies. Can Vet J. 1997 Jun; 38(6): 379–382.
  38. Joachim Geyer, Christina Janko. Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones. Curr Pharm Biotechnol. 2012 May; 13(6): 969–986. Published online 2012 May. doi: 10.2174/138920112800399301
  39. FLYNN RJ. Demodectic and sarcoptic mange of dogs successfully treated with aramite. J Am Vet Med Assoc. 1959 Feb 15;134(4):177-9.
  40. KOUTZ FR. Demodex folliculorum studies. I. The use of phenamidine as internal medication for the treatment of demodectic mange in the dog. J Am Vet Med Assoc. 1952 Dec;121(909):470-3.
  41. Nolan TJ1, Lok JB. Macrocyclic lactones in the treatment and control of parasitism in small companion animals. Curr Pharm Biotechnol. 2012 May;13(6):1078-94. 
  42. Mueller RS1, Bettenay SV. A proposed new therapeutic protocol for the treatment of canine mange with ivermectin. J Am Anim Hosp Assoc. 1999 Jan-Feb;35(1):77-80.
  43. Merola V1, Khan S, Gwaltney-Brant S. Ivermectin toxicosis in dogs: a retrospective study. J Am Anim Hosp Assoc. 2009 May-Jun;45(3):106-11.
  44. Morsy TA1, Haridy FM. Effect of ivermectin on the brown dog tick, Rhipicephalus sanguineus. J Egypt Soc Parasitol. 2000 Apr;30(1):117-24.
  45. Houston DM, Parent J, Matushek KJ. Ivermectin toxicosis in a dog. J Am Vet Med Assoc. 1987 Jul 1;191(1):78-80.
  46. Merola V1, Khan S, Gwaltney-Brant S. Ivermectin toxicosis in dogs: a retrospective study. J Am Anim Hosp Assoc. 2009 May-Jun;45(3):106-11.
  47. Fourie LJ1, Kok DJ, du Plessis A, Rugg D. Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of demodectic mange in dogs. Vet Parasitol. 2007 Dec 15;150(3):268-74. Epub 2007 Oct 17.
  48. Rugg D1, Hair JA, Everett RE, Cunningham JR, Carter L. Confirmation of the efficacy of a novel formulation of metaflumizone plus amitraz for the treatment and control of fleas and ticks on dogs. Vet Parasitol. 2007 Dec 15;150(3):209-18. Epub 2007 Oct 17.
  49. Sabnis S1, Zupan J, Gliddon M. Topical formulations of metaflumizone plus amitraz to treat flea and tick infestations on dogs. Vet Parasitol. 2007 Dec 15;150(3):196-202. Epub 2007 Oct 18.
  50. Viviana D Tarallo,1 Riccardo P Lia,1 Mariateresa Sasanelli,1 Claudia Cafarchia, Domenico Otranto. Efficacy of Amitraz plus Metaflumizone for the treatment of canine demodicosis associated with Malassezia pachydermatis. Parasit Vectors. 2009; 2: 13. Published online 2009 Mar 5. doi: 10.1186/1756-3305-2-13 
  51. Fourie LJ1, Kok DJ, du Plessis A, Rugg D. Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of demodectic mange in dogs. Vet Parasitol. 2007 Dec 15;150(3):268-74. Epub 2007 Oct 17.
  52. Mojzisová J1, Paulík S, Bajová V, Baranová D. [Immunomodulatory effect of levamisole and administration of amitraz in dogs with uncomplicated generalized demodicosis]. Vet Med (Praha). 1997 Oct;42(10):307-11.
  53. Ristic Z1, Medleau L, Paradis M, White-Weithers NE. Ivermectin for treatment of generalized demodicosis in dogs. J Am Vet Med Assoc. 1995 Nov 15;207(10):1308-10.
  54. Ristic Z1, Medleau L, Paradis M, White-Weithers NE. Ivermectin for treatment of generalized demodicosis in dogs. J Am Vet Med Assoc. 1995 Nov 15;207(10):1308-10.
  55. Anderson DL, Roberson EL. Activity of ivermectin against canine intestinal helminths. Am J Vet Res. 1982 Sep;43(9):1681-3.
  56. Campbell WC, Benz GW. Ivermectin: a review of efficacy and safety. J Vet Pharmacol Ther. 1984 Mar;7(1):1-16.
  57. Hadrick MK1, Bunch SE, Kornegay JN. Ivermectin toxicosis in two Australian shepherds. J Am Vet Med Assoc. 1995 Apr 15;206(8):1147-50; discussion 1150-2.
  58. Manon Paradis, Alain Villeneuve. Efficacy of Ivermectin against Cheyletiella yasguri Infestation in Dogs. Can Vet J. 1988 Aug; 29(8): 633–635.
  59. Paul AJ, Tranquilli WJ, Seward RL, Todd KS Jr, DiPietro JA. Clinical observations in collies given ivermectin orally. Am J Vet Res. 1987 Apr;48(4):684-5.
  60. Tranquilli WJ, Paul AJ, Seward RL, Todd KS, Dipietro JA. Response to physostigmine administration in collie dogs exhibiting ivermectin toxicosis. J Vet Pharmacol Ther. 1987 Mar;10(1):96-100.
  61. Paul AJ1, Tranquilli WJ, Hutchens DE. Safety of moxidectin in avermectin-sensitive collies. Am J Vet Res. 2000 May;61(5):482-3.
  62. Tranquilli WJ1, Paul AJ, Seward RL. Ivermectin plasma concentrations in collies sensitive to ivermectin-induced toxicosis. Am J Vet Res. 1989 May;50(5):769-70.
  63. Hopper K1, Aldrich J, Haskins SC. Ivermectin toxicity in 17 collies. J Vet Intern Med. 2002 Jan-Feb;16(1):89-94.
  64. Vaughn DM1, Simpson ST, Blagburn BL, Whitmer WL, Heddens-Mysinger R, Hendrix CM. Determination of homovanillic acid, 5-hydroxyindoleacetic acid and pressure in the cerebrospinal fluid of collie dogs following administration of ivermectin. Vet Res Commun. 1989;13(1):47-55.
  65. Fassler PE1, Tranquilli WJ, Paul AJ, Soll MD, DiPietro JA, Todd KS. Evaluation of the safety of ivermectin administered in a beef-based formulation to ivermectin-sensitive Collies. J Am Vet Med Assoc. 1991 Aug 15;199(4):457-60.
  66. Suvendu Kumar Behera , Umesh Dimri, Shanker Kumar Singh, Ranjan Kumar Mohanta. The curative and antioxidative efficiency of ivermectin and ivermectin + vitamin E-selenium treatment on canine Sarcoptes scabiei infestation. Veterinary Research Communications April 2011, Volume 35, Issue 4, pp 237-244
  67. Saridomichelakis M1, Koutinas A, Papadogiannakis E, Papazachariadou M, Liapi M, Trakas D. Adult-onset demodicosis in two dogs due to Demodex canis and a short-tailed demodectic mite. J Small Anim Pract. 1999 Nov;40(11):529-32.
  68. Holm BR1. Efficacy of milbemycin oxime in the treatment of canine generalized demodicosis: a retrospective study of 99 dogs (1995-2000). Vet Dermatol. 2003 Aug;14(4):189-95.
  69. Tranquilli WJ1, Paul AJ, Todd KS. Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies. Am J Vet Res. 1991 Jul;52(7):1170-2.
  70. Sasaki Y1, Kitagawa H, Murase S, Ishihara K. Susceptibility of rough-coated collies to milbemycin oxime. Nihon Juigaku Zasshi. 1990 Dec;52(6):1269-71.
  71. Wagner R1, Wendlberger U. Field efficacy of moxidectin in dogs and rabbits naturally infested with Sarcoptes spp., Demodex spp. and Psoroptes spp. mites. Vet Parasitol. 2000 Nov 10;93(2):149-58.
  72. Huang HP, Lien YH. Treatment of canine generalized demodicosis associated with hyperadrenocorticism with spot-on moxidectin and imidacloprid. Acta Vet Scand. 2013 May 10;55:40. doi: 10.1186/1751-0147-55-40.
  73. Fourie JJ1, Delport PC, Fourie LJ, Heine J, Horak IG, Krieger KJ. Comparative efficacy and safety of two treatment regimens with a topically applied combination of imidacloprid and moxidectin (Advocate) against generalised demodicosis in dogs. Parasitol Res. 2009 Aug;105 Suppl 1:S115-24. doi: 10.1007/s00436-009-1502-1. 
  74. Griffin J1, Fletcher N, Clemence R, Blanchflower S, Brayden DJ. Selamectin is a potent substrate and inhibitor of human and canine P-glycoprotein. J Vet Pharmacol Ther. 2005 Jun;28(3):257-65.
  75. Dupuy J1, Larrieu G, Sutra JF, Eeckhoutte C, Alvinerie M. Influence of verapamil on the efflux and metabolism of 14C moxidectin in cultured rat hepatocytes. J Vet Pharmacol Ther. 2001 Jun;24(3):171-7.
  76. Brayden DJ1, Griffin J. Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers. Vet Res Commun. 2008 Jan;32(1):93-106. Epub 2007 Jun 20.
  77. Monahan CM1, Chapman MR, Taylor HW, French DD, Klei TR. Comparison of moxidectin oral gel and ivermectin oral paste against a spectrum of internal parasites of ponies with special attention to encysted cyathostome larvae. Vet Parasitol. 1996 Jun;63(3-4):225-35. 
  78. Wagner R1, Wendlberger U. Field efficacy of moxidectin in dogs and rabbits naturally infested with Sarcoptes spp., Demodex spp. and Psoroptes spp. mites. Vet Parasitol. 2000 Nov 10;93(2):149-58.
  79. Vanapalli SR1, Hung YP, Fleckenstein L, Dzimianski MT, McCall JW. Pharmacokinetics and dose proportionality of oral moxidectin in beagle dogs. Biopharm Drug Dispos. 2002 Oct;23(7):263-72.
  80. Michael W Dryden, Vicki Smith, Tashina Bennett, Lisa Math,corresponding author James Kallman, Kathleen Heaney, Fangshi Sun. Efficacy of fluralaner flavored chews (Bravecto®) administered to dogs against the adult cat flea, Ctenocephalides felis felis and egg production. Parasit Vectors. 2015; 8: 364. Published online 2015 Jul 11. doi: 10.1186/s13071-015-0965-4 
  81. Six RH1, Liebenberg J2, Honsberger NA3, Mahabir SP4. Comparative speed of kill of sarolaner (Simparica(™)) and fluralaner (Bravecto(®)) against induced infestations of Ctenocephalides felis on dogs. Parasit Vectors. 2016 Feb 19;9(1):92. doi: 10.1186/s13071-016-1373-0.
  82. Ohmes CM1, Hostetler J, Davis WL, Settje T, McMinn A, Everett WR. Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Fluralaner Chewable Tablet (Bravecto®) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial. Parasitol Res. 2015 Aug;114 Suppl 1:S95-108. doi: 10.1007/s00436-015-4516-x.
  83. Fourie JJ1, Liebenberg JE2, Horak IG3, Taenzler J4, Heckeroth AR5, Frénais R6. Efficacy of orally administered fluralaner (Bravecto™) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs. Parasit Vectors. 2015 Mar 28;8:187. doi: 10.1186/s13071-015-0775-8.
  84. Susanne Kilp, Diana Ramirez, Mark J Allan, Rainer KA Roepke, Martin C Nuernberger. Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration. Parasit Vectors. 2014; 7: 85. Published online 2014 Mar 7. doi: 10.1186/1756-3305-7-85
  85. Feli M Walther, Mark J Allan, Rainer KA Roepke, Martin C Nuernberger. Safety of fluralaner chewable tablets (BravectoTM), a novel systemic antiparasitic drug, in dogs after oral administration. Parasit Vectors. 2014; 7: 87. Published online 2014 Mar 7. doi: 10.1186/1756-3305-7-87
  86. Walther FM1, Allan MJ2, Roepke RK3. Plasma pharmacokinetic profile of fluralaner (Bravecto™) and ivermectin following concurrent administration to dogs. Parasit Vectors. 2015 Oct 6;8:508. doi: 10.1186/s13071-015-1123-8.
  87. Josephus J Fourie, Julian E Liebenberg, Ivan G Horak, Janina Taenzler, Anja R Heckeroth, Regis Frénais. Efficacy of orally administered fluralaner (BravectoTM) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs. Parasit Vectors. 2015; 8: 187. Published online 2015 Mar 28. doi: 10.1186/s13071-015-0775-8
  88. Borkow G1, Gabbay J, Zatcoff RC. Could chronic wounds not heal due to too low local copper levels? Med Hypotheses. 2008;70(3):610-3. Epub 2007 Aug 6.
  89. Freeman LM1. Beneficial effects of omega-3 fatty acids in cardiovascular disease. J Small Anim Pract. 2010 Sep;51(9):462-70. doi: 10.1111/j.1748-5827.2010.00968.x. Epub 2010 Jul 29.
  90. Roush JK1, Dodd CE, Fritsch DA, Allen TA, Jewell DE, Schoenherr WD, Richardson DC, Leventhal PS, Hahn KA. Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc. 2010 Jan 1;236(1):59-66. doi: 10.2460/javma.236.1.59.
  91. Smith CE1, Freeman LM, Rush JE, Cunningham SM, Biourge V. Omega-3 fatty acids in Boxer dogs with arrhythmogenic right ventricular cardiomyopathy. J Vet Intern Med. 2007 Mar-Apr;21(2):265-73.
  92. Mooney MA1, Vaughn DM, Reinhart GA, Powers RD, Wright JC, Hoffman CE, Swaim SF, Baker HJ. Evaluation of the effects of omega-3 fatty acid-containing diets on the inflammatory stage of wound healing in dogs. Am J Vet Res. 1998 Jul;59(7):859-63.
  93. Mueller RS1, Fieseler KV, Fettman MJ, Zabel S, Rosychuk RA, Ogilvie GK, Greenwalt TL. Effect of omega-3 fatty acids on canine atopic dermatitis. J Small Anim Pract. 2004 Jun;45(6):293-7.
  94. S. K. Singh , Mritunjay Kumar, R. K. Jadhav, S. K. Saxena. An Update on Therapeutic Management of Canine Demodicosis. Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India Division of Animal Biotechnology, National Dairy Research Institute, Karnal-132001
  95. Sauter SN1, Benyacoub J, Allenspach K, Gaschen F, Ontsouka E, Reuteler G, Cavadini C, Knorr R, Blum JW. Effects of probiotic bacteria in dogs with food responsive diarrhoea treated with an elimination diet. J Anim Physiol Anim Nutr (Berl). 2006 Aug;90(7-8):269-77.
  96. Baillon ML1, Marshall-Jones ZV, Butterwick RF. Effects of probiotic Lactobacillus acidophilus strain DSM13241 in healthy adult dogs. Am J Vet Res. 2004 Mar;65(3):338-43.
  97. Mukhtar Taha Abu-Samra, Yassir Adam Shuaib. A Study on the Nature of Association between Demodex Mites and Bacteria Involved in Skin and Meibomian Gland Lesions of Demodectic Mange in Cattle. Vet Med Int. 2014; 2014: 413719. Published online 2014 Aug 6. doi: 10.1155/2014/413719
  98. Gao YY1, Di Pascuale MA, Li W, Baradaran-Rafii A, Elizondo A, Kuo CL, Raju VK, Tseng SC. In vitro and in vivo killing of ocular Demodex by tea tree oil. Br J Ophthalmol. 2005 Nov;89(11):1468-73.
  99. Gao YY1, Di Pascuale MA, Elizondo A, Tseng SC. Clinical treatment of ocular demodecosis by lid scrub with tea tree oil. Cornea. 2007 Feb;26(2):136-43.
  100. Kheirkhah A1, Casas V, Li W, Raju VK, Tseng SC. Corneal manifestations of ocular demodex infestation. Am J Ophthalmol. 2007 May;143(5):743-749. Epub 2007 Mar 21.