Every political or social revolution forces, winners, and losers. The same is true for the ongoing information revolution: Technology continues to be a primary driver, and consumers are winning in terms of the convenience, breadth, and accessibility of content.

The casualties of this revolution have included traditional news outlets such as newspapers and television, which have been replaced by social media as the most popular source of news. To survive in this tumultuous era, shrewd content producers know that their value and future depend on their ability to consistently provide reliable, useful information.

 content platform but for veterinary practices as well. The digital revolution has given practices an unprecedented opportunity to reach pet owners and grow their businesses.

At the FUSE technology and media conference last fall, conference chair Jeffrey Litvack highlighted important trends that publishers should be translating into strategies for growth.1 Content personalization is increasingly crucial, he said; 56% of websites and 67% of emails have some level of personalization, and consumers are responding positively.

Litvack also noted that reader engagement with newsletters continues to rise. Time spent on email increased by 17% from 2015 to 2016 with,2 perhaps not surprisingly, millennials spending more time with email than any other age group—all because of their phones.

 is improving the services we offer to veterinary professionals. We recently upgraded our email platform to help optimize subscribers’ experience. Recipients may not notice a difference, but that’s the point: We want to continuously and seamlessly improve the user experience and are investing in systems to do this.

All of our newsletters link to our websites, which offer a host of articles and videos covering not only clinical news and information but also practice management and business-related content that you can use to improve your online presence and build your business.

 Is your practice website engaging and interactive? Is it updated regularly? Does it contain a library of articles and blogs that pet owners can turn to when they have questions related to the health of their 4-footed family members? Is your website mobile- friendly? Does it spur the user into action?

Do you send a practice newsletter to your clients? Are you following email best practices? Are your emails personalized? Do they offer a link for recipients to visit your website, Facebook, Instagram, or Pinterest page? Do you use your newsletter as a vehicle for asking your clients to leave online reviews for your practice? Does your newsletter convey trust and a sense of partnership?

If you answered no to most of these questions, then it’s probably time to rethink your electronic marketing strategy. To remain engaged with current clients and win new customers, practices today absolutely must be using technology to their advantage. We are committed to helping veterinary practices—and their clients and patients&mdash;be counted among the winners in the information revolution.

Articles

Letter from the Chairman

Technology continues to be a primary driver, and consumers are winning in terms of the convenience, breadth, and accessibility of content.

The Information Revolution: We Can All Benefit

) Draining tracts on the foot of a dog with pyoderma. (

Bacterial pyoderma is one of the most commonly diagnosed dermatologic diseases in dogs. Although β-lactam antibiotics such as cephalexin were once effective in treating pyoderma, the growing emergence of resistant bacteria, particularly methicillin-resistant 

, has made treatment of this condition much more complicated. At the 2018 Midwest Veterinary Conference in Columbus, Ohio, Paul B. Bloom, DVM, DACVD, DABVP (Canine & Feline), discussed the diagnosis and treatment of pyodermas, with a particular focus on using a bacterium’s minimum inhibitory concentration (MIC) to select the proper antibiotic.

New Findings on the Pathogenesis of Canine Demodicosis

ACVC 2017: Understanding Skin Disease in Cats

The frequency of antibacterial resistance in both human and veterinary medicine has been increasing. This increased resistance heightens the risk of spreading antibacterial resistance genes between animals and people, said Dr. Bloom, an adjunct assistant professor in the Department of Small Animal Clinical Sciences at Michigan State University College of Veterinary Medicine and a practitioner at the Allergy, Skin and Ear Clinic for Pets in Livonia, Michigan. Previous studies, for example, have reported the transfer of drug-resistant 

Pyodermas are typically caused by a staphylococcus. In recent years, methicillin-resistant 

)—has been identified increasingly in canine pyodermas.

Superficial bacterial folliculitis (SBF), a superficial pyoderma, is characterized by such clinical signs as variable pruritus, multifocal alopecia, follicular papules or pustules, and epidermal collarettes. In addition, serous serocelluar crusts can be found on the trunk and abdomen, and in axillary regions. Short-haired breeds with SBF may present with a moth-eaten appearance. Notably, cocker spaniels with SBF can present with vegetative plaques that can be mistaken for seborrheic plaques.

Deep pyodermas are characterized typically by nodules, hemorrhagic bullae, and serosanguineous to purulent draining tracts. Deep pyoderma lesions can be found on the nose, chin, elbows, hocks, and interdigital spaces.

Diagnosing bacterial pyodermas requires a systematic approach, which includes obtaining a thorough history and performing a dermatologic examination.

Obtaining a detailed history involves asking numerous questions about a dog’s condition:

When did the signs first occur? Have they progressed rapidly or gradually?

Has the dog been treated previously for skin or ear disease? If yes, what was used and for how long? What was the dog’s response?

Does the dog live indoors, outdoors, or both?

Is the dog pruritic? If so, did the rash develop first, or did the pruritus and rash begin simultaneously?

Compared with the first appearance of signs, is today’s clinical presentation better, worse, or about the same?

Are there other pets living in the household? If so, do they have skin problems?

What medication is the dog currently receiving?

The dermatologic examination serves to identify primary lesions (eg, papules, pustules, nodules) and secondary (eg, ulcerations, crusts) lesions, detect ectoparasites, observe evidence of self-trauma, and determine hair coat quality and skin appearance. The exam should include an impression smear of a lesion, in which infectious agents, neoplastic cells, inflammatory cells, and pemphigus foliaceus—associated acantholytic keratinocytes can be evaluated. Skin scrapings for ectoparasites and flea combing are essential parts of a dermatology minimum database.

The patient history and results of the dermatologic examination form the basis for the differential diagnosis. This list is important, given that canine pyodermas are never primary diseases and are always “due to” something, Dr. Bloom noted. Potential differentials include hypersensitivities (eg, atopy), endogenous or exogenous steroid exposure, ectoparasites, hypothyroidism, and follicular dysplasias.

It is especially important to rule out demodicosis in dogs with lesions that are consistent with SBF. In addition, the presence of pustules requires ruling out pemphigus foliaceous.

) Mini-tip culturette versus standard culturette. (

Culture and susceptibility (C/S) testing is an important diagnostic component and is recommended for poorly responsive SBF. It is also warranted at the first visit for the following scenarios:

Deep bacterial pyoderma with predominantly rods on cytology

There are several ways to obtain samples for C/S testing. For example, mini-tip culturettes, rather than large swabs, are ideal for sampling from draining tracts and pustules. A papule, Dr. Bloom mentioned, can be sampled like a pustule in which the papule or pustule is ruptured with a needle and then the swab is touched carefully to the surface of the lesion. For patients with epidermal collarettes, he recommended swabbing just underneath the collarette’s edge. Because lesions can have bacterial strain heterogeneity, which can lead to different antibiotic susceptibilities, samples should be taken from 3 or 4 locations but all can be sampled with the same swab.

Sampling can be done while a patient is on antibiotics; to date, there is no empiric evidence to support waiting until the end of antibiotic therapy to obtain a sample for C/S testing. “When a client is there and you can do something,” Dr. Bloom emphasized, “go ahead and do it [right] then,” because clients may be too busy or may not see the importance of returning to the veterinary office for a recheck of the pyoderma, particularly if the signs have improved.

That said, if a dog is not currently on antibiotics, Dr. Bloom advised waiting until after culture results come back before starting antibiotic therapy, unless the dog has a fever or a life-threatening illness. Starting antibiotic therapy before the results come back could result in altered susceptibility patterns, thus complicating results.

The old method of C/S testing was the disk diffusion method (Kirby-Bauer method), which determines susceptibility (susceptible, intermediate, resistant) based on the zone of inhibition in a solid medium. This method, however, does not provide an accurate measure of how susceptible a bacterial strain is to a particular antibiotic.

The tube dilution method, which is quantitative, is the preferred method of C/S testing. Each test tube contains the same concentration of bacteria (105/mL) and serially increasing antibiotic concentrations (which vary among antibiotics); each tube contains double the antibiotic concentration as the previous tube. This method tells how susceptible a bacterial strain is to an antibiotic by reporting the MIC: the concentration of the first tube in which there is no visible bacterial growth.

Simply having the MIC is not enough to determine which antibiotic to use to treat bacterial pyodermas. Another value—the “break-point”&mdash;is also important. The breakpoint is a standard concentration for specific antibiotics that determines susceptibility or resistance: MICs below the breakpoint indicate susceptibility and MICs above the breakpoint represent resistance. A document developed by Michigan State University’s Diagnostic Center for Population & Animal Health contains a list of breakpoint values for antibiotics commonly used in animals.

 These values, Dr. Bloom noted, do not change.

Selecting the most appropriate antibiotic requires calculating the efficacy ratio, which can be done as follows:

From the C/S results, select the antibiotics with MICs reported as “≤ X,” where X is any number.

Divide the breakpoint by X for each individual antibiotic. The higher the calculated number, the higher the susceptibility will be.

Rank the antibiotics in order from greatest to least susceptibility.

 bacterial strain that has an MIC of ≤ 1 μg/mL to enrofloxacin (breakpoint = 4) and an MIC of ≤ 4 μg/mL to cephalexin (breakpoint = 32). The efficacy ratio is 4 for enrofloxacin (4/1) and 8 for cephalexin (32/4), indicating that the bacterium is most susceptible to cephalexin. This same calculation can be performed for antibiotics for which the MIC is not reported as “≤ X.”

Calculating this efficacy ratio is particularly important because of the bacterial strain heterogeneity and subsequent antibiotic susceptibility variation within pyoderma skin lesions.

Although the ratio is key to appropriate antibiotic selection, other factors influencing antibiotic selection should be considered, including adverse events, level of tissue penetration, cost, and convenience.

Formularies, Dr. Bloom mentioned, list dose ranges and varying administration frequencies, making it potentially difficult to decide which dose and administration frequency to choose. These recommendations, he explained, are based on susceptibility and the MIC: The closer the MIC is to an antibiotic’s breakpoint, the higher the dose and more frequent the administration needs to be. For empiric antibiotic therapy, the highest listed dose should be used; however, Dr. Bloom warned, this increases cost and the risk of adverse events.

) Pustule and epidermal collarette in a dog with pyoderma. (

) Draining tracts and crusts in a dog with deep pyoderma.

Despite a calculated approach to appropriate antibiotic selection for pyoderma treatment, combatting methicillin-resistant 

 (MRSS, MRSP, MRSA) remains a challenge. Traditionally, clindamycin has been used widely in veterinary medicine for treating 

—that can mutate spontaneously and confer antibiotic resistance. 

confers resistance to macrolides (ie, erythromycin), and erm confers resistance to lincosamides (clindamycin and lincomycin).

These resistance-conferring mutations, which occur every 107 to 1010 mutations, are unlikely to show up on C/S testing, though, because of the bacterial concentration used for the tube dilution method; the concentration is not high enough for bacterial replication to produce enough mutations for the resistance-conferring mutations to occur.

This is important because clindamycin resistance may not be observed during C/S testing. For MRSA cases with the 

 mutation, clindamycin resistance may go undetected until after treatment begins. To circumvent this treatment complication when dealing with any methicillin-resistant 

for which the culture indicates resistance to erythromycin, Dr. Bloom strongly advised against using clindamycin even if the culture shows susceptibility to clindamycin because the bacteria will likely develop resistance to the medication.

Resistance to systemic antibiotics warrants the use of topical therapies for treating bacterial pyodermas. Topical therapy can reduce or even eliminate the need for systemic antibiotic treatment. However, its use may be limited by an owner’s time constraints as well as cost constraints if the affected skin area is large.

Bathing with shampoos that contain ingredients such as chlorhexidine or benzoyl peroxide is an important topical therapy, Dr. Bloom explained, because doing so gets bacteria off the skin. Which ingredient is the most effective is difficult to determine, though, because of the lack of systematic reviews and randomized double-blinded controlled studies evaluating the ingredients. However, in a review of studies on shampoo therapy, chlorhexidine had the highest evidence of effectiveness, followed by benzoyl peroxide— containing shampoos.

Although 10 to 15 minutes of contact time is typically recommended for baths, there are no studies that justify this recommendation. Notably, a study evaluating bathing with 2% chlorhexidine found that just 1 to 2 minutes of contact time every other day for a week was as effective as 10 minutes every other day.

Bleach is another effective topical therapy. One option is to use Dakin’s solution, which is commercially available dilute bleach. You can mix it up yourself, daily, using 2 oz of bleach (6%-8%) with 32 oz of water and 0.5 tsp baking soda. Allow a 1- to 2-minute contact time for the shampoo and then rinse. Then bathe the dog with an antimicrobial shampoo and apply a moisturizer.

Because shampoos are not considered a drug, Dr. Bloom advised using high-quality shampoos only from companies that follow Current Good Manufacturing Practices, which are FDA regulations that ensure proper manufacturing.

Clipping is another component of topical therapy, facilitating visualization of the full extent of skin lesions.

When treating SBF with topical antibiotics, treat for either 21 days or 14 days past clinical resolution (as determined by a veterinarian), whichever is longer. Deep pyodermas require at least 6 weeks of treatment or 21 days past clinical resolution, whichever is longer. Regarding glucocorticoids, a 21-day tapering dose of prednisone can be used in SBF if there is intense pruritus and the dog has a fairly localized pyoderma; glucocorticoids should never be used for deep pyodermas.

When discussing systemic antiobiotic therapy for bacterial pyoderma, Dr. Bloom focused on the use of third-generation cephalosporins (cefpodoxime, cefovecin) and fluoroquinolones.

The higher-generation cephalosporins have broad-spectrum activity against gram-negative bacteria. Using broad-spectrum antibiotics in a “go big or go home” approach, though, can select for resistance in nontargeted and nonpathogenic microorganisms; these microorganisms can then spread resistance genes to pathogenic bacteria. In particular, third-generation cephalosporins and fluoroquinolones increase the incidence of extended-spectrum β-lactamase—producing bacteria, which are frequently multidrug resistant.

Not only does the extended-spectrum β-lactamase enzyme have a comparatively broader range of activity than standard β-lactamase enzymes, its resistance spreads through plasmid, widening its distribution among humans and animals.

Given the risk of widespread multidrug resistance, human and veterinary health organizations have developed consensus statements and guidelines regarding the use of higher-generation cephalosporins and fluoroquinolones. For example, Swedish Veterinary Association guidelines state that “third- or fourth-generation cephalosporins should only be used in situations where their use is considered of the utmost importance to the animal’s welfare and where there is a sound basis to suspect that alternative treatments will not have the desired effect.”

 The American College of Veterinary Internal Medicine consensus statement indicates that “limiting use of classes such as the third-generation cephalosporins and fluoroquinolones is widely accepted and consistent with principles of antimicrobial stewardship.”

On the human side, the World Health Organization has categorized antibiotics as critically important, highly important, or important, according to their usefulness in human health. Among the critically important antibiotics, third- and fourth-generation cephalosporins and fluoroquinolones are further classified as “highest priority.” Moreover, the European Medicines Agency has designated third- and fourth-generation cephalosporins and fluoroquinolones as the most important critically important antibiotics.

For treating canine bacterial pyoderma, Dr. Bloom emphasized that veterinarians should be very selective with antibiotics, particularly third- and fourth-generation cephalosporins and fluoroquinolones. As a concluding thought, he said that “we have to look at the impact on human medicine when selecting an antibiotic in veterinary medicine.”

Dr. Pendergrass received her DVM from the Virginia-Maryland College of Veterinary Medicine and completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. She is the founder and owner of JPen Communications, LLC, a medical communications company. 

Harada K, Okada E, Shimizu T, Kataoka Y, Sawada T, Takahashi T. Antimicrobial resistance, virulence profiles, and phylogenetic groups of fecal 

 isolates: a comparative analysis between dogs and their owners in Japan. 

Manian FA. Asymptomatic nasal carriage of mupirocin-resistant, methicillin-resistant 

 (MRSA) in a pet dog associated with MRSA infection in household contacts. 

Boost MV, O'Donoghue MM, James A. Prevalence of 

Michigan State University Diagnostic Center for Population & Animal Health. Resistance breakpoints for antimicrobials used in animals. Michigan State University website. 

https://animalhealth.msu.edu/sections/bacteriology/webcd.bact.ref.011.pdf

. Published January 31, 2014. Accessed May 30, 2018.

Murayama N, Nagata M, Terada Y, et al. Contact time of 2% chlorhexidine acetate for canine superficial pyoderma. 

Swedish Veterinary Association. Guidelines for the clinical use of antibiotics in the treatment of dogs and cats. Swedish Veterinary Association website. 

svf.se/Documents/S%C3%A4llskapet/Sm%C3%A5djurssektionen/Policy%20ab%20english%2010b.pdf

Weese JS, Giguère S, Guardabassi L, et al. ACVIM consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance.

J Vet Intern Med. 2015;29(2):487-498. doi: 

Conference Coverage

Growing antibiotic resistance has complicated the treatment of bacterial skin conditions. Here’s what to consider when making therapeutic decisions for your patients.

Antibiotic Selection in Pyoderma

Many common household plants, such as aloe, can be toxic to pets.

When 20-month-old Jessie started vomiting, her owners, Catherine and Bruce Campbell of Wilmington, North Carolina, were puzzled. The rambunctious golden retriever hadn’t gotten into dinner scraps, and nothing seemed out of place. The Campbells went to bed assuming Jessie would be better in the morning.

But Jessie wasn’t better. In fact, she had become so lethargic that the Campbells rushed her to Hanover Regional Animal Hospital, where John Manolukas, DVM, PhD, referred them to a specialty hospital in Cary, 2 hours away. The doctors there started treating Jessie for shock and questioned whether she had gotten into an ant nest or a bee hive or had eaten candy containing xylitol. Finally, the veterinarian asked whether the Campbells had sago palms in their yard. They did, several of them. Bruce went out to check and found that Jessie had chewed up numerous budding fronds.

IVECCS 2017: Advances in Companion Animal Toxicology

Jessie was given plasma transfusions because she had started bleeding out of her anus. Once she was stable, the Campbells returned with her to Wilmington, where Dr. Manolukas continued treatment. But nothing worked. “We saw Jessie on Saturday, and I could see that she had turned yellow from jaundice,” Catherine said. “My husband had left the room, and Jessie let out a huge puddle of blood. It was very disturbing. I had worked as an administrator at a veterinary hospital, so I knew what was happening. I was hoping they could save her, but the sago palm destroyed her insides. She died the following Monday.”

Although he has been a professional landscaper for more than 20 years, Bruce Campbell, like most pet owners, had no idea that sago palms are extremely toxic to dogs. As a result of their experience with Jessie, the Campbells immediately had every sago palm removed from their property. In an effort to educate others, Catherine created a brochure about the risk, which she hands out to the pet owners she meets while walking. “I just want people to be aware so they don’t go through the same thing we did,” she said.

The sago palm is just 1 example of the many popular plants that can be toxic to pets if ingested. According to Tina Wismer, DVM, DABVT, DABT, medical director of the American Society for the Prevention of Cruelty to Animals (ASPCA) Animal Poison Control Center in New York City and master gardener, this plant was once found only in warm regions of the United States, but miniature sago palms are now sold at many nurseries and home supply stores, giving pets even greater access to a deadly plant. “Sago palms usually are not labeled in stores, so people will buy them not knowing how toxic they can be,” she said. “It’s important that pet owners do some research before bringing a plant into their home or new plants to be used for landscaping.”

Increasing the risk for family pets is the common misconception that dogs and cats intuitively know which plants are OK to chew on and which are not. Such is not the case, said David Dorman, DVM, PhD, DABVT, DABT, professor of toxicology at North Carolina State University College of Veterinary Medicine in Raleigh. “Owners don’t quite appreciate that animals are just like us—they don’t know what’s good for them; they don’t know which plants are toxic,” Dr. Dorman explained. “Pets are just as ignorant as we are.”

Just how common are cases of toxic plant ingestion? According to Dr. Wismer, plant ingestion comprised 5.4% of the more than 199,000 calls received by the ASPCA Animal Poison Control Center in 2017. “That’s more than 10,700 calls for the year, or around 29 calls a day,” Dr. Wismer reported.

Dogs and cats, because they commonly explore their environment by chewing or licking, are the largest patient cohorts in terms of plant ingestion calls, Dr. Wismer added. “They make up probably 96% of our cases. The next largest group is rabbits, followed by birds, which get into houseplants if allowed to fly inside the home.”

 come in all types and affect the body in different ways, noted Bruce Kornreich, DVM, PhD, DACVIM, associate director of education and outreach at the Cornell Feline Health Center and clinical cardiologist in the Department of Clinical Sciences at Cornell University College of Veterinary Medicine in Ithaca, New York. Lilies, for example, are extremely toxic to cats and can result in renal failure and death, while plants such as foxglove—from which the heart medication digoxin is derived&mdash;can result in an abnormal cardiac rhythm, low blood pressure, and other potentially life-threatening effects. And the sago palm can result in liver failure, among other conditions.

“Some common houseplants, such as dieffenbachia and philodendron, contain insoluble oxalate crystals, which look like little needles,” Dr. Wismer added. “When an animal eats these plants, the crystals shoot into their tongue and gums, resulting in drooling as well as vomiting and gagging. It’s not life-threatening in most cases, but it can be extremely painful.”

Wild mushrooms, while not plants, are another area of concern. Identification is vital, Dr. Wismer noted, because the effects of wild mushrooms can range from mild gastrointestinal (GI) upset to liver failure and death. Unfortunately, owners may have no idea what their pets got into, and early symptoms may mimic those of other disorders. The treatment for mushroom toxicity is similar to that for toxic plant ingestion.

Pet owners should also be cautious about the use of herbs around their pets. Most herbs commonly used in cooking are relatively harmless, perhaps resulting in mild stomach upset, but concentrated herbs may cause more serious problems. Dr. Wismer recalled a cat that had licked some concentrated oregano oil and experienced burns in its mouth. “If it had just 

eaten the plant, we would expect stomach upset,” she said. “But the oil was a whole magnitude greater in concentration.”

Treatment for toxic plant ingestion is dependent on a variety of factors, including the type of plant, the amount ingested, and the plant’s effects on specific organ systems. Treatment typically begins by identifying the plant, if possible, and then performing blood tests to determine which organ systems might be damaged. “In the case of liver damage, you might find elevated enzymes,” Dr. Kornreich noted. “In the case of kidney damage, you might find elevations in the by-products that are normally removed from the bloodstream by the kidneys.”

In some cases, induced vomiting might be warranted to remove the plant material from the stomach. If that is not an option, activated charcoal may be used to absorb toxic substances in the GI tract. From there, gastric protectants such as sucralfate may be used to protect areas of the stomach damaged by local irritation or chemical principles within the plant, Dr. Kornreich explained.

The final stage of treatment is addressing the effects of the plant on specific organ systems, such as the heart, liver, kidneys, and GI system. “In dealing with the acute effects on organ systems, there may be chronic effects,” Dr. Kornreich warned. “If a cat ingests lilies and survives, it may be that the cat will experience kidney problems for the rest of its life and may benefit from dietary modification and other approaches to treat that specific organ.”

Toxic plant ingestion is an issue that veterinarians see often, and it falls on practitioners to remind clients regularly of the potential risk through email blasts, practice newsletters, and handouts featuring specific resources. Foremost is the 

ASPCA Animal Poison Control Center website

. In addition to providing treatment information to veterinarians and pet owners, the site features an extensive list of plants and their potential for toxicity.

“The most critical thing is prevention,” Dr. Dorman concluded. “In a lot of ways, I believe we in the veterinary tend not to be as proactive as we should be about informing pet owners, especially new owners of companion animals, about potential hazards they might encounter. Directing clients to resources such as the ASPCA website and other poison control websites is a good way to educate them about which plants to avoid. Prevention should always be our main goal.”

Don Vaughan is a freelance writer based in Raleigh, North Carolina. His work has appeared in Military Officer, Boys’ Life, Writer’s Digest, MAD, and other publications. 

Clinical Focus

Ingesting certain plants can be deadly for dogs and cats. Here’s what you need to know to educate your clients and keep your patients safe.

Code Green: The Risk From Toxic Household Plants

Growing cultures of B burgdorferi viewed with dark field microscopy.

Lyme disease is the most commonly reported vector-borne disease in humans in the United States.

 Its incidence in dogs has been increasing steadily due to expanding tick populations.

 In a webinar hosted by online continuing education provider 

, Richard T. Marconi, PhD, talked about the technology his laboratory used to develop a new Lyme disease vaccine for dogs. This chimeric recombinant vaccine, Vanguard crLyme, is produced by Zoetis, the webinar sponsor.

“Lyme disease is a very serious illness, and prevention is very, very important,” said Dr. Marconi, a professor in the Department of Microbiology and Immunology at Virginia Commonwealth University Medical Center. Lyme vaccines and tick control products have not been sufficient to stop the spread of the disease, he added.

CDC Warning Echoes Parasite Council's Predictions About Vector-borne Disease

Tick Exposure and Kidney Disease Risk in Dogs

Dr. Marconi began by describing the morphology of 

, the causative agent of Lyme disease. The mechanism of motility of these spiral-shaped bacteria, or spirochetes, is similar to that of a drill bit. Once a spirochete enters a mammal’s body, Dr. Marconi said, “that corkscrew motility allows the Lyme disease bacteria to penetrate quickly through tissue and disseminate to distal organs and tissue sites throughout the body.”

Treatment of Lyme disease can be difficult once the spirochetes have penetrated deep into tissues and organs, he said. Three to 4 weeks of antibiotic treatment are required to clear an infection; in some cases it may be necessary to repeat treatment. For this reason, coupled with the serious clinical consequences associated with Lyme disease, prevention is crucial.

How Spirochetes Adapt to Different Environments

To be maintained in nature, the Lyme spirochetes must cycle between 

ticks and mammals (enzootic cycle). Once spirochetes establish an infection in ticks, they reside for extended periods of time in the tick midgut, a harsh environment with few nutrients. When ticks ingest a blood meal, however, there

is a dramatic increase in available nutrients, which allows the spirochetes to ramp up their metabolic activity, divide and begin transit from ticks to mammals (

However, this is a complicated process and spirochetes must be able to adapt rapidly to the radically different environments they encounter in the unfed tick, fed tick, and mammals. “One of the key things we need to know to develop an effective vaccine is exactly how the spirochetes adjust to these radically different environments,” Dr. Marconi said.

He used the analogy of human clothing to explain spirochete environmental adaptation. People wear different types of clothes in summer than in winter; that is, we change some of our surface properties to respond to changes in environmental conditions. Lyme spirochetes do the same thing, he said.

Outer surface proteins (Osps) “play important roles in the biology and adaptive responses of the Lyme disease spirochetes,” Dr. Marconi explained. They have also been at the center of Lyme disease research and vaccine development efforts. The 2 Osps that have received the most attention are OspA and OspC. These proteins are important in spirochete survival in ticks and in the transmission and infection process, respectively. The differential production of OspA and OspC is controlled by environmental conditions. OspA is a dominant protein on the surface of spirochetes residing in unfed ticks. However, as ticks feed, OspA production is turned off as OspC production is turned on. Upon entering a mammal, spirochetes are producing large amounts of OspC but no OspA.

Lyme disease vaccine development focused on OspA for many years, Dr. Marconi said. However, he added, the efficacy of OspA- targeting vaccines was approximately 72%. If a spirochete does not express OspA once it’s in a vaccinated animal, then how does a vaccine targeting OspA work at all? Dr. Marconi explained that the blood of an OspA-vaccinated mammal that has received sufficient booster immunizations contains anti-OspA antibodies. When a tick ingests this blood, the anti-OspA antibodies pass with the blood into the tick where they have the potential to kill spirochetes before they can transition to the production of OspC. “A transmission-blocking vaccine is a very attractive concept,” he remarked.

The problem, he continued, is α antibody levels in blood decline over time, eventually dropping below the threshold required to kill spirochetes inside the tick. Because the spirochetes that make it into a mammal lack OspA, they cannot be targeted by vaccine-induced antibody in the mammal. In addition, vaccines against OspA do not induce immune memory because a vaccinated animal’s memory cells are never exposed to OspA antigen during a natural infection.

“We realized that OspC had significant potential to help improve the Lyme disease vaccine,” Dr. Marconi said. Spirochetes express very low levels of OspC while they are in an unfed tick. After the tick takes a blood meal, OspC expression is upregulated dramatically in response to changes in temperature and pH. Spirochetes continue to express high levels of OspC after they have entered a mammal. A vaccine that targets OspC, therefore, can kill

spirochetes inside a vaccinated animal. In addition, an OspC-based vaccine also has the potential to trigger immune memory.

Vaccines that target OspA are transmission-blocking vaccines: They prevent infectious organisms from entering the body. However, an animal must have a high antibody titer for an OspA vaccine to be protective. The function of OspC-targeting vaccines is to clear infection, and these vaccines also provide immune memory. Combining the 2 targets in a single vaccine should improve vaccine efficacy by eliciting protection through 2 synergistic mechanisms, Dr. Marconi said.

He discussed 2 general types of vaccines used in veterinary medicine: bacterins and subunit vaccines. He described bacterins as “bacterial soups.” Lyme disease bacterin vaccines are generated by growing the bacteria in the laboratory. The bacteria are then collected, inactivated, and homogenized to render them more amenable to injection. Bacterins contain extraneous ingredients that do not contribute to protective immune responses. “In the context of veterinary medicine, where you are delivering multiple vaccines during a single visit, it would really be preferable to have vaccines that are of higher purity” and have fewer unnecessary ingredients, he said.

Subunit vaccines consist of 1 or more highly purified recombinant proteins that are produced in a laboratory under controlled conditions, Dr. Marconi said. His group’s aim was to create a combination OspA and OspC subunit vaccine.

Developing the OspA component was simple, he said, because this protein does not vary substantially among Lyme spirochetes. In other words, a single version of OspA in a vaccine will induce antibodies that are effective against many strains of 

OspC, on the other hand, has about 30 different variants. Most are designated with letters: OspC type A, OspC type B, and so forth. OspC variants are all the same protein, Dr. Marconi said, but their amino acid configurations differ. “Understanding the variation and diversity in this protein turned out to be critical in figuring out how to design a vaccine that could kill all the different strains that exist in nature,” he noted.

Dr. Marconi’s team found that dogs with positive Lyme antibody tests all had anti-OspC antibodies, but their antibodies were to different variants of the protein. Their next step was to isolate the specific parts of the OspC protein that induce antibody production. The parts of a protein that elicit anti- body production are referred to as epitopes. “We reasoned that if we could identify the epitopes of OspC that we could then utilize those defined portions of OspC to make a focused, refined, and broadly protective vaccine,” he said.

Dr. Marconi’s group ran immunoblot analyses on OspC subfragments and located 2 epitopes that induce antibody formation. These epitopes became the basis of the new vaccine.

“The process that we applied is a new technology that we refer to as chimeritope technology,” Dr. Marconi said. The word 

. “Chimeric indicates that we are joining things together and what we are joining together are OspC epitopes derived from many different strains. Chimeritopes are desirable vaccine anti- gens because they contain only the immunologically relevant parts of many different OspC type proteins,” he said. Dr. Marconi explained that a protein constructed this way “can trigger the formation of [antibodies] to the diverse OspC type proteins that exist in nature and, therefore, provide broad protection.”

Further testing showed that a vaccine made with the OspC chimeritope induced the production of antibodies that could kill 

. The spirochete elimination rate in the laboratory was higher with an experimental combination vaccine that contained both OspA and the chimeric OspC. Results from efficacy studies showed that compared with placebo and single-component vaccines, the combination vaccine significantly reduced lesions in the skin and joints of vaccinated dogs exposed to ticks carrying 

Tests of the chimeritope vaccine that was eventually brought to market confirmed that the vaccine prevented infection, protected dogs against skin and joint lesions after exposure to ticks carrying 

, and caused no major adverse effects. The most common immediate postvaccination reaction (<30 minutes after vaccination) was vocalization upon injection, occurring in 0.73% of dogs. The most common late postvaccination reaction (>30 minutes to 14 days after vaccination) was injection-site edema, which occurred in 3.81% of dogs.

Vanguard crLyme received approval from the Food and Drug Administration in January 2016, said Dr. Marconi. It is administered by subcutaneous injection. Dogs should receive an initial series of 2 doses given 3 weeks apart. A 15-month duration of immunity has been established for Vanguard crLyme.

Dr. Walden received her doctorate in veterinary medi- cine from North Carolina State University in 1994. After an internship at Auburn University College of Veterinary Medicine, she returned to North Carolina, where she has been in companion animal general practice for over 20 years. Dr. Walden is also a board-certified editor in the life sciences and owner of Walden Medical Writing. 

Centers for Disease Control and Prevention website

. cdc.gov/lyme/stats/. Updated November 13, 2017. Accessed April 29, 2018.

Littman MP, Gerber B, Goldstein RE, Labato MA, Lappin MR, Moore GE. 

ACVIM consensus update on Lyme borreliosis in dogs and cats

zoetisus.com/products/dogs/vanguard-crlyme/resources/vanguard-crlyme-efficacy-information.pdf

. Published December 2015. Accessed April 27, 2018.

Recent advances such as chimeritope technology could potentially be used to develop vaccines against other tickborne diseases as well.

Developing a Vaccine for Lyme Disease

Increasingly, treatment for a host of conditions and ailments is based on electroceuticals rather than pharmaceuticals. Instead of prescriptions for chemical molecules, some doctors are prescribing specific frequencies, waveforms, and amplitudes for their patients. This is not science fiction—it's happening right now.

It’s not really a stretch to see how this can be. Every day, car engines are started and doors are opened from a distance using a fob. This is made possible by matching frequency signals (waves) that are programmed to initiate a ligand—receptor type of reaction, allowing people to enter a warm space and be on their way. Photos and messages are relayed daily by the millions from one phone to another. Images and videos (waves, frequencies) travel through space, not getting crossed with others and reaching their intended destinations intact.

Simply, electroceuticals, which are sometimes called bioelectronics, are electric waveforms that stimulate the nervous system electronically and modify bodily functions. Waveforms, frequencies, and microamperes—collectively called microcurrent electrical therapy (MET) and cranial electrotherapy stimulation (CES)&mdash;are being used to stimulate cell regeneration and treat injuries, acute and chronic pain, anxiety, depression, and insomnia.

Are Electroceuticals the Future of Veterinary Medicine?

How Electroceuticals Reduce Anxiety, Stress in Pets

MET and CES work because the nervous system and tissues function electrochemically and can be modulated readily by electrical intervention. Low-frequency current effectively targets cell receptors, activating them through frequency matching in a manner similar to that of chemical ligands.

Robert O. Becker, MD, an orthopedic surgeon known as the father of electromedicine and electrochemically induced cellular regeneration, began studying electric current therapy in 1970. Fifteen years later, he demonstrated that electric current is the trigger that stimulates healing, growth, and regeneration in all living organisms. Signals come from an electric control system that he called the current of injury, which is conducted through Schwann cells and the myelin surrounding neurons.

In 1980, Candace Pert, PhD, published her research on ligand—receptor binding, providing a new understanding of cellular physiology and the connection between mind and body.

 Bjorn Nordenstrom, MD, proposed a model of biologically closed electric circuits analogous to closed circuits in electronic technology. He postulated in 1998 that mechanical blood circulation is closely integrated anatomically and physiologically with a controlling bioelectric system.

Taking the research findings of these and other pioneers, neurobiologist Daniel L. Kirsch, PhD, DAAPM, FAIS—whose mentor was Dr. Becker&mdash;patented a unique waveform. He collaborated with engineer Raymond Chan to design medical devices for implementing pain and stress control technologies into clinical systems. His Alpha-Stim technology was the first dual electromedical device (MET and CES) to be cleared by the Food and Drug Administration to market in 1981. Dr. Kirsch remains at the forefront of research in this field.

 Today, the Alpha-Stim and Fisher Wallace Stimulator (formerly Liss Cranial Stimulator) are the primary electroceutical devices on the market.

Microcurrent electrical therapy on the elbow of a dog with degenerative joint disease.

As for many drugs, early research on MET and CES was conducted using animals. Once safety was established, the focus turned to human studies and clinical trials. Because the current is subsensory, it lends itself well to double-blind placebo-controlled crossover studies.

Animal studies in neurophysiology and electromedicine continue to yield new discoveries on the efficacy of this therapeutic approach. Measurements have shown that CES current across the head sends electric impulses through every area of the brain. CES directly stimulates the brain’s neuromatrix, including the limbic area, or emotion center, of the brain.

Results of an experimental study in rats with CES documented as much as a 3-fold increase in beta-endorphins after only a single CES treatment.

 Results of a double-blind study looking at 33 behavioral traits in horses treated with CES showed that all the changes were highly intercorrelated and strongly indicated a reduction in the horses’ state of arousal following CES treatment that was not noted in the sham treatments (

Neurosurgeon C. Norman Shealy, MD, assessed beta-endorphin and serotonin levels in plasma and cerebrospinal fluid (CSF) following a 20-minute session of CES and found that beta-endorphins measured 98% higher in plasma and 219% higher in CSF. Serotonin levels were 15% to 40% higher in plasma and 50% to 200% higher in CSF.

Results from further research have shown the effectiveness of CES in treating fibromyalgia, posttraumatic stress disorder, spinal cord injury, cancer pain, and dental anxiety in humans.

 Results of low-resolution electromagnetic tomography and functional magnetic resonance imaging studies have shown that select waveforms can reach most cortical and subcortical areas of the brain, thereby altering the brain’s emotional centers (ie, thalamus, hypothalamus, basal ganglia, reticular activating system, cerebral cortex, and limbic system) where the amygdala controls the strength of emotional responses, especially for fear and anger.

Cells throughout the body manufacture peptides that act as ligands to surface receptors on other remote cells, communicating via the extracellular fluid and circulatory system. Cells within a specific organ or tissue system communicate through specific frequencies in the microamperage range, activating the current of injury and causing the system to tend toward homeostasis. Neuromodulation imparts an electric signal with a frequency that perfectly matches the receptors in the body to resonate and activate intracellular responses.

MET can act similarly to ligands in activating receptors to send their messages into cells and produce effects resembling a wide range of chemical messengers. MET can be viewed as a catalyst in initiating and sustaining the numerous chemical and electrical reactions that occur in the healing process. An effective biphasic, squared, long-pulse-width waveform in the microamperage range (1000 times less than that of a transcutaneous electrical nerve stimulation device and below sensation threshold) will use resonant frequencies to activate central pain modulatory mechanisms.

The sensation of pain is transmitted through the body along billions of nerve cells that are designed specifically to transmit messages through electrochemical signals. Physics controls chemical reactions in the body, and most bodily functions can be normalized electrically. It is the application protocol that affects the peripheral pain site directly and accesses the central nervous system by directing the current through the spine. Combining MET and CES addresses all 4 pain pathways: transduction, transmission, modulation, and perception.

The resultant central and peripheral effects of CES include calmness, relaxation, reduced agitation and aggression, stabilized mood, improved sleep, and reduced pain. Results will vary with the exact technology used, the pathology of the disease being treated, the overall health and hydration of the patient, and owner compliance. Patient history, prior medical interventions, previous injuries, and surgical scars can affect overall outcome as well.

Waveforms can be used effectively to activate the body’s natural electric impulses.

CES and MET have been used extensively in the clinical setting for nearly 2 decades to initiate cellular regeneration and control not only acute and chronic pain situations, such as arthritis, spinal injury, nerve conduction deficiencies, cancer, sprains, strains, wounds, and surgical pain, but also such stress-related conditions as anxiety, insomnia, cognitive dysfunction states, noise phobia, and depression. Prescription MET and CES devices are long lasting, cumulative, safe, effective, easy to use, portable, and nonaddictive, and have no known tolerance concerns. Adverse effects are minor and self-limiting, primarily consisting of skin irritation.

Treatments can be applied in clinic by the technical team, and devices can be prescribed for use at home with a short in-clinic training session. Initially, the best results will be achieved when treatments are applied twice a day, but in-clinic treatments administered 2 to 3 times per week will also be beneficial. Follow-up patient assessment includes clinical observation, range of motion, change in posture, use of extremities, calmness, improved sleep, appetite, attitude, and behavior.

As an aid to endogenous bioelectric currents, electroceuticals can accomplish miraculous things. They may in fact work better in the absence of any interference from factors based on our previous, limited, chemical-dominant view of physiology. Today and in the future, disorders of both the body and mind might be better treated using a range of frequencies that have the potential to treat a variety of pathologies effectively without the risk of harmful adverse effects.

Dr. Frick is a leading authority in the application of microcurrent therapy for animals. Her focus on physiotherapy has spanned over 20 years and her research has been published in the Journal of Equine Veterinary Science, Innovative Veterinary Care Journal, and the Journal of the American Holistic Veterinary Medical Association. 

Frick A, McCauley D. Microcurrent electrical therapy. 

Kirsch DL, Marksberry JA. The evolution of cranial electrotherapy stimulation for anxiety, insomnia, depression, and pain and its potential for other indications. In: Rosch P, ed.  

Bioelectromagnetic and Subtle Energy Medicine

. 2nd ed. Boca Raton, FL: CRC Press; 2015: 189-211. 

Tan G, Rintala D, Jensen M, et al. Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase. 

Taylor AG, Anderson JG, Riedel SL, et al. Cranial electrical stimulation improves symptoms and functional status in individuals with fibromyalgia. 

Winick, Reid L. Cranial electrotherapy stimulation (CES): a safe and effective low cost means of anxiety control in a dental practice. 

Although still in its infancy in veterinary medicine, targeting neural circuits with electricity offers huge potential to provide focused, personalized treatment for a variety of ailments.

July 2018

The Information Revolution: We Can All Benefit

Antibiotic Selection in Pyoderma

Code Green: The Risk From Toxic Household Plants

Developing a Vaccine for Lyme Disease

Electroceuticals: The Wave of the Future Is Now

Canine Urinary Incontinence

Noteworthy FDA Approvals