The Lyme-positive dog: Is it necessary to treat a blue dot?

Photo: Bigstock/Ivan Popovych Lyme disease represents a real threat to our veterinary patients and a One Health concern. It is caused by the spirochete Borrelia burgdorferi and transmitted by the Ixodes species (see Figure 1) of hard ticks. In small animal medicine, we most commonly associate clinical disease with our canine friends. Figure 1. Tick life series illustration from the Centers for Disease Control and Prevention. According to the Companion Animal Parasite Council (CAPC), 2024 Lyme seroprevalence data showed one in 20 pets, or 4.32 percent of patients throughout the U.S., tested positive for Lyme with 12,289,296 total tested (Figure 2). (Keep in mind this is only from commercial labs and reported test results and does not include those in-house tests not reported.) However, Pennsylvania has the highest Lyme prevalence, and the data suggests one in 10, or 9.55 percent—at minimum—of the population reported was positive. Given the numerous in-clinic tests and, thus, tests not counted, I guarantee this is a gross underestimate of the seroprevalence. In 2019, CAPC suggested the data represented 30 percent of actual U.S. cases. This percentage has likely increased given the vector’s spreading home range and the spread of clinical cases across the U.S. CAPC suspects true canine seropositivity well exceeds 1 million. So, do we treat all 9.55 percent that test positive, even if they are asymptomatic and testing confirms exposure but cannot tell us which ones will, if ever, develop clinical signs? That is a lot of antibiotics to doll out for often asymptomatic patients. Sadly, because the disease is not reportable in animals, we have a much less clear picture of the true incidence of clinical cases than in human medicine, which also has significant underreporting concerns. Figure 2: Companion Animal Parasite Council (CAPC)'s 2024 Lyme seroprevalence data. This is Pennsylvania as an example; all U.S. states are available: https://capcvet.org/maps/#/2024/all-year/lyme-disease/dog/united-states/pennsylvania Antimicrobial stewardship As a veterinarian and public health expert, I am accountable to individual patients, my profession, and the global health community to implement evidence-based medicine and ensure my veterinary practices protect animal, public, and environmental health. I believe it is essential to utilize antimicrobials and other medications conservatively, safely, and appropriately. Therefore, the concern for developing antimicrobial resistance (AMR) and protecting against it is essential to me.1 Drug-resistant infections, encompassing viral and bacterial strains, are projected to surpass 10 million individuals globally by 2050.1–3 To ensure effective antimicrobial stewardship, it is essential to have a comprehensive understanding of drug classes and their appropriate indications for use. I recommend all veterinarians consistently evaluate the guidelines and recommendations provided by organizations such as the International Society for Companion Animal Infectious Diseases (ISCAID) and the World Small Animal Veterinary Association (WSAVA) among others, concerning specific conditions and antibiotic selections. Furthermore, it is essential for veterinarians to comprehend the disease conditions we are addressing and to stay informed about the latest therapies and the evidence that supports or refutes treatment options. In general, veterinarians possess a deeper understanding of the implications of One Health than many others. We comprehensively understand zoonotic diseases, herd health, herd immunity, and various related topics. However, although we are aware of it, there are instances where we may not fully grasp the broader context. Implementing effective antimicrobial stewardship practices allows us to reduce the risk of antimicrobial resistance emerging in our patients and the wider population.1,4 Annual tickborne testing: yay or nay? Working in Pennsylvania, screening asymptomatic dogs for tickborne diseases is itself debatable. Routine annual heartworm screening is recommended by the American Heartworm Society (AHS) for dogs over seven months via microfilaria and antigen testing.5 However, should we routinely screen healthy dogs for tickborne diseases? Positive results (in asymptomatic pets) have benefits: they show exposure, may assist in reinforcing our recommendations and need for preventatives, and permit a discussion of pet parent risks of infectious disease and their exposure rate. However, are we going to treat every asymptomatic dog with doxycycline? Would treating every positive blue dot be practicing proper antimicrobial stewardship? Doxycycline, the first line therapy for Lyme disease, is classified as a highly important antimicrobial by the World Health Organization (WHO),6 and represents an antibiotic that treats numerous conditions in humans and animals alike. Tetracyclines (of which doxy is our mainstay of use) are regarded as highly important, meaning that they meet one of two key criteria: “Sole, or one of the limited available therapies, to treat serious bacterial infections in people.”6 “Used to treat infections caused by bacteria (1) possibly transmitted from non-human sources, or (2) with resistance genes from non-human sources.”6 Thus, this drug should be used cautiously, and we must ensure proper antimicrobial stewardship when considering its use. We want to ensure organisms do not develop resistance and all parties can utilize the drug when necessary. However, if we dish it out like candy, are we setting ourselves up for resistance? Are we utilizing a human antibiotic that should be preserved unless clinically necessary? Lyme disease in people According to the Centers for Disease Control and Prevention (CDC), Lyme disease is the number one tickborne disease in people. Because Lyme is reportable in people, its prevalence is much more readily appreciated than in animals.7–9 Lyme cases reported through the routine national surveillance pathways from state health departments and Washington D.C. as of 2022 showed greater than 63,000 annual cases of Lyme. Estimates using various other means of identifying cases and via projections suggest more than 475,000 people annually may contract and receive treatment for Lyme (clinical and exposed cases).8 Clinical signs in people usually start with the almost pathognomonic bullseye rash (erythema migrans) (EM). (See Figure 3.) However, the rash may be less well-defined, and patients may also have vague flu-like symptoms, leading to misdiagnosis or delayed diagnosis. Left untreated, it can progress to musculoskeletal (e.g., myalgias) and neurologic symptoms, e.g., headache, stiff neck, facial palsy, dizziness, or nerve pain. Additionally, meningitis, paresthesia, or shooting pains in the hands and feet may develop. Finally, cardiac complications can arise, ranging from arrhythmias to endocarditis.10 Figure 3. Erythematous bull's-eye rash depicting Lyme Disease. ID # 9874. Photo by James Gathany for the Centers for Disease Control and Prevention. Humans are most commonly treated with amoxicillin, doxycycline, or cefuroxime axetil, with azithromycin being a final choice in those allergic to the primary options. The duration of therapy varies with the patient population and factors such as age, severity of clinical signs, pregnancy, and allergies.11 The CDC does not routinely recommend a dose of doxycycline after a single tick bite in low-risk areas for people with recent tick bite exposure. However, healthcare providers may differ on this recommendation in highly endemic areas, e.g., Pennsylvania.11 The 2021 Practice Guidelines from the American Family Physician based on the American Academy of Neurology (AAN), American College of Rheumatology (ACR), and the Infectious Diseases Society of America (IDSA) suggest if a tick was attached for 36 hours or more in a high-risk area, a single dose of doxycycline (200 mg for adults and 4.4. mg/kg up to 200 mg for children) for Lyme disease prophylaxis is warranted. If evidence of the EM manifests, the treatment duration is seven to 14 days, depending on the selected therapy.12–14 The literature does not readily discuss issues addressing the One Health concerns of using a single dose of doxycycline, but the disquiet about AMR development is real.15 This should be addressed moving forward. However, because of this recommendation in endemic areas, for therapy for exposure when ticks are removed and treatment occurs within 72 hours of that attachment/removal,12–14 we must recognize in veterinary medicine the need to minimize the use of this medication to preserve efficacy for human use. While obviously not our preference, as our main priorities lie with our patients, it is our duty to protect not only our patients but preserve the efficacy of medications for human and animal use. We must view this with a One Health lens, even if our physician counterparts may not. Lyme disease in animals Wouldn’t it be nice if our four-legged friends were to present with an EM and make our jobs easier? Instead, Lyme disease signs in dogs, are often vague, e.g., leg-shifting lameness, exercise intolerance, ADR, stiffness, myalgia, low-grade fever, hypo- to anorexia, joint swelling or limb edema, and in more advanced cases, nephropathy with expected signs, and rarely endocarditis.1,16 Though the prevalence of this condition varies from state to state, veterinarians often forget to ask owners about travel history outside of their local region, as well as about dog parks, trail walking/hiking, and property characteristics. These include: Is their property about a large wooded area? Along with the standard, is your dog on any flea/tick preventative, and what product is it? If it is one of the newer oral preventatives, tickborne diseases may still be possible but are less likely than when using some of the older, less-effective, possibly resistant preventatives or sprays. Some owners also feel their dogs are not exposed because they are “really house dogs.” It always amuses me when I ask, “Does your dog go outside to go to the bathroom?” They usually answer, “Yes.” Thus, are they really only indoor dogs? Tick prevention is a key One Health discussion we recognize as necessary with pet owners. Pets act as sentinels. If they come inside with ticks, the pet parent and family members are exposed when they go outside, too. Thus, the very presence of the ticks permits an opening to discuss the zoonotic nature of tickborne diseases, preventatives, signs to watch for in both animals and people, and a plug that if humans in the home have received tick bites, they should seek care/mention to their physicians. Treating Lyme non-clinical positive dogs: yay or nay? Lyme disease exemplifies veterinarians’ role in public health and the One Health initiative. One Health tackles global health challenges through the lenses of environmental, human, and animal factors. It offers a perspective through diverse expertise that allows us to comprehend the overarching context. As small animal veterinarians, we generally tend to individual animals, although it is essential to maintain awareness of the broader context. Our treatment decisions can adversely affect organisms, resulting in selection pressures and AMR.15 Contributing to this resistance may transfer to humans and hinder our capacity to treat/cure illnesses, such as Lyme disease. Given Lyme disease’s rising incidence and expanding geographical exposure, the last factor we want is the addition of AMR. Thus, should we administer treatment for a blue dot or not? While the experts do not fully agree on this specific issue, we must first discuss Lyme disease, including our observations and any inquiries we may pose to determine whether treatment is warranted. When discussing Lyme disease in our canine patients, it isn’t simply a matter of whether they have clinical signs. We need to acknowledge the human factors, the notion of animals as sentinels, the risk of AMR, and the need to practice antimicrobial stewardship while balancing the clinical evidence and guidelines available. We do this by understanding the One Health ramifications of the presence of the spirochete of concern, Borrelia burgdorferi, and ensuring we have all the facts at hand before establishing a protocol. It isn’t a one size fits all. Variables including disease prevalence, patient risk, owner perceptions, and knowledge, among other factors, play a role in this far-from-black-and-white topic. In a 2018 study, Liu et al. evaluated canine Lyme seroprevalence and compared it to human data. They determined it to be a good surrogate for human incidence and risks in those areas. Their findings suggested the “mean incidence in humans increases with canine seroprevalence until the seroprevalence in dogs reaches approximately 30 percent.”17 Their findings help to emphasize the use of canines as sentinels for human disease risk in key geographical regions of concern.17 This suggests that screening healthy animals may have positive One Health implications. However, not all those animals need to be treated, as less than 10 percent likely will manifest clinical signs. Clinical symptoms may emerge in about five to 10 percent of all positive dogs. On average, it takes two to five months or longer for signs to manifest.18 So, do we treat the 90 percent that won’t develop signs? Antibiotic use risks include the development of AMR and individual patient risks, including side effects, negative impacts on the GI microbiome, and overall health. Administration can be challenging for some owners, and the duration of treatment is still not fully elucidated. Thus, before reaching for doxycycline, just because you receive a positive Lyme test on your in-house or send-out panel, consider the One Health ramifications and individual animal health and pet-parent concerns. Given AMR is now considered one of the top 10 global threats to public health,19,20 what are possible One Health ramifications of unchecked doxycycline use? Increased global deaths due to AMR. Inability to treat tickborne diseases. (The use in human medicine includes a single dose of 200 mg for exposure in at-risk individuals with EM.)1,13,14,21 Ever increasing risk of resistant sexually transmitted infection (STIs). (Use in humans in a subset of the population for certain STIs, including highly resistant gonorrhea strains, may be given a single doxycycline dose after possible exposure.)22,23 We already see resistance in human medicine of various organisms to doxycycline. Could unchecked use increase the risk of AMR to this very important antimicrobial? What do we do with an asymptomatic positive dog? Ok, you have a positive dog that is asymptomatic. Do you: Watch and wait? Conduct additional diagnostics? Vaccinate? Provide client education for prevention of future exposure and about what a positive test means? Treat with antibiotics? All of the above or some combination of the above? What do the experts say? Let’s take a case example and decide what we would do before discussing what the experts recommend. Keep in mind the geographical location, exposure risk, the severity of clinical disease in the affected animal, and other factors. An owner has three large breeds dogs with free access to numerous acres in Eastern Pennsylvania (a highly endemic area). They were obtained from the South and, thus, have the potential for exposure to numerous additional vectorborne diseases. The pet parents were treated for Lyme on two separate occasions. Despite this, they failed to consistently use preventatives (or effective ones) on their dogs. One of the dogs, a 3.5-year-old MN mixed breed dog presented to me on emergency with a three to four-week history of slow weight loss and declining appetite. The dog stopped eating dog food the past week but still ate filet mignon. He was finally presented because of epistaxis. Negative for heartworm, he was positive for Ehrlichia, Anaplasma, and Lyme. Chest and abdominal radiographs were confirmed normal by a board-certified radiologist. She was thrombocytopenic at 32,000, mildly anemic (34 percent), moderately azotemic, and had low albumin with proteinuria. His urine culture was negative. Obviously, we treat this dog for his tickborne diseases, as they are likely the cause of clinical signs. The owners understandably ask if they should get the other dogs tested. Since their exposure is high and humans and animals have shown seroprevalence and clinical manifestations of tickborne illness, testing them will likely yield positive results. Would you treat? My recommendation to these owners was to get them tested. If positive, I would treat them because of the endemic location, human cases, risk of re-exposure, and severity of clinical signs in the affected individual (granted they waited so long, the sequelae may have been preventable if treated early). However, what if you were to diagnose a patient positive in Idaho, where seroprevalence is much lower? Would you treat a positive dog in a family where pets and pet parents have had illness? Would you treat a pet in a family without this history, with no travel history, with no clinical signs? Recommendations currently favor not treating a positive dog in a low-risk area, given the low rate of clinical signs developing and the risks of antimicrobial use. In the few commentaries made on the consensus statement, now relatively old from 2018, on Lyme disease by the American College of Veterinary Internal Medicine (ACVIM), there are points for and against treatment in positive asymptomatic dogs, including:24 Signs may be subclinical, but the disease may still be present and not cleared by the immune system. However, what are you treating if the disease is subclinical, and how would response be gauged? Because of the risk (albeit low) of Lyme nephritis, we should treat it. However, no evidence to date proves that treating asymptomatic dogs will prevent nephritis or that not treating them will lead to it. Further, it is a rare complication, and evidence does not support treating cases of a rare disease in large groups of animals. Treatment is not going to hurt. We know the use of antibiotics can cause harm, including side effects and drastic changes to the gut microbiome, which can have lasting negative implications. Treating may reduce the risk of the organism hiding in tissue. However, dogs seroconvert long after they have been infected, and it is highly probable the organism has already reached distant or protected sites (g., collagen). Most, if not all, discussions about treating asymptomatic dogs lack the One Health component, concerns about AMR, and the preservation of a drug needed to treat clinical animals and humans for numerous conditions. Generally speaking, for most cases of asymptomatic Lyme disease, experts agree prophylactic therapy is not indicated.24–26 Lyme disease isn’t going anywhere Sadly, Lyme disease is here to stay, and its ability to gain momentum and increase global reach only provides more concern for the threat it poses to animals and people. Maintaining our ability to treat clinical patients (human and animal alike) is paramount. PreventingAMR remains a key focus of One Health, and the AVMA recognizes we, as veterinarians, need to act as “stewards in preserving the effectiveness of antimicrobials.”27 Thus, before reaching for doxycycline just because you find a dog positive for Lyme, take a step back and consider the many variables. Do you need to treat that patient? Could you be causing more harm than good? Are there new guidelines, reports, or studies further supporting only treating clinical patients or those at very high risk of developing disease? Erica Tramuta-Drobnis, VMD, MPH, CPH, is the CEO and founder of ELTD One Health Consulting, LLC (https://eltdonehealth.com/). Dr. Tramuta-Drobnis works as a public health professional, emergency veterinarian, freelance writer, consultant, and researcher. She is passionate about One Health issues and believes pet health, food safety, agricultural health, and more can address the interconnection of human, animal, and environmental health. References Tramuta-Drobnis EL. Treating a Blue Dot or Not: doxycycline use and antimicrobial stewardship, Lyme disease as an example. Keynote Discussion Panel & Lecture presented at: 3 ivers Symposium, PVMA; November 13, 2022; Mars, PA. O’Neill J. Tackling Drug-Resistant Infections Globally: Final Report and Recommendations: The Review on Antimicrobial Resistance. Published online 2016. Accessed November 6, 2022. https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf British Small Animal Veterinary Association (BSAVA). Guidelines for responsible antibiotic use. British Small Animal Veterinary Association (BSAVA). Accessed December 2, 2024. https://www.bsavalibrary.com/content/formulary/backmatter/canine-and-felineguidelinesforresponsibleantibioticuse American Veterinary Medical Association (AVMA). Antimicrobial stewardship definition and core principles. American Veterinary Medical Association. 2021. Accessed October 21, 2021. https://www.avma.org/resources-tools/avma-policies/antimicrobial-stewardship-definition-and-core-principles American Heartworm Society. Heartworm Guidelines. American Heartworm Society. 2024. Accessed January 6, 2025. https://www.heartwormsociety.org/veterinary-resources/american-heartworm-society-guidelines World Health Organization. Critically Important Antimicrobials for Human Medicine 6th Revision 2018. 6th ed. World Health Organization. Regional Office for South-East Asia; 2022. Accessed November 4, 2022. https://apps.who.int/iris/bitstream/handle/10665/312266/9789241515528-eng.pdf Office of the Assistant Secretary for Health, Department of Health and Human Services (DHHS). Tick-Borne Disease Working Group. U.S. Department of Health and Human Services. July 14, 2017. Accessed January 7, 2025. https://www.hhs.gov/ash/advisory-committees/tickbornedisease/index.html Centers for Disease Control & Prevention (CDC). Lyme Disease Surveillance and Data. Lyme Disease. May 20, 2024. Accessed January 7, 2025. https://www.cdc.gov/lyme/data-research/facts-stats/index.html Companion Animal Parasite Council (CAPC). Lyme Disease - CAPC’s Guidelines. Companion Animal Parasite Council (CAPC). May 15, 2019. Accessed October 20, 2022. https://capcvet.org/guidelines/lyme-disease/ Centers for Disease Control & Prevention (CDC). Signs and Symptoms of Untreated Lyme Disease. Lyme Disease. August 20, 2024. Accessed January 7, 2025. https://www.cdc.gov/lyme/signs-symptoms/index.html Centers for Disease Control & Prevention (CDC). Treatment and Intervention for Lyme Disease. Lyme Disease. August 16, 2024. Accessed January 7, 2025. https://www.cdc.gov/lyme/treatment/index.html Williams AL, Bevan J, Arnold MJ. Lyme Disease: Updated Recommendations from the IDSA, AAN, and ACR. Am Fam Physician. 2021;104(6):652-654. Sutton D, Spry C. One Dose of Doxycycline for the Prevention of Lyme Disease: A Review of Clinical Effectiveness and Guidelines. Canadian Agency for Drugs and Technologies in Health; 2019. Accessed January 7, 2025. http://www.ncbi.nlm.nih.gov/books/NBK545493/ Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with Single-Dose Doxycycline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite. N Engl J Med. 2001;345(2):79-84. doi:10.1056/NEJM200107123450201 Chavarría-Bencomo IV, Nevárez-Moorillón GV, Espino-Solís GP, Adame-Gallegos JR. Antibiotic resistance in tick-borne bacteria: A One Health approach perspective. J Infect Public Health. 2023;16:153-162. doi:10.1016/j.jiph.2023.10.027 Merck Veterinary Manual. Lyme Disease (Lyme Borreliosis) in Dogs - Dog Owners. Merck Veterinary Manual. October 2022. Accessed November 3, 2022. https://www.merckvetmanual.com/dog-owners/disorders-affecting-multiple-body-systems-of-dogs/lyme-disease-lyme-borreliosis-in-dogs Liu Y, Nordone SK, Yabsley MJ, Lund RB, McMahan CS, Gettings JR. Quantifying the relationship between human Lyme disease and Borrelia burgdorferi exposure in domestic dogs. Geospatial Health. 2019;14(1). doi:10.4081/gh.2019.750 Animal Health Diagnostic Center, Cornell University. Lyme Disease. Cornell University College of Veterinary Medicine. February 5, 2019. Accessed November 3, 2022. https://www.vet.cornell.edu/animal-health-diagnostic-center/laboratories/serology-immunology/lyme-disease The World Health Organization (WHO). Antimicrobial resistance. The World Health Organization (WHO). November 21, 2023. Accessed January 7, 2025. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance National Center for Emerging and Zoonotic Infectious Diseases. Global Health Priorities 2023-2026. Published online 2024. Accessed January 7, 2025. https://www.cdc.gov/ncezid/media/pdfs/2024/10/NCEZID_GlobalHealthPriorities_April-2024_Final.pdf Harms MG, Hofhuis A, Sprong H, et al. A single dose of doxycycline after an ixodes ricinus tick bite to prevent Lyme borreliosis: An open-label randomized controlled trial. J Infect. 2021;82(1):98-104. doi:10.1016/j.jinf.2020.06.032 Tramuta-Drobnis EL. Reducing STI Risk With Doxycycline: Is It a Good Idea? HealthNews. November 1, 2022. Accessed November 3, 2022. https://healthnews.com/health-conditions/immunity-infections/reducing-sti-risk-with-doxycycline-is-it-a-good-idea/ University of California, San Francisco. Evaluation of Doxycycline Post-Exposure Prophylaxis to Reduce Sexually Transmitted Infections in PrEP Users and HIV-Infected Men Who Have Sex With Men. clinicaltrials.gov; 2022. Accessed October 25, 2022. https://clinicaltrials.gov/ct2/show/NCT03980223 Littman MP, Gerber B, Goldstein RE, Labato MA, Lappin MR, Moore GE. ACVIM consensus update on Lyme borreliosis in dogs and cats. J Vet Intern Med. 2018;32(3):887-903. doi:10.1111/jvim.15085 Lee JA. Lyme Disease: Treatment of Acute and Chronic Manifestations. Published online 2014. Accessed January 7, 2025. https://vetgirlontherun.com/wp-content/uploads/2014/05/LymeJLEE52014.pdf Evason M, Stull J. Lyme Disease Fact Sheet: Lyme Disease (Borreliosis) Information for Dog Owners. Published online September 2016. Accessed January 7, 2025. https://vet.osu.edu/sites/default/files/documents/Lyme%20Disease%20Fact%20Sheet%2020200123.pdf American Veterinary Medical Association (AVMA). Antimicrobial use and antimicrobial resistance. American Veterinary Medical Association. Accessed October 21, 2021. https://www.avma.org/resources-tools/one-health/antimicrobial-use-and-antimicrobial-resistance

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The Lyme-positive dog: Is it necessary to treat a blue dot?

Antimicrobial stewardship and the treatment of asymptomatic individuals that test positive for tick-borne diseases

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