Infectious Disease Updates

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1 Infectious Disease Updates Richard B. Ford, DVM, MS Emeritus Professor of Medicine Diplomate ACVIM and ACVPM (Hon) North Carolina State University Raleigh, North Carolina A. Canine Lyme Disease Update B. Feline Viral Upper Respiratory Disease-Unique Management Strategy C. Rabies and Rabies Antibody Titers A. Canine Lyme Disease in the Northwestern US (Updated: January 2017) 1. Prevalence of Lyme Disease In August 2013, preliminary results from 3 complementary studies conducted through the Centers for Disease Control and Prevention (CDC) suggest that a mean of 300,000 people (as high as 444,000 in one year) in the U.S. are diagnosed with Lyme disease each year, a significant increase from 2012 estimates of 30,000 reported cases. Of reported cases, 96% occurred in 13 states, particularly the northeastern U.S. and Upper Midwest; this distribution did not change from 2012 to What s more, cases of human Lyme disease are not only occurring with increasing frequency in known endemic States, but the number of confirmed cases is expanding into States, and regions within States, that have not previously documented the infection. In veterinary medicine, there can be little argument over the fact that a dog s risk of exposure to ticks, and to tick-borne diseases, dramatically exceeds that in people. Because tick-borne diseases are not reportable in dogs in the US, precise estimates of prevalence are not available. Published estimates suggest that up to 85% of dogs living in Lyme endemic States are antibody positive (and likely to be infected) for Lyme disease. Today, it must be assumed that many dogs are infected with one, or more, tick-borne diseases, yet remain undetected. Canine Lyme disease risk is certainly present in Oregon, especially within coastal counties, but there is nothing to suggest geographic expansion to the extent currently recognized in the Eastern US. The Companion Animal Parasite Council estimates that <1% of dogs tested in Oregon have a positive test result. Lyme Disease: Ehrlichia canis: Anaplasma: 1 positive in 118 dogs tested 1 positive in 105 dogs tested 1 positive in 63 dogs tested 2. Significance of a Positive Test C6 vs Quant C6 vs OspC gets confusing. The C6 antibody test is a proprietary test developed and sold exclusively through IDEXX. It is available as a qualitative point-of-care test platform (SNAP 4Dx and 4Dx Plus) and a laboratory (send-out) quantitative test (QUANT C6). I think it s important to understand that the C6- based technology has been used for well over 10 years and, largely, has been used in epidemiologic studies of 1

2 canine Lyme disease in the US and Canada. ALSO, the C6 antibody test for Lyme Disease has recently been licensed for use in humans and is recognized as a significant improvement over the conventional IFA + Western Blot testing criteria to establish a diagnosis of human Lyme disease. In dogs with little exception a Positive SNAP Test for C6 antibody denotes a dog that is currently infected ( vs. previously exposed). Furthermore, Lyme disease vaccination does NOT interfere with the C6 antibody test. Other multiplex test platforms are available that detect antibody to various surface proteins of B. burgdorferi (eg, OspA antibody and OspC antibody). Dogs that have been previously vaccinated may have a False positive test result when using this test methodology. 3. Consequences of infection While the majority of humans that are infected with B. burgdorferi can be expected to develop clinical illness, most dogs develop subclinical infection; a small percentage (5% to 20% estimated) actually manifest clinical signs on presentation. For that reason, many veterinarians elect NOT to recommend vaccination, despite documented risk. Considering the fact that antibiotic therapy does NOT clear spirochetes from infected dogs, what are the implications for the patient that is re-infected? Is there a yet-to-be defined threshold of antigen mass above which clinical lameness appears? AND is there an infectious tipping point that, once reached, ultimately leads to clinical illness? 4. Lyme disease is a disease to prevent NOT a disease to treat. A consensus on diagnostic criteria defining a diagnosis of Canine Lyme Disease has not (surprisingly) been established in practice, it is reasonable to base clinical diagnosis of Lyme disease on the following: a) recognition of acute-onset mono- or poly-articular lameness, sometimes myalgia, b) a positive C6-Ab [SNAP] test, and c) rapid clinical improvement (within 3 to 5 days) following administration of oral doxycycline. Clinically speaking, Canine Lyme Disease has been defined by (single) point-in-time studies; we do not know the implications of repeated exposure to infected ticks over time in the individual dog. 5. Doxycycline is neither curative nor prophylactic. Antibiotic therapy is indicated to treat dogs that manifest clinical signs associated with Lyme disease. Treatment does quickly reduce clinical signs of disease. Treatment does NOT, however, clear the infection nor is prescribing doxycycline to prevent consequences of exposure indicated. Vaccination, on the other hand, is indicated to minimize the risk of infection and clinical illness among the at-risk population. B. Feline Viral Upper Respiratory Disease: Unique Management Strategy (Updated January 2017) Cats vaccinated against feline herpesvirus-1 (FHV-1) and feline calicivirus (FCV) do not enjoy complete protection. The immunity derived following vaccination (as well as infection) is deemed non-sterile. In other

3 words, vaccinated cats do derive protection from developing severe clinical disease however, they are not protected against infection if exposed. Even if immunized, cats can (likely) become infected and develop a chronic carrier state if exposed. For this reason, chronic carrier cats are highly prevalent throughout the US. At issue, is the fact that the chronic carrier is also shedding virulent virus either constantly (FCV) or intermittently (FHV-1). By serving as virus reservoirs, the carrier cat represents a significant threat to susceptible cats especially kittens. ALSO chronic carrier cats, as adults, often manifest persistent (albeit mild) upper respiratory signs characterized by: paroxysmal sneezing episode, mucopurulent nasal and/or ocular discharge. Empiric antibiotic treatment typically resolves the clinical signs, but only during the time the treatment is being administered. Within 3 days following discontinuation of the antibiotic, clinical signs return. New information, based on observational experience and laboratory studies, has shown an opportunity to manage the chronic sneezing adult cat using topical vaccine as therapy. INTRANASAL (IN) VACCINATION: Modified live, bi-valent (FHV-1/FCV) vaccines are licensed for administration to cats (Zoetis 0.5 ml volume and Heska 0.2mL volume). While these vaccines do protect as well as the parenterally administered (SQ) vaccines, they have been shown to protect from challenge within 72 hours v. 6 to 7 days for SQ vaccines. The quality of local immunity conferred by topical IN vaccination, however, may be moot as any local (secretory) antibody induced does not appear to prevent local infection nor establishment of a carrier state. SOMETHING TO TRY! Intranasal VACCINATION FOR THE TREATMENT OF CHRONIC URD FOR YOUR CONSIDERATION: Topical FHV-1 and FCV vaccines, although having limited global distribution, have been shown to lessen, and in some cases eliminate, clinical signs of rhinitis in chronic carrier cats. Prior to administering vaccine, 2-3 days of pretreatment with an antimicrobial may be necessary to reduce the amount of nasal discharge. A single dose of intranasal vaccine is administered in accordance with manufacturers recommendations. A response can be expected within 10 to 14 days as the volume of discharge and associated sneezing diminishes significantly. If there is no initial response, some cats may respond to a second dose administered 30 days following the first dose. We have routinely re-isolated virus from cats despite the diminution of clinical signs. Topical administration of vaccine to chronic carrier cats is NOT expected to eliminate the chronic carrier state. Studies have shown that topical vaccination induces a non-specific (cytokine-mediated) immune response that, in many cats, will significantly reduce (or eliminate) signs of chronic sneezing, nasal/ocular discharge. Annual re-vaccinated is recommended in cats that respond to treatment. We have encountered some cats that re-develop clinical signs within a year following intranasal vaccination in these cases, vaccination every 6 months has been effective and affords the client an opportunity to effectively (in most cases) manage a significant, chronic problem at reasonable cost. TOPICAL UPPER RESPIRATORY CURRENTLY AVAILABLE IN THE US (FHV-1 and FCV and Panleukopenia) Felocell FVR C (Zoetis Animal Health): modified live, herpesvirus-1 and calicivirus. (0.5 ml) Feline Ultranasal FVRC Vaccine-Bivalent (Heska-Elanco): modified live, feline herpesvirus-1 and calicivirus. (0.2 ml) (This preparation is recommended over the Panleukopenia-containing preparation-below) Feline Ultranasal FVRCP Vaccine-Trivalent (Heska-Elanco): modified live, feline panleukopenia in addition to herpesvirus-1 and calicivirus. (0.2 ml)

4 C. Rabies and Rabies Antibody Titers: Reasons for FAILURE (Updated January 2017) An on-going State-by-State study of rabies laws/regulations has revealed considerable confusion, misunderstanding among veterinarians regarding the use of rabies antibody titers in practice. With the growing popularity of antibody testing in lieu of vaccination, the question arises over the appropriate use, and interpretation, of a rabies titer in dogs & cats. Only a limited number of laboratories in the US are licensed to perform rabies virus antibody titers. 1. Kansas State University s RABIES LABORATORY, Manhattan, KS, and 2. Atlanta Health Associates, Inc., Cumming, Georgia It is important for all veterinarians to understand that a rabies titer is NOT a legal index of immunity in lieu of re-vaccination. In other words, a titer does not (legally speaking) correspond with protective immunity. Dogs/Cats exported to rabies-free regions/countries may be required to provide rabies antibody test results (FAVN) before the pet is permitted to enter the country. The FAVN antibody titer is ONLY an indication of prior vaccination it does not define immunity. Throughout the US today, a rabies titer can NOT be used as a get out of jail FREE card to save the owner the expense of re-vaccinating their pet or, in the case of overdue pet becoming exposed to a rabid animal (some States are reviewing this now and may offer limited use of titers [Prospective Serologic Monitoring] as means of shortening the quarantine period.) But, there is NEW INFORMATION on rabies titers that will be useful for veterinarians who are examining patients prior to exportation, especially young dogs/cats. Studies recently conducted at the KSU RABIES LABORATORY have provided new insight on serologic responses to vaccination. Some facts to consider: Based on a study involving ~8,300 dogs vaccinated with a killed (inactivated) rabies vaccine Size of the dog: Large/Giant breeds have a higher test FAILURE rate than Small breed dogs probably associated with the standard 1.0 ml dose (amount of Ag per pound of dog is higher in smaller vs. larger breeds). Breed Effect: data evaluated did not show a difference in PASS/FAIL rates among different breeds although, they were able to show a difference in PUREBRED DOGS (higher FAIL rates) compared to MIXED Breed DOGS. IMPORTANT: Considering that most (canine) rabies free countries require proof of rabies vaccination prior to traveling/entering the country, the following represents new and relevant information on exportation and testing of young dogs: - Dogs < 1 year of age, after receiving their initial vaccine dose (between 12 and 16 weeks of age) are expected to have a high risk for test FAILURE: REASONS: - it s their FIRST DOSE (no anamnestic response) - it s a KILLED vaccine (2 doses induce a higher, sustained serologic response)

5 - young dogs have a less mature response to vaccine THE BIGGEST REASON FOR TEST FAILURE IN YOUNG DOGS FOLLOWING THEIR INITIAL VACCINE DOSE IS.Timing of the blood draw following vaccine administration. There is a HIGH RISK OF FAILURE when blood is drawn PIROR to 8 days and AFTER 77 days. TARGET time to draw blood following administration of the initial dose of rabies vaccine: 16 to 35 days best chance for a PASS. (think 2 to 4 weeks post-initial vaccination) Here s another point to consider: if a pet fails the TITER TEST, there are serious consequences for the owner: - Expense associated with Re-vaccination & Re-Testing requirement - Travel Delay: Waiting for new Test Results (several weeks) - Denied Entry - Expense & Safety: In-Country quarantine - Euthanasia REF: Master s Thesis (MPH); Dr. Anna Pees (KSU, Rabies Laboratory), 2016.

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