Chapter 271 Borreliosis Meryl P. Littman, Philadelphia, Pennsylvania Lyme disease (Lyme borreliosis) in dogs is caused by a unicellular microaerophilic gram-negative motile spirochete, Borrelia burgdorferi, generally transmitted via Ixodes tick bites. In the United States, 95% of human Lyme disease is reported in just 12 endemic states: New Jersey, Pennsylvania, Wisconsin, New York, Massachusetts, Connecticut, Minnesota, Maryland, Virginia, New Hampshire, Delaware, and Maine. After 2 to 4 days of tick attachment, down-regulation of the spirochete’s expression of OspA (the organism’s outer surface protein, which attaches it to the tick’s midgut) allows its passage into the new host. Migrating interstitially, this extracellular organism lives near collagen and fibroblasts, usually causing little if any inflammation in most hosts. Antigenic variation allows new antigens to be expressed over time by the spirochete in carriers, thereby evading the host’s immune system. Borrelia spp. of the relapsing fever group may also cause illness in dogs. The most common form of canine Lyme disease is the subclinical (asymptomatic) carrier. In endemic areas, up to 70% to 90% of healthy dogs are seropositive. In field studies, 95% of seropositive dogs had no signs of Lyme disease by history or at 20-month follow-up. Less than 5% of seropositive dogs show signs of Lyme arthritis (lameness ± fever/inappetence), which is self-limiting or quickly responsive to antibiotics. The least common but most serious form is Lyme nephritis, seen mostly in Labrador and golden retrievers. The incidence is unknown but thought to be very low (less than 1% to 2%) because proteinuria is uncommon even among seropositive retrievers. Other human manifestations (e.g., rash or cardiac or neurologic signs) are not well documented in dogs. The experimental model for inducing Lyme disease in dogs (beagles) showed a self-limiting arthritis in puppies; adults became seropositive but remained subclinical. Puppies age 6 to 12 weeks of age exposed to endemic Ixodes ticks showed a 4-day self-limiting illness after a 2- to 5-month incubation, with fever, anorexia, and lameness or joint swelling or lymphadenopathy in the leg closest to where ticks fed. One to six similar self-limiting episodes several weeks apart in the same or different leg may follow because of migration of spirochetes expressing new antigens. Older pups (13 to 26 weeks) showed milder and fewer signs as well as number of days and episodes involved. Cultures and polymerase chain reaction (PCR) testing of skin biopsies from where ticks fed more than 1 year earlier showed that dogs remain subclinical carriers if not treated with antibiotics, and 10% to 15% of treated dogs were still not cleared. None developed Lyme nephritis, so the factors related to onset, progression, treatment, or prevention are unknown. Approximately 35% to 45% of these tick-exposed experimental dogs were coinfected with Anaplasma phagocytophilum, and a few were coinfected with Babesia microti. Lyme nephritis (LN) was described first in seropositive dogs with protein-losing nephropathy (PLN) and a unique combination of renal histopathologic changes, including immune-mediated (usually membranoproliferative) glomerulonephritis (IMGN), diffuse tubular necrosis and regeneration, and lymphoplasmacytic interstitial nephritis. Affected dogs were younger than other dogs with PLN (5.6 ± 2.6 years vs. 7.1 ± 3.6 years), and almost half were Labrador or golden retrievers (Shetland sheepdogs also were overrepresented). Less than 30% of the dogs had a history of lameness. Most clinical findings were due to renal failure with primary glomerular disease (proteinuria, hypoalbuminemia, hypercholesterolemia, ascites or effusions, thromboembolic events, hypertension) and secondary tubular involvement (glycosuria sometimes, eventually isosthenuria). Mild to moderate thrombocytopenia also sometimes was seen, possibly because of consumption related to the hypercoagulability of PLN or because of coinfections. Studies show LN is a sterile nephritis, caused by immune-complex deposition rather than renal invasion of spirochetes. Affected dogs have on average higher levels of circulating B. burgdorferi–specific immune complexes than unaffected seropositive dogs, although the level is not predictive because many unaffected dogs also have high levels. The entity LN probably occurs during the chronic or carrier phase when antibody levels are high, although signs may appear as acute, chronic, mild, moderate, or severe. Some dogs progress rapidly and become oliguric or anuric soon after presenting with vomiting. One study showed positive staining of B. burgdorferi–specific immune complexes in 84% of renal cortical biopsies from suspect cases using immunohistochemistry (IHC) and rabbit antibodies directed against B. burgdorferi antigens p83, p34 (OspB), p31 (OspA), and lower molecular weight B. burgdorferi antigens. Other studies found involvement of B. burgdorferi antigens p39, p41 (flagellin), p22, and p31 (OspA). Whether there are immune-complex deposits not specific to B. burgdorferi in these cases is unknown. Without an inducible experimental model, it is unknown if there are specific Borrelia spp. strains that trigger LN. A genetic predisposition may involve immune dysregulation or a structural or functional glomerulopathy. Most seropositive dogs (even seropositive retrievers) are not affected with LN and are not proteinuric. Renal biopsies were described in severely affected dogs either at necropsy or end-stage disease. Without an experimental model for LN the appearance of the lesion and the clinical progression during earlier stages is unknown. There may be a time when occult proteinuria exists with milder glomerular changes, when intervention may be most helpful, before azotemia and/or tubular damage occurs. Diagnostic Tests Positive serology, supportive clinical signs, consideration of differentials, and response to therapy are clues, but Lyme disease easily is overdiagnosed because B. burgdorferi antibodies are common in healthy dogs, clinical signs are not pathognomonic, and response to therapy may be coincidental. In addition, no test predicts which seropositive dogs will become ill. Serology The organism does not circulate in blood and is found rarely in fluids or tissues, so antigen assays (e.g., culture or PCR assays) are not as useful. Measurement of serum antibodies against B. burgdorferi antigens is the test most widely used to aid in the diagnosis of Lyme disease. The magnitude of any B. burgdorferi antibody titer does not predict illness because many dogs with subclinical infections also have high titers. The most commonly used test for natural exposure is the C6 peptide antibody test (SNAP-4DxPlus, SNAP-3Dx, Lyme C6Quant) against part of the VlsE antigen, which is not expressed in ticks, in vitro, or in any of the B. burgdorferi vaccines. Antibodies against the C6 peptide reach detectable levels 3 to 5 weeks after infection, well before clinical signs are recognized in experimentally infected dogs. A Lyme C6Quant level more than 30 confirms exposure but does not prove the organism is the cause of the clinical signs. Comparisons of pretreatment and 6-month posttreatment C6Quant levels may be helpful (if a dog is treated); a 50% decline or more may indicate decreased antigenic load and possible clearance, even if the qualitative SNAP test is still positive. In addition, the new baseline quantitative value may be useful for future comparison if clinical signs suggestive of Lyme disease recur. It currently is unclear whether the failure to achieve a decreased C6Quant level after treatment can be used as a prognostic indicator. Whole-cell immunofluorescent antibody (IFA) and enzyme-linked immunosorbent assay (ELISA) antibody tests are available but do not differentiate antibodies induced by vaccination from those induced by natural exposure and may cross-react with other spirochetal antigens. Determination of IgM titers independent of IgG titers is not needed because dogs are not ill until after seroconversion to IgG, and IgM peaks can reoccur in carriers because of antigenic variation. Western immunoblot immunoassays may be useful to distinguish vaccinated from exposed dogs if a sole antibody band at p31 is seen after giving a subunit ospA vaccination. Otherwise banding patterns may not differentiate clearly antibodies induced by administration of B. burgdorferi bacterin vaccines from natural exposure antibodies. This is because B. burgdorferi carriers may recognize similar B. burgdorferi antigens found in dogs administered bacterins as the organism shows the host its antigenic repertoire, including antigens usually expressed in ticks, in vitro, or in bacterins. Some laboratories (e.g., New York State Diagnostic Laboratory and Antech Laboratories) are reporting serologic responses against multiple B. burgdorferi antigens; common targets include OspA, OspC, and OspF. OspA antibodies rise and fall after vaccination, but the protective titer level is unknown. OspA is not seen as commonly after natural exposure, although antigenic variation during the chronic phase may allow a nonvaccinated host to have anti-OspA antibodies. OspA expression is down-regulated during tick feeding, but a few OspA molecules may slip in, thus OspA antibodies may be seen transiently soon after infection. In contrast, OspC expression is up-regulated during tick feeding; OspC antibodies generally are detectable 2 to 3 weeks after infection and wane at 3 to 5 months (possibly before signs of illness). Because of reexposure, finding these “early antibodies” are a clue when the dog was last infected but not necessarily when it was first infected. The Nobivac Lyme vaccine may induce OspC antibodies, mimicking natural exposure antibodies. OspF antibodies generally are detectable 6 to 8 weeks after infection and persist; it is unknown whether posttreatment levels of OspF antibodies decline as C6 peptide antibodies do (whole-cell IFA and ELISA antibodies do not decline as much). More information is needed to determine optimal serologic assays.< div class='tao-gold-member'> Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Chapter 13: Complicated Diabetes Mellitus Diagnostic Approach to Hepatobiliary Disease Chapter 54: Oropharyngeal Dysphagia Chapter 49: Esophagitis Stay updated, free articles. Join our Telegram channel Join Tags: Kirks Current Veterinary Therapy XV Jul 18, 2016 | Posted by admin in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Borreliosis Full access? Get Clinical Tree
Chapter 271 Borreliosis Meryl P. Littman, Philadelphia, Pennsylvania Lyme disease (Lyme borreliosis) in dogs is caused by a unicellular microaerophilic gram-negative motile spirochete, Borrelia burgdorferi, generally transmitted via Ixodes tick bites. In the United States, 95% of human Lyme disease is reported in just 12 endemic states: New Jersey, Pennsylvania, Wisconsin, New York, Massachusetts, Connecticut, Minnesota, Maryland, Virginia, New Hampshire, Delaware, and Maine. After 2 to 4 days of tick attachment, down-regulation of the spirochete’s expression of OspA (the organism’s outer surface protein, which attaches it to the tick’s midgut) allows its passage into the new host. Migrating interstitially, this extracellular organism lives near collagen and fibroblasts, usually causing little if any inflammation in most hosts. Antigenic variation allows new antigens to be expressed over time by the spirochete in carriers, thereby evading the host’s immune system. Borrelia spp. of the relapsing fever group may also cause illness in dogs. The most common form of canine Lyme disease is the subclinical (asymptomatic) carrier. In endemic areas, up to 70% to 90% of healthy dogs are seropositive. In field studies, 95% of seropositive dogs had no signs of Lyme disease by history or at 20-month follow-up. Less than 5% of seropositive dogs show signs of Lyme arthritis (lameness ± fever/inappetence), which is self-limiting or quickly responsive to antibiotics. The least common but most serious form is Lyme nephritis, seen mostly in Labrador and golden retrievers. The incidence is unknown but thought to be very low (less than 1% to 2%) because proteinuria is uncommon even among seropositive retrievers. Other human manifestations (e.g., rash or cardiac or neurologic signs) are not well documented in dogs. The experimental model for inducing Lyme disease in dogs (beagles) showed a self-limiting arthritis in puppies; adults became seropositive but remained subclinical. Puppies age 6 to 12 weeks of age exposed to endemic Ixodes ticks showed a 4-day self-limiting illness after a 2- to 5-month incubation, with fever, anorexia, and lameness or joint swelling or lymphadenopathy in the leg closest to where ticks fed. One to six similar self-limiting episodes several weeks apart in the same or different leg may follow because of migration of spirochetes expressing new antigens. Older pups (13 to 26 weeks) showed milder and fewer signs as well as number of days and episodes involved. Cultures and polymerase chain reaction (PCR) testing of skin biopsies from where ticks fed more than 1 year earlier showed that dogs remain subclinical carriers if not treated with antibiotics, and 10% to 15% of treated dogs were still not cleared. None developed Lyme nephritis, so the factors related to onset, progression, treatment, or prevention are unknown. Approximately 35% to 45% of these tick-exposed experimental dogs were coinfected with Anaplasma phagocytophilum, and a few were coinfected with Babesia microti. Lyme nephritis (LN) was described first in seropositive dogs with protein-losing nephropathy (PLN) and a unique combination of renal histopathologic changes, including immune-mediated (usually membranoproliferative) glomerulonephritis (IMGN), diffuse tubular necrosis and regeneration, and lymphoplasmacytic interstitial nephritis. Affected dogs were younger than other dogs with PLN (5.6 ± 2.6 years vs. 7.1 ± 3.6 years), and almost half were Labrador or golden retrievers (Shetland sheepdogs also were overrepresented). Less than 30% of the dogs had a history of lameness. Most clinical findings were due to renal failure with primary glomerular disease (proteinuria, hypoalbuminemia, hypercholesterolemia, ascites or effusions, thromboembolic events, hypertension) and secondary tubular involvement (glycosuria sometimes, eventually isosthenuria). Mild to moderate thrombocytopenia also sometimes was seen, possibly because of consumption related to the hypercoagulability of PLN or because of coinfections. Studies show LN is a sterile nephritis, caused by immune-complex deposition rather than renal invasion of spirochetes. Affected dogs have on average higher levels of circulating B. burgdorferi–specific immune complexes than unaffected seropositive dogs, although the level is not predictive because many unaffected dogs also have high levels. The entity LN probably occurs during the chronic or carrier phase when antibody levels are high, although signs may appear as acute, chronic, mild, moderate, or severe. Some dogs progress rapidly and become oliguric or anuric soon after presenting with vomiting. One study showed positive staining of B. burgdorferi–specific immune complexes in 84% of renal cortical biopsies from suspect cases using immunohistochemistry (IHC) and rabbit antibodies directed against B. burgdorferi antigens p83, p34 (OspB), p31 (OspA), and lower molecular weight B. burgdorferi antigens. Other studies found involvement of B. burgdorferi antigens p39, p41 (flagellin), p22, and p31 (OspA). Whether there are immune-complex deposits not specific to B. burgdorferi in these cases is unknown. Without an inducible experimental model, it is unknown if there are specific Borrelia spp. strains that trigger LN. A genetic predisposition may involve immune dysregulation or a structural or functional glomerulopathy. Most seropositive dogs (even seropositive retrievers) are not affected with LN and are not proteinuric. Renal biopsies were described in severely affected dogs either at necropsy or end-stage disease. Without an experimental model for LN the appearance of the lesion and the clinical progression during earlier stages is unknown. There may be a time when occult proteinuria exists with milder glomerular changes, when intervention may be most helpful, before azotemia and/or tubular damage occurs. Diagnostic Tests Positive serology, supportive clinical signs, consideration of differentials, and response to therapy are clues, but Lyme disease easily is overdiagnosed because B. burgdorferi antibodies are common in healthy dogs, clinical signs are not pathognomonic, and response to therapy may be coincidental. In addition, no test predicts which seropositive dogs will become ill. Serology The organism does not circulate in blood and is found rarely in fluids or tissues, so antigen assays (e.g., culture or PCR assays) are not as useful. Measurement of serum antibodies against B. burgdorferi antigens is the test most widely used to aid in the diagnosis of Lyme disease. The magnitude of any B. burgdorferi antibody titer does not predict illness because many dogs with subclinical infections also have high titers. The most commonly used test for natural exposure is the C6 peptide antibody test (SNAP-4DxPlus, SNAP-3Dx, Lyme C6Quant) against part of the VlsE antigen, which is not expressed in ticks, in vitro, or in any of the B. burgdorferi vaccines. Antibodies against the C6 peptide reach detectable levels 3 to 5 weeks after infection, well before clinical signs are recognized in experimentally infected dogs. A Lyme C6Quant level more than 30 confirms exposure but does not prove the organism is the cause of the clinical signs. Comparisons of pretreatment and 6-month posttreatment C6Quant levels may be helpful (if a dog is treated); a 50% decline or more may indicate decreased antigenic load and possible clearance, even if the qualitative SNAP test is still positive. In addition, the new baseline quantitative value may be useful for future comparison if clinical signs suggestive of Lyme disease recur. It currently is unclear whether the failure to achieve a decreased C6Quant level after treatment can be used as a prognostic indicator. Whole-cell immunofluorescent antibody (IFA) and enzyme-linked immunosorbent assay (ELISA) antibody tests are available but do not differentiate antibodies induced by vaccination from those induced by natural exposure and may cross-react with other spirochetal antigens. Determination of IgM titers independent of IgG titers is not needed because dogs are not ill until after seroconversion to IgG, and IgM peaks can reoccur in carriers because of antigenic variation. Western immunoblot immunoassays may be useful to distinguish vaccinated from exposed dogs if a sole antibody band at p31 is seen after giving a subunit ospA vaccination. Otherwise banding patterns may not differentiate clearly antibodies induced by administration of B. burgdorferi bacterin vaccines from natural exposure antibodies. This is because B. burgdorferi carriers may recognize similar B. burgdorferi antigens found in dogs administered bacterins as the organism shows the host its antigenic repertoire, including antigens usually expressed in ticks, in vitro, or in bacterins. Some laboratories (e.g., New York State Diagnostic Laboratory and Antech Laboratories) are reporting serologic responses against multiple B. burgdorferi antigens; common targets include OspA, OspC, and OspF. OspA antibodies rise and fall after vaccination, but the protective titer level is unknown. OspA is not seen as commonly after natural exposure, although antigenic variation during the chronic phase may allow a nonvaccinated host to have anti-OspA antibodies. OspA expression is down-regulated during tick feeding, but a few OspA molecules may slip in, thus OspA antibodies may be seen transiently soon after infection. In contrast, OspC expression is up-regulated during tick feeding; OspC antibodies generally are detectable 2 to 3 weeks after infection and wane at 3 to 5 months (possibly before signs of illness). Because of reexposure, finding these “early antibodies” are a clue when the dog was last infected but not necessarily when it was first infected. The Nobivac Lyme vaccine may induce OspC antibodies, mimicking natural exposure antibodies. OspF antibodies generally are detectable 6 to 8 weeks after infection and persist; it is unknown whether posttreatment levels of OspF antibodies decline as C6 peptide antibodies do (whole-cell IFA and ELISA antibodies do not decline as much). More information is needed to determine optimal serologic assays.< div class='tao-gold-member'> Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Chapter 13: Complicated Diabetes Mellitus Diagnostic Approach to Hepatobiliary Disease Chapter 54: Oropharyngeal Dysphagia Chapter 49: Esophagitis Stay updated, free articles. Join our Telegram channel Join
