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| + | *Lyme disease |
| − | Also known as: '''''Borreliosis — Lyme Borreliosis
| + | **Caused by ''[[Borrelia burgdorferi]]'' |
| | + | **Reported in humans, dogs, horses, cattle, sheep |
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| − | ==Introductions==
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| − | [[File:Borreliose.png|thumb|Map of the areas where ''Borrelia spp'' are endemic<br><small>Sourced from Percherie 2006 Wikimedia Commons]]</small>
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| − | Lyme disease descibes the clinical syndrome caused by infection with ''[[Borrelia burgdorferi]]'' sensu lato in humans, dogs, horses, cattle and sheep. The disease is named after the town of [http://townlyme.org/ Lyme] in Connecticut, USA where clinical cases were first described in humans in 1975. Since its identification, analysis of historical samples of ticks has shown that ''B. burgdorferi'' has been present in Europe and North America since at least the start of the twentieth Century<ref>Marshall WF 3rd, Telford SR 3rd, Rys PN, Rutledge BJ, Mathiesen D, Malawista SE, Spielman A, Persing DH. '''Detection of Borrelia burgdorferi DNA in museum specimens of Peromyscus leucopus.''' ''J Infect Dis. 1994 Oct;170(4):1027-32.''</ref><ref>Hubbard MJ, Baker AS, Cann KJ. '''Distribution of Borrelia burgdorferi s.l. spirochaete DNA in British ticks (Argasidae and Ixodidae) since the 19th century, assessed by PCR.''' ''Med Vet Entomol. 1998 Jan;12(1):89-97.''</ref>.
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| − | ===Epidemiology===
| + | **Ticks are the vector, which acquire the infection from small rodents, the reservoir hosts |
| − | Currently, the bacterium is known to be present in Europe, Asia and North America (see image) and the prevalence of antibodies to ''B. burgdorferi'' sensu lato in French dogs was 1.09% when this was investigated in 2009<ref>Pantchev N, Schaper R, Limousin S, Norden N, Weise M, Lorentzen L. '''Occurrence of Dirofilaria immitis and tick-borne infections caused by Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato and Ehrlichia canis in domestic dogs in France: results of a countrywide serologic survey.''' ''Parasitol Res. 2009 Aug;105 Suppl 1:S101-14.''</ref>.
| + | **Ticks transmit the infection to large mammals such as deer and sheep |
| − | | + | **''Ixodes ricinus'' is the most common tick vector in Europe |
| − | The bacterium is transmitted by ticks of which the most common is ''[[Ixodes spp.|Ixodes ricinus]]'' in the UK. ''I. ricinus'' is a three host tick that acquires ''B. burgdorferi'' bacteria when it obtains a blood meal from small rodents as a larva and then transmits it to large mammals as a nymph or adult, demonstrating trans-stadial transmission. Lyme disease therefore occurs when domestic animals and humans enter areas of tick habitat and ticks must be attached for at least 48 hours for the organisms to multiply and transfer to the mammalian host.
| + | **Pathogenesis |
| − | | + | ***Virulence of the borreliae requires a change in expression of an outer membrane protein following ingestion of blood by the tick |
| − | ===Pathophysiology===
| + | ***Borreliae multiply in the blood stream of susceptible hosts and disseminate throughout the body |
| − | The virulence of the borreliae is associated with changes in expression of outer membrane proteins (OMPs) after introduction into the mammalian host. In the majority of hosts, the bacteria remain at the site of introduction but do not cause clinical disease. Antibodies are produced in response to the bacteria but, despite this, they are not eliminated and they may persist for the life of the host. In a small proportion of infected animals, the bacteria multiply and migrate through the connective tissues and disseminate via the blood stream. The migrant bacteria localise particularly in the skin, joints, brain, nerves, eyes and heart and clinical syndromes may involve any of these organs. The immune response to the bacterial OMPs cross-reacts with epitopes present of host proteins and the lesions that are observed in Lyme disease may in part be caused by this immune response. It is not currently known why only a small proportion (5-10%) of infected animals develop clinical disease.
| + | ***Localisation in joints, brain, nerves, eyes and heart can occur |
| − | | + | ***The associated lesions may be in part caused by the host immune response |
| − | ==Signalment==
| + | **CLinical signs |
| − | Affected animals often have a history of exposure to ticks but this may occur months before clinical disease is detected. Ticks are most abundant in particular types of habitat, as discussed [[Tick Life Cycle|here]]. For unknown reasons, a sample of Bernese Mountain dogs in Switzerland was found to have a much higher seroprevalence for ''B. burgdorferi'' sensu lato than a control population but it is not known if this is true in other regions<ref>Gerber B, Eichenberger S, Wittenbrink MM, Reusch CE. '''Increased prevalence of Borrelia burgdorferi infections in Bernese Mountain Dogs: a possible breed predisposition.''' ''BMC Vet Res. 2007 Jul 12;3:15.''</ref>.
| + | ***May be subclinical in endemic areas |
| − | | + | ***Clinical manifestation depends on the site of localisation of organisms |
| − | ==Diagnosis==
| + | ***Disease in dogs may cause fever, lethargy, arthritis, cardiac, renal or neurological disturbance |
| − | Lyme disease is '''very rare''' and care should be taken not to perform specific tests unnecessarily. A positive result on serological or PCR tests also does not necessarily support a diagnosis of Lyme disease as most infections are asymptomatic. A period of '''2-5 months usually elapses before clinical signs are observed''' in infected animals and it is therefore unlikely that animals recently infested with ticks will have Lyme disease.
| + | ***Horses suffer similar clinical signs but also lameness, uveitis, nephritis, hepatitis and encephalitis |
| − | | + | ***Cattle and sheep may suffer from lameness |
| − | ===Clinical Signs===
| + | **Diagnosis |
| − | The exact clinical signs shown depend on the species of ''Borrelia'' with which the animal is infected and on the area of the World in which infection occurs. Clinical signs are often vague, intermittent and variable between individuals, reasons why the disease was not identified until late in the twentieth Century. The exact clinical manifestation also depends on the site of localisation of the organisms. In the UK, animals infected with ''Borrelia burgdorferi sensu lato'' may show the following signs:
| + | ***Laboratory confirmation difficult due to low numbers of organisms and fastidious growth requirements |
| − | | + | ***History of exposure to ticks in an endemic region and clinical signs |
| − | '''Dogs'''
| + | ***Rising antibody titre to ''Borrelia burgdorferi'' detected by ELISA |
| − | *A '''local cutaneous reaction''' may occur at the site of the tick bite but this usually resolves within a week. This is not the equivalent of the erythema migrans described in infected humans. | + | ***Immunofluorescence |
| − | *Transient or intermittent '''pyrexia''' and '''lethargy'''. | + | ***Culture in Barbour-Stoenner-Kelly medium for 6 weeks under microaerophilic conditions |
| − | *Generalised '''lymphadenopathy'''.
| + | ***PCR |
| − | *Infection of the joints may result in non-erosive '''arthritis''', causing intermittent bouts of shifting lameness.
| + | **Treatment and control |
| − | *Disease in the heart may cause [[Myocarditis|'''myocarditis''']] with [[Atrio-Ventricular Block|atrio-ventricular block]] and dysrhythmias. This is rare in the UK. | + | ***Amoxycillin and oxytetracycline in the acute phase; prolonged treatment in the chronic phase |
| − | *'''Lyme Nephritis''' is a form of '''glomerulonephritis''' that may result in acute [[:Category:Renal Failure|renal failure]]. This form of renal failure has been described in dogs that were seropositive for ''B. burgdorferi'' sensu stricto in the USA but extensive molecular searches failed to reveal the presence of actual bacteria in the kidneys of affected dogs<ref>Hutton TA, Goldstein RE, Njaa BL, Atwater DZ, Chang YF, Simpson KW. '''Search for Borrelia burgdorferi in kidneys of dogs with suspected "Lyme nephritis".''' ''J Vet Intern Med. 2008 Jul-Aug;22(4):860-5.''</ref>. This form of disease has never been replicated in experimental infections. Associations have been suggested between proteinuria and ''Borrelia'' seroprevalnce, particularly in the Bernese Mountain dog breed. Lyme nephritis, if it is a true phenomenon, occurs much more commonly in the USA than in Europe.
| + | ***Tick control and removal |
| − | *Presence of organisms in the brain or spinal cord may cause '''neurological signs''' due to meningitis or encephalitis.
| + | ***Vaccines including whole cell bacterins and recombinant subunit vaccines available for dogs |
| − | | + | [[Category:To_Do_-_James]] |
| − | '''Horses''' may suffer similar clinical signs of shifting '''lameness''', '''uveitis''', '''nephritis''', '''hepatitis''' and '''encephalitis'''.
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| − | '''Cattle''' and '''sheep''' may suffer from '''shifting lameness'''. Other tickborne infections may be introduced concurrently, including ''[[Tick-Borne Fever|Anaplasma phagocytophilum]]'', ''[[Staphylococcus aureus]]'' and [[Louping Ill]].
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| − | ===Laboratory Tests===
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| − | Definitive diagnosis relies on detection of ''Borrelia'' bacteria.
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| − | ====Serology====
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| − | Care should be taken not to overdiagnose infection based on seroprevalence as the majority of infected animals will never develop clinical signs. Paired serology samples are not useful as antibody persists at high levels for a long period after infection. False negative test results are unlikely and, in experimental infections, antibody titres rise shortly before clinical signs are observed, increasing the likelihood that animals with clinical signs have Lyme disease if the test is positive.
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| − | The method of measurement of antibody titres is important as traditional methods (ELISA and immunofluorescence) may detect antibodies induced by other bacteria. The modern C6 ELISA test has the highest specificity and sensitivity of the tests currently available as it detects antibodies to one invariant region of a protein molecule that is conserved among strains of the ''B. burgdorferi'' sensu lato complex<ref>Gerber B, Haug K, Eichenberger S, Reusch CE, Wittenbrink MM. '''Comparison of a rapid immunoassay for antibodies to the C6 antigen with conventional tests for antibodies to Borrelia burgdorferi in dogs in Europe.''' ''Vet Rec. 2009 Nov 14;165(20):594-7.''</ref><ref>Levy S, O'Connor TP, Hanscom JL, Shields P. '''Utility of an in-office C6 ELISA test kit for determination of infection status of dogs naturally exposed to Borrelia burgdorferi.''' ''Vet Ther. 2002 Fall;3(3):308-15.''</ref>. The C6 ELISA also correlates well with the infectious load of bacteria, falling rapidly after antibiotic therapy is instituted<ref>Levy SA, O'Connor TP, Hanscom JL, Shields P, Lorentzen L, Dimarco AA. '''Quantitative measurement of C6 antibody following antibiotic treatment of Borrelia burgdorferi antibody-positive nonclinical dogs.''' ''Clin Vaccine Immunol. 2008 Jan;15(1):115-9. Epub 2007 Nov 14.''</ref>.
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| − | ====Polymerase Chain Reactions====
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| − | PCR has a high specificity for the detection of ''Borrelia'' organisms but it is best performed on skin samples taken from near to the site of tick attachment or on synovial fluid or cerebro-spinal fluid from animals suspected of having Lyme arthritis or meningitis. Although the sensitivity of a PCR test is good, infection may still be present in another part of the body besides the one that was sampled. Blood is not usually used for detection as the bacteria are never present in blood in large numbers. Like the C6 ELISA, PCR tests can be used to monitor responses to treatment<ref>Wodecka B, Rymaszewska A, Sawczuk M, Skotarczak B. '''Detectability of tick-borne agents DNA in the blood of dogs, undergoing treatment for borreliosis.''' ''Ann Agric Environ Med. 2009 Jun;16(1):9-14.''</ref>.
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| − | In joints that have been infected by ''Borrelia'' organisms, small fragments of DNA may remain and give false positive results on PCR analysis.
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| − | ====Culture====
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| − | Bacteria may be cultured in Barbour-Stoenner-Kelly medium after 6 weeks under microaerophilic conditions. The best samples for culture are skin samples from near to the site of tick attachment (as the bacteria remain within the local connective tissues) but the test is not sensitive as the bacteria will be present in low numbers.
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| − | ==Treatment==
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| − | Both [[Penicillins|amoxycillin]] and [[Tetracyclines|oxytetracycline]] may be used for treatment in the acute phase but, in some cases, prolonged treatment may be needed to control the clinical signs. The organisms may never be eradicated, even after this prolonged treatment.
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| − | Tick control and removal are vital in the prevention of new infections. In areas with high numbers of ticks, owners should check their pets every day in areas of likely attachment (such as at the front of the body) and remove any ticks with the whole head intact. Repellents such as the permethrins can be used in areas of high tick density<ref>Endris RG, Cooke D, Amodie D, Sweeney DL, Katz TL. '''Repellency and efficacy of 65% permethrin and selamectin spot-on formulations against Ixodes ricinus ticks on dogs.''' ''Vet Ther. 2002 Spring;3(1):64-71.''</ref>. | |
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| − | Vaccines including whole cell bacterins and recombinant subunit vaccines are available for dogs in the USA. | |
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| − | ==Prognosis==
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| − | Prognostication is difficult as the clinical presentation varies so widely between animals. With the exception of those animals with Lyme nephritis, the response to treatment is generally good, even if the bacteria are eliminated.
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| − | {{Learning
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| − | |literature search = [http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=Lyme&occuring1=title&rowId=2&options2=OR&q2=Borreliosis&occuring2=title&rowId=3&options3=AND&q3=&occuring3=freetext&publishedstart=2000&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all&x=61&y=12 Borreliosis publications]
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| − | |full text = [http://www.cabi.org/cabdirect/FullTextPDF/2009/20093115231.pdf ''' Lyme disease and the Lyme vaccine.''' Goldstein, R. E.; The North American Veterinary Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Orlando, Florida, USA, 17-21 January, 2009, 2009, pp 618-620]
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| − | [http://www.cabi.org/cabdirect/FullTextPDF/2007/20073017453.pdf '''Lyme disease - an emerging zoonotic diseases.''' Pillai, U. N.; Vijayakumar, K.; Intas Pharmaceuticals Ltd, Ahmedabad, India, Intas Polivet, 2006, 7, 2, pp 337-340, 11 ref.]
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| − | [http://www.cabi.org/cabdirect/FullTextPDF/2005/20053193213.pdf ''' Equine Lyme disease: a review of experimental disease production, treatment efficacy, and vaccine protection.''' Divers, T. J.; Chang, Y. F.; McDonough, S. P.; American Association of Equine Practitioners (AAEP), Lexington, USA, Proceedings of the 49th Annual Convention of the American Association of Equine Practitioners, New Orleans, Louisiana, USA, 21-25 November 2003, 2003, pp 391-393, 15 ref.]
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| − | ==References==
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| − | {{review}}
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| − | [[Category:Urological Diseases - Dog]][[Category:Musculoskeletal Diseases - Dog]][[Category:Cardiovascular Diseases - Dog]][[Category:Musculoskeletal Diseases - Sheep]][[Category:Musculoskeletal Diseases - Cattle]][[Category:Zoonoses]]
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| − | [[Category:Expert_Review]]
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| − | [[Category:Musculoskeletal Diseases - Horse]][[Category:Liver Diseases - Horse]][[Category:Neurological Diseases - Horse]]
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