Lyme Disease
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This article is still under construction. |
| Also known as: | Borreliosis Lyme Borreliosis |
Description
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 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[1][2].
Epidemiology
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[3].
The bacterium is transmitted by ticks of which the most common is 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.
Pathophysiology
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.
Signalment
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 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[4].
Diagnosis
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.
Clinical Signs
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:
Dogs
- 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.
- Transient or intermittent pyrexia and lethargy.
- Generalised lymphadenopathy.
- Infection of the joints may result in non-erosive arthritis, causing intermittent bouts of shifting lameness.
- Disease in the heart may cause myocarditis with atrio-ventricular block and dysrhythmias. This is rare in the UK.
- Lyme Nephritis is a form of glomerulonephritis that may result in acute 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[5]. 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.
- Presence of organisms in the brain or spinal cord may cause neurological signs due to meningitis or encephalitis.
Horses may suffer similar clinical signs of shifting lameness, uveitis, nephritis, hepatitis and encephalitis.
Cattle and sheep may suffer from shifting lameness. Other tickborne infections may be introduced concurrently, including Anaplasma phagocytophilum, Staphylococcus aureus and Louping Ill.
Laboratory Tests
Definitive diagnosis relies on detection of Borrelia bacteria.
Serology
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.
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[6][7]. The C6 ELISA also correlates well with the infectious load of bacteria, falling rapidly after antibiotic therapy is instituted[8].
Polymerase Chain Reactions
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[9].
In joints that have been infected by Borrelia organisms, small fragments of DNA may remain and give false positive results on PCR analysis.
Culture
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.
Treatment
Both amoxycillin and 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.
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[10].
Vaccines including whole cell bacterins and recombinant subunit vaccines are available for dogs in the USA.
Prognosis
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.
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.