Lyme-Disease - a „consensus statement“   Lyme-Disease - a „consensus statement“ (391 KB)

First associated 1975 with illness in humans in Lyme/Connecticut/USA the infection with Borrelia burgdorferi is now as well known in the veterinary practice.  Dogs, horses and even cats get infected and show clinical signs. Because of the association with the tick vector Ixodes ricinus, prevalence varies geographically. While Borrelia burgdorferi infection is occasionally transmitted transplacentally, tick-borne transmission is considered most likely.
  
Because of the wide distribution of the agent and the high prevalence in the canine population the diagnosis and diagnostic of Lyme disease often causes a problem.
A large number of questions and as well as a disparity of opinions and interpretations exist concerning Borrelia infections in animals. Thus, recently Diplomates of the American College of Veterinary Internal Medicine, practitioners in endemic areas and scientists from different universities in the USA were questioned in order to establish a  “consensus statement ". This was established including a summary of studies, publications and practical experiences.
 
The “consensus statement " was presented at the 23rd ACVIM Forum in Baltimore/USA in June, 2005 and is posted on the ACVIM website   http://www.acvim.org/ .
This LABOKLIN aktuell will summarise the important facts and will refer to the situation in Middle Europe. In addition we will provide you with a diagnostic guideline.
 
What clinical syndromes are associated with Lyme disease and when should I include a test in my differential diagnostic list?
Apart from acute illness with pyrexia, lethargy and erythema migrans rash at the site of the tick bite possibly cardiac and neurological signs can be seen.
Chronic arthritis, intermittent lameness and back pain are signs to test for Lyme after excluding orthopaedic problems.

Are there other infectious agents that can cause similar signs?
Anaplasma phagozytophilum, Neospora canis or Toxoplasma gondii can be responsible for similar clinical syndromes. Co-infections can be relevant too. To have a clear result is essential for the right treatment and for prevention.

Glomerulonephritis as a consequence of Lyme-Infection?
There are more and more reports of proteinuria in dogs with Lyme disease.
Histopathological investigations of renal tissue show lesions including immune-mediated glomerulonephritis, diffuse tubular necrosis and regeneration, as well as lymphocytic/plasmacytic interstitial nephritis. This phenomenon is possibly the cause of plaques due to immun complex deposition in the kidney.
A presumable increased appearance of clinical signs in the Bernese Mountain Dog was not confirmed in recent studies.
But fact is that there is a higher prevalence of proteinuria in clinically unremarkable seropositive dogs. Therefore the protein/creatinine-ratio (U/P-C) can be used to make the decision regarding the choice of antibiotic treatment. Only renal failure or cystitis limits this investigation.
 
How is canine Lyme disease diagnosed?
Detection of the Borrelia burgdorferi by culture is very difficult and special culture medium is necessary. Therefore the usual diagnosis is done by the detection of antibodies. Two kinds of tests are normally used. An indirect immunofluorescence (IFT), using the whole organism as a test antigen or an ELISA test using ultrasound lysed Borrelia burgdorferi is available.
In both cases IgM and IgG antibodies are detected.  IgM is the marker of the first immune response and is detected in the acute stages of infection and at the first contact with the organism. IgG antibodies appear later and classify the specific affinity of the immune response. IgM titres decrease physiologically after a while, whereas IgG titres in Borrelia burgdorferi infections normally persist over a long time even without new exposure.
Because of the variability of the immune response in dogs   high antibody titres are not necessary seen only in sick dogs. Therefore it is useful to test additionally by Western blot immunoassay. To differentiate the source of the antibody response banding patterns towards certain antigenetic structure of the organism are detected.  Certain banding patterns can be assigned to different stages of the infection. In the early stage the immune response aims towards the 41kD-protein (flagellin antigen). Unfortunately there are similarities of the 41kD-protein with other flagellate organisms and some dogs show a positive 41kD pattern without contact to Borrelia burgdorferi. Antibody response against the outer surface protein OspA (31kD-protein) is not common. Around 17% of chronically infected dogs show positive patterns. In general OspA it is only expressed in the tick and during in vitro culture (and so it is present in Lyme vaccines). Thus, positive reactions generally suggest the animal had been vaccinated, not infected. In contrast the OSP C (24kD) and the 39kD-proteins can be detected in infected animals. In the later stages if the infection the 100kD-protein is suited best. The immune response to the 100kD-protein is usually late, but there is not known cross reaction and is therefore pathognomonic.
Amplification of the Borrelia burgdorferi genome by PCR (polymerase chain reaction) is possible. While the method itself is very sensitive, the choice of the sample is crucial to obtain a reliable result. Because there is no classical bacterinaemia a detection in the blood is not sufficiently sound. A positive result can be detected in ticks, skin biopsy, CSF or joint tabs. Regarding our experiences the interpretation of a positive result should be discussed individually.

Are results from paired assays needed to diagnose canine Lyme disease?
Since there were no signs of illness in the experimental studies in dogs even months after tick exposure and well after seroconversion, there is no evidence that paired titres are necessary for the initial diagnosis of Lyme disease. In addition, titre magnitude is not associated with the presence or absence of disease.  Especially IgG-titres can persist for a long time. Therefore paired titres or follow up controls like in other infections are normally not necessary. 


Is it reasonable to test healthy dogs?
An antibody titre check should be performed if the owner wants to vaccinate the dog to decrease the risk of an immune-mediated reaction. Only seroneagtive dogs should be vaccinated.  A “routine-check†in a healthy dog is not recommended. A positive titre is often “over-interpreted†and unnecessary therapy can cause drug resistance. In case of a positive result in a dog without clinical signs the animal should be tested for proteinuria and eventually monitored to start a therapy if necessary.
 
What antibiotics can be used in the treatment of Lyme disease in dogs?
In most studies and reports administration of doxycycline at 10 mg/kg/day PO for a minimum of one month is recommended. Doxycycline has anti-inflammatory properties and was recommended most frequently because of the possibility of other coinfections like Anaplasma phagozytophilum that respond to that drug. Polyarthropathy may be immune-mediated and improve faster with added glucocorticoids. Dogs with presumed Lyme nephropathy may require longer duration of doxycycline therapy and usually are treated with adjunctive therapies such as ACE inhibitors, low dose aspirin, omega-3 fatty acids and dietary therapy.
If it is possible to clear Borrelia burgdorferi from an animal is unknown.  PCR test results on skin samples from the site of the tick bites were reported positive even a year after treatment and without clinical signs.  It is not clear if those PCR results could have been due to non-viable remnant spirochetes or “DNA-blebsâ€.

How often is a positive titre seen in our lab?
Between October 2004 and September 2005 sera from 13086 dogs were tested by ELISA for IgM ad IgG antibodies.  Test results were classified in three groups.
Antibody titres < 25 U/l were classified negative according to the test producer's recommendations. Further classification gives a second group with titres between 25-60 U/l and a third one with titres > 60 U/l. More than two third of all dogs showed to be IgG- negative and 85 % were negative for IgM. On the other hand 35% of all dogs were seropositive. Unfortunately in most cases we do not have access to the anamnesis. Positive IgM titres were only seen in 13.4% of the cases.   In most of theses dogs colleagues report acute symptoms.
An important fact is: according ACVIM studies dogs do not show clinical signs prior to seroconversion.
Thus a negative sample seems to rule out suspect borreliosis. 
  
  
 
 

    

   



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