2013年9月22日星期日

Lyme Disease or Borreliosis

Lyme Disease or Borreliosis


In the United States, Lyme Borreliosis is the most commonly reported tick-transmitted disease in humans.  Lyme disease is caused by Borrelia burgdorferi which is a spirochete (corkscrew-shaped bacteria) that is transmitted by various Ixodes ticks. Lyme disease is also seen in Europe, Asia, South America, Africa and Australia.


 


In the United States it is seen primarily on the Atlantic seaboard, upper Midwest and Pacific coast.  Ixodes pacificus, also known as the blacklegged tick, is the primary tick transmitting the disease on the west coast and I. scapularis is the primary tick transmitting the disease elsewhere in the U.S.  In some regions of Connecticut, New York, Rhode Island and surrounding areas of the Northeast U.S., 50 to 90% of the I. Scapularis ticks are infected with the bacteria.   These ticks are 3-host ticks that have a 2 to 3 year life cycle. Larva and nymph forms of the tick feed primarily on rodents, small mammals and reptiles.  Adult ticks feed on deer or larger mammals. Pets may be infected by nymphs or adult ticks.


Natural transmission of the spirochete requires 36-48 hours of tick attachment. Blood transfusions may also serve as an incidental transmitter of infection.  Dogs are the primary pet species affected although they are considered to be an incidental host.  Young puppies from 6 to 26 weeks of age are more likely to develop clinical disease, although any age dog may be affected.   Other incidental hosts may include cattle, horses, and humans.  Preferred hosts include migratory birds, mice, raccoons, skunks and deer.  Cats may be exposed to the bacteria but to date natural disease in this species has not been reported.


Although the tick is considered to be the primary vector for B. burgdorferi, the organism has been isolated from mosquitoes, deer flies and fleas.


Originally the bacteria proliferate locally in the skin at the site of tick attachment.  Characteristic skin lesions consisting of small, reddened lesions of expanding erythema (redness and inflammation) around a tick bite do not typically occur in the dog or are transient in appearance.  From the skin, the bacteria then spreads throughout the body and may localize in the joints, connective tissues, the central nervous system, kidneys and sometimes other organs such as the heart. Up to 95% of infected dogs will remain asymptomatic once they become infected.  Clinical signs of disease are primarily a result of the body’s immune response to the bacteria and will often resolve within 3 days, only with antibiotic therapy in some cases.


Clinical signs of Lyme disease typically develop 2 to5 months after tick exposure.  Lyme disease is usually characterized by a high fever (103º to 105º F), polyarthritis (inflammation and swelling of several joints), lameness which is exhibited as an intermittent or lameness that shifts from one leg to another, lymphadenopathy (enlarged lymph nodes) and the animal being lethargic.  More serious but less common


disease syndromes with Lyme disease include Lyme nephritis (kidney disease), cardiac disease (myocarditis) and neurologic disease.


Lyme nephritis is characterized by protein losing inflammation, uremia (build up of ammonia levels), and hyperphosphatemia (increase in phosphorous levels).  The kidney inflammation typically does not respond to therapy and is generally fatal.  The Labrador and golden retriever breeds show a higher prevalence for the development of Lyme nephritis (Kidney Disease) than other dog breeds.


The cardiac form is characterized by cardiac arrhythmias, typically heart block and bradycardia (slow heart rate).  In the neurologic form of the disease seizures and facial paralysis may be seen.


Serology is the most common diagnostic method used to verify a case of Lyme disease. A positive antibody response will occur 3 to 5 weeks after infection with the bacteria.


Antibodies produced to B. burgdorferi may be detected by ELISA, IFA and Western Blot methods.  Current serologic tests do not indicate disease but rather exposure and seroreactivity.  Vaccination with the B. burgdorferi bacterin stimulates antibody production and will result in false positive results on most ELISA and IFA tests.  One test which does not cross-react with antibodies from vaccines is the Idexx Laboratories’ 3DX SNAP® test which detects antibodies specific to the C6 peptide.  This test is highly sensitive and specific for the disease causing organism.  In endemic areas, most animals may have antibodies without ever developing clinical signs of illness. It is also important to include blood film evaluation in the diagnostic process because neutrophils (a type of while blood cell) may contain the presence of inclusions which will aid in the diagnosis.  Diagnosis by bacterial culture is often difficult and unreliable.


The drug of choice for treatment of Lyme disease is doxycycline at a level of 10 mg/kg every 24 hours.  In order to avoid enamel staining that occurs with doxycycline use in young puppies, amoxicillin is often used at a dose of 11 to 22 mg/Kg every 8 to 12 hours. Improvement in clinical disease often occurs within 1 to 2 days of starting treatment.  A 30 day course of antibiotic treatment is recommended to control the bacterial infection.  Even after 30 days antibiotic therapy is unlikely to clear all the B. burgdorferi organisms from the pet’s body.  Current treatment recommendations for chronic infections suggest repeating the 30 day treatment four or five times at a 3 month interval.  The use of glucocorticoids may exacerbate the illness or cause relapse to occur.


Serology is not recommended as an accurate indicator of the response to treatment in either humans or dogs.  The SNAP® test for the C6 peptide will indicate a negative test 6 to 9 months following successful treatment.  Those animals with chronic infections will remain positive after this same time period and should be retreated.  Unfortunately, antibody levels are not a good indicator of the effectiveness of treatment.


Patients with Lyme nephritis (kidney disease) should be monitored for their kidney function.


Since transmission of the Borrelia organism occurs no sooner than 18 to 24 hours from the beginning of a blood meal, ticks may be removed daily or preferably immediately after exposure in order to prevent transmission.  Unfortunately it is often hard to find every tick on a pet.  Ticks will often be found hiding in the ear canals, under the leg, etc.


An effective measure used to prevent exposure to ticks may include acaricides such as fipronil or Frontline® produced by Merial.  Alternatives to frontline include Amitraz used in a tick collar known as Preventic® distributed by Virbac which is also available as a spot-on known as ProMeris® available from Fort Dodge Animal Health.  A permethrin contained within the spot-on treatment K9 Advantix® is available from Bayer, are all generally effective against ticks when used according to label directions.


Two types of bacterins (much like a vaccine but contain bacteria or bacterial antigens and not viruses) are commercially available to protect against Lyme disease.  One bacterin is composed of whole-cells while the other is a recombinant outer surface protein A (OspA) single antigen bacterin.  Both bacterins are effective in stimulating antibody production. The antibodies actually work in the gut of a tick to bind the bacteria during a blood meal. Once the bacteria have reached the body of the dog these antibodies are not effective because the surface proteins covering the bacteria change upon entry into the body of a mammal.


The bacterin manufactured by Fort Dodge Animal Health is called Lymevax®.  This particular bacterin contains whole-cell antigen and is recommended for dogs 12 weeks of age and older in areas endemic for the bacteria.  One dose of vaccine is given followed by a second dose of vaccine 2 to 3 weeks later.  Annual revaccination is then recommended.  The problem with vaccination is that it may interfere with antibody testing for Lyme disease.  Vaccination is recommended even in dogs testing positive for antibodies to the bacteria since the level of immunity and infection status would still be in question. As with any vaccination program the B. burgdorferi bacterin may not be 100% effective in disease prevention and animals exhibiting clinical signs of disease should be treated with antibiotics.  Alternatively dogs exposed to a tick should not be prophylaxically treated with antibiotics unless clinical signs of disease result.


A vaccine against the OspA surface antigen is manufactured by Intervet and is sold under the name of ProLyme® or Continuum Lyme Vaccine®.  The Intervet vaccine is available for dogs 4 weeks and older with an initial two doses which are given 3 to 4 weeks apart.  Annual revaccination is then suggested in endemic areas. 


Lyme vaccine is not considered to be a core vaccine.  The decision on whether to immunize or not should be based on the prevalence and severity of the disease in your residing area.  In general, when >20% of the canine population tests seropositive on screening tests, immunization should be considered.  In a recent survey, 55% of the dog owning public in the United States does not vaccinate their dog for Lyme disease. The potential for each particular pet to be exposed to ticks and subsequently the bacteria is another helpful criterion that may be used to determine whether use of the bacterin is warranted.


Infections that fail to respond to treatment should be checked for concurrent infections with other tick-borne diseases.  Both treated and untreated dogs will generally recover from B. burgdorferi exposure without severe complications with the exception of Lyme nephritis.  Lyme nephritis may be fatal weeks to months after diagnosis even with treatment.


Lyme disease is not a zoonotic infection, at least notin the classical sense.  People become infected from a tick and not directly from an infected mammal. In cases of concurrent infection it is likely that both people and pets gain exposure to Lyme disease through to the same infested population of ticks. “Lyme arthritis”, was first identified in humans in the United States in 1975 when two women from Lyme, Connecticut, noticed their children experiencing episodes of flue-like symptoms, rashes arthritis, neck stiffness and headaches.  Other members of the community, adults and children alike in the area often experienced similar symptoms.   A Yale University rheumatologist identified the tick was involved in the transmission of the condition but the causative agent was not identified until 1981 when Dr. Willy Burgdorferi identified the causative agent as a spirochete.


References:


Datz, Craig.  “Lyme Disease in Dogs”.  Clinician’s Brief.  May 2007. Vol 5. No. 5. Pp. 9-12.


Ettinger, Stephen and Edward Feldman. Textbook of Veterinary Internal Medicine. Sixth Edition. Vol. l. Elsevier Inc. 2005. pp 619-622.


Goldstein, Richard.  “Rational Use of Canine Lyme Vaccines and How to Implement a Lyme disease Protocol.”   NAVC/WVC Proceedings.  Merial 2008. Pp. 10-13.


Hoskins, Johnny DVM. PhD Editor. The Veterinary Clinics of North America Small Animal Practice.  “Tick-Transmitted Diseases”.  Pp. 51-63.


Kahn, Cynthia Editor:  The Merck Veterinary Manual.  9th Edition.  Pp. 485-486.


“Owners know little about Lyme Disease.”  Veterinary Forum.  April 2009.  P.17.


Ryan, William and Doug Carithers.  “Reducing the Risk of Tick-Borne Diseases.”  Clinician’s Brief, Supplement to NAVC Clinician’s Brief.  November 2007.  P. 2.

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