Friday, January 10, 2014

Lyme Disease in Dogs

Lyme disease has been recognized in Europe for nearly a century but was not described in humans in the United States until 1975. We have since learned that clinical disease also occurs in dogs and, to a lesser extent, in horses, cattle, and cats, while many wildlife mammals and birds become subclinically infected and serve as reservoirs for tick infection. During the 1980s the disease incidence in both dogs and humans increased dramatically; Lyme disease is now the most common arthropod-borne disease of humans in the United States, and one of the most common in dogs.

Lyme disease is caused by Borrelia burgdorferi, a corkscrew-shaped bacterium of the spirochete group. Among the spirochetes, it is most closely related to B. hermsii, which causes tick-borne relapsing fever in the southwestern United States. Better known but more distantly related spirochetes cause such diseases as leptospirosis and syphilis.

Deer ticks, hard-shelled ticks of the genus Ixodes, transmit B. burgdorferi by attaching to and feeding on various hosts. Other bloodsucking insects may be involved, but there is little evidence that they are important vectors. The primary way in which an animal or human becomes infected is by tick bite.
After a tick attaches and begins to feed, spirochetes residing in the midgut of the tick begin to migrate to the salivary glands and from there move into the host. The danger of infection increases when ticks are allowed to feed for prolonged periods and become engorged. There is believed to be little danger of infection during the first 12 hours of tick feeding. Beyond this point, risk of infection increases exponentially.
Ixodes ticks require three hosts and four different developmental steps to complete their two-year life cycle. The female ticks lay about 2000 eggs in the spring. The larvae that emerge from the eggs do not carry sufficient bacteria to induce infection. In the northeastern United States, the larvae feed mainly on the white-footed mouse, Peromyscus leucopus. Many infected mice harbor B. burgdorferi for long periods of time without developing disease themselves. The larvae become infected by ingesting the blood of persistently infected mice, then drop off the host and enter a resting stage for the winter.
The larvae molt into nymphs the following spring. Up to 25 percent of unfed nymphs in the northeastern United States are infected with B. burgdorferi. During spring and early summer the nymphs feed on new hosts, again white-footed mice or any of a wide range of animals, including dogs and humans. An infected nymph may infect its new host during the four-day feeding period. Conversely, an uninfected nymph becomes infected by feeding on a previously infected animal. Our studies of dogs indicate that nymphs are less effective vectors than adult ticks.
In the fall of the second year, nymphs molt again and enter the adult stage. An average of 50 percent of the adult ticks in infested areas of the Northeast may be carrying B. burgdorferi, and infected adult ticks are the most important source of infection for dogs. As long as temperatures remain above 2°C (35°F), adult ticks can be found on shrubs, where they are high enough off the ground to attach to the white-tailed deer and other larger animals.
Adult ticks mate on the host. Male ticks tend to stay on the host and die, but the females engorge for five to seven days and then drop off into the leaves, where they live through the winter. The following spring they lay eggs and complete the two-year cycle. Adult ticks that do not find a host in the fall may survive over the winter and become active again from early spring until about mid-May.
Discoveries by Cornell investigators indicate that exposure to B. burgdorferi-infected adult ticks in the fall and early spring months is more dangerous for dogs than exposure to infected nymphs later in the spring. Only repeated exposure to nymphs induces infection and disease.
In the southern United States, I. Scapularis larvae and nymphs feed primarily on lizards, which do not maintain infection with B. burgdorferi. Consequently, nymphal and adult infection rates are low, often less than one percent. Rates of infection with B. burgdorferi are also low (between one and five percent) in California.
In contrast to human cases of Lyme disease, where three different stages are well known, Lyme disease in dogs is primarily and acute or subacute arthritis. The acute form may be transient and may recur in some cases. The devastating chronic stage in humans with systemic disease has rarely been seen in dogs.
Dogs show sudden lameness and sometimes signs of severe pain. One or more joints may be involved. Joints are often swollen, hot, and painful upon manipulation. Dogs may have fever and be off-feed and lethargic. Some become severely depressed and are reluctant to move. Lameness may recur after a period of recovery lasting several weeks.
Work at the Baker Institute has shown that the incubation period in dogs is longer than previously believed. Lameness in dogs occurs an average of two to five months after tick exposure.
The first stage of human Lyme disease, a skin rash called erythema chronica migrans, is rarely seen in dogs. Some symptoms associated with the later stages of Lyme disease in humans have also been reported in rare instances in dogs. They include heart block, kidney failure, and neurological changes such as seizures, aggression, and other behavior changes.
How likely is it that a dog will get Lyme disease?
The proportion of infected dogs that develop clinical disease is far smaller than it is for humans. Serological studies suggest that while more than 75 percent of the dog population in hyper-endemic areas may be exposed to infected ticks, only about five percent of those exposed actually develop clinical signs that might be attributable to Lyme disease. Within endemic areas, “hot spots” of tick infestation where dogs have a much greater probability of acquiring an infection are intermingled with non-infested areas where the habitat is not favorable to the vector tick. There may be age, breed, and genetic differences in the susceptibility of dogs to Lyme disease, but little is known yet about these factors.
Our studies indicate that bitches that become infected while pregnant do not transmit infection to their fetuses. Furthermore, our studies have shown no evidence that the pups of an infected bitch acquire the infection from her after birth.

There are several ways to examine the immune response of dogs to B. burgdorferi infection. The enzyme-linked immunsorbent assay (ELISA) performed by our collaborates in the Diagnostic Laboratory of the College of Veterinary Medicine is very useful if the dog has not yet been vaccinated against Lyme disease – many vaccinated dogs develop antibodies that the ELISA and other tests cannot distinguish from a dog’s antibody response to tick exposure. Our colleagues have found through ELISA testing that antibody can first be detected in dogs between four and six weeks after exposure to infected ticks. Antibody titers, which are the measurement of an immune response, increase for several weeks and then remain constant for at least 18 months in the absence of re-exposure. Despite high ELISA titers, viable B. burgdorferi organisms can be shown to persist in dogs for at least 18 months, the longest period studied. It is possible that antibody and organisms persist together in dogs for several years.
The western blot is a technique that determines antibodies against multiple antigens of B. burgdorferi. In dogs as in humans, this method can identify specific antibodies to the organism. The western blot can distinguish between dogs that have been or are infected with B. burgdorferi and dogs that have been vaccinated against Lyme disease. It can also detect the dog that has been both infected and vaccinated. While the ELISA is a quantitative determination of all the antibodies produced against many antigenic components of B. burgdorferi, the western blot determines the unique pattern of antibodies produced against antigens of a tick-induced infection, which is different than the pattern produced following vaccination.
There are now several kits available commercially that allow veterinarians to test for Lyme antibody in dogs without sending samples to diagnostic laboratories. However, well-controlled ELISAs and western blots run in reputable diagnostic laboratories are probably the most reliable option.
Is it possible to isolate the organism itself?
The definitive means for diagnosing bacterial infections is to isolate the causative organism. In veterinary and human studies, B. burgdorferi has been extremely difficult to culture from body fluids and tissues, apparently because of the lack of organisms in the samples. In our experimental studies, the only locus from which B. burgdorferi was consistently isolated over a period of several months after tick exposure was the site of bites by infected ticks. If the site of a tick bite is known, a skin biopsy from that area provides the best chance for successful isolation of the organism. Even if the area of the bite is not known, there is a better chance of isolating the organism from the skin, even from sites distant from the bite, than from the blood or urine. This approach is not recommended however, because isolation of the organism is time-consuming and expensive.
What are the criteria for diagnosing Lyme disease?
We consider four criteria important in establishing the diagnosis of Lyme disease in dogs:
  1. History of exposure to ticks in an endemic area.
  2. Typical clinical signs (lameness with or without fever).
  3. A positive antibody test.
  4. A prompt response to antibiotic therapy.
One or two of these criteria alone are usually not sufficient to confirm a diagnosis. For example, if a dog has never been in an area known to be infected with Ixodes ticks carrying B. burgdorferi, it is very unlikely that the dog will have Lyme disease. A diagnosis based on clinical signs often remains questionable, for there are several other conditions, such as immune-mediated disease and rheumatoid arthritis, that cause lameness and pain in dogs. A positive antibody titer alone tells very little. Many dogs with high antibody titers fail to have clinical signs. The presence of a specific type of antibody (IgM) is a good indicator of recent infection with some diseases, but in cases of Lyme disease, IgM antibodies persist. The diagnosis of Lyme disease is strengthened by a good response to antibiotic therapy, but other infectious diseases that mimic Lyme disease, such as Rocky Mountain spotted fever and Ehrlichia canis infection, also respond to antibiotics.
Antibiotics are the treatment of choice for Lyme disease in dogs, as in humans. Several tetracyclines, such as doxycycline, and penicillin-like antibiotics, including amoxicillin and ceftriaxone, are very effective. Tetracyclines should not be given to growing dogs. Because B. burgdorferi has the tendency to persist in dogs, antibiotics should be given for three or four weeks, even though a beneficial effect can be seen after a few days of treatment. The long duration of therapy is also warranted because of the very slow multiplication rate of the organism, which takes 12 hours or more to double in number, as opposed to the minutes in which most bacteria do the same. Considering the fact that Lyme disease appears to be self-limiting, the need for a long-duration therapy may be arguable. However, there are now reports that tetracyclines may have a direct ameliorating effect on arthritis.
Dogs with recurrent episodes of Lyme disease, whether acquired from reinfestation with infected ticks or a relapse from an initial infection, are highly responsive to antibiotics given at the same doses as for a primary episode. Humans in the chronic stage of Lyme disease do not respond as favorably to antibiotics as dogs do.
Corticosteroids and other anti-inflammatory drugs are sometimes used for treatment of Lyme disease in dogs. Although the initial result may be impressive, these drugs do not have a true healing effect and can mask the diagnostic value of antibiotic treatment.
Should antibiotic treatment be initiated on dogs found carrying Ixodes ticks?
The question is only relevant in endemic areas. If dogs are exposed frequently to ticks, treatment is impractical. Besides, infection of dogs only occurs after at least partial engorgement of ticks. The risk of infection, therefore, is greatly reduced if the ticks are removed from dogs on a daily basis. Because treatment in dogs is highly effective, many veterinarians initiate treatment only after the onset of clinical signs.
What is the prognosis for dogs with Lyme disease?
Dogs respond very well to antibiotic treatment. There may be recurrent disease, but dogs again respond well to treatment. Complete recovery can be expected in the vast majority of cases. As noted above, chronic disease, which can be devastating in humans, has rarely been seen in dogs. Furthermore, our studies have shown that dogs may recover spontaneously without antibiotic therapy.
Can humans get the disease from dogs?
Some have speculated that B. burgdorferi in the saliva or urine of infected dogs may be transmissible to humans. Experiments however have failed to provide any evidence of urine or saliva shed. Organisms are rarely found in the kidneys of infected dogs. Borrelia organisms also deteriorate quickly in the urine and saliva, and there is so far no evidence of human infection resulting from contact with dogs. It has also been speculated that dogs might carry home loosely attached infected ticks, which could then transfer to human hosts and induce infection. No such instance has been documented.
There are two approaches to preventing infection in dogs. One is to limit tick engorgement on dogs by controlling the tick population, using tick repellents, and/or grooming daily. The other is vaccination.
Attempts to reduce the deer tick population by radically reducing the deer population, even by as much as 70 percent, have been only partially successful. Other wildlife can replace the deer as hosts, and efforts to reduce the population of white-footed mice are not feasible.
Selective chemical control of ticks appears to be more promising, although only relatively small areas can be covered. The Boston-based company Eco Health, Inc. has developed one approach, biodegradable tubes containing permethrine-treated cotton batting (Damminix®) that can be placed in infested areas. Mice use the cotton for nesting material. The acaricide-covered nesting material rapidly kills exposed I. scapularis larvae and nymphs. Contradictory reports have appeared about the effectiveness of this approach.
The Borrelia burgdorferi Bacterin from Ford Dodge Laboratories is currently the only licensed Lyme disease vaccine for dogs. Several million doses have been sold, and, other than transitory fever, dogs do not appear to have any immediate adverse reactions to its use. In a limited field study it was concluded that the incidence of disease (4.7 percent in infected, non-vaccinated dogs) was reduced to about one percent. However, the vaccine does not protect against actual infection. We do not yet have experimental data to show whether B. burgdorferi persisting in dogs vaccinated after tick exposure might cause later disease.
The fact that dogs showing antibody response only to vaccination, not to tick-induced vaccination, have been observed to develop classical signs of Lyme disease may indicate that the risk of vaccination with the whole-cell bacterin is greater than previously thought. If only one or two percent of vaccinated dogs in endemic areas experience this phenomenon, the possible advantages of the vaccine, which is reported to reduce cases of Lyme disease from about four and one-half percent to one percent of dogs at risk, would probably be offset by the risk of its use. However, the basis for the observation that vaccinated dogs develop Lyme disease is not understood and must be investigated further before firm conclusions can be drawn.
We cannot recommend vaccination of dogs in endemic areas with the whole-cell bacterin until questions are resolved about clinical Lyme disease developing in dogs that have been properly vaccinated. The risk of not vaccinating is minimal since the disease in dogs is probably self-limiting in the majority of cases and is effectively treated with antibiotics, even in cases of recurrent disease. Furthermore, the risk of ever developing clinical Lyme disease appears to be relatively low.

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