Lyme disease (Proceedings)

Agent

• Tick-transmitted disease caused by the spirochete Borrelia burgdorferi.

• “Borrelia burgdorferi sensu lato" is name given to the overall category. In North America there is just one genospecies variant - Borrelia burgdorferi sensu stricto. In Europe there are three categories Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii.

• B. lonestari causes a “southern tick-associated rash syndrome” in the U.S.

Epidemiology

• Worldwide distribution

• In the US, occurs mostly (> 90%) in the northeast, Minnesota and Wisconsin, less common in southeast, and midwest regions.

• Recognized vectors:

• Ixodes scapularis, in the northeastern and north central US

• I. pacificus in the western US

Transmission

• Ticks

• In the northeastern US from Maine to Maryland and in the north central states of Wisconsin and Minnesota

• Highly efficient, horizontal cycle of B. burgdorferi transmission occurs among larval and nymphal I. scapularis ticks and certain rodents, particularly white-footed mice and chipmunks.

• This cycle results in high rates of infection among rodents and nymphal ticks and many new cases of human Lyme disease during the late spring and early summer months.

• Nymphs are the life stage most commonly involved in transmitting B. burgdorferi to dogs and humans.

• White-tailed deer, which are not involved in the life cycle of the spirochete, are the preferred host of adult I. scapularis, Deer are not competent hosts for B. burgdorferi – their role is to maintain the ticks, not the Borrelia. Dogs, horses, cows, people, etc. are accidental victims of a hungry tick!

• Vector ecology is different in other parts of the US where prevalence is lower.

• Do not infect host until attached for 24 hours. This time is required for the bacteria to migrate from the tick midgut to the salivary glands

• Dogs

• Experimentally-infected dogs

• Beagle pups

• Clinical illness 2-5 months after exposure

• Inappetence, lethargy, and lymphadenopathy

• Episodic shifting leg lameness of 3-6 day duration

• Arthritis develops first in the joint closest to the tick bite

• After about 6 months, all arthritic episodes resolve

• Adult beagles do not develop the disease

• Natural disease not well characterized

• Difficult to reproduce in an experimental setting.

• Based on seroprevalence studies, only 5-10% of naturally infected dogs develop clinical signs.

• Seroprevalence in endemic areas can be as high as 90%.

• Considered a generalized, systemic infection

• Connective tissues

• Joint capsules

• Muscle

• Lymph nodes

• Lyme disease can be seen throughout the active tick season, but it is most often diagnosed in late spring and fall, rather than in midsummer

• Cats

• Develop clinical signs if experimentally-infected

• Clinical signs do not consistently develop in naturally-infected cats

• More resistant than dogs?

• Better at removing ticks

• Rate of seropositivity is lower than in dogs

• Connective tissues

Clinical Findings

• Polyarthritis

• Most common manifestation in dogs

• May be septic or immunemediated

• Transient, respond to antibiotic therapy

• Few or many joints

• Often subclinical

• Chronic, non-erosive arthritis (persistent infection)

• Systemic signs

• Anorexia, weight loss, lethargy, lymphadenomegaly

• Renal disease

• Protein-losing nephropathy

• Acute progressive renal failure (Lyme nephritis)

• Syndrome described in Borrelia-seropositive dogs

• Etiology not clearly established

• Circumstantial evidence

• Unique histopathologic lesions

• Mostly in Labrador and Golden retrievers

• Other manifestations

• Lyme myocarditis

• CNS inflammation (reported but poorly described)

Laboratory findings

• Leukocytosis with left shift, monocytosis, mild anemia

• Proteinuria

• Azotemia

• Joints

• Neutrophilic inflammation

Diagnosis

• Clinical Signs + Serology

• Prevalence of seropositivity is much higher than prevalence of disease

• Whole cell body antibodies (ELISA or IFA)

• Should not be used anymore

• Poor specificity

• Subclinical infection is common

• Cross-reaction with vaccine

• Non-specific reactivity

• Snout test: so Sensitive that a Negative result rules OUT the disease

• IgM cannot be used as an indicator of recent infection because IgM titers remain elevated for prolonged periods of time after infection

• Western-blot

• Can differentiate between vaccine and natural exposure

• Some non-vaccinated dogs previously exposed to B. burgdorferi show Western-blot pattern compatible with both, vaccination and natural exposure.

• C6 antibodies

• “Snap-test” or Quantitative C6

• Antibodies against C6 peptide

• Not a part of OspA

• Not affected by vaccination

• Highly specific

• Detectable 3 weeks post-exposure

• May be able to use titer to gauge treatment succes

What to do with a seropositive dog?

• Consider

• Clinical signs

• Proteinuria

• Asymptomatic, non-proteinuric

• No therapy

• Symptomatic, non-proteinuric

• Treat Lyme

• Asymptomatic, proteinuric:

• Recheck proteinuria periodically. If persistent or severe

• Treat Lyme and proteinuria

• Symptomatic, proteinuric

• Treat Lyme and proteinuria

Therapy

• Doxycycline 10 mg/kg q12h for 28 days

• Longer if nephropathy (?)

• Drug of choice

• Early treatment decreases titers and organism load

• Clearance is not complete

• Amoxicillin 20 mg/kg q8-12h for 28 days

• Ceftriaxone is used in humans with menigitis

Prevention

• Strict tick-control

• Vaccine

• Bacterins + adjuvant vaccines: Reduce incidence of signs in seropositive dogs from 4.7% to 1%. Value is questionable

• Single protein vaccines (OspA): protect from infection and disease

• OspA antibodies block migration of the organism from the tick into the dog

• Do not clear infection in the dog, because the change in temperature from the low temperature tick to the high temperature dog shifts expression of OspA to OspC.

• OspC antibodies are not borrelicidal

• Vaccinate at risk dogs before the tick season

• Duration of immunity is at least 6 months

• Western-blot and C6 antigen differentiate vaccine from exposure

Vaccine X Arthritis

• Arthritis

• Major clinical sign in human beings and dogs

• Also detected in human beings following vaccination with Borrelia OspA and in dogs with the whole cell vaccine and presumably OspA vaccine

• Arthritis is also found in animals following Borrelia vaccination with whole cell and OSPA followed by infection.

• Should we vaccinate?

• Arthritis is seen in about 3% of naturally-infected dogs

• If prevalence of post-vaccination arthritis is assumed to be 0.04% (it is not known)

• What would be the outcome in 3 different areas? (1,000 dogs, vaccine 70% effective)

• High prevalence:  75% of dogs get infected

• Without vaccine: 23 dogs with arthritis (Lyme-induced)

• With vaccine: 11 dogs with arthritis (7 with Lyme, 4 vaccine-induced)

• Moderate prevalence: 25% of dogs get infected

• Without vaccine: 8 dogs with arthritis (Lyme-induced)

• With vaccine: 6 dogs with arthritis (2 with Lyme, 4 vaccine-induced)

• Low prevalence: 10% of dogs get infected

• Without vaccine: 3 dogs with arthritis (Lyme-induced)

• With vaccine: 5 dogs with arthritis (1 with Lyme, 4 vaccine-induced)

References

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