Lyme disease (Proceedings)

2011-10-01
Helio Autran de Morais, DVM, PhD, DACVIM (internal medicine and cardiology)

Tick-transmitted disease caused by the spirochete Borrelia burgdorferi.

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)

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