Lyme Disease 2010: Diagnosis, Treatment & Prevention

[Mark Billadeau]

While looking up some information I came across this on Lyme disease and I thought others may be interested in it. I will copy the entire 6 page article here to make it easier to view.

 

Mark

Lyme Disease 2010: Diagnosis, Treatment & Prevention

Richard E. Goldstein

Cornell University, College of Veterinary Medicine, Ithaca, NY, USA

 

OVERVIEW OF THE ISSUE

Canine Lyme and the causative agent Borrelia burgdorferi have become a huge problem in many areas of

the United States and Europe over the last 20 years. Over the last 5 years the disease has spread and the

incidence has risen considerably, even in areas of the Northeast that previously only had sporadic cases.

The dilemmas facing practitioners regarding this disease are many. Regarding clinical Lyme cases the

first dilemma is how to diagnose the disease. How to verify that a dog that is sick, and serologically

positive—actually has Lyme disease. What diagnostics are appropriate in a case like this? The second,

and often easier decision the practitioner must make is regarding treatment—with what? How much?

and for how long. Often the harder question are regarding non-clinical dogs. When and then how to

monitor non-clinical dogs for evidence of Borrelia burgdorferi infection? And, most importantly, how to

prevent Lyme disease? How good is tick control? Should we or should we not vaccinate? Who should we

vaccinate and do vaccines prevent or promote the most severe manifestation of Lyme disease—Lyme

nephritis? This talk will briefly review the most updated information regarding the practical aspects of

the diagnosis and treatment of canine Lyme disease. It will then focus on prevention of clinical Lyme

disease. Should we monitor non-clinical dogs for Borrelia burgdorferi infection? And if we do—what do we

do with a positive result? Does treatment prevent clinical disease? Should all dogs be treated or are there

ways to pick and choose? And then should we vaccinate? What vaccines are there? Do the vaccines work?

How do they work? Are there risks to vaccinating Lyme negative dogs? Lyme positive dogs? Using new

data this talk will revolve around the ways that veterinarians can answer those questions best in their practice.

 

OBJECTIVES OF THE PRESENTATION

To familiarize the attendees with the current state of knowledge regarding Lyme disease and Lyme

disease prevention. To provide the tools with which each veterinarian can better diagnose Lyme disease

in sick dogs, devise a strategy for screening and handling non-clinical Lyme positive dogs, and design a

Lyme disease prevention strategy for his or her practice.

GENERAL KEY POINTS

 Lyme Disease is common in many areas of the US and Europe.

 The practical diagnosis of Borrelia burgdorferi infection is performed by serology, most commonly by

using the IDEXX SNAP-3Dx or SNAP-4Dx assays in conjunction with appropriate clinical signs,

additional diagnostics and response to therapy.

 Screening dogs annually for positive Lyme serology is advantageous in many ways.

 Lyme prevention is a combination of:

o

Tick control

o

Vaccination in endemic regions

 

 Dogs testing positive for previous infection are not protected from future infections and should be

considered for vaccination.

 Vaccines should not be used in sick dogs for a therapeutic effect.

 Lyme nephritis is associated with renal immune complexes and does not appear to be induced by

vaccines to a large extent.

 

OVERVIEW OF THE ISSUE

Lyme Disease: Clinical Signs

The lack or apparent lack of clinical signs in most dogs with active Lyme infection makes both the

diagnosis and the study of this disease very difficult. In dogs, clinical signs are observed only in82nd Western Veterinary Conference

approximately 10% of infected cases. These signs tend to occur 2–5 months after the infection and include

lameness–mono or polyarthritis, lymphadenopathy, lethargy, and fever. Skin lesions are uncommon in

dogs. These signs typically resolve within approximately 3 days, in some case only with antibiotic

therapy. Some questions remain regarding more serious, less common syndromes that have been

associated with Lyme infection in dogs including: Renal disease (Lyme nephritis), Cardiac disease

(myocarditis) and neurological disease. Another question yet to be answered is whether some dogs get

the devastating chronic recurrent disease as seen in some infected humans.

 

Diagnosis

What Diagnostic Tools are Available?

1. Bacterial culture or PCR. This is very difficult in the case of Borrelia due to the small number of

infecting organisms and the complicated techniques involved in their successful culturing. Blood

PCR testing is not recommended as a screening test for this organism as many infected dogs will

have a negative PCR result.

2. Serology. Clinically today we must rely on serology in conjunction with clinical signs to diagnosethis disease. There are currently 3 types of serological testing commercially available:

 

a. Non-specific ELISA. This is a very sensitive test aimed at identifying any antibodies

produced against

Borrelia

whole cell antigen. It does NOT differentiate between

antibodies produced in reaction to Lyme infection vs. Lyme vaccination and will be

positive in both instances. Since we can usually never be sure of infection status and

many times of vaccination status a positive non-specific ELISA should ideally be

followed up with an additional test that would conform infection like a Western blot or a

C

6

antibody test

b. C

6

antibody testing. There are currently two commercially available tests for canine

antibodies against the Lyme C

6

protein. This protein is expressed only during infection,

therefore these tests are meant to be positive only in the event of natural exposure and

negative in naive dogs or dogs vaccinated for Lyme. These tests include the in-house 3Dx

or 4Dx SNAP tests and the quantitative C

6

antibody test available through IDEXX. Logical

use of these tests:

i. The SNAP 4Dx is an excellent test for screening dogs for Lyme infection.

This can be done as part of a screening program for asymptomatic dogs or when

Lyme disease is suspected. A positive result is indicative of active Lyme

infection.

ii. The quantitative C

6

antibody test tests for similar antibodies as the 4Dx

but in a quantitative fashion. The value of knowing the quantitative C

6

titer is still

unproven at this time, but we have shown that the titer correlated very well with

circulating anti-Lyme immune complexes and is likely a very useful tool in

treatment decisions of non-clinical dogs. The practical questions of when and

how to use this tool will be addressed using new data. Briefly, it appears that the

pre-treatment serum quantitative C

6

antibody concentration does predict

immune complex load and can be used to assess value of therapy or possibly risk

of vaccination. A follow up C

6

antibody concentration does suggest successful

treatment.

 

c. Western blot. This technique involves a blot smeared with Lyme antigens located in

known locations. This is a relatively expensive and labor intensive type of test and its

interpretation requires expertise. Therefore this will never be in-house technology. As we

have learned more about the 4Dx and quantitative C

6

assays, they have taken some of the

role of the Western blot as a confirmatory assay. At this time I would recommend using

the Western blot only in dogs where the vaccinal status is important to the veterinarian.

 

Lyme Prevention

Tick removal: It takes time for an infected tick to transmit Borrelia to a dog, this typically can happen no

sooner than 48 hours from the beginning of the blood meal. Therefore daily tick removal especially

immediately after possible tick exposure is beneficial. People should handle possible infected ticks with

care though, since there is the potential for transmission to the person from the tick. Daily tick removal

and tick control should be seen and the base of the Lyme prevention pyramid, and are crucial as part of

the prevention strategy. Tick control should be used even in low incidence areas. Without concurrent tick

control it is likely that the success of our prevention will decrease even if vaccines are appropriately used

as well.

Should We Vaccinate??

Whenever contemplating the use of a vaccine one needs to take weigh the pros and cons. These are the

considerations that should be evaluated in such cases in my opinion:

How common is the pathogen? How common is the disease? How severe is the disease? How

treatable is the disease? How good is the natural immunity? How expensive, reliable, and safe is the

vaccine? Is there a zoonotic potential? Now all that has to be done is to answer the above questions for

the vaccine we are considering.

1. Common? The disease is very common. Even though most dogs are asymptomatic the infection rate

is so high in the Northeast that it is a very common disease. 10% clinical signs of 50–75% of the dogs

in some areas is a lot!

2. Severity? Maybe not that bad in some cases, although the pain associated with acute clinical signs

can be quite severe. What we do not know is the prevalence of more severe syndromes such as

Lyme nephritis and chronic recurrent disease. We do know that Lyme nephritis does occur; it is

associated with Borrelia burgdorferi infection and is often fatal, with young healthy dogs dying

within a few weeks of showing signs of clinical disease. Once you have seen one of these, I believe

the severity issue takes on a whole new meaning.

3. Treatable? Acute arthritic and febrile Lyme are pretty treatable in most cases in terms of eliminating

clinical signs. But in many if not most dogs we think based on experimental studies we never get rid

of the bacteria even with antibiotic therapy. So maybe not that treatable. And then of course there is

Lyme nephritis which at best seems very hard to treat.

4. Natural immunity? Not very good. Since the immune response appears to dampen over time. This

is likely a result of the bacteria hiding themselves from the immune system by "hiding" in

synovium and down-regulating their immunogenic surface proteins.

5. How expensive, reliable, and safe is the vaccine? There are 3 kinds of commercially available

vaccines. All are relatively inexpensive. Two are whole cell bacterin based vaccines and the other a

recombinant outer surface protein A (OspA) single antigen vaccine. There is some company

generated published safety data, but it is limited and mostly relates to acute reactions in relatively

small numbers of dogs. All 3 vaccines are approved for dogs and so had to go through USDA

required safety testing. All 3 types of vaccine are likely to be effective. How do they work? We

know that all 3 vaccines primarily work by providing dogs with outer surface protein A (OspA)

antigen. Subsequently the dogs develop antibodies against OspA. These antibodies are taken up by

the tick, during the blood meal and actually work in the gut of the tick to bind the bacteria during

the blood meal. Once the bacteria have reached the body of the dog then the anti-OspA

vaccinational antibodies are not effective as the surface proteins covering the bacteria change they

enter the mammalian body. OspC is the main immunogenic protein exhibited by the tick in the

dog's body during natural infection. A new vaccine that has just been released (Nobivac® Lyme)

also includes OspC antigens that are generated in culture by a unique strain of Borrelia burgdorferi,

in addition to OspA antigen from a more conventional strain also found in the vaccine. To date

though, there is no published data regarding the added benefit of the OspC antigen content of the

vaccine.

6. Zoonosis? Not really, although there is some risk from infected ticks that are removed before

finishing the blood meal. When given a choice the ticks tend to only feed on one species at a time.

The Safety of Lyme Vaccines

There are different aspects to this question:

1. Regarding acute vaccine reactions: Simplistically one could say: All the dogs in the vaccine studies

seemed fine so the vaccine must be safe. Obviously that is not good enough. The vaccine studies are

too small to pick up uncommon reactions, are too short in duration, are invariably conducted by the

vaccine companies themselves and most of them are never published. There are actually also safety

studies conducted on every vaccine that are much larger, but also typically looking for acute

reactions and most often not published.

2. The more pressing question is: Do vaccines contribute to clinical signs associated with Lyme disease

or to the syndrome known as Lyme nephritis? A large amount of new and exciting data will be

presented to try to answer this question. And it is a good question because we now know that Lyme

nephritis is not caused by an inflammatory response to renal invasion of Borrelia burgdorferi

organisms. Lyme nephritis is a condition associated with an accumulation of immune complexes in

the kidney. We have shown that all Lyme positive dogs have a measurable level of Lyme specific

circulating immune complexes in their blood. More recently we have been able to purify renal

immune complexes from kidneys of dogs that died of Lyme nephritis and to identify Lyme specific

antibodies are present within those immune complexes. Studies are still ongoing regarding possible

co-infections or other antigen-antibody complexes in those kidneys. We have recently concluded a

series of studies assessing the possible contribution of vaccination to circulating immune complexes.

Briefly we can say that the effect of Lyme vaccines on immune complexes in Lyme negative dogs is

very transient and likely of little to no clinical significance. In Lyme positive dogs the story may be

different and strategies to treat first and then vaccinate will be discussed. Possible differences

between the different types of vaccines regarding their safety and potential contribution to immune

complexes will be demonstrated

My Recommendations (Based on the Above Criteria)

1. Vaccinate in endemic areas? Yes—To prevent infection from ticks. What defines an endemic area?

That is a good question. Through screening the prevalence should be determined in each practice.

In an area with high prevalence (over 20%?) It may be logical to vaccinate all dogs. In an area with

less prevalence possibly identifying dogs at increased risk is the wise way to do it. This should be in

addition to good tick control!

2. Vaccinate Lyme negative dogs? Yes.

3. Vaccinate positive dogs? Yes—To prevent reinfection from the tick as the immune system may or

may not be able to prevent active disease even if the dog is Lyme positive. Here is the most relevant

place for the concern over the immune complex issue Studies are currently ongoing that will

hopefully aid in providing data to enable more precise recommendations in the near future.

4. How often to vaccinate? Annually at this time with the currently available vaccines.

5. Even in vaccinated dogs tick control must be stressed to the owners since a very heavy Lyme

burden may override vaccinal protection.

Lyme Treatment

I believe there is little question about treating Lyme positive dogs with clinical signs. What should we

use? There is no proven benefit in vaccinating a dog with clinical Lyme disease from a therapeutic

standpoint. So we are left with antibiotics. Amoxicillin and doxycycline both work well although there is

some evidence that doxycycline may be better, and should be used for 4–6 weeks. Doxycycline will also

likely be better at treating additional organisms that may have co-infected our patient along with Lyme

disease. The harder question is what about the non-clinical majority. Why not treat them all? Although it

is hard to look the concerned owner of a young Lyme positive Golden Retriever in the eye and refuse to

treat a possibly fatal disease, theoretically we should approach the treatment question from a risk-costbenefit

standpoint. At this time I am not sure we have enough information to make an informed choice in this matter.

What do we know?

1. Lyme positive dogs may remain infected with Lyme at low numbers with or without treatment.

2. There is some evidence to show that in many cases treatment tends to lower Lyme titers faster than

they would decline without treatment. This may be true for bacterial load as well as serological titers.

3. Based on experimental and a growing number of field studies data IDEXX laboratories is currently

recommending treatment above a certain C6 quantitative titer and then rechecking titers 6 months

later to evaluate treatment afterwards. As we gain experience with this approach and controlled

field studies are published we will have a clearer understanding of the question to treat or not to

treat?

 

ADDITIONAL DETAIL

Lyme Nephritis

Current Recommendations for Screening and Treatment of Dogs with Suspected Lyme Nephritis. (These are based on limited experience, theory and not yet on strong clinical data!).

1. Monitor dogs in endemic areas for Lyme infection.

2. Screen all positive dogs for signs of proteinuria or microalbuminuria.

3. Screen all dogs that present with proteinuria or microalbuminuria for Lyme.

4. Consider treating any dogs positive for both Lyme and proteinuria or microalbuminuria with 4–6

weeks of doxycycline.

5. If proteinuria persists or worsens (based on urine protein/creatinine ratio):

a. Continue doxycycline

b. Consider low protein diet and an ACE inhibitor

c. Consider renal biopsy

 

6. If the renal biopsy is consistent with immune mediated GN consider immunosuppression with

drugs like mycophenolate, azathioprine, chlorambucil, or cyclosporine.KEY DRUGS, DOSAGES AND INDICATIONS

 

Key Drug: Doxycycline

Drug Class:Antibiotic

Dose Range: 10mg/kg (4.6mg/lb)

Frequency: Per day

Route: PO

Indications: Clinical or non-clinical Lyme positive dogs if the decision has been made to treat

SUMMARY

Lyme disease is an extremely important infectious disease in many areas of the US and Europe, coinfectious

should be evaluated and expected in Lyme positive dogs. Practitioners should consider

screening annually for Lyme serology. Treatment of non-clinical dogs is controversial because it has not

been proven to prevent future disease but factors such as proteinuria and the magnitude of the C6 titer

are reasonable considerations when considering treatment. Doxycycline 10/mg/kg/day is the drug of

choice for clinical and non-clinical dogs. Practitioners should stress a prevention package to their clients

which includes daily tick removal, tick control products and annual in vaccination in endemic areas.

REFERENCES

1. Greene CE, Straubinger RK. Borreliosis. In: Greene CE, ed. Infectious diseases of the dog and cat 3rd ed.Philadelphia: WB Saunders Co, 2006;417–435.

2. Levy S, O'Connor TP, Hanscom JL, et al. 2002, Utility of an in-office C6 ELISA test kit for determination of infection status of dogs naturally exposed to Borrelia burgdorferi. Vet Ther 3:308–315.

3. Liang FT, Jacobson RH, Straubinger RK, et al. 2000, Characterization of a Borrelia burgdorferi VlsE invariable region useful in canine Lyme disease serodiagnosis by enzyme-linked immunosorbent assay. J Clin Micro 38:4160–4166.

4. Levy SA, O'Connor TP, Hanscom JL, Shields P, Lorentzen L, Dimarco AA. Quantitative measurement of C6 antibody following treatment of Borrelia burgdorferi antibody-positive nonclinical dogs. Clin Vaccine Immunol. Clin Vaccine Immunol. 2008 Jan;15(1):115–9. Epub 2007 Nov 14.

5. Goldstein RE, DZ Atwater. Serologic and circulating immune complex analysis in dogs naturally infected with Borrelia Burgdorferi. ACVIM Forum 2006 (abstract).

6. Jacobson R, McCall J, Hunter J, et al. the ability of fipronil to prevent transmission of Borrelia burgdorferi, the causative agent of lyme disease to dogs. JARVM vol 2, no 1, 2004

7. Straubinger RK, Straubinger AF, Summers BA, et al. Status of Borrelia burgdorferi infection after antibiotic treatment and the effects of corticosteroids: An experimental study. J Infect Dis. 2000;181:1069–1081.

8. Hutton TA, Goldstein RE, Njaa BL, et al. The search for Borrelia burgdorferi in kidneys of dogs with suspected "lyme nephritis" J Vet Intern Med 2008;22(4):860–5.

9. Littman MP, Goldstein RE, Labato MA, Lappin MR, Moore GE. ACVIM small animal consensus statement on Lyme disease in dogs: diagnosis, treatment, and prevention. J Vet Intern Med. 2006 Mar–Apr;20(2):422–34.

10. Goldstein RE, Atwater DZ. Serology and circulating immune complexes in dogs naturally infected with Borrelia burgdorferi before and after doxycycline therapy. ACVIM Forum 2006 (abstract)

[Alchemist]

Mark: thanks so much for posting this. I live in "Tick Central, USA", and this has validated the approach we've been taking (tick preventative + vaccination + checking). I should weigh whether we should get periodic screening done as well, I guess...

[pucksfurcoat]

Excellent post - thanks so much!

[alligande]

Thank you Mark, for a very helpful article.