The Diagnosis and

Management of Lyme Disease

in Nova Scotia

Todd F Hatchette MD FRCPC

93rd Dalhousie Annual Refresher Course

November 28, 2019

Faculty/Presenter Disclosure

• Faculty: TF Hatchette

• Relationships with commercial interests:

– Grants/Research Support: Investigator initiated grant form GSK – Vaccine

effectiveness in Influenza

– Speakers Bureau/Honoraria: None

– Consulting Fees: None

• Other:

– Provincial Co-Chair for the CPHLN Lyne Diagnostic Working group

– President – AMMI Canada

– Chair of AMMI Lyme disease working group

Objectives

• Discuss the epidemiology of Lyme disease in Nova

Scotia

• Identify the signs and symptoms of Lyme disease.

• Identify currently available diagnostic tests for the

disease, their limitations and how to properly interpret

their results.

• Discuss treatment recommendations for both adult and

pediatric populations

Key Messages

• Prevent/remove BLTs – No tick No Lyme

• Think about Lyme disease in your differential in NS

• Early Infection is a clinical diagnosis

– circular rash in an unusual site for cellulitis (torso, neck, stomach). Not always bulls eye

– Unsure if tick reaction – follow to see if the rash expands

• Serology poor in early localized infection – Good in late infection

• No evidence to support prolonged antibiotic therapy

EPIDEMIOLOGY OF LYME

Lyme Disease – the microbe

• Caused by Borrelia species– B. burgdorferi Europe & North America

– B. afzelii

– B. garinii

• Spirochete phylum– Motile, corkscrew shaped bacteria

• New species• B. miyamotoi

• B. mayoni

Europe & Asia

Lyme disease – the vectors

• Only Ixodes tick species

– Ixodes scapularis – northeastern and

midwestern Canada & US

– Ixodes pacificus – west coast Canada & US

cdc.gov

vs

Ixodes scapularis (BLT) Dermacentor (Dog tick)

cdc.govcdc.gov

Lyme disease – the hosts

• Rodents (exact one varies from vector-vector and geographic area)

• Larvae:

– Usually feed on mice

– Need to have their first blood meal to get infected…then infected for life.

• White-tailed deer

(critical for tick survival)

Risk Depends on Duration of Attachment AND Prevalence of infection

• Unengorged ticks pose essentially no risk

Tick needs to be attached for > 24 hrs to transmit

• Overall risk 1.2-3.2% in endemic area

• (≥20% of ticks infected)

• Risk increases with degree of engorgement (10-25%)

• Equates with duration of attachment

CID 2006;43:1089-134

PHAC

Number of reported cases of Lyme disease by case classification and year, Nova Scotia, 2008-2017

Source: DHW

Lyme is Here and Increasing in NS

https://novascotia.ca/dhw/CDPC/lyme.asp

• Western Zone the highest rate • 2017: 241.8/100,000 population

Lyme disease elsewhere(Ask where your patients has been)

• US ~ 30,000 cases/year (likely 10x higher)

• Northeast - Maine to Virginia

• Midwest

– Wisconsin, Minnesota, and Michigan

• West

– Northern California

• Europe

• Germany

• Austria

• Slovenia

• Sweden

http://www.eea.europa.eu/data-and-maps/indicators/vector-borne-diseases-1/assessment

cdc.gov

CLINICAL PRESENTATION OF LYME DISEASE

Lyme Disease Clinical Course

Acute cutaneous disease

Early disseminated disease

Late disseminated disease

http://ocw.jhsph.edu/courses/EpiInfectiousDisease/PDFs/EID_lec15_Griffin.pdf

Erythema migrans

• Typically within 7-14d (3-30) of bite

• In 70-80% at site of the tick bite

• Should be at least 5 cm for secure diagnosis

• Usually expands in size over 24-48 hours

• Secondary lesions may be < 5 cm

• Can vary in appearance (oval, round, ± central clearing, ±partially purpuric, ± central vesicles/pustules)

https://novascotia.ca/dhw/CDPC/lyme.asp

Early disseminated Lyme

• Systemic symptoms:– malaise, headache, fever & chills, myalgias, regional

adenopathy

• MSK

• Cardiac involvement

• Multiple EMs (20%)

• CNS involvement– Sometimes have evidence of meningitis (headache &

neck pain)

– Cranial nerve palsies

– Motor or sensory radiculoneuritis

– Mononeuritis multiplex

– After several weeks-months: ~15% in US develop frank neurologic abnormalities

Late Lyme Disease

Neurologic (less common in NA)

• Encephalomyelitis

• Peripheral neuropathy

• Encephalopathy

Rheumatologic

• Monoarticular or oligoarticular arthritis

• Typically the knee

• Often intermittent if untreated

• Inflammatory synovial fluid

• 84% do not recall tick bite

DIAGNOSIS OF LYME DISEASE

Standard two-tiered testing (STTT)

Enzyme Immunoassay

(EIA)

IgM and IgG

Immunoblot

Acute sample

(clinical presentation

≤ 30 days)

IgG Immunoblot

only

Negative

result

Travel history to

Europe

Consider alternative

diagnosis

OR

If signs/symptoms

consistent with Lyme

disease persist, submit a

single follow-up

sample 3 – 6 weeks later

Positive or

Equivocal

result

Convalescent sample

or

(clinical presentation ≥ 30 days)

European

Immunoblots

First

Test

Second

Test

Performance of Serology Depends On The

Stage Of The Disease

* Sera obtained after abx treatment

Molins et al 2014 JCM 52:10

Lyme Disease SerologyTwo Tier Testing

• Performance of testing depends on the stage of illness

– early-poor ; late-good

• Diagnosis of Early Localized infection is a predominantly clinical

• Western blots can not be used independent of EIAs

– IgM western blots have poor specificity. Only diagnostic if used in first 6 weeks of infection

– European species can be falsely negative on NA WB – Travel history is important

Aguero-Rosenfeld and Wormser, 2015. Exprt Rev Mol Diagn 15:1-4DeBiasi. 2014. Curr Infect Dis Rep 16:450-455

Alternative Methods can Lead to Spurious Results

• Fallon et al., 2014. Clin Infect Dis 59(12):1705–10• In-house laboratory criteria for a positive IgM WB at Specialty Laboratory B were ≥2 of the following bands: 23–25, 31, 34, 39, 41, 83/93. Criteria

for a positive IgG WB were ≥2 of the following bands: 23–25, 31, 34, 39, 41, 83/93.

LD - Diagnostic Challenges

• Poor performance of serology in early infection

• Turn Around Time can be prolonged

• Seroconversion may not occur with early treatment

• No test of cure –

• serology can persist for a decade

• Diagnosis of re-infection is a challenge

• Influence of biodiversity needs to be explored further

• No current diagnostic testing for PLDS

Negative

result

Positive or

Equivocal result

EIA 1 EIA 2

Negative

Positive or

Equivocal

result

Second Test

Consider alternative diagnosis

OR

If signs/symptoms consistent with Lyme

disease persist, submit a single follow-up

sample 3 – 6 weeks later

First Test

Modified Two Tier Testing (MTTT)

FDA approves MTTT

Treatment

https://novascotia.ca/dhw/CDPC/documents/statement_for_managing_LD.pdf

Spectrum App

Lyme Disease - Treatment

Adults (IDSA/NICE guidelines)

• Early local & disseminated (no neuro or 3ºAV block):

– doxycycline/amoxicillin 14-21d

• Meningitis, radiculopathy, late CNS, 3ºAV block

– IV* ceftriaxone/cefotaxime/penicillin 14-28d

• CN VII Palsy: PO doxy (unless coexistent meningitis)

• Arthritis

– doxycycline/amoxicillin 28d

• Persistent or recurrent arthritis

– doxycycline/amoxicillin another 28d or IV* 2-4w

• Late CNS: IV* ceftriaxone/cefotaxime/pen 2-4 w

Children <8 years (Red Book)

• Early localized disease:

– Amoxicillin 50 mg/kg per day, orally, divided into three doses (max 1.5g/day) for 14.

– For children allergic to penicillin, cefuroxime 30 mg/kg per day, orally, in two divided doses (maximum 1g/day) for 14 days.

• Macrolides (erythromycin and azithromycin) are less effective.

• Early disseminated and late disease:

– multiple EM: as above for 14 days

– isolated facial palsy: Doxycyline 4.4mg/kg/day x 14 d

– first episodes of arthritis: as above for 28 days

– For persistent arthritis, carditis, and meningitis/encephalitis: same drugs as for adults using pediatric dosing (14-21 days.

• CID 2006; 43:1089-134• https://novascotia.ca/dhw/cdpc/documents/statement_for_

managing_LD.pdf

Lyme Disease - Prophylaxis

When to consider

1. The attached tick is a BLT attached for ≥ 36 h Prophylaxis can be started within 72 h of removal

2. Exposure to an area where rate of infection of these ticks with B. burgdorferi is ≥ 20%– the purposes of prophylaxis, physicians may

wish to consider higher and medium risk areas to have tick infection rates in this range.

3. Doxycycline is not contraindicated.

What to use

• Adults (including pregnant women) and children of any age:

• SINGLE DOSE doxycycline 200 mg po(4.4mg/kg for patients < 45kg)

Post Treatment Lyme Disease Syndrome

(PTLDS)

Patients with Lyme Disease improve with

time

• 101 patients in natural history study

• Followed for 3.9 yrs (0.5 – 11.3 yrs)

Physical health scores Mental health scores

US pop

Wilis et al. 2016 Clin Infec Dis. 1546 -1551

PTLDS - What Is It

• 10-15% develop Post Treatment LD Syndrome (PTLDS) after treatment

– Documented LD

– Patient Reported Symptoms

• fatigue, widespread musculoskeletal pain, and/or complaints of cognitive difficulties.

• continuous or relapsing for at least 6 months after initial treatment

– Functional impairment

• must be severe enough to reduce the patient’s functional ability

– Exclusion of other somatic or psychiatric causes of symptoms.

(Wormser et al., 2006 )

Aucott et al., International Journal of Infectious Diseases 17 (2013) e443–e449)

Antibiotics have no effect on

PTLDS

• 5 randomized trials for antibiotics in PTLDS

• 3 trials no significant difference between Abx / Placebo (Klempner et al., N

Engl J Med 2001; 345:85–92; Berende et al., N Engl J Med 2016; 374:1209–1220)

• 1 had improvement in fatigue from 1-6 months but no change in

cognition (Krupp et al., Neurology 2003; 60:1923–30)

• 1 had initial improvement in cognition at 12 weeks but no

difference between placebo at 24 weeks (Fallon et al., Neurology 2008; 70:992–

1003)

• Side effects are common – up to 26% in Fallon et al. 2008

• Reviewed in Klempner et al., Am J Med 2013; 126:665–669.

Is Lyme Chronic?

• The patient suffering is real an can be debilitating

• What is causing them is not clear

• IDSA assessment that there is “no convincing biologic

evidence for the existence of symptomatic chronic B.

burgdorferi infection among patients after receipt of

recommended treatment regimens for Lyme disease”.

Symptoms attributed to Lyme disease based on alternative

serologic criteria, clinical criteria alone

• Alternative Serology - Not CDC / CPHLN criteria

• Clinical Criteria - Horowitz questionnaire

1. Unexplained fevers, sweats, chills, or flushing

2. Unexplained weight change; loss or gain

3. Fatigue, tiredness

4. Unexplained hair loss

5. Swollen glands

6. Sore throat

7. Testicular or pelvic pain

8. Unexplained menstrual irregularity

9. Unexplained breast milk production; breast pain

10. Irritable bladder or bladder dysfunction

11. Sexual dysfunction or loss of libido

12. Upset stomach

26. Eyes/vision: double, blurry27. Ears/hearing: buzzing, ringing, ear pain28. Increased motion sickness, vertigo29. Light-headedness, poor balance,

difficulty walking30. Tremors31. Confusion, difficulty thinking32. Difficulty with concentration or reading33. Forgetfulness, poor short-term

memory34. Disorientation: getting lost; going to

wrong places35. Difficulty with speech or writing36. Mood swings, irritability, depression37. Disturbed sleep: too much, too little,

early awakening38. Exaggerated symptoms or worse

hangover from alcohol

13. Change in bowel function

14. Chest pain or rib soreness

15. Shortness of breath or cough

16. Heart palpitations, pulse skips, heart block

17. History of a heart murmur or valve prolapse

18. Joint pain or swelling

19. Stiffness of the neck or back

20. Muscle pain or cramps

21. Twitching of the face or other muscles

22. Headaches

23. Neck cracks or neck stiffness24. Tingling, numbness, burning, or stabbing sensations25. Facial paralysis (Bell’s palsy)

Patients Have Significant Deficits But Are

Phenotypically the Same as CFS

• CFS and ALD both had significant functional impairment

by standardized measures compared to controls

• No difference between CFS and ALDPatrick et al., 2015 Clin Infect Dis (2015) 61 (7): 1084-1091

•BC Complex Chronic Disease Study

Approach To The Patient With Persistent

Symptoms

• Assessment:

– Recognize that their symptoms and suffering are real.

– Complete history and physical examination.

– Some objective measurement of cognition can be helpful to assess the

patients function as well as assessing for affective disorders.

– Look for potential mimickers.

• (eg. depression, fibromyalgia, sleep apnea, endocrine abnormalities

such as hypothyroidism)

– Investigations based on differential diagnosis.

We Need Evidence Based Approach

Clin Infect Dis. 2015 Jun 15;60(12):1776-82.

• Patients spend thousand of dollars on unproven therapies

Prevention

• White clothes make them easier to see

• Tick repellants

– DEET / Permethrin-containing products

• Frequent tick checks

CDC

Removal of Ticks

• Use fine–tipped tweezers (forceps)

• Grasp the tick as close to the skin’s surface as possible

• Pull upward with steady, even pressure

• Do NOT twist or jerk

• Clean the bite area

• AVOID folklore remedies (nail polish, petroleum jelly, heat)

Key Messages

• Prevent/remove BLTs – No tick No Lyme

• Think about Lyme disease in your differential in NS

• Early Infection is a clinical diagnosis

– circular rash in an unusual site for cellulitis (torso, neck, stomach)

– Unsure if tick reaction – follow to see if the rash expands

• Serology poor in early localized infection – Good in late infection

• No evidence to support prolonged antibiotic therapy