Current Status of Lyme Disease and Co-Infections

Sam T Donta MD

Infectious Diseases

Professor of Medicine (ret)

Introduction/Overview

Diagnosis of Lyme Disease Clinical Aspects

Stages of Lyme Disease Differential Diagnosis of Lyme Disease

Laboratory Diagnosis Routine Bloodwork Lyme Serologic Testing

Adjunctive Studies MRI Brain SPECT scan

Treatment of Lyme Disease

Stages of Lyme Disease Early Lyme Disease Early Disseminated Lyme Disease Late or Chronic Lyme Disease

Early Lyme Disease Tick Bite Rash

Typical Erythema Migrans (EM) Atypical Rash(es)

Diagnosis Clinical Serology

Treatment of Tick Bite Empiric vs waiting for tick results

Double dose doxycycline? 2-3 weeks of doxycycline or amoxicillin?

What to do if tick bite, but no tick Wait to see if symptoms develop? Any value to serologic testing? Double dose doxycycline? 2-3 weeks of doxycycline or amoxicillin?

Early Disseminated Lyme Disease

Clinical Rash “Flu-like” Symptoms

Diagnosis Clinical Serology

Late Lyme Disease Early/Late LD Symptoms/Signs

Bell’s Palsy Meningitis Carditis

Arthritis-Oligoarthritis Encephalopathy Diagnosis

Chronic Lyme Disease Clinical

Major Criteria Fatigue MusculoSkeletal Neurocognitive

Minor Criteria

“Minor” Symptoms & Signs Headaches Eye Symptoms Ear Symptoms Jaw/Tooth Pain Bell’s Palsy Dysequilibrium Dyspnea

Chest/Rib Pains Palpitations Paresthesias Tremors GI Symptoms GU Symptoms Fevers/Sweats

Spectrum of Lyme Disease Generalized Symptoms Neurologic Symtoms/Manifestations Rheumatologic Symptoms/Signs

Chronic Fatigue Syndrome

Definition: New Onset Severe, Unexplained Fatigue >6mo

Other Symptoms (4 of 8) Memory or Concentration Sore Throat Tender Lymph Nodes Muscle Pain Multijoint Pain New Pattern Headache Unrefreshed Sleep Postexertional Malaise>24hrs

Fibromyalgia

Definition: Pain in fibrous tissues & muscles Specific Symptoms:

Pain (widespread)-myalgias, stiffness Fatigue Sleep Disorder Mental Concentration problems Mood Changes Headaches Abdominal Pain/Diarrhea Paresthesias (Numbness, Tingling, Itching Dizziness Facial Rashes Urinary Urgency Fluid Retention

Gulf War Veterans’ Illness

Definition: New Onset Fatigue, Musculoskeletal, and/or Neurocognitive symptoms (2/3) arising after deployment to the Persian Gulf, and persisting >6mo

Specific Symptoms Headaches Sleep Disorder Paresthesias Fatigue Abdominal Pain Sore Throat Arthralgias Diarrhea Cough Myalgias Weight Gain Chest Pain Memory Shortness of Breath Sweats, fevers Concentration Decreased Libido Lymph Nodes Irritability Depression Rashes, sores

Chronic Lyme and Lyme-like Illnesses

Symptom Lyme CFS Fibro GWI Fatigue + + + + Myalgias + + + + Arthralgias + + + + Memory + + + + Confusion + + + + Mood Changes + + + + Headache + + + + Paresthesias + ? + + Sore Throat + + ? + Lymph Nodes + + ? + Sleep Disorder + + + + Abd pain/Diarrhea + ? ? + Urinary Frequency + ? ? ? Fevers/Sweats + + ? + Palpitations + ? ? + Rashes/Sores + ? ? + Weight Gain + + ? +

Etiology of Chronic or “Post-Treatment” Lyme Disease

Persisting Infection Autoimmunity Post-infectious sequelae

Pathogenesis of Symptoms Infection

Where do bacteria go? Do they persist? How do you know if they’re gone?

Mechanisms Neurotoxicity? Borrelia/Host Interaction?

Auto-Immunity Cross-reaction between bacteria and neural

gangliosides? Need for continuing infection?

Damage Other ?, Disease Tolerance

Laboratory Issues

Serologic Tests EIA, ELISA Western Blot

IgM vs IgG in early vs chronic disease-?dysregulation of IgM vs IgG response

Numbers of bands vs specificity of bands Specific bands: 23,31,34,39,83/93

Lymphocyte Stimulation PCR-DNA Culture Spinal Fluid

Serologic Testing CDC Criteria

Surveillance vs Clinical Diagnosis Two-step testing

EIA/ELISA Western Blot-IgM, IgG

Imaging Studies

MRI 15% T2 Signals

Brain SPECT Scan 75% perfusion defects

Brain SPECT Scans in Patients with Chronic Lyme Disease

0

5

10

15

20

25

30

35

40

45

50

TEMPORAL FRONTAL PARIETAL OCCIPITAL PERIVENTRIC OTHER

MILD

MODERATE

SEVERE

Issues Regarding Treatment of Chronic Lyme Disease

In vitro antibiotic sensitivities Antibiotic treatment studies

Beta-lactam antibiotics Tetracyclines Macrolides Others

Klempner/Steere Treatment Trial of Chronic Lyme Disease

Assumptions Equivalence of Doxycycline and

Ceftriaxone Duration of Treatment

Conclusions No analysis of Other Treatment Options ?No need for further Treatment Trials

Doxycycline v Tetracycline

Dose differences 200mg/d v 1500mg/d

Protein Binding differences 90+ protein bound v 40% protein bound

Ceftriaxone Questions Duration of Treatment

1 months v 3-6 months Mechanism of Action

Reconciling in vitro v in vivo observations Antibiotic v Glutamate Receptor

Upregulation

Macrolide Antibiotics inTreatment of Lyme Disease

In vitro activities Resolving lack of in vivo efficacy

Macrolide MICs of B.burgdorferi

Cell Trafficking

Maurin M, Benoliel AM, Bongrand P, and Raoult D. Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the Coxiella burnetii paradigm. J Infect Dis 1992, 166:1097-102.

Inhibition of Acidification

Macrolide Therapy of Chronic Lyme Disease

OUTCOME AT 2 AND 3 MONTHS

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

1 0 0

2 m o 3 m o

< 2 5 %

2 5 - 5 0 %

5 0 - 7 5 %

> 7 5 %

Prior Symptom Duration vs Outcome of Rx

CURE IMPROVEMENT FAILUREPRIOR Sx DURATION

<1 YR 33 (28%) 78 (67%) 6 ( 5%)

1-3 YR 9 (15%) 45 (75%) 6 (10%)

>3 YR 7 (11%) 43 (70%) 11 (18%)

Gender vs OutcomeCURE IMPROVEMENT FAILURE

MALE 27 (32%) 51 (61%) 6 ( 7%)

FEMALE 22 (14%) 115 (75%) 17 (11%)

Other Treatment Issues Vitamin Supplements

B Vitamins Vitamin C

Mineral Supplements Hyperbaric Oxygen Heat

Questions/Future Directions Is there persistent/latent infection?

Where are the bacteria in chronic disease? Where were the bacteria before treatment? Evidence points to intracellular reservoir

Identification of Lyme-specific products for diagnosis and monitoring treatment

Development of New Vaccines Controlled Clinical Treatment Trials

Validation or refutation of other treatment regimens Importance of duration of treatment

Ixodes Tick Co-Infections

Babesiosis Clinical Aspects Laboratory Diagnosis

Ehrlichia/Anaplasma Clinical Aspects Laboratory Diagnosis

Bartonella Clinical Aspects Laboratory Diagnosis