Tick-Borne Diseases

Stephen J. Gluckman, M.D.

Tick-Borne Diseases

Lyme Disease Babesiosis Ehrlichiosis “Tick Typhus”

Rocky Mountain Spotted Fever

African Tick Typhus

Tularemia Relapsing fever Powassan Tick Paralysis STARI

An adult female Ixodes scapularis (blacklegged tick)

An adult female Dermacentor variabilis(American dog tick)

An adult female Amblyomma americanum(lone star tick)

Lyme DiseaseClinical Presentations

A few things to clarify Erythema migrans Carditis

Transient heart block Myocarditis

Neurological VII CN palsy Aseptic meningitis Radiculoneuritis Lyme Encephalopathy

Rheumatologic Acute pauci-articular arthritis

Where Do You See Lyme Disease?

Throughout the world

National Lyme Disease Risk Map with Four Categories of

Risk

(CDC)

Borrelia BurgdorferiB. burgdorferi is not from Mars

B. Burgdorferi is not from another dimension

B. Burgdorferi is just another bug

How Big is the Ixodes Tick?

1-2 mm

Ixodes Ticks

Diagnosing Erythema Migrans

ANY LARGE RED PATCH WITHOUT ANOTHER EXPLANATION IS ERYTHEMA MIGRANS

EM or Tick Bite Reaction?

EM Tick Bite

Incubation 7-10 days Hours

Local Symptoms Rare Pruritus

Size > 5 cm Small

Expands Over Days Over Hours

Resolves Over Weeks Over Days

Systemic Symptoms

Common Rare

Erythema Migrans

Things to remember It is a clinical diagnosis, not a laboratory

diagnosis It is NEVER an emergency “Target” lesion only occurs in 30%

Any big red patch is EM unless you have another explanation

Lyme Disease and VII CN Palsy

Differential Diagnosis HSV (was idiopathic) HIV Herpes Zoster Local Infection/Trauma/Tumor Sarcoidosis Lyme

More likely with: preceding or present erythema migrans

Lyme Disease and VII CN Palsy

Should you treat empirically? Tick time of year Potential tick exposure Bilateral

“Diagnosis” Lyme Serology

Lumbar Puncture?

Lyme Radiculoneuropathy

Differential Diagnosis Diabetes Herpes zoster (sine herpete) Herniated disc Collapsed Vertebral body Syphilis

Case 45 year old who has had several years of

“low grade” fevers, painful lymph nodes, scratchy throat, and mental cloudiness

He has been treated with oral doxycycline, azithromycin, and paromomycin.

He has also been treated with three courses of IV ceftriaxone totaling 5 months He has had line related of Staphylococcus

aureus bacteremia and ceftriaxone induced acute cholecystitis

Is this resistant neuroborreliosis?

LYME ENECEPHALOPATHY

TO DIAGNOSE NEED BOTH Objective evidence of neurological disease Objective evidence of B. burgdorferi in the

CNS Lack of response related to:

Incorrect diagnosis Impatience Permanent damage

When Should One Think of Lyme Arthritis?

Monoarticular or pauciarticular Typically knee Differential Diagnosis: septic, crystal,

rheumatoid, Reiter’s Class II fluid Arthralgias can be part of early Lyme

Disease, but they are usually associated with EM and do not become chronic

Major Clinical Error

Chronic fatigue, chronic diffuse aching, recurrent sore throats, lymphadynia, and “low grade” fevers are not symptoms of active Lyme disease.

Lyme Serology

Misunderstandings about the use of serological testing for Lyme disease is the primary reason for the misunderstanding of this relatively uncomplicated infectious disease. “Real” Lyme disease is generally easy to

diagnose and treat Diseases misdiagnosed as Lyme disease are not

There is NO TEST for Lyme Disease

Interpreting Lyme Serology

What is a positive test? Positive screening by ELISA or IFA plus a

positive western blot What is a negative test?

Negative screening or positive screening with a negative Western Blot

(2nd National Conf. on Serol Dx of LD MMWR 1995;4:590)

What is a positive western blot?

An IGM Western Blot is considered positive if 2 of 3 specific bands are present.

An IGG Western Blot is considered positive if 5 of 10 specific bands are present.

Otherwise they are negative AND a positive screening serology with a negative WB is a negative test.

Other Diagnostic Tests

Culture Low sensitivity, high specificity

Unapproved tests PCR on blood or urine Urinary Antigen Testing Borreliacidal Antibody Test (Gundersen test) Immune Complex Disruption T-cell Proliferative Response

Common Testing Errors

Not establishing a true positive test Not understanding that a positive serology does

not mean disease Treating to eliminate antibodies

Antibodies persist and vary in titer Treating a positive IgM alone: IgM may persist

and is not helpful in disease beyond 1 month Believing that a false negative test is frequent:

False negatives are very rare other than in EM Treating on the basis of an unestablished test

So, what is the consequence of misunderstanding the serology?

THE CREATION OF MYTHS An entire syndrome (disease?) has been

created that does not exist

A belief that the serology is not good.

A belief that Lyme disease is difficult to treat.

How Good is the Treatment of Lyme Disease?

VERY GOOD

There Rarely is a Reason to Retreat a Patient

Lyme Disease Treatment

Oral Doxycycline 100 mg BID Amoxicillin 500 mg TID Cefuroxime axetil 500 mg BID

Parenteral Ceftriaxone 2 gm IV daily Cefotaxime 2 gm IV Q8H

Lyme Disease Treatment

Erythema migrans Oral x 10-21 d

VII cranial nerve palsy Oral x 14-21 d

Acute meningitis Parenteral x 14-28 d (can finish with oral)

Cardiac 1st or 2nd degree block: Oral x 14-21 d 3rd degree block or myocarditis: parenteral x 14-21 d

Lyme Disease Treatment

Arthritis Oral x 28 d

Encephalopathy Parenteral x 28 d

Neuropathy Parenteral x 28 d

Persistent arthritis after two courses of therapy or other chronic symptoms Symptomatic therapy

What About the Newer Antibiotics for Lyme Disease

There is no advantage for azithromycin, clarithromycin, cefixime, cefuroxime, etc….

Do Not Use Them!

LYME DISEASEConcept Summary

23 year old with 4 months of diffuse aching and fatigue.

Lyme serology: EIA (+)IgG Western Blot: 2 bandsIgM Western Blot: 1 band

Is this Lyme disease?

NO

LYME DISEASEConcept Summary

41 year old who has had difficulty remembering names for the past several years.

Lyme serology: EIA: (-) Western blot IgG (-)

Western blot IgM (+)Is this Lyme disease?

NO

LYME DISEASEConcept Summary

35 year old who presented several months ago with typical rash of erythema migrans.

Treated with 3 weeks of doxycycline Rash resolves after 4 days, but she continues with malaise and

diffuse myalgias Repeat testing:

Lyme serology: EIA (+)Western blot IgG (+)IgM (+)

Does this patient need more treatment?

NO

LYME DISEASEConcept Summary

31 year old with the non-pruritic, non-painful skin lesions seen on the following slide.

Lyme serology: EIA (-)Western blot IgG (-)Western blot IgM (-)

Does this patient have Lyme disease?

YOU BETCH

A

Babesiosis What is it?

An intracellular protozoan parasite Where is it?

Northeast (Northwest)

What is the clinical syndrome? “FLU” – like: fever, chills, headache, fatigue

Hemolytic anemia Serious especially in asplenic persons Relapses can occur - especially in immunosuppressed

persons

BabesiosisDiagnosis and Treatment

Diagnosis Peripheral blood smear PCR on blood Serology has the same problems as that for Lyme

disease. A positive test does not mean disease. Don’t treat a positive test; treat a person with a

positive test an a compatible clinical syndrome

Treatment Quinine and Clindamycin Atovaquone and azithromycin

Babesiosis

Ehrlichiosis and Anaplasmosis

What are they? Rickettsiaceae family

Human Monocytic Ehrlichiosis (HME) Lone star tick

Human Granulocytic Anaplasmosis (HGA) Ixodes ticks

Where is it? Everywhere

Human Monocytic Ehrlichiosis

E. chaffeensis First described in 1987 Primarily infects mononuclear cells Reservoir: deer, dogs, goats Vector: Lone star tick (Amblyomma americanum)

Human Granulocytic Anaplasmosis

First described in 1994 Organism recently named Anaplasma

phagocytophilum. Reservoir: deer, rodents, elk Vector: Ixodes ticks

Ehrlichiosis and Anaplasmosis

SIGNS AND SYMPTOMS Incubation period: 5 - 10 days Early symptoms are non-specific (“flu-like”)

Fever, headache, myalgias GI symptoms can occur Rash variable

Laboratory Leucopenia, thrombocytopenia, abnormal

liver enzymes

Ehrlichiosis and Anaplasmosis

COMPLICATIONS Can be very severe

Renal failure ARDS DIC Encephalitis

3% mortality Worse in patients with impaired host defenses Watch out for dual or triple infections with

Borrelia burgdorferi and Babesia

Ehrlichiosis and Anaplasmosis

DIAGNOSIS Peripheral smear looking for morulae Serology PCR (state laboratories) Culture Treat based on epidemiologic and clinical

clues. Do not delay while waiting for confirmation.

Ehrlichiosis and Anaplasmosis

Morulae

Ehrlichiosis and Anaplasmosis

TREATMENT Treatment should not be delayed until

laboratory confirmation is obtained Doxycycline: 100 mg PO/IV

Until 3 days after fever abates Expect response in 24 - 72 hours

Pregnancy and children ??? Rifampin 600 mg IV/PO has been used

Rocky Mountain Spotted Fever

Clinical Spectrum from mild to fulminant Throughout the Western Hemisphere Vector: Dermacentor

Dog or Wood Ticks

Rocky Mountain Spotted Fever

Rocky Mountain Spotted FeverClinical Manifestations

Incubation Period: 3 - 14 days (ave 5 - 7) Non-specific

Fever Headache Myalgias GI

Rash Mortality about 25% if treatment delayed

Rocky Mountain Spotted FeverRash

Begins on day 3 - 5 Only 15% have a rash on the first day 10% never get a rash

Do not wait for a rash to initiate therapy Starts on ankles and wrists Spreads centrally and to palms/soles

                     

Rocky Mountain Spotted FeverDiagnosis

Initially made clinically on suspicion and epidemiology

Serology Used to confirm diagnosis Takes at least 10-14 days to seroconvert

Skin biopsy Rapid, if available (requires special stains) 70% sensitive

Rocky Mountain Spotted FeverTreatment

Can not overstress the importance of early therapy Mortality related to when treatment initiated

< 5 days 6.5%> 5 days 22.9% (most saw a physician

within the first five days) Doxycycline for adults and children Chloramphenicol is the alternative

Tick Typhus

Throughout the world All have rashes

Typically on trunk Most with tick bite site eschar

All diagnosed serologically All treated with doxycycline Consider the diagnosis in a febrile returning

traveler

Tick Typhus

STARI“Southern Tick-Associated Rash Illness”

Rash similar to erythema migrans in persons living in the SE USA First reported in 1996 and organism identified

in 2001 Different vector than Lyme disease

Amblyomma rather than Ixodes Same life cycle and ecology

Different pathogen Borrelia lonestari (?)

Amblyomma americanum “Lone Star” Tick

STARI“Southern Tick-Associated Rash Illness” Distribution of Lone Star Ticks in the USA

STARI“Southern Tick-Associated Rash Illness”

Diagnosis Unable to culture at this time PCR on biopsy of rash Lyme disease serology is negative

Treatment ? Doxycycline

Sequellae None known to date

Managing a Tick Bite

You get a phone call at 5:30 on a Friday evening from a patient who says that he just found a tick behind the ear of his wife. They ask: How should they remove it? Should she get antibiotics?

Removing a Tick

Do not use Vaseline, kerosene, matches, gasoline

Use a hemostat or forceps and grasp tick as close to the skin as possible

Pull back gently and firmly perpendicular to the skin

Don’t squeeze or crush Don’t worry about residual mouth parts

Antibiotic ?

Need to address three questions Type of tick? Attached or engorged? Duration of attachment?

Prophylactic antibiotics generally not indicated

SINGLE DOSE DOXYCYCLINE? If:

> 8 years old Attached tick was nymph or adult Ixodes

scapularis Attached for at least 36 hours Prophylaxis can be started within 72 hours of tick

removal Local prevalence of Lyme disease is > 20% No contraindication to doxy

Otherwise observation alone is recommended

Questions?