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Tick Borne Infections

Daniel J Anderson, MD

EpidemiologyEcologyClinical CharacteristicsDiagnosisTreatmentPrevention

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Tick-Borne InfectionsChallenges

Expanding / changing geography of ticks / infections

New infections / newly recognized “old” infections

Newly identified -- new Ehrlichia species 2011

Old infections | new to MN -- Powassan fever, RMSF

Clinical clues that might suggest tick-borne infection

Fever plus [rash, severe headache, mild hepatitis]

low blood cell counts [esp platelets]]

Diagnostic tests -- blood smear, serology, PCR

Daniel J Anderson, MD

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EpidemiologyEcologyClinical

DiagnosisDifferential Diagnosis

Daniel J Anderson, MD

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EPIDEMIOLOGY

Tick Borne Infections - MN/WI

Daniel J Anderson, MD

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Lyme disease

Anaplasmosis

Ehrlichiosis

Babesiosis

Powassan Fever

RMSF (Rocky Mountain Spotted Fever)

Tick Borne Infections - MN/WI

Daniel J Anderson, MD

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Tick Borne Infections - MN

Daniel J Anderson, MD

Lyme1,293 cases in 2010

(21 % increase from 2009)

Anaplasma720 cases in 2010

( > 100 % increase from 2009)

Ehrlichia New species of Ehrlichia reported 2011

Babesia 56 cases in 2010 (31 in 2009)

Powassan(50 cases in all of US 1958-2009 )

6 MN cases 2008 - 20101 MN death from Powassan 2011 (at ANW)

RMSF2000 cases / year in all of US

Sporadic cases in MN1 death in MN 2009

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http://www.health.state.mn.us/divs/idepc/diseases/lyme/highrisk.html

Risk of Tick-borne infection is not uniform throughout the state. The highest risk is central and SE sections

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More Anaplasma than Lyme in Aitkin, Beltrami, Cass,

Crow Wing & Hubbard counties

The risk of different tick-borne infections also is not

uniform throughout the state

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RMSF annualincidence isincreasing

Daniel J Anderson, MD

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Ecology

Tick Borne Infections - MN/WI

Daniel J Anderson, MD

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Ticks <> Diseases

Daniel J Anderson, MD

TICK

Ixodes scapularis

AnaplasmosisLyme disease

BabesiosisPowassan Fever

Ambyloma americanum

EhrlichiosisRMSFSTARI

Tularemia

Dermacentor variabilis Dermacentor andersoni

RMSFTularemia

DISEASEORIGIN

Endogenous

“Imported” (returning from travel)

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Comparison of ticks

Lyme, Anaplasma, Babesia, Powassan

Ehrlichia, STARI, Tularemia, RMSF

RMSF, Tularemia

Daniel J Anderson, MD

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Blacklegged tick (Deer Tick)Ixodes scapularis

Lyme, Anaplasmosis, Babesiosis,& Powassan

Daniel J Anderson, MD

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Lone Star tickAmblyoma americanum

Ehrlichia, RMSFSTARI, Tularemia

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American dog tickDermacentor variablis

RMSF, Tularemia,Human Monocytic Ehrlichiosis

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Brown dog tickRhipicephalus sanguineus

RMSF

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Clinical

Tick Borne Infections - MN/WI

Daniel J Anderson, MD

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Tick Borne IllnessesFever, chills, myalgias, arthralgias

Fever, chills, rash

Fever, chills, CNS findings

(encephalitis / paresis / paralysis / focal findings)

Hepatitis / transaminitis

Leukopenia, thrombocytopenia, anemia

Daniel J Anderson, MD

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Diagnostic Clues / HintsAppropriate Exposure Potential

Suggestive Symptoms

Fever, rash, arthralgias, headache, neurologic findings

Exam

Rash, splenomegaly

Labs

Low peripheral blood cell counts (esp thrombocytopenia)

Mild transaminitis / hepatitis

Blood smear, serologies, nucleic acid based tests (NATs)

CSF analysis

Daniel J Anderson, MD

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Lyme

3-30 days after tick bite (BEFORE fever)Erythema migrans (EM) 70 - 80 % of patients get rash

STARIVery similar to Lyme disease“expanding Bull’s Eye” lesions

RMSF

90 % -- usually 2 - 5 days AFTER feverInitially small pink macules on wrists / anklesLATER petchial

TularemiaSkin ulcer w regional lymphadenopathy

RASH

Daniel J Anderson, MD

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Hgb Platelets LFTs WBC

Lyme Disease

RMSF anemialow

plateletstransaminitis leukopenia

AnaplasmosisEhrlichiosis

Babesiosis

PowassanFever

anemia transaminitisleukopenia

then leukocytosis

Daniel J Anderson, MD

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Lyme Disease

Daniel J Anderson, MD

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LymePathogen. Borrelia burgdorferi (spirochete)

Clinical

EM rash, Bell’s palsy, AV block, CNS, Arthropathy

Co-infection -- ~ 5-10 % with Anaplasma || ~ 2 % with Babesia

Dx

IgM: HGA can cause false + IgM for Lyme

IgM can persist for years (even if no clinical disease)

After 8 weeks, should always have + IgG

Treatment -- no data for prolonged therapy

Prevention -- Doxycycline 200 mg if engorged tick < 72 h after bite

Daniel J Anderson, MD

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Lyme DiagnosisClinical diagnosis (ie no serology needed) if exposure to deer tick AND

Bilateral Bell’s Palsy

III ° AV block or complete heart block [CHB]

Characteristic erythema migrans [EM] rash

Daniel J Anderson, MD

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Daniel J Anderson, MD

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Lyme SerologyCriteria for positive

Western blot IgG ≥ 5 bands

Western blot IgM ≥ 2 bands

Chronology

Early IgM +

After 4-8 weeks

nearly all IgG + (regardless of RST test strain used)

SO, if IgG still negative > 8 weeks illness, then “+ IgM” is false +

IgM

HGA can cause false + IgM

+ IgM can persist for years ... may NOT correlate at all w clinical state

Daniel J Anderson, MD

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Lyme Testing:Unvalidated tests with unproven use

Test assays whose accuracy and clinical usefulness have not been adequately established. Unvalidated tests available as of 2011 include:

• Capture assays for antigens in urine

• Culture, immunofluorescence staining, or cell sorting of cell wall-deficient or cystic forms of B. burgdorferi

• Lymphocyte transformation tests

• Quantitative CD57 lymphocyte assays

• “Reverse Western blots”

• In-house criteria for interpretation of immunoblots

Measurements of antibodies in joint fluid (synovial fluid)

IgM or IgG tests without a previous ELISA/EIA/IFADaniel J Anderson, MD

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Lyme PCR

Most useful for late arthritis if done on synovial fluid

Limited use in CSF

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Lyme Disease Treatment

Oral Therapy for all except neurological / late arthritis or initially for high degree AV block

IV therapy: for meningitis, late arthritis or initially for high degree AV block

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Lyme Disease Rx Duration2-3 weeks for most early infections - tho’ some data suggest 10 days sufficient

2-4 weeks for meningitis / arthritis

4-8 weeks for late arthritis

Prolonged courses of therapy? .

No proven benefit

There are proven adverse consequences (C diff, death, IV clots, ...)

Daniel J Anderson, MD

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Lyme Disease Treatment

Reinfection rate rare (approximately 4 %)

Post Exposure Prophylaxis (PEP) -

single dose doxycycline 200 mg if < 72 hours

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Anaplasmosis

Daniel J Anderson, MD

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Human Granulocytic Anaplasomsis [HGA]

Pathogen Anaplasma phagocytophilum

Clinical

up to 35 % coinfected with Lyme and/or Babesia

fever, chills, headache, myalgia, and malaise,cough, diarrhea, confusion, and lymphadenopathy,

17 % severe multisystem organ failure / SIRS / even death (Lyme does not do this)

rash is not common

Data

leukopenia, thrombocytopenia,

mild hepatitis / transaminitis

Daniel J Anderson, MD

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Human Granulocytic Anaplasomsis [HGA]

Dx

Peripheral blood smear (in WBCs)

30 - 80 % + morulae

seen in granulocytes

Serology

NATs (PCR)

Treatment

Doxycycline (will also cover potential Lyme coinfection)

Daniel J Anderson, MD

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Ehrlichiosis

Daniel J Anderson, MD

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Human Monocytotropic Ehrlichiosis [HME]

Pathogens

E canis / E chaffeensis / / E muris

Clinical

< 50 % with rash (but more often than with HGA)

More common farther south than Anaplasmosis (HGA)

Data -- Lymphopenia, morulae RARE on blood smear (vs HGA)

Dx -- Serology, PCR

Treatment - doxycycline

Daniel J Anderson, MD

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Daniel J Anderson, MD

AnaplasmosisHGA

EhrlichiosisHME

Farther northMN & WI

Farther southIowa & Missouri

~ 50 % morulaeon blood smear

RARELY seemorulae in blood smear

rash is RARErash more common

(though still < 50 %)

serology / PCR blood smear

serology / PCR

doxycycline doxycycline

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Babesiosis

Daniel J Anderson, MD

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Babesiosis

Pathogen Babesia microtii (MN, WI, East coast), B divergens & B duncani in other locations

Clinical

fatigue/weakness/malaise followed within days by fever (>38° C) and one or more of the following: shaking chills, sweats, headache, myalgia, arthralgia, and anorexia

Malaise, myalgia, arthralgia, and shortness of breath differentiate babesiosis from other febrile illnesses

fatigue and malaise persist for several months

Daniel J Anderson, MD

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BabesiosisDiagnosis

Blood smear (in RBCs)

Tetrad of ring forms

“Maltese Cross”

Serology

PCR

Treatment

Mild: atovaquone + azithromycin

Severe: clindamycin + quinine + exchange transfusion

Daniel J Anderson, MD

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Less Common

Daniel J Anderson, MD

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Powassan Encephalitis

Pathogen: Flavivirus

Same viral family as Dengue, Yellow Fever, West Nile

Clinical

50 % w focal neurologic signs / symptoms

Olfactory hallucinations & temporal lobe seizures (DDx Herpes encephalitis)

Daniel J Anderson, MD

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Powassan EncephalitisData

Leukopenia first (the high WBC), thrombocytopenia, transaminitis

CSF lymphocytosis (usually < 100 cells)

MRI => thalamic, basal ganglia lesions

Dx => IgM (serum / CSF) /4 x increase serum IgG

Treatment => supportive

Dx => serologic (some cross reactivity with other flaviviruses (for example Dengue fever)

Daniel J Anderson, MD

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RMSFPathogen Rickettsiae rickettsii

Clinical (2 - 14 day [median 7] incubation)

fever, headache, nausea / emesis / diarrhea

rash usually ~ 3 days AFTER other signs

begins wrists / ankles

Data

thrombocytopenia (sometimes anemia) WBC often nl

coagulopathy, DIC, CXR changes

Dx serology (? PCR on clinical specimens)

Treatment

doxycycline early in course illness

Daniel J Anderson, MD

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Differential

Diagnosis

Tick Borne Infections - MN/WI

Daniel J Anderson, MD

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Differential DiagnosesParalytic illnesses

Polio, Tick Paralysis, Guillain-Barré, Cervical cord lesion

Encephalitidies

Herpes simplex encephalitis (HSE) -- critical diagnosis because of the urgent need for intravenous acyclovir for HSE

Febrile illnesses with rash

Parvovirus B19, Measles, Meningococcal disease, others

Fever with transaminitis

Lyme, HGA, Babesiosis, Acute hepatitis (HBV, HAV, HCV)

Daniel J Anderson, MD

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Diagnosis

Daniel J Anderson, MD

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DiagnosisClinical

Lyme (rash, bilateral Bell’s palsy, III° AV block in o/w healthy pt)

Serological

Lyme, HGA, RMSF, Powassan

Blood / CSF (in CSF only IgM <> indicates local production)

NAT (Nucleic Acid based Tests)

Powassan Fever, HGA, Babesiosis

Blood / CSF

Peripheral Blood Smear evaluation

Babesiosis, HGA, HGE

Daniel J Anderson, MD

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Clinical Summary

Daniel J Anderson, MD

LymeAseptic meningitis

Heart BlockRash, Arthritis

Anaplasma headache, low platelets, hepatitis, renal failure

Ehrlichia Headache, low cell counts, renal failure, hepatitis

Babesia fever, headache, pancytopenia

Powassan Encephalitis

RMSF Fever, severe headache, ... 3 days later rash

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Diagnosis Summary

Daniel J Anderson, MD

LymeClinical (III ° AV block, Bell’s Palsy, EM Rash)

Serology, Lumbar puncture

Anaplasma Blood smear, PCR, serology

Ehrlichia Blood smear, PCR, serology

Babesia Blood smear, PCR, serology

PowassanSerology

supporting evidence by head MRI

RMSF Serology

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Treatment Summary

Daniel J Anderson, MD

Lyme

Anaplasma doxycycline/ azithromycin

Ehrlichia doxycycline / azithromycin

Babesiaatovaquone + azithromycin

(for severe disease clindamyin + quinine + exchange transfuse)

Powassan supportive care

RMSF doxycycline

PO doxycycline / amoxicillin

IV ceftriaxone

2-4 weeks early4-8 weeks late disease /

arthritisno “long term” Rx

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Tick-borne InfectionsTick ecology changing (expanding geography of ticks)

New / Newly recognized infections

Fever, rash, low cell counts (esp thrombocytopenia), transaminitis

New diagnostic modalities (esp NAT-based testing)

Lyme testing (even western blot IgM) not necessarily definitive

Doxycycline -- Rx of choice - Lyme, Anaplasma / Ehrlichia, RMSF

Tick avoidance / prevention is the best

Daniel J Anderson, MD

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Tick RemovalGrab Tick with tweezers close to skin

Pull steadily straight up

Clean area [alcohol, iodine, soap & H20]

Daniel J Anderson, MD

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Daniel J Anderson, MD

Lyme, Babesia, HGAPowassan Fever

RMSF, Tularemia.Human Monocytic Ehrlichiosis

Ticks / Illnesses & Geography

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ReferencesThe Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clin Infect Dis. (2006) 43 (9): 1089-1134 http://cid.oxfordjournals.org/content/43/9/1089.full

National Institue of Allergy and Infectious Diseases. Tickborne Diseases website. http://www.niaid.nih.gov/topics/tickborne/pages/default.aspx