1

Tick-Borne Diseases and Update

Melissa Kemperman, MPHMinnesota Department of Health

Acute Disease Investigation & Control

Essentia HealthEssentia HealthHot Topics in Pediatrics Conference

Duluth, MNApril 20, 2012

Objectives

• Identify signs and symptoms of tick-borne diseases (TBDs)

• Explain regional endemicity of TBDs, including emerging diseases and incidence

• Describe available testing for TBDs and appropriate use of testing

• Identify practical approaches for diagnosis and• Identify practical approaches for diagnosis and treatment of the patient with a possible TBD

• Summarize current guidelines on prevention and treatment of TBDs

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Audience Response System:Case Presentation

• In June, a previously-healthy 10-year-old girl i it li i ith 2 d hi t f fvisits your clinic with a 2-day history of fever,

muscle aches, fatigue, and headache

• She lives on a wooded property near Cloquet, Minnesota (MN), where her family notices a lot of “deer ticks or wood ticks”

• Her mom asks whether you can test her for Lyme disease

Audience Response System:Case Presentation (cont.)

What tick-borne disease/s would you consider most strongly in this patient?

1. Lyme disease

2. Babesiosis

3. Human anaplasmosis

4. Human ehrlichiosis

5. Rocky Mountain spotted fever (RMSF)

6. Powassan (POW)

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Audience Response System:Case Presentation (Discussion)

What tick-borne disease/s would you consider most strongly in this patient?

Febrileillness

Affects children

Endemicto MN

Lyme X X X

Babesiosis X (rarely) X

Anaplasmosis X (rarely) X

Ehrlichiosis (EML) X (rarely) X

Ehrlichiosis (E. chaffeensis) X (rarely)

RMSF X X X (rare)

POW X X X (rare?)

Ticks of Concern in Minnesota (MN) and the Upper Midwest

4

N h

Blacklegged Tick(“Deer Tick”)

Ixodes scapularis

Nymph

Adult(female)

Larva

Blacklegged Tick (Deer Tick)Nymphy p

5

Blacklegged Tick Habitat

Minnesota Biomes

C if

TallgrassAspen

Coniferousand Mixed Forest

pParkland

Minneapolis-St. PaulMetropolitan Area

Duluth

PrairieGrassland

DeciduousForest

Modified from Minnesota DNR, http://www.dnr.state.mn.us/biomes/index.html

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Blacklegged Tick (Deer Tick) Distribution in the United States

http://www.cdc.gov/ncidod/dvbid/lyme/tickmap.htm

Seasonality of Ixodes scapularisHost-Seeking Activity

ADULT FEMALE

NYMPH

Images and Graph modified from American Lyme Disease Foundation, http://www.aldf.com/deerTickEcology.shtml

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Engorged Blacklegged Tick(Deer Tick)

MDH

Diseases from Blacklegged Ticks(Deer Ticks) in MN

DISEASE AGENT TYPE OF AGENT

Lyme disease Borrelia burgdorferi Bacterium (spirochete)

Babesiosis Babesia microti,

Babesia spp.

Protozoan

Human anaplasmosis (HA)

Anaplasma phagocytophilum

Bacterium (Rickettsial)anaplasmosis (HA) phagocytophilum

Human ehrlichiosis(HE)

Ehrlichia muris-like (EML) agent

Bacterium (Rickettsial)

Powassan Powassan virus Virus

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Transmission of Disease Agents from Blacklegged Ticks to Humans

• Bacterial or protozoan

– Must be nymph or an adult female

– Must be attached for a long time

• 24-48 hours (Lyme disease)

• 12-24 hours (anaplasmosis)

P i• Powassan virus

– Might be transmitted by all tick stages

– Transmission time <15 minutes in mice

Other Tick Vectors and Potential Tick-Borne Diseases (TBDs) in MN

TICK DISEASE AGENT

American dog tick Rocky Mountain RickettsiaAmerican dog tick

(Dermacentor

variabilis)

-Very common

in MN

Rocky Mountain spotted fever (RMSF)

Rickettsia rickettsii

Lone star tick Human EhrlichiaLone star tick

(Amblyomma

americanum)

-Not common

In MN, but isolated

specimens have been found

Human ehrlichiosis

(HE)

Ehrlichiachaffeensis

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I just got bit by a tick!

Question from Your Patient

j g yCan I get doxycycline to prevent Lyme disease?

. . .

Prophylaxis for Lyme Disease Following a Tick Bite: Questions

• What kind of tick?

• How long was tick attached?

• How long ago did you remove the tick?

• Where did patient acquire the tick?

• What is this patient’s age and contraindications to doxycycline?doxycycline?

• How effective is this against Lyme disease?

• Will this protect against other tick-borne diseases?

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Tick Bite Prophylaxis

• 200-mg dose of oral doxycycline, when

– Tick is a blacklegged tick (deer tick)

– Tick was attached at least 36 hours

– Doxycycline can be started <72 hours after removing tick

– 20% or more of local ticks infected

– Patient is adult or child 8 years of age

• 87% efficacy in preventing Lyme disease (NEJM 2001;345:79-84)

• Only studied for Lyme disease

Tick-Borne Diseases (TBDs) to Consider in Minnesota (MN) and

the Upper Midwest

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Lyme Disease

• Agent: Borrelia burgdorferi

• Stages

– Early localized (3-30 days after infection)

• Erythema migrans (EM rash)

– Disseminated

• Early (days to weeks after infection)

• Late (months after infection)

Early and LateDisseminated Lyme Disease

• Multiple EM lesions

• Constitutional signs and symptoms

• Lyme carditis (usually AV block)

• Neuroborreliosis

– Peripheral nervous system (e.g., Bell’s palsy, di l th )radiculopathy)

– Central nervous system (e.g., meningitis)

• Lyme arthritis (large joints; intermittent)

• Severe fatigue

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Erythema Migrans (EM)

Lyme Arthritis

• Large joints, especially the knee

• Intermittent

• Usually not painful or red (may be hot)

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Audience Response System:Case Presentation

• You examine the 10-year-old girl who came to ith 2 d f b il illyou with a 2-day febrile illness

• Upon examination, you find a 3-inch bulls-eye rash on her abdomen

• Her family first noticed the rash 1-2 days ago and says it has grown in sizey g

• You feel it is consistent with the EM rash seen in Lyme disease

Audience Response System:Case Presentation (cont.)

• What is your next step?

1. Order Lyme disease serology and treat with amoxicillin if test results are positive

2. Order Lyme disease serology and begin treatment with amoxicillin now

3. Do not order any Lyme disease serology and begin treatment with amoxicillin now

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Audience Response System:Case Presentation (Discussion)

• What is your next step?

1. Order Lyme disease serology and treat with amoxicillin if test results are positive

2. Order Lyme disease serology and begin treatment with amoxicillin now

3. Do not order any Lyme disease serology and begin treatment with amoxicillin now

Lyme Disease Diagnosis

• History of exposure to ticks or woods• Serology

Not needed for early Lyme disease with single– Not needed for early Lyme disease with single EM rash; antibodies may not be detectable for 2-3 weeks

– Important for diagnosing disseminated Lyme or illness without EM; if ill >30 days, Western blot IgG should be positive

• PCR– Usefulness limited to joint fluid, if paired with

serology

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Lyme Disease Treatment *• Oral regimen

– Doxycycline (not for children < 8 yrs), amoxicillin, cefuroxime axetil

• Parenteral regimen

– Ceftriaxone (preferred), cefotaxime, penicillin G

• Duration: 2-4 weeks

– Long-term treatment not recommended

* Wormser et al. CID 2006; 43:1089-134

IDSA Guidelines:Recommended Lyme Disease Antibiotics

Refer to paper for footnotes:Wormser et al. CID 2006;43:1089-134

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IDSA Guidelines:Recommended Lyme Disease Therapies

Refer to paper for footnotes:Wormser et al. CID 2006; 43:1089-134

Post-Lyme Disease Syndrome• After proper treatment for objective signs of Lyme

disease• Persistent ( >6 months) subjective symptoms:Persistent ( >6 months) subjective symptoms:

myalgia, arthralgia, fatigue, cognitive difficulties• Not due to active infection with B. burgdorferi• Causes may include:

– Post-infectious inflammatory processCoinfection– Coinfection

– Unrelated process

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“Chronic Lyme Disease”

From Feder et al. 2007. NEJM 357:1422-30.

“Chronic Lyme Disease” (cont.)• Some patients seek long-term or repeated antibiotic

therapy for persistent symptoms attributed to chronic B burgdorferi infectionchronic B. burgdorferi infection

• Interpretation of tests often questionable

• Often lack current or previous objective evidence of Lyme disease

• In 2009, MDH Clostridum difficile surveillance ,detected a C. difficile-associated fatality in a woman receiving prolonged antibiotic therapy for Lyme disease (CID 2010;51[3]:369-70)

* Minnesota Medicine 2008;91(7):37-41

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Babesiosis

Babesia microtiin red blood cell

CDC Pubic Health Image Library

Babesiosis Signs & Symptoms

• Agent: Babesia microti, other Babesia spp.

• Many infections are asymptomatic, especially in young or healthy individuals

• Symptomatic persons can have fever, chills, headache, muscle aches, fatigue, loss of appetite, anemia, low platelets

• Severe infections leading to organ failure and g gdeath can occur (most likely if elderly, asplenic, or otherwise immune compromised)

• Persistent infections can occur in symptomatic or asymptomatic individuals

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Babesiosis Diagnosis and Treatment

• Diagnostic tests

– Ideally order PCR plus either peripheral blood smear or serology

• Treatment

– Milder cases: Atovaquone-azithromycin

– Severe cases: Clindamycin-quinine

M d d bl d ll t f i• May need red blood cell transfusion

• With certain forms of immune compromise, multiple treatment courses may be necessary* *Krause et al 2008. CID 46:370-6

Human Anaplasmosis/Ehrlichiosis

Anaplasmaphagocytophilumi l f hitin vacuole of white blood cell

Dumler et al. 2005.EID 11(12)

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Anaplasmosis versus Ehrlichiosis

• Anaplasmosis (Anaplasma phagocytophilum)

Expected in MN– Expected in MN

– Affects granulocytes (neutrophils)

• Ehrlichiosis (Ehrlichia chaffeensis)

– Affects agranulocytes (monocytes)

– NOT expected in MNNOT expected in MN

• Ehrlichiosis (Ehrlichia muris-like [EML] agent)

– Expected in MN

Anaplasmosis/EhrlichiosisSigns and Symptoms

• Many infections are asymptomatic, especially in young or healthy individualsy g y

• Symptomatic persons have acute onset within 3-21 days after tick bite

– High fever, chills, shaking, severe headache, muscle aches

L hit bl d ll l l t l t l t d– Low white blood cells, low platelets, or elevated liver enzymes

• Severe complications (e.g. organ failure) and death can occur

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Anaplasmosis/Ehrlichiosis Diagnosis and Treatment

• Diagnostic testsOrder PCR plus either peripheral blood smear or– Order PCR plus either peripheral blood smear or serology

– Serologic cross-reactivity occurs between Anaplasma, E. chaffeensis, and EML agent; to differentiate, compare strength of titers or, ideally, order PCR

• Treatment

– Begin empiric treatment with doxycycline for suspect cases while test results pending

– Cases usually improve within 3 days

*Krause et al 2008. CID 46:370-6

Powassan (POW) Disease

• Agent: Powassan virus (POWV), flavivirus closely related to West Nile virus (WNV);

Li II t i (“d ti k i ”) i d b– Lineage II strain (“deer tick virus”) carried by blacklegged ticks

• Manifestations

– Encephalitis or meningitis: of known cases, 10-15% die; half have long-term sequelae

Some infections may cause only febrile illness or be– Some infections may cause only febrile illness or be asymptomatic

• Rarely identified: ~60 cases in N. America, 1958-2010

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POW Diagnosis

• Available tests

– Serology: POWV-specific IgM and IgG

– Molecular: PCR

– Specimens: serum, CSF

• Few laboratories in the U.S. offer POWV testing

St t bli h lth l b C t f Di C t l– State public health labs or Centers for Disease Control and Prevention (CDC)

Audience Response System:Case Presentation

• A 15-year-old boy comes to the emergency i S t b ith 4 d hi t froom in September with a 4-day history of

fever, headache, fatigue, and spotty rash

• His symptoms have worsened over the past day, and he is becoming disoriented

• He had spent August working at a boy scout p g g ycamp and had multiple tick bites

• He has a lumbar puncture; CSF has 75 WBC

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Audience Response System:Case Presentation (cont.)

• You would like to test his serum and CSF for POWV. How do you proceed?

1. Send specimens to a reference lab requesting a POWV test

2. Send specimens to a reference lab requesting a West Nile virus test, which is cross-reactive to POWV

3. Send specimens to the MN Department of Health (MDH) lab, requesting a POWV or arboviral disease test

4. Call MDH to consult on the case

Audience Response System:Case Presentation (Discussion)

• You would like to test his serum and CSF for POWV. How do you proceed?

1. Send specimens to a reference lab requesting a POWV test

2. Send specimens to a reference lab requesting a West Nile virus test, which is cross-reactive to POWV

3. Send specimens to the MN Department of Health (MDH) lab, requesting a POWV or arboviral disease test

4. Call MDH to consult on the case

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Rocky Mountain Spotted Fever (RMSF)

Images: http://www.cdc.gov/ncidod/dvrd/rmsf/Signs.htm

• Agent: Rickettsia rickettsii

• Classic illness: maculopapular or petechial rash, fever thrombocytopenia

RMSF

fever, thrombocytopenia

• Suspect RMSF for patients with this presentation and tick/outdoor exposure

– Note that rash is not always present when fever first arises

• Do not delay treatment with tetracycline if RMSF is suspected, even for young children

– Prognosis and severity markedly worsen if docycycline not started by Day 5 of illness

Images: http://www.cdc.gov/ncidod/dvrd/rmsf/Signs.htm

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Epidemiology of TBDs in Minnesota

Reported Tick-Borne Disease Cases,MN, 1986-2010

(n = 14,923)1,200 Lyme disease

Human anaplasmosis

400

600

800

1,000

um

ber

of

Rep

ort

ed C

ases

Human anaplasmosis

Babesiosis

0

200

400

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year of Report

Nu

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Reported and Confirmed Lyme Disease Cases in Saint Louis County Residents, 2006-2010

200

Met confirmatory surveillance

Reported to MDH

100

150

Nu

mb

er

Met confirmatory surveillancecase criteria

0

50

2006 2007 2008 2009 2010

Year of Report

Human Anaplasmosis: Percent of Total Reported I. scapularis-Borne Diseases Cases,

MN, 1996-201040%

By 2010, about one-third of

20%

30%

Per

cen

t o

f to

tal

bo

rne

dis

ease

cas

es

By 2010, about one third of tick-borne disease reports

statewide were anaplasmosis.

0%

10%

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

Year of Report

tick

-

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Distribution of Lyme Disease Cases by County of Residence, MN, 1996-2010

2006-20102001-20051996-2000

Incidence Rate (cases/100,000 person-years)No Cases >0.0-10.0 >10.0-100.0 >100.0-160.0

Lyme Disease in Wisconsin

Mean annual Lyme disease cases per 100,000 persons by county of residence, 2002-2006

http://www.dhs.wisconsin.gov/communicable/tickborne/lymedisease/graphics/LymeMap.htm

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Vector-Borne Disease Cases by Month of Onset, MN, 1986-2009

F ll

Spring-Mid Summer

Tick-Borne DiseaseMid Summer - Fall

W t Nil Vi

20%

30%

40%

50%

of

Dis

ease

Cas

es

Fall

Tick-BorneDisease

West Nile Virus

0%

10%

20%

Apr May Jun Jul Aug Sep Oct Nov

Month of Illness Onset

Per

cen

t o

Reported Tick-Borne Disease Casesby Age at Onset, Minnesota, 1999-2008

(n = 9,247*)

30%

35%

Cas

es

5%

10%

15%

20%

25%

erce

nt

of

Rep

ort

ed C

0%

0-12

13-1

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70+

0-12

13-1

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70+

0-12

13-1

9

20-2

9

30-3

9

40-4

9

50-5

9

60-6

9

70+

Lyme disease Human anaplasmosis Babesiosis

Age at Onset (Years)

Pe

* Excluding cases with unknown age

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Marshall

Koochiching

Lakeof theWoods

RoseauKittson

Human Ehrlichiosis due to EML Agent:MN, 2009-2011

• 18 cases, 2009-2011

Pine

Aitkin

CassHubbard

Wilkin

Itasca

St. Louis

Cook

Lake

Carlton

Kanabec

MilleLacs

Crow Wing

Morrison

Wadena

Todd

DouglasGrant

Ottertail

BeckerClay

ClearWater

MahnomenNorman

Red Lake

PenningtonPolk

Beltrami

Marshall g

• EML identified by PCR performed by Mayo Medical Labs

Exposed in areas of

Hennepin

Murray

Wash-ing-ton

Le Sueur

Rice Goodhue

NoblesRock Jackson

Martin Faribault FreebornMower

Fillmore Houston

WinonaOlmsted

DodgeSteeleWasecaBlue EarthWatonwanCottonwood

Pipestone

Nicollet Wabasha

DakotaScott

Chisago

Isanti

Brown

Sibley

Carver

WrightMeeker

Kandiyohi

Renville

Redwood

Sherburne

LyonLincoln

Yellow Medicine

Lac Qui Parle

Swift

Big Stone

PopeStevensTraverse

Chippewa

Stearns

Benton

McLeod

Ram-sey

Anoka

• Exposed in areas of MN (grey on map) or Wisconsin endemic for blacklegged ticks and Lyme disease

POW in MN, 2008-2011• 2008-2011: 17 cases (11 in 2011)

• Severity

– 10 encephalitis (1 death), 5 meningitis

– 2 fever

– 41% had sequelae

• Median age 49 years (range, 3 mos – 70 yrs)

• 82% male

• 35% immunosuppressed

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POW Cases by Month of Illness Onset, MN, 2008-2011 (n=17)

Powassan CaseE C ti

POW Cases by Counties of Exposure,2008-2011 (n=17*)

Exposure Counties

0.0

0.1 – 10.0

Lyme Disease Incidence Rate (cases/100,000 person‐years), 2006‐2010

10.1 – 100.0

100.1 – 130.0

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RMSF in MN• Thought to be rare in MN

– Most reported cases have recent travel histories to endemic states or unconvincing illnesses or titersendemic states or unconvincing illnesses or titers

• One PCR-confirmed fatal case reported in 2009 from Minnesota (Dakota County) in a pediatric case with no travel

• Primary vector (dog/wood tick) very common th h t MN i i lthroughout MN in spring, early summer

• Also carried by brown dog tick, which can be in dog kennels year-round

TBD Risk from Blood Transfusions, Minnesota

• Babesiosis: Increased numbers of transfusion-associated cases in recent years in MN and ynationwide

• HA: Two well-documented cases in MN, 2007-2008

• POW: plausible, although no transfusion-acquired cases identifiedacquired cases identified

• No screening of donated blood products performed routinely at this time for TBDs

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Prevention Messages for Your Patients

Avoid Tick Bites

• Be aware of high-risk times and places

• Walk in the center of trails to avoid picking up ticks from brush

• Wear long pants, light-colored clothing, and repellentrepellent

• Perform tick checks

• Control ticks at home

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Use Effective Tick Repellents

• DEET

U d t ith t 30% DEET– Use product with up to 30% DEET

– Apply to skin or clothing

– Focus below the knees

• Permethrin

Apply to clothing only– Apply to clothing only

– Lasts through multiple washings

– Good choice for people outside frequently

CDC: DVBID

Check for Ticks

• Ticks are easier to spot against light-colored clothing than dark clothingthan dark clothing

• Look for ticks while outside and again at home

• Under clothes, ticks tend to attach at points of constriction

• Parents should check young children

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Control Blacklegged Ticks at Home

• Modify landscape

– Remove leaf litter and brush from yardy

– Construct landscape barrier between lawn and woods

• Apply acaricide (pesticide) to low-lying vegetation

Clinical Pearls: Tick-Borne Diseases and Pediatric Patients in MN

• A patient with a classic erythema migrans rash and• A patient with a classic erythema migrans rash and signs/symptoms <30 days should be started on antibiotic treatment for Lyme disease without Lyme disease serology, which is likely to be negative within 2-3 weeks of illness onset

• If a patient with signs/symptoms suggestive of Lyme• If a patient with signs/symptoms suggestive of Lyme disease has been ill for >30 days but the Lyme disease Western blot IgG result is negative, consider etiologies other than Lyme disease

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Clinical Pearls: Tick-Borne Diseases and Pediatric Patients in MN (cont.)

• For patients with history of tick exposure and• For patients with history of tick exposure and spring, summer, or fall onset of central nervous system disease of apparent infectious etiology, consider Powassan virus and submit CSF and serum specimens to the MN Department of Health

Thank You!

• Clinicians

• Infection preventionists

• Clinical laboratory staff

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References• Aguero-Rosenfeld ME et al. Diagnosis of Lyme borreliosis. Clinical Microbiology

Reviews 2005; 1893:484-509.• Chapman AS et al. Diagnosis and management of tickborne rickettsial

diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis—United States. MMWR 2006; 55(RR-4):1-27.

• Dumler JS et al. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. CID 2007; 45:S45-51.

• Ebel GD. Update on Powassan virus: emergence of a North American tick-borne flavivirus. Annu Rev Entomol 2010; 55:95-110.

• Holzbauer SM et al. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. CID 2010;51(3):369-70.

• Kemperman MM et al. Dispelling the chronic Lyme disease myth. Minnesota Medicine 2008; July:37-41.K l P i d l i b b i i i i i d• Krause et al. Peristent and relapsing babesiosis in immunocompromised patients. CID 2008; 46(3);370-6.

• Wormser GP et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. CID 2006; 43:1089-134.

For More Information

Minnesota Department of HealthMinnesota Department of Health

651-201-5414

Melissa.Kemperman@state.mn.us

David.Neitzel@state.mn.usDavid.Neitzel@state.mn.us

www.health.state.mn.us