A Clinicians Guide to A Clinicians Guide to Tick Borne Infections Tick Borne Infections

Alan M. SandersAlan M. SandersUpstate Infectious Diseases Upstate Infectious Diseases

AssociatesAssociatesAlbany, N.Y.Albany, N.Y.

Introduction to theIntroduction to theTick-borne Tick-borne DiseasesDiseases

The Vectors The Vectors and and

PathogensPathogens

Human Tick-borne DiseasesHuman Tick-borne Diseases Each of the specific infections are associated Each of the specific infections are associated

with a host of potentially related symptoms, with a host of potentially related symptoms, yet have unique features that should allow yet have unique features that should allow the clinician the opportunity to make:the clinician the opportunity to make: an accurate diagnosis an accurate diagnosis prescribe an appropriate course of prescribe an appropriate course of

antibioticsantibiotics achieve a timely cure in all patientsachieve a timely cure in all patients

Human Tick-borne DiseasesHuman Tick-borne DiseasesIn the United StatesIn the United States

An array of regional tick species in the United An array of regional tick species in the United States are responsible for the transmission of a States are responsible for the transmission of a wide variety of infections to human hosts:wide variety of infections to human hosts:

RickettsialRickettsial Rocky Mountain Spotted FeverRocky Mountain Spotted Fever ( (Rickettsia rickettsiiRickettsia rickettsii)) Human Monocytic EhrlichiosisHuman Monocytic Ehrlichiosis ( (Ehrlichia chaffeensis)Ehrlichia chaffeensis) AnaplasmosisAnaplasmosis ( (Anaplasma phagocytophilumAnaplasma phagocytophilum))

(also known as Human Granulocytic Anaplasmosis HGA)(also known as Human Granulocytic Anaplasmosis HGA) SpirochetalSpirochetal

Lyme DiseaseLyme Disease ( (Borrelia burgdorferiBorrelia burgdorferi)) ParasiticParasitic

BabesiosisBabesiosis ( (Babesia microtiBabesia microti))

Human Tick-borne DiseasesHuman Tick-borne Diseasesin the United States cont.in the United States cont.

TularemiaTularemia ( (Tularemia francesisTularemia francesis) ) STARISTARI – Southern Tick Associated Rash – Southern Tick Associated Rash

IllnessIllness Tick-borne Relapsing FeverTick-borne Relapsing Fever – –

((Borrelia speciesBorrelia species)) NOTE: Bartonella infections have not NOTE: Bartonella infections have not

been proven to be tick - associatedbeen proven to be tick - associated

Human Tick-borne Diseases:Human Tick-borne Diseases:A Focus on the Capital Region of A Focus on the Capital Region of

New York StateNew York State Lyme DiseaseLyme Disease Anaplasmosis Anaplasmosis BabesiosisBabesiosis Human Monocytic EhrlichiosisHuman Monocytic Ehrlichiosis

Update on Update on EpidemiologyEpidemiology

Tick-borne Diseases Tick-borne Diseases in New York State and in New York State and

the Capital Regionthe Capital Region

Lyme and other Tick-borne Diseases Lyme and other Tick-borne Diseases Incidence New York State 2007-11Incidence New York State 2007-11Excludes NYC. 2011 data provisional. Sources - CDC, Excludes NYC. 2011 data provisional. Sources - CDC,

NYSDOH. NYSDOH.

0100020003000400050006000700080009000

2007 2008 2009 2010 2011

Lyme DiseaseOther TBD

Tick-borne Diseases Excluding Tick-borne Diseases Excluding Lyme Disease in New York StateLyme Disease in New York State

2007 2007 (Cases – 452) (Cases – 452) to 2011 to 2011 (Cases – 730)(Cases – 730)Excludes NYC. 2011 data provisional. Sources - CDC, Excludes NYC. 2011 data provisional. Sources - CDC,

NYSDOH.NYSDOH.

0

50100150200250

300350400

2007 2008 2009 2010 2011

AnaplasmosisBabesiosisEhrlichiosis

Capital Region Lyme Disease Capital Region Lyme Disease Reported CasesReported Cases

Albany, Columbia, Greene, Rensselaer, Saratoga Albany, Columbia, Greene, Rensselaer, Saratoga and Schenectady Countiesand Schenectady Counties

0

100

200

300

400

500

600

700

2007 2008 2009 2010 2011

AlbanyColumbiaGreeneRensselaerSaratogaSchenectady

Lyme Disease Lyme Disease

Clinical FeaturesClinical FeaturesDiagnosisDiagnosisTreatmentTreatment

Lyme Disease:Lyme Disease:ObjectivesObjectives

Provide a more sound approach to the Provide a more sound approach to the diagnostic work-up of Lyme Diseasediagnostic work-up of Lyme Disease

Review the current serologic tests, Review the current serologic tests, and their contribution to accurate and their contribution to accurate diagnoses.diagnoses.

Recognize the limited utility of Recognize the limited utility of serologies in a disease that by in large serologies in a disease that by in large depends upon a clinical diagnosis. depends upon a clinical diagnosis.

Clinical Stages of Lyme Clinical Stages of Lyme DiseaseDisease

EARLY LOCALIZEDEARLY LOCALIZED Days to MonthDays to Month post tick bite post tick bite

EARLY DISSEMINATEDEARLY DISSEMINATED Weeks to MonthsWeeks to Months post tick bite post tick bite

LATE LYME DISEASELATE LYME DISEASE Months to YearsMonths to Years post tick bite post tick bite

Early Localized Lyme DiseaseEarly Localized Lyme DiseaseDays – One MonthDays – One Month

ERYTHEMA MIGRANS ERYTHEMA MIGRANS (EM)(EM) May occur in 80% May occur in 80% ““Cellulitis” in an atypical localeCellulitis” in an atypical locale May see a necrotic centerMay see a necrotic center

ASSOCIATED SYMPTOMSASSOCIATED SYMPTOMS Fever Fever Flu symptomsFlu symptoms AdenopathyAdenopathy HeadacheHeadache

Early Disseminated Lyme Early Disseminated Lyme DiseaseDisease

Weeks - MonthsWeeks - Months CARDITISCARDITIS 5% untreated patients5% untreated patients AV blocks/Cardiomyopathy/MyopericarditisAV blocks/Cardiomyopathy/Myopericarditis

NEUROLOGICNEUROLOGIC 15% untreated patients15% untreated patients Lymphocytic meningitis, encephalitis, cranial Lymphocytic meningitis, encephalitis, cranial

neuropathy (III, VI, VII), radiculopathy neuropathy (III, VI, VII), radiculopathy SKINSKIN

Days to weeks after EM with multiple Days to weeks after EM with multiple irregular sized lesionsirregular sized lesions

Disseminated Lyme RashDisseminated Lyme Rash

Late Lyme DiseaseLate Lyme Disease MUSCULOSKELETALMUSCULOSKELETAL

Seen in about Seen in about 10%10% of untreated patients of untreated patients Mono-oligoarticular arthritis - mostly knee(s) Mono-oligoarticular arthritis - mostly knee(s) Expect 20-30K PMN-predominant joint fluid Expect 20-30K PMN-predominant joint fluid May include chronic synovitis or a Baker’s cystMay include chronic synovitis or a Baker’s cyst

CUTANEOUSCUTANEOUS Acrodermatitis chronica atrophicansAcrodermatitis chronica atrophicans Morphea-like lesions (Europe) Morphea-like lesions (Europe)

NEUROLOGICNEUROLOGIC ? incidence? incidence because few cases because few cases Encephalomyelitis (cognitive), peripheral neuropathyEncephalomyelitis (cognitive), peripheral neuropathy

Lyme Disease DiagnosticsLyme Disease Diagnostics Clinical diagnosis with serologic Clinical diagnosis with serologic

confirmation for all stages of Lyme Diseaseconfirmation for all stages of Lyme Disease ELISA screening and Western Blot IgM & IgG ELISA screening and Western Blot IgM & IgG

for confirmation utilizing CDC criteriafor confirmation utilizing CDC criteria C6 antibody testing may assist with C6 antibody testing may assist with

equivocal WB resultsequivocal WB results Fluid analysis for serologic testing and PCRFluid analysis for serologic testing and PCR

Detection in synovial and CSF samplesDetection in synovial and CSF samples

LYME TESTING LYME TESTING SUPPORTIVE – NOT SUPPORTIVE – NOT

DIAGNOSTICDIAGNOSTIC As with most serologic tests, the As with most serologic tests, the pre-test pre-test

probabilityprobability of the disease must be of the disease must be considered. considered.

IDSA and ACP guidelines have both IDSA and ACP guidelines have both concluded that a clinician should NOT test concluded that a clinician should NOT test a patient in whom the assessment does a patient in whom the assessment does not suggest a high likelihood of Lyme not suggest a high likelihood of Lyme (<20%)(<20%)

A positive serologic test does not A positive serologic test does not constitute proof of active Lyme Disease constitute proof of active Lyme Disease without clinical support.without clinical support.

SEROLOGIC TEST FOR LYMESEROLOGIC TEST FOR LYMEA TWO-TIER APPROACHA TWO-TIER APPROACH

FIRST TIER TESTING-FIRST TIER TESTING- ELISA or IFA which ELISA or IFA which are very sensitive (re: false +).are very sensitive (re: false +).

IF A FIRST TIER TEST IS NEGATIVE- NO IF A FIRST TIER TEST IS NEGATIVE- NO ADDITIONAL TESTING IS NEEDEDADDITIONAL TESTING IS NEEDED..

SECOND TIER TESTINGSECOND TIER TESTING – WESTERN BLOT – WESTERN BLOT for both IgM and IgG. Indicated for both for both IgM and IgG. Indicated for both equivocal and positive equivocal and positive ELISA/IFA. ELISA/IFA.

Inter-laboratory variability exists for both Inter-laboratory variability exists for both tests, notably with WB interpretation.tests, notably with WB interpretation.

TIMING OF TIMING OF SEROCONVERSIONSEROCONVERSION

IgMIgM – Will be positive in 1-2 weeks – Will be positive in 1-2 weeks afterafter

a bite/ECM. Therefore, expect a a bite/ECM. Therefore, expect a positive test for positive test for early localizedearly localized (ECM) in (ECM) in only only 20-40%20-40% of patients. of patients.

Most sensitive in early disseminated Most sensitive in early disseminated disease stage (neuritis/carditis) -disease stage (neuritis/carditis) -90%+90%+

IgG IgG – tend to convert from 4-6 weeks – tend to convert from 4-6 weeks after bite/ECM. after bite/ECM.

When Is An IgM WB When Is An IgM WB Helpful ?Helpful ?

Narrow window with early disseminated Narrow window with early disseminated disease (carditis/neuritis) with no rash hx. disease (carditis/neuritis) with no rash hx. High positivity (90%) vs IgG WB (30-40%).High positivity (90%) vs IgG WB (30-40%).

Must reconcile a positive IgM and Must reconcile a positive IgM and negative IgG WB in all other clinical negative IgG WB in all other clinical presentations where timing does not presentations where timing does not support serology and assume a support serology and assume a FALSE FALSE POSITIVEPOSITIVE test test

IgM WB and “Chronic Lyme”IgM WB and “Chronic Lyme” Recognize that CDC guidelines limit the Recognize that CDC guidelines limit the

application of IgM testing to the first month of application of IgM testing to the first month of illness. Misuse/misinterpretation of IgM WB has led illness. Misuse/misinterpretation of IgM WB has led to overdiagnosis of Lyme in pts with other to overdiagnosis of Lyme in pts with other illnesses.illnesses.

When is an exclusive positive IgM WB helpful in When is an exclusive positive IgM WB helpful in cases of chronic complaints – fatigue, myalgias, cases of chronic complaints – fatigue, myalgias, arthralgias, cognitive ?arthralgias, cognitive ?

EVER ?EVER ? NEVER ?NEVER ? CORRECT ANSWER: CORRECT ANSWER: NEVER EVERNEVER EVER

LYME C6 TESTINGLYME C6 TESTINGAnother Second Tier TestAnother Second Tier Test

Steere et al. CID 2008;47:188-95Steere et al. CID 2008;47:188-95Branda et al. CID 2010;50:20-26Branda et al. CID 2010;50:20-26

Another tool in Lyme sero-diagnosis is an IgG Another tool in Lyme sero-diagnosis is an IgG ELISA from the C6 region of the variable ELISA from the C6 region of the variable major protein-like sequence-expressed (VlsE) major protein-like sequence-expressed (VlsE) lipoprotein of lipoprotein of B.burgdorferi B.burgdorferi - Lyme C6. - Lyme C6.

In prospective studies against two-tier In prospective studies against two-tier testing, the C6 ELISA proved to have a high testing, the C6 ELISA proved to have a high sensitivity (100%) of and specificity(96%) in sensitivity (100%) of and specificity(96%) in pts with stage 2 or 3 disease.pts with stage 2 or 3 disease.

EM cases only about 30% sensitive with both EM cases only about 30% sensitive with both methods.methods.

LYME C 6 TestingLYME C 6 Testingin a 2 Tier IgG-only Approachin a 2 Tier IgG-only Approach

Using only C6 test as a Using only C6 test as a second tier test after a second tier test after a positive ELISA screenpositive ELISA screen

C 6 peptide ELISA IgG proved C 6 peptide ELISA IgG proved positive earlier in the positive earlier in the progression of stages of LD progression of stages of LD (Stage 2) in 2 independent (Stage 2) in 2 independent labs.labs.

This approach eliminates the This approach eliminates the need for, and confusion with, need for, and confusion with, IgM testing.IgM testing.

As a “stand alone” test, C6 As a “stand alone” test, C6 had a lower sensitivity (96%) had a lower sensitivity (96%) and specificity (96%) in late and specificity (96%) in late LD than 2-tier testing LD than 2-tier testing

0%10%20%30%40%50%60%70%80%90%

100%

Stage1

Stage2

Stage3

Std. 2 tierC6 2-tierIgM WB

CAVEATS WITH LYME CAVEATS WITH LYME SEROLOGIESSEROLOGIES

Early/appropriate antibiotic therapy may often Early/appropriate antibiotic therapy may often abort a seroconversion.abort a seroconversion.

Background rates of seropositivity in highly Background rates of seropositivity in highly endemic areas maybe higher than 5%.endemic areas maybe higher than 5%.

High rates of p23 band positivity (false+) in the High rates of p23 band positivity (false+) in the general population.general population.

WB are semi-quantitative/subjective –faint WB are semi-quantitative/subjective –faint bands “+”bands “+”

Both ELISA and WB (IgM/IgG) positivity may Both ELISA and WB (IgM/IgG) positivity may persist for 10-20 years. Subsequent infection persist for 10-20 years. Subsequent infection can only be made clinically. 79% had + 2-tier can only be made clinically. 79% had + 2-tier testing when asymptomatic as controls in testing when asymptomatic as controls in prospective study.prospective study.

MISUSE OF LYME MISUSE OF LYME SEROLOGIESSEROLOGIES

There is no serologic “test of cure”, so There is no serologic “test of cure”, so repeated testing after treatment has no repeated testing after treatment has no prognostic utility- simply adds to patient prognostic utility- simply adds to patient anxiety, and repeated courses of anxiety, and repeated courses of antibiotics.antibiotics.

There is no marginal change in WB band There is no marginal change in WB band conversions – ie: declining number of conversions – ie: declining number of bands to monitor response to treatment.bands to monitor response to treatment.

UTILITY and FUTILITY OF UTILITY and FUTILITY OF SEROLOGIC TESTING FOR LYME SEROLOGIC TESTING FOR LYME

DISEASEDISEASE Use serologic studies to support clinical findings of Use serologic studies to support clinical findings of

disease stages.disease stages. Have a clear understanding of seroconversion timing and Have a clear understanding of seroconversion timing and

rates based on large data bases (rates based on large data bases (IDSA GUIDELINES: CID IDSA GUIDELINES: CID 2006;43:1089)2006;43:1089)

Sequential testing may prove useful in evolving cases ie: Sequential testing may prove useful in evolving cases ie: flu sxs/headache (neg. test) followed by flu sxs/headache (neg. test) followed by neuritis/carditis/arthritis.neuritis/carditis/arthritis.

Once serologically positive, future testing for subsequent Once serologically positive, future testing for subsequent infections become futile. Must base dx on clinical findings infections become futile. Must base dx on clinical findings alone.alone.

THERE IS NO TEST OF CURE !THERE IS NO TEST OF CURE !

Early Lyme DiseaseEarly Lyme DiseaseTreatment RecommendationsTreatment Recommendations

Doxycycline or Amoxicillin for 10 Doxycycline or Amoxicillin for 10 to 14 daysto 14 days

Erythema MigransErythema Migrans Disseminated skin lesionsDisseminated skin lesions Early neurologic - cranial neuropathyEarly neurologic - cranial neuropathy

Parenteral Ceftriaxone for 28 daysParenteral Ceftriaxone for 28 days Early neurologic – meningitis/radiculitisEarly neurologic – meningitis/radiculitis

Late Lyme Disease Late Lyme Disease Treatment RecommendationsTreatment Recommendations

Doxycycline or Amoxicillin po for 28 Doxycycline or Amoxicillin po for 28 daysdays

Arthritis Arthritis Recurrent arthritis (see below)Recurrent arthritis (see below)

Ceftriaxone 2 gm IV qdCeftriaxone 2 gm IV qd Central or peripheral nervous system diseaseCentral or peripheral nervous system disease Recurrent arthritis Recurrent arthritis Cardiac diseaseCardiac disease

Treatment Recommendations Treatment Recommendations Secondary and Late Stage Secondary and Late Stage

LymeLyme IV therapy should be reserved for neurologic disease, IV therapy should be reserved for neurologic disease,

cardiac involvement or chronic arthritiscardiac involvement or chronic arthritis Do not expect serologies to become negative with Do not expect serologies to become negative with

treatment. There is no role for sequential testing for treatment. There is no role for sequential testing for cure.cure.

There is no data supporting treatment for longer than There is no data supporting treatment for longer than six weeks.six weeks.

Consequences of prolonged antibiotic therapy Consequences of prolonged antibiotic therapy include:include: Development of resistant bacteriaDevelopment of resistant bacteria C. difficile diarrheaC. difficile diarrhea Cholecystitis (Ceftriaxone therapy)Cholecystitis (Ceftriaxone therapy) Line–associated bacteremia and venous Line–associated bacteremia and venous

thrombosis.thrombosis.

Single Dose Therapy Single Dose Therapy for Tick Exposurefor Tick Exposure

Considered effective therapy to Considered effective therapy to prevent Lyme disease in the following prevent Lyme disease in the following settings:settings: If tick is attached for at least 36 hours - If tick is attached for at least 36 hours -

engorgedengorged If endemic areaIf endemic area If tick bite occurred within 72 hoursIf tick bite occurred within 72 hours

Doxycycline 200 mg PO x 1 doseDoxycycline 200 mg PO x 1 dose

BECOME LYME LITERATEBECOME LYME LITERATEOur Patients Deserve ItOur Patients Deserve It

Clinical Practice Guidelines by IDSA: Lyme, HGA Clinical Practice Guidelines by IDSA: Lyme, HGA and Babesiosis CID 2006:43;1089-1134.and Babesiosis CID 2006:43;1089-1134.

Clinical Appraisal of “Chronic Lyme Disease” Clinical Appraisal of “Chronic Lyme Disease” Feder, et al. NEJM 2007;357: 1422-30.Feder, et al. NEJM 2007;357: 1422-30.

2-Tiered Antibody Testing for Early and Late 2-Tiered Antibody Testing for Early and Late Lyme Disease using IgG Blot with C-6 test> Lyme Disease using IgG Blot with C-6 test> Branda, et al. CID 2010;50:20-26.Branda, et al. CID 2010;50:20-26.

Final Report of the Lyme Disease Review Panel Final Report of the Lyme Disease Review Panel of IDSA. Lantos,et al. CID 2010;51:1-5 of IDSA. Lantos,et al. CID 2010;51:1-5

AnaplasmosisAnaplasmosis

Clinical Features of Clinical Features of Infection and DiseaseInfection and Disease

Human Granulocytic Human Granulocytic AnaplasmosisAnaplasmosis

Cellular PathogenesisCellular Pathogenesis Obligate intracellular organisms that replicate Obligate intracellular organisms that replicate

within phagosomes of host cells (PMN) and within phagosomes of host cells (PMN) and form microcolonies within vacuoles – form microcolonies within vacuoles – MORULAEMORULAE

Anaplasma phagocytophilumAnaplasma phagocytophilum binds binds preferentially to neutrophil surfaces, and preferentially to neutrophil surfaces, and monocytes are resistant due to inability to monocytes are resistant due to inability to bind/uptake.bind/uptake.

Once in neutrophils, Once in neutrophils, AnaplasmaAnaplasma evades evades oxidative killing, and inhibits PMN phagocytosis.oxidative killing, and inhibits PMN phagocytosis.

Anaplasmosis Trends:Anaplasmosis Trends:New York State and the Capital New York State and the Capital

RegionRegion Over the period 2007 through 2011, the Over the period 2007 through 2011, the

number of Anaplasmosis cases reported in number of Anaplasmosis cases reported in NYS rose 1.6 fold, from 205 to 318.NYS rose 1.6 fold, from 205 to 318.

Over the same period, the number of cases Over the same period, the number of cases in the six-county Capital Region rose over 3.6 in the six-county Capital Region rose over 3.6 fold, from 31 to 113. fold, from 31 to 113.

The Capital Region represented only 15% of The Capital Region represented only 15% of NYS cases in 2007, but nearly 37% in 2011.NYS cases in 2007, but nearly 37% in 2011.

The Capital Region accounted for 73% of the The Capital Region accounted for 73% of the total rise in NYS Anaplasmosis cases over total rise in NYS Anaplasmosis cases over this five (5) year period.this five (5) year period.

Anaplasmosis and EhrlichiosisAnaplasmosis and Ehrlichiosis Age Distribution of Cases Age Distribution of Cases

Historically, both Anaplasmosis (HGA) and Historically, both Anaplasmosis (HGA) and Ehrlichiosis (HME) have had the highest age-Ehrlichiosis (HME) have had the highest age-specific incidence in the 60 – 69 and > 70 age specific incidence in the 60 – 69 and > 70 age groups.groups.

Sub-clinical cases most likely exist in the younger Sub-clinical cases most likely exist in the younger age groups, as tick exposures would be more age groups, as tick exposures would be more predictable. Infection clears without treatment.predictable. Infection clears without treatment.

Theoretically, the waning immune status of Theoretically, the waning immune status of healthy, elderly individuals healthy, elderly individuals ( “immunosenescence” ) plays a role in the ( “immunosenescence” ) plays a role in the development of symptomatic disease with both development of symptomatic disease with both HGA and HME.HGA and HME.

Transmission of AnaplasmosisTransmission of Anaplasmosis Anaplasmosis may be transmitted via blood Anaplasmosis may be transmitted via blood

transfusion, vertically maternal-child, and by transfusion, vertically maternal-child, and by direct contact with a slaughtered deer.direct contact with a slaughtered deer.

A review of nine (9) woman who were diagnosed A review of nine (9) woman who were diagnosed and successfully treated during pregnancy and successfully treated during pregnancy (rifampin or doxycycline). (rifampin or doxycycline). CID 2007;45:589CID 2007;45:589

A single perinatal transmission to a newborn was A single perinatal transmission to a newborn was confirmed and successfully treated.confirmed and successfully treated.

Anaplasmosis: Clinical Anaplasmosis: Clinical PresentationPresentation

Fever – otherwise undetermined - Fever – otherwise undetermined - 93%93% Malaise – Malaise – 94 %94 % Headache - Headache - 76 %76 % Myalgias - Myalgias - 77 %77 % Arthralgias – Arthralgias – 46 %46 % Nausea (Nausea (38%38%), Vomiting (), Vomiting (26%26%), ),

Diarrhea (Diarrhea (16%16%)) Rash is Rare – Rash is Rare – 6 % 6 % Yet , in HME – Yet , in HME – 31 %31 %

Anaplasmosis: ComplicationsAnaplasmosis: Complications Rarely, fulminant cases of untreated Rarely, fulminant cases of untreated

Anaplasmosis and HME can occur.Anaplasmosis and HME can occur. Complications may include acute renal failure, Complications may include acute renal failure,

respiratory failure and shock.respiratory failure and shock. Immunocompromised patients, including HIV, Immunocompromised patients, including HIV,

may have a complicated course, especially may have a complicated course, especially with HME.with HME.

Case fatality rates are low. Case fatality rates are low. Anaplasmosis - < 1%Anaplasmosis - < 1% and and HME about 3%.HME about 3%.

AnaplasmosisAnaplasmosis

Laboratory Findings Laboratory Findings and Diagnostic and Diagnostic

TestingTesting

Anaplasmosis in the Capital Anaplasmosis in the Capital RegionRegion

2007 2007 ( Cases - 31) ( Cases - 31) – 2011 – 2011 (Cases – 113) (Cases – 113) Source - NYSDOHSource - NYSDOH

0

10

20

30

40

50

60

2007 2008 2009 2010 2011

AlbanyColumbiaGreeneRensselaerSaratogaSchenectady

Anaplasmosis Laboratory Anaplasmosis Laboratory FeaturesFeatures

Several very suggestive laboratory findings Several very suggestive laboratory findings often bundledoften bundled

Leukopenia Leukopenia Immature neutrophils – Marked left shiftImmature neutrophils – Marked left shift Atypical lymphocytesAtypical lymphocytes ThrombocytopeniaThrombocytopenia Inverse relationship between mean WBC and Inverse relationship between mean WBC and

platelet count and probability of Anaplasmosisplatelet count and probability of Anaplasmosis Rise in LFT’s, notably transaminases and LDHRise in LFT’s, notably transaminases and LDH

Anaplasmosis DiagnosticsAnaplasmosis Diagnostics Peripheral Blood SmearPeripheral Blood Smear to search for to search for

morulae in neutrophils with sensitivity of morulae in neutrophils with sensitivity of 20 – 80% . 20 – 80% . PCRPCR for both Anaplasmosis and HME with for both Anaplasmosis and HME with

sensitivity of 55 - 87%. Expect a drop in sensitivity of 55 - 87%. Expect a drop in sensitivity > 1 week after illness, and also sensitivity > 1 week after illness, and also after treatment onset.after treatment onset.

SerologySerology – selective IFA of ELISA for – selective IFA of ELISA for Anaplasmosis and HME. Look for a rise in Anaplasmosis and HME. Look for a rise in convalescent titer 4 weeks after illness onset.convalescent titer 4 weeks after illness onset.

MorulaMorula

Anaplasmosis TreatmentAnaplasmosis Treatment

Doxycycline 100 bid for at least 3 days after Doxycycline 100 bid for at least 3 days after defervescence, or 7 – 10 days total.defervescence, or 7 – 10 days total.

Chloramphenicol is an option.Chloramphenicol is an option. Rifampin for pregnant women.Rifampin for pregnant women. Quinolones have variable in vitro efficacy.Quinolones have variable in vitro efficacy. American Academy of Pediatrics revised American Academy of Pediatrics revised

guidelines in 1997 and recommends guidelines in 1997 and recommends doxycycline as safe for short-course doxycycline as safe for short-course treatment of tick-borne diseases in children treatment of tick-borne diseases in children of all ages.of all ages.

Anaplasmosis TreatmentAnaplasmosis Treatment Beta-lactam and macrolide agents have no Beta-lactam and macrolide agents have no

efficacy against Anaplasmosis or HME.efficacy against Anaplasmosis or HME. Will see prompt response to treatment in 24 - 48 Will see prompt response to treatment in 24 - 48

hrs. Persistent fever would suggest another hrs. Persistent fever would suggest another diagnosis.diagnosis.

There is no reported relapse after effective There is no reported relapse after effective therapy and no syndrome of chronic disease.therapy and no syndrome of chronic disease.

With objective evidence of concurrent Lyme With objective evidence of concurrent Lyme disease, doxycycline can be trusted to treat both disease, doxycycline can be trusted to treat both infections infections

(10 - 14 days).(10 - 14 days).

BabesiosisBabesiosis

Clinical FeaturesClinical FeaturesDiagnostic TestingDiagnostic Testing

TreatmentTreatment

BabesiosisBabesiosisClinical FeaturesClinical Features

Similar clinical presentation to malaria, but may Similar clinical presentation to malaria, but may range from asymptomatic to fulminant.range from asymptomatic to fulminant.

Most severe in asplenics and Most severe in asplenics and immunocompromised.immunocompromised.

Fevers, chills, sweatsFevers, chills, sweats Myalgias and arthralgiasMyalgias and arthralgias One-fourth of adults, and one-half of children, may One-fourth of adults, and one-half of children, may have asymptomatic infection as evidenced by IgG have asymptomatic infection as evidenced by IgG

serologies.serologies.

BabesiosisBabesiosisLaboratory Features Laboratory Features

AnemiaAnemia Often hemolytic anemiaOften hemolytic anemia

ThrombocytopeniaThrombocytopenia Elevated LFT’sElevated LFT’s NOTNOT the leukopenia and atypical the leukopenia and atypical

lymphocytosis as evidenced in lymphocytosis as evidenced in Anaplasmosis.Anaplasmosis.

Babesiosis Babesiosis Diagnostic TestingDiagnostic Testing

Because of non-specific clinical features, a Because of non-specific clinical features, a specific diagnosis is made via :specific diagnosis is made via : Giemsa staining of thin blood smears to detect Giemsa staining of thin blood smears to detect intraerythrocytic ring-like structuresintraerythrocytic ring-like structures PCR testing of blood is more sensitive than PCR testing of blood is more sensitive than

microscopymicroscopy Antibody testing, with paired convalescent Antibody testing, with paired convalescent

samples 4 - 6 weeks after illness are most samples 4 - 6 weeks after illness are most often positiveoften positive

It is NOT reasonable to make a diagnosis of Babesiosis It is NOT reasonable to make a diagnosis of Babesiosis based solely on serology, without other features of based solely on serology, without other features of disease, especially in an endemic setting with disease, especially in an endemic setting with background of asymptomatic disease.background of asymptomatic disease.

BabesiosisBabesiosisTreatment RecommendationsTreatment Recommendations

AtovaquoneAtovaquone 750 b.i.d. and 750 b.i.d. and AzithromycinAzithromycin 500 mg x 500 mg x 1 followed by 250 mg qd for seven (7) days.1 followed by 250 mg qd for seven (7) days.

Alternative is Clindamycin 600 mg t.i.d. and Alternative is Clindamycin 600 mg t.i.d. and Quinine 650 mg t.i.d.. This may be used in more Quinine 650 mg t.i.d.. This may be used in more severe cases, and immunocompromised.severe cases, and immunocompromised.

Exchange RBC transfusions may have to be Exchange RBC transfusions may have to be considered in cases of high parasitemia ( >10%).considered in cases of high parasitemia ( >10%).

Repeated smears to insure clearance of Repeated smears to insure clearance of parasitemia.parasitemia.

BartonellaBartonella Only 3 of 22 distinct species cause human disease- Only 3 of 22 distinct species cause human disease- B. B.

henselae henselae ,,B. quintana, B.bacilliformisB. quintana, B.bacilliformis Disease states include cat scratch fever, bacillary Disease states include cat scratch fever, bacillary

angiomatosis, endocarditis, peliosis/splenitis (HIV), and angiomatosis, endocarditis, peliosis/splenitis (HIV), and Oroya fever.Oroya fever.

Vectors are unique: Vectors are unique: B.henselae B.henselae (fleas/cat bite-scratch)(fleas/cat bite-scratch) B.quintanaB.quintana (louse), (louse), B.baciliiformis B.baciliiformis (sandflies).(sandflies).

With such a wide array of syndromes and exposures, the With such a wide array of syndromes and exposures, the inclusion of Bartonella disease in a inclusion of Bartonella disease in a chronic fatiguechronic fatigue work-up work-up is not warranted.is not warranted.

There is no evidence of transmission of any Bartonella There is no evidence of transmission of any Bartonella species by tick bite to human (species by tick bite to human (EID Journal v.16 n.3 Mar 2010EID Journal v.16 n.3 Mar 2010))

Therefore, Bartonella infection should not be included in a Therefore, Bartonella infection should not be included in a differential diagnosis of tick borne illnesses at this time. differential diagnosis of tick borne illnesses at this time.

Summary of Tick-borne Summary of Tick-borne DiseaseDisease

Antibody TestingAntibody Testing Recognize that serologic testing for all of the Recognize that serologic testing for all of the

tick-borne diseases is only a useful tool when tick-borne diseases is only a useful tool when well-recognized, clinical and associated well-recognized, clinical and associated laboratory findings are present.laboratory findings are present.

Positive IgG serologies for any of these Positive IgG serologies for any of these diseases are not the basis for diagnosing diseases are not the basis for diagnosing disease, or initiating antibiotic therapy, disease, or initiating antibiotic therapy, especially when no chronic syndrome exists especially when no chronic syndrome exists (Anaplasmosis, Babesiosis, HME).(Anaplasmosis, Babesiosis, HME).

Consider a positive IgG a possible marker of Consider a positive IgG a possible marker of prior exposure, a potential false positive, but prior exposure, a potential false positive, but NOT an exclusive tool to diagnose an active NOT an exclusive tool to diagnose an active infection.infection.