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Lyme Disease and Southern Tick Associated Lyme Disease and Southern Tick Associated Rash Illness (STARI) in Texas:Rash Illness (STARI) in Texas:
What we know; what we need to knowWhat we know; what we need to know
Stephen Waring, DVM, PhDStephen Waring, DVM, PhDAssociate ProfessorAssociate Professor
Epidemiology, Biological SciencesEpidemiology, Biological Sciences
Lyme DiseaseLyme DiseaseEcologyEcology
Lyme Disease:Lyme Disease:EpidemiologyEpidemiology
• Number of cases – US: 1993 - 2007Number of cases – US: 1993 - 2007
Lyme Disease:Lyme Disease:EpidemiologyEpidemiology
• Number of cases – Texas: 1993 - 2007Number of cases – Texas: 1993 - 2007
Lyme Disease:Lyme Disease:EpidemiologyEpidemiology
• Incidence in US: 2007Incidence in US: 2007
Source: CDC
* Among states reporting at least one case
Incidence per Incidence per 100,000100,000
USUS 9.19.1
Combined Incidence (Range)*Combined Incidence (Range)*States above US States above US
averageaverageStates below US States below US
averageaverage
39.2 (12.4 – 87.3)39.2 (12.4 – 87.3)0.8 (0.1 – 4.6)0.8 (0.1 – 4.6)
TexasTexas 0.40.4
Lyme Disease:Lyme Disease:Clinical Clinical
Early localized (1 - 4 weeks)Early localized (1 - 4 weeks)
• Flu-like (with or without rash)Flu-like (with or without rash)– fatiguefatigue– chillschills– feverfever– headacheheadache– muscle/joint achesmuscle/joint aches– swollen lymph nodesswollen lymph nodes
• Erythema migrans (70-80%)Erythema migrans (70-80%)– site of tick bite 3 – 30 day delay in appearancesite of tick bite 3 – 30 day delay in appearance
Source: CDC; WebMD
Lyme Disease:Lyme Disease:ClinicalClinical
Early disseminated (1 - 4 months)Early disseminated (1 - 4 months)
• facial nerve paralysis (Bell’s palsy)facial nerve paralysis (Bell’s palsy)• meningitis (headaches, neck stiffness, dizziness)meningitis (headaches, neck stiffness, dizziness)• cognitive deficits (memory, concentration)cognitive deficits (memory, concentration)• migrating painmigrating pain• heart palpatationsheart palpatations
Source: CDC; WebMD
Lyme Disease:Lyme Disease:ClinicalClinical
Late persistent infection (> 4 months)Late persistent infection (> 4 months)
Feder et al NEJM 2007
Feder et al NEJM, 2007
Lyme Disease: Lyme Disease: Laboratory diagnosisLaboratory diagnosis
Test Technique/Use Limitations Role in Chronic LD
Antibodies Two-tier testing• + ELISA or IFA• + IgM immunoblotAcute phase – should be pos if untreated
Supportive of clinical diagnosis; no proven utility in absence of symptoms
Not essential
Antigen PCROften positive in arthritis samples
Not well standardized; not recommended
Not validated
Culture BSK mediumSensitive in cutaneous samples; not routinely used
Slow growth; limited availability
Not validated
Urine antigen Antigen-capture ELISANot routinely used
Lack of accuracy Not validated
Feder et al NEJM, 2007
Lyme Disease:Lyme Disease:ClinicalClinical
Results of clinical trials on Category 4 patients:
Substantial risk with little or no benefit of continued antibiotics after appropriate initial treatment of Lyme disease
Source: Nature Medicine 2008
ProsPros ConsCons
Argument Persistent infection resistant to antibiotics
B. burgdorferi sensitive to antibiotics
Solution Long-term antibiotics Consider other diagnosis
Endorsements LDA, ILADS IDSA, NIAID, CDC
Scientific basis •Peer-review validation ?•More obscure literature
•Rigorous scientific review in high-profile journals•Reproducible findings
Legal issues • IDSA guidelines restrict treatment•antitrust suit by AG in CT
• IDSA – nothing wrong with guidelines but agreed to re-assess with new panel•Solid evidence that long-term
treatment not the answer
Chronic debate over chronic Lyme DiseaseChronic debate over chronic Lyme Disease(Post-Lyme disease syndrome)(Post-Lyme disease syndrome)
Post Lyme Disease Syndrome:Post Lyme Disease Syndrome:Confounding factors with subjective symptomsConfounding factors with subjective symptoms
• Patients told they have Lyme but do notPatients told they have Lyme but do not– >50% in one study at major tertiary care center had symptoms more >50% in one study at major tertiary care center had symptoms more
likely explained by fibromyalgia and chronic fatigue syndromelikely explained by fibromyalgia and chronic fatigue syndrome– Lack of laboratory evidenceLack of laboratory evidence– Improper advise based on testing that lacks validation (high rates of Improper advise based on testing that lacks validation (high rates of
false positives) (warning in MMWR, 2005)false positives) (warning in MMWR, 2005)
• High prevalence of subjective symptoms in general population High prevalence of subjective symptoms in general population creates considerable ‘noise’ - can be even higher than that creates considerable ‘noise’ - can be even higher than that reported for Lyme diseasereported for Lyme disease– Hence long standing directives not to perform diagnostic tests for Hence long standing directives not to perform diagnostic tests for
Lyme for subjects with only subjective symptomsLyme for subjects with only subjective symptoms
Source: Auwaerter CID 2007
Source: Point (A/CounterpointCID 2007
Post Lyme Disease Syndrome:Post Lyme Disease Syndrome:Long-term antibiotic therapyLong-term antibiotic therapy
Bottom line: more research needed
• Highly vocal debate fueled by frustrations stemming from:Highly vocal debate fueled by frustrations stemming from:• unmet needs of patientsunmet needs of patients• incomplete understanding of post-Lyme syndromeincomplete understanding of post-Lyme syndrome
Lyme Disease: Lyme Disease: Recent findingsRecent findings
• GenotypingGenotyping– 4 genotypes in outer surface protein C gene (OspC) account for 4 genotypes in outer surface protein C gene (OspC) account for
>80% of cases with EM from NY >80% of cases with EM from NY (Wormser et al, JID 2008)(Wormser et al, JID 2008)
• ClimateClimate– climate-associated variability in the timing of I. scapularis host
seeking contributes to geographic heterogeneities in frequencies of B. burgdorferi genotypes (Gatewood et al, App Environ Microbiol 2009)
• Virulence factor– bacterial protein (BmtA) associated with transporting manganese
across membrane important in growth of organism (Ouyang et al PNAS 2009)
Lyme-like Disease (STARI)Lyme-like Disease (STARI)EcologyEcology
Distribution of Amblyomma americanum, 2006 (courtesy of M. Yabsley, U Georgia)
Vector: Amblyomma americanum (Lone State tick)All stages are aggressive feeders and bite humans
Transmission earlier in year than Lyme disease due to feeding
habits of adults/nymphs
Lyme-like Disease (STARI)Lyme-like Disease (STARI)Clinical Clinical
Compared to Lyme disease:Compared to Lyme disease:• Milder flu-like symptomsMilder flu-like symptoms
– regional lymphadenopathy less likelyregional lymphadenopathy less likely– patients less symptomatic at time of rashpatients less symptomatic at time of rash
• Erythema migrans (100%)Erythema migrans (100%)– site of tick bitesite of tick bite– patients more likely to report tick bitepatients more likely to report tick bite
• More rapid recovery from treatmentMore rapid recovery from treatment
Masters et al Inf Dis Clin NA 2008
Lyme-like Disease (STARI)Lyme-like Disease (STARI)Diagnosis Diagnosis
• Causative organism undetermined– Borrelia lonestari isolated from dermatological biopsy of one
case but later series have failed to isolate organism– Therefore, no serological test available at present
• Clinical diagnosis based on presence of rash
Masters et al Inf Dis Clin NA 2008
Comparison of Lyme Disease and STARIComparison of Lyme Disease and STARI
Lyme DiseaseLyme Disease STARISTARIEtiologic agent B. burdorferi ??
Region NE US, upper Midwest SE US
Vector
Stage
Black-legged tick(I. scapularis, pacificus)
Nymph (primarily)
Lone Star tick(A. americanum)
All stages
Clinical presentationRash (frequency)Flu-like symptomsChronic manifestations
EM (70%)CommonCommon
EM (100%)Less likely
Less likely, less severe
Case definition Yes No
Lyme and Lyme-like DiseaseLyme and Lyme-like DiseaseWhat next? What next?
• Role of co-infection
Primary Tick Vector Associated human pathogens
Ixodes scapularis/pacificusIxodes scapularis/pacificus Borrelia burgdorferiBorrelia burgdorferiAnaplasma phagocytophilaAnaplasma phagocytophila
Babesia microtiBabesia microtiBartonella spp.Bartonella spp.
Amblyomma americanumAmblyomma americanum Ehrilichia chaffiensisEhrilichia chaffiensisEhrilichia ewingiiEhrilichia ewingiiBorrelia lonestariBorrelia lonestari
Rickettsia amblyommaRickettsia amblyomma
Lyme and Lyme-like DiseaseLyme and Lyme-like DiseaseWhat next? What next?
• Transmission studies– role of outer surface proteins (OspA & Osp B) -essential for
colonization and survival of Bb in ticks– role of gene BptA (Borrelia persistence in ticks-Gene A) - major role
in virulence and survival of organism in vector– Role of global warming favoring emergence of more
persistent/virulent strains in endemic regions with lower incidence (Upper Midwest) and in non-endemic regions
Lyme and Lyme-like DiseaseLyme and Lyme-like DiseaseWhat next for Texas? What next for Texas?
• Burning question: why such a low prevalence of tick-borne zoonoses (human cases) with so many ticks, so many people, and such a high risk for exposure?– Systematic surveillance (ticks and reservoir hosts)– Comparative studies of phenology (ecologic and climatic influences
on ticks and persistence/virulence of pathogens– What is the etiologic agent for STARI and is it just one mutation
away from producing a much more serious Lyme-like illness?– Does tick behavior in defined ecologic niches favor a vector that is
just less efficient in transmitting virulent human disease?– The role of co-infection with animal and human pathogens in
modifying infectivity/virulence (ex: could B. lonestari be a primary animal pathogen that just ‘outcompetes’ B. burgdorferi?
Stay tuned…
Lyme and Lyme-like DiseaseLyme and Lyme-like DiseaseWhat next? What next?
• Genomics/phylogenetics– Ex: study ‘in press’ indicates B. burgdorferi isolates from northern
US not genetically distinct from isolates in the southern US (M. Yabsley, personal communication)
• Role of pathogen-host relationships in tick-borne zoonoses– Ex: borreliacidal saliva in Ambloymma in modifying virulence
• Ecological characteristics– Ex: geospatial analytic methods to study factors in emergence and
to inform transmission cycles (sylvatic, peridomestic, domestic)