Stephen Waring, DVM, PhD Associate Professor Epidemiology, Biological Sciences

1. Lyme Disease and Southern Tick Associated Rash Illness (STARI) in Texas:What we know; what we need to know Stephen Waring, DVM, PhD Associate Professor Epidemiology, Biological Sciences

2. Lyme DiseaseEcology

3. Lyme Disease:Epidemiology • Number of cases – US: 1993 - 2007

4. Lyme Disease:Epidemiology • Number of cases – Texas: 1993 - 2007

5. Lyme Disease:Epidemiology • Incidence in US: 2007 * Among states reporting at least one case Source: CDC

6. Lyme Disease:Clinical Early localized (1 - 4 weeks) • Flu-like (with or without rash) • fatigue • chills • fever • headache • muscle/joint aches • swollen lymph nodes • Erythemamigrans (70-80%) • site of tick bite 3 – 30 day delay in appearance Source: CDC; WebMD

7. Lyme Disease:Clinical Early disseminated (1 - 4 months) • facial nerve paralysis (Bell’s palsy) • meningitis (headaches, neck stiffness, dizziness) • cognitive deficits (memory, concentration) • migrating pain • heart palpatations Source: CDC; WebMD

8. Lyme Disease:Clinical Late persistent infection (> 4 months) Feder et al NEJM 2007

9. Lyme Disease: Laboratory diagnosis Feder et al NEJM, 2007

10. Lyme Disease:Clinical • 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 Feder et al NEJM, 2007

11. Chronic debate over chronic Lyme Disease (Post-Lyme disease syndrome) Source: Nature Medicine 2008

12. Post Lyme Disease Syndrome:Confounding factors with subjective symptoms • Patients told they have Lyme but do not • >50% in one study at major tertiary care center had symptoms more likely explained by fibromyalgia and chronic fatigue syndrome • Lack of laboratory evidence • Improper advise based on testing that lacks validation (high rates of false positives) (warning in MMWR, 2005) • High prevalence of subjective symptoms in general population creates considerable ‘noise’ - can be even higher than that reported for Lyme disease • Hence long standing directives not to perform diagnostic tests for Lyme for subjects with only subjective symptoms Source: Auwaerter CID 2007

13. Post Lyme Disease Syndrome:Long-term antibiotic therapy • Highly vocal debate fueled by frustrations stemming from: • unmet needs of patients • incomplete understanding of post-Lyme syndrome Bottom line: more research needed Source: Point (A/CounterpointCID 2007

14. Lyme Disease: Recent findings • Genotyping • 4 genotypes in outer surface protein C gene (OspC) account for >80% of cases with EM from NY (Wormser et al, JID 2008) • Climate • climate-associated variability in the timing of I. scapularishost seeking contributesto 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)

15. Lyme-like Disease (STARI)Ecology Distribution of Amblyomma americanum, 2006 (courtesy of M. Yabsley, U Georgia) Transmission earlier in year than Lyme disease due to feeding habits of adults/nymphs Vector: Amblyomma americanum (Lone State tick) All stages are aggressive feeders and bite humans

16. Lyme-like Disease (STARI)Clinical Compared to Lyme disease: • Milder flu-like symptoms • regional lymphadenopathy less likely • patients less symptomatic at time of rash • Erythemamigrans (100%) • site of tick bite • patients more likely to report tick bite • More rapid recovery from treatment Masters et al Inf Dis Clin NA 2008

17. Lyme-like Disease (STARI)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

18. Comparison of Lyme Disease and STARI

19. Lyme and Lyme-like DiseaseWhat next? • Role of co-infection

20. Lyme and Lyme-like DiseaseWhat next? • Transmission studies • role of outer surface proteins (OspA & Osp B) -essential for colonization and survival of Bb in ticks • role of gene BptA (Borreliapersistence 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

21. Lyme and Lyme-like DiseaseWhat 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…

22. Lyme and Lyme-like DiseaseWhat 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)

23. Lyme Disease and Lyme-like Disease in Texas:What we know; what we need to know The art of medicine consists of amusing the patient while nature cures the disease. Voltaire