1. Epidemiology, Biological Sciences
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 Disease Ecology

3. Lyme Disease: Epidemiology
Number of cases – US:

4. Lyme Disease: Epidemiology
Number of cases – Texas:

5. Lyme Disease: Epidemiology
Incidence in US: 2007
Incidence per 100,000 US
9.1
Combined Incidence (Range)*
States above US average
States below US average
39.2 (12.4 – 87.3)
0.8 (0.1 – 4.6)
Texas
0.4
* 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
Erythema migrans (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
Test
Technique/Use
Limitations
Role in Chronic LD
Antibodies
Two-tier testing
+ ELISA or IFA
+ IgM immunoblot
Acute phase – should be pos if untreated
Supportive of clinical diagnosis; no proven utility in absence of symptoms
Not essential
Antigen
PCR
Often positive in arthritis samples
Not well standardized; not recommended
Not validated
Culture
BSK medium
Sensitive in cutaneous samples; not routinely used
Slow growth; limited availability
Urine antigen
Antigen-capture ELISA
Not routinely used
Lack of accuracy
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)
Pros
Cons
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
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. 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)

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
Erythema migrans (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
Etiologic 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 presentation
Rash (frequency)
Flu-like symptoms
Chronic manifestations
EM (70%)
Common
EM (100%)
Less likely
Less likely, less severe
Case definition
Yes No

19. Lyme and Lyme-like Disease What next?
Role of co-infection
Primary Tick Vector
Associated human pathogens
Ixodes scapularis/pacificus
Borrelia burgdorferi
Anaplasma phagocytophila
Babesia microti
Bartonella spp.
Amblyomma americanum
Ehrilichia chaffiensis
Ehrilichia ewingii
Borrelia lonestari
Rickettsia amblyomma

20. Lyme and Lyme-like Disease 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

21. Lyme and Lyme-like Disease 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…

22. Lyme and Lyme-like Disease 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)

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