Georgia epidemiology report, Vol. 17, no. 8 (Aug. 2001)

August 2001

volume 17 number 08

Division of Public Health http://health.state.ga.us
Kathleen E. Toomey, M.D., M.P.H. Director
State Health Officer
Epidemiology Branch http://health.state.ga.us/epi
Paul A. Blake, M.D., M.P.H. Director
State Epidemiologist
Mel Ralston Public Health Advisor
Georgia Epidemiology Report Editorial Board
Carol A. Hoban, M.S., M.P.H. - Editor Kathryn E. Arnold, M.D. Paul A. Blake, M.D., M.P.H.
Susan Lance-Parker, D.V.M., Ph.D. Kathleen E. Toomey, M.D., M.P.H.
Angela Alexander - Mailing List Jimmy Clanton, Jr. - Graphic Designer
Georgia Department of Human Resources
Division of Public Health Epidemiology Branch Two Peachtree St., N.W. Atlanta, GA 30303-3186 Phone: (404) 657-2588 Fax: (404) 657-7517
Please send comments to: Gaepinfo@dhr.state.ga.us
The Georgia Epidemiology Report is a publication of the Epidemiology Branch,
Division of Public Health, Georgia Department of Human Resources

Tick Bites and Erythema Migrans in
Georgia: It Might NOT be Lyme Disease!
Lyme disease is caused by the spirochete Borrelia burgdorferi and is the most commonly reported vector-borne disease in the United States. Endemic foci for Lyme disease occur in the Northeast, Upper Midwest, and Pacific Coast regions of the U.S.; however, there is much controversy over the risk of acquiring Lyme disease in the Southeast. Clinicians in this region frequently report erythema migrans (EM) and a clinical syndrome that resembles Lyme disease, but B. burgdorferi has never been isolated from these lesions and patients are typically seronegative when tested for Lyme disease by standard methods. So, is there indigenous transmission of Lyme disease to humans in Georgia?
Borrelia burgdorferi is maintained in a variety of rodent reservoirs by Ixodes scapularis (the "black-legged tick" or "deer tick") in the Northeast and Upper Midwest regions of the U.S. and by Ixodes pacificis (the "western black-legged tick") in the Pacific Coast region. Ixodes scapularis is present in the Southeast. However, the prevalence of B. burgdorferi in this vector species collected from southern states is low compared to its prevalence in ticks collected from Lyme-endemic areas of the northeast. Recent studies have estimated the prevalence of B. burgdorferi in adult I. scapularis collected from the Northeast to be as high as 52-56% while only 0-3% of ticks in southern states have been found to be infected with the spirochete. Furthermore, immature I. scapularis ticks in the south do not commonly feed rodents or other warm-blooded mammals that are known reservoirs of B. burgdorferi in endemic areas; rather, they feed on a wider variety of hosts that includes several species of lizards. Thus, while the potential risk of human exposure to B. burgdorferi in the Southeast does exist, it is considerably lower than in other regions of the US.
The incidence of human Lyme disease or Lyme-like illness in GA cannot currently be estimated. The diagnosis of Lyme disease is complicated and although Lyme disease is physician and laboratory reportable in GA, the submission of clinical data as well as laboratory data is required to meet the surveillance case definition. During 2000, the Georgia Division of Public Health (GDPH) received 245 laboratory reports of positive serological tests for B. burgdorferi. Of these 245 reports, 4 were accompanied by physician reports, but still did not meet the surveillance case definition set forth by the Centers for Disease Control and Prevention (CDC). An additional 3 physician reports had presumptive diagnoses based upon clinical presentations without laboratory testing. Most of the laboratory reports did not list a physician name or any patient contact information, making additional follow-up nearly impossible.
The tick bite-associated EM lesions that occur in the southern U.S. appear to be associated with bites of Amblyomma americanum (the "Lone Star tick"), which is the most common human-biting tick in the region but is not a competent vector of B. burgdorferi. The etiology of this "Southern tick-associated rash illness" (STARI) is unknown, but studies to date have failed to implicate B. burgdorferi. A novel ticktransmitted spirochete called Borrelia lonestari is being evaluated as a possible etiologic agent. B. lonestari has been detected by molecular methods in two Amblyomma americanum ticks collected as part of an investigation of a cluster of STARI in Alabama.

CLINICAL SYMPTOMS OF LYME DISEASE AND STARI Table 1. Lyme disease: Surveillance Case Definition (Centers for Disease Control and Prevention)

Clinical Case Definition A case with Erythema Migrans or a case with at least one late manifestation (as defined below) that is laboratory confirmed

Erythema Migrans (EM)

EM is a skin lesion that typically begins as a red macule or papule and expands over a period of days to weeks in an annular manner, often with partial central clearing. A solitary lesion must reach at least 5 cm in diameter to meet the surveillance definition. The primary lesion occurs at the site of a bite of an infected tick and multiple (secondary) lesions may also occur. Annular erythematous lesions that occur within several hours after a tick bite represent hypersensitivity reactions and are not indicators of disease transmission. EM is usually accompanied by nonspecific symptoms that may include fever, malaise, fatigue, headache, stiff neck, myalgia, and migratory arthralgia and/or lymphadenopathy. The incubation period from infection to onset of symptoms is typically 7 to 10 days (range 3 to 32 days). If left untreated, EM will fade spontaneously after several weeks.

Late Manifestations

Musculoskeletal System

(when an alternate

Recurrent brief attacks (lasting weeks or months) of objective joint swelling in one or a few joints, sometimes followed by

explanation is not found) chronic arthritis in one or a few joints. Manifestations not considered criteria for diagnosis include chronic progressive arthritis not preceded by brief attacks and chronic symmetrical polyarthritis. Arthralgia, myalgia, or fibromyalgia syndromes alone are

not criteria for musculoskeletal involvement.

Nervous System

Any of the following, alone or in combination: lymphocytic meningitis; cranial neuritis, particularly facial palsy (may be

bilateral); radiculoneuropathy; or, rarely, encephalomyelitis. Encephalomyelitis must be confirmed by showing antibody

production against B. burgdorferi in the CSF, demonstrated by a higher titer of antibody in CSF than in serum. Headache, fatigue,

paraesthesia, or mild stiff neck alone are not criteria for neurologic involvement.

Cardiovascular System

Acute-onset, high-grade (2nd or 3rd degree) atrioventricular conduction defects that resolve in days to weeks and are sometimes

associated with myocarditis. Palpitations, bradycardia, bundle-branch block, or myocarditis alone are not criteria for cardiovascu-

lar involvement.

Laboratory Criteria for Diagnosis and Specimen Requirements


Serum: 2-step process for early disease: 1) EIA or IFA IgG and IgM 2) if positive, do Western blot IgG and IgM. If late disease: IgG Western blot. If neuroborreliosis: EIA-IgG serum and CSF. Calculate index if EIA elevated. Skin biopsy: isolation and culture of B. burgdorferi OR CSF: isolation and culture of B. burgdorferi OR Synovial fluid: isolation and culture of B. burgdorferi

Serum: 5 mL serum (red-top tube) collected both at disease onset and 4-6 weeks later
Skin biopsy: 2-4 mm skin lesion in transport medium collected in acute phase of the illness CSF: 5-10 mL in sterile tube Synovial fluid: 5-10 mL in sterile tube

Note: This surveillance case definition is a public health tool intended for the surveillance of health events in populations. It is not intended for use in clinical diagnosis or management decisions in individual cases. In geographic areas where Lyme disease occurs infrequently or not at all, the positive predictive value of this case definition is low (i.e. cases that meet or appear to meet the definition will have a low likelihood of being true cases).

Southern Tick-Associated Rash Illness (STARI) is characterized blood, CSF, and synovial fluid, but PCR has not been standardized for routine

by an expanding annular erythema, mild constitutional symptoms, a spring- diagnosis of Lyme disease. A Lyme urinary antigen test (LUAT) is commer-

summer seasonality, a recent antecedent tick bite at the site of the skin

cially available, but it has been shown to give contradictory results and it yields

rash in many cases, an absence of antibodies to Borrelia burgdorferi using

a high rate of false-positives. The LUAT has not been approved by the FDA

standardized methods, and negative results of skin biopsy cultures. STARI and should not be used for diagnosing active or suspected Lyme disease.

is believed to be a self-limited disease in most cases; late sequelae or

There is currently no diagnostic test available for STARI. The agent of

disseminated disease are rare.

STARI, presumably B. lonestari, has not been successfully cultivated from

Amblyomma ticks or from biopsy specimens of EM lesions, or from other

DIAGNOSIS OF LYME DISEASE AND STARI

human tissues or blood. An experimental PCR test to be used on skin biopsy

The diagnosis of Lyme disease should be based primarily upon clinical specimens is available from the CDC. Serologic specimens obtained from

findings that are supported by serologic testing. When Lyme disease is

patients with STARI might yield a positive or equivocal Lyme disease (B.

suspected based on clinical findings, a sensitive screening test such as an

burgdorferi) ELISA screening test, but will probably be negative when tested by

enzyme-linked immunosorbent assay (ELISA) or immunofluorescent

the more specific WB.

antibody (IFA) test should be performed. Positive test results should

be interpreted with caution because cross-reacting ELISA and

TREATMENT

IFA antibodies may produce false positive reactions in patients

Early Lyme disease responds to antibiotic therapy in almost all patients.

with syphilis, relapsing fever, leptospirosis, HIV infection, Rocky Oral antibiotic therapy shortens the duration of rash and generally prevents

Mountain spotted fever (RMSF), infectious mononucleosis, lupus, development of late sequelae. While it is appropriate to treat patients with

or rheumatoid arthritis. Samples with positive or equivocal ELISA or early disease solely on the basis of objective signs and a known exposure, the

IFA results should be further tested with the more specific Western

prophylactic treatment of tick bites is NOT recommended since the incidence

immunoblot (WB) test. Although antibiotic treatment in early-localized

of infection after a tick bite is low and treatment of early disease is very

disease may blunt or abrogate the antibody response, patients with early

effective. There are currently no recommendations specific to STARI;

disseminated or late disseminated disease usually have strong serological

however, rash and other constitutional symptoms resolved quickly after the

reactivity and demonstrate expanded IgG banding patterns on WB.

initiation of doxycycline therapy in almost all published case reports

Antibodies often persist for months or years following successfully treated

or untreated infection. Thus, seroreactivity alone cannot be used as a

SUMMARY

marker of active disease. Repeated infection with B. burgdorferi has been

There is much controversy over the etiology of EM rashes in the

documented.

Southeast. It is plausible that a newly recognized species of Borrelia is

Although Borrelia burgdorferi can be cultured from 80% or more of

transmitted by Amblyomma americanum ticks and is responsible for a Lyme-like

biopsy specimens taken from early EM lesions, the diagnostic usefulness of syndrome called STARI. Healthcare providers in GA are urged to keep an

this procedure is limited because of the need for a special bacteriologic

open mind and consider the following as they evaluate and treat patients with

medium and protracted observation of cultures. Polymerase chain reaction potential tick exposure:

(PCR) has been used to amplify genomic DNA of B. burgdorferi in skin, -2 -

The best way to prevent tick-borne disease is to reduce or

patients presenting with a febrile flu-like illness, especially during the spring

eliminate exposure to ticks and to promptly remove attached

and summer months and regardless of whether or not the patient recalls a

ticks. Studies have shown that the transmission of the Lyme disease

tick bite. Due to the potentially severe or fatal outcome of HME or

spirochete is more likely with prolonged tick attachment (at least 24

RMSF, empiric treatment of these should be administered for suspect cases,

hours) and the transmission of the agents of Rocky Mountain spotted

even without laboratory confirmation. Prophylactic treatment after tick

fever (RMSF) or human monocytic ehrlichiosis (HME) requires at least

exposure or bites is NOT currently recommended.

10 hours of tick attachment. The prompt and proper removal of ticks Continue to report cases that meet the CDC case definition of Lyme disease

should be emphasized to patients to minimize their risk of infection.

to GDPH and provide additional clinical information when requested. This

Patients should also be educated about how to prevent tick bites. An

is critical for us to determine the etiology and epidemiology of EM illnesses

educational brochure for patients is available by calling the Epidemiology

in GA and to assess the impact of these illnesses on the health of Georgians.



Branch or online at http://health.state.ga.us/epi/vbd.shtml. Not all ticks are infected with pathogenic agents and not all tick



Consider enrolling your patients in appropriate research studies or public health interventions. The CDC is currently conducting a study to determine

bites transmit disease.

the etiology of STARI. They are soliciting skin biopsy, urine, whole blood,

A human recombinant outer-surface-protein vaccine (LYMErix-

and acute and convalescent serum specimens from patients in the southeast-

SmithKline Beecham) against Lyme disease is available in the U.S. for

ern U.S. (including GA) who present with a tick bite-associated expanding

people 15 to 70 years old who live or work in moderate-to high-risk areas

erythematous rash lesion. If you would like more information about this

and are exposed to ticks frequently or for long periods of time. All of GA study or would like to enroll one of your patients, please contact Ned Hayes

is classified as either a low risk or a no risk area. Vaccinated individuals

(970-221-6474) or Barbara Johnson (970-221-6463) at the Fort Collins

should still avoid tick bites because the vaccine does not protect against

office.

other tick-transmitted diseases such as RMSF and HME.

For more information about Lyme disease and other vector-borne diseases,

Allergic reactions to tick salivary components may be confused with EM

to learn about reporting requirements, or to view photographs of common

lesions. Annular erythematous lesions that appear within several hours

tick vectors in Georgia, please visit the GDPH website at http://

after tick bites could be caused by allergic or toxic reactions to tick bites.

health.state.ga.us/epi/vbd.shtml or the CDC website at http://

Tick-borne illnesses, including RMSF FanigduHreM3E: , sPhrooupldorbtieocnonosfidWeroemd feonr with Swinwgwle.ctdonc.gVoevr.sus

Multiple Gestation Pregnancies by Site of Delivery and

Table 2: Comparison of EpidemiolRogeysidaenndceC,liGneicoarlgiPar,e1s9e9n4ta-tio19n9s6of Tick-borne Diseases

Lyme

STARIa

HME

RMSF

Agent

Borrelia burgdorferi

Borrelia lonestari

Ehrlichia chaffeensis

Rickettsia rickettsii

Primary tick vector

Ixodes scapularis

Amblyomma americanum Amblyomma americanum Dermacentor variabilis

(Black-legged tick)

(Lone Star tick)

(Lone Star tick)

(American dog tick)

Signs/Symptoms/Laboratory Indications (% of cases)

Average incubation (range) 7 days (3-32)

6 days (0-42)

7 days (1-28)

Fever

16-59

23

97-100

Headache

42-64

50

44-81

Chills or rigors

39-59

16

67-75

Myalgia

43-44

38

43-68

Malaise

80

--

84

Nausea

14-17

19

33-73

Vomiting

10-14

12

27-38

Rash

13b

--

0-36

Cough

5-6

14

7-26

Lymphadenopathy

41

--

25

Arthralgia

44-48

36

9-67

Stiff Neck

35-48

42

22

Erythema migrans

75

100

--

Leukopenia

3-4

--

50-100

Thrombocytopenia

2

--

68-88

Elevated AST

18-19

--

75-100

Elevated ALT

15-26

--

74-88

Anemia

3-12

--

45-63

Death

~0%

None reported

2-5

aCompiled from references 1, 2, and 3. Data on the clinical features of STARI are still limited. bMalar rash

7 days (2-14) 99-100 53-92 11-27 45-83 95 30-66 40 88-92 33 27 17-25 -- -- -- 32-52 36-62 40 5-24 4-8

REFERENCES and SUGGESTED READING 1. Campbell GL, WS Paul, ME Schriefer, et al. Epidemiologic and diagnostic studies of patients with suspected early Lyme disease, Missouri, 1990-1993. J Infect Dis 1995;172:470-80. 2. Kirkland KB, TB Klimko, RA Meriwether, et al. Erythema migrans-like rash illness at a camp in North Carolina. A new tick-borne disease? Arch Intern Med 1995;157:2635-2641. 3. Masters E, S Granter, P Duray, P Cordes. Physician-diagnosed erythema migrans and erythema migrans-like rashes following lone star tick bites. Arch Dermatol 1998;134:955-60. 4. TR Burkot, GR Mullen, R Anderson, et al. Borrelia lonestari DNA in adult Amblyomma americanum ticks, Alabama. Emerg Infect Dis 2001; In Press. 5. Barbour AG. Does Lyme disease occur in the South?: a survey of emerging tick-borne infections in the region. Am J Med Sci 1996;311:34-40. 6. Barbour AG, Maupin GO, Teltow GJ, et al. Identification of an uncultivable Borrelia species in the hard tick Amblyomma americanum: possible agent of a Lyme disease-like illness. J Infect Dis 1996;173:403-9. 7. Melski, JW. Language, logic, and Lyme disease. Arch Dermatol 1999;135:1398-1400 8. Oliver JH. Lyme borreliosis in the southern United States: a review. J Parasitol 1996;82(6):926-35. 9. American College of Physicians. Guidelines for laboratory evaluation in the diagnosis of Lyme disease: clinical guideline parts 1 and 2. Annals of Internal Medicine 1997; 128(12):1106-1123. 10. Klempner MS, Schmid CH, Hu L, et al. Intralaboratory reliability of serologic and urine testing for Lyme disease. Am J Med 2001;110:217-19. 11. Goodman, JL. The diagnosis of Lyme disease: good news, bad news. Editorial. Am J Med 2001;110:236-38. 12. Nadelman, RB, et al. Prophylaxis with Single-Dose Doxycyline for the Prevention of Lyme Disease after an Ixodes scapularis Tick Bite, http://www.nejm.org/earlyrelase/index.asp. 13. Klempner, MS, et al. Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease, http://www.nejm.org/earlyrelase/index.asp. 14. Steere, AC. Medical Progress: Lyme Disease, http://www.nejm.org/earlyrelase/index.asp. 15. Shapiro, ED. Doxycycline for Tick Bites, http://www.nejm.org/earlyrelase/index.asp.
Authors | Catherine Rebmann, M.P.H. and Susan Lance-Parker, D.V.M., Ph.D.
-3 -

The Georgia Epidemiology Report Epidemiology Branch Two Peachtree St., NW Atlanta, GA 30303-3186

PRESORTED STANDARD U.S. POSTAGE
PAID ATLANTA, GA PERMIT NO. 4528

August 2001

Volume 17 Number 08

Reported Cases of Selected Notifiable Diseases in Georgia Profile* for May 2001

Selected Notifiable Diseases
Campylobacteriosis Chlamydia trachomatis Cryptosporidiosis E. coli O157:H7 Giardiasis Gonorrhea Haemophilus influenzae (invasive) Hepatitis A (acute) Hepatitis B (acute) Legionellosis Lyme Disease Meningococcal Disease (invasive) Mumps Pertussis Rubella Salmonellosis Shigellosis Syphilis - Primary Syphilis - Secondary Syphilis - Early Latent Syphilis - Other ** Syphilis - Congenital Tuberculosis

Total Reported for May 2001
2001 46
1868 8 2 88
891 9
85 32 1 0 3 0 1 0 101 19 4 13 36 34 0 32

Previous 3 Months Total

Ending in May

1999

2000 2001

186

158

142

9252

7905

6806

47

31

22

4

7

4

237

258

234

5889

4684

3389

24

24

38

149

69

237

44

68

86

0

3

3

0

0

0

24

13

15

1

1

5

11

11

5

0

0

0

310

262

241

65

78

64

30

34

16

64

68

55

188

157

131

205

181

154

4

5

2

154

174

121

Previous 12 Months Total

Ending in May

1999 2000 2001

818

636

607

28243

30636

30828

193

149

174

85

46

41

1297

1366

1146

20904

20876

18970

79

83

102

772

352

606

166

266

406

5

9

11

1

0

0

81

65

54

2

5

7

40

63

32

0

0

1

1972

1886

1684

811

296

314

126

150

99

250

290

260

823

601

508

812

736

726

17

19

16

606

670

641

* The cumulative numbers in the above table reflect the date the disease was first diagnosed rather than the date the report was received at the state office, and therefore are subject to change over time due to late reporting. The 3 month delay in the disease profile for a given month is designed to minimize any changes that may occur. This method of summarizing data is expected to provide a better overall measure of disease trends and patterns in Georgia.
** Other syphilis includes latent (unknown duration), late latent, late with symptomatic manifestations, and neurosyphilis.

Report Period
Latest 12 Months: 06/00 - 05/01 Five Years Ago: 06/95 - 05/96 Cumulative: 7/81 - 05/01

Total Cases Reported*

Percent Female

AIDS Profile Update
Risk Group Distribution (%) MSM IDU MSM&IDU HS Blood Unknown

1339

25.6

28.4

9.3

2.0

10.6

1.6

48.0

2394

17.8

48.7

19.0

5.1

17.3

1.0

8.9

23193

16.8

48.3

18.2

5.6

13.0

1.9

13.0

MSM - Men having sex with men

IDU - Injection drug users

HS - Heterosexual

* Case totals are accumulated by date of report to the Epidemiology Section

- 4 -

Race Distribution (%) White Black Other

18.9 76.7

4.4

36.8 60.3

2.9

35.5 62.3

2.2