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