Update on Lyme Disease Surveillance in Wisconsin for Providers and Laboratories

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Update on Lyme Disease Surveillance in Wisconsin for Providers and Laboratories Christopher Steward Division of Public Health Wisconsin Department of Health Services 04/10/14 Protecting and promoting the health and safety of the people of Wisconsin

Overview Lyme disease epidemiology and statistics. Laboratory testing and interpretations. Treatment and prevention. Review of reporting requirements in Wisconsin. 2

Lyme Disease Borrelia burgdorferi 3

Most Frequently Reported Notifiable Diseases in Wisconsin, 2012 Reported Cases 1. Chlamydia 23,969 2. Pertussis 6,461 3. Gonorrhea 4,741 4. Hepatitis C 2,634 5. Lyme disease 1,960 6. Influenza-associated hospitalization 1,489 7. Campylobacteriosis 1,320 8. Mycobacterial (non-tuberculous) 1,196 9. Salmonellosis 889 10. Cryptosporidiosis 637 4

Reported Lyme Disease Cases (n=28,446) 4000 3600 3200 329 437 470 384 399 370 407 486 607 516 658 653 1103 767 1191 1479 1487 1838 1496 1948 1487 2511 2376 545 636 473 1113 987 1233 2800 2400 2000 1600 1200 800 400 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008* 2009 2010 2011 2012 No. of Cases Year of Illness Onset 70 60 50 Incidence Estimated Cases Probable Cases Confirmed Cases Incidence per 100,000 *Surveillance case definition change to include probable cases Reporting criteria change Rev 01/30/2014 40 30 20 10 0 5

Lyme Disease 3-Year Average Incidence, 1990-2010 1990-1992 1993-1995 1996-1998 1999-2001 2002-2004 2005-2007 2008-2010 6

Early Localized Stage: Erythema Migrans (EM) Rash Skin lesions typically begin as a red macule or papule and expands over a period of days to weeks to form a large round lesion, often with partial central clearing. Located at site of the tick bite after 3-30 days, with an average of 11 days, in ~70% of infected persons. A rash that is 5cm (2 in) is diameter is considered diagnostic, laboratory testing is not needed. Erythematous lesions occurring within several hours of a tick bite may be the result of a hypersensitivity reaction, which would not be considered an EM rash. 7

Erythema Migrans (EM) Rash Source: CDC.gov 8

Lyme Disease: Early Disseminated Stage Occurs days to weeks after tick bite. Multiple disseminated EM rashes. Arthritis (asymmetrical, larger joints). Cranial neuritis (Bell s palsy). Radiculoneuropathy. Lymphocytic meningitis. Second and third degree atrioventricular block. Fever and chills. Headaches. Malaise or fatigue. Myalgia and arthralgia. Dizziness. Generalized lymphadenopathy. Myocarditis. Palpitations. 9

Lyme Disease: Late Persistent Stage Occurs months to years after tick bite. Arthritis (asymmetrical, larger joints). Encephalomyelitis. Other neurologic abnormalities. Cardiovascular abnormalities. Fatigue. Numbness in hands and feet. Cognitive impairment. 10

Clinical Manifestations of Confirmed Lyme Disease Cases, United Sates, 2001-2010 Source: CDC.gov 11

Rev 05/09/2011 Confirmed Lyme Disease Cases Wisconsin 2012 (n=1,487) 12 Jan Feb Mar April May June July Aug Sept Oct Nov Dec 41 33 57 38 25 15 93 83 108 200 341 453 500 400 300 200 100 0 Month of Illness Onset No. of Confirmed Cases Updated 01/30/2014

Confirmed Lyme Disease Cases Wisconsin 2012 (n=1,487) 13

Laboratory Testing 14

Lyme Disease Testing Methods Serologic assays Enzyme immunoassay (EIA) tests. Immunofluorescent assays (IFA). Western Blot test. PCR Molecular method of detecting DNA of organism (synovial fluid). Culture Detects growth of organism to confirm active infection. 15

Lyme Disease - Antibody Response Both IgM and IgG can persist for 10-20 years. IgM response Produced earlier than IgG. Peaks within the first several weeks. Less specific than IgG. Less reliable as a marker for Lyme disease, particularly for patients with later stages of illness. 16

Lyme Disease - Antibody IgG Response IgG response Produced a few weeks after IgM. Peaks months to years. More specific then IgM. More reliable marker for Lyme disease. 17

CDC Laboratory Criteria: 2008 Case Definition Lyme Disease Two-Tiered Testing 1st tier: EIA or IFA test (sensitive but less specific) Screening test EIA result is reported as an index number IFA result is reported as a titer 2nd tier: WB test (specific but less sensitive) Results are reported out as bands IgM (2 out of 3 bands): 41, 39, 21-25 kda IgG (5 out of 10 bands): 18, 21-15, 28, 30, 39, 41, 45, 58, 66, 93 kda 18

Source: CDC.gov 19

Testing Limitations A negative result during the EM phase or in a PCR test does not exclude the possibility of infection with B. burgdorferi. A positive result is not definitive evidence of current infection with B. burgdorferi, clinical signs and symptoms are needed. Other conditions including syphilis, periodontal disease, rheumatoid arthritis, and systemic lupus erythematosus can cross react with antibody tests. Antibodies can persist for 10-20 years. Use testing as supportive evidence of infection. 20

Laboratory Tests Whose of Questionable Use Detection of antigens in urine. Detection of cell wall deficient or cystic forms of B.burgdorferi. Reverse Western blot. Lymphocyte based assays. Measurements of antibodies in synovial fluid. Certain culture and PCR techniques that have not been peer-reviewed. In-house criteria for interpreting immunoblots. 21

Treatment and Prevention 22

Lyme Disease - Treatment CDC follows the Infectious Diseases Society of America (IDSA) guidelines. Antibiotics are very effective if treated early. Recurrent symptoms may require a additional courses of antibiotics. Long-term intravenous courses (months to years) have not been shown to be beneficial and may cause more complications. Cholecystitis and gallstones, catheter-associated bloodstream infections, fatal Clostidium difficile infection. 23

Lyme Disease - Treatment 2009 Red Book, 28 th edition, pages 430-435. The Clinical Assessment, Treatment and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Wormser GP et al CID 2006;43:1089-1134. http://cid.oxfordjournals.org/content/43/9/1089.full 24

Recommended Treatment Early localized disease Age > 8 years Age <8 years or unable to tolerate doxycycline Doxycycline* 100 mg PO BID for 14-21 days Amoxicillin 50 mg/kg/d PO divided into 3 doses (maximum 1.5 g/d) for 14-21 days -OR- Cefuroxime 30 mg/kg/d PO in 2 divided doses (maximum 1.0 g/d) for 14-21 days *Tetracyclines contraindicated during pregnancy. 25

Recommended Treatment Early disseminated and late disease Arthritis Same PO regimen as for early localized disease but for 28 days Persistent or recurrent arthritis* Ceftriaxone sodium, 75-100 mg/kg IV or IM once daily (max 2g/d) for 14-28 days Penicillin 300,000 U/kg IV in divided doses q4h (max 20 m U/d) for 14-28 days -OR- -OR- Same oral regimen as for early disease *Objective evidence of synovitis exists at least 2 months after treatment initiated. 26

Recommended Treatment Early disseminated and late disease Multiple erythema migrans Isolated facial palsy Carditis Meningitis or encephalitis Same PO regimen as for early localized disease but for 21 days Same PO regimen as for early localized disease but for 21-28 days* Ceftriaxone or penicillin: see persistent or recurrent arthritis Ceftriaxone IV or penicillin IV: see persistent or recurrent arthritis *Corticosteroids should not be given. Rx has no effect on the resolution facial nerve palsy; it s purpose is to prevent late disease. 27

Prevention Avoid tick exposures when possible. Use tick repellents. 20-30% DEET. Permethrin on clothes. http://cfpub.epa.gov/oppref/insect/ No currently available vaccine. No lasting immunity. Prophylaxis. 28

Prophylaxis Patient is bitten by an Ixodes scapularis tick (blacklegged tick; deer tick) in Wisconsin. Was the tick attached to the patient for 24 hours? Yes Has it been 72 hours since the tick was removed from the patient? Yes No No Prophylaxis treatment is not recommended. Prophylaxis treatment is not recommended. Is doxycycline contraindicated for the patient (less than 8 years of age, pregnant, etc.)? No Yes Prophylaxis treatment is not recommended. Prophylaxis treatment is recommended. Guidelines are based on those recommended by the ISDA. Prophylaxis Treatment: A single dose of doxycycline, 4 mg/kg up to a maximum dose of 200 mg. 29

Ixodes scapularis ticks demonstrating changes in blood engorgement after various durations of attachment. A: Nymphal stage. B: Adult stage. The pictures are a generous gift from Dr. Richard Falco (Fordham University). 30

Lyme Disease Reporting 25

Reporting Requirements as of June 2012 Required reporting: Laboratories continue to report all Lyme positive results. Health care providers continue to report all cases of erythema migrans (EM 5 cm and diagnosed by a physician or medical personnel). Continue to report date of illness onset and patient demographic information (address, birth date, gender, race, and ethnicity). Optional reporting: Reporting of Lyme disease cases without EM rash (including non- EM confirmed and probable cases) is optional, unless requested by the local health departments. Reporting of signs and symptoms other than EM rash, exposure, and treatment information is now optional, unless requested by the LHDs. 32

How to Report Lyme Disease Cases Electronically via the Wisconsin Electronic Disease Surveillance System (WEDSS). Contact Division of Public Health WEDSS staff. DHSWEDSS@wisconsin.gov Mail or fax the Wisconsin Lyme Disease Case Report Form to the appropriate Local Health Department or to the Division of Public Health. http://www.dhs.wisconsin.gov/communicable/epinetcasereport Forms/EpiCRFLyme.pdf Acute and Communicable Disease Case Report. http://www.dhs.wisconsin.gov/forms/f4/f44151.pdf Phone call to LHD or any other means of reporting. 33

References 1. Feder HM Jr., Johnson BJB, O Connell S, et al. A critical appraisal of chronic Lyme disease. NEJM 2007;357:1422-1430 (plus correction of author listing NEJM 2008;358:1084). 2. Nadelman RB, Nowakowski J, Fish D et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. NEJM 2001;345:79-84. 3. Warshafsky S, Lee DH, Francois LK et al. Efficacy of antibiotic prophylaxis for the prevention of Lyme disease: an updated systematic review and meta-analysis. J Antimicrob Chemother 2010;65:1137-1144. 4. Wormser GP, Dattwyler RJ, Shapiro ED et al. The Clinical Assessment, Treatment and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. CID 2006;43:1089-1134. 34

Resources http://www.dhs.wisconsin.gov/communica ble/tickborne/index.htm http://www.cdc.gov/ticks/index.html http://www.cdc.gov/lyme/ http://www.cdc.gov/lyme/healthcare/clinici ans.html 35

Additional Questions For all vectorborne questions: Diep (Zip) Hoang Johnson, Epidemiologist Phone: (608) 267-0249 E-mail: diep.hoangjohnson@wisconsin.gov For Lyme disease: Christopher Steward, Research Analyst Phone: (608) 261-8354 Email: christopher.steward@wisconsin.gov 39