Tick-Borne Diseases

1. Tick-Borne Diseases Stephen J. Gluckman, M.D.

2. Lyme Disease Babesiosis Ehrlichiosis “Tick Typhus” Rocky Mountain Spotted Fever African Tick Typhus Tularemia Relapsing fever Powassan Tick Paralysis STARI Tick-Borne Diseases

3. An adult female Ixodes scapularis (blacklegged tick) An adult female Dermacentor variabilis (American dog tick) An adult female Amblyomma americanum (lone star tick)

5. Lyme DiseaseClinical PresentationsA few things to clarify • Erythema migrans • Carditis • Transient heart block • Myocarditis • Neurological • VII CN palsy • Aseptic meningitis • Radiculoneuritis • Lyme Encephalopathy • Rheumatologic • Acute pauci-articular arthritis

6. Where Do You See Lyme Disease? Throughout the world

7. National Lyme Disease Risk Map with Four Categories of Risk (CDC)

8. Borrelia Burgdorferi B. burgdorferi is not from Mars B. Burgdorferi is not from another dimension B. Burgdorferi is just another bug

9. How Big is the Ixodes Tick? 1-2 mm

10. Ixodes Ticks

11. Diagnosing Erythema Migrans ANY LARGE RED PATCH WITHOUT ANOTHER EXPLANATION IS ERYTHEMA MIGRANS

14. EM or Tick Bite Reaction?

15. Erythema Migrans • Things to remember • It is a clinical diagnosis, not a laboratory diagnosis • It is NEVER an emergency • “Target” lesion only occurs in 30% Any big red patch is EM unless you have another explanation

16. Lyme Disease and VII CN Palsy • Differential Diagnosis • HSV (was idiopathic) • HIV • Herpes Zoster • Local Infection/Trauma/Tumor • Sarcoidosis • Lyme • More likely with: preceding or present erythema migrans

17. Lyme Disease and VII CN Palsy • Should you treat empirically? • Tick time of year • Potential tick exposure • Bilateral • “Diagnosis” • Lyme Serology • Lumbar Puncture?

18. Lyme Radiculoneuropathy • Differential Diagnosis • Diabetes • Herpes zoster (sine herpete) • Herniated disc • Collapsed Vertebral body • Syphilis

19. Case • 45 year old who has had several years of “low grade” fevers, painful lymph nodes, scratchy throat, and mental cloudiness • He has been treated with oral doxycycline, azithromycin, and paromomycin. • He has also been treated with three courses of IV ceftriaxone totaling 5 months • He has had line related of Staphylococcus aureus bacteremia and ceftriaxone induced acute cholecystitis • Is this resistant neuroborreliosis?

20. LYME ENECEPHALOPATHY • TO DIAGNOSE NEED BOTH • Objective evidence of neurological disease • Objective evidence of B. burgdorferi in the CNS • Lack of response related to: • Incorrect diagnosis • Impatience • Permanent damage

21. When Should One Think of Lyme Arthritis? • Monoarticular or pauciarticular • Typically knee • Differential Diagnosis: septic, crystal, rheumatoid, Reiter’s • Class II fluid • Arthralgias can be part of early Lyme Disease, but they are usually associated with EM and do not become chronic

22. Major Clinical Error • Chronic fatigue, chronic diffuse aching, recurrent sore throats, lymphadynia, and “low grade” fevers are not symptoms of active Lyme disease.

23. Lyme Serology • Misunderstandings about the use of serological testing for Lyme disease is the primary reason for the misunderstanding of this relatively uncomplicated infectious disease. • “Real” Lyme disease is generally easy to diagnose and treat • Diseases misdiagnosed as Lyme disease are not

24. There is NO TEST for Lyme Disease

25. Interpreting Lyme Serology • What is a positive test? • Positive screening by ELISA or IFA plus a positive western blot • What is a negative test? • Negative screening or positive screening with a negative Western Blot (2nd National Conf. on Serol Dx of LD MMWR 1995;4:590)

26. What is a positive western blot? • An IGM Western Blot is considered positive if 2 of 3 specific bands are present. • An IGG Western Blot is considered positive if 5 of 10 specific bands are present. • Otherwise they are negative AND a positive screening serology with a negative WB is a negative test.

27. Other Diagnostic Tests • Culture • Low sensitivity, high specificity • Unapproved tests • PCR on blood or urine • Urinary Antigen Testing • Borreliacidal Antibody Test (Gundersen test) • Immune Complex Disruption • T-cell Proliferative Response

28. Common Testing Errors • Not establishing a true positive test • Not understanding that a positive serology does not mean disease • Treating to eliminate antibodies • Antibodies persist and vary in titer • Treating a positive IgM alone: IgM may persist and is not helpful in disease beyond 1 month • Believing that a false negative test is frequent: False negatives are very rare other than in EM • Treating on the basis of an unestablished test

29. So, what is the consequence of misunderstanding the serology? THE CREATION OF MYTHS • An entire syndrome (disease?) has been created that does not exist • A belief that the serology is not good. • A belief that Lyme disease is difficult to treat.

30. How Good is the Treatment of Lyme Disease? VERY GOOD There Rarely is a Reason to Retreat a Patient

31. Lyme Disease Treatment • Oral • Doxycycline 100 mg BID • Amoxicillin 500 mg TID • Cefuroxime axetil 500 mg BID • Parenteral • Ceftriaxone 2 gm IV daily • Cefotaxime 2 gm IV Q8H

32. Lyme Disease Treatment • Erythema migrans • Oral x 10-21 d • VII cranial nerve palsy • Oral x 14-21 d • Acute meningitis • Parenteral x 14-28 d (can finish with oral) • Cardiac • 1st or 2nd degree block: Oral x 14-21 d • 3rd degree block or myocarditis: parenteral x 14-21 d

33. Lyme Disease Treatment • Arthritis • Oral x 28 d • Encephalopathy • Parenteral x 28 d • Neuropathy • Parenteral x 28 d • Persistent arthritis after two courses of therapy or other chronic symptoms • Symptomatic therapy

34. What About the Newer Antibiotics for Lyme Disease • There is no advantage for azithromycin, clarithromycin, cefixime, cefuroxime, etc…. Do Not Use Them!

35. LYME DISEASEConcept Summary • 23 year old with 4 months of diffuse aching and fatigue. Lyme serology: EIA (+) IgG Western Blot: 2 bands IgM Western Blot: 1 band Is this Lyme disease? NO

36. LYME DISEASEConcept Summary • 41 year old who has had difficulty remembering names for the past several years. Lyme serology: EIA: (-) Western blot IgG (-) Western blot IgM (+) Is this Lyme disease? NO

37. LYME DISEASEConcept Summary • 35 year old who presented several months ago with typical rash of erythema migrans. • Treated with 3 weeks of doxycycline • Rash resolves after 4 days, but she continues with malaise and diffuse myalgias • Repeat testing: Lyme serology: EIA (+) Western blot IgG (+) IgM (+) Does this patient need more treatment? NO

38. LYME DISEASEConcept Summary • 31 year old with the non-pruritic, non-painful skin lesions seen on the following slide. Lyme serology: EIA (-) Western blot IgG (-) Western blot IgM (-) Does this patient have Lyme disease?

39. YOU BETCHA

40. Babesiosis • What is it? • An intracellular protozoan parasite • Where is it? • Northeast • (Northwest) • What is the clinical syndrome? • “FLU” – like: fever, chills, headache, fatigue • Hemolytic anemia • Serious especially in asplenic persons • Relapses can occur - especially in immunosuppressed persons

41. BabesiosisDiagnosis and Treatment • Diagnosis • Peripheral blood smear • PCR on blood • Serology has the same problems as that for Lyme disease. A positive test does not mean disease. • Don’t treat a positive test; treat a person with a positive test an a compatible clinical syndrome • Treatment • Quinine and Clindamycin • Atovaquone and azithromycin

42. Babesiosis

43. Ehrlichiosis and Anaplasmosis • What are they? • Rickettsiaceae family • Human Monocytic Ehrlichiosis (HME) • Lone star tick • Human Granulocytic Anaplasmosis (HGA) • Ixodes ticks • Where is it? • Everywhere

44. Human Monocytic Ehrlichiosis • E. chaffeensis • First described in 1987 • Primarily infects mononuclear cells • Reservoir: deer, dogs, goats • Vector: Lone star tick (Amblyomma americanum)

45. Human Granulocytic Anaplasmosis • First described in 1994 • Organism recently named Anaplasma phagocytophilum. • Reservoir: deer, rodents, elk • Vector: Ixodes ticks

46. Ehrlichiosis and Anaplasmosis SIGNS AND SYMPTOMS • Incubation period: 5 - 10 days • Early symptoms are non-specific (“flu-like”) • Fever, headache, myalgias • GI symptoms can occur • Rash variable • Laboratory • Leucopenia, thrombocytopenia, abnormal liver enzymes

47. Ehrlichiosis and Anaplasmosis COMPLICATIONS • Can be very severe • Renal failure • ARDS • DIC • Encephalitis • 3% mortality • Worse in patients with impaired host defenses • Watch out for dual or triple infections with • Borrelia burgdorferi and Babesia

48. Ehrlichiosis and Anaplasmosis DIAGNOSIS • Peripheral smear looking for morulae • Serology • PCR (state laboratories) • Culture • Treat based on epidemiologic and clinical clues. Do not delay while waiting for confirmation.

49. Ehrlichiosis and Anaplasmosis Morulae

50. Ehrlichiosis and Anaplasmosis TREATMENT • Treatment should not be delayed until laboratory confirmation is obtained • Doxycycline: 100 mg PO/IV • Until 3 days after fever abates • Expect response in 24 - 72 hours • Pregnancy and children ??? • Rifampin 600 mg IV/PO has been used