1. Thomas M File, Jr MD MSc MACP FIDSA FCCP Chair, Infectious Disease Division Summa Health System Akron, Ohio; Professor of Internal Medicine, Chair ID Section Northeast Ohio Medical University Rootstown, O Interpretation of Lyme and Quantiferon Tests

2. Lyme-stages  Early (days to weeks after tick bite; minority recall)  Erythema migrans (80%), fatigue, malaise, HA, myalgia, arthralgia, regional lymphadenopathy  Early disseminated: (weeks to months) Musculoskelatal; neuro 15% (lymph meningitis, cranial neruropathy); carditis 1%  Late (months to years)  MS 60%; Neurologic

3. Early Lyme Characteristic Rash Reaction as bacteria move through body; not multiple bites 3 Photo: T File MD

4. Lyme-Diagnosis  Early-clinical with rash; serology little value  Serology  2 tiered: ELISA (10% false +) then Western Blot  VisE C6 ELISA Measures AB to major protein sequence More accurate, also good for European strains  Antibodies may persist for years after Lyme disease has been treated and cured  PCR

5. LYME: WESTERN BLOT

6. Criteria for Western Blot for Lyme Type of Infection IsotopeBands for Dx First few weeks IgMTwo of: 24,39,41 After monthIgGFive of: 18,23,30,39,41,45,58,6 6,93

7. Lyme-Diagnosis ?? 1.Patient with Erythema Migrans ELISA negative 2. Patient with chronic fatigue ELISA Positive; Western Blot IgG and IgM + band 41* (+ ANA) 3.Patient with knee swelling X 2 weeks ELISA Positive; Western Blot: IgM no bands; IgG + 18,23,28,30,39,41,45,58,66,93 4.Patient referred for “ Lyme test” ELISA 1.13 (reference < 0.91); Western Blot: IgM Neg.; IgG + 41 * Common cross reactions * Common cross reaction

8. Lyme-Diagnosis ?? 5. 37 y/o female with 4 months of neurologic symptoms and fatigue ELISA positive; Western Blot-IgM neg.; IGG-5 + bands 6. 41 y/o female with burning of feet ELISA low +; Western Blot- IgM + one band; IgG-+ 2 bands 7.38 y/o female with headaches ELISA +; Wesern Blot IgM neg.; IgG +1 band 8. 57 y/o malePatient with knee swelling X 2 weeks ELISA +; Western Blot: IgM +1 band; IgG +10 bands * Common cross reactions

9. 9 Southern Tick Associated Rash Illness ( STARI) B. lonestari; A. americanum feed on white- tailed deer. Mild illness with onset of skin lesions Doxy 100 mg BD or Amox 500 mg TD X 10 days.

10. Transmission of M. tuberculosis  M. tb spread via airborne particles called droplet nuclei  Expelled when person with infectious TB coughs, sneezes, shouts, or sings  Transmission occurs when droplet nuclei inhaled and reach the alveoli of the lungs, via nasal passages, respiratory tract, and bronchi

11. Pathogenesis Droplet nuclei containing tubercle bacilli are inhaled, enter the lungs, and travel to the alveoli. Tubercle bacilli multiply in the alveoli.

12. Pathogenesis A small number of tubercle bacilli enter the bloodstream and spread throughout the body. The tubercle bacilli may reach any part of the body, including areas where TB disease is more likely to develop (such as the brain, larynx, lymph node, lung, spine, bone, or kidney).

13. Pathogenesis Within 2 to 8 weeks, special immune cells called macrophages ingest and surround the tubercle bacilli. The cells form a barrier shell, called a granuloma, that keeps the bacilli contained and under control (LTBI). If the immune system cannot keep the tubercle bacilli under control, the bacilli begin to multiply rapidly (TB disease). This process can occur in different areas in the body, such as the lungs, kidneys, brain, or bone.

14. Latent TB Infection (LTBI)  Granulomas may persist (LTBI), or may break down to produce TB disease  2 to 8 weeks after infection, LTBI can be detected via TST or interferon-gamma release assay (IGRA)  The immune system is usually able to stop the multiplication of bacilli  Persons with LTBI are not infectious and do not spread organisms to others

15. TB Classification System ClassStage of Disease 0No exposure, no infection 1 Exposure, no evidence of infection 2TB infection, no disease 3TB, clinically active 4TB, not clinically active 5TB suspect

16. Latent TB infection vs TB Disease 16 Latent TBITB Disease Positive Skin test or Interferon Gamma Release Assay (IGRA) Skin Test or IGRA usually + CXR normalCXR usually Abnormal No signs or symptomsSigns, symptoms present Culture neg.Smear, Culture + 50%

17. Latent TB (Quantiferon)  Less subjectively than Skin Test  No affect of BCG; but may have cross reactivity with M. kansaii, marinum or szulgari  Interpretation of Quantiferon test 17 QuantiferonResultcomment Mitogen – NilShould be > 0.5If < 0.5= “indeterminant” TB Ag – NilPositve > 0.35; Neg. < 0.35 BUT most < 1.0 are unlikely LTBI!!

18. General Recommendations for Using IGRAs  Preferred when testing persons  Who might not return for TST reading  Who have received BCG vaccination  Immune suppressed  Generally should not be used to test children <5 years of age, unless used in conjunction with TST

19. Interpret Quantiferon tests (CXR neg.) PatientControl Mitogen TB antigenTreat for LTBI? 50 y/o Healthcare Provider 105 55 y/o; on steroids; for Anti TNF Rx <0.5<0.1 45 y/o for Anti TNF Rx 32 40 y/o for AntiTNF Rx 2.5 19

20. Interpret Quantiferon tests (CXR neg.) PatientControl Mitogen TB antigenTreat for LTBI? 50 y/o Healthcare Provider 105yes 55 y/o; on steroids; for Anti TNF Rx <0.5<0.1No; Repeat periodically after anti-TNF Rx 45 y/o for Anti TNF Rx 32yes 40 y/o for Anti TNF Rx 2.5Repeat Test; Individualize 20