Contracts Carla Chee, MHS May 8, 2012

Transcription

1 Moving Past the Basics of Tuberculosis Phoenix, Arizona May 8-10, 2012 Contracts Carla Chee, MHS May 8, 2012 Carla Chee, MHS has the following disclosures to make: No conflict of interests No relevant financial relationships with any commercial companies pertaining to this educational activity 1

2 Tuberculosis (TB) Carla Chee, MHS Program Manager Tuberculosis Control Program Arizona Department of Health Services Objectives Describe the stages of tuberculosis Latent tuberculosis infection TB disease Progression from TB infection to TB disease Explain the transmission of TB Process of transmission Probability of transmission 2

3 Latent TB Infection (LTBI) Quiescent infection with M. tuberculosis Bacteria is dormant or Bacteria is slowly metabolically active and is controlled by your immune system Usually within 2 to 8 weeks, the immune system intervenes, preventing further spread Not infectious TB 101 for Health Care Workers, CDC, WebCourse. Active TB Disease Active infectious process involving the lungs ± other organs Immune system cannot keep bacilli under control Person may feel sick and may spread TB to others TB 101 for Health Care Workers, CDC, WebCourse. 3

4 TB Transmission The spread of an organism from one person to another Mycobacteria that cause TB: M. tuberculosis M. bovis M. africanum M. microti M. canetti Depends on Transmission Probability Infectiousness of Active TB case Length of exposure Environment in which exposure occurred Virulence of the tubercle bacilli 4

5 Chain of Infection Susceptible Host Human Infectious Agent MTB Reservoir Human Means of Entry Inhale droplet nuclei Mode of Transmission Airborne Means of Exit Exhale droplet nuclei Coughing Sneezing Speaking Singing Fate of M. tuberculosis Aerosols Large droplets settle to the ground quickly Smaller droplets form droplet nuclei of 1 5 µin diameter Droplet nuclei can remain airborne 5

6 TB Pathogenesis How an infection or disease develops in the body A small number of tubercle bacilli enter bloodstream and spread throughout body Latent TB Infection How can we tell if someone has LTBI? Positive TST or IGRA Tuberculin skin test (TST) Interferon Gamma Release Assay (IGRA) No Symptoms suggestive of Active TB A normal or stable CXR Negative AFB sputum smear and culture results Not infectious now, but Dormant TB bacilli present At risk for development of Active TB disease in the future 6

7 How Does TB Present? Typical Case Positive TST or IGRA History of exposure + Risk factors Fever, night sweats, cough, weight loss Abnormal CXR cavitary + AFB sputum smear/ + NAAT Other Presentations Immunocompromised patient Normal CXR (CT may not be) Extrapulmonary TB Lymph node Abdominal Genitourinary CNS Miliary disease on CT Childhood contact 50% will be clinically well Who Should be Tested for LTBI? Contacts of persons with Active TB HIV positive individuals Recent immigrants (<5 yrs) from high prevalence countries Injection Drug Users Residents and Employees of high risk congregate settings: Correctional facilities and Homeless Shelters Hospitals, Clinics, Nursing Homes, Substance Abuse Facilities Newest Category: Patients considering treatment with TNF α Antagonists 7

8 LTBI Progression to Active TB LTBI 10% lifetime risk of Active TB Disease 90% lifetime risk of no active TB ~0.1% per year thereafter 2 3% Second Year 5% First Year Active TB Disease (10%) No TB Disease (90%) LTBI Progression to Active TB Lifetime risk Annual risk Normal immunity 10 % < 1 year old 43 % 1-5 year old 24 % Adolescent 15 % HIV 7-10 % 8

9 Contacts of Active TB Case Among close contacts to a TB Case: 30% have LTBI 1 3% have active TB disease Without LTBI treatment: 10% with LTBI develop Active TB Approximately 5% of contacts with newly acquired LTBI progress to TB disease within 2 years The other 5% activate > 2 years after acquisition Tumor Necrosis Factor α Inhibitors Block TNF α activity which is required for granuloma formation and control of TB infection Used for rheumatoid arthritis, Crohn s disease, psoriasis and a variety of other immune mediated diseases Remicaid (inflixamab) Enbrel (entanercept) Humira (adalimubab) Cimzia (certolizumab) 9

10 Latent TB Infection Identification of LTBI allows us to Treat & prevent an Active TB case Prevent all secondary cases that one Active TB case may have caused Ultimately, should be a cost effective approach Is this combination approach working? Reported TB Cases, United States, * No. of Cases *Updated as of July 21, 2011 Year 10

11 Active TB Cases U.S., Year No. Rate* , , , , , , : 84,304 TB Cases/52.6 cases per 100,000 US Population *Cases per 100,000. Updated as of March 23, 2012 TB Case Rates,* U.S., 2011 *Cases per 100,000 11

12 Active TB in the U.S. Basic Principles of TB Control in the U.S. 1. Promptly detect and report persons with Active TB 2. Protect close contacts of patients with infectious TB from contracting TB infection and disease 3. Identify those at highest risk for progression from LTBI to Active TB through targeted testing and LTBI treatment 4. Identify settings at high risk for transmission and apply effective infection control measures to reduce risk Number and Rate of TB Cases among U.S. born and Foreign born Persons U.S., * *Updated as of March 23,

13 LTBI Diagnostics TB Skin Test Interferon Gamma Release Assays TB Skin Test Purified Protein Derivative (PPD): Concentrated Filtrate of heat killed TB PPD is given via intradermal injection Read induration, not erythema, at hrs 13

14 TB Skin Test Pros: Inexpensive Simple to perform More Sensitive than IGRA Cons: Must return in hrs Difficult to interpret False Negatives: Immunosuppressed False Positives: Low risk populations NonTuberculous Mycobacteria Reading the TB Skin Test Measure induration, not erythema. 14

15 Induration of 5mm Considered a Positive TST HIV positive persons Recent contacts of TB cases Fibrotic Changes on CXR c/w prior TB Patients with organ transplants or other immunosuppression Prednisone therapy 15 mg/day > 1 month CDC. June 2000 Induration of 10mm Considered a Positive TST Recent arrivals (<5 yrs) high prevalence countries IVDU Residents/employees high risk congregate facilities (health care, prisons, shelters, etc.) TB lab personnel Children <4 yrs or exposed to adults at risk Persons with high risk medical conditions CDC. June

16 Induration of 10mm Considered a Positive TST Persons with high risk medical conditions Silicosis Diabetes Chronic Renal Failure Hematologic Disorders/Leukemia/Lymphoma Cancers, particularly Head/neck and Lung Low Body weight less than 10% below Ideal body weight Gastrectomy Jejunal Bypass CDC. June 2000 Induration of 15mm Considered a Positive TST Persons with no risk factors CDC. June

17 Interferon Gamma Release Assays Blood tests for detecting M. tuberculosis infection Sensitized white blood cells will release IFNgamma in response to contact with TB antigens Two Tests currently available: T SPOT TB (Oxford Immunotec) Quantiferon TB Gold In Tube (Cellestis) Oxford Immunotec, T-SPOT.TB Cellestis, QFT Interferon Gamma Release Assays Pros Patient does not have to return for second visit No Cross reactivity with BCG Vaccination Less Cross reactivity with other NTMs More Specific than TST Cons Expensive Does not differentiate LTBI from active disease 17

18 No Cross reactivity to BCG and Most NTMs Tuberculosis Complex Antigens Environmental Strains Antigens ESAT-6 CFP 10 ESAT-6 CFP 10 M. tuberculosis + + M. abcessus - - M. africanum + + M. avium - - M. bovis + + M. branderi - - BCG substrain M. celatum - - gothenburg - - M. chelonae - - moreau - - M. fortuitum - - tice - - M. gordonae + + tokyo - - M. intracellulare - - danish - - M. kansasii + + glaxo - - M. malmoense - - montreal - - M. marinum + + pasteur - - M. oenavense - - M. scrofulaceum - - M. smegmatis - - M. szulgai + + M. terrae - - M. vaccae - - M. xenopii - - Update on IGRAs: review of 38 studies on performance of IGRAs CI = confidence interval 18

19 Within Subject Variability and Boosting of T Cell Interferon γ Responses after Tuberculin Skin Testing 26 South African participants with varying TB exposure risk, HIV negative, BCG + QFT Gold, QFT Gold IT, T Spot repeated 4 times over 21 days pre TST and then on days 3,7, 28 and 84 post TST All 5 low risk patients were IGRA negative and remained IGRA negative 7/21 medium to high risk subjects had conversion or reversion, 1º with T spot The results of this study confirm that short term variability commonly occurs with both IGRA s. AJRCCM 2009, 180; 49 Within Subject Variability and Boosting of T Cell Interferon γ Responses after Tuberculin Skin Testing Boosting: A significant increase in mean QFT Gold IFN γ responses was noted by day 7 post TST that persisted for up to 3 months after the TST Author proposals for QFT Gold interpretation: Borderline or uncertainty zone: IU/ml Conversion threshold: Increase from <0.35 to >0.7 IU/ml AJRCCM 2009, 180; 49 19

20 QFT Gold Testing for Health Care Workers: Summary Significant intra individual variability in test results with serial short term testing Results can be boosted by TST (between 3 days and 3 months). QFT Gold testing should not be done more than 3 days after TST Multiple factors (some known, some unknown) likely can influence QFT Gold results For low risk HCW s, low level positive results must be viewed with caution and generally should be repeated (clinical judgment required for medium to high risk) QFT Gold Testing for Health Care Workers: Summary Know the numbers Do not accept positive or negative as the only written result You can only interpret indeterminate result if you know the numbers and you know the patient 20

21 Standard Components of TB/LTBI Evaluation If TST or IGRA Positive Patient History Physical examination Radiologic evaluation Laboratory results Physical Exam Lungs Palpate liver Look for anything that will complicate therapy 21

22 Radiologic Exam CXR must be done Must be normal Or IF abnormal: Not consistent with Active TB Stable abnormality confirmed over a 3 month period Clinical Evaluation: CXR Findings associated with higher risk of TB (require further evaluation and possible treatment for TB) Noncalcified nodular lesions Fibrotic scars Findings consistent with TB disease (require further evaluation and possible treatment for TB) Enlarged hilar, mediastinal or subcarinal lymph nodes Atelectasis Alveolar consolidation Interstitial infiltrates, cavitary and non cavitary Pleural effusion Focal mass Hyperinflation in children If CXR is abnormal, do not just treat for LTBI You must rule out Active TB 22

23 TST+/IGRA+ with Abnormal CXR Class 4 TB Not Clinically Active Must exclude active disease Abnormal CXR Any Abnormality NODULES/ FIBROTIC LESIONS OF OLD TB PLEURAL THICKENING CALCIFIED GRANULOMA BRONCHIECTASIS Is CXR Stable (compared to an old film) or is this a CXR with no comparison? Management of TST+/IGRA + With Abnormal CXR If patient has any signs or symptoms of TB disease: The patient is a TB Suspect Start 4 drugs Never start a single drug in a patient with possible active TB 23

24 Management of TST+/IGRA + With Abnormal CXR If patient has no symptoms of Active TB: Collect 3 sputum for smears and culture Evaluate for symptoms If no symptoms Wait Repeat CXR If CXR stable at 2 3 months and cultures negative, treat LTBI Case Management Patient Education Directly Observed Therapy (DOT) Laboratory Monitoring Treatment lasting 6 months to 2 years Discharge planning 24

25 Summary Remember major similarities and differences between LTBI and TB disease Know conditions that appear to increase risk for progression from LTBI to TB disease Rule out Active TB before deciding LTBI 25

26 ADHS TB Control Program (fax) Guidelines on Diagnosis and Treatment of LTBI CDC. Targeted TB Testing and Treatment of LTBI. June ATS/CDC/IDSA. Controlling Tuberculosis in the U.S. November NTCA/CDC. Guidelines for the Investigation of Contacts of Persons with Infectious Tuberculosis. December CDC. Guidelines for Using the QuantiFERON-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States. December 2005 CDC. TB Elimination, Treatment Options for Latent Tuberculosis Infection. November