1. 1.8 million tuberculosis infection llion deaths eaths Leading - PDF document

 10/3/2017 Disclosures I have nothing to disclose Updates in Tuberculosis Chris Keh, MD Assistant Clinical Professor, Division of Infectious Diseases, UCSF TB Controller, TB Prevention and Control Program, Population Health Division, SFDPH Global Tuberculosis, WHO 2015 Objectives report  Demonstrate and apply the USPSTF guidelines for latent TB infection in practice 10.4 million new  List three benefits of molecular testing and identify the settings in which to order this test cases*  Describe at least one treatment regimen to treat latent 1. 1.8 million tuberculosis infection llion deaths eaths Leading Infectious Killer in the World and Leading Killer of People Living with HIV * Additional one-third of the world’s population are infected 4  1

 10/3/2017 TB in the U.S.- what lies beneath How far are we from elimination? TB elimination: <1 case per million 9557 cases United States, 2015 30 cases per million (all) 1 out of 5 12 cases per million (U.S.‐born) non-U.S. born 151 cases per million (non‐U.S.‐born) 10-15 million has LTBI San Francisco, 2016 persons with 116 cases per million (all) 1 out of 8 LTBI Asian-born 23 cases per million (U.S. born) has LTBI 291 cases per million (non‐U.S.‐born) www.cdc.gov 6 USPSTF, Update for LTBI 2016 Incidence Projections to 2060 Cut in transmission Increase LTBI treatment, 2x or 4x more Recommendation: Grade: B  Screen for latent tuberculosis infection in asymptomatic adults at increased risk of infection Hill et al., Epidemiol Infect, 2012  2

 10/3/2017 TB as a spectrum of disease Diagnostics  Evidence of progression / regression of FDG-avid granulomas in non-human primates  Re-think binary definitions: LTBI vs Active Disease  Nomenclature change?: (Latent) Tuberculosis Infection 10 Screening Tools for LTBI Rapid Molecular Testing (Active TB)  Examples: GeneXpert, PCR, Pyrosequencing TST ( e.g. PPD) I GRA ( e.g. QFT, T-spot) Potential for false positive in Preferred in prior BCG  Provides rapid identification BCG vaccinated individuals vaccinated individuals Subjective Less subjective (although  Cultures are still necessary for drug susceptibilities issue with indeterminate)  Rapid turnaround time (2-3 hours compared to 4-6 Booster effect No booster effect weeks for culture) Injection, ≥ 2 visits Blood draw, single visit  Earlier initiation of effective tx Limited in young (2-5 yo)  Decreased period of infectiousness  Improved pt outcome  Earlier involvement of MDR expert  Earlier request for 1 st /2 nd line susceptibilities  Potential use in discontinuation of airborne isolation http://www.tbcontrollers.org/docs/resources/NTCA_APHL_GeneXpert_Consens us_Statement_Final.pdf 12  3

 10/3/2017 Xpert MTB/RIF Test Performance Xpert MTB/RIF Report Sensitivity Specificity  MTB DETECTED or NOT Sm ear pos. 95-98% TB DETECTED 99% Sm ear neg. 60-72%  Rif Resistance DETECTED or TB NOT DETECTED 98-99% 99-100% Rifam pin “R” NEJM 361:1005, 2010; Am J Crit Care Med 184:132, 2011 • Provides both MTB identification and detection of RIF resistance (rpoB) • Send on any patient with moderate-high suspicion for active TB • Can remain positive for months-years after adequate tx 13 14 LTBI Treatment Options Treatment Regimens for Latent TB Infection Drug(s) Duration Interval Minimum Doses Isoniazid 9 months Daily 270 Twice weekly 76 6 months Daily 180 Twice weekly 52  Isoniazid Isoniazid & 3 months Once weekly 12  Isoniazid + Rifapentine (3HP) Rifapentine  Rifampin  Isoniazid + Rifampin Rifampin 4 months Daily 120  4

 10/3/2017 INH + Rifapentine (3HP)  Once weekly x 12 weeks (12 doses)  Recommended as an equal alternative to INH x 9 mo  Current recommendation for directly observed therapy (may change in the next year)  Not recommended in: INH‐RPT INH  Children <2yo  HIV-infected patients on ART No. of patients 3,986 3,745  Pregnant or planning to become pregnant Self‐administered Administration Directly‐observed therapy  Contact to INH/RIF resistant cases therapy  Prior adverse events / hypersensitivity to INH/RIF Frequency Weekly Daily Duration 12 weeks 9 months  Recommendations for Use of an Isoniazid–Rifapentine Regimen with Direct Observation to Treat Sterling TR, et al; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and Latent Mycobacterium tuberculosis Infection. MMWR 2011;60:1650–1653 isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155‐66.  https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/TBCB‐INH‐RIF‐LTBI‐ fact‐sheet.pdf Prevent TB Study Results Side effects- 3HP  Possible hypersensitivity (3.8%) INH‐RPT INH P‐value  Rash (0.8%)  Hepatotoxicity (0.4%) Non‐  Thrombocytopenia (rare) Effectiveness 1.9 per 1,000 4.3 per 1,000 inferior  Other toxicities (3.2%) Completion 82.1% 69.0% P<0.001 rate  Monitoring- similar to INH or RIF  RFP drug-drug interactions similar to RIF Hepatotoxicity 0.4% 2.7% P<0.001 Sterling TR, et al; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011 Dec 8;365(23):2155‐66.  Recommendations for Use of an Isoniazid–Rifapentine Regimen with Direct Observation to Treat Latent Mycobacterium tuberculosis Infection. MMWR 2011;60:1650–1653  https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/TBCB‐INH‐RIF‐LTBI‐ fact‐sheet.pdf  5

 10/3/2017 Risk Assessment Tools  CA Risk Assessment California Tuberculosis Risk Assessment Adults ฀ Use this tool to identify asymptomatic adults for latent TB infection (LTBI) testing.  Adult, Pediatric, ฀ Re-testing should only be done in persons who previously tested negative, and have new risk factors since the last assessment. ฀ For TB symptoms or abnormal chest x-ray consistent with active TB disease: Evaluate for active TB disease College/University Students, Evaluate for active TB disease with a chest x-ray, symptom screen, and if indicated, sputum AFB smears, cultures and nucleic acid amplification testing. A negative tuberculin skin test or interferon gamma release assay does not rule out active TB disease. School Staff / Volunteers Check appropriate risk factor boxes below. LTBI testing is recommended if any of the 3 boxes below are checked. Additional New Tools If LTBI test result is positive and active TB disease is ruled out, LTBI treatment is recommended.  BCG Atlas ฀ Foreign-born person from a country with an elevated TB rate ฀ Includes any country other than the United States, Canada, Australia, New Zealand, or a country in western or northern Europe (www.bcgatlas.org) ฀ If resources require prioritization within this group, prioritize patients with at least one medical risk for progression (see the California Adult Tuberculosis Risk Assessment User Guide for this list) ฀ Interferon Gamma Release Assay is preferred over Tuberculin Skin Test for foreign-            ฀           Database of BCG practices ฀ Immunosuppression , current or planned HIV infection, organ transplant recipient, treated with TNF-alpha antagonist (e.g., infliximab, etanercept, others), steroids                          ฀     day    ฀                                            ฀ Close contact to someone with infectious TB disease at any time See the California Adult Tuberculosis Risk Assessment User Guide for more information about using this tool. Provider: ________________________________________ Patient Name: ___________________________________ Assessment Date: ________________________________ Date of Birth: ____________________________________ (Place sticker here if applicable) To ensure you have the most current version, go to the RISK ASSESSMENT page at: https://cdph.ca.gov/tbcb June 2017 https://www.cdph.ca.gov/Programs/CID/DCDC/Pages/TB-Risk- Assessment.aspx TST / IGRA Interpreter www.TSTin3d.com  Estimates risk of active TB  Limited to up to age 80  Accounts for risk factors Results Slide 23 Slide 24  6

 10/3/2017 Video Directly Observed Therapy Summary  Observation of medication ingestion by video  Asians have one of the highest case rates in the U.S. (30x higher than Caucasians)  Live vs Recorded  Patients born / residing in Asia have a high risk of TB  Smartphone application, cloud based infection  Can be used for active disease and LTBI  TB Elimination Movement- national, state, local  Cost-effective and ensures adherence  Newer tools can assist in TB elimination  Rapid diagnostics  IGRA  Shorter-course treatments  LTBI toolkits (e.g. CDC, CTCA/CDPH, in development)  LTBI registry (in development)  Updated guidelines  Risk assessment tools  VDOT http://www.calit2.net/newsroom/release.php?id=2211 Assistance is right around the corner…  TB Warmline Consultation (Curry International TB Center): 1-877-390-6682  Local Public Health Dept / TB Control  California Dept of Public Health, TB Control Branch, https://www.cdph.ca.gov/Progra ms/CID/DCDC/Pages/TBCB.aspx (510) 620-3000 (or your State TB Control Branch)  7