Case Presentations Part 2

Case Presentations Part 2 Connie A. Haley, MD MPH University of Florida, Infectious Diseases and Global Medicine Megan Ninneman, PA Jackson Memorial Hospital, Miami FL Objectives Demonstrate the ability to apply principles of transmission and pathogenesis to case situations to effectively treat and improve outcomes of complex cases. Discuss the risk factors and clinical conditions associated with tuberculosis to ensure appropriate evaluation and initiation of treatment for TB. 1

Background United States tuberculosis (TB) rates are highest among the elderly and the foreign born populations. Louisville mirrors that pattern & accounts for most of Kentucky TB morbidity. Definitions: Refugees flee from persecution or armed conflict Migrants move for cultural, economic reasons, but not forcibly moved Kentucky TB in Kentucky 67 cases of TB reported in 2015; ranked 34 th among states. Refugees in Kentucky Estimated 1,990 refugees resettled in FY 2015 (ACF, 2016) Approximately 3% of all refugees Approximately 10,800 refugees were resettled in or moved to the Louisville between 1994 2004 (Kentucky Wilson Fish Project, 2005) 2

Louisville TB in Louisville Approximately 30 active TB cases annually 80% are among foreign born Drug budget $60,000 annually Refugees in Louisville Most refugees settle in Louisville Refugee agencies locally are Catholic Charities of Louisville and Kentucky Refugee Ministries Case study 54 y.o. male born in Bhutan, requires interpreter 1 6 2012 arrived in US from Nepali refugee camp How should you evaluate him for TB/LTBI? 3

Case study 2 1 12 T spot was positive Nil (negative) Panel A spot 13 Panel B spot 12 Positive control spot count >20 03 16 12: Evaluated by LHD Reported shortness of breath and weight loss No cough, fever, chills, night sweats, chest pain, hemoptysis, appetite loss, fatigue, or lymphadenopathy or other physical findings Current CXR: RUL apical scarring 4

Case study What additional history should you get? Case study What should you do now? 5

No Loose Solution For patients with a positive TST or IGRA and an abnormal CXR suggestive of TB, including possibly prior TB with fibronodular changes: Obtain cultures and susceptibilities with molecular test Start 4 drug therapy for TB disease (INH, RIF, PZA, EMB) Re evaluate for clinical/radiographic improvement at 2 mo If no improvement, stop therapy and close as having completed LTBI therapy. If improved, treat for culture negative TB disease (4 mo.) If risk of drug resistance (e.g., foreign born, previously treated, exposed to MDR TB) continue all 4 drugs for 4 mo. Case study Prescribed 9 months of INH 7 10 12: Reports weakness, weight loss, burning pain in legs, referred to PCP 09 18 12: PCP evaluated him but complaints had resolved; Dx DM (HGbA1C 10.3), OA both knees Burning in legs persisted during therapy Reported he completed INH 12 13 2012 6

Case study 11 27 2015: Presented to ER reporting sudden fever, shaking, felt chilled prior week, denied cough or SOA 11 27 15: CXR patchy airspace disease RML, both LL Concerning for small L effusion Case study What is the most appropriate step at this time? 7

Case study 11 30 15 CT Chest: Acute LLL pneumonia with predominately posterior subpleural consolidation; Irreg nodular airspace disease RML, likely acute pneumonia Now he reports having prior TB. What would you do at this point? Case study 12 14 15: AFB culture from 11 28 15 grew MTB. 12 22 15 CXR: compared to 03 06 2012, new irregular opacity on periphery of R mid lung. Chronic R. apical scarring 8

Case study GeneXPERT (+) rifampin resistance (rpob mutation) Isolate sent to CDC for MDDR* Held initiation of treatment until MDDR results available to guide appropriate therapy Home isolation *MDDR= molecular detection of drug resistance Case study: Overseas Screening Hx Treated for TB in Asia, 1990 (not reported at immigration screening?) Contact to a TB case in the neighborhood. Grew very ill with fatigue, appetite loss, and cough. Received TB Tx for 12 months; first 90d was daily shot and one pill; remaining 9 mos was one pill/d (possibly was SM + INH or combination pill of rifamate=rif/inh or rifateur=inh/rif/pza). CXR showed resolution after treatment Screened overseas, despite abnormal CXR of R upper lobe scarring, negative cultures, allowed to immigrate without treatment for TB 9

Case study MDDR confirmed resistance to RIF, INH, PZA, EMB, Streptomycin, PAS, Ethionamide Susceptible to ofloxacin, capreomycin, amikacin But, sample was collected before he was treated with LQ Susceptible to linezolid and bedaquiline (CDC research panel ; will report on request) Susceptible to cycloserine (National Jewish lab) Repeat C&S, MDDR on sample collected after he completed levaquin susceptibility ultimately confirmed http://www.currytbcenter.ucsf.edu/products/cover pages/drug resistant tuberculosis survival guide clinicians 3rd edition 10

Building a Treatment Regimen for MDR TB http://www.currytbcenter.ucsf.edu/products/cover pages/drug resistant tuberculosis survival guide clinicians 3rd edition Case study Pre XDR Regimen: 1. Bedaquiline 2. Capreomycin 3. Cycloserine 4. Linezolid 5. Imipenem + clavulanate (iv) 6. Clofazamine 7. Moxifloxacin (didn t count it until confirmed susceptible) 8. B6 9. +7 other medicines 11

CXR 13 months into therapy TB Program Resources Treated with 4 drugs at cost of $77,000 annually, total 2 yrs. Louisville HD costs $33,000 55% of TB drug budget Large contact investigation in the home and community required significant additional resources 12

Contact Investigation Setting Adult Day Care (ADC) caters to immigrant and refugees Daily census 50 to 100 clients, elderly & chronic illness Daily routine includes meals and activities Multiple community rooms for TV and games and other activities Clients primarily elderly with range of medical problems including dementia Contact Investigation Results After 2 nd round Family 6 members All contact investigations completed 4 family members started on LTBI therapy 2 family members had negative TSTs/IGRA & X rays ADC clients 94 attendees 92 contact investigations complete; 2 lost to follow up 17 clients had positive TST/IGRA & negative X rays clients had negative TST/IGRA & negative X rays 4 clients started on LTBI therapy 1 client died; not related to TB ADC workers (n=26)/transport (n=1) 27 total 27 contact investigations complete 0 workers started on LTBI therapy 27 workers had negative TST/IGRA & X rays 13

Conclusions One case of MDR TB resulted in large local requirements of staff time and local cost expenditures Contact investigation will require one additional year of effort to monitor the contacts Similar cases can be expected given Louisville s resettlement of large numbers of refugees and immigrants Contact investigations in settings such as this ADC are especially difficult given the chronic health problems 2016 Global TB Report http://www.who.int/tb/publications/global_report/en/ 14

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D. Posey, NTCA 2017: http://www.tbcontrollers.org/docs/conference/2017/general_session_ii_02_posey_04 18_Final.pdf 16

P LoBue, NTCA 2017 17

Overseas Screening Program Immigrants and Refugees Panel Physicians, Department of State (DOS), and DGMQ CBP Quarantine Stations Abbreviations: Customs and Border Patrol (CBP) Immigrant, Refugee, Migrant Health (IRMH) Electronic Disease Notification System (EDN) IRMH (EDN) Health Departments 18

CDOT TB TI, 2007 WHO Incidence 20/100,000 2 14 years of age 15 Years of age TST or IGRA Medical history, physical exam TST<10mm/IRGA ( ) TST 10mm/IRGA (+) CXR No TB Classification Travel within 6 months Normal Signs or symptoms, CXR suggestive of TB, or HIV Infection If TST/IGRA not required ( 15 years old): No TB Classification Travel within 6 months If TST 10mm/IRGA (+): Class B2 LTBI Evaluation Travel within 6 months Applicants with HIV infection who have negative smears/cultures are No Class for TB and Class B Other, HIV infection; Travel within 3 months* 1 positive smear or culture Class A TB DST on positive culture DOT according to ATS/CDC/IDSA guidelines until therapy complete Class B1 TB Travel within 3 months* Three sputum smears and cultures for Mycobacterium tuberculosis All negative Class B1 TB Travel within 3 months* *Of date culture result reported CDOT TB TI, 2007 WHO Incidence <20/100,000 15 Years of age Medical history, physical exam CXR Normal Signs or symptoms, CXR suggestive of TB, or HIV Infection If TST/IGRA not required ( 15 years old): No TB Classification Travel within 6 months If TST 10mm/IRGA (+): Class B2 LTBI Evaluation Travel within 6 months Applicants with HIV infection who have negative smears/cultures are No Class for TB and Class B Other, HIV infection; Travel within 3 months* 1 positive smear or culture Class A TB DST on positive culture DOT according to ATS/CDC/IDSA guidelines until therapy complete Class B1 TB Travel within 3 months* Three sputum smears and cultures for Mycobacterium tuberculosis All negative Class B1 TB Travel within 3 months* *Of date culture result reported 19

Current Culture and DOT (CDOT) TB TI Classifications Class Status No classification Class A Class B1 Pulmonary Class B1 Extrapulmonary Class B2 Class B3 Normal evaluation Tuberculosis disease Abnormal CXR, sputum smears and cultures negative Extrapulmonary tuberculosis Latent TB Infection evaluation TB contact evaluation Implementation of CDOT TB screening requirements, 2007 2014 Preliminary analysis of crude indicators reported by panel physicians found increased detection of active TB disease using new CDOT TB TI requirements - ~1,100 immigrants dx with TB during 2012 (most recent data) - ~ 60% were smear ( )/culture (+) - 14 diagnosed with MDR TB Possible annual crude savings > $15 million Posey et al. MMWR Morb Mortal Wkly Rep. 2014 Mar 21;63(11):234 6. 20

TB Control Priorities in the U.S. 1. Detection and treatment of persons with active tuberculosis (TB) 2. Investigation of infectious cases to detect contacts who may have active TB or may be infected with risk of future TB 3. Prevent TB disease through targeted testing and treatment of LTBI 21

US Preventive Services Task Force (USPSTF) Recommendation in 2016 *B Recommendation = USPSTF recommends this service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. 2016 USPSTF Recommendation This recommendation applies to asymptomatic adults 18 years of age who are at increased risk for TB and are seen in primary care settings. Born in, or former residents of, countries with increased tuberculosis prevalence (e.g., Mexico, Philippines, Vietnam, India, China, Haiti, Guatemala) Currently live in, or have lived in, high risk congregate settings (e.g., homeless shelters, long term care facilities, correctional facilities) It does not apply to adults with symptoms of TB disease or children and adolescents 22

Additional Populations at Risk for LTBI The recommendation does not address the additional need for LTBI testing in other high risk populations. CDC recommends the following populations continue to be tested for LTBI as part of other screening efforts: Persons with immunosuppression (e.g. HIV/AIDS, immunosuppressive medications, silicosis): TB testing is conducted by specialists. Persons who are contacts of persons with active TB disease: TB testing is conducted as part of public health programs. Health care workers and workers in high risk congregate settings: TB testing is conducted as part of employee health programs. 23

Evaluation of Persons with Positive TB Test Results Person has a positive test for TB infection TB disease ruled out Consider for LTBI treatment Person accepts and is able to receive treatment of LTBI If person refuses or is unable to receive treatment for LTBI, follow up TST or IGRA and serial chest radiographs are unnecessary Develop a plan of treatment with patient to ensure adherence CDC: http://www.cdc.gov/tb/publications/slidesets/ltbi/default.htm Educate patient about the signs and symptoms of TB disease Isoniazid Isoniazid LTBI Treatment Susceptible Disease Recommended regimens Drug Frequency Duration Issues Abbrev Daily Twice weekly 9 months (6 months) 9 months (6 months) Long duration, poor adherence Directly observed, long duration 9H 9H DOT Rifampin Daily 4 months** Drug interactions 4R Isoniazid + rifapentine Isoniazid + rifampin Rifampin + pyrazinamide Once weekly 3 months DOT 3HP Daily Other regimens (not recommended in the US) Daily or 2x/week 3 months 2 months ** 4 months of Rifampin now recommended for children Not in U.S. recommendations Potentially fatal: NOT RECOMMENDED 3HR 2RZ 24

1 800 4TB INFO Resources CURE TB (Bi national referrals between US and Mexico) Website: http://www.sandiegocounty.gov/hhsa/programs/phs/cur e_tb/ Forms and instructions: http://publichealth.lacounty.gov/tb/forms/bi tbformsinstruction.pdf Global Plan to Stop TB http://www.stoptb.org/global/plan/ 25

Resources Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection MMWR 2000; 49 (No. RR 6) http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.h tm Recommendations for Use of an Isoniazid Rifapentine Regimen with Direct Observation to Treat Latent Mycobacterium tuberculosis Infection http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6048a3.htm?s_cid=mm6048a3_w Latent Tuberculosis Infection: A Guide for Primary Health Care Providers http://www.cdc.gov/tb/publications/ltbi/default.htm Resources Saukkonen, et al. 2006. An official ATS statement: hepatotoxicity of antituberculosis therapy. Am J Respir Crit Care Med 174:935 52. http://ajrccm.atsjournals.org/content/174/8/935.full.pdf+html Severe Isoniazid Associated Liver Injuries Among Persons Being Treated for Latent Tuberculosis Infection United States, 2004 2008. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5908a3.h tm?s_cid=mm5908a3_e Managing Drug Interactions in the Treatment of HIV Related Tuberculosis http://www.cdc.gov/tb/publications/guidelines/tb_hiv_drugs /default.htm 26

Resources Fact Sheets TB in Hispanic/Latinos http://www.cdc.gov/tb/publications/factsheets/specpop/tu berculosis_in_hispanics_latinos.htm TB information for international travelers http://www.cdc.gov/tb/publications/factsheets/general/tbtr avelinfo.htm BCG Vaccine http://www.cdc.gov/tb/publications/factsheets/prevention/ bcg.htm Bovine Tuberculosis in Humanshttp://www.cdc.gov/tb/publications/factsheets/gen eral/mbovis.htm Resources Country Guides: Individualized Country Guides support the provider foreign born client relationship by giving countryspecific background information, epidemiological data, common misperceptions and beliefs about TB and HIV/AIDS, as well as information about general health practices, cultural beliefs and courtesies to observe. http://sntc.medicine.ufl.edu/products.aspx Quick Reference Guides: Two page guide for certain countries provides essential background information, epidemiology, common misperceptions and beliefs about TB and HIV/AIDS, general practices and cultural courtesies. http://sntc.medicine.ufl.edu/products.aspx 27

Figure (not our patient) demonstrates right upper lobe linear opacities, apical pleural thickening, and volume loss. Note the elevation of the right hilum and hemi diaphragm. Post primary tuberculosis often associated with significant fibrosis. The resultant scarring can cause volume loss of the involved lung or lobe. Fibrotic lesions may indicate either active or prior TB can only distinguish with clinical and microbiological evaluation. Presence of parenchymal opacities representing old healed TB increases risk of progression to TB in individuals who received inadequate prior treatment for TB or LTBI. http://www.vdh.virginia.gov/tb/healthprofessionals/documents/cxrch2.pdf Fibrotic Lesion in Left Upper Lobe on CT scan http://jjmicrobiol.com/?page=article&article_id=5179 28

Case 30 yo Asian woman noted to have abnormal CXR prior to employment screening as a health care worker. She had a positive TST 4 years earlier, for which she was treated 9 months of INH. She denies symptoms, has no underlying medical conditions, and is a non smoker Case 29

Case Based on your reading of this CXR, what is the best next step? 1. Collect 3 sputums for AFB smear and culture (and genexpert) 2. Begin treatment of LTBI with INH 3. Repeat the TST 4. Repeat the CXR in 6 months Case She was started on 4 drugs for 2 months, then reevaluated. Cultures were negative. Follow up CXR was obtained. 30

Case Case Which of the following is the most appropriate next step? 1. Continue multi drug therapy for TB disease 2. Obtain a CT scan 3. Perform a FNA of the nodule 4. Perform a bronchoscopy to obtain a better respiratory specimen 31