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Drug Resistant Tuberculosis- U.S. Stories & Perspectives European Respiratory Society Amsterdam Congress Sep 11 Timothy R. Aksamit, MD Associate Professor of Medicine Consultant Pulmonary Disease and Critical Care Medicine Mayo Clinic Rochester, Minnesota USA Timothy R. Aksamit, MD Associate Professor of Medicine Consultant Pulmonary Disease and Critical Care Medicine Mayo Clinic Rochester, Minnesota USA

Drug Resistant Tuberculosis- U.S. Stories & Perspectives DISCLOSURE Relevant Financial Relationship(s) NoneDISCLOSURE None

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Cases Cases Clinical points Clinical points Summary Summary Cases Cases Clinical points Clinical points Summary Summary

Drug Resistant Tuberculosis- U.S. Stories & Perspectives HPI: 31 y.o. female never smoker pharmacist from India March 2008: cough, sputum, dyspnea, fever, and hemoptysisMarch 2008: cough, sputum, dyspnea, fever, and hemoptysis No anorexia, wt loss; no chest x-rayNo anorexia, wt loss; no chest x-ray 37 weeks pregnant, azithromycin and acetaminophen37 weeks pregnant, azithromycin and acetaminophen May 2008: CXR markedly abnormalMay 2008: CXR markedly abnormal June 2008: 3 sputa; all smear –ve; 2/3 +ve MAC; chest CT bilat nodules, RLL consolidationJune 2008: 3 sputa; all smear –ve; 2/3 +ve MAC; chest CT bilat nodules, RLL consolidation Aug 2008: 3 sputa; 1/3 weakly smear +ve, 1/3 AFB cx +ve no IDAug 2008: 3 sputa; 1/3 weakly smear +ve, 1/3 AFB cx +ve no ID No Rx!No Rx! Employed as pharmacist, continued at workEmployed as pharmacist, continued at work Persist cough and fatiguePersist cough and fatigue Aug 2009: Chest CT bilateral nodular infiltrates, cavity RB6Aug 2009: Chest CT bilateral nodular infiltrates, cavity RB6 Sep 2009: Bronch – TBBx non-caseating granulomas, smear –ve, cx –ve for AFBSep 2009: Bronch – TBBx non-caseating granulomas, smear –ve, cx –ve for AFB MAC Rx started – rash on RBT, placed on EMB, Cipro, and ClariMAC Rx started – rash on RBT, placed on EMB, Cipro, and Clari HPI: 31 y.o. female never smoker pharmacist from India March 2008: cough, sputum, dyspnea, fever, and hemoptysisMarch 2008: cough, sputum, dyspnea, fever, and hemoptysis No anorexia, wt loss; no chest x-rayNo anorexia, wt loss; no chest x-ray 37 weeks pregnant, azithromycin and acetaminophen37 weeks pregnant, azithromycin and acetaminophen May 2008: CXR markedly abnormalMay 2008: CXR markedly abnormal June 2008: 3 sputa; all smear –ve; 2/3 +ve MAC; chest CT bilat nodules, RLL consolidationJune 2008: 3 sputa; all smear –ve; 2/3 +ve MAC; chest CT bilat nodules, RLL consolidation Aug 2008: 3 sputa; 1/3 weakly smear +ve, 1/3 AFB cx +ve no IDAug 2008: 3 sputa; 1/3 weakly smear +ve, 1/3 AFB cx +ve no ID No Rx!No Rx! Employed as pharmacist, continued at workEmployed as pharmacist, continued at work Persist cough and fatiguePersist cough and fatigue Aug 2009: Chest CT bilateral nodular infiltrates, cavity RB6Aug 2009: Chest CT bilateral nodular infiltrates, cavity RB6 Sep 2009: Bronch – TBBx non-caseating granulomas, smear –ve, cx –ve for AFBSep 2009: Bronch – TBBx non-caseating granulomas, smear –ve, cx –ve for AFB MAC Rx started – rash on RBT, placed on EMB, Cipro, and ClariMAC Rx started – rash on RBT, placed on EMB, Cipro, and Clari

Drug Resistant Tuberculosis- U.S. Stories & Perspectives HPI: 31 y.o. female never smoker pharmacist from India Jan 2010: Cough, scant purulent sputum, fatigueJan 2010: Cough, scant purulent sputum, fatigue No recurrent hemoptysis, F, C, S, pleuritic cp,No recurrent hemoptysis, F, C, S, pleuritic cp, No pyrosis, reflux, dysphagia, odynophagiaNo pyrosis, reflux, dysphagia, odynophagia Sinuses stableSinuses stable HPI: 31 y.o. female never smoker pharmacist from India Jan 2010: Cough, scant purulent sputum, fatigueJan 2010: Cough, scant purulent sputum, fatigue No recurrent hemoptysis, F, C, S, pleuritic cp,No recurrent hemoptysis, F, C, S, pleuritic cp, No pyrosis, reflux, dysphagia, odynophagiaNo pyrosis, reflux, dysphagia, odynophagia Sinuses stableSinuses stable

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

HPI: 31 y.o. female never smoker pharmacist from India Jan 2010:Jan 2010: Sputum:Sputum: AFB smear: –veAFB smear: –ve AFB cx: +veAFB cx: +ve M. TB complexM. TB complex M. abscessusM. abscessus Age 10 - treated with 3 months (single) TB medicationAge 10 - treated with 3 months (single) TB medication Childhood exposure: aunt active TB diseaseChildhood exposure: aunt active TB disease India visitor 1 week before coming ill 2008India visitor 1 week before coming ill : chest x-ray –ve2004: chest x-ray –ve 2008: IGRA QFT Gold +ve (no value available)2008: IGRA QFT Gold +ve (no value available) M. TB sent to CDC for rapid molecular susceptibility tests:M. TB sent to CDC for rapid molecular susceptibility tests: Molecular Detection of Drug Resistance (MDDR) programMolecular Detection of Drug Resistance (MDDR) program Resistance (molecular): INH (katG), RIF (rpoB) (as well as EMB (embB) and PZA (pncA))Resistance (molecular): INH (katG), RIF (rpoB) (as well as EMB (embB) and PZA (pncA)) HPI: 31 y.o. female never smoker pharmacist from India Jan 2010:Jan 2010: Sputum:Sputum: AFB smear: –veAFB smear: –ve AFB cx: +veAFB cx: +ve M. TB complexM. TB complex M. abscessusM. abscessus Age 10 - treated with 3 months (single) TB medicationAge 10 - treated with 3 months (single) TB medication Childhood exposure: aunt active TB diseaseChildhood exposure: aunt active TB disease India visitor 1 week before coming ill 2008India visitor 1 week before coming ill : chest x-ray –ve2004: chest x-ray –ve 2008: IGRA QFT Gold +ve (no value available)2008: IGRA QFT Gold +ve (no value available) M. TB sent to CDC for rapid molecular susceptibility tests:M. TB sent to CDC for rapid molecular susceptibility tests: Molecular Detection of Drug Resistance (MDDR) programMolecular Detection of Drug Resistance (MDDR) program Resistance (molecular): INH (katG), RIF (rpoB) (as well as EMB (embB) and PZA (pncA))Resistance (molecular): INH (katG), RIF (rpoB) (as well as EMB (embB) and PZA (pncA))

Drug Resistant Tuberculosis- U.S. Stories & Perspectives HPI: 31 y.o. female never smoker pharmacist from India Feb 2010:Feb 2010: TB medications started:TB medications started: Moxifloxacin 400 mg dailyMoxifloxacin 400 mg daily Amikacin 510 mg (15 mg/kg/d) dailyAmikacin 510 mg (15 mg/kg/d) daily Cycloserine 250 mg twice dailyCycloserine 250 mg twice daily Linezolid 600 mg dailyLinezolid 600 mg daily PAS 4 gm dailyPAS 4 gm daily DST – Broth (Versatrek Method)DST – Broth (Versatrek Method) Isoniazid (0.1 ug/mL) R Isoniazid (0.4 ug/mL) RIsoniazid (0.1 ug/mL) R Isoniazid (0.4 ug/mL) R Rifampin (1 ug/mL) R Ethambutol (5 ug/mL) SRifampin (1 ug/mL) R Ethambutol (5 ug/mL) S Ethambutol (8 ug/mL) SEthambutol (8 ug/mL) S 22 month old – TST negative, ? LTBI22 month old – TST negative, ? LTBI HPI: 31 y.o. female never smoker pharmacist from India Feb 2010:Feb 2010: TB medications started:TB medications started: Moxifloxacin 400 mg dailyMoxifloxacin 400 mg daily Amikacin 510 mg (15 mg/kg/d) dailyAmikacin 510 mg (15 mg/kg/d) daily Cycloserine 250 mg twice dailyCycloserine 250 mg twice daily Linezolid 600 mg dailyLinezolid 600 mg daily PAS 4 gm dailyPAS 4 gm daily DST – Broth (Versatrek Method)DST – Broth (Versatrek Method) Isoniazid (0.1 ug/mL) R Isoniazid (0.4 ug/mL) RIsoniazid (0.1 ug/mL) R Isoniazid (0.4 ug/mL) R Rifampin (1 ug/mL) R Ethambutol (5 ug/mL) SRifampin (1 ug/mL) R Ethambutol (5 ug/mL) S Ethambutol (8 ug/mL) SEthambutol (8 ug/mL) S 22 month old – TST negative, ? LTBI22 month old – TST negative, ? LTBI

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

HPI: 71 y.o. male from China Cough and dyspneaCough and dyspnea Came to U.S. to visit childrenCame to U.S. to visit children HPI: 71 y.o. male from China Cough and dyspneaCough and dyspnea Came to U.S. to visit childrenCame to U.S. to visit children

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

HPI: 71 y.o. male from China Cough and dyspneaCough and dyspnea Came to U.S. to visit childrenCame to U.S. to visit children Treated multiple times in China for tuberculosis without successTreated multiple times in China for tuberculosis without success Smear +ve, cx +ve M. TB (prior to MDDR)Smear +ve, cx +ve M. TB (prior to MDDR) Resistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQResistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQ Treated:Treated: EthionamideEthionamide CapreomycinCapreomycin CycloserineCycloserine PASPAS LinezolidLinezolid HPI: 71 y.o. male from China Cough and dyspneaCough and dyspnea Came to U.S. to visit childrenCame to U.S. to visit children Treated multiple times in China for tuberculosis without successTreated multiple times in China for tuberculosis without success Smear +ve, cx +ve M. TB (prior to MDDR)Smear +ve, cx +ve M. TB (prior to MDDR) Resistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQResistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQ Treated:Treated: EthionamideEthionamide CapreomycinCapreomycin CycloserineCycloserine PASPAS LinezolidLinezolid

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

HPI: 71 y.o. male from China Cough and dyspneaCough and dyspnea Came to U.S. to visit childrenCame to U.S. to visit children Treated multiple times in China for tuberculosis without successTreated multiple times in China for tuberculosis without success Smear +ve, cx +ve M. TB (prior to MDDR)Smear +ve, cx +ve M. TB (prior to MDDR) Resistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQResistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQ Treated:Treated: EthionamideEthionamide CapreomycinCapreomycin CycloserineCycloserine PASPAS LinezolidLinezolid Sputum conversion: 3 months, smear and cx –veSputum conversion: 3 months, smear and cx –ve Hospitalized 4 monthsHospitalized 4 months Surgery consideredSurgery considered Returned to ChinaReturned to China HPI: 71 y.o. male from China Cough and dyspneaCough and dyspnea Came to U.S. to visit childrenCame to U.S. to visit children Treated multiple times in China for tuberculosis without successTreated multiple times in China for tuberculosis without success Smear +ve, cx +ve M. TB (prior to MDDR)Smear +ve, cx +ve M. TB (prior to MDDR) Resistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQResistance: INH, RIF, RBT, EMB, PZA, STM, AMK, FLQ Treated:Treated: EthionamideEthionamide CapreomycinCapreomycin CycloserineCycloserine PASPAS LinezolidLinezolid Sputum conversion: 3 months, smear and cx –veSputum conversion: 3 months, smear and cx –ve Hospitalized 4 monthsHospitalized 4 months Surgery consideredSurgery considered Returned to ChinaReturned to China

Drug Resistant Tuberculosis- U.S. Stories & Perspectives HPI: 19 y.o. male from India Back painBack pain University engineering studentUniversity engineering student Diagnosed with TB vertebral osteomyelitis and paraspinal abscessDiagnosed with TB vertebral osteomyelitis and paraspinal abscess Cx +ve M. TBCx +ve M. TB Resistance: INH, RIF, RBT, STM, EMBResistance: INH, RIF, RBT, STM, EMB Return home (India) for treatmentReturn home (India) for treatment Receives RIFEReceives RIFE Returned to U.S. to restart schoolReturned to U.S. to restart school Seizures and comaSeizures and coma HPI: 19 y.o. male from India Back painBack pain University engineering studentUniversity engineering student Diagnosed with TB vertebral osteomyelitis and paraspinal abscessDiagnosed with TB vertebral osteomyelitis and paraspinal abscess Cx +ve M. TBCx +ve M. TB Resistance: INH, RIF, RBT, STM, EMBResistance: INH, RIF, RBT, STM, EMB Return home (India) for treatmentReturn home (India) for treatment Receives RIFEReceives RIFE Returned to U.S. to restart schoolReturned to U.S. to restart school Seizures and comaSeizures and coma

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

HPI: 19 y.o. male from India Back painBack pain University engineering studentUniversity engineering student Diagnosed with TB vertebral osteomyelitis and paraspinal abscessDiagnosed with TB vertebral osteomyelitis and paraspinal abscess Cx +ve M. TBCx +ve M. TB Resistance: INH, RIF, RBT, STM, EMBResistance: INH, RIF, RBT, STM, EMB Return home (India) for treatmentReturn home (India) for treatment Receives RIFEReceives RIFE Returned to U.S. to restart schoolReturned to U.S. to restart school Seizures and comaSeizures and coma LP, CT, MRI c/w TB Meningitis; no organism isolated from CSFLP, CT, MRI c/w TB Meningitis; no organism isolated from CSF 3 years of multiple 2 nd line agents and linezolid with corticosteroids3 years of multiple 2 nd line agents and linezolid with corticosteroids Graduates with engineering degree, residual motor deficitsGraduates with engineering degree, residual motor deficits Lost to follow upLost to follow up HPI: 19 y.o. male from India Back painBack pain University engineering studentUniversity engineering student Diagnosed with TB vertebral osteomyelitis and paraspinal abscessDiagnosed with TB vertebral osteomyelitis and paraspinal abscess Cx +ve M. TBCx +ve M. TB Resistance: INH, RIF, RBT, STM, EMBResistance: INH, RIF, RBT, STM, EMB Return home (India) for treatmentReturn home (India) for treatment Receives RIFEReceives RIFE Returned to U.S. to restart schoolReturned to U.S. to restart school Seizures and comaSeizures and coma LP, CT, MRI c/w TB Meningitis; no organism isolated from CSFLP, CT, MRI c/w TB Meningitis; no organism isolated from CSF 3 years of multiple 2 nd line agents and linezolid with corticosteroids3 years of multiple 2 nd line agents and linezolid with corticosteroids Graduates with engineering degree, residual motor deficitsGraduates with engineering degree, residual motor deficits Lost to follow upLost to follow up

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Cases Cases Clinical points Clinical points Summary Summary Cases Cases Clinical points Clinical points Summary Summary

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

Highly mobile global population Emergence of drug-resistant TB Global TB disease burden

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology

Drug Resistant Tuberculosis- U.S. Stories & Perspectives TB Incidence Rates 2008 WHO Global tuberculosis control-a short update to the 2009 report

Drug Resistant Tuberculosis- U.S. Stories & Perspectives TB control and elimination Lancet 375: 1814, 2010

Global TB rates and TB-related mortality are falling 2008 Global TB rates and TB-related mortality are falling million incident cases up (9.3 in 2007) 9.4 million incident cases up (9.3 in 2007) Population growth Population growth Incidence 139/ 100k (peak 143/100k in 2004) Incidence 139/ 100k (peak 143/100k in 2004) 22 high-burden countries account for 80% of the global tuberculous burden 22 high-burden countries account for 80% of the global tuberculous burden 2 billion with LTBI worldwide 2 billion with LTBI worldwide Global TB rates and TB-related mortality are falling 2008 Global TB rates and TB-related mortality are falling million incident cases up (9.3 in 2007) 9.4 million incident cases up (9.3 in 2007) Population growth Population growth Incidence 139/ 100k (peak 143/100k in 2004) Incidence 139/ 100k (peak 143/100k in 2004) 22 high-burden countries account for 80% of the global tuberculous burden 22 high-burden countries account for 80% of the global tuberculous burden 2 billion with LTBI worldwide 2 billion with LTBI worldwide Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology – MDR new cases WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology – MDR previously Rx cases WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report

Estimated 440,000 new cases in 2008 Estimated 440,000 new cases in 2008 Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology - MDR

Estimated 440,000 new cases in 2008 Estimated 440,000 new cases in 2008

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology - MDR Estimated 440,000 new cases in 2008 Estimated 440,000 new cases in 2008 Only 7% were reported to WHO Only 7% were reported to WHO 6000 treated in GLC approved program (16 of 22 high burden countries no MDR in GLC- programmes) 6000 treated in GLC approved program (16 of 22 high burden countries no MDR in GLC- programmes) Cost of Rx (US$) estimated $250,000/case Cost of Rx (US$) estimated $250,000/case Estimated 440,000 new cases in 2008 Estimated 440,000 new cases in 2008 Only 7% were reported to WHO Only 7% were reported to WHO 6000 treated in GLC approved program (16 of 22 high burden countries no MDR in GLC- programmes) 6000 treated in GLC approved program (16 of 22 high burden countries no MDR in GLC- programmes) Cost of Rx (US$) estimated $250,000/case Cost of Rx (US$) estimated $250,000/case

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology - XDR

58 countries with at least one confirmed case of XDR 58 countries with at least one confirmed case of XDR 8 countries reported XDR-TB in more than 10% of MDR-TB cases (E Europe, Central Asia) 8 countries reported XDR-TB in more than 10% of MDR-TB cases (E Europe, Central Asia) Cost of Rx (US$) estimated $500,000/case Cost of Rx (US$) estimated $500,000/case 58 countries with at least one confirmed case of XDR 58 countries with at least one confirmed case of XDR 8 countries reported XDR-TB in more than 10% of MDR-TB cases (E Europe, Central Asia) 8 countries reported XDR-TB in more than 10% of MDR-TB cases (E Europe, Central Asia) Cost of Rx (US$) estimated $500,000/case Cost of Rx (US$) estimated $500,000/case Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology - XDR WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009 WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009

Contributing factors drug-resistance: lack of DOT, ineffective standardized retreatment regimens, lack of DST, lack of reliable second- line drugs, lack of new drugs Contributing factors drug-resistance: lack of DOT, ineffective standardized retreatment regimens, lack of DST, lack of reliable second- line drugs, lack of new drugs Drug Resistant Tuberculosis- U.S. Stories & Perspectives Epidemiology - XDR WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009 WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009

Global estimates Global estimates 214 million international migrants worldwide 214 million international migrants worldwide 3.1% world population are migrants 3.1% world population are migrants Global estimates Global estimates 214 million international migrants worldwide 214 million international migrants worldwide 3.1% world population are migrants 3.1% world population are migrants Drug Resistant Tuberculosis- U.S. Stories & Perspectives Migrant trends United Nations’ Trends in Total Migrant Stock: The 2008 Revision

Global trends Global trends Total number of international migrants has increased : 150 to 214 million from 2000 – 2008 (up 43%) Total number of international migrants has increased : 150 to 214 million from 2000 – 2008 (up 43%) Migration distributed widely across more countries – Top 10 countries of destination (2008) receive a smaller share of all migrants than in 2000 Migration distributed widely across more countries – Top 10 countries of destination (2008) receive a smaller share of all migrants than in 2000 Global trends Global trends Total number of international migrants has increased : 150 to 214 million from 2000 – 2008 (up 43%) Total number of international migrants has increased : 150 to 214 million from 2000 – 2008 (up 43%) Migration distributed widely across more countries – Top 10 countries of destination (2008) receive a smaller share of all migrants than in 2000 Migration distributed widely across more countries – Top 10 countries of destination (2008) receive a smaller share of all migrants than in 2000 Drug Resistant Tuberculosis- U.S. Stories & Perspectives Migrant trends United Nations’ Trends in Total Migrant Stock: The 2008 Revision

Global trends Global trends Many migrants come from the 22 countries with highest TB-disease burden which make up 80% of global TB cases and a substantial proportion of MDR and XDR TB cases Many migrants come from the 22 countries with highest TB-disease burden which make up 80% of global TB cases and a substantial proportion of MDR and XDR TB cases (source control) Global trends Global trends Many migrants come from the 22 countries with highest TB-disease burden which make up 80% of global TB cases and a substantial proportion of MDR and XDR TB cases Many migrants come from the 22 countries with highest TB-disease burden which make up 80% of global TB cases and a substantial proportion of MDR and XDR TB cases (source control) Drug Resistant Tuberculosis- U.S. Stories & Perspectives Migrant trends United Nations’ Trends in Total Migrant Stock: The 2008 Revision

1999 – 2005: 2,714,223 U.S. bound screened 1999 – 2005: 2,714,223 U.S. bound screened c. 400k immigrants, 50-70k refugees /yr c. 400k immigrants, 50-70k refugees /yr TB rates (U.S.): TB rates (U.S.): foreign born 11 times U.S. born (2009) foreign born 11 times U.S. born (2009) Refugees: 10.4/ 1000 Immigrants 9.6 / 1000 Refugees: 10.4/ 1000 Immigrants 9.6 / 1000 Inactive TB: 28.4/ 1000 (ref) 8.4/1000 (immig) Inactive TB: 28.4/ 1000 (ref) 8.4/1000 (immig) 1999 – 2005: 2,714,223 U.S. bound screened 1999 – 2005: 2,714,223 U.S. bound screened c. 400k immigrants, 50-70k refugees /yr c. 400k immigrants, 50-70k refugees /yr TB rates (U.S.): TB rates (U.S.): foreign born 11 times U.S. born (2009) foreign born 11 times U.S. born (2009) Refugees: 10.4/ 1000 Immigrants 9.6 / 1000 Refugees: 10.4/ 1000 Immigrants 9.6 / 1000 Inactive TB: 28.4/ 1000 (ref) 8.4/1000 (immig) Inactive TB: 28.4/ 1000 (ref) 8.4/1000 (immig) Drug Resistant Tuberculosis- U.S. Stories & Perspectives TB Sceening new immigrants: US immigrants and refugees NEJM 360: 2406, 2009 MMWR 59: 289, 2010 NEJM 360: 2406, 2009 MMWR 59: 289, 2010

Top 5 birth countries of immigrants with overseas dignosis of TB: Top 5 birth countries of immigrants with overseas dignosis of TB: Phillipines, Vietnam, China, Mexico, India Phillipines, Vietnam, China, Mexico, India Top 5 birth countries of refugees with overseas diagnosis of TB: Top 5 birth countries of refugees with overseas diagnosis of TB: Ukraine, Vietnam, Somalia, Bosnia/ Herzegovina, Sudan Ukraine, Vietnam, Somalia, Bosnia/ Herzegovina, Sudan Top 5 birth countries of immigrants with overseas dignosis of TB: Top 5 birth countries of immigrants with overseas dignosis of TB: Phillipines, Vietnam, China, Mexico, India Phillipines, Vietnam, China, Mexico, India Top 5 birth countries of refugees with overseas diagnosis of TB: Top 5 birth countries of refugees with overseas diagnosis of TB: Ukraine, Vietnam, Somalia, Bosnia/ Herzegovina, Sudan Ukraine, Vietnam, Somalia, Bosnia/ Herzegovina, Sudan Drug Resistant Tuberculosis- U.S. Stories & Perspectives TB Sceening new immigrants: US immigrants and refugees Liu et al NEJM 360: 2406, 2009 MMWR 59: 289, 2010 NEJM 360: 2406, 2009 MMWR 59: 289, 2010

Improvements in overseas screening Improvements in overseas screening Mycobacterial cultures Mycobacterial cultures Drug susceptibility testing Drug susceptibility testing Directly observed therapy Directly observed therapy TST for children 2 – 14 years TST for children 2 – 14 years Shorter interval between screening and departure for the U.S. Shorter interval between screening and departure for the U.S. Improvements in overseas screening Improvements in overseas screening Mycobacterial cultures Mycobacterial cultures Drug susceptibility testing Drug susceptibility testing Directly observed therapy Directly observed therapy TST for children 2 – 14 years TST for children 2 – 14 years Shorter interval between screening and departure for the U.S. Shorter interval between screening and departure for the U.S. Drug Resistant Tuberculosis- U.S. Stories & Perspectives TB Sceening new immigrants: US 2007 Technical Instructions NEJM 360: 2406, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives TB Sceening new immigrants: US 2007 Technical Instructions

Source: U.S. Department of Homeland Security, 2003 (2002 data) Status adjusters in U.S.: 679,305 Immigrants and refugees 411,266 Undocumented migrants ~ 275,000 ???? Non-immigrant visas 27,907,139 N= ~ 59,000,000 Visitors without visas ~ 30,000,000 Estimated Migrants “Entering” U.S.

Tuberculosis Incidence Rates per 100,000 Population, United States and Minnesota,

Trends in Tuberculosis-United States, 2010 (MMWR 3/25/11) 3.6 cases/100,000 pop (3.9% ↓ since 2009) 3.6 cases/100,000 pop (3.9% ↓ since 2009) Ca, Tx, NY, Fl > 500 cases/state, 49% all TB Ca, Tx, NY, Fl > 500 cases/state, 49% all TB U.S. born 1.6 cases/100, %↓ since ’09, 78% ↓ since ’93. U.S. born 1.6 cases/100, %↓ since ’09, 78% ↓ since ’ % TB patients co-infected with HIV 8.6% TB patients co-infected with HIV 3.6 cases/100,000 pop (3.9% ↓ since 2009) 3.6 cases/100,000 pop (3.9% ↓ since 2009) Ca, Tx, NY, Fl > 500 cases/state, 49% all TB Ca, Tx, NY, Fl > 500 cases/state, 49% all TB U.S. born 1.6 cases/100, %↓ since ’09, 78% ↓ since ’93. U.S. born 1.6 cases/100, %↓ since ’09, 78% ↓ since ’ % TB patients co-infected with HIV 8.6% TB patients co-infected with HIV

Trends in Tuberculosis-United States, 2010 (MMWR 3/25/11) Foreign born 60.5% TB cases, 18.1 cases/100,000 Foreign born 60.5% TB cases, 18.1 cases/100,000 Foreign born account for 89.4% of MDR cases in the U.S. (rate 5X higher in previously treated patients than patients without previous history of TB). Foreign born account for 89.4% of MDR cases in the U.S. (rate 5X higher in previously treated patients than patients without previous history of TB). 1.3% of all TB is MDR 1.3% of all TB is MDR Foreign born 60.5% TB cases, 18.1 cases/100,000 Foreign born 60.5% TB cases, 18.1 cases/100,000 Foreign born account for 89.4% of MDR cases in the U.S. (rate 5X higher in previously treated patients than patients without previous history of TB). Foreign born account for 89.4% of MDR cases in the U.S. (rate 5X higher in previously treated patients than patients without previous history of TB). 1.3% of all TB is MDR 1.3% of all TB is MDR

Unless the fundamental causes of MDR TB and XDR TB are addressed in the United States and internationally, the United States is likely to experience a growing number of cases of MDR TB and XDR TB that will be difficult, if not impossible to treat or prevent. Unless the fundamental causes of MDR TB and XDR TB are addressed in the United States and internationally, the United States is likely to experience a growing number of cases of MDR TB and XDR TB that will be difficult, if not impossible to treat or prevent. Drug Resistant Tuberculosis- U.S. Stories & Perspectives CDC Plan to Combat Extensively Drug-Resistant TB MMWR 58: 13 Feb 2009 RR-3

Number of Tuberculosis Cases by Place of Birth, Minnesota,

Foreign-Born Tuberculosis Cases by Region of Birth and Year of Diagnosis, Minnesota, Region of Birth Number of Cases

Foreign-Born Tuberculosis Cases by Country of Birth, Minnesota, Somalia (35%) Ethiopia (13%) Mexico (7%) Vietnam (5%) Laos (5%) India (5%) Other Countries (22%) N = 869 Liberia (5%) Kenya (4%)

Refugee Health Program, Minnesota Department of Health *First resettled in Minnesota Refugee Arrivals to Minnesota by Region of World,

Tuberculosis Cases by Site of Disease and Place of Birth, Minnesota, (47%) * Includes cases with both extrapulmonary and pulmonary sites of disease (53%) (63%) (37%)

Think globally! Act locally!

Think and act globally! Think and act locally!

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Role of rapid testing for the identification of rifampicin- and isoniazid-resistance Similar to ISTC 1 – 4Similar to ISTC 1 – 4 Risk assessment based on signs, symptoms, and risk factors for TB infectionRisk assessment based on signs, symptoms, and risk factors for TB infection When risk factors present multiple sputa to be collected with rapid testing for rifampicin- and isoniazid-resistanceWhen risk factors present multiple sputa to be collected with rapid testing for rifampicin- and isoniazid-resistance Role of rapid testing for the identification of rifampicin- and isoniazid-resistance Similar to ISTC 1 – 4Similar to ISTC 1 – 4 Risk assessment based on signs, symptoms, and risk factors for TB infectionRisk assessment based on signs, symptoms, and risk factors for TB infection When risk factors present multiple sputa to be collected with rapid testing for rifampicin- and isoniazid-resistanceWhen risk factors present multiple sputa to be collected with rapid testing for rifampicin- and isoniazid-resistance

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

Chest 137: 393, 2010 Hallym University Medical Center Gyeonggi, KoreaHallym University Medical Center Gyeonggi, Korea

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Chest 137: 393, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Chest 137: 393, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Chest 137: 393, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Chest 137: 393, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives

Isolation of both M. TB and Nontuberculous mycobacteria - COMMON Treat M. TB first then re-assess NTM pulmonary diseaseTreat M. TB first then re-assess NTM pulmonary disease Not all smear +ve (in U.S.) is NTM;Not all smear +ve (in U.S.) is NTM; Not all smear +ve (in developing) is M. TBNot all smear +ve (in developing) is M. TB Isolation of both M. TB and Nontuberculous mycobacteria - COMMON Treat M. TB first then re-assess NTM pulmonary diseaseTreat M. TB first then re-assess NTM pulmonary disease Not all smear +ve (in U.S.) is NTM;Not all smear +ve (in U.S.) is NTM; Not all smear +ve (in developing) is M. TBNot all smear +ve (in developing) is M. TB

Drug Resistant Tuberculosis- U.S. Stories & Perspectives IJTLD 14: 654, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives IJTLD 14: 654, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives IJTLD 14: 654, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives IJTLD 14: 654, 2010

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009 Taipei, TaiwanTaipei, Taiwan 2133 patients with pulmonary tuberculosis2133 patients with pulmonary tuberculosis Taipei, TaiwanTaipei, Taiwan 2133 patients with pulmonary tuberculosis2133 patients with pulmonary tuberculosis

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Resp Med 103: 1484, 2009

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Eur Radiol 16: 1934, 2006 Samsung Medical Center Seoul, South KoreaSamsung Medical Center Seoul, South Korea

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Eur Radiol 16: 1934, 2006

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Eur Radiol 16: 1934, 2006

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Eur Radiol 16: 1934, 2006

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Eur Radiol 16: 1934, 2006

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Eur Radiol 16: 1934, 2006

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Eur Radiol 16: 1934, 2006

Drug Resistant Tuberculosis- U.S. Stories & Perspectives Cases Cases Clinical points Clinical points Summary Summary Cases Cases Clinical points Clinical points Summary Summary

World population is increasing and more mobile World population is increasing and more mobile Drug-resistance is man-made Drug-resistance is man-made Not all AFB positive sputa (in U.S.) is NTM Not all AFB positive sputa (in U.S.) is NTM Risk assessment Risk assessment Molecular tools Molecular tools Varied epidemiology Varied epidemiology World population is increasing and more mobile World population is increasing and more mobile Drug-resistance is man-made Drug-resistance is man-made Not all AFB positive sputa (in U.S.) is NTM Not all AFB positive sputa (in U.S.) is NTM Risk assessment Risk assessment Molecular tools Molecular tools Varied epidemiology Varied epidemiology Drug Resistant Tuberculosis- U.S. Stories & Perspectives Summary

World population is increasing and more mobile World population is increasing and more mobile Drug-resistance is man-made Drug-resistance is man-made Not all AFB positive sputa (in U.S.) is NTM Not all AFB positive sputa (in U.S.) is NTM Risk assessment Risk assessment Molecular tools Molecular tools Varied epidemiology Varied epidemiology World population is increasing and more mobile World population is increasing and more mobile Drug-resistance is man-made Drug-resistance is man-made Not all AFB positive sputa (in U.S.) is NTM Not all AFB positive sputa (in U.S.) is NTM Risk assessment Risk assessment Molecular tools Molecular tools Varied epidemiology Varied epidemiology Drug Resistant Tuberculosis- U.S. Stories & Perspectives Summary

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