Thank you for viewing this presentation. We would like to remind you that this material is the property of the author. It is provided to you by the ERS for your personal use only, as submitted by the author.  2010 by the author

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance European Respiratory Society Barcelona Congress Sep 10 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

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance DISCLOSURE Relevant Financial Relationship(s) NoneDISCLOSURE None

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance

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

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. Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance CDC Plan to Combat Extensively Drug-Resistant TB MMWR 58: 13 Feb 2009 RR-3

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Incidence Rates 2008 WHO Global tuberculosis control-a short update to the 2009 report

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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology Lancet 375: 1814, 2010

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology – MDR new cases WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology - MDR

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

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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) 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) Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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 NEJM 363: 1050, 2010 WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009 NEJM 363: 1050, 2010

Cost of XDR Rx (US$) estimated $500,000/case Cost of XDR Rx (US$) estimated $500,000/case Between million cases MDR/XDR Between million cases MDR/XDR Cost US$ 16,000,000,000 Cost US$ 16,000,000,000 Est. budgets combined billion Est. budgets combined billion MDR funding Xs current 2010 funding MDR funding Xs current 2010 funding Cost of XDR Rx (US$) estimated $500,000/case Cost of XDR Rx (US$) estimated $500,000/case Between million cases MDR/XDR Between million cases MDR/XDR Cost US$ 16,000,000,000 Cost US$ 16,000,000,000 Est. budgets combined billion Est. budgets combined billion MDR funding Xs current 2010 funding MDR funding Xs current 2010 funding Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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 NEJM 363: 1050, 2010 WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009 NEJM 363: 1050, 2010

Contributing factors drug-resistance: Contributing factors drug-resistance: funding short fall funding short fall lack of DOT lack of DOT infection control nosocomial transmission infection control nosocomial transmission ineffective standardized retreatment regimens ineffective standardized retreatment regimens lack of DST and laboratory services lack of DST and laboratory services lack of reliable second-line drugs lack of reliable second-line drugs lack of new drugs lack of new drugs lack of comprehensive provider buy-in lack of comprehensive provider buy-in Contributing factors drug-resistance: Contributing factors drug-resistance: funding short fall funding short fall lack of DOT lack of DOT infection control nosocomial transmission infection control nosocomial transmission ineffective standardized retreatment regimens ineffective standardized retreatment regimens lack of DST and laboratory services lack of DST and laboratory services lack of reliable second-line drugs lack of reliable second-line drugs lack of new drugs lack of new drugs lack of comprehensive provider buy-in lack of comprehensive provider buy-in Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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 NEJM 363: 1050, 2010 WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009 NEJM 363: 1050, 2010

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary

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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Migrant trends United Nations’ Trends in Total Migrant Stock: The 2008 Revision

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary

Assessment of yield of active screening for TB among new immigrants at point of entry Assessment of yield of active screening for TB among new immigrants at point of entry Migrants to Western Europe, Kuwait, Australia, New Zealand, & USA (low prevalence, ) Migrants to Western Europe, Kuwait, Australia, New Zealand, & USA (low prevalence, ) Assessment of yield of active screening for TB among new immigrants at point of entry Assessment of yield of active screening for TB among new immigrants at point of entry Migrants to Western Europe, Kuwait, Australia, New Zealand, & USA (low prevalence, ) Migrants to Western Europe, Kuwait, Australia, New Zealand, & USA (low prevalence, ) Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: systematic review and meta-analysis Arshad, et al Eur Respir J 35: 1336, 2010

Overall, 3.5 cases / 1000 screened (*) Overall, 3.5 cases / 1000 screened (*) Refugees 11.9*, asylees 2.8*, and reg immigr 2.7* Refugees 11.9*, asylees 2.8*, and reg immigr 2.7* Prevalence ratio immigrants-autochthonous 48.2 Prevalence ratio immigrants-autochthonous 48.2 Overall, 3.5 cases / 1000 screened (*) Overall, 3.5 cases / 1000 screened (*) Refugees 11.9*, asylees 2.8*, and reg immigr 2.7* Refugees 11.9*, asylees 2.8*, and reg immigr 2.7* Prevalence ratio immigrants-autochthonous 48.2 Prevalence ratio immigrants-autochthonous 48.2 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: systematic review and meta-analysis Arshad, et al Eur Respir J 35: 1336, 2010

1999 – 2005: 2,714,223 U.S. bound screened 1999 – 2005: 2,714,223 U.S. bound screened c. 400k immigrants, 50-75k refugees /yr c. 400k immigrants, 50-75k 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 / – 2005: 2,714,223 U.S. bound screened 1999 – 2005: 2,714,223 U.S. bound screened c. 400k immigrants, 50-75k refugees /yr c. 400k immigrants, 50-75k 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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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

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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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. Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: US 2007 Technical Instructions NEJM 360: 2406, 2009

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: US 2007 Technical Instructions

U.S. TB case rate 3.8 / 100,000 in 2009 U.S. TB case rate 3.8 / 100,000 in % decrease from 2008 (4.2) 11.4% decrease from 2008 (4.2) “ The 2009 rate showed the greatest single-year decrease ever recorded and was the lowest recorded rate since national TB surveillance began in 1953.” “ The 2009 rate showed the greatest single-year decrease ever recorded and was the lowest recorded rate since national TB surveillance began in 1953.” U.S. TB case rate 3.8 / 100,000 in 2009 U.S. TB case rate 3.8 / 100,000 in % decrease from 2008 (4.2) 11.4% decrease from 2008 (4.2) “ The 2009 rate showed the greatest single-year decrease ever recorded and was the lowest recorded rate since national TB surveillance began in 1953.” “ The 2009 rate showed the greatest single-year decrease ever recorded and was the lowest recorded rate since national TB surveillance began in 1953.” Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Programmatic Opportunities - Epidemiology U.S. MMWR 59: 289, 2010

? New technical instructions for pre- immigration TB screening ? New technical instructions for pre- immigration TB screening ? Other: improved TB control, population- demographic shifts, under-reporting/diagnosis, reductions in immigration / return home (Mexico), census adjustment ? Other: improved TB control, population- demographic shifts, under-reporting/diagnosis, reductions in immigration / return home (Mexico), census adjustment ? New technical instructions for pre- immigration TB screening ? New technical instructions for pre- immigration TB screening ? Other: improved TB control, population- demographic shifts, under-reporting/diagnosis, reductions in immigration / return home (Mexico), census adjustment ? Other: improved TB control, population- demographic shifts, under-reporting/diagnosis, reductions in immigration / return home (Mexico), census adjustment Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Programmatic Opportunities - Epidemiology U.S. MMWR 59: 289, 2010

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.

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

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

Number of Tuberculosis Cases by Place of Birth, Minnesota,

Tuberculosis Cases by Drug Susceptibility Patterns and Place of Birth, Minnesota, Tuberculosis Cases by Drug Susceptibility Patterns and Place of Birth, Minnesota, Place of Birth Place of Birth * Culture-confirmed cases with drug susceptibility results available TotalTotal Cases With SusceptibilitySusceptibility Results * Any Drug Resistance † No. (%) 97 (15) 12 ( 9) 109 (14) INH-INH- ResistantResistant ** No. (%) 75 (11) 8 ( 6) 8 ( 6) 83 (10) MDR-TBMDR-TB ‡ No. (%) 12 ( 2) 4 ( 3) 4 ( 3) 1616 § ( 2) U.S.-Born Cases Foreign-Born Cases † Resistance to at least one first-line anti-TB drug [i.e., isoniazid (INH), rifampin, pyrazinamide (PZA), or ethambutol] ** INH-resistant cases (also may have resistance to other drugs) ‡ Multi-drug resistant TB, with resistance to at least INH and rifampin § Two of these cases were resistant to INH, rifampin, PZA, and ethambutol.

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%)

Foreign-Born Tuberculosis Cases by Interval Between Arrival in U.S. and Diagnosis of Tuberculosis, Minnesota, Interval (years) Cases No. ( %) Cases < > 5 UnknownTotal < > 5 UnknownTotal 247 (28) 170 (19) 165 (19) 296 (33) 9 ( 1) 9 ( 1) 887 (100) 247 (28) 170 (19) 165 (19) 296 (33) 9 ( 1) 9 ( 1) 887 (100)

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary Epidemiology Epidemiology Migrant trends Migrant trends Programmatic opportunities Programmatic opportunities Summary Summary

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. Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance CDC Plan to Combat Extensively Drug-Resistant TB MMWR 58: 13 Feb 2009 RR-3

Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 2006 WHO Stop TB Strategy 1.Pursue high-quality DOTS expansion Political commitment with increased and sustained fundingPolitical commitment with increased and sustained funding Case detection rate through quality-assured bacteriologyCase detection rate through quality-assured bacteriology Standardized treatment, with supervision and patient supportStandardized treatment, with supervision and patient support An effective drug supply and management systemAn effective drug supply and management system Monitoring and assessment system, and impact measurementMonitoring and assessment system, and impact measurement 2.Address TB/HIV, MDR-TB, and other challenges Implement TB/HIV collaborative activitiesImplement TB/HIV collaborative activities Prevent and control MDR-TBPrevent and control MDR-TB Address prisoners, refugees, and other high-risk groups, and special situationsAddress prisoners, refugees, and other high-risk groups, and special situations 1.Pursue high-quality DOTS expansion Political commitment with increased and sustained fundingPolitical commitment with increased and sustained funding Case detection rate through quality-assured bacteriologyCase detection rate through quality-assured bacteriology Standardized treatment, with supervision and patient supportStandardized treatment, with supervision and patient support An effective drug supply and management systemAn effective drug supply and management system Monitoring and assessment system, and impact measurementMonitoring and assessment system, and impact measurement 2.Address TB/HIV, MDR-TB, and other challenges Implement TB/HIV collaborative activitiesImplement TB/HIV collaborative activities Prevent and control MDR-TBPrevent and control MDR-TB Address prisoners, refugees, and other high-risk groups, and special situationsAddress prisoners, refugees, and other high-risk groups, and special situations

World population is increasing and more mobile World population is increasing and more mobile Drug-resistance is man-made Drug-resistance is man-made Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical World population is increasing and more mobile World population is increasing and more mobile Drug-resistance is man-made Drug-resistance is man-made Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance 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 Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical World population is increasing and more mobile World population is increasing and more mobile Drug-resistance is man-made Drug-resistance is man-made Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLI- EXPAND TB) is critical Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Summary