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•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 2010 20 Sep 10 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) None Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance • Epidemiology • Migrant trends • Programmatic opportunities • Summary Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Global TB disease burden Highly mobile global population Emergence of drug-resistant TB Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance CDC Plan to Combat Extensively Drug-Resistant TB • 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. MMWR 58: 13 Feb 2009 RR-3 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance • Epidemiology • Migrant trends • Programmatic opportunities • 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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology • Global TB rates and TB-related mortality are falling 2008 • 9.4 million incident cases up (9.3 in 2007) • Population growth • Incidence 139/ 100k (peak 143/100k in 2004) • 22 high-burden countries account for 80% of the global tuberculous burden • 2 billion with LTBI worldwide 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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology - MDR • 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 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology - MDR • Estimated 440,000 new cases in 2008 • • Only 7% were reported to WHO • Cost of Rx (US$) estimated $250,000/case 6000 treated in GLC approved program (16 of 22 high burden countries no MDR in GLCprogrammes) Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology – XDR Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology - XDR • 58 countries with at least one confirmed case of XDR • 8 countries reported XDR-TB in more than 10% of MDR-TB cases (E Europe, Central Asia) WHO Multidrug and extensively drug-resistant TB (M/XDR-TB) 2010 Global report MMWR 58: 13 Feb 2009 RR-3 Chest 136: 333, 2009 NEJM 363: 1050, 2010 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Epidemiology - XDR • • Cost of XDR Rx (US$) estimated $500,000/case Between 2010-2015 1.3 million cases MDR/XDR • Cost US$ 16,000,000,000 • Est. budgets combined 2010 - 0.5 billion • MDR funding 2015 16Xs current 2010 funding 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 - XDR • Contributing factors drug-resistance: • funding short fall • lack of DOT • infection control nosocomial transmission • ineffective standardized retreatment regimens • lack of DST and laboratory services • lack of reliable second-line drugs • lack of new drugs • lack of comprehensive provider buy-in 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 • Migrant trends • Programmatic opportunities • Summary Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Migrant trends • Global estimates • 214 million international migrants worldwide • 3.1% world population are migrants United Nations’ Trends in Total Migrant Stock: The 2008 Revision http://esa.un.org/migration Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Migrant trends • Global trends • 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 United Nations’ Trends in Total Migrant Stock: The 2008 Revision http://esa.un.org/migration Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance • Epidemiology • Migrant trends • Programmatic opportunities • Summary Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: systematic review and meta-analysis Arshad, et al • 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, 1980-2006) Eur Respir J 35: 1336, 2010 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: systematic review and meta-analysis Arshad, et al • • • Overall, 3.5 cases / 1000 screened (*) Refugees 11.9*, asylees 2.8*, and reg immigr 2.7* Prevalence ratio immigrants-autochthonous 48.2 Eur Respir J 35: 1336, 2010 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: US immigrants and refugees Liu et al • 1999 – 2005: 2,714,223 U.S. bound screened • c. 400k immigrants, 50-75k refugees /yr • TB rates (U.S.): • foreign born 11 times U.S. born (2009) • Refugees: 10.4/ 1000 Immigrants 9.6 / 1000 NEJM 360: 2406, 2009 MMWR 59: 289, 2010 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: US immigrants and refugees Liu et al • Top 5 birth countries of immigrants with overseas dignosis of TB: • Phillipines, Vietnam, China, Mexico, India • Top 5 birth countries of refugees with overseas diagnosis of TB: • Ukraine, Vietnam, Somalia, Bosnia/ Herzegovina, Sudan NEJM 360: 2406, 2009 MMWR 59: 289, 2010 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: US 2007 Technical Instructions • Improvements in overseas screening • Mycobacterial cultures • Drug susceptibility testing • Directly observed therapy • TST for children 2 – 14 years • Shorter interval between screening and departure for the U.S. NEJM 360: 2406, 2009 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance TB Sceening new immigrants: US 2007 Technical Instructions Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Programmatic Opportunities - Epidemiology U.S. • • • U.S. TB case rate 3.8 / 100,000 in 2009 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.” MMWR 59: 289, 2010 Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Programmatic Opportunities - Epidemiology U.S. • ? New technical instructions for preimmigration TB screening • ? Other: improved TB control, populationdemographic shifts, under-reporting/diagnosis, reductions in immigration / return home (Mexico), census adjustment MMWR 59: 289, 2010 Estimated Migrants “Entering” U.S. Visitors without visas ~ 30,000,000 Non-immigrant visas 27,907,139 Immigrants and refugees 411,266 Undocumented migrants ~ 275,000 ???? N= ~ 59,000,000 Status adjusters in U.S.: 679,305 Source: U.S. Department of Homeland Security, 2003 (2002 data) Refugee Arrivals to Minnesota by Region of World, 1979-2007 8000 Number of arrivals 7000 6000 5000 4000 3000 2000 Southeast Asia Sub-Saharan Africa Refugee Health Program, Minnesota Department of Healthof Refugee Health Program, Minnesota Department Health Eastern Europe FSU 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1982 1981 1980 0 1979 1000 Other *First resettled in Minnesota Tuberculosis Incidence Rates per 100,000 Population, United States and Minnesota, 19922008 United States 12 Minnesota Healthy People 2000 Objective* Healthy People 2010 Objective 8 6 4 2 0 19 92 19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 20 06 20 07 20 08 Cases per 100,000 10 Year of Diagnosis Number of Cases Number of Tuberculosis Cases by Place of Birth, Minnesota, 1999-2008 240 220 200 180 160 140 120 100 80 60 40 20 0 Total Foreign-Born U.S.-Born 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 Year of Diagnosis Tuberculosis Cases by Drug Susceptibility Patterns and Place of Birth, Minnesota, 2004-2008 Place of Birth Cases With Any Drug INH‡ † ** MDR-TB Susceptibility Resistance Resistant No. (%) Results* No. (%) No. (%) Foreign-Born Cases U.S.-Born Cases 660 132 97 (15) 12 ( 9) 75 (11) 8 ( 6) 12 ( 2) 4 ( 3) Total 792 109 (14) 83 (10) 16 ( 2) § * Culture-confirmed cases with drug susceptibility results available † 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. Percentage of Cases Tuberculosis Cases by Site of Disease and Place of Birth, Minnesota, 2004-2008 100 90 80 70 60 50 40 30 20 10 0 (63%) (47%) (53%) (37%) Foreign-Born Pulmonary U.S.-Born Extrapulmonary* * Includes cases with both extrapulmonary and pulmonary sites of disease Foreign-Born Tuberculosis Cases by Interval Between Arrival in U.S. and Diagnosis of Tuberculosis, Minnesota, 2003-2007 Interval (years) Cases No. ( %) <1 1-2 3-5 >5 Unknown Total 247 (28) 170 (19) 165 (19) 296 (33) 9 ( 1) 887 (100) Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance • Epidemiology • Migrant trends • Programmatic opportunities • Summary Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance CDC Plan to Combat Extensively Drug-Resistant TB • 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. 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 funding Case detection rate through quality-assured bacteriology Standardized treatment, with supervision and patient support An effective drug supply and management system Monitoring and assessment system, and impact measurement 2. Address TB/HIV, MDR-TB, and other challenges • • • Implement TB/HIV collaborative activities Prevent and control MDR-TB Address prisoners, refugees, and other high-risk groups, and special situations Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Summary • World population is increasing and more mobile • Drug-resistance is man-made • Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLIEXPAND TB) is critical Treatment of Migrants with Tuberculosis in an Era of Emerging Drug Resistance Summary • World population is increasing and more mobile • Drug-resistance is man-made • Increased screening in conjunction with international initiatives (STOP-TB, GLC, GLIEXPAND TB) is critical