THE FEW REMAINING (IMPOSSIBLE) CASES AG Holley 60 th Anniversary Celebration AG Holley State Hospital Lantana, FL July 21, 2010 Lee B. Reichman, MD, MPH AG Holley 60th Anniversary Celebration 1
TB Historical Permutation 17th - 18th centuries TB took 1 in 5 adult lives 1850-1950 one billion people died d of TB Next decade 2010-2020 300 million new infections 90 million new cases 30 million deaths More people died from TB last year than any year in history TB Could Be Eliminated Because We Understand It We know its: Cause Transmission Treatment Prevention AG Holley 60th Anniversary Celebration 2
TB Isn t Eliminated Because: Nobody seems to care This wouldn t be tolerated for any other disease Deaths Due To: TB (annually) 1,800,000 SARS 813 H1N1 18,311 Anthrax 5 Mad Cow Disease 1(Cow) Smallpox 0 AG Holley 60th Anniversary Celebration 3
Latest Global TB Estimates - 2008 All forms of TB Greatest number of cases in Asia; greatest rates per capita in Africa Multidrug-resistant TB (MDR-TB) Extensively drug-resistant TB (XDR-TB) HIV-associated TB Estimated number of cases 9.4 million (139 per 100,000) 440,000 (3.6% of cases) ~50,000 5.4% of MDR (58 countries) 1.4 million (15%) Estimated number of deaths 1.8 million (27 per 100,000) ~150,000 (Updated June 2010) ~30,000 456,000 The Global Burden of TB, 2008 http://www.who.int/tb/publications/global_report/en/index.html Estimated 9.4 million new cases 7.9 million (84%) in Asia and sub-saharan Africa 8% of new TB cases are HIV-infected 22% of new TB cases in Africa are HIV-infected 1.8 million people died of TB (98% of deaths in developing world) 456,000 HIV-infected patients 1/3 of the world is infected with M. tb (2 billion people) AG Holley 60th Anniversary Celebration 4
Estimated Numbers of New Cases, 2006 Estimated number of new TB cases (all forms) No estimate 0 999 1000 9999 10 000 99 999 100 000 999 999 1 000 000 or more The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved Estimated TB Burden, 2006 22 high burden countries # of new cases # of new cases 1. India 1,933,000 12. Vietnam 149,000 2. China 1,311,000,000 13. Kenya 141,000 3. Indonesia 534,000 14. Tanzania 123,000 4. South Africa 454,000 15. Uganda 106,000 5. Nigeria 450,000 16. Brazil 94,000 6. Bangladesh 351,000 17. Mozambique 93,000 7. Ethiopia 306,000 18. Thailand 90,000 8. Pakistan 292,000 19. Myanmar 83,000 9. Philippines 248,000 20. Zimbabwe 74,000 10. DR Congo 237,000 21. Cambodia 71,000 11. Russia 153,000 22. Afghanistan 42,000 TOTAL: 7,335,000 AG Holley 60th Anniversary Celebration 5
Global TB Control: Background 1991 World Health Assembly recognized the growing g importance of TB as a public health problem A new framework for TB control was developed A global strategy called DOTS was introduced (originally stood for Directly Observed Treatment, Short Course) International TB Control Strategy DOTS : 1991-2005 Political commitment Case detection using sputum microscopy among persons seeking care for prolonged cough Standardized short-course chemotherapy under proper case-management conditions including DOT Regular drug supply Standardized recording and reporting system that allows assessment of individual patients as well as overall program performance AG Holley 60th Anniversary Celebration 6
World Health Assembly Targets for Global TB Control By 2000: Detect 70% of all new sputum smear-positive cases every year Successfully treat 85% of these cases The slow progress of many countries prior to 2000 led to the revision of the target year to 2005 2005 targets narrowly missed: Case detection: 63%; treatment success: 85% Difficulties of managing TB in Africa and Eastern Europe linked to HIV/AIDS and drug resistance International TB Control Strategy Stop TB Strategy: 2006 - current 1. Pursue high-quality DOTS expansion and enhancement 2. Address TB/HIV, MDR-TB and other challenges 3. Contribute to health system strengthening 4. Engage all care providers 5. Empower people with TB, and communities 6. Enable and promote research AG Holley 60th Anniversary Celebration 7
Emergence of worst-case TB scenarios Co-infection between TB and HIV Multidrug-resistant TB (MDR-TB) Resistance to isoniazid and rifampin the 2 most powerful anti-tb drugs Extensively-drug resistant TB (XDR-TB) MDR-TB plus resistance to any fluoroquinolone l and at least 1 second-line injectable (AMI, KAN, CAP) The Global Burden of TB/HIV 1/3 of 33 million people living with HIV/AIDS co-infected with TB (>10 million people) Without treatment, 90% will die within months HIV and TB form a lethal combination, each speeding the other's progress TB is the leading cause of death among HIVpositive people (up to 50% of all patients worldwide) AG Holley 60th Anniversary Celebration 8
Co-Existence of HIV & TB infection TB Infection HIV Infection 10% per lifetime 10% per year.0017% per year Risk of Active TB Estimated HIV Prevalence in New TB Cases, 2006 HIV prevalence in TB cases, (%) No estimate 0 4 5 19 20 49 50 or more The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. WHO 2006. All rights reserved AG Holley 60th Anniversary Celebration 9
MDRTB/XDRTB - The Big Problem! 500,000 new MDR-TB cases estimated annually XDR-TB in 58 countries <5% of estimated MDR-TB cases detected in 2006 10% of MDR-TB cases projected to be treated in 2008 and 3% only under GLC standards About 85% of the global MDR-TB burden in 27 countries Sources: Global TB Report, 2008 and IV Global DRS Report, 2008 Use of One Drug Knowingly or Unknowingly Sensitive bacilli killed Resistant bacilli multiply unimpeded Resistant bacilli become dominant Efficacy of Fluroquinolones in TB and non Efficacy of Fluroquinolones in TB and non TB infection suggests increases in cross species resistance will increase as has already been shown AG Holley 60th Anniversary Celebration 10
Distribution of countries and territories reporting at least one case of XDR-TB as of January 2010 Source: WHO M/XDR-TB, 2010 Global Report Distribution of proportion of MDR-TB among new TB cases, 1994-2009 Source: WHO M/XDR-TB, 2010 Global Report AG Holley 60th Anniversary Celebration 11
Distribution of proportion of MDR-TB among previously treated TB cases, 1994-2009 Source: WHO M/XDR-TB, 2010 Global Report Estimated proportion and number of MDR-TB cases in the 27 MDR-TB high burden countries, 2008 Source: WHO M/XDR-TB, 2010 Global Report AG Holley 60th Anniversary Celebration 12
Unsexy Tuberculosis Concern and attention re: XDR-TB is appropriate, but skips the more important message XDR-TB, MDR-TB, and drug-sensitive tuberculosis are all the same disease The only difference is that MDR-TB is drug-sensitive tuberculosis modified by inappropriate treatment or drug taking, and XDR-TB is MDR-TB thus modified We need to recognize that there are more than 9,000,000 new active drugsensitive cases of tuberculosis globally that could be feeding drug resistance It might be a less sexy concept, but they all must be appropriately treated with current strategies (as well as new diagnostics, drugs, vaccines, and proper infection control measures) to avoid preventable MDR-TB and XDR- TB, which are always lurking Preventing active, drug-sensitive tuberculosis, or treating it properly, should be everybody s priority; it is the only way to prevent MDR-TB and XDR-TB Reichman, LB The Lancet, 2009 AG Holley 60th Anniversary Celebration 13
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Inadequacies in Physician Practices Major Recurring Practice Delays in diagnosis and errors in treatment Resulting In Increased risk and likelihood of disease transmission More advanced and complicated disease Lengthened hospital stays Increased medical costs Development of MDR-TB and XDR-TB AG Holley 60th Anniversary Celebration 16
International Standard for TB Care: Diagnosis All persons with otherwise unexplained cough lasting for 2-3 weeks or more should be evaluated for tuberculosis AG Holley 60th Anniversary Celebration 17
International Standard for TB Care: Diagnosis Microbiological evaluation (smear ± culture) is essential for all patients (including children, extra-pulmonary, and persons with radiographic abnormalities) International Standard for TB Care: Treatment The provider is responsible for prescribing an adequate regimen and ensuring adherence AG Holley 60th Anniversary Celebration 18
International Standard for TB Care: Treatment A patient-centered, individualized approach to treatment should be developed for all patients. A central element is direct observation by a treatment supporter. Progress Towards Global Targets 70/85 by 2005 2007 Case detection rate: 63% (target 70%) 2006 Treatment success: 85% (target 85%) AG Holley 60th Anniversary Celebration 19
Where Are The Missing Cases? They are not detected due to poor laboratory capacity Where Are The Missing Cases? At home, if services are not accessible AG Holley 60th Anniversary Celebration 20
Where Are The Missing Cases? In other un-connected public systems (prisons) Where Are The Missing Cases? In the private sector AG Holley 60th Anniversary Celebration 21
Patient Involvement in Medical Care Patients and their families have become increasingly gy involved and influential in all aspects of medical care In the mid-eighties, as the first anti-viral drugs for treating AIDS were being developed, activists demanded to participate in the design of clinical trials directed by the National Institutes of Health and pharmaceutical companies Laypeople now routinely sit on committees on the N.I.H. and on hospitals institutional review boards, which assess the ethicality and scientific merit of clinical trials The Patient s Charter for Tuberculosis Care AG Holley 60th Anniversary Celebration 22
The Patient s Charter for Tuberculosis Care Companion document to International Standards Initiated and developed by patients from around the world Outlines rights and responsibilities of people with tuberculosis Affirms that empowerment is catalyst for effective collaboration of the patient with health providers and authorities Patient s Rights You have the right to: Care; Dignity; Information; Choice; Confidence; Justice; Organization; Security Source: Patient s Charter for TB Care, 2006 AG Holley 60th Anniversary Celebration 23
Patient s Responsibilities You have the responsibility to: Share information; Follow treatment; Contribute to Community Health; Show Solidarity Source: Patient s Charter for TB Care, 2006 The Global Burden of Tuberculosis NO NEW DRUGS / NO NEW TOOLS Last new drug class specifically for TB - Rifampin i (1968 Europe, 1974 US) Most widely used diagnostic test - Tuberculin (1890) Ineffective most widely used vaccine - BCG (1919) Wouldn t one think that largest killer of any single infection deserves better, newer tools? AG Holley 60th Anniversary Celebration 24
Approved & Major Experimental ARV Drugs (1987-2008) ARV Class Approved Experimental Under Investigation Experimental Interrupted NRTI 8 12 8 NNRTI 4 9 6 PI 10 5 4 Entry Inhibitors 2 17 10 Integrase Inhibitors 1 5 2 Maturation Inhibitors 0 3 0 Gene Therapy 0 4 0 TOTAL 25 55 30 Vitoria MAA, October 2008 TB at a Crossroad of Global TB Control Domestic decline of TB since prior to development of drugs Resurgence of TB during the 1980s and 1990s, largely due to neglect Massive and effective response TB on the radar screen domestically TB on the radar screen internationally AG Holley 60th Anniversary Celebration 25
TB Remains a Global Killer Why does TB still infect one-third of the world s population o and remain a global health threat despite the fact that highly cost-effective drugs are available to eradicate it? Challenges in TB Control Insufficient financial and human resources Inadequate healthcare infrastructure Weak laboratory capacity and lack of new rapid diagnostic tools Lack of new drugs that would cure TB in a shorter time Lack of effective vaccine that would prevent TB Poor use of infection control in healthcare settings Minimal social mobilization for TB control and minimal population awareness stigma HIV and MDR/XDR threats AG Holley 60th Anniversary Celebration 26
Annik Rouillion Defaulters and Motivation to default is the natural reaction of normal, sensible people: The person who continues to swallow drugs or have injections with complete regularity in the absence of encouragement and help from others is the abnormal one. - Bull IUAT 1972; 47:68-75 AG Holley 60th Anniversary Celebration 27
As we cure increasing numbers, the remaining i cases are those most difficult to treat, with impossible social problems, and/or severe, virtually untreatable but still transmissible, drug resistance THE FEW REMAINING CASES This talk has concentrated on the difficult remaining TB cases With DOTS and case management along with funding, interest and involvement in developing new tools and strategies for combating TB we have taken care of the easy ones and Expertise decreases Funding decreases The few remaining cases increase especially in High incidence areas Florida, New York, California, Texas victims of populations that they serve high foreign born, high HIV and high MDR & XDR TB care under specific categorized effective funding AG Holley 60th Anniversary Celebration 28
So What is the Answer Either continued failure in the cure of these difficult cases, bouncing in and out of hospitals whenever the utilization review offices stops by or specialized centers such as AG Holley who cost effectively know what they are doing and to fund it We need to set up a major exemption for funding the care of patients who have failed usual treatment, through Medicare and Medicaid It is in everybody s interest to get legislatures out of the TB business - to put TB cases and control as well as specialized care of impossible cases where it belongs such as here TB in the US -1 TABLE. Number and rate* of tuberculosis cases and percentage change, by race/ethnicity --- United States, 2008--2009 Race/Ethnicity 2008 2009 % change from 2008 to 2009 Population Rat Rat No. No. No. Rate 2008 2009 e e Hispanic 3,799 8.1 3,386 7.0-10.9-13.6 46,943,613 48,431,199 Non-Hispanic Black 3,293 8.9 2,859 7.6-13.2-14.0 37,171,750 37,533,254 Asian 3,401 25.7 3,170 23.4-6.8-9.0 13,237,698 13,562,701 White 2,151 1.1 1,828 0.9-15.0-15.2 199,491,458 199,877,195 Other 246 3.4 222 3.0-9.8-12.0 7,215,205 7,398,669 Unknown 15 --- 75 --- --- --- --- --- Total 12,905 4.2 11,540 3.8-10.6-11.4 304,059,724 306,803,018 * Per 100,000 population. Data updated as of February 16, 2010. Data for 2009 are provisional. Based on U.S. Census population data. Persons included in this category are American Indian/Alaskan Native (2009, n = 102, rate: 4.3 per 100,000; 2008, n = 137, rate: 5.9 per 100,000); Native Hawaiian or other Pacific Islander (2009, n = 80, rate: 18.1 per 100,000; 2008, n = 69, rate: 15.9 per 100,000); and multiple race (2009, n = 40, rate: 0.9 per 100,000; 2008, n = 40, rate: 0.9 per 100,000). - CDC, 2010 AG Holley 60th Anniversary Celebration 29
TB in the US -2 FIGURE 1. Rate* of tuberculosis (TB) cases, by state/area --- United States, 2009 SOURCE: National TB Surveillance System. * Per 100,000 population. Data are updated as of February 16, 2010, and are provisional. 19 states had TB case rates of 2.0 (range: 0.37--1.90) per 100,000, 20 states had TB case rates of 2.0--4.0 (range: 2.15--3.84) per 100,000, and 11 states and the District of Columbia had TB case rates of 4.0 (range: 4.01--9.11) per 100,000. - CDC, 2010 TB in the US -3 FIGURE 2. Number and rate* of tuberculosis (TB) cases among U.S.-born and foreign-born persons, by year reported --- United States, 1993--2009 SOURCE: National TB Surveillance System. * Per 100,000 population. Data are updated as of February 16, 2010. Data for 2009 are provisional. - CDC, 2010 AG Holley 60th Anniversary Celebration 30
Tuberculosis Control and Elimination 2010-50: Cure, Care, and Social Development - 1 Rapid expansion of the standardised approach to tuberculosis diagnosis and treatment that is recommended by WHO allowed more than 36 million people to be cured between 1995 and 2008, averting up to 6 million deaths Tuberculosis remains a severe global public health threat Although the overall target related to the Millenium Development Goals of halting and beginning to reverse the epidemic might have already been reached, the more important long-term elimination target set for 2050 will not be met with present strategies and instruments - Lonnroth, Castro, Chakaya, et al, Lancet, 2010 Tuberculosis Control and Elimination 2010-50: Cure, Care, and Social Development - 2 Several key challenges persist: Many vulnerable people do not have access to affordable services of sufficient quality Technologies for diagnosis, treatment, and prevention are old and inadequate Multi-drug resistant tuberculosis is a serious threat in many settings HIV/AIDS continues to fuel the tuberculosis epidemic, especially in Africa Other risk factors and underlying social determinants help to maintain tuberculosis - Lonnroth, Castro, Chakaya, et al, Lancet, 2010 AG Holley 60th Anniversary Celebration 31
Tuberculosis Control and Elimination 2010-50: Cure, Care, and Social Development - 3 Acceleration of the decline towards elimination of this disease will need invigorated actions in four broad areas Continued scale-up of early diagnosis and proper treatment for all forms of tuberculosis Development and enforcement of bold health-system policies Establishment of links with the broader development agenda Promotion and intensification of research towards innovations - Lonnroth, Castro, Chakaya, et al, Lancet, 2010 Why do we need to care about TB in the rest of the world? AG Holley 60th Anniversary Celebration 32
Our Challenge How to maintain services to those with the disease and prevent the development and transmission to those without TB in a climate of declining resources? What Do We Need To Do? Ask our leaders to encourage: Serious discussions on mechanisms needed to preserve the TB public health infrastructure Determine what resources will be needed to perform TB control, including the level needed (local vs. regional) Identify existing resources and assure proper legal authority and procedures available to assure access to expert care for all Maintain adequate funding for infrastructure including establishing unique funding for particular threats to the public s health AG Holley 60th Anniversary Celebration 33
Lessons from Andrew Speaker TB has not gone away, it remains with us, highly prevalent and transmissible Anybody can get tuberculosis, not only poor people, minorities, or the foreign-born TB anywhere is TB everywhere All resistant TB, MDR and XDR TB is preventable by proper TB diagnosis and treatment Good public health is a silent secret, but when there is a small glitch, it becomes major news We desperately need new tools for TB diagnosis and treatment You don t want to sit on an airplane for 8 hours next to an untreated coughing person with any kind of TB, be it drug sensitive, MDR or XDR AG Holley 60th Anniversary Celebration 34
INFORMATION LINE 1 800 4TB DOCS (482-3627) www.umdnj.edu/globaltb AG Holley 60th Anniversary Celebration 35