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Tuberculosis: A Global Emergency. 1993: WHO declares TB a global public health emergency8 million new cases per year (and increasing)2 million deaths per year = 5,500 per day = 1 every 15 seconds1/3 of the world's population is infected with Mycobacterium tuberculosis. Global Emergency II. More than 100,000 children will die this yearHIV and TB co-infection are producing explosive epidemicsHundreds of thousands of children will become TB orphans this yearMDR is seriously threatening global TB control.
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1. Plagues of Poverty: TB and the Neglect of the Poor Social Medicine, Human Rights, and the PhysicianEmory MEDI 645 Timothy Holtz, MD, MPH
February 14, 2005
With assistance from Peter Cegielski, MD, MPH and Kayla Laserson, ScD
2. Tuberculosis: A Global Emergency 1993: WHO declares TB a global public health emergency
8 million new cases per year (and increasing)
2 million deaths per year = 5,500 per day = 1 every 15 seconds
1/3 of the worlds population is infected with Mycobacterium tuberculosis
Multi drug Resistance = MDR
Multi drug Resistance = MDR
3. Global Emergency II More than 100,000 children will die this year
HIV and TB co-infection are producing explosive epidemics
Hundreds of thousands of children will become TB orphans this year
MDR is seriously threatening global TB control
Multi drug Resistance = MDR
Multi drug Resistance = MDR
4. History
TB emerged as a major cause of morbidity and mortality during 17th century feudal Europe with growth of crowded cities and widespread poverty
Peaked in late 18th century causing 25% of all deaths, the White Plague
Robert Koch discovered Mycobacterium tuberculosis and proved it was the cause of TB in 1882, later developing diagnostic tests
If the number of victims which a disease claims is the measure of its significance, then all diseases, particularly the most dreaded infectious diseases, such as Bubonic Plague, Asiatic Cholera, et cetera, must rank far behind Tuberculosis.
Robert Koch, 1882
Multi drug Resistance = MDR
Multi drug Resistance = MDR
5. Who has succumbed? Brönte sisters
Percy Bushe Shelley
Lord Byron
John Keats
Robert Louis Stevenson
George Orwell
Eleanor Roosevelt
6. Dubos Tuberculosis is a social disease, and presents problems that transcend the conventional medical approach
its understanding demands that the impact of social and economic factors on the individual be considered as much as the mechanisms by which tubercle bacilli cause damage to the human body.
7. The Evolution of Epidemics
8. The White Plague The industrial revolution brought with the exploitation of labor
Crowding
Poor working and living conditions
1796 report of a commission appointed by the Manchester Board of Health:
Children and others who work in the large cotton factories are peculiarly disposed to be affected by the contagion of fever, and when such infection is received, it is rapidly propagated, not only amongst those who are crowded together in the same departments, but in the families and neighborhoods to which they belong.
9. The social disease of the 19th Century 1830-Mortality in Boston, NYC, Philadelphia was approximately 400/100,000
1880-Outbreak among 2800 Sioux prisoners
Mortality 10X higher than the worst European epidemics
QuAppelle Valley Reservation in W. Canada: TB mortality 9,000/100,000
Wars:
1871 TB mortality surge in Paris during the siege by the Prussian Army
WW I, WW II TB became known as the social disease of the 19th century the estimated mortality of TB in Boston, NYC and Philadelphia in 1830 was 400/100,000.
Reliable national mortality rates are not available until around 1900 at 200/100,000.
By 1950 that had decreased to 26/100,000.
TB became known as the social disease of the 19th century the estimated mortality of TB in Boston, NYC and Philadelphia in 1830 was 400/100,000.
Reliable national mortality rates are not available until around 1900 at 200/100,000.
By 1950 that had decreased to 26/100,000.
10. The social disease of the 19th Century Reform demanded
Late 19th century anti-TB campaigns led to the institution of control measures:
Austrias Society of the Establishment of Sanatoria for the Consumptive Poor
Denmarks National League for the Campaign against Tuberculosis
Frances French League against Tuberculosis
By 1850 reformers had begun attacking social problems by political action to improve the working and living conditions. Access to clean water, food and living conditions, fresh air sunshine, became a right. The campaign for social reform gained momentum
Reliable national mortality rates are not available until around 1900 at 200/100,000.
By 1950 that had decreased to 26/100,000.
It had become obvious that tuberculosis was most prevalent and most destructive in the poorest elements of the population and that healthy living could mitigate its harmful effects
Anti-TB campaigns gained momentum and carried social prestige these were presided over by royalty, chiefs of state and leaders of the political and social world
Supported by the press
Involvement by sociologists, businessmen, philanthropists as well as physicians By 1850 reformers had begun attacking social problems by political action to improve the working and living conditions. Access to clean water, food and living conditions, fresh air sunshine, became a right. The campaign for social reform gained momentum
Reliable national mortality rates are not available until around 1900 at 200/100,000.
By 1950 that had decreased to 26/100,000.
It had become obvious that tuberculosis was most prevalent and most destructive in the poorest elements of the population and that healthy living could mitigate its harmful effects
Anti-TB campaigns gained momentum and carried social prestige these were presided over by royalty, chiefs of state and leaders of the political and social world
Supported by the press
Involvement by sociologists, businessmen, philanthropists as well as physicians
11. A communicable disease of social importance America: the 1899 Medico-Legal Society of the City of New York and the American Congress on Tuberculosis
Legislative measures
Education
A new approach to controlling a social disease:
Political commitment
Emphasis on prevention and control measures
Financial support
Health education of the general public: Tuberculosis as a Disease of the Masses and How to Combat it. Knopf, 1901. In America, the first organized national scale movement was led by a group of lawyers, scientists and physicians interested in social problems known as the Medico-Legal Society of the City of New York. This group organized an American Congress on tuberculosis to address laws regarding TB and its treatment.
Emphasis shifted from treatment of the individual patient to control of disease in society (new relationship between the medical profession and the public)
Role of physicians
Role of public health officials and social workers - - legislative and educational approach, community action
Education:
Knopfs pamphlet: Tuberculosis as a Disease of the Masses and How to Combat It in 1901 was translated into 27 languages and distributed world wide
In America, the first organized national scale movement was led by a group of lawyers, scientists and physicians interested in social problems known as the Medico-Legal Society of the City of New York. This group organized an American Congress on tuberculosis to address laws regarding TB and its treatment.
Emphasis shifted from treatment of the individual patient to control of disease in society (new relationship between the medical profession and the public)
Role of physicians
Role of public health officials and social workers - - legislative and educational approach, community action
Education:
Knopfs pamphlet: Tuberculosis as a Disease of the Masses and How to Combat It in 1901 was translated into 27 languages and distributed world wide
12. The White Plague Dramatic decrease in TB mortality in the 20th century:
A consequence of control measures or improved standard of living?
A luxury of prosperous communities?
13. The White Plague
Public health is purchasable. Within natural limitations, any community can determine its own death rate.
Hermann Biggs
14. How did we get here? TB incidence was decreasing in U.S. and W. Europe after early 1900s
improved nutrition & living conditions
Discovery of effective treatment 1943-1972 led to widespread optimism
Trends improving in many low income countries by 1970s
Scientific and public health interest waned, funding decreased in the 1970s
Multi drug Resistance = MDR
Multi drug Resistance = MDR
15. How did we get here? Infrastructure for TB control deteriorated through the 1980s
HIV epidemic started late 1970s, HIV/TB co-infection produced (-ing) explosive epidemics
Multidrug-resistant TB (MDR TB) started threatening global TB control in many countries, circa 1990
Multi drug Resistance = MDR
Multi drug Resistance = MDR
16. How did we really get here? Increasing poverty in low and middle income countries
Worsening economic inequality
No international commitment to TB control
Collapse of public health infrastructure
Political violence
Racism
17. The Global TB SituationOutline: TB in the USA
Global burden and distribution of TB
Co-epidemics of TB and HIV/AIDS
Drug-resistant TB
Global efforts to control TB
18. TB in the United States
20. Reported TB Cases US, 1983-2002
21. Excess TB cases 1985-92 After more than three decades of a steady decline in TB morbidity, averaging 5-6% annual decrease, our nation experienced a resurgence of tuberculosis from 1985 through 1992, with an estimated excess of 52,100 persons who should have never developed this disease had previous morbidity trends continued. To add insult to injury, there was a concurrent widespread occurrence of multidrug-resistant TB
Several factors were associated with this resurgence, and have been documented in previous publications. Perhaps the single most important factor that set the stage for this mess consisted of the dismantling of TB clinical services during the disappearance of categorical funds in the late 1970s and early 1980s. After more than three decades of a steady decline in TB morbidity, averaging 5-6% annual decrease, our nation experienced a resurgence of tuberculosis from 1985 through 1992, with an estimated excess of 52,100 persons who should have never developed this disease had previous morbidity trends continued. To add insult to injury, there was a concurrent widespread occurrence of multidrug-resistant TB
Several factors were associated with this resurgence, and have been documented in previous publications. Perhaps the single most important factor that set the stage for this mess consisted of the dismantling of TB clinical services during the disappearance of categorical funds in the late 1970s and early 1980s.
22. TB in NYC in 1980s TB public health program underfunded due to fiscal crisis in late 1970s-1980s
Cure rate 50%, <2% on DOT
Over-reliance on inpatient treatment
No special program for homeless, alcoholics
In Harlem 90% of cases never completed therapy, 27% readmitted
Treatment default a major cause of problem
70% increase in cases during 1980s
23. Arresting the NYC epidemic Find active cases
Incentive program-free meals, rides, coupons, vouchers
Directly Observed Therapy Short Course
Shelter for homeless with TB
Mandatory detention for refractory, chronic defaulters
25. TB Morbidity US, 1997-2002
26. TB Case Rates, US, 2002
27. Reported TB Cases by Race/Ethnicity, US, 2001
28. Number of TB Cases inUS-born vs. Foreign-born Persons, US, 1992-2002*
29. Countries of Birth for Foreign-born Persons Reported with TB US, 2002*
30. Socioeconomic Characteristics of TB in the US More than ˝ of TB cases occur in immigrants
Among non-immigrants, TB significantly associated with
Poverty and unemployment
Homelessness
Congregate settings
Incarceration
Alcoholism and drug abuse
HIV infection rates also high in some of these populations
31. Global distribution and burden of disease
32. Leading Infectious Disease Causes of Death, 1998
33. Estimated Annual Incidence of TB Selected High Burden Countries, 2001
36. Geographical Distribution of Notified Cases of TB, 2001
38. Travesty Leading infectious cause of preventable death
No tumbling down of death rate in developing world
1.5-2 million deaths annually despite 60+ years of effective therapy
39. TB / HIV Co-epidemics
45. Drug-resistant and Multidrug-resistant TB
46. The Development and Spread of Drug- and Multidrug-resistant TB
47. Introduction of Anti-TB Drugs Streptomycin 1943
Isoniazid 1952
Pyrazinamide 1956
Ethambutol 1960s
Rifampin 1970s
48. Drug Resistant Pattern Predicted by misuse of drugs over time
Date drug first available for use in humans
Penetration into local marketplace (changes in cost, duty, regulatory approval)
Evolution of NTP regimen
Introduction of free-of-charge Tx by NTP
53. The Russian TB Epidemic: Key Features TB case notification more than doubled from 34/100,000 in 1991 to 92 per 100,000 in 2001
Rooted in political changes, economic crises, and social disruption
Reported case rates > 3,000 per 100,000 prisoners in several oblasts in 1999
TB again a major cause of young adult deaths
Primary and acquired drug resistance common
56. Causality? Re-emergence of TB due to HIV and MDR TB are not biologic phenomena but social phenomena
Those falling ill continue to be the marginalized, homeless, prisoners, unemployed
57. Immodest claims of causality Non-compliance with therapy
Lack of knowledge
Etiologic beliefs about health and TB
Vs.
Lack of commitment
Lack of access to resources
Lack of effective adherence strategies
58. Sins of social scientists Conflating cultural difference with structural violence
Social diseases hide amidst the poor population
Minimizing the role of poverty
Re-emergence was from the ranks of the poor
Exaggerating patient agency
Those least likely to comply are those least able to comply
Romanticizing folk healing
Unfair distribution of worlds medical resources
59. Which social forces? Poverty, racism, gender inequality?
Homelessness, injection drug use?
Structural violence?
The World Health Organization?
60. WHO and MDR TB Through 1998, WHO policy was to treat all relapsed cases of MDR with Regimen 2 adding Strep to 4-drug regimen
WHO, and some current experts, argue against treating MDR TB; that DOTS for TB will take care of MDR problem
The poor at risk not only to develop MDR TB, but at risk of not finding adequate therapy
61. Tailoring a time-bomb MDR TB being cultivated even in the face of an effective TB program (Peru)
Enrollment of patients into standard treatment algorithms
Amplification in hot spots
MDR TB only seen in places where inequality is entrenched
Cannot eliminate TB without also dealing with problem of drug-resistance
62. Arguments against not treating MDR TB Clinical No expertise, diagnosis is complex
DOTS will fail to treat drug-resistant TB
Epidemiologic Treating MDR will destabilize DOTS
No data showing DOTS will lower MDR case rates where it is already established
Without treatment, transmission of MDR will continue
Social Analysis Too expensive to treat
Or too expensive NOT to treat?
Moral Poor countries cannot handle the challenges
Treatable in the US, but not in Russia? Differential valuation of life? Victims are the poor.
63. Social diseases cannot be eradicated or eliminated without a social response
64. Social approach Determine the mechanisms by which social forces promote or retard the transmission of TB
Identify and rank the barriers preventing those afflicted from having access to the best care available
Become engaged in multidisciplinary trials
Expose the mechanisms that entrench medical inequities
65. Global TB Control
66. Global TB Control Global control of TB is a leading health priority
DOTS
WHO global strategy
National case management of populations
March 1997, declared to represent the most important public health breakthrough of the decade, in terms of the lives which will be saved To tell class the main objectives for this lectureTo tell class the main objectives for this lecture
67. WHO DOTS Strategy for TB This cartoon illustrates the 5 elements of the DOTS strategy. First, is the government commitment to consider TB control a priority, along with necessary resources for the program. Second is the reliance on microscopy-based sputum examinations as the basis to diagnose the presence of this infectious organism. Third is the use of standardized rifampin-based short-course chemotherapy under direct observation (at least during the first two months of treatment). Fourth is assuring an uninterrupted supply of quality anti-TB medicines. Fifth is the creation of a record-keeping system and training for program supervision, monitoring, and evaluation.This cartoon illustrates the 5 elements of the DOTS strategy. First, is the government commitment to consider TB control a priority, along with necessary resources for the program. Second is the reliance on microscopy-based sputum examinations as the basis to diagnose the presence of this infectious organism. Third is the use of standardized rifampin-based short-course chemotherapy under direct observation (at least during the first two months of treatment). Fourth is assuring an uninterrupted supply of quality anti-TB medicines. Fifth is the creation of a record-keeping system and training for program supervision, monitoring, and evaluation.
68. DOTS is Effective In Malawi, Mozambique, and Tanzania, DOTS led to cure rates between 86% to 90%
In Beijing, China, DOTS led to a decrease of smear-positive TB from 127/100,000 to 16/100,00 in 11 years with cure rates > 90%
In Bangladesh, DOTS led to cure rates > 80%
In India, DOTS led to cure rates of ~75% to 80%
70. DOTS Can Reduce the Burden of TB
71. DOTS Can Reduce Drug Resistance
74. In 1993, the World Bank determined that DOTS was one of the most cost-effective of any health care intervention
77. Status of DOTS Globally, 2000 WHO Stop-TB partnership, significant momentum
Countries implementing DOTS strategy, 155/210 (74%)
All 22 high-burden countries have adopted DOTS
61% worlds population, including those in high burden countries, had access to DOTS
Vietnam is the only high burden country meeting WHO target for case detection (75%) and cure (80%)
Worldwide, DOTS programs will have to increase the number of additional patients enrolled annually by a factor of 2.5 to meet 2005 WHO targets
78. Can TB Be Controlled Globally? Inadequate political commitment
Incomplete DOTS coverage
Impact of HIV on TB epidemiology
Cost and management of MDR TB
Slow development of new tools
79. Expand DOTS coverage, especially in high burden countries
Face challenges of HIV, MDRTB, and weak health systems and find solutions
Ensure DOTS is patient-centered
Build the necessary broad coalition to ensure
control efforts are effective and sustained
research is effective to identify new tools
80. Beyond DOTS DOTS-plus treatment for MDR TB
Screening and treatment of latent infection
The prospects for new drugs and vaccines
81. Working Group DOTS-Plus Formed in 1999
Composed of members of academia, civic organizations, donor agencies, bilateral donors, governments, UN
82. Increase access to drugs for MDRTB
Lower costs and increase control
New, more effective, less toxic drugs needed
Build technical capacity for DOTS-Plus
- Ensure DOTS is fully in place
Hot Spots require urgent attention
Build Laboratory Capacity for DOTS-Plus
Advocacy to mobilize resources
83. Treating MDR TB (1) Rationale
Patients with MDR TB are generally not cured by standard 4-5 drug short-course chemotherapy (the cornerstone of DOTS)
Drug-resistant TB is present and increasing in many countries
Significant transmission of MDR TB may still occur in DOTS-based countries
The potential spread of MDR TB could be a threat to the success of DOTS
84. Treating MDR TB (2) Feasibility
In industrialized countries, treatment with expensive 2nd-line drugs is based on the use of individual DST
Feasibility of these regimens in low and middle income countries unknown
85. DOTS-Plus DOTS prevents drug resistance, but DOTS alone is not adequate in regions of high drug resistance
Once solid DOTS program is in place, initiate projects to manage MDR TB
Infrastructure development, capacity building
Demonstration and pilot treatment projects
Develop evidence base for global guidelines and recommendations
Assess cost and sustainability
86. Creation of DOTS-Plus Projects Decision to create DOTS-Plus Pilot Programs
Case-management initiative designed to manage MDR TB within the DOTS strategy in low/ middle income countries
Uses Individualized (ITR) and Standardized (STR) regimens
Green Light Committee to assist in the procurement of low cost second-line drugs
Requires evaluation of the cost, feasibility, and effectiveness of these regimens and projects
Goal: To develop appropriate, evidence-based global policy for the treatment and management of MDR TB
87. Strong DOTS programs
Laboratory capacity for DST
On-going drug resistance surveillance
Advocacy
- Maintain momentum
- Increase visibility with public-private partnerships
88. Green Light Committee Subgroup of Working Group on MDR TB
Based on model for distributing meningitis vaccine
Work with pharmaceutical companies to provide concessional prices for GLC-approved projects, enables a pooled procurement mechanism to buy 2nd line drugs
Objectives are
Review applications
Evaluate the projects
Report to WHO
89. GLC Approach Determine category of drug
Single negotiator (MSF)
Drugs submitted for inclusion to the WHO Model List of Essential Drugs
Direct negotiation strategy
Advantages to suppliers highlighted
Access to 2nd line drugs only given to those who meet DOTS-Plus criteria
90. Effect on 2nd-line drug prices
91. Examples of Countries Implementing DOTS-Plus Pilot Projects Peru (ITR/STR)
Bolivia (ITR)
Mexico (STR)
Latvia (ITR)
Estonia (ITR)
Russia (various Oblasts, ITR)
Philippines (ITR)
South Africa (STR)
92. Summary TB is a major global public health problem
TB is a quintessential social disease that demands a social response
HIV and drug resistance are seriously challenging global TB control efforts
TB control efforts must be a global priority
93. New Global Initiatives STOP TB Partnership
Global Drug Facility
Global Alliance for TB Drug Development
Green Light Committee
Global Fund Against AIDS, TB and Malaria