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J2J Lung Health Media Training

Lee B. Reichman, M.D., M.P.H. Paris, France October 30, 2013

Rutgers, The State University of New Jersey

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TB Historical Permutation
17th - 18th centuries TB took 1 in 5 adult lives 1850 - 1950 one billion people died of TB This 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

The Global Burden of TB -2011

Estimated number of cases
8.7 million

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Estimated number of deaths

1.4 million*

All forms of TB HIV-associated TB Multidrugresistant TB Childhood TB

(8.39.0 million)
1.1 million (13%)

(1.31.6 million)
430,000

(1.01.2 million)
630,000

(400,000460,000)

(460,000-790,000)
out of ~12 million prevalent TB cases

490,000

Unknown, but probably > 150,000 64,000**

Source: WHO Global Tuberculosis Report 2012 ** Excluding deaths attributed to TB/HIV

(58,000 71,000) (470,000510,000) ~ 5.6% of the total burden * Including deaths attributed to HIV/TB

Incidence Rates, 2011

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024 2549 50149 150299 300

Per 100 000

Highest rates in Africa, linked to high rates of HIV population infection

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Global TB Control: Background 1991 World Health Assembly recognized the growing 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)

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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 casemanagement conditions including DOT Regular drug supply Standardized recording and reporting system that allows assessment of individual patients as well as overall program performance

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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

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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 and at least 1 second-line injectable (AMI, KAN, CAP)

Totally Drug Resistant TB (TDR-TB)

Resistant to all anti-TB drugs

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The Global Burden of TB/HIV

1/3 of 33 million people living with co-infected with TB (>10 million people) HIV/AIDS

Without treatment, 90% will die HIV and TB form a lethal combination, each speeding the other's progress TB is the leading cause of death among HIV-positive people (up to 50% of all patients worldwide)

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Co-Existence of HIV & TB infection

TB Infection HIV Infection

10% per lifetime

10% per year .0017% per year

Risk of Active TB

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Estimated HIV Prevalence in New TB Cases, 2010

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WHO TB/HIV Policy: 12 Point Policy Package

Mechanism for integrated TB and HIV services Activities to reduce TB burden in PLHIV Activities to reduce HIV burden in TB patients

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MDRTB/XDRTB - The Big Problem!

630,000 new MDR-TB cases estimated annually with 150,000 deaths XDR-TB in 84 countries 19% of estimated MDR-TB cases detected 44-58% (overall 48%) successfully completed treatment About 85% of the global MDR-TB burden found in 27 countries

Sources: Global TB Report, 2012

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Use of One Drug Knowingly or Unknowingly

Sensitive bacilli killed Resistant bacilli multiply unimpeded Resistant bacilli become dominant

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Pathogenesis of Drug Resistance

INH RIF PZA EMB

R Z I E I

INH
I

I I I I

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Pathogenesis of Drug Resistance

I I I I
I I I I I I IR IR IR IR IR IR IR

I I
IP IP

IR

INH RIF

IRP

Never add a single drug to a failing regimen

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Why 4 drugs, why DOT ?

Large population of highly active growing bacilli

Random Mutations Frequency of mutations that confer drug resistance INH SM RIF 8 1 in 1,000,000 1 in 1,000,000 1 in 100,000,000 or 10-6 10-6 1010David HL. Probability distribution of drugresistant mutants in unselected populations of Mycobacterium tuberculosis. Appl Microbio l970;20:810-14.

EMB 1 in 100,000 5

The likelihood of an organism spontaneously resistant to 2 antibiotics is the product of their probabilities i.e., for Isoniazid & Rifampin 1 in 10-14 , for 3 drugs IRE 1 in 10-20)

Schema Courtesy B. Mangura, 2013

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Estimated Absolute Number of MDR-TB Cases, 2009

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Countries that had reported at least one XDR-TB case by end 2010

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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 8,700,000 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 everybodys priority; it is the only way to prevent MDR-TB and XDR-TB Reichman, LB The Lancet, 2009

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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 Development of TDR-TB?

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World TB Day 2006 - Dr Lee launches the International Standards for TB Care & the Patients' Charter for TB Care

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International Standards for TB Care

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ISTC: Key Partners in Implementation

National (and local) tuberculosis control programs Influential professional societies Professional (medical and nursing) schools NGOs Patient and community organizations Technical agencies Funding agencies

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International Standard for TB Care: Diagnosis

All persons with otherwise unexplained cough lasting for 2-3 weeks or more should be evaluated for tuberculosis

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International Standard for TB Care: Diagnosis

Microbiological evaluation (smear culture) is essential for all patients (including children, extra-pulmonary, and persons with radiographic abnormalities)

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International Standard for TB Care: Treatment

The provider is responsible for prescribing an adequate regimen and ensuring adherence

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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.

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Where Are The Missing Cases?

They are not detected due to poor laboratory capacity

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Where Are The Missing Cases?

At home, if services are not accessible

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Where Are The Missing Cases?

In other un-connected public systems (prisons)

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Where Are The Missing Cases?

In the private sector

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Patient Involvement in Medical Care

Patients and their families have become increasingly involvedand influentialin 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

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The Patients Charter for Tuberculosis Care

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The Patients 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

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Patients Rights
You have the right to: Care; Dignity; Information; Choice; Confidence; Justice; Organization; Security

Source: Patients Charter for TB Care, 2006

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Patients Responsibilities
You have the responsibility to: Share information; Follow treatment; Contribute to Community Health; Show Solidarity

Source: Patients Charter for TB Care, 2006

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Reported TB Cases in the United States, 1982-2012*

No. of Cases

Historically low 9,951 Cases Rate 3.2/100,000

Impact of HIV Epidemic, Poverty, Homelessness Failure of Public Health Infrastructure

*Updated as of March 22, 2013 with provisional 2012 data

r a e Y

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US Response to 1990s MDR Epidemic Turning the Tide

Strong public health advocacy to obtain increased funding from Congress Rebuilt the weakened infrastructure for TB services and research Implemented routine drug susceptibility testing with liquid media Implemented and monitored infection control precautions in healthcare and congregate settings Strengthened public-private partnerships Supported centers of excellence National Institute of Healths 5-10 year investment in TB academic awardees

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2012 U.S. TB
9,951 TB cases 3.2 cases per 100,000 population Decline of 6.1% from 2011 case rate

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TB at a Crossroad of Global TB Control

US domestic decline of TB since prior to development of drugs US 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

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BUT TB Remains a Global Killer

Why does TB still infect one-third of the worlds population and remain a global health threat despite the fact that highly cost-effective drugs are available to eradicate it?

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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 HIV and MDR/XDR threats Minimal social mobilization for TB control and minimal population awareness stigma

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Why Do We Need New Drugs To Treat TB?

Shorter overall treatment duration Lower relapse rates Development of regimens with fewer adverse effects, particularly less hepatotoxicity Development of regimens that can be given easily and safely in combination with antiretroviral therapy Development of regimens that are effective in treating MDR-TB/XDR-TB

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Second Line Drugs in People with MDRTB

Prospective Study in eight countries 1,278 patients
43.7% resistance to one SLD 20.0% resistance to one SL Injectable 12.9% resistance to one Fluroquinolone 6.7% XDRTB

Previous treatment with SLD strong consistant risk factor

Tracy Dalton et al (CDC) - Lancet, 2012

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Drugs In The Clinical Pipeline For The Worlds Leading Causes Of Mortality
Leading causes of global mortality:
1. Ischemic heart disease 2. Stroke 3. COPD 4. Lower respiratory infection 5. Lung cancer 6. HIV/AIDS 7. Diarrhea 8. Road traffic accidents 9. Diabetes 10. Tuberculosis 11. Malaria
Drugs in clinical development:
Heart Disease and stroke: 299 COPD: 54 Antibacterials and antivirals: 89 Cancer: > 900 (includes vaccines) Lung Cancer: 121 HIV/AIDS: 70 Diabetes: 221 Anti-tuberculosis: 5-8 Anti-malarials: 6

Sources: The Global Burden of Disease Report, 2012 Courtesy, Neil Schluger, MD The Pharmaceutical Research and Manufacturers of America 2013 (www.pharma.org)

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Courtesy, David Alland, 2012

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As we cure increasing numbers, the remaining cases are those most difficult to treat, with impossible social problems, and/or severe, virtually untreatable but still transmissible, drug resistance

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THE FEW REMAINING 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 Innovative Initiatives are de-emphasized or even forgotten

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Tuberculosis Control and Elimination 2010-50: Cure, Care, and Social Development
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 Updated 2012

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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

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Why do we need to care about TB in the rest of the world?

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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 dont 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

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INFORMATION LINE 1-800-4TB-DOCS (482-3627) globaltb.njms.rutgers.edu