Tuberculosis: Forgotten, But Not Gone

7/27/2019 Tuberculosis: Forgotten, But Not Gone

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Rutgers, The State University of New Jersey

Forgotten But Not Gone

J2J Lung Health Media Training

Lee B. Reichman, M.D., M.P.H.

Paris, FranceOctober 30, 2013


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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


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Estimated numberof cases Estimated numberof deaths

1.4 million*

(1.31.6 million)

8.7 million

(8.39.0 million)

630,000

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

TB cases

All forms of TB

Multidrug-

resistant TB

HIV-associated TB1.1 million (13%)

(1.01.2 million)430,000

(400,000460,000)

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

The Global Burdenof TB-2011

Unknown, but

probably >150,000

Childhood TB490,000

(470,000510,000)

~ 5.6% of the total

burden

64,000**(58,000 71,000)


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Forgotten But Not GoneIncidence Rates, 2011

Highest rates in Africa, linked to high rates of HIVinfection

Per 100 000

population

30015029950149

024

2549


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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 wasdeveloped

A global strategy called DOTS was introduced

(originally stood for Directly ObservedTreatment, 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 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


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International TB Control Strategy

Stop TB Strategy: 2006 - current1. 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 HIV/AIDSco-infected with TB(>10 million people)

Without treatment, 90% will die

HIV and TB form a lethal combination, each speeding theother's progress

TB is the leading cause of death among HIV-positivepeople (up to 50% of all patients worldwide)


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Co-Existence of HIV & TB infection

Risk of Active TB

10% per year10% per lifetime

.0017% per year

TB Infection

HIV Infection


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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

Z

R

I

I

I

I

I

I

I

INH

RIF

PZA

EMB

INHE


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Pathogenesis of Drug Resistance

I

I

I IR

IR

IR

INH

RIF

I

I

I

I

IPIP

IRP

I

I

I

I

I

I

I

IR

Never add a single drug to a failing regimen

IRIR

IRIR


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Why 4 drugs, why DOT ?

Large

population

of highly

activegrowing

bacilli

Random Mutations

Frequency of mutations that

confer drug resistance

INH 1 in 1,000,000 or 10-6

SM 1 in 1,000,000 10-6

RIF 1 in 100,000,000 10-

8

EMB 1 in 100,000 10-

5 David HL. Probability distribution of drug-resistant mutants in unselected populations of

Mycobacterium tuberculosis. Appl Microbio

l970;20:810-14.

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 3drugs 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 tuberculosismodified 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 drug-

sensitive cases of tuberculosis globally that could be feedingdrug resistance

It might be a less sexy concept, but they all must be

appropriately treated with current strategies (as well as newdiagnostics, drugs, vaccines, and proper infection controlmeasures) to avoid preventable MDR-TB and XDR-TB, which arealways lurking

Preventing active, drug-sensitive tuberculosis, or treating itproperly, 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: DiagnosisMicrobiological evaluation (smear culture) is essential for all patients (including

children, extra-pulmonary, and persons with radiographic abnormalities)

F B N G


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International Standard for TB Care: Treatment

The provider is responsible for prescribing an adequate regimen andensuring adherence

F tt B t N t G


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International Standard for TB Care: TreatmentA patient-centered, individualized approach to treatment should be developed

for all patients.A central element is direct observation by a treatment supporter.

F tt B t N t G


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Where Are The Missing Cases?

They are not detected due to poor laboratory capacity

F tt B t N t G


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At home, if services are not accessible

F tt B t N t G


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In other un-connected public systems (prisons)


Forgotten B t Not Gone


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In the private sector




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Patient Involvement in Medical Care

Patients and their families have become increasingly involvedandinfluentialin 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 ofclinical 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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No.ofCases

Year

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

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

Impact of HIV Epidemic, Poverty, Homelessness

Failure of Public Health Infrastructure

Historically low

9,951 Cases

Rate 3.2/100,000



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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 worldspopulation 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

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

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

Sources: The Global Burden of Disease Report, 2012The Pharmaceutical Research and Manufacturers of America

(www.pharma.org)

Courtesy, Neil Schluger, MD

2013



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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, drugresistance



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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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g

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 helpfrom others is the abnormal one.

- Bull IUAT1972; 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 andtransmissible

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 anykind 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

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Tuberculosis: Forgotten, But Not Gone