Why can’t we eliminate tuberculosis?

Neil W. Schluger, M.D.

Professor of Medicine, Epidemiology and Environmental Health Sciences

Columbia University

Chief Scientific Officer

World Lung Foundation

Current trajectory of the global TB epidemic

year

Dye et al. Ann Rev Pub Health 2013; 34: 271-286

What we need to do to eliminate tuberculosis

• Invest in public health

• Invest in research

• Embrace new ideas and new technology

• Take MDR-TB seriously

• Stop doing stupid stuff

• Speak with a louder voice

What we need to do to eliminate tuberculosis

• Invest in public health

• Invest in research

• Embrace new ideas and new technology

• Take MDR-TB seriously

• Stop doing stupid stuff

• Speak with a louder voice

Invest in public health, with money, effort and energy

• Better surveillance

• Improve access to care

• Insure drug supply

• Do a better job of monitoring and encouraging adherence to therapy

Notifications of TB cases have stabilized in recent years, and in 2013 represented 64% (range, 61–66%) of estimated incident cases. The gap between notifications and incident cases – an estimated total of 3.3 million cases – can be explained by a mixture of underreporting of diagnosed TB cases (for example, failure to notify cases diagnosed in the private sector) and under-diagnosis due to poor access to health care and/or failure to detect cases when people visit health care facilities. Major efforts are needed to ensure that all cases are detected, notified to national surveillance systems, and treated according to international standards.

WHO Global TB Report 2014, pg. 39

WHO, Global TB Report 2014

Costs of tuberculosis care as a percentage of annual income

Tanimura et al. Eur Resp J 2014; 43: 1763-1775

Financial coping strategies of tuberculosis patients

Tanimura et al. Eur Resp J 2014; 43: 1763-1775

MMWR 2013; 62: 398

Drug shortages

A tale of two cities: New York and London

TB Incidence 2013: 8.6/100,000 Source: NYC DOHMH

TB Incidence 2013: 37/100,000 Source: Public Health England

A tale of two countries: U.S. and South Korea

TB, Republic of Korea, 1990-2013

TB Incidence 2013: 97/100,000 Source: WHO

TB Incidence 2013: 3.1/100,000

Turning the tide--TB control in New York

• Implementation of

directly observed

therapy (DOT)

– Public health advisors

– Rebuild TB clinics

• Infection control

• Use of standardized

regimens for treatment

• $40 million annually

from CDC

Frieden et al. N Eng J Med 1995; 333: 229-233

What we need to do to eliminate tuberculosis

• Invest in public health

• Invest in research

• Embrace new ideas and new technology

• Take MDR-TB seriously

• Stop doing stupid stuff

• Speak with a louder voice

TAG Report 2014

TAG Report 2014

TAG Report 2014

TAG Report 2014

Deaths 1.5 million 1.6 million 0.62 million 0

TAG Report 2014

The cost of underinvestment in TB research

• Only 2 new drugs approved in 40 years

– In that time period, HIV infection has become manageable, and hepatitis C infection has become curable.

• No prospect of approval of a more effective vaccine in the next 10 years

• In most places in the world, TB is diagnosed the same way it was diagnosed over 120 years ago

• The pace of clinical trials is agonizingly slow

Drugs in the clinical pipeline for the

world’s leading causes of mortality

Drugs in clinical development:

- Heart disease and stroke: >200

- COPD: >50

- Antibacterials and antivirals: 394 (drugs and vaccines)

- (“124 for pneumonia and TB”)

- Cancer: 800

- Lung Cancer: 121

- Breast Cancer: 111

- HIV/AIDS: 44 (includes vaccines)

- Diabetes: 180

- 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

The Pharmaceutical Research and Manufacturers of America (www.pharma.org), accessed Feb. 25, 2015

TB trials are too slow

2500 study subjects Trial initiated 2007

Paper published 2014

8000 study subjects Trial initiated 2001

Paper published 2011

Why so slow? Endpoints are the same as those used since the original BMRC streptomycin trial in 1948, and clinical trials capacity is limited.

What we need to do to eliminate tuberculosis

• Invest in public health

• Invest in research

• Embrace new ideas and new technology

• Take MDR-TB seriously

• Stop doing stupid stuff

• Speak with a louder voice

The TB community’s attitude towards new technology?

Lancet 2014; 383: 424-435

Xpert MTB/RIF

• What it does do:

– Diagnoses TB and determines susceptibility to rifampin accurately and rapidly

• What it does not do:

– Fix your TB control program

– Cure cancer

– Achieve world peace

Interventions and their effect on TB cases

Dye et al. Ann Rev Pub Health 2013; 34: 271-286

What we need to do to eliminate tuberculosis

• Invest in public health

• Invest in research

• Embrace new ideas and new technology

• Take MDR-TB seriously

• Stop doing stupid stuff

• Speak with a louder voice

WHO 2010 Global Report

Total MDR cases:

480,000

WHO Global TB Report, 2014

Distribution and prevalence of MDR-TB

New cases Retreatment cases

MDR-TB in Africa: the more you look, the more you find

Underreported Threat of MDR TB in Africa

Report published in 2004 have MDR TB rates >2.0% of all

combined TB cases. This fi nding suggests that completing

DRSs for all or most countries in the AFRO region is ur-

gently needed and that the MDR TB threat in Africa could

be much higher than originally assessed by WHO in its

previous report in 2004. Drug-resistant strains, along with

HIV/AIDS, are causing the biggest challenge to effi cient

management and control of TB.

The lower rates of MDR TB in Africa, when compared

with rates in Eastern Europe or South America, could be

Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 14, No. 9, September 2008 1349

Table 2. Descriptive statistics for country-specific MDR rates an d other TB-related factors, Africa*

Average, presurvey years (1995 to survey year)

Average, postsurvey years (year after survey to 2005)

Wilcoxon signed rank test†

Factor No., mean,

median Range SDNo., mean,

median Range SDZ-score, p

value‡

MDR rates 39, 2.21, 1.9 0.0–5.8 1.2

Incidence rate/100,000/ y 39, 116, 109 22–228 40.6 33, 152, 150 25–308 70.2 –3.92, 0.0001§

Case detection rate (new ss+) 39, 47.2, 49.8 8.2–86.0 22.4 32, 55.5, 56.2 13.6–112.2 27.5 –1.52, 0.130

Treatment indicators

Cured 36, 50.9, 52.3 17.1–74.6 14.2 32, 56.2, 59.0 16.6–78.4 14.5 –3.58, 0.0001§

Completed 39, 14.3, 12.4 3.1–47.4 9.8 32, 13.9, 11.1 1.3–38.5 8.9 1.27, 0.206

Died 36, 6.7, 6.1 2.6–19.5 3.3 32, 7.4, 7.2 0.7–17.1 3.5 –0.36, 0.721

Failed 36, 1.8, 1.6 0.0–7.8 1.5 32, 1.7, 1.3 0.2–5.3 1.2 –0.34, 0.738

Defaulted 36, 14.1, 13.2 4.4–41.4 6.8 32, 11.9, 10.9 2.6–39.7 7.4 2.48, 0.013§

Succeeded 36, 65.2, 67.0 33.0–83.5 10.3 32, 70.0, 70.5 37.1–90.3 10.3 –3.56, 0.0001§

Retreatment indicators

Cured 35, 47.1, 48.0 11.1–71.3 16.2 29, 48.5, 52.0 2.9–72.4 17.3 –1.22, 0.221

Completed 35, 14.1, 12.7 0.0–46.6 8.7 29, 13.4, 9.8 0.5–40.8 10.0 1.49, 0.135

Died 35, 7.9, 7.7 0.0–22.7 4.1 29, 10.4, 10.1 1.6–21.4 4.5 –2.27, 0.023§

Failed 35, 3.6, 2.8 0.2–14.6 2.8 29, 3.2, 3.0 –8.9 2.2 0.18, 0.861

Defaulted 35, 14.6, 12.8 4.6–29.3 6.9 29, 11.9, 10.9 2.7–26.7 6.2 1.49, 0.135

Succeeded 35, 61.1, 62.6 30.3–81.3 13.1 29, 61.9, 64.6 23.1–81.8 14.2 0.18, 0.861

Year 2005 only variables

Prevalence/100,000 38, 497, 513 55–936 178

TB mortality rate/100,000/ y 39, 79, 73 2–304 48

HIV/TB co-infection, % 39, 26.8, 19.0 0.5–75.0 20.5

Male/female ratio: case notifications

36, 1.5, 1.5 0.7–2.6 0.4

Health expenditures (US $ per capita)

39, 107, 51 15–689 131

*MDR, multidrug resistance; TB, tuberculosis; ss+, sputum sample positive. †Based on presurvey minus postsurvey values. A negative Z-score is indicative of an increase over time. ‡Marginally statistically significant trend (p<0.10). §Statistically significant trend (p<0.05).

Figure. Prevalence of multidrug resistance (MDR) in Africa among combined tuberculosis cases. A) Data collected from the Third Global

Report on Anti-tuberculosis Drug Resistance in the World of the World Health Organization (WHO) published in 2004 (40). B) Data from

various recent WHO publications, peer-reviewed journal articles, and WHO’s Fourth Global Report (1). C) Formulaic estimates of Zignol

et al. (11). AFRO, WHO Regional Offi ce for Africa.

Emerg Infect Dis 2008; 14: 1345-1352

Diagnosis and treatment of MDR TB in the

world

WHO Global TB report, 2014

What we need to do to eliminate tuberculosis

• Invest in public health

• Invest in research

• Embrace new ideas and new technology

• Take MDR-TB seriously

• Stop doing stupid stuff

• Speak with a louder voice

What we need to do to eliminate tuberculosis

• Invest in public health

• Invest in research

• Embrace new ideas and new technology

• Take MDR-TB seriously

• Stop doing stupid stuff

• Speak with a louder voice

First performance 1853 First performance 1896