FORGOTTEN BUT NOT GONE

International Journalists as
Global Health Advocates

Lee Reichman, MD, MPH

Berlin, Germany
November 2010
TB Historical Permutation

• 17th - 18th centuries TB took 1 in 5 adult

lives
• 1850 - 1950 one billion people died of TB

• Current decade 2000-2010

– 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
TB Isn’t Eliminated

Because:
• Nobody seems to care
This wouldn’t be tolerated
for any other disease
 Deaths Due To:

TB (annually) 1,770,000
SARS 813
Avian Influenza 6,250
Anthrax 5
Mad Cow Disease 1 (Cow)
Smallpox 0
 What is Tuberculosis?
• Infectious disease caused by a germ called
Mycobacterium tuberculosis
• It is spread through the air

• Usually affects the lungs although it can

affect any organ
• Is spread when someone who is sick with
TB disease of the lungs coughs or sneezes,
releasing germs and a person nearby
breathes in these infected droplets
 What happens when you
breathe in TB germs?
• A person infected with the TB bacteria is
not necessarily sick
– TB infection: The natural defense system can
keep the bacteria under control and person is
not sick
– TB disease (active TB) : Immune system
cannot keep the bacteria under control and
they multiply rapidly, making the person sick
Factors that impact transmission
• Infectiousness of the person with TB disease
– Number of bacteria
– Type of TB: pulmonary vs. extra-pulmonary

• Environment
– Volume of shared space
– Ventilation and direct sunlight

• Length of exposure

• Intensity of exposure
– Disease of lungs, upper airways, larynx
– Cough
– Incorrect or incomplete treatment
 Most effective way to stop
transmission
• Isolate patients with suspected or confirmed
TB disease immediately
• Start treatment with anti-TB medicine

As long as TB patient is on
appropriate TB medicines and takes
medications as directed, the potential
to infect other people will decline
rapidly.
 Development of TB disease
• HIV-negative: about 10% of people infected with TB
will develop TB disease within their lifetime
• Anyone can get TB!

• However, there are some groups at greater risk for

developing TB disease:
– People with HIV infection
– Those infected in the last 2 years
– Babies and young children
– People who inject illegal drugs or abuse alcohol
– People sick with other diseases that weaken the immune
system
– Elderly people
 Diagnosis of TB Disease
• A person suspected of having TB disease
may have these symptoms:
– Fever, cough (≥3 weeks), chest pain, night
sweats, weight loss, fatigue, coughing up
blood, decreased appetite

• Diagnosis:
– Patient history and clinical exam
– Laboratory tests
– Chest x-rays
Treatment of TB Disease
• TB is curable!

• TB treatment strategy (DOTS)

– Standardized, short-course
– Proper patient management

• Treatment
– 6 months
• 4 antibiotic-drugs for 2 months
• 2 antibiotic-drugs for 4 months
 TB/HIV
• TB/HIV is a lethal
combination, each speeding
the other’s progress
• Risk of progression of TB
disease much greater in HIV-
infected persons
– About 10% chance every
year
• TB is leading cause of death
in those with HIV
Co-Existence of HIV & TB infection

TB
Infection
HIV
Infection

10% per lifetime 10% per year

.0017% per year

Risk of Active TB
 HIV Drives the TB Epidemic:
TB Trends in Africa 1980-2006
700
Zimbabwe Kenya Malawi
Tanzania Cote d'Ivoire South Africa

600
N o tifica tio n ra te (a ll fo rm s )/1 0 0 k

500

400

300

200

100

0
1980 1985 1990 1995 2000 2005
 Drug Resistant TB
• Man-made phenomenon
• Causes:
– Inadequate or incomplete
treatment
– Interruption in the supply
of essential drugs
– Poor quality drugs
• Treatment of MDR-TB
– Very long – 18-24 months
– Toxic 2nd line drugs
– Expensive
• Persons at increased risk
– With history of TB
treatment
– Received inadequate
treatment for >2 weeks
– Contacts of known drug-
resistant patients
– Born or living in areas
with high prevalence of
drug-resistant TB
Pathogenesis of Drug Resistance – 1

INH
RIF
PZA

I
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INH I
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Pathogenesis of Drug Resistance – 2

I I
I IR
I
I I
I I
I I IP
INH
I I
RIF
IR
I IR
IR
I IR
I I IR
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I IR
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IR
IR
 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 drug-sensitive 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
 TB Remains a Global Killer
Why does TB still infect one-third of
the world’s population and remain a
global health threat despite the fact
that highly cost-effective drugs are
available to eradicate it?
The Global Burden of Tuberculosis
NO NEW DRUGS / NO NEW TOOLS

• Last new drug class specifically for TB -

Rifampin (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?
 Approved & Major Experimental
ARV Drugs (1987-2008)

ARV Class Approved Experimental Experimental

Under Interrupted
Investigation
NRTI 8 12 8
NNRTI 4 9 6

PI 10 5 4
Entry Inhibitors 2 17 10
Integrase 1 5 2
Inhibitors
Maturation 0 3 0
Inhibitors
Gene Therapy 0 4 0
TOTAL 25 55 30

Vitoria MAA, October 2008

 NEW TOOLS

• There are now 3 major global efforts to alleviate

this problem
• Foundation for Innovative New Drugs (FIND)

• AERAS Global Vaccine Foundation

• Global Alliance for TB Drug Development

 Aeras Global TB Vaccine
Foundation

Mission:

To develop new TB vaccines and ensure their

availability to all who need them

Goals:

- To obtain regulatory approval and ensure supply of

a new TB vaccine regimen to prevent TB in the next 7-
10 years

- To introduce 2nd generation vaccines with improved

product profiles and efficacy against latent TB in 9-15
years
 About Aeras
• International non-profit organization with 14 current partners,
among them:
– Crucell NV (Netherlands), Statens Serum Institut (Denmark),
GSK (Belgium), Max Planck Institute (Germany), UCLA (USA),
University of Cape Town (S. Africa), St. Johns Medical College
(India)

• Aeras forms joint development teams with partners to

develop promising TB vaccine candidates – currently there
are 3 leading candidate regimens

• Primary funding provided by the Bill & Melinda Gates

Foundation with additional funding from CDC, NIH, and
Danida
 Global Alliance for Tuberculosis
Drug Development

Growing Epidemic
5% increase in annual incidence in Africa
1% increase in annual incidence globally
Current status
9 million new cases annually
2 million deaths annually
Reference: Global tuberculosis control: surveillance, planning, financing. WHO
Report 2005.

The Problem:
Current TB therapy, though efficacious, is inadequate to control the
global TB epidemic - too long and too complex
 The TB Alliance
• Founded in 2000 (Cape Town Declaration)
• Independent Non-Profit Organization
• International Public-Private Partnership
• Based in New York with offices in Brussels and
Cape Town
 The TB Alliance

Mission
•Develop new, better drugs for TB

•Ensure affordability, access and

adoption (AAA)
•Coordinate and catalyze TB drug
development activities worldwide
 The Solution

New drugs combined into

shorter, simpler regimens
 TB Alliance Priorities
Based on impact and feasibility

1. Active disease
2. MDR-TB
3. TB/HIV co-infection
4. Latent infection (LTBI)
 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
Why do we need to care about
TB in the rest of the world?
 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
INFORMATION LINE
1•800•4TB•DOCS (482-3627)
www.umdnj.edu/globaltb