tuberculosis: forgotten but not gone (lee b. reichman, m.d., m.p.h.)
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Tuberculosis: Forgotten but not Gone (Lee B. Reichman, M.D., M.P.H.)TRANSCRIPT
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FORGOTTEN BUT NOT GONEFORGOTTEN BUT NOT GONE
Lee B. Reichman, MD, MPHLille, France
October 2011
Lee B. Reichman, MD, MPHLille, France
October 2011
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TB Historical PermutationTB 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
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TB Could Be Eliminated Because We Understand It
TB Could Be Eliminated Because We Understand It
We know its:
• Cause
• Transmission
• Treatment
• Prevention
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TB Isn’t EliminatedTB Isn’t Eliminated
Because:
• Nobody seems to care
This wouldn’t be tolerated for any other disease
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Deaths Due To:Deaths Due To:
TB (annually)
1,770,000
SARS
813
Avian Influenza
18,000
Anthrax
5
Mad Cow Disease
1 (Cow)
Smallpox
0
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What is Tuberculosis?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
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Estimated number of
cases
Estimated number of
deaths
1.45 million(range: 1.2–1.6 million)
8.8 million(range: 8.5–9.2 million)
650,000(460,000 – 870,000)
All forms of TB
Multidrug-resistant TB (Prevalent)
HIV-associated TB
1.1 million (13%) (range: 1.0–1.2 million)
350,000(range: 320,000–390,000)
The Global Burden of TB 2010
about 150,000
Source: WHO Global Tuberculosis Control Report 2011
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Estimated MDR-TB incidence rates, 2009 (new and previously treated)
Estimated MDR-TB incidence rates, 2009 (new and previously treated)
MDR-TB cases emerging annually, per 100,000 population
African countries with estimated MDR-TB incidence rates ≥ 15 MDR-TB cases per 100,000 populationBotswana: 27 / 100,000Mozambique: 16 / 100,000Namibia: 17 / 100,000Rwanda: 16 / 100,000South Africa: 26 / 100,000Swaziland: 23 / 100,000Zimbabwe: 19 / 100,000
India: 8 / 100,000
Selected countries of the former Soviet Union:Estonia: 7 / 100,000Kazakhstan: 57 / 100,000Russia: 27 / 100,000Tajikistan: 59 / 100,000
China: 7 / 100,000
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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
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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
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Most effective way to stop transmission
Most effective way to stop transmission
• Isolate patients with suspected or confirmed TB disease immediately
• Start treatment with anti-TB medicine
As long as the TB patient is on appropriate TB medicines and takes medications as directed, the potential to
infect other people will decline rapidly.
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Development of TB diseaseDevelopment 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
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Diagnosis of TB DiseaseDiagnosis 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
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Treatment of TB DiseaseTreatment 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
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Co-Existence of HIV & TB infectionCo-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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HIV Drives the TB Epidemic:HIV Drives the TB Epidemic:TB Trends in Africa 1980-2006TB Trends in Africa 1980-2006
0
100
200
300
400
500
600
700
1980 1985 1990 1995 2000 2005
No
tifi
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tio
n r
ate
(a
ll f
orm
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10
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Zimbabwe Kenya MalawiTanzania Cote d'Ivoire South Africa
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Drug Resistant TBDrug 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
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Pathogenesis of Drug Resistance – 1
IP
R
INH RIF PZA
INH I
I
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I
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Pathogenesis of Drug Resistance – 2
INHRIF
I
I
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I
I
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II
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IP
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IR
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IRIR
IR
IRIR
IRIRP
IR
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Unsexy TuberculosisUnsexy 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
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TB Remains a Global KillerTB 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?
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The Global Burden of TuberculosisNO NEW DRUGS / NO NEW TOOLS The Global Burden of TuberculosisNO 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?
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NEW TOOLSNEW 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
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Aeras Global TB Vaccine Foundation
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
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About AerasAbout 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
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The Problem:The Problem:Current TB therapy, though efficacious, is inadequate to control the global TB epidemic - too long and too complex
Global Alliance for Tuberculosis Drug Development
Growing Epidemic 5% increase in annual incidence in Africa 1% increase in annual incidence globally
Current status9 million new cases annually 2 million deaths annually
Reference: Global tuberculosis control: surveillance, planning, financing. WHO Report 2005.
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The TB AllianceThe 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
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The TB AllianceThe TB Alliance
Mission
•Develop new, better drugs for TB
•Ensure affordability, access and adoption (AAA)
•Coordinate and catalyze TB drug development activities worldwide
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The SolutionThe Solution
New drugs combined into shorter, simpler regimens
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1. Active disease
2. MDR-TB
3. TB/HIV co-infection
4. Latent infection (LTBI)
TB Alliance Priorities Based on impact and feasibility
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Challenges in TB Control 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
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Why do we need to care about TB in the rest of the world?
Why do we need to care about TB in the rest of the world?
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Lessons from Andrew SpeakerLessons 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
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