The Management of LTBI and Tuberculosis Disease in HIVInfected Patients

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TB BASICSRefresher What is tuberculosis?The
Lung Health ProgramInternational Journalists as
Global Health Advocates
Lee Reichman, MD, MPHCancun, MexicoDecember
1-7, 2009
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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
• 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

• We know its
• Cause
• Transmission
• Treatment
• Prevention

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TB Isnt Eliminated

• Because
• Nobody seems to care
• This wouldnt be tolerated
• for any other disease

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Deaths Due To

• TB (annually) 1,770,000
• SARS 813
• Avian Influenza 6,250
• Anthrax 5
• Mad Cow Disease 1 (Cow)
• Smallpox 0

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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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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

• 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.

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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

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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

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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

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TB/HIV

• TB/HIV is a lethal combination, each speeding the
  others 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

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Co-Existence of HIV TB infection
TB Infection
HIV Infection
10 per year
10 per lifetime
.0017 per year
Risk of Active TB
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HIV Drives the TB Epidemic TB Trends in Africa
1980-2006
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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 gt2 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
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Pathogenesis of Drug Resistance 2
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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 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 everybodys
  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 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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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)

Wouldnt one think that largest killer of any
single infection deserves better, newer tools?
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Approved Major Experimental ARV Drugs
(1987-2008)
Vitoria MAA, October 2008
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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

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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 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

• 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.

• Current TB therapy, though efficacious, is
  inadequate to control the global TB epidemic -
  too long and too complex

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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

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The 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 Solution
New drugs combined into shorter, simpler regimens
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TB Alliance Priorities Based on impact and
feasibility

• Active disease
• MDR-TB
• TB/HIV co-infection
• Latent infection (LTBI)

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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
• 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?
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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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