TB Tools

1
TB Tools

• OSI Grantee Orientation
• September 27, 06
• Istanbul, Turkey

2
Need for Improved TB Diagnostics

• Microscopy
• Microscopy is most commonly used to detect TB
  (1882).
• -In field conditions detects only 45-60 cases,
  requires 2-3 visits
• -Doesnt detect smear negative or extra pulmonary
  cases
• -HIV-TB coinfected communities have higher rates
  of smear negative (upto 61) and extra pulmonary
  (upto 40) TB.

3
Diagnostics Need. Estimated cases by AFB Status
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Need for Improved TB Diagnostics

• Chest X-Ray
• X-rays alone arent very reliable (26-43)
• Immune compromised PLWH have different patterns
  of abnormality (more abnormalities in the lower
  and middle part of the lungs as opposed to upper)
• Technology isnt available easily and requires
  upkeep

5
Need for Improved TB Diagnostics

• PPD (Purified Protein Derivative)
• The test looks for immune response to TB
  particles
• Not recommended for severely immune compromised
  people (CD4 lt200)
• Cant tell between latent or active TB infection

6
Need for Improved TB Diagnostics

• Culture (Solid)
• Is very accurate but takes 4-6 weeks
• Needs somewhat sophisticated laboratory capacity,
  electricity, and water to work
• Culture (Liquid)
• Is very accurate and takes 11 days
• Is much more expensive and is not available

7
Strategies and Products in Diagnostics Pipeline

• New
• Eiken- LAMP (loop-mediated isothermal
  amplification). IDs TB in 1 hr
• Biotec- FASTPlaque. IDs Rif Resistance in 2 days
  among SS
• Salubris-TK Medium (14 days)
• Oxford Immunotec-T-SPOT TB blood test
• Demonstration Projects
• MGIT BACTEC rapid culture (2 weeks) - Understand
  its application in for case finding in TB/HIV,
  smear-negative pulmonary, extrapulmonary, MDR,
  pediatric TB

8
Need for new TB drugs

• 6 months is a long time, 4 HRZE, 2HR
• Rifampicin-ARV drug interactions (nevirapine,
  protease inhibitors)
• Overlapping side effects
• High pill counts
• MDR TB 450,000 new cases/year

9
TB Drugs in Clinical Trials

• Gatifloxin
• LL-3858 Sudoterb- in
• TMC 207
• Moxifloxicin
• PA824
• OPC67683

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New TB Vaccine

• BCG protects from meningeal and
  miliary/disseminated TB among infants and in
  early childhood
• Uncertain/low/no protection in adults
• Estimated 1/3 of worlds population is TB
  infected- so a more effective vaccine could
  reduce global TB infection as well as disease

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Vaccine Pipeline

• M72f
• MVA-85A
• rBCG30
• AG85/ESAT-6
• rBCG?UreHly

12
Challenges

• New diagnostic, drug, vaccine pipelines need
  basic science and greater investment to stay
  robust
• Few research sites capable of studying new TB
  diagnostics/drugs/vaccines scale-up
  capacity/infrastructure needed
• Difficult issues re trial design for smear
  negative, extrapulmonary, pediatric, TBHIV, MDRTB
  (Dec 12-13)
• Need new lab tests/lab markers to measure
  effectiveness of new tools
• Insufficient research infrastructure
• Operational research needs to be well addressed
  to facilitate uptake
• Community involvement just beginning

13
Some Research Priorities

• What is the impact of IPT on TB infection, will
  it lead to greater INH resistance?
• StudyThibela TB (Prevent TB) Carried out in
  gold mines located in South Africa, this study
  will determine whether TB preventive therapy
  given to an entire high risk community is more
  effective than TB preventive therapy given to
  high risk individuals only.
• Botswana is doing IPT in their ARV program.
  Information from there will answer this question

14
Some Research Priorities (Contd)

• How can TB/HIV care be integrated?
• StudyZAMSTAR
• -24 cmties in Zambia and South Africa 6 receives
  community-based improved case finding of TB, 6
  receives household level TB/HIV integrated
  activities, 6 receives community-based improved
  case finding of TB plus household level TB/HIV
  integrated activities.  6 will serve as the
  control.
• -MSF programs in Khayelitsha South Africa also
  studied how TB/HIV care can be integrated

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Role of Community Advocates

• As advocates for good research amongst our
  communities
• Supporting resource mobilization for research
• In partnering with research institutions to make
  sure that communities priorities are reflected in
  research agenda
• In ensuring research is conducted ethically and
  address relevant community concerns
• In ensuring that research gets translated into
  programs and policies

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Resources

• Global Alliance for TB Drug Development
  (Tballiance.org)
• Stop TB Partnership (Stoptb.org)
• Aeras Vaccine Foundation (aeras.org)
• Treatment Action Group (treatmentactiongroup.org)
• Foundation for New and Innovative Diagnostics
  (Finddiagnostics.org)