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TB Tools. OSI Grantee Orientation September 27, 06 Istanbul, Turkey. 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
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TB Tools OSI Grantee Orientation September 27, 06 Istanbul, Turkey
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 -Doesn’t 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.
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
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 <200) • Cant tell between latent or active TB infection
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
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
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
TB Drugs in Clinical Trials • Gatifloxin • LL-3858 Sudoterb- in • TMC 207 • Moxifloxicin • PA824 • OPC67683
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 world’s population is TB infected- so a more effective vaccine could reduce global TB infection as well as disease
Vaccine Pipeline • M72f • MVA-85A • rBCG30 • AG85/ESAT-6 • rBCGUreHly
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
Some Research Priorities What is the impact of IPT on TB infection, will it lead to greater INH resistance? Study:Thibela – 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
Some Research Priorities (Contd) How can TB/HIV care be integrated? Study:ZAMSTAR -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
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
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)