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 -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.

3. Diagnostics Need. Estimated cases by AFB Status

4. 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 <200) 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

10. 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

11. 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? 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

14. 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

15. 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

16. 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)