1. 1 TB Diagnostics* Vinand M Nantulya *Presentation at TAC/TAG First Africa Region TB/HIV Advocacy, 19-21 June 2006, Cape Town, South Africa

2. 2 Fundamental diagnostic: 1882 Fundamental diagnostic: 2006 Market uptake Lack of progress in TB diagnostics Discovery Science Product Development Targets & Reagents Companies & Platforms Performance testing Evaluation & Approval Need & Access

3. 3 Current global direct expenditures on TB diagnostic tests The diagnostic yield of this expenditure is limited, with only 19% of all TB cases detected and reported as smear-positive.*

4. 4 Availability of diagnostic services Among 22 high burden countries there is an average of 1.12 microscopy centers per 100,000 population BUT 50% do not work due to logistical problems (missing or broken materials, strikes, lack of trained personnel) making access to microscopy difficult

5. 5 In Lima, 22% of 259 TB patients first sought health care from pharmacists. But only 56% of TB patients were requested to submit sputum specimens and did so. In Chennai, 13% of 1000 patients being evaluated for symptomatic respiratory disease did not complete the diagnostic process, and 11% of patients in whom TB was detected were not notified of the diagnosis. In Lusaka, on the other hand, due primarily to the necessity for patients to purchase the sputum collection container, only 0.5% of patients completed the diagnostic process and only 6 of 600 patients even submitted a single sample.

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7. 7 Although DOTS provides free diagnosis and treatment, repeated visits to health facilities are required. The cost of transportation and food, coupled with low income because of time away from work, may be more than poor TB patients or families can afford. A study from Malawi estimated that on average, TB patients spent US$ 13 and lost 22 days from work at the diagnosis stage alone. Patients presenting for diagnosis in a study in Ho Chi Minh City contacted 1.3 different health providers with an average of 2.5 visits per health care provider. Moving from one provider to the next delays treatment and involves considerable cost to the patient. Economic barriers

8. 8 Delays to diagnosis within the health system varied widely, but were in many cases substantial, and could be limited by introducing technologies that could be used more peripherally, where patients first seek care.

9. 9 FIND was established in 2003 by World Health Assembly resolution A public / private partnership Based in Geneva as a Swiss tax-exempt foundation Current portfolio includes TB, Malaria and sleeping sickness, each run as an independent business unit Currently funded by Bill and Melinda Gates Foundation, but there is need for funds from public sector donors A brief background about FIND

10. 10 FIND is pursuing a two-pronged strategy Develop and evaluate better diagnostic tools Explore creative, sustainable ways to strengthen overall quality of diagnostic services in both public and private health sector, using new tools as catalyst

11. 11 Purpose Case Detection Drug susceptibility testing Latent TB Infection Test Indications Detect pulmonary TB with high bacterial load (SS+) Detect pulmonary TB with low bacterial load (SS -, Cx +) Detect extra-pulmonary and pediatric TB Detect MDR-TB for treatment Detect LTBI for treatment Priority # 1 # 2 # 3 # 4 # 5 Priority setting

12. 12 Levels of health system FIND’s strategy is driven by customer requirements and the different levels of health system Few hours Less than 1 hour NAAT Cultures Microscopy Only 19 % (1.7 million) of new cases detected by microscopy (smear +) 5 days 15 days 1 day 2 M undetected unreported smear + patients 45 days 5 days

13. 13 Feasibility Contra ct phase Develo pment phase Evalu ation phase Demonst ration phase Glob al Polic y 2365471 Customer Requirements Specifications Tactic: Milestones for Process and Outputs PHASES Milestones 8 Natio nal Practi ce Imp act Customer support document WHO guidelines Effectiveness Efficacy Product in box Effectiveness & Access Registration FIND PARTNER Output Access Customer support document

14. 14 Development Evaluation Feasibility DistrictLab PeripheralLab TB Product pipeline – Status 2006 Clinic Health post Demonstration MGIT- MTB SPECIATION MGIT-DST PHAGE RIF RESIST REAL TIME PCR TK-MEDIA E-NOSE FLUOR MICROSCOPE URINE LAM ELISA LAMP ISOTHERMAL NAT URINARY DNA DETECTION AG DISCOVERY PROJECTS RAPID ANTIBODY TEST FLURESCENCE STRIP METER FOR AB DETECTION ANTIGEN LAT FLOW URINE LAM LAT FLOW Access FEASIBILITY DEVELOPMEN T EVALUATION DEMONSTRATI ON POLICY

15. 15 FEASIBILITY Bottlenecks to success Bottleneck Inadequate proven principles Action More investments in product driven discovery research Civil society DEVELOPME NT EVALUATIO N DEMONSTRATI ON POLICYNATIONAL PRACTICE Bottleneck? Reluctance or slow process Action Strategic communication & finance activities & civil society Bottleneck: Training Maintenance Trouble shooting, QC/QA Access for underprivileged Action Involve industry, partners & civil society Creative solutions Bottleneck? Clinical, management & infrastructure capacity Action Continuous partner involvement including civil society

16. 16 Project sites and demonstration goals Study sites MGIT in established lab MGIT in new lab (district level) Impact on clinical outcome Cost-effectiveness ZAMSTAR: Lusaka, Cape Town NRL in Lusaka, TB lab at Stellenbosch Impact of MGIT for AFB- TB on care Overall cost of MGIT for AFB- TB cases THIBELO: gold mines in 3 regions in South Africa NHLS laboratory in Johannesburg Relative diagnostic yield in AFB- TB cases Expected value of clinical information THRio: HIV care clinics in Rio de Janeiro TB lab in national research center Relative diagnostic yield in AFB- TB cases QUALYs gained by MGIT vs no culture Tanzania: Dar es Salaam and Iringa Region National TB Reference lab in Dar New TB lab in IringaTBD Eldoret: HIV care program New TB lab in AMPATH program TBD Cambodia: two to four provinces with TB/HIV activities New TB labsTBD

17. 17 Mbeya Medical Research Programme, Tanzania