TB Diagnostics *

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

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. Availability of diagnostic services Among 22 high burden countries there is an average of 1.12 microscopy centers per 100,000 population BUT50% do not work due to logistical problems (missing or broken materials, strikes, lack of trained personnel) making access to microscopy difficult

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.

7. Economic barriers • 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.

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. A brief background about FIND • 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

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. Purpose Test Indications Priority Case Detection Drug susceptibility testing Latent TB Infection • 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 • # 1 • # 2 • # 3 • # 4 • # 5 Priority setting

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

13. Tactic: Milestones for Process and Outputs Customer support document Access Registration Contract phase Feasibility Development phase Evaluation phase Demonstration phase Global Policy National Practice Impact PHASES 1 2 3 4 5 6 7 8 Milestones Customer Requirements Specifications Product in box Efficacy Effectiveness WHO guidelines Customer support document Effectiveness & Access Output PARTNER FIND

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

15. DEVELOPMENT EVALUATION DEMONSTRATION POLICY NATIONAL PRACTICE Bottlenecks to success FEASIBILITY 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 Inadequate proven principles Action More investments in product driven discovery research Civil society Bottleneck? Clinical, management & infrastructure capacity Action Continuous partner involvement including civil society

16. Project sites and demonstration goals

17. Mbeya Medical Research Programme, Tanzania