In Vitro Diagnostic Platforms for the Developing World. David Kelso Oak Ridge April 20, 2012

Transcription

1 In Vitro Diagnostic Platforms for the Developing World David Kelso Oak Ridge April 20, 2012

2 Center for Innovation in Global Health Technologies Academia Key Contributions: Project Coordination, New Technology, Market Research and Product Development, Field Experience Current Partners: McCormick School of Engineering Center for Innovation in Global Health Technology (CIGHT) Kellogg School of Management Global Health Initiative (GHI) Feinberg School of Medicine Industry Philanthropy Key Contributions: Technology, Manufacturing, Regulatory, Distribution, Current Partners: Key Contributions: R&D Funding, Mission, Field Experience Partners: 2

3 Northwestern Global Health Foundation Non-profit distributor of medical devices in developing world Researches markets Funds technology transfer Contracts with device manufacturers Conducts field evaluations Supports and services products 3

4 Need for point-of-care early infant HIV diagnostic, EID 1.4 million infants were born to HIV-positive women in thousand infants infected If not diagnosed and started on antiretroviral therapy, 35% of infected infants will die by age 1 year, 52% by age million adjusted life years could be saved annually assuming 100% sensitivity and availability of ART 4

5 Testing sites in the developing world Level: National and Private Hospitals & Reference Lab, Research Institute Regional or Provincial Hospital District Hospital / Urban Hospitals County Hospital Rural Health Care Center or VCT Outreach Programs 5

6 EID test volumes in Uganda Uganda Daily Testing Analysis % of all tests Cumulative % Across health facilities, test volumes ranged from 1 to 14 tests per day Overall, health facilities had a median volume of 1 test per day (IQR:1, 2) 96.8% of all tests performed took place on days where the facility performed 5 tests or less Tests per Day per Facility Source: 2008 Kellogg field research 6

7 Technical challenges Obtain plasma without centrifuge Disrupt immune complex Add liquids without pipets Detect pm concentrations of p24 antigen Turnaround time < 1 hr. Function in ambient temperatures > 40C Send results to central lab

8 Plasma without centrifugation by filtration

9 Variation of plasma volume

10 Disrupt immune complex by heat shock

11 Disrupts antibody-antigen complex C for 5 min required for high avidity patients p24 antigen refolds, epitopes of test antibodies intact Gel forms in specimens with high IgG levels Effects of heat shock

12 Transfer liquids without pipets By SafeTech capillary By absorbent pad By unit dose dispenser

13 Detect p24 antigen by immunochromatographic assay

14 Antibody coated carbon nanoparticles Biotinylated capture antibody SA on capture line Anti-mouse IgG on control line pm limit of detection ICA components

15 p24 antigen ICA clinical performance 389 samples tested in NHLS lab in Cape Town South Africa 24 (6.2%) were positive by PCR p24 antigen ICA detected 23 for sensitivity of 95.8% (95% confidence limits: %) 2 false positives for specificity of 99.4% (95% CI: %), Turnaround time 45 min.

16 p24 antigen correlation with viral load 18 samples tested with viral loads 345 to 2 million All samples positive except the 3 with the lowest viral loads Lowest viral load detected was 6,580 copies/ml

17 Global temperature ranges J F M A M J J A S O N D Timbuktu, Mali Lhasa, Tibet

18 Function in temperatures > 40 C Peltier heats and cools tube Reaction temperature 30 C

19 Communicate with central lab Cellular modem with SIM card Push buttons to enter P, N, I Results stored in flash memory Phones lab at pre-scheduled time Transmits results

20 Kenya planned communica2ons network Health Facility: USSD/ SMS Query for test results Reference Laboratories Online SQL database on Server rendered by PHP to any web browser Becton Dickenson FACSCalibur for CD4 testing EMR Patient test results SYSMEX Hematology analyzer PC software controlling the analyzer Health Facility: GSM Printers on GPRS or SMS Health Facility: PCs accessing data over the Internet Roche CAP/CTM Analyzer (EID and Viral Load)

21 p24 plans Transfer production to contract manufacturers Test in Mozambique & Malawi clinics 3 rd quarter FDA export certificate required Conduct studies in Zambia, Uganda, Kenya, Nigeria, India Develop test strip reader

22 Need for point-of-care HIV viral load monitor 34M people living with AIDS 23M in sub-saharan Africa 15M in need of anti-retroviral therapy 6.6M receiving ART 22

23 Need for point-of-care TB diagnostic 8.8M new TB cases in high burden countries Multi-drug resistant, MDR Extensively drug-resistant XDR 23

24 NAT Technical Challenges Viral load PCR detection limit HIV VL 50c/ml Viral load precision to monitor changes Obtain plasma without centrifugation TB culture detection limit 10 cfu/ml Safe handling of TB sputum specimens Workloads in large treatment clinics TB turnaround time < 1 hr HIV turnaround time < 2 hrs

25 Critical attributes Useful Affordable Appropriate Accurate Robust Reliable