David Kelso Oak Ridge April 20, 2012

In Vitro Diagnostic Platforms for the

Developing World

2  

Center for Innovation in Global Health Technologies

Industry

Academia

Philanthropy

Key Contributions: • Technology, Manufacturing, Regulatory,

Distribution, Current Partners:

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

Key Contributions: • R&D Funding, Mission,

Field Experience Partners:

3  

Northwestern Global Health Foundation

¡  Researches markets ¡  Funds technology transfer ¡  Contracts with device manufacturers ¡  Conducts field evaluations ¡  Supports and services products

Non-profit distributor of medical devices in developing world

Need for point-of-care

early infant HIV diagnostic, EID

4  

¡  1.4 million infants were born to HIV-positive women in 2007 ¡  390 thousand infants infected ¡  If not diagnosed and started on antiretroviral therapy,

35% of infected infants will die by age 1 year, 52% by age 2

¡  2.8 million adjusted life years could be saved annually assuming 100% sensitivity and availability of ART

5  

National and Private Hospitals & Reference Lab, Research

Institute

Regional or Provincial Hospital

District Hospital /

Urban Hospitals

County Hospital

Outreach Programs

Rural Health Care Center or VCT

Level:

Testing sites in the developing world

Source: 2008 Kellogg field research

EID test volumes in Uganda

Tests per Day per Facility

% o

f all

test

s

Cum

ulat

ive

%

• 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

Uganda Daily Testing Analysis

6  

¡  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

Technical challenges

Plasma without centrifugation by filtration

Variation of plasma volume

Disrupt immune complex by heat shock

Effects of heat shock

¡  Disrupts antibody -antigen complex

¡  90-95 °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

By SafeTech capillary By absorbent pad By unit dose dispenser

Transfer liquids without pipets

Detect p24 antigen by immunochromatographic assay

ICA components

•  Antibody coated carbon nanoparticles •  Biotinylated capture antibody •  SA on capture line •  Anti-mouse IgG on control line •  pM limit of detection

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: 79.8 – 99.3%) ¡  2 false positives for specificity of 99.4% (95% CI: 98.0 –

99.8%), ¡  Turnaround time 45 min.

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

Global temperature ranges

Timbuktu, Mali http://www.world66.com/africa/mali/timbuktu/lib/climate

-20

-10

0

10

20

30

40

J F M A M J J A S O N D

Lhasa, Tibet http://www.asia-planet.net/china/temperature2.htm

Function in temperatures > 40°C

•  Peltier heats and cools tube •  Reaction temperature 30 °C

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

Kenya  planned  communica2ons  network  

Roche CAP/CTM Analyzer(EID and Viral Load)

Online SQL database on Server rendered by PHP to any web browser

Health Facility: USSD/ SMS Query for test results

Health Facility: PCs accessing data over the Internet

PC software controlling the analyzer

Becton Dickenson FACSCalibur for CD4 testing

SYSMEX Hematology analyzer

Reference  Laboratories  

Health Facility: GSM Printers on GPRS or SMS

EMR Patient test results

p24 plans

¡  Transfer production to contract manufacturers ¡  Test in Mozambique & Malawi clinics 3rd quarter

FDA export certificate required ¡  Conduct studies in Zambia, Uganda, Kenya, Nigeria, India ¡  Develop test strip reader

Need for point-of-care HIV viral load monitor

22  

¡  34M people living with AIDS ¡  23M in sub-Saharan Africa ¡  15M in need of anti-retroviral therapy ¡  6.6M receiving ART

Need for point-of-care

TB diagnostic

23  

¡  8.8M new TB cases in 2010 ¡  22 high burden countries ¡ Multi-drug resistant, MDR ¡  Extensively drug-resistant XDR

¡  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

NAT Technical Challenges

¡  Useful ¡  Affordable ¡  Appropriate ¡  Accurate ¡  Robust ¡  Reliable

Critical attributes