Purdues Global Impact: Responding to the tragedy of HIVAIDS in Africa

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Purdues Global Impact Responding to the tragedy
of HIV/AIDS in Africa

• J. Paul Robinson
• SVM Professor of Cytomics,
• School of Veterinary Medicine, Professor of
  Biomedical Engineering,College of Engineering,
• Bindley Bioscience Center,
• Discovery Park,
• Purdue University

Bindley Bioscience Center
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A mother with AIDS
Magongo is from a small village in Swaziland. She
has HIV/AIDS and has a CD4 count of 39. A normal
CD4 count is 500-1500. Anyone under 200 should be
on therapy. At under 50, her chances of survival
are very slim. She does not have the 30 Rand each
way to get to the nearest clinic for treatment.
The checkup is 3 Rand. For the sake of 9 she
does not have, she may not get treatment.

• Her 2 year old child may or may not survive.
  She survives on the food she can grow in her
  garden. Why does Magongo have to walk 30 miles
  to a clinic that can not even do her CD4? Why is
  it that no-one in rural Africa has access to a
  technology that is required for survival?
• This photo of Magongo and her baby was taken
  by a Purdue Public Health Science graduate
  student Annie Elbie in March 2008 when on a
  Purdue program exploring the needs and
  opportunities for service in Africa. (Used with
  permission)

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• Stephen Lewis addressed the XXIII congress of
  the International Society for Analytical Cytology
  on May 21, 2006.
• He spoke passionately about the devastation of
  families and villages impacted by the AIDS
  epidemic as he addressed 1,400 of the worlds
  leaders in cell analysis and flow cytometry

Lewis basic message .If you are such smart
scientists, why cant you solve the problem of
cheap CD4 tests?
Cytometry for Life www.cytometryforlife.org
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First 136 days of 2008 Africans died of
HIV/AIDS- 1,156,000

• In some countries over 1/3 of the population is
  HIV positive

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The World from 1569
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The Problem
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Comparative Land Areas
Great Britain
Africa
USA
Australia
Greenland
(Pop)
300 million
20 million
60 million
57,000
900 million
(Area Sq.Mi)
3.7 million
3 million
94,000
800,000
11.6 million
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Population of Africa
Indiana Area 92,896 km2 Pop. 6.5
million Texas Area 678,000 km2 Pop 22 million

• Countries by Size (61 countries)
• Nigeria 140 million 923,000 km²
• Egypt 70 Million
• Ethiopia 68 million 1.13 million km2
• Congo 55 Million
• South Africa 44 million
• Tanzania 37 Million
• Kenya 31 million
• Morocco 31 Million 447,000 km2
• Uganda 25 million 235,000 km2
• Mozambique 20 million 802,000 km2
• Total Population 900,000,000

Africa covers 6 of the Earth's total surface
area and 20.4 of the total land
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Map of world
Peters projection - equal land area
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Some facts about Africa

• Africa is 11.6 million sq. miles
• USA is 3.5 million sq. miles
• Africa population is 900 million
• USA is 300 million
• USA average lifespan is about 75 years
• Lesotho average lifespan is 42 years
• Healthcare spending
• In the USA we spend around 6700/person/year
• In Africa, the some countries spends
  1/person/year

Comparative land area
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Purdues Globalization goals
Meeting Global Challenges

• Define the role of Purdue in the 21st century
  entrepreneurial culture with a visionary program
  as a national model, focusing on University-wide
  talent, along with intellectual and physical
  resources, to maximize leverage, and providing
  transparent and coordinated access to
  intellectual resources.
• Link research initiatives to market needs and
  trends through partnerships with business and
  industry in support of the model for
  discovery-to-delivery.
• Inform public policy and provide informed
  leadership to policy discussions by way of a
  public policy institute that conducts analyses
  and impact assessments, and promotes coordination
  between large-scale research and economic
  development, leading to increased investment
  funds and Indianas impact on national as well as
  the global economy.

From the new draft Strategic Plan presented by
President Cordova
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Lewis spoke of CD4 machines-which measure the
number of CD4 immune cells and indicate whether
someone with AIDS should be treated-that are
bulky, difficult to use and, at about 50,000
each, vastly out of reach of most of the
continent. -Apoorva Mandavilli , Nature Medicine
12 (10) , October 2006
Lewis continues to speak against what he sees as
unconscionable neglect and reckless
indifference to AIDS. I think the global
community has responded lamentably, he says,
his voice rising. Were fighting for human
lives, what in Gods name is wrong with these
people? -Apoorva Mandavilli , Nature Medicine
12 (10) , October 2006
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Exponential epidemic growth
lt 40 million

Millions of infections
WHO 40 M infected 2000
lt 300k
lt 2k
origin
Year
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Another disturbing fact

• Children born of HIV positive mothers in the USA
  or Europe are only 0.2 likely to be HIV positive
  themselves. They will survive and probably
  thrive.
• In some places in Africa, 80 of babies born to
  HIV infected mothers contract the disease. These
  babies will probably die before they reach the
  age of 2

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CD4 and HIV/AIDS

• CD4-T cells are white blood cells
• They are destroyed by the HIV virus
• Without CD4-T cells your immunity is destroyed
• Normal levels of CD4 are 500-1500/microliter
• lt200 CD4/uL you must go on therapy
• A CD4 test will occur every 3-4 months for
  patients on therapy for life

The Bottom line Ready access to CD4 counts is an
absolute necessity in Africa
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Mack FulwylerInventor Innovator(1937-2001)

• A wonderful print of Mack Fulwyler by SVM
  Professor David Williams

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Cell Sorter - 500,000
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Cell Analyzer - 150,000
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The 3 Essentials for HIV/AIDS

• 1. Determine if the patient is HIV
• 2. Perform a CD4 test to determine immune status
  (CD4 lt200/µ must have therapeutics)
• 3. Provide antiretroviral therapy (ART)

Dipstick test is now available solution evident
Major problem in this critical path component
Foundations Governments working towards solution
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How do you measure CD4
Complex systems do multiple tests
Flow cytometry is a technique for counting,
analyzing and sorting microscopic particles that
have been suspended in reagent or stream of
fluid. It allows concurrent multiparametric
analysis of chemical and/or physical
characteristics of single cells flowing through
an optical and/or electronic detection apparatus.
Image Source http//openlearn.open.ac.uk/file.ph
p/2651/SK120_1_005i.jpg
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Current Model in Africa

• Create large central labs that can do everything
• Fill them with expensive instruments
• Try to train technicians and keep them (cant)
• Ship all the samples to central labs
• Send the results back to the remote places
• If lab is overloaded, buy more automated
  expensive instruments

The Bottom line It sounds very good, but does it
work?
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Diagnostic tests in Africa

• only 384 (40) of 964 patients with recurrent
  smear-positive pulmonary tuberculosis had their
  specimens arrive at the Central Reference
  Laboratory.

Cathy A. Petti, Christopher R. Polage, Thomas C.
Quinn, Allan R. Ronald, and Merle A.
Sande Laboratory Medicine in Africa Clinical
Infectious Diseases 42377-382, 2006
The Bottom line The current system does not work
well at all
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The results of the present system

• All the patients have to travel to the city or
  large centers
• The laboratories become overloaded and demand
  more automated instruments (automation is not
  always effective)
• Majority of people in rural communities do not
  receive needed diagnostics or therapeutics

The Bottom line Who will argue that this system
is successful?
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Current Diagnostic Tools

• Designed for Western health care system
• Driven by
• Large market of people who will pay
• Centralize system of management
• Multifunctional, extendable, upgradeable tools
• Large infrastructure, electricity, water, etc
• Databases and networks, automation

The Bottom line The Western health care system
is NOT good for Africa!!
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Impact on Africa

• Creation of inappropriate instrument base in
  Africa
• Many require significant infrastructure which is
  not there
• Use complex multi-test instruments require
  enormous training
• Instruments designed to do many tests but only
  one test (CD4) is mostly performed

The Bottom line Why is there no small cheap
device that does ONLY CD4 ?
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• Dont reinvent the wheel,
• just realign it

Anthony J. D'Angelo
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Location Related Issues
gt70 of AIDS patients in Africa are in rural
areas. User need Assessment 2006-7 220 medical
professionals. Useful instruments

• Have to be small and light
• Must be easy quick to set up
• Use finger stick not venipuncture
• Must be easy to operate (minimal training)
• Must be easy to clean
• Must be robust accurate
• Must operate in high temp/humidity
• Must be low cost/test (around 1)
• Must be manufacturable

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What is needed in Africa?
The C4L Solution
C4L Cytometry For Life
cytometryforlife.org
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Who will build these instruments?

• What incentive is there to design an instrument
  that has uncertain return-on-investment?
• It is hard enough to survive in the Western
  global market with all the existing incentives
• What possible advantages could a company have for
  moving to an unpredictable, complex, and
  difficult to manage market?

The Bottom line In reality, for diagnostic
instruments, the African market is not a good ROI
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The C4L Solution - point-of-care cytometer
SAMPLE

• No Automation
• No Computer
• No complex fluidics
• No complex optics
• Very compact
• Very robust

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• Housed in a small, solid carrying case.
• Contains battery, necessary containers, reagents
  and all other needed components.
• Weight less than 12 pounds.
• GPS link to network
• Phone-link for data or USB
• Lifetime of test data collected can be stored on
  chip

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Re-use of mass-produced technologies
Avalanche Photo Diode Bulk price
estimates based on 2007 information
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The C4L technology
Low Cost
Portable
Battery operated (totally portable)
Accurate (as good as any other system)
Single Purpose (easy to train use)
180/22
GPS (Location of most need)
Cell Phone (data transfer)

• Ability to track instrument and CD4 count
  remotely for epidemiological purposes
• Identify regions of therapeutic need
• Transfer data by cell phone or blue-tooth
• Potential for evaluation of drug resistance

Every CD4 count is mapped onto a location map so
we know where the most important areas to treat
are located
This concept uses very traditional chemistry and
assay design because this is mature and well
understood but the implementation is innovative
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ChipsR-in
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GPS system

• Track every instrument location
• Operational condition of units
• Transmission of data
• Epidemiological studies?
• We can locate area of need
• We may be able to monitor resistance

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Where are we today on this project?

• We have developed and tested a finger-stick based
  single tube CD4 test using 20 microliters of
  blood
• We have an operating prototype
• We have several collaborations on the ground in
  Africa
• We are in process of designing the electronics
  (GPS, Cellphone, DSP) systems
• We are identifying new partners to make this a
  successful implementation

The Bottom line Dont assume that someone else
will do it!
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How do you measure CD4?
Requires Lab, Electricity, a variety of lab
tools, Computer, software, significant time
factor,
How will we measure CD4 in future?
Requires No lab, no electricity, a single lab
tool (auto pipette), no computer, no software,
takes 10 minutes start to finish
Image Source http//openlearn.open.ac.uk/file.ph
p/2651/SK120_1_005i.jpg
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Conclusions

• We have excellent complex instruments for
  diagnostics but they dont satisfy the needs in
  remote areas
• The more people who go on therapy, the greater
  the demand will be for CD4 testing
• Our initial CD4 solution is an immediate (next 5
  years) solution to an immediate problem
• Next-generation tools will hopefully follow
  they are clearly not effective now despite the
  promises hopefully they will be here within 5
  years
• A simple, manual, single-test only device will be
  very effective in remote regions of Africa
  where the majority of HIV/AIDS patients are
• We need to meet the challenge!!!

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The Cytometry-For-Life team
Lova Rakotomalala
J. Paul Robinson Gary Durack
Hildred Rochon
National Coordinator
Postdoc
C4L Founders
And the many volunteers helping to make this
project a reality in Africa
Funding Parker Hannifin, private donations,
Purdue University
Dont reinvent the wheel, just realign it
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You can help this project by donating to SVM
directly or to the Cytometry for Life program.
See page for details www.cytometryforlife.org
Magongo