A Global Perspective on Healthcare
Conference Program Puts Spotlight on Needs of Developing World
By Bill Malone
Last year Paul Yager, PhD, Professor and Acting Chair of the Department of Bioengineering at the University of Washington, Seattle, made a trip to South Africa to attend a meeting for principal investigators of the Bill & Melinda Gates Foundation’s Grand Challenges in Global Health initiative. During his stay, Yager visited a township with an HIV infection rate of 29% and very hight rate of TB infection. While walking around this very poor area, he noticed a lot of the locals using cell phones. “So I whipped out my cell phone—from Seattle—flipped it open, and I got five bars. And then I went and took a picture with my phone, and that picture ended up back in my hotel on my laptop before I got there. So I asked a guy, ‘Does everyone have cell phones here? And he said ‘Oh, yes, everyone.’ And he took a look at my phone and said, ‘And most of ours are much nicer than yours.’”
Yager wasn’t visiting South Africa to study cell phones—he’s developing a rugged POC device for infectious diseases—but the ubiquity of cell phones there represents a solid example of how certain technologies have been able to ‘leapfrog’ older technologies and penetrate regions of the world that are remote, very poor, and experiencing severe health problems—areas referred to as low-resource settings. “You look at that situation and say, ‘If that technology can make it, how can we piggyback on that existing cell phone technology, for example, and use the strength of that in order to bring in relatively sophisticated diagnostic equipment?’ ” Yager said. He is one of three speakers at today’s afternoon symposium “Diagnostics for the Developing World,” in room 146C. Bala Manian, PhD, of RealMetrix (San Carlos, Calif.) and Hans-Georg Batz, PhD, of ArteBioConsulting (Tutzing, Germany) will also be speaking.
The symposium is one of several events at the 2008 AACC Annual Meeting that fall under the rubric of global health, a subject that has interested Ann Gronowski, PhD, Chair of the 2008 Annual Meeting Organizing Committee, since she volunteered in Eritrea in 2006. She worked with a group of volunteers called Pathologists Overseas, who conduct training and help arrange for supplies and equipment to improve pathology and diagnostic services in developing countries. “I taught the medical students in their new medical school, and it really opened my eyes about global healthcare,” Gronowski said. “We don’t think about global healthcare, or everybody else’s health, on an everyday basis. We focus on our own little world. But to think that the health of people all around the world doesn’t affect us is like putting your head in the sand.” Gronowski is an Associate Professor of Pathology and Immunology, Obstetrics and Gynecology at Washington University School of Medicine in St. Louis.
Gronowski spearheaded the effort to bring global health to the forefront of the educational program this year, starting with the opening plenary by Roy Vagelos, MD, former CEO of Merck & Co., who played a key role in providing free drugs to treat river blindness in developing countries. Then on Tuesday morning, Mark Perkins, PhD, chief scientific officer of the Foundation for Innovative New Diagnostics (FIND) will delve into the technical needs for IVDs in developing countries. Later, a full-day symposium, “Challenges in Global Infectious Diseases,” will tackle emerging global health issues and what strategies governments and NGOs are using to build up laboratories in low-resource settings.
Smaller is Better
With funding from the Bill & Melinda Gates Foundation, Yager’s lab is leading a collaboration with the Stayton lab at the University of Washington, PATH, Nanogen, and Micronics to develop a POC diagnostic platform for low-resource settings that can diagnose a wide range of diseases using parallel, nucleic acid-based assays, and immunoassays.
The instrument, with an internal working name of the DxBox, features a compact, portable, shoe box-size reader, as well as disposable “lab cards” that use microfluidic circuits to perform up to six different tests from a few drops of blood. Importantly, all of the necessary reagents and buffers will be in a form that allows the cards to be stored for up to a year at ambient temperatures, and all sample cleanup and metering takes place within the card. “A capability that could not possibly have been extended to the developing world because of limitations of power, cost, reagent delivery, reagent storage, cold chain limitations, and transportation limitations—these things are now possible,” said Yager. “We can really extend some of our most sophisticated mechanisms of diagnosing disease to the remote ends of the diagnostic world. It’s not like we have to send the developing world our lowest quality, mediocre test—we can actually send them some of the best tests. That’s pretty exciting, particularly on the nucleic acid side.” The initial panel of tests on the cards will diagnose rapid-onset fevers, such as malaria, dengue, measles, Rickettsia, and Salmonella.
The DxBox tackles many of the problems inherent to low-resource testing: lack of reliable power, harsh environments, and a dearth of trained personnel available to draw blood, perform testing, or maintain equipment. “Having been to Africa myself, you realize they have way different needs than we do,” said Gronowski. “Both their instruments and their reagents are frequently exposed to huge fluctuations in temperature, or must endure a really sandy environment, or fluctuations in power supply—just extreme conditions. Also maintenance: when things break down in Eritrea, it’s days and days for a person they have in Africa to get there. So these have to be reliable instruments, and they have to be very easy to use. Moreover, quality control is often times not well understood, so these need to be very stable instruments that are very forgiving.”
Developed by a collaboration of Paul Yager’s and Patrick Stayton’s labs at the University of Washington, along with PATH, Nanogen, and Micronics, this shoe box-sized platform, called the DxBox, employs advanced microfluidic technology to offer reliable and low-cost testing for a wide range of diseases. The system uses credit-card sized, disposable ‘lab cards’ that perform up to six tests from a small patient sample for POCT in low-resource settings.
David Kelso, PhD, Associate Professor of Biomedical Engineering at Northwestern University, will moderate this afternoon’s “Diagnostics for the Developing World” session. He also stresses the need for simplicity. “The simpler you make the device, the more complexity that is in it. It’s either chemical complexity, or computer complexity, or mechanical complexity. You have to do something to make it simple to use,” said Kelso. “So a lot of times, that requires getting into new technologies that have never been applied to diagnostics in the developing world. You really have to push the technology a lot further in these settings than you do for the developed world.” Current rapid tests used in low-resource settings include lateral flow strips or immunochromatographic strips that are generally qualitative, can be stored for long periods of time, and are relatively inexpensive. However, these strips have not lived up to expectations, mainly due to user error. “What people have found is that the performance of those tests is often not as good in developing world circumstances as they are back in the labs,” said Yager. “So one of the things we’re attempting to do is minimize the amount of user intervention required, so that user variability is no longer a factor, and environmental variability is not as much of a factor as it would be otherwise.”
A Spectrum of Needs
Kelso also emphasized another factor in low-resource diagnostics: understanding the unique needs of each country or setting. “Really understanding what the customer requirements are is the top challenge in developing low-resource diagnostics, in the very broadest sense,” said Kelso. “We think a point-of-care test, taking it right out to primary care, would be the best solution. But you go out to those primary care sites, and a lot of times there isn’t somebody there that is certified to draw blood. So then you follow the patient to when they get tested, and it’s at a district hospital, and that’s not where we envisioned the test. So we’re trying to understand the structure of how care is delivered and what resources are in what locations.”
Yager’s focus is on delivering POC tests in low-resource settings that can be used by anybody. “Clearly there is a range of circumstances in the developing world. The cities often have nicely equipped hospitals and laboratories with power and most everything else they need, but the issues you have tend to mostly be in remote areas, where you don’t have continuous power, where you may not have air conditioning, and where you probably don’t have highly-trained technicians and can’t get supplies in on a regular basis.” However, Yager noted that instruments such as the DxBox can attend to needs across the spectrum. “The particular things that people want depends on the particular end user. Some of the people in the more sophisticated hospitals want quantitative results; the people in the lowest socioeconomic levels generally are looking at the quick and qualitative answer, like ‘Is it malaria or isn’t it?’ Not ‘How much malaria?’—just ‘Which drug do I use to treat the patient as quickly as possible before they go home?’ Turnaround is a very big deal in all these locations.”
Coming Soon to a Clinic Near You?
Although the DxBox and other POC instruments being developed for low-resource settings aim mainly to overcome environmental, economic, and personnel problems much different from those in U.S. labs, Kelso and others stress that these cutting-edge technologies will likely become very useful in developed countries in the near future as our healthcare system changes and evolves. “One trend that’s obvious is these clinics that are starting to appear in Wal-Mart and all kinds of alternative sites,” said Kelso. “They are, in my mind, a lot like the walk-in clinics over in Africa. It’s not low-resource, but it’s a situation where it’s incredibly important to get the results of your diagnostic test while the patient is right there. There are lots of situations where having a rapid, point-of-care test improves the ability of the physician to treat the patient.”
Other potential uses of speedy and inexpensive low-resource methods include non-traditional healthcare settings like natural disasters, suggested Kelso, such as after a hurricane, when the usual laboratory infrastructure is wiped out. Mobile clinics or storefront clinics in impoverished areas could use them as well. Yager also put forward that hospitals might want something like his DxBox in certain circumstances. “Being able to have a rapid, nucleic acid-based test that can be done at the point-of-care is really a critical capability. And if you do that, you don’t want the instrument to be incredibly expensive, because hospitals can’t afford to put in a large number of extremely expensive instruments that duplicate capabilities in the centralized lab. So the development of these technologies for point-of-care use in the developing world enables the cost to be driven down far enough that you can bring the technology back to sites in the developed world.”
Low-resource-type diagnostics might also someday become routine in developed countries who increasingly are seeking ways to care for poor and uninsured citizens. “Eventually our healthcare system is going to evolve to take care of the 40 million poorest people, and they’re probably not going to be cared for in the same way that the richest 40 million are cared for,” noted Kelso. “So those clinics, those healthcare delivery systems are going to be different and will have functional aspects of the way South Africans or Ugandans take care of their population.”
Shifting to a Global Health Perspective
Although global healthcare doesn’t always mean low-resource healthcare, it does represent a different world view when it comes to laboratory medicine. “I would challenge people to think about more than just themselves in what they perceive as their immediate patient base,” said Gronowski. “We in healthcare have to take responsibility for the health of the world. In the long run, I believe it will affect the people in your small circle. If the health of people worldwide is good, then I don’t have to worry about Ebola virus, and bird flu, and SARS. I think we have to be knowledgeable about global health so that we can perhaps help others, but then ultimately down the road, to help ourselves as well.”