The Present and Future of Low-Cost Diagnostics

A new class of portable, easy-to-use products is increasing access to health care around the world, yet challenges remain .

Imagine you’re in a rural health clinic in a Kenyan village. A child comes in with a fever. It could be any one of a number of life-threatening infectious diseases. There’s no refrigeration, no access to sophisticated laboratory equipment, and no highly trained personnel. How do you go about diagnosing and treating this child?

Seeing situations like these in person inspired scientists at the University of Washington to create a simple, disposable test that could quickly analyze a patient’s blood sample and differentiate between six pathogens that are likely culprits of fever in the developing world.

Paul Yager.

Paul Yager.

Dubbed the DxBox, it’s a wallet-sized Mylar card that contains dehydrated reagents that can withstand warm temperatures for months—no refrigeration or electricity necessary. The team that developed the DxBox was led by Paul Yager (Figure 1, right), a professor of bioengineering at the University of Washington, and funded by the Gates Foundation’s Grand Challenges in Global Health Initiative.

It’s one of a new class of products aimed at bringing inexpensive, portable, easy-to-use diagnostics to low-resource settings around the world. Diagnostic devices that are robust enough to withstand use in the field yet simple enough to be used by nearly anyone are increasing access to health care in the developing world. Scientists, public health professionals, biotech companies, and nonprofits are all working on promising new tests for a variety of global health problems. Some take advantage of established technologies like the home pregnancy test, while others represent new scientific advances.

The DxBox uses microfluidics, the manipulation of liquids at very small scales, to process results. Clinicians only need a drop of the patient’s blood, which travels through tiny channels in the device to the sites where dried antibodies are stored. Within minutes, the pattern of colored spots created when infected blood binds to the appropriate antibody tells the clinician the cause of the fever.

Pat Stayton.

Pat Stayton.

Yager along with his University of Washington colleague Patrick Stayton (Figure 2, right) has gone on to develop this kind of next-generation reagent system for use in other types of diagnostic tests, like paper-based lateral flow tests. Lateral flow tests, such as home pregnancy tests, are robust but tend to be limited in sensitivity.

“We developed some systems to enrich and purify targets out of samples such as blood and then capture them in such a way that they could be directly placed on existing lateral flow tests,” says Stayon. “This increased the sensitivity of malaria lateral flow tests.”

Yager says that their goal is to create diagnostics that are cheap, fully disposable, more sensitive than current tests, and able to be stored at room temperature for up to a year (Figure 3). The researchers are focusing on influenza and other respiratory viruses, as well as urinary and blood-borne pathogens like Dengue virus.

Figure 3: A prototype of one of Yager’s devices funded by the U.S. Defense Advanced Research Projects Agency. (Photo courtesy of Paul Yager.)

Figure 3: A prototype of one of Yager’s devices funded by the U.S. Defense Advanced Research Projects Agency. (Photo courtesy of Paul Yager.)

The device can be extremely simple, and the papers are manufactured in large quantities and are therefore inexpensive,” says Yager. “We take a lot of really astounding technology for granted in the United States,” he adds. “What motivates me is to try to get technologies to people who don’t have access to 21st-century medical technology and to keep the costs low enough that they can actually afford it.”

Bringing Better Diagnostics to the People

Many of the new low-cost diagnostics are known as point-of-care (POC) tests: they can be performed near the patient or treatment facility, have a rapid turnaround time, and often don’t require much infrastructure support. In resource-limited settings where infrastructure is underdeveloped and underfunded, POC diagnostics can help increase access to health care and timely treatment.

David Dowdy.

David Dowdy.

Traditional tuberculosis testing, for instance, includes X-rays, blood tests, and a trained expert to look at samples under a microscope, all of which are resource intensive. As a result, says David Dowdy (Figure 4, right), a professor of epidemiology at Johns Hopkins Bloomberg School of Public Health, millions of people worldwide have undetected and, therefore, untreated tuberculosis infections. The World Health Organization estimates that each untreated individual will spread the infection to 10–15 people every year.

Dowdy studies the implementation of new diagnostic tests and evaluates how these tests perform in the field. He and his colleagues are currently looking at one new POC test for tuberculosis called GeneXpert. It’s a molecular test that provides results to patients in about two hours.

“It’s described almost like a cappuccino machine,” says Dowdy. “You take someone’s sputum sample, shake it around by hand a couple times, and then throw it in this machine, which starts whirring and making noise. In less than two hours you know whether the patient has tuberculosis, and whether or not it is a drug-resistant strain.”

Dowdy and his colleagues are studying the implementation of GeneXpert across 19 clinics in Uganda, comparing nine that are using the test and ten that are not. “We look at things like how many tests were performed over the past year, how many of those tests were positive, and how many people tested were successfully treated and compare it to situations without this new test,” explains Dowdy. Using that data, the researchers evaluate cost effectiveness as well as construct models of the population to see the overall impact on tuberculosis incidence and mortality.

Dowdy says that evaluating how POC diagnostics actually perform in the field is crucial. “When tests are developed, everyone assumes they’re going to be running at high volume, making lots of diagnoses, etc. But a lot of times, when they get into the field, they don’t get used quite as well as people think they will be.”

Over the past decade, detection and treatment of tuberculosis have improved dramatically. However, there were still an estimated 3.5 million cases of tuberculosis that went undiagnosed and untreated in 2009. Although new diagnostic tools are being developed, adoption and implementation of these tools remains a substantial challenge in many developing countries.

A PATH to Better Health Care

Figure 5: Tala de los Santos in the PATH diagnostics lab. (Photo courtesy of PATH/Patrick McKern.)

Tala de los Santos.

For the past 40 years, the Seattle-based organization PATH has been a pioneer in staging ideas in global health and translating them into solutions. Its diagnostics division, led by Tala de los Santos (Figure 5, right: Tala de los Santos in the PATH diagnostics lab. (Photo courtesy of PATH/Patrick McKern.)), focuses on developing affordable, portable, and easy-to-use diagnostics for a number of infectious and chronic diseases.

One area of focus right now is neglected tropical diseases, a term applied to 17 bacterial and parasitic infections. De los Santos says these affect some of the poorest and most vulnerable people in the world. ”They are diseases of the poor, and they keep people poor,” she says. “They don’t necessarily kill people, but they often result in profound disfigurement, disability, and social stigma.” They’re also extremely common: one in six people globally suffers from one of these neglected tropical diseases.

One such disease, onchocerciasis, or river blindness, affects about 26 million people worldwide. It is a parasitic infection transmitted to humans by the bite of the blackfly. Onchocerciasis causes itching and skin disfiguration, and can even lead to permanent blindness. In some areas of the world, such as Africa, we are approaching elimination of onchocerciasis. The last bastions for the infection in the Americas are in Brazil and Venezuela.

Previously, the best test for onchocerciasis was an invasive, labor-intensive procedure known as a skin snip. Moving from infection control to infection elimination will require better diagnostic tools, says de los Santos.

PATH and its partners have recently developed an affordable, rapid, and practical field diagnostic test for onchocerciasis. The new POC test is based on the detection of antibodies to a parasite antigen called Ov16. The test detects exposure to the parasite that causes onchocerciasis by looking for these antibodies in a single drop of blood. It is fast, accurate, easy-to-use, and less painful for patients than the skin-snip test.

De los Santos says it is especially important to monitor areas currently free of infection for signs of recurrence as well as to detect new cases in lowprevalence areas. These efforts require continuous, community-wide testing, allowing control programs to target infections as they are detected.

“In January 2012, a group of nonprofits, governments, and pharmaceutical companies came together to declare they would work to eliminate ten of these neglected tropical diseases by 2020,” says de los Santos. “Our work at PATH is supporting this so-called London Declaration by making sure the diagnostic tools are ready. The onchocerciasis test is what we hope to be the first among a suite of diagnostic tools that we and our partners will be launching together.”

Challenges to Global Health

While low-cost POC diagnostics have the potential to revolutionize health care in the developing world, there are several hurdles to creating and implementing these new tools. De los Santos says that in diagnostics, there are three major problems that must be addressed—availability, access, and utilization: “It has to be easy to use, relatively low-cost, and robust enough to be used under some pretty harsh conditions.”

Dowdy warns that as diagnostic testing gets more sophisticated, the machinery often becomes more expensive. “It’s a challenge to develop technologies that are simple enough to use in clinics that may see a hundred different conditions a day, that are durable enough to sit around and not be used for several months, and that are cheap enough to distribute widely,” he says.

Stayton sees it as an interesting engineering problem. “The test still has to work to the same standards of accuracy and sensitivity and yet be simple enough for use by untrained workers in a low-resource setting,” he says. “We call these tests simple and easy to use, but that refers to the end-product attributes, not the engineering challenge that goes into designing these tools.”

Yager recalls one clinic in South Africa where there was a refrigerator, but power was intermittent. “Every time the power would go out, which was two or three times a month, they had to pack everything from their fridge and drive it 20 miles to a hospital where there was a refrigerator they could use,” he says. “With those kinds of infrastructure problems, you have to strip away all the unnecessary stuff and keep it as simple as possible.”

Muhammad Zaman, a professor of biomedical engineering at Boston University, cautions that there is often more hype than substance in the world of POC diagnostics. “It’s not because of a lack of effort but a lack of integration,” he says. “There’s a lot of action in development of new diagnostic tools but only a trickle of products get into the field and used.”

Zaman attributes this to several reasons. “The first and most fundamental aspect is that the people who are developing these kinds of technologies often have absolutely no idea of what is important in the field, in terms of technology as well as social infrastructure and culture,” he says.

Another issue is lack of interest from the private sector or other funding agencies who would take a promising technology to scale. Zaman says there is also lack of interest on the part of the academic community in terms of scaling technology. “That means people create technologies and may do fantastic pilot studies in controlled settings, but there is little interest in scaling it so that it’s self-sustaining. That’s why you do not have much action on the ground.”

“The problem is much more than whether the technology does or doesn’t work,” he adds. “I’m certain that we’ll solve the technology problem. But it’s a lot harder to solve the problem of cultural misunderstanding, or limited knowledge of what does work in the field, or issues of financing, or scaling up the technology. These are the main challenges.”