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It must be among the worst sorts of limbo: You're pregnant, you're worried you may have been infected with the Zika virus, but the testing is tricky and the results slow to come, so you have to wait to know for sure whether you may indeed be putting the fetus you carry at risk for Zika-related birth defects.
A new paper in the journal Science Translational Medicine offers a potential step forward for Zika testing: a fast-acting "dipstick"-type test much like a pregnancy test that costs as little as $5 per strip and can distinguish between Zika and dengue fever — a difficult challenge because the viruses are similar.
It could be ready for broad use within a couple of years, says co-author Kimberly Hamad-Schifferli, associate professor of engineering at University of Massachusetts Boston. I spoke with her and co-author Lee Gehrke, professor in the Institute for Medical Engineering and Science at MIT. Our conversation, lightly edited:
How would you sum up what you report in this paper?
KH-S: We made a paper test that diagnoses for both dengue and Zika, and we were able to detect whether or not a patient is infected with Zika. The paper test is low cost, it's under $5 a strip, and you can go from a sample to an answer within about 15 minutes.
How does this move us forward?
LG: What's important about this technology is that we're able to distinguish the four different types of dengue virus, and Zika virus. A problem that has plagued the field is that these tests can cross-react, so a dengue test can cross-react with Zika and vice versa, and this leads to false positives. That is not an ideal situation for patient care or for doing surveillance in order to be able to know what viruses are present in the environment.
So I think our technology for screening large numbers of antibodies against a panel of closely related viral proteins has allowed us to specifically identify antibodies that recognize only one of the viral antigens, and that gives us a great deal of specificity in our test, and goes a long way toward solving this problem of cross-reactivity.
How long is it likely to be before we might see this used in the field?
KH-S: We're actually pretty close, amazingly. The technology to make rapid tests already exists. What we found was the limiting factor were the antibodies to do this, so I think it may be out there within a couple years or so.
How will it be used?
KH-S: Most likely it will be used in a similar format to other rapid point-of-care tests — by end-users or clinicians in endemic areas where you just add the sample and read out the results by looking at it, by eye.
And purple spots mean Zika?
KH-S: Right, it's just like a pregnancy test — two spots, it's positive; one spot, it's negative.
And why purple?
KH-S: The purple color is due to the presence of gold nanoparticles, that's what gives them the color.
LG: There are two different ways that the detection can be used. One is for surveillance, to detect what viruses are in the environment. And the second is to have a clinical point of care diagnostic, where it's used at the bedside or in a clinic to be able to diagnose these viruses.
Is this a first in viral detection?
LG: I think it's a first in having tests that don't cross-react. That is really a key point of this, that we've been able to detect and distinguish the four types of dengue and Zika and show that we can do this without cross-reactivity. And secondly, we've been able to use mobile phone technology to be able to image the test results and quantify them so that they're read objectively rather than subjectively.
So you have an app that goes with the test?
KH-S: We don't have a stand-alone app, but we wrote some code that would do it, essentially, and it's based only on a mobile phone image. All the code is open to the public and people can use it and edit it as they see fit.
Any financial interest to disclose here?
LG: MIT has applied for patents to allow us to commercialize the test, but there are no companies or anything that need to be disclosed.
What was the scientific secret sauce that allowed you to be able to do this, to test without cross-reactivity?
KH-S: The breakthrough for this was really with the antibodies — finding antibodies that do not cross react. That was the hard part.
So how did you crack it?
LG: Part of it was just a lot of hard work. I wish I could tell you it was more elegant than that. There were two parts to it: one was just a lot of hard work in screening these antiodies, and by that we mean we were testing each individual antibody for its reactivity against a panel of multiple different viral proteins and looking for the ones that reacted more strongly.
The second part of it was that we used a more analytical approach where we did a technique called epitope mapping. So we were actually screening against specific regions of the protein that we knew were more or less different among all these different proteins and different viruses, looking for those that would give us the greatest advantage in telling them apart. So it was a mixture of just hard work by a number of very talented people and part of it was doing predictive analytical work with the epitope mapping.
So why does this matter?
LG: The reason I'm very excited is that it is a test that can be used with greater confidence.
The second thing I think is really important is we've approached this as a platform, in that our goal is not to stop with dengue and Zika. We're interested and looking ahead to be able to diagnose viruses that may be lurking in the environment but have not yet emerged, those viruses that are on the cusp of appearing in the environment and causing severe human disease.
So by trying to prepare these diagnostics, predict what viruses might be a problem in the future, we would like to apply this technology to being not just reactive but proactive in trying to protect human health.
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