Zika and dengue virus "pregnancy test"

28 September 2017

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Dipstick test for Zika and dengue viruses

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A dipstick test that can rapidly and accurately tell Zika infection from dengue has been developed by US researchers.

Zika virus is an emerging infection first detected in the Americas in 2015. It's a close relative of dengue, and both viruses produce confusingly similar symptoms, including fever and a rash, making the infections hard to tell apart. 

One important difference between the two agents though is that unlike dengue, which can cause severe infections during pregnancy but does not cause congenital damage to a developing baby, Zika virus preferentially targets cells in the developing nervous system. So infection early in pregnancy can lead to the condition microcephaly, and affected infants are born with damaged brains and abnormally small heads. This can lead to considerable anxiety for parents, who may even consider termination owing to the grim prognosis.

But distinguishing between dengue and Zika infections, which are both spread by the Aedes mosquitoes and therefore circulate in similar geographies, is extremely difficult. Both agents are members of the same viral family, called flaviviruses, so tests for one virus can "cross-react" against the other, often making accurate interpretation impossible. It is possible to tell the two apart using genetic techniques, but the cost and equipment needed to do so are often a barrier in the resource-poor settings in which dengue and Zika tend to circulate.

Now a team at MIT in Boston, US, have used the same technique at play in a pregnancy test to produce a US$5 highly-sensitive and accurate diagnostic that can be used on symptomatic patients to distinguish Zika from dengue cases.

Irene Bosch and her colleagues have used a viral marker released into the bloodstream early during infection and called NS1 as the basis for their test. NS1 differs subtley between dengue and Zika, so they team made pure forms of this marker from each virus in cultured cells and then injected it into lab mice, which in turn made antibodies against the injected NS1.

Next, the researchers took blood samples from the mice and were able to isolate groups of immune cells that were making antibodies targeting either exclusively Zika or dengue NS1. Grown in a dish, these cells could produce large quantities of antibody. 

The test built by the MIT team consists of an NS1-recognising antibody for each virus stuck to a piece of card. A second antibody, that also recognises the same NS1, is also added to the card, but is not stuck down and instead is linked to a bright red nanoparticle. 

To activate the test, the card is stood up in a drop of plasma from an infected patient. The plasma soaks up the card, picking up the coloured nano-particle-bearing antibodies as it goes. If NS1 is present in the plasma, these antibodies lock on to it. 

Further up the card, the plasma meets the second population of antibodies, which are the ones fixed in place. These grab the NS1 that is present and hold on to it. And because it is already covered in the red-coloured antibody that it encountered first, this makes a red blob appear in that location on the test card. This can be seen by the naked eye, but the researchers have also invented an app that uses the camera on a smartphone to more accurately discriminate the test results.

The new techinique accurately detected viruses grown in cultured cells as well as infections in real clinical cases. The sensitivity was 75-100%, and the specificity (meaning that a negative result on the test really was negative) was between 86-100%. These results are on-par with other clinical assays used in acute settings like this. 

The test is useful only during the window while a patient is actively infected with dengue or Zika virus, so other tests would be required to make retrospective diagnoses. But, as the team point out in their paper describing the work in Science Translational Medicine this week, "our rapid approach and reagents have immediate application in clinical diagnosis of acute Zika and dengue cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses." 

Indeed, the authors note that their design approach was guided by the World Health Organization’s acronym ASSURED, which describes ideal diagnostics: affordable, sensitive, specific, user-friendly, rapid, equipment-free, and delivered to those who need them.

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