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Infectious disease

Diagnostic blood test distinguishes between Ebola and similar illnesses

The simple method uses Raman scattering to identify pathogens and requires no electricity or refrigeration

by Megha Satyanarayana
December 12, 2018

A diagnostic test that uses Raman light scattering from gold-based nanoparticles to distinguish between Ebola, Lassa fever, and malaria infection.
Credit: Science Translational Medicine
A diagnostic uses antibody-coated gold nanotags (red, blue, and yellow) and antibody-coated magnetic beads (black) to sandwich proteins from Ebola virus, Lassa fever virus, and the malaria parasite, allowing a user to distinguish between the pathogens through Raman spectroscopy.

During the 2014 Ebola virus outbreak in West Africa, public health workers realized quickly that one of their biggest challenges was properly diagnosing an illness that, at least clinically, mimics others endemic to the region, like Lassa fever and malaria. In regions rife with these illnesses, the molecular standard for identifying Ebola is polymerase chain reaction (PCR), says Robert Garry, a microbiologist at Tulane University Medical School who was part of a team working on Ebola diagnosis during the 2014 outbreak. PCR is a sensitive and relatively fast technique for amplifying nucleic acids from pathogens like Ebola virus, but it’s not always practical in places where electricity and refrigeration aren’t constant, and hospitals with trained lab personnel might be hours away.

With those challenges in mind, an international team of researchers in the US and West Africa report a prototype diagnostic that needs no refrigeration nor electricity, minimizes health-worker exposure to infected bodily fluids, and can, through a simple spectroscopic measurement, distinguish between Ebola, Lassa fever, and malaria, even in one person who may have more than one infection (Sci. Trans. Med. 2018 DOI: 10.1126/scitranslmed.aat09).

“There’s tremendous impact to be had by a test that can be used by a minimally trained, nonlaboratory person,” says Kristin Weidemaier, a researcher at Becton, Dickinson, and Company who colead the project.

The diagnostic works through Raman spectroscopy and can detect various infections. To distinguish between Ebola, Lassa fever, and malaria, the team created three types of gold nanoparticles with distinct tags that produce a characteristic Raman signal when excited by near infrared light. The researchers coupled each type of nanotag to antibodies against either Ebola, Lassa fever, or malaria parasite proteins. To test a blood sample, a user adds it to a tube containing both the nanotags and magnetic beads that are also coated with antibodies specific to the three pathogens. The antibodies on both particle types sandwich viral or parasitic proteins in the blood sample, and using a magnet, a user can pull the particle sandwiches to one side of the tube. To read the sample, a health worker with minimal training can use a small, battery-powered Raman spectrometer to determine if any of the pathogens are present.

The team tested the diagnostic on Rhesus macaques infected with Ebola, as well as on preserved human serum samples from the 2014 outbreak. They conducted a field trial for detecting malaria in a rural region of Senegal. In these tests, the team could diagnose Ebola with nearly 97% accuracy and malaria with near perfect accuracy.

But the diagnostic is far from ready for deployment in the field, says John Connor, a Boston University microbiologist who colead the study with Wiedemaier. The team is seeking governmental and nongovernmental organization partnerships to do further trials of the diagnostic, including during an active Ebola outbreak. But building these relationships is not easy, Connor says, and because outbreaks are unpredictable, timing human tests is a challenge.

For example, the current Ebola outbreak in a war-torn region of the Democratic Republic of the Congo has proven a challenge for teams trying to test vaccines and Ebola treatments, Garry says.

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Also, this new method has competition: There are other non-PCR diagnostics for Ebola approved by the World Health Organization for emergency use during an outbreak. Each of these methods has its advantages and disadvantages.

Finally, Garry says, there is the issue of cost. How, he asks, will resource-poor countries with great health care needs outside of outbreaks pay to deploy a new test in the field? “How does this get prioritized in the whole range of other things that are needed?”

But Garry thinks the technology behind the diagnostic is promising. It uses a single tube and a transportable reader to produce sensitive and specific readings, he says. “These are the things you need. Getting it simplified and out there, that’s a challenge.”

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