Rapid diagnosis of Ebola may be possible with new technology: Washington University School of Medicine in St. Louis

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Faster diagnosis could help limit fatal outbreaks

National Institute of Allergy and Infectious Diseases

A new tool can quickly and reliably identify the presence of the Ebola virus in blood samples, according to a study by researchers at the Washington University School of Medicine in St. Louis and colleagues from other institutions.

The technology, which uses so-called microring optical resonators, could potentially be turned into a rapid diagnostic test for the deadly Ebola virus disease, which kills up to 89 percent of infected people. Since it was discovered in 1976, the Ebola virus has caused dozens of outbreaks, mainly in Central and West Africa. Most notable was an outbreak that started in 2014 that killed more than 11,000 people in Guinea, Sierra Leone and Liberia; in the United States, the virus caused 11 cases and two deaths. Rapid and early diagnosis could help public health workers monitor the spread of the virus and implement strategies to limit outbreaks.

The study, which also involved researchers from the University of Michigan, Ann Arbor and Integrated Biotherapeutics, a biotechnology company, was published June 8 in Cell Reports Methods.

“Whenever an infection can be diagnosed earlier, it is possible to allocate health resources more efficiently and promote better outcomes for the individual and the community,” said co-first author Abraham Qavi, MD, PhD, researcher. postdoc from Washington University. “Using an Ebola infection biomarker, we have shown that we can detect Ebola infection in the crucial first few days after infection. A few days make a big difference in terms of providing people with the medical care they need and breaking the cycle of transmission. “

The Ebola virus is transmitted by contact with body fluids. It causes fever, body aches, diarrhea and bleeding, non-specific symptoms that can easily be mistaken for other viral infections or malaria. Effective vaccines and therapies for Ebola have been developed in recent years, but they are not widely available. Instead, health officials control the deadly virus by containing outbreaks. The strategy is based on rapid identification of infected people and prevention of transmission by encouraging health care workers to wear protective clothing.

Qavi had previously worked with Ryan C. Bailey, PhD, Robert A. Gregg Professor of Chemistry at the University of Michigan and senior co-author of this paper, to co-develop microring optical resonators, a kind of tunnel-mode device. whisperer used for molecular detection. The name comes from the Whispering Gallery of St. Paul’s Cathedral in London. A whisper uttered on a walkway in the dome above the nave can be clearly heard more than 100 feet away as the sound waves increase in amplitude as they bounce around the circular wall. The builders of the 18th century accidentally built a gigantic demonstration of the principle of acoustic resonance, in which sound waves increase in amplitude if they interact in exactly the right way. The same phenomenon occurs with light waves on a much smaller scale.

When Qavi joined the lab by co-senior author Gaya K. Amarasinghe, PhD – an Ebola expert and Alumni Endowed Professor of Pathology & Immunology and professor of molecular biochemistry and biophysics and molecular microbiology at the University of Washington – they decided to apply the technology to create a better diagnostic test for Ebola. Qavi collaborated with Bailey, co-first author Krista Meserve, a graduate student in Bailey’s lab, and co-author Lan Yang, PhD, Edwin H. and Florence G. Skinner Professor of Electrical and Systems Engineering at McKelvey School of Washington University Engineering, to develop a tool capable of detecting small amounts of Ebola-related molecules in blood samples using microring resonators.

“We hold light in the resonators and use resonance to enhance and enhance our signal,” said Qavi. “By monitoring where this resonant wavelength occurs, we can tell how much molecule we have.”

The key was to find the right molecule. Current diagnostic tests detect the genetic material of the virus or a glycoprotein, a sugar-coated protein, made by the virus. But they aren’t reliable until the virus has multiplied to high levels in the body, a process that can take days. Senior co-author Frederick Holtsberg, PhD, vice president of manufacturing and bioanalysis at Integrated Biotherapeutics, has developed a highly sensitive antibody capable of detecting viral soluble glycoprotein at low levels.

The researchers incorporated the antibody into their device and tested it using blood from infected animals. They found that their technique could detect glycoprotein as early as or before the most sensitive test for viral genetic material. Importantly, the technology has also allowed them to quantify the amount of viral glycoprotein in the blood. The higher the level, the worse the infected animals fare. Furthermore, the test took only 40 minutes from start to finish.

“Looking at this data, we can say: ‘If you are above these levels, your chances of survival are low; if you are below it, your chances of survival are high, ‘”Qavi said.” We have yet to validate it in infected individuals, but if it holds up, doctors could use this information to tailor treatment plans for individual patients. and assigning scarce drugs to patients who are most likely to benefit.

“We showed the fundamental scientific works,” he added. “Now it’s just a matter of miniaturizing the devices and taking them to the field.”

Qavi AJ, Meserve K, Aman MJ, Vu H, Zeitlin L, Dye J, Froude J, Leung DW, Yang L, Holtsberg FW, Bailey RC, Amarasinghe GK. Rapid detection of an Ebola biomarker with microring optical resonators. Methods of cell relations. 8 June 2022. DOI: 10.1016 / j.crmeth.2022.100234

This study was supported by the National Institutes of Health (NIH), grant numbers CA009547, P01AI120943, R01AI123926, R01AI141591, and R01AI107056.

The 1,700 physicians of Washington University’s medical school are also the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is a leader in medical research, teaching and patient care and is currently the No. 4 in research funding from the National Institutes of Health (NIH). Through its affiliations with Barnes-Jewish Children’s Hospitals and St. Louis Children, the School of Medicine is linked to BJC HealthCare.

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