From Mobile Technology to Predictive Markers, Finding New Ways to Accurately Diagnose Zika

While the US Centers for Disease Control and Prevention (CDC) has reported that the United States does not have any reported cases of Zika acquired through presumed local mosquito-borne transmission so far this year, research groups across the world are working to develop new testing procedures to better identify the virus in areas where the virus is still active.

The Zika virus is transmitted by the Aedes mosquito, which also transmits dengue virus (DENV); due to the similarity in their symptoms—fever, rash and muscle paint—differentiating between the 2 viruses has proven especially difficult.

After finding current diagnosis guidelines from the CDC and the World Health Organization (WHO) to be insufficient, researchers at the National University Hospital in Singapore decided to conduct a case-control study to determine if distinguishing symptoms could provide markers to differentiate between the two viruses. At the same time, researchers from Brigham and Women’s Hospital are working to develop nanotechnology that can be used via mobile devices to better diagnose Zika cases.

In Singapore, the researchers studied clinical information collected from 121 patients who had visited the hospital in 2016 and were treated for Zika or DENV. The researchers analyzed demographics, symptomatology, examination findings, lab investigations, blood counts, and liver function tests. The researchers used laboratory tests to confirm diagnosis; 34 were confirmed to have had Zika and 87 were confirmed to have DENV.

The researchers studied the clinical information and reported that they were able to draw predictors that differentiated between the 2 infections. For the patients with Zika, they noted the prevalence of conjunctivitis, along with normal platelet and monocyte counts, and no abnormalities in the liver. By contrast, DENV patients more commonly had myalgia and headaches, along with thrombocytopenia and monocytosis, biochemical evidence of liver injury with hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels greater than 2 times the upper reference limit.

In the future, it is important for these clinical predictors to be validated through prospective studies, but in the meantime, the researchers are confident that these markers—conjunctivitis and blood count parameters—will be useful to differentiate between viruses in areas such as South America and Southeast Asia where both viruses are endemic and there are limited accessibility to health resources.

Meanwhile, the research team from Brigham and Women’s Hospital have taken a unique approach to detect intact copies of the Zika virus. Their approach included the use of nanotechnology to develop platinum nanomotors that target Zika and the microbeads that bind the virus. When both components are added to a sample containing Zika, they form a 3D complex that moves when it detects the presence of hydrogen peroxide.

Additionally, the technology is able to differentiate between Zika and other closely related viruses, including DENV, through motion. The 3D complex moves rapidly when Zika is detected, and slowly when other viruses are detected. The approach is referred to as the nanomotor-based bead-motion cellphone system (NBC). Researchers have reported that the system has successfully predicted Zika in the presence of other viruses and in small samples with viral concentrations as low as 1 particle per microliter.

"The NBC system has the potential to be used at the point of care for disease detection in both developed and developing countries," said lead author Mohamed Shehata Draz, PhD, an instructor in the BWH Division of Engineering in Medicine in a recent statement. "This is an important way to eliminate the social stress related to Zika virus infection and health problems specifically related to newborns."

The researchers are hopeful that the tool could provide at-home testing for couples who are trying to conceive in locations with high risk of infection.