Yaleresearchersand private firm develop bloodless malaria test

Aug. 12—Cyto means "pertaining to cells" so this is literally a "cell phone," a device that can listen to cells, the researchers say.

"It's a light-absorbing crystal that absorbs light more than the surrounding blood cells," said Vladamir Zharov, chief scientific officer for CytoAstra and professor at the University of Arkansas for Medical Sciences. "When the laser heats up the hemozoin the heat causes very fast thermal expansion and that expansion ... creates an acoustic wave."

In very basic terms, the device detects the sound of malaria poop heating up as it flows through a person's blood.

Malaria is one of the largest causes of death globally. Nearly half the world's population, according to the World Health Organization, live in areas where malaria is endemic. These areas are likely to expand with climate change.

In 2021, there were an estimated 247 million cases of malaria and 619,000 deaths. Pregnant women and young children are the most vulnerable to malaria infection. Its symptoms occur in cycles, bursts of worsening fever and weakness as the parasites consume the host's red blood cells.

While malaria is no longer endemic to the United States, it was until the turn of the 20th century. Cases were detected as far north as Massachusetts and Connecticut in the 1800s and the mosquitos that transmit the disease never went extinct. Cases of domestic malaria are rare but an outbreak has been recently reported in Texas and Florida.

Malaria is often misdiagnosed, particularly in early stage pediatric infections because fever and weakness are common symptoms of many infections. Many more people are asymptomatic and serve as reservoirs for mosquitos to spread malaria to infect new hosts. Together, these factors make malaria hard to prevent, control and eliminate.

Traditional malaria testing involves taking a blood sample and looking at it under a microscope to find parasites in the blood. Antibody-based cartridges, sort of like a COVID-19 test strip, are used as rapid tests. There are also PCR tests that looks for the genetic material of malaria, but they too require skilled technicians in laboratory settings.

Both microscopy and rapid antigen tests suffer from low sensitivity, however, particularly when there are few parasites in the blood, often rendering results inconclusive. Both also require a blood sample, explained Dr. Jeffery Dvorin, professor of pediatrics at Harvard Medical School who studies malaria.

"If this new technology is as sensitive down to the single digits of parasites per microliter of blood, that's almost an order of magnitude better than our blood stick smears and certainly an order of magnitude better than our rapid diagnostic tests," Dvorin said.

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Early research in animals indicates that the cytophone device is extremely sensitive to hemozoin. Zharov told CT Insider that it was able to detect an active infection just four hours after test animals were experimentally infected with malaria.

How does it work?

The current prototype of the cytophone is about the size of a desktop computer. A patient touches their arm to a spot where the laser and ultrasound device are held.

The cytophone uses laser pulses focused such that they don't harm the skin. The lasers are tuned to a wavelength of light that is readily absorbed by the hemozoin crystals. When the light hits the crystals they heat up quickly, and expand. This generates sound waves that can be picked up by an ultrasound transducer on the skin.

The technology was originally developed to detect circulating melanoma cancer cells, which also absorb light more readily than blood cells as they over produce skin pigment.

As a result, researchers say they can detect malaria at far lower concentrations in the blood, partially because the device is capable of testing a higher volume of blood than traditional tests. The device is listening for the echoes of malaria in circulating blood rather than a single sample from a test tube or strip. The longer a person's blood is listened to, the more blood circulates past the laser, and more blood is tested.

The test also bypasses much of the evasive behavior of malaria. Some malaria parasites during infection attach themselves to the lining of blood vessels to hide from the immune system. These parasites don't circulate as readily in the blood stream and are potentially harder to detect.

But all human-infecting malaria make hemozoin as part of their metabolism. And hemozoin travels in the blood, regardless of whether a malaria parasite is hiding or moving through the circulatory system.

"We don't think there's ever going to be a situation where hemozoin wouldn't be present in over the life cycle of the parasite," said Dr. Sunil Parikh, a professor of infectious diseases at Yale Medical School.

Sunil partnered on the project after he met Zharov at a malaria symposium in Uganda in 2017. Sunil organized the pilot clinical studies in Cameroon with collaborators from Doctors Without Borders. Zharov constructed the first generation prototype.

The Bill and Melinda Gates Foundation awarded the researchers $500,000 to build upgraded prototypes, software and conduct extensive field testing in Burkina Faso where malaria is endemic. The money will help the researchers iron out some of the kinks in the technology, making it more accurate and tolerant of small arm movements, particularly in young patients. They also hope to refine the technology so that it can be used to screen for multiple diseases at the same time.

A study by the research team reporting field results from Cameroon is currently under review for publication.

The researchers hope that the device will be used in clinics as a screening tool to help drain the reservoir of asymptomatic cases of malaria. Catching low-grade or early infections and treating them is key to preventing malaria from spreading and killing. Identifying asymtomatic cases would certainly help.

"The sensitivity becomes extremely important as we get closer to the goal of elimination and eradication where we really want to get people with subclinical and sub-microscopic parasites," Dvorin said with excitement, adding that the prospects for the technology should be cheap, portable and user-friendly, making it useful for mass malaria screening.

"I think that as it gets sturdier and cheaper and more robust it may have a real role," he said of the device.