New Haven, Conn. — Almost half of the world's population is at risk of malaria infection, with children and pregnant women at the highest risk of getting sick and dying from the disease. Current methods to detect this potentially deadly infection rely on obtaining an invasive blood sample, and each test has significant limitations that restrict their utility.
In new research published in Nature Communications , Yale School of Public Health epidemiologist Sunil Parikh, MD, MPH, and colleagues from Cameroon and the University of Arkansas for Medical Sciences present a new noninvasive test that could dramatically alter the global malaria testing landscape by providing reliable, safe, and sensitive testing to low- and middle-income countries that have been plagued by the deadly mosquito-borne disease.
Best of all, the new test can detect malaria without taking a single drop of blood.
The test is performed using a device called a Cytophone that applies targeted lasers and ultrasound to detect malaria-infected cells circulating in the bloodstream, said Jillian N. Armstrong, a former Ph.D. student in Parikh's lab and one of the study's lead authors. About the size of a table-top printer, the Cytophone prototype can determine whether infection is present within minutes via a small noninvasive probe placed on the back of a person's hand above a targeted vein.
Shimmering crystals
The Cytophone's noninvasive detection is possible, Armstrong said, because when infected with malaria parasites, red blood cells accumulate a by-product called hemozoin, an iron crystal. These nanocrystals, when exposed to a laser, heat up and absorb more light than normal hemoglobin giving them magnetic and optical properties that the Cytophone probe can detect.
In tests with 20 adult patients diagnosed with symptomatic malaria in Cameroon, the Cytophone was able to detect malaria infections with 90% sensitivity and 69% specificity, as good — and in some instances better than — the current gold standards for malaria testing that require drawing blood from patients.
"Our study showed that the Cytophone was safe and had comparable diagnostic performance to current point-of-care options when compared to highly sensitive quantitative PCR as the gold standard," Armstrong said.
Precise detection
The Cytophone was conceived by bioengineer Vladimir P. Zharov, who led a research team from the University of Arkansas that initially created the technology to detect cancerous melanoma cells in the circulatory system. Zharov's team developed this portable prototype for malaria detection and shares co-senior authorship of the current study with Parikh.
When used for malaria testing, the Cytophone successfully detected Plasmodium falciparum, the most common and deadliest species of malaria parasite, as well as less common species.
"That was a really exciting proof of concept with the first generation of this platform," said Parikh, who has been conducting malaria research in Africa for over 20 years. "I think one key part of the next phase is going to involve determining and demonstrating whether or not the device can detect and distinguish between species."
The device also detected the decline of parasite presence when patients were retested after treatment. The results confirmed the Cytophone was sensitive enough to be able to detect both high and low levels of parasites in infected blood.
Collaboration key
In discussing the study, Parikh and Armstrong praised the work of their Cameroonian collaborators, who they said were instrumental in testing the device during the COVID-19 pandemic.
"The trainees in Cameroon were amazing and enabled us to test this device with little advanced training", said Parikh.
Armstrong described Professor Yap Boum II, director of the Medicine Sans Frontiers Epicenter in Cameroon's capital city of Yaoundé and another co-senior author of the study, as the "driving force" of the project who continued testing in Cameroon when the rest of the international team was forced to stay home due to COVID-19 restrictions.
"I believe that these kinds of transdisciplinary projects between engineers and epidemiologists are crucial to reduce the global burden of disease," Armstrong said.
Through this collaboration, the team aims to continue working on a new generation of Cytophones that they anticipate will be more sensitive, more advanced, and potentially battery-powered.
Malaria continues to be a major global health problem, with a quarter of a billion cases and over 600,000 deaths estimated to occur annually. The World Health Organization has set a goal of reducing malaria cases by at least 90% globally and to eliminate malaria from 35 countries by 2030. The Cytophone technology offers an exciting new point-of-care diagnostic tool with potential to assist in this effort by improving detection of malaria cases and helping to initiate treatment.
