A novel testing platform under development by researchers on the Yale School of Public Health (YSPH) and CytoAstra, LLC could provide a recent noninvasive test for malaria that does not require a blood sample.

The platform technology, often known as cytophone, detects malaria infection in blood cells using lasers and ultrasound. Researchers developing the platform consider it could provide more sensitive and reliable testing results in comparison with the more traditional blood tests for malaria, which require a blood sample and are inclined to detect malaria only at higher parasite burdens, hindering effective detection and treatment.

The research team recently received a $500,000 grant from the Bill & Melinda Gates Foundation that can allow them to construct two improved prototypes of the testing platform and to do extensive field testing in Burkina Faso, where malaria is endemic, said Dr. Sunil Parikh, an associate professor of epidemiology (microbial diseases) at YSPH and of infectious diseases on the Yale School of Medicine. Parikh is a co-principal investigator on the project.

Malaria is an unlimited health problem globally. In 2021 (essentially the most recent 12 months for which data is offered), nearly half of the world’s population lived in an area where malaria is endemic, in accordance with the World Health Organization (WHO). There have been an estimated 247 million malaria cases that 12 months — a rise of two million compared with 2020 — and 619,000 deaths, in accordance with the WHO. Young children, pregnant women, and nonimmune travelers are essentially the most vulnerable to severe infection.

Parikh’s co-principal investigator is Vladimir Zharov, director of the Arkansas Nanomedicine Center on the University of Arkansas for Medical Sciences and co-founder of CytoAstra, an organization advancing cytophone research. CytoAstra is a sub-award recipient of the muse grant. Zharov, a pioneer in noninvasive technologies for medical applications, has previously applied cytophone technology for the noninvasive detection ofcirculating melanoma cells. Realizing the platform’s potential application for human malaria, Zharov teamed up with Parikh, whose research centers on malaria interventions in Africa, to develop a conveyable cytophone prototype that would detect malaria infection in people living in endemic settings.

For malaria, the cytophone technology uses lasers at specific wavelengths focused on superficial blood vessels. When the parasites that cause malariainfection enter red blood cells, they use the hemoglobin inside those cells to liberate amino acids.

A byproduct of this process is the discharge of hemozoin, a compound containing iron. When hit by a laser, hemozoin absorbs more of the laser’s energy than hemoglobin, meaning cells infected with malaria parasites absorb greater than noninfected cells. This absorbed energy is transformed into heat, and the warmth expansion generates acoustic waves. The cytophone technology detects these waves using a small ultrasound transducer placed on the skin. After software evaluation, peaks within the detected acoustic waves can discover malariainfection.

In a previous study published in Scientific Reports, Zharov and Parikh showed their device could discover infection in mice using a rodent species of malaria parasite and in blood using a human malaria parasite.

The Zharov team then developed a conveyable version of the device and the researchers jointly accomplished a human proof-of-concept study in malaria-infected adults in Cameroon with Professor Yap Boum, currently executive director of the Pasteur Institute of Bangui, and a long-standing collaborator of the Parikh lab. The outcomes were promising and are under review for journal publication, Parikh said.

Parikh praised the multidisciplinary collaborative effort with Zharov and their Cameroonian colleagues in advancing the technology. Working together “opened doors that we’d never have been capable of open individually,” he said.

The cytophone technology could represent a giant improvement in diagnosing, treating, and understanding malaria, said Parikh.

Malaria is currently diagnosed by two methods. In light microscopy, long the usual for diagnosis, blood is smeared on a slide, stained, and studied under a microscope. But because this requires resources and expertise, it’s being replaced in lots of areas by rapid antigen blood tests. These are designed to react to the presence of a selected antigen, or protein found on the surface of a pathogen, in a sample.

An issue with each methods is that they are not very sensitive.

You’ll be able to have a really large parasite load with each microscopy and rapid diagnostic tests before you will have a positive test.”

Dr Sunil Parikh, Associate Professor of Epidemiology and Infectious Disease,  School of Medicine, Yale University

Since the cytophone technology can potentially scan a much larger volume of blood, it ought to be much more sensitive than current tests, Parikh said. The technology also could address an emerging problem with some antigen tests, he added.

In Africa, essentially the most common antigen tests seek for an antigen on Plasmodium falciparum, the locally dominant of the five species of protozoa that cause human malaria, and essentially the most dangerous. But researchers are finding increasingly more samples of the parasite with deletions of that antigen. In some places, many of the parasites now not express that antigen, Parikh said.

Since cytophone uses hemozoin, which all species of malaria parasites produce as a part of their life cycle, as a marker, it could avoid this problem, Parikh said.

“We do not think that there is ever a situation where hemozoin would not be present over the life cycle of the parasite,” he said.

Along with diagnosis problems, a challenge plaguing malaria treatment in the long run is that the parasites grow to be proof against medications. For the reason that technology focuses on hemozoin, it could possibly be useful to researchers attempting to develop and study recent antimalarial drugs that focus on this pathway in humans, noninvasively, Parikh said. “I believe that may be a very exciting avenue for this device.”