Pass the paper

New study reports a 98-percent sensitivity rate for an origami-style field test for malaria

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Malaria affects millions worldwide, with the World Health Organization estimating that there were roughly 219 million cases of malaria in 2017 globally, with 435,000 deaths. At present, tests for diagnosing malaria often utilize polymerase chain reaction (PCR), a process that takes a few hours and can only be performed under laboratory conditions, or light microscopy, which cannot diagnose asymptomatic patients. Given the fact that some individuals infected with malaria often don't present with any symptoms, convenient field tests would be a significant help in stopping the spread of the disease.
Such a test could soon be available, thanks to a team led by scientists from the University of Glasgow in Scotland, in collaboration with Shanghai Jiao Tong University in China and members of the Ministry of Health in Uganda. Their work was published in the Proceedings of the National Academy of Sciences (PNAS) in a paper titled “Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities.”
“These are challenging environments for any test of this type, with no access to the kinds of refrigeration, special equipment and training that more traditional diagnostic procedures require, so it’s very encouraging that the diagnostic techniques we’ve developed have proven to be so sensitive and reliable,” said Dr. Julien Reboud of the University of Glasgow’s School of Engineering, part of the team that developed this new approach. “With malaria infections on the increase in 13 affected countries according to a World Health Organization report released last year, it’s vital that new forms of diagnosis reach the people who need them, and we’re committed to developing our approach to paper-based LAMP diagnostics further after this encouraging study.”
The paper-based microfluidics approach in question uses far simpler tools for diagnosis—according to a University of Glasgow press release, it relies on paper folded like origami, and is prepared with just a printer and a hot plate. Rather than PCR, this test utilizes a detection process known as loop-mediated isothermal amplification (LAMP). Using a commercially available printer, paper is coated with patterns of water-resistant wax, which is consequently melted on a hotplate to bond the wax to the paper. To test for malaria, a patient pricks their finger for a blood sample, which is then placed in a channel in the wax. When the paper is folded, it directs the sample into a channel and then three small chambers, which the LAMP machine uses to test for Plasmodium falciparum, the parasite that causes malaria. The test is simple enough to conduct onsite, and takes less than 50 minutes.
For this study, the research team worked with the Ministry of Health in Uganda to test 67 children from two primary schools in Uganda. They found the test to be highly accurate, and confirmed its results with PCR testing at the University of Glasgow.
“The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study," the authors reported. "Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay.”
Prof. Jonathan Cooper of the University of Glasgow’s School of Engineering, lead author for the paper, said, “It’s a very encouraging result which suggests that our paper-based LAMP diagnostics could help deliver better, faster, more effective testing for malaria infections in areas which are currently underserved by available diagnostic techniques."
This research builds on previous work investigating these origami-style, paper-based diagnostics. In early 2018, University of Glasgow researchers—including Cooper and Dr. Zhugen Yang, another author on the 2019 PNAS paper—worked with members of the Indian Veterinary Research Institute and the Animal & Plant Health Agency in the U.K. to develop tests for identifying a trio of reproductive infections in cattle, specifically Brucella, Leptospira and bovine herpes virus-1 infections. Their work was published in the paper “Rapid Veterinary Diagnosis of Bovine Reproductive Infectious Diseases from Semen using Paper-Origami DNA Microfluidics,” which appeared in ACS Sensors.

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