Noninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon
Aayire C. Yadem, Jillian N. Armstrong, Mustafa Sarimollaoglu, C. Massa, Jean-Michel Ndifo, Yulian A. Menyaev, Anastasie Mbe, Kacey Richards, Martina Wade, Yushun Zeng, Ruimin Chen, Qifa Zhou, Elvis Meten, Rodrigue Ntonè, Yves Le Grand Napa Tchuedji, Sami Ullah, Ekaterina I. Galanzha, Lucrèce Eteki, Hortense Kamga Gonsu, Alexandru S. Biris, James Y. Suen, Yap Boum, Vladimir P. Zharov, Sunil Parikh
Abstract
Current malaria diagnostics are invasive, lack sensitivity, and rapid tests are plagued by deletions in target antigens. Here we introduce the Cytophone, an innovative photoacoustic flow cytometer platform with high-pulse-rate lasers and a focused ultrasound transducer array to noninvasively detect and identify malaria-infected red blood cells (iRBCs) using specific wave shapes, widths, and time delays generated from the absorbance of laser energy by hemozoin, a universal biomarker of malaria infection. In a population of Cameroonian adults with uncomplicated malaria, we assess our device for safety in a cross-sectional cohort (n = 10) and conduct a performance assessment in a longitudinal cohort (n = 20) followed for 30 ± 7 days after clearance of parasitemia. Longitudinal cytophone measurements are compared to point-of-care and molecular assays (n = 94). Cytophone is safe with 90% sensitivity, 69% specificity, and a receiver-operator-curve-area-under-the-curve (ROC-AUC) of 0.84, as compared to microscopy. ROC-AUCs of Cytophone, microscopy, and RDT compared to quantitative PCR are not statistically different from one another. The ability to noninvasively detect iRBCs in the bloodstream is a major advancement which offers the potential to rapidly identify both the large asymptomatic reservoir of infection, as well as diagnose symptomatic cases without the need for a blood sample. Improved diagnostics for malaria are desired. Here the authors present first-in-human data for a non-invasive device based on detection of hemozoin in malaria-infected red blood cells, and show that it is safe with comparable performance to current point-of-care diagnostics without the need for a blood sample.