Nature Communications (Oct 2024)

Noninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon

  • Aayire C. Yadem,
  • Jillian N. Armstrong,
  • Mustafa Sarimollaoglu,
  • Civian Kiki Massa,
  • Jean-Michel Ndifo,
  • Yulian A. Menyaev,
  • Anastasie Mbe,
  • Kacey Richards,
  • Martina Wade,
  • Yushun Zeng,
  • Ruimin Chen,
  • Qifa Zhou,
  • Elvis Meten,
  • Rodrigue Ntone,
  • Yves Le Grand Napa Tchuedji,
  • Safi Ullah,
  • Ekaterina I. Galanzha,
  • Lucrèce Eteki,
  • Hortense Kamga Gonsu,
  • Alexandru Biris,
  • James Y. Suen,
  • Yap Boum,
  • Vladimir P. Zharov,
  • Sunil Parikh

DOI
https://doi.org/10.1038/s41467-024-53243-z
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 15

Abstract

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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.