Noninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon
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.
Authors
- Hortense Kamga Gonsu
- Yulian A. Menyaev (ORCID: https://orcid.org/0000-0001-5861-3641)
- Aayire C. Yadem (ORCID: https://orcid.org/0000-0002-4923-7792)
- Yushun Zeng (ORCID: https://orcid.org/0000-0001-5995-4085)
- Kacey Richards (ORCID: https://orcid.org/0000-0002-5624-9791)
- Yap Boum (ORCID: https://orcid.org/0000-0002-6823-8539)
- Vladimir P. Zharov (ORCID: https://orcid.org/0000-0003-4773-0548)
- Alexandru S. Biris
- Mustafa Sarimollaoglu (ORCID: https://orcid.org/0000-0003-0246-9702)
- Jillian N. Armstrong (ORCID: https://orcid.org/0000-0002-4593-7804)
- Martina Wade (ORCID: https://orcid.org/0000-0003-2898-1296)
- C. Massa
- Sunil Parikh (ORCID: https://orcid.org/0000-0001-9411-5180)
- Yves Le Grand Napa Tchuedji (ORCID: https://orcid.org/0000-0002-2644-8538)
- Rodrigue Ntonè
- Lucrèce Eteki
- Ekaterina I. Galanzha (ORCID: https://orcid.org/0000-0002-1734-3179)
- Qifa Zhou (ORCID: https://orcid.org/0000-0003-1527-3020)
- Ruimin Chen (ORCID: https://orcid.org/0000-0002-5338-359X)
- Sami Ullah (ORCID: https://orcid.org/0000-0002-9669-5737)
- James Y. Suen
- Elvis Meten
- Jean-Michel Ndifo
- Anastasie Mbe
Institutions
- University of Arkansas at Little Rock (US)
- University of Southern California (US)
- Université de Yaoundé I (CM)
- University of Arkansas Medical Center (US)
- Yale University (US)
- Yale New Haven Health System (US)
- BioVentures (United States) (US)
- University of Arkansas for Medical Sciences (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-25
- DOI
- https://doi.org/10.1038/s41467-024-53243-z
- Citations
- 5
- Primary Topic
- Photoacoustic and Ultrasonic Imaging
- Type
- article
- Field-Weighted Citation Impact
- 0.92
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Fogarty International Center