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.
Journal Article > ResearchFull Text
Nat Commun. 2024 May 9; Volume 15 (Issue 1); 3927.; DOI:10.1038/s41467-024-48077-8
Kho S, Seung KJ, Huerga H, Bastard M, Khan PY, et al.
Nat Commun. 2024 May 9; Volume 15 (Issue 1); 3927.; DOI:10.1038/s41467-024-48077-8
Sputum culture reversion after conversion is an indicator of tuberculosis (TB) treatment failure. We analyze data from the endTB multi-country prospective observational cohort (NCT03259269) to estimate the frequency (primary endpoint) among individuals receiving a longer (18-to-20 month) regimen for multidrug- or rifampicin-resistant (MDR/RR) TB who experienced culture conversion. We also conduct Cox proportional hazard regression analyses to identify factors associated with reversion, including comorbidities, previous treatment, cavitary disease at conversion, low body mass index (BMI) at conversion, time to conversion, and number of likely-effective drugs. Of 1,286 patients, 54 (4.2%) experienced reversion, a median of 173 days (97-306) after conversion. Cavitary disease, BMI < 18.5, hepatitis C, prior treatment with second-line drugs, and longer time to initial culture conversion were positively associated with reversion. Reversion was uncommon. Those with cavitary disease, low BMI, hepatitis C, prior treatment with second-line drugs, and in whom culture conversion is delayed may benefit from close monitoring following conversion.
Journal Article > ResearchFull Text
Nat Commun. 2021 February 19; Volume 12 (Issue 1); DOI:10.1038/s41467-021-21187-3
Pascucci M, Royer G, Adamek J, Al Asmar M, Aristizabal D, et al.
Nat Commun. 2021 February 19; Volume 12 (Issue 1); DOI:10.1038/s41467-021-21187-3
Antimicrobial resistance is a major global health threat and its development is promoted by antibiotic misuse. While disk diffusion antibiotic susceptibility testing (AST, also called antibiogram) is broadly used to test for antibiotic resistance in bacterial infections, it faces strong criticism because of inter-operator variability and the complexity of interpretative reading. Automatic reading systems address these issues, but are not always adapted or available to resource-limited settings. We present an artificial intelligence (AI)-based, offline smartphone application for antibiogram analysis. The application captures images with the phone's camera, and the user is guided throughout the analysis on the same device by a user-friendly graphical interface. An embedded expert system validates the coherence of the antibiogram data and provides interpreted results. The fully automatic measurement procedure of our application's reading system achieves an overall agreement of 90% on susceptibility categorization against a hospital-standard automatic system and 98% against manual measurement (gold standard), with reduced inter-operator variability. The application's performance showed that the automatic reading of antibiotic resistance testing is entirely feasible on a smartphone. Moreover our application is suited for resource-limited settings, and therefore has the potential to significantly increase patients' access to AST worldwide.
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Nat Commun. 2020 July 27; Volume 11; DOI:10.1038/s41467-020-17446-4
Cross RW, Bornholdt ZA, Prasad AN, Geisbert JB, Borisevich V, et al.
Nat Commun. 2020 July 27; Volume 11; DOI:10.1038/s41467-020-17446-4
A replication-competent vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.
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Nat Commun. 2024 October 25; Volume 15 (Issue 1); 9228.; DOI:10.1038/s41467-024-53243-z
Yadem AC, Armstrong JN, Sarimollaoglu M, Kiki Massa C, Ndifo JM, et al.
Nat Commun. 2024 October 25; Volume 15 (Issue 1); 9228.; DOI:10.1038/s41467-024-53243-z