Transdermal Diagnosis of Malaria Using Vapor Nanobubbles

Rebelo, Maria; Grenho, Rita; Orbán, Ágnes; Hänscheid, Thomas

doi:10.3201/eid2202.151203

Cited by 13 publications

(11 citation statements)

References 5 publications

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“…Moreover, complete suppression of background from pigmented skin through time-resolved detection of PA signals from deep vessels ( Fig. 6(a)) provided an additional sensitivity improvement in parasitemia detection at the level of 0.00000001% that is approximately 10 4 -fold better than in the existing malaria detection methods [12][13][14][15][16][17]. The circulation of whole blood volume (~2 ml) in large ~1 mm mouse blood vessels takes just around 40-60 seconds (Table 1) that allows quick detection of just one iRBC among billions of nRBCs.…”

Section: Discussionmentioning

confidence: 99%

“…In spite of global efforts, around 0.6 million people die each year from malaria [10][11][12]. The sensitivity of existing detection methods is not adequate for early malaria diagnosis before disease symptoms manifest and when treatment is more effective (see [12][13][14][15][16][17] and references there). Multiple theoretical and experimental studies (e.g., see the references in [18]) revealed that malaria pigment hemozoin more strongly absorbs light in the infected red blood cells (iRBCs) compared to normal RBCs (nRBCs).…”

Section: Introductionmentioning

confidence: 99%

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Preclinical photoacoustic models: application for ultrasensitive single cell malaria diagnosis in large vein and artery

Menyaev¹,

Carey²,

Nedosekin³

et al. 2016

Biomed. Opt. Express

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photoacoustic flow cytometry (PAFC) has demonstrated potential for early diagnosis of deadly diseases through detection of rare circulating tumor cells, pathogens, and clots in nearly the entire blood volume. Before clinical application, this promising diagnostic platform requires verification and optimization using adequate preclinical models. We show here that this can be addressed by examination of large mouse blood vessels which are similar in size, depth and flow velocity to human vessels used in PAFC. Using this model, we verified the capability of PAFC for ultrasensitive, noninvasive, label-free, rapid malaria diagnosis. The time-resolved detection of delayed PA signals from deep vessels provided complete elimination of background from strongly pigmented skin. We discovered that PAFC's sensitivity is higher during examination of infected cells in arteries compared to veins at similar flow rate. Our advanced PAFC platform integrating a 1060 nm laser with tunable pulse rate and width, a wearable probe with a focused transducer, and linear and nonlinear nanobubble-amplified signal processing demonstrated detection of parasitemia at the unprecedented level of 0.00000001% within 20 seconds and the potential to further improve the sensitivity 100-fold in humans, that is approximately 10 times better than in existing malaria tests.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preclinical photoacoustic models: application for ultrasensitive single cell malaria diagnosis in large vein and artery

Menyaev¹,

Carey²,

Nedosekin³

et al. 2016

Biomed. Opt. Express

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show abstract

“…35 To date, the results of this approach have only been reported in a single patient and questions have been raised about the study method, in terms of the reliability of the diagnosis and the rationale for failing to determine parasitemia at the time of the device test rather than hours before and after. 36 …”

Section: Five-year Viewmentioning

confidence: 99%

Hemozoin detection may provide an inexpensive, sensitive, 1-minute malaria test that could revolutionize malaria screening

Grimberg

2016

Expert Review of Anti-infective Therapy

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Malaria remains widespread throughout the tropics and is a burden to the estimated 3.5 billion people who are exposed annually. The lack of a fast and accurate diagnostic method contributes to preventable malaria deaths and its continued transmission. In many areas diagnosis is made solely based on clinical presentation. Current methods for malaria diagnosis take more than 20 minutes from the time blood is drawn and are frequently inaccurate. The introduction of an accurate malaria diagnostic that can provide a result in less than 1 minute would allow for widespread screening and treatment of endemic populations, and enable regions that have gained a foothold against malaria to prevent its return. Using malaria parasites’ waste product, hemozoin, as a biomarker for the presence of malaria could be the tool needed to develop this rapid test.

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“…Attempts to develop portable, magneto-optical, point-of-care diagnostic technologies that detect haemozoin have been made but no commercial product has yet emerged. Earlier efforts to use haemozoin as a biomarker for malaria were largely unsuccessful [ 21 , 22 ]. In addition, the parasite stage targeted influenced the results, such as immature forms that were established to have little or no detectable haemozoin [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Performance of a sensitive haemozoin‐based malaria diagnostic test validated for vivax malaria diagnosis in Brazilian Amazon

Melo

Netto

Mwangi

et al. 2021

Malar J

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Background Vivax malaria diagnosis remains a challenge in malaria elimination, with current point of care rapid diagnostic tests (RDT) missing many clinically significant infections because of usually lower peripheral parasitaemia. Haemozoin-detecting assays have been suggested as an alternative to immunoassay platforms but to date have not reached successful field deployment. Haemozoin is a paramagnetic crystal by-product of haemoglobin digestion by malaria parasites and is present in the food vacuole of malaria parasite-infected erythrocytes. This study aimed to compare the diagnostic capability of a new haemozoin-detecting platform, the Gazelle™ device with optical microscopy, RDT and PCR in a vivax malaria-endemic region. Methods A comparative, double-blind study evaluating symptomatic malaria patients seeking medical care was conducted at an infectious diseases reference hospital in the western Brazilian Amazon. Optical microscopy, PCR, RDT, and Gazelle™ were used to analyse blood samples. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa values were calculated. Results Out of 300 patients, 24 test results were excluded from the final analysis due to protocol violation (6) and inconclusive and/or irretrievable results (18). Gazelle™ sensitivity was 96.1 % (91.3–98.3) and 72.1 % (65.0–78.3) when compared to optical microscopy and PCR, respectively whereas it was 83.9 % and 62.8 % for RDTs. The platform presented specificity of 100 % (97.4–100), and 99.0 % (94.8–99.9) when compared to optical microscopy, and PCR, respectively, which was the same for RDTs. Its correct classification rate was 98.2 % when compared to optical microscopy and 82.3 % for PCR; the test’s accuracy when compared to optical microscopy was 98.1 % (96.4–99.7), when compared to RDT was 95.2 % (93.0–97.5), and when compared to PCR was 85.6 % (82.1–89.1). Kappa (95 % CI) values for Gazelle™ were 96.4 (93.2–99.5), 88.2 (82.6–93.8) and 65.3 (57.0–73.6) for optical microscopy, RDT and PCR, respectively. Conclusions The Gazelle™ device was shown to have faster, easier, good sensitivity, specificity, and accuracy when compared to microscopy and was superior to RDT, demonstrating to be an alternative for vivax malaria screening particularly in areas where malaria is concomitant with other febrile infections (including dengue fever, zika, chikungunya, Chagas, yellow fever, babesiosis).

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Transdermal Diagnosis of Malaria Using Vapor Nanobubbles

Cited by 13 publications

References 5 publications

Preclinical photoacoustic models: application for ultrasensitive single cell malaria diagnosis in large vein and artery

Preclinical photoacoustic models: application for ultrasensitive single cell malaria diagnosis in large vein and artery

Hemozoin detection may provide an inexpensive, sensitive, 1-minute malaria test that could revolutionize malaria screening

Performance of a sensitive haemozoin‐based malaria diagnostic test validated for vivax malaria diagnosis in Brazilian Amazon

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