Volume 22, Number 2—February 2016
Letter
Transdermal Diagnosis of Malaria Using Vapor Nanobubbles
To the Editor: Establishing reliable noninvasive methods for diagnosis of malaria has been a challenge. Lukianova-Helb et al. should be applauded for developing such a method on the basis of hemozoin (Hz) detection (1). The authors reported a proof of principle and are preparing for “large-scale studies in humans” (2). Such large endeavors should be based on firm evidence, so it is surprising that the results presented were from a single patient, remarkable for the unusual quadruple drug treatment (2). In such a scenario, to compensate for the limited data, the results should be of convincing scientific quality.
However, the case described raises several doubts that could have been addressed, such as the reliability of the diagnosis if only a thin film and a rapid test were used (co-infection excluded) and why parasitemia was not determined at the time of the device test (instead of 4 hours before and 9 hours after). What developmental stages were the parasites in at the time of the evaluation (for example, already early trophozoites containing Hz or Hz-rich gametocytes)? Why was the patient not re-evaluated to find out if repeated measurements would become appropriately negative (test-of-cure)?
The methods and results used in the study contrast with the extraordinary numbers for the limit of detection (LOD): 0.0001% in human blood and 0.00034% in a rodent model (1,2). However, the LOD is a virtual, inferred parasitemia rate based on the detection of free Hz added to uninfected blood (1). An LOD can be obtained from serially diluted cultures or samples (3). In rodent models, detection of Hz tends to be much easier (4). Moreover, in Plasmodium falciparum infections, only immature forms have been observed, with little or no detectable Hz (5).
The prospects of a noninvasive test for malaria are exciting. However, in times of cost restraints, any diagnostic test or intervention should provide sufficiently convincing results before consideration of resource-intensive large-scale trials.
References
- Lukianova-Hleb EY, Campbell KM, Constantinou PE, Braam J, Olson JS, Ware RE, Hemozoin-generated vapor nanobubbles for transdermal reagent- and needle-free detection of malaria. Proc Natl Acad Sci U S A. 2014;111:900–5. DOIPubMedGoogle Scholar
- Lukianova-Hleb E, Bezek S, Szigeti R, Khodarev A, Kelley T, Hurrell A, Transdermal diagnosis of malaria using vapor nanobubbles. Emerg Infect Dis. 2015;21:1122–7. DOIPubMedGoogle Scholar
- Orbán Á, Butykai Á, Molnár A, Pröhle Z, Fülöp G, Zelles T, Evaluation of a novel magneto-optical method for the detection of malaria parasites. PLoS ONE. 2014;9:e96981. DOIPubMedGoogle Scholar
- Rebelo M, Tempera C, Bispo C, Andrade C, Gardner R, Shapiro HM, Light depolarization measurements in malaria: A new job for an old friend. Cytometry A. 2015;87:437–45. DOIPubMedGoogle Scholar
- Rebelo M, Shapiro HM, Amaral T, Melo-Cristino J, Hänscheid T. Haemozoin detection in infected erythrocytes for Plasmodium falciparum malaria diagnosis-prospects and limitations. Acta Trop. 2012;123:58–61. DOIPubMedGoogle Scholar
Medline reports the first author should be "Orbán A" not "Orbán Á" in reference 3 "Orbán, Butykai, Molnár, Pröhle, Fülöp, Zelles, et al., 2014".
Medline reports the first author should be "Orbán A" not "Orbán Á" in reference 3 "Orbán, Butykai, Molnár, Pröhle, Fülöp, Zelles, et al., 2014".
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Table of Contents – Volume 22, Number 2—February 2016
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Please use the form below to submit correspondence to the authors or contact them at the following address:
Thomas Hänscheid, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Av Prof Egas Moniz, P-1649-028 Lisbon, Portugal
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