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, inPlasmodium 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.

Maria Rebelo, Rita Grenho, Agnes Orban, and Thomas Hänscheid

Author affiliations: Instituto de Medicina Molecular, Lisbon, Portugal (M. Rebelo, R. Grenho, T. Hänscheid); Budapest University of Technology and Economics, Budapest, Hungary (A. Orban); MTA-BME Lendulet Magneto-optical Spectroscopy Research Group, Budapest (A. Orban)

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. DOI PubMed
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. DOI PubMed
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. DOI PubMed
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. DOI PubMed
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. DOI PubMed

Suggested citation for this article: Rebelo M, Grenho R, Orban A, Hänscheid T. Transdermal diagnosis of malaria using vapor nanobubbles [letter]. Emerg Infect Dis. 2016 Feb [date cited]. http://dx.doi.org/10.3201/eid2202.151203

DOI: 10.3201/eid2202.151203

Medline reports the first author should be "Orbán A" not "Orbán Á" in reference 3 "Orbán, Butykai, Molnár, Pröhle, Fülöp, Zelles, et al., 2014".