Laboratory evaluation on the sensitivity and specificity of a novel and rapid detection method for malaria diagnosis based on magneto-optical technology (MOT)

Abstract

Background: This study describes the laboratory evaluation of a novel diagnostic platform for malaria. The Magneto Optical Test (MOT) is based on the bio-physical detection of haemozoin in clinical samples. Having an assay time of around one minute, it offers the potential of high throughput screening.

Methods: Blood samples of confirmed malaria patients from different regions of Africa, patients with other diseases and healthy non-endemic controls were used in the present study. The samples were analysed with two reference tests, i.e. an histidine rich protein-2 based rapid diagnostic test (RDT) and a conventional Pan-Plasmodium PCR, and the MOT as index test. Data were entered in 2 x 2 tables and analysed for sensitivity and specificity. The agreement between microscopy, RDT and PCR and the MOT assay was determined by calculating Kappa values with a 95% confidence interval.

Results: The observed sensitivity/specificity of the MOT test in comparison with clinical description, RDT or PCR ranged from 77.2 - 78.8% (sensitivity) and from 72.5 - 74.6% (specificity). In general, the agreement between MOT and the other assays is around 0.5 indicating a moderate agreement between the reference and the index test. However, when RDT and PCR are compared to each other, an almost perfect agreement can be observed (k = 0.97) with a sensitivity and specificity of >95%.

Conclusions: Although MOT sensitivity and specificity are currently not yet at a competing level compared to other diagnostic test, such as PCR and RDTs, it has a potential to rapidly screen patients for malaria in endemic as well as non-endemic countries.

Figure 1

(a) Schematic diagram of the diagnostic device, a sample cell containing a lysed blood sample is placed within the poles of a magnet supplying a magnetic field up to 0.6 Tesla. A polarised laser beam passes through the sample and the transmitted intensity is recorded using a photodetector. The intensity is recorded against time with and without a magnetic field. If haemozoin crystals are present, the transmitted intensity is magnetic field dependent. (b) When no magnetic field is applied, crystals are randomly orientated and a base line intensity is recorded (c) In a magnetic field, the crystals become aligned along the direction of applied field, inducing as an increase in recorded intensity [9].

Figure 2

Overview of the MOT diagnostic device, showing the main components including the optical head, magnet, sample cell inlay and computer controlled unit.

Figure 3

Photographs of the measurement platform (a) and measurement procedure (b-d). (b) The operator loads an empty sample cell within the device's loading mechanism, (c) a lysed blood sample (150 μl) is pipetted into the sample cell, (d) the sample cell is placed within the magnet using the sample loading mechanism. Once the loading procedure is complete an automated measurement routine can be initiated via the dedicated control software. Typical data output is shown in (e), recorded from a 32,500 parasites/μl sample and clearly showing an intensity change; regions of maximum signal coincide with an applied magnetic field while regions of minimum signal are recorded with no applied field.