Fig. 1: Overview of the present study.

a Comparison of existing malaria diagnostic techniques to RMOD (b), and working principle of RMOD (c–e). a Overview of the study population in Madang, Papua New Guinea (base map was created with paintmaps.com). A total of 956 suspected malaria cases were enrolled of whom 355 were found positive by RDT. Samples from 32 malaria naïve and long-term malaria-free patients were also included. b Comparison of existing diagnostic techniques with RMOD in terms of their target, approximate testing time^{26,39,40,41,42}, level of training^{39,40,41,42,70}, limit of detection^{26,71,72,73,74}, and cost per sample^{39,40,41,42,70}. * LOD of PCR depends on the volume of blood subjected to the reaction and can be much lower; ** LOD determined using dilution series of Plasmodium falciparum cultures. c Hemozoin crystals formed by Plasmodium falciparum, as imaged by scanning electron microscopy. The scanning electron microscopy image was produced by the authors based on the methodology described in Orban et al.²⁶ with slight modifications. In peripheral blood, hemozoin can be present inside infected red blood cells or phagocytosed in leukocytes. d RMOD principle. Polarization of the incoming laser beam is tilted due to the linear dichroism of hemozoin crystals. The rotating magnet drives a synchronous rotation of the crystals in lysed blood, which leads to a periodic tilting of the polarization resulting in a periodic modulation of the intensity of the outgoing laser beam. e The ratio of the modulated intensity and the mean intensity provides the magneto-optical (MO) signal in mV/V, which is a highly sensitive quantitative measure of hemozoin concentration and, thus, proportional to the parasite density.