Abstract

200 million patients suffer from malaria, a parasitic disease caused by protozoans of the genus Plasmodium. Reliable diagnosis is crucial since it allows the early detection of the disease. The development of rapid, sensitive and low-cost diagnosis tools is an important research area. Different studies focused on the detection of hemozoin, a major by-product of hemoglobin detoxification by the parasite. Hemozoin and its synthetic analog, β-hematin, form paramagnetic crystals. A new detection method of malaria takes advantage of the paramagnetism of hemozoin through the effect that such magnetic crystals have on Nuclear Magnetic Resonance (NMR) relaxation of water protons. Indeed, magnetic microparticles cause a shortening of the relaxation times. In this work, the magnetic properties of two types of β-hematin are assessed at different temperatures and magnetic fields. The pure paramagnetism of β-hematin is confirmed. The NMR relaxation of β–hematin suspensions is also studied at different magnetic fields and for different echo-times. Our results help to identify the best conditions for β–hematin detection by NMR: T2 must be selected, at large magnetic fields and for long echo-times. However, the effect of β-hematin on relaxation does not seem large enough to achieve accurate detection of malaria without any preliminary sample preparation, as microcentrifugation.

Highlights

  • In 2015, 200 million patients were suffering from the tropical disease malaria, and half a million died from the infection the same year[1]

  • Magnetic nano- and micro-particles cause a shortening of the relaxation times T1 and T2 of water protons, a phenomenon which is at the origin of the use of iron oxide particles as Magnetic Resonance Imaging (MRI) contrast agents

  • Their micromagnetic resonance relaxometry system uses the transverse relaxation of Red Blood Cells (RBC) pellets – obtained after microcentrifugation of a patient’s blood sample – to detect parasitemia levels of less than 10 parasites per μl, which is comparable to the detection limit of light microscopy, the gold standard

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Summary

Introduction

In 2015, 200 million patients were suffering from the tropical disease malaria, and half a million died from the infection the same year[1]. A few years later, Peng et al.[18] and Kong et al.[20] reported a new technique for the rapid and sensitive detection of Plasmodium infected RBC using the measurement of T2 Their micromagnetic resonance relaxometry system uses the transverse relaxation of RBC pellets – obtained after microcentrifugation of a patient’s blood sample – to detect parasitemia levels of less than 10 parasites per μl, which is comparable to the detection limit of light microscopy, the gold standard. The marked discording conclusions of the two studies led to a reaction of Karl et al.[21] who questioned the sensitivity reported by Peng et al. In this work, the magnetic properties of two types of β-hematin will be assessed, to discriminate between paramagnetic and superparamagnetic behaviours, and the NMR relaxation of β-hematin-containing suspensions will be studied at different magnetic fields, in order to determine the best experimental conditions for the hemozoin and malaria detection by NMR

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