Malaria long-term elimination depends on parasite transmission control. Plasmodium sexual stage maturation in the mosquito, including egress from the host erythrocyte, is one of the prime targets for ...transmission-blocking interventions. This work aims to identify candidate molecules potentially involved in gamete emergence from the host erythrocyte, as novel transmission blocking targets. We analyzed by quantitative mass spectrometry the proteins released/secreted by purified Plasmodium falciparum gametocytes upon induction of gametogenesis. The proteome obtained showed a good overlap (74%) with the one previously characterized in similar conditions from gametocytes of the rodent malaria parasite P. berghei. Four candidates were selected based on comparative analysis of their abundance values in released vs total gametocyte proteome. We also characterized the P. falciparum orthologue of the microgamete surface protein (MiGS), a marker of male gametocyte secretory vesicles in murine models of malaria. The findings of this study reveal that all the selected candidate proteins are expressed in both genders and localize to vesicle-like structures that respond to gametogenesis stimuli. This result, together with the fact that the selected proteins are released during gamete emergence in both Plasmodium species, makes them interesting candidates for future functional studies to investigate their potential role in the gametogenesis process.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Recent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of
malaria by providing a "niche" for the maturation of the parasite gametocytes, responsible for ...human-to-mosquito transmission. Suitable humanized
models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.
We report a novel experimental system based on the infusion of immature
gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.
We demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.
Our model represents a powerful tool to study BM function and the interplay essential for parasite transmission in
malaria and can be extended to study other infections in which the human BM plays a role.
Malaria remains the most important mosquito‐borne infectious disease worldwide, with 229 million new cases and 409.000 deaths in 2019. The infection is caused by a protozoan parasite which attacks ...red blood cells by feeding on hemoglobin and transforming it into hemozoin. Despite the WHO recommendation of prompt malaria diagnosis, the quality of microscopy‐based diagnosis is frequently inadequate while rapid diagnostic tests based on antigens are not quantitative and still affected by non‐negligible false negative/positive results. PCR‐based methods are highly performant but still not widely used in endemic areas. Here, a diagnostic tool (TMek), based on the paramagnetic properties of hemozoin nanocrystals in infected red blood cells (i‐RBCs), is reported on. Exploiting the competition between gravity and magnetic forces, i‐RBCs in a whole blood specimen are sorted and electrically detected in a microchip. The amplitude and time evolution of the electrical signal allow for the quantification of i‐RBCs (in the range 10–105 i‐RBC µL−1) and the distinction of the infection stage. A preliminary validation study on 75 patients with clinical suspect of malaria shows on‐field operability, without false negative and a few false positive results. These findings indicate the potential of TMek as a quantitative, stage‐selective, rapid test for malaria.
Malaria is caused by the Plasmodium parasite which feeds on hemoglobin and produces paramagnetic hemozoin crystals within red blood cells (RBCs). A quantitative and stage‐selective pan‐malaria diagnostic test is disclosed, based on a simple concept implemented on a microchip: the sorting and electrical detection of infected RBCs, thanks to the competition between magnetic and gravity forces.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This paper presents a custom, low-cost electronic system specifically designed for rapid and quantitative detection of the malaria parasite in a blood sample. The system exploits the paramagnetic ...properties of malaria-infected red blood cells (iRBCs) for their magnetophoretic capture on the surface of a silicon chip. A lattice of nickel magnetic micro-concentrators embedded in a silicon substrate concentrates the iRBCs above coplanar gold microelectrodes separated by 3 μm for their detection through an impedance measurement. The sensor is designed for a differential operation to remove the large contribution given by the blood sample. The electronic readout automatically balances the sensor before each experiment and reaches a resolution of 15 ppm in the impedance measurement at 1 MHz allowing a limit of detection of 40 parasite/μl with a capture time of 10 minutes. For better reliability of the results, four sensors are acquired during the same experiment. We demonstrate that the realized platform can also detect a single infected cell in real experimental conditions, measuring human blood infected by Plasmodium falciparum malaria specie.
In article 2004101, Marco Giacometti, Riccardo Bertacco and co‐workers reported on a diagnostic tool (TMek) based on paramagnetic properties of hemozoin nanocrystals in infected red blood cells ...(i‐RBCs). Exploiting the competition between gravity and magnetic forces, i‐RBCs in a whole blood specimen are sorted and electrically detected in a microchip. The findings indicate the potential of TMek as a quantitative, stage‐selective, rapid test for malaria. Cover designed by Tommaso Pravettoni and Jonathan Barsotti.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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