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Elimination of malaria is a global health priority. Detecting an asymptomatic carrier of Plasmodium parasites to receive treatment is an important step in achieving this goal. Current available tools for detection of malaria parasites are either expensive, lacking in sensitivity for asymptomatic carriers, or low in throughput. We investigated the sensitivity of an impedimetric biosensor targeting the malaria biomarker Plasmodium lactate dehydrogenase (pLDH). Following optimization of the detection protocol, sensor performance was tested using phosphate-buffered saline (PBS), and then saliva samples spiked with pLDH at various concentrations. The presence of pLDH was determined by analyzing the sensor electrical properties before and after sample application. Through comparing percentage changes in impedance magnitude, the sensors distinguished pLDH-spiked PBS from non-spiked PBS at concentrations as low as 250 pg/mL (p = 0.0008). Percentage changes in impedance magnitude from saliva spiked with 2.5 ng/mL pLDH trended higher than those from non-spiked saliva. These results suggest that these biosensors have the potential to detect concentrations of pLDH up to two logs lower than currently available best-practice diagnostic tools. Successful optimization of this sensor platform would enable more efficient diagnosis of asymptomatic carriers, who can be targeted for treatment, contributing to the elimination of malaria.

Malaria elimination is a global public health priority. To fulfil the demands of elimination diagnostics, we have developed an interdigitated electrode sensor platform targeting the Plasmodium falciparum Histidine Rich Protein 2 (PfHRP2) protein in saliva samples. A protocol for frequency-specific PfHRP2 detection in phosphate buffered saline was developed, yielding a sensitivity of 2.5 pg/mL based on change in impedance magnitude of the sensor. This protocol was adapted and optimized for use in saliva with a sensitivity of 25 pg/mL based on change in resistance. Further validation demonstrated detection in saliva spiked with PfHRP2 from clinical isolates in 8 of 11 samples. With a turnaround time of ~2 hours, the label-free platform based on impedance sensors has the potential for miniaturization into a point-of-care diagnostic device for malaria elimination.

In a randomised trial comparing intermittent screening and treatment (IST) with dihydroartemisinin-piperaquine (DP) and intermittent preventive therapy against malaria in pregnancy (IPT) with sulfadoxine-pyrimethamine (SP) in Malawi, the impacts of IST-DP and IPT-SP on the development and maintenance of malaria antibody immunity were compared. Pregnant Malawian women were randomised to receive IST-DP or IPT-SP. In a nested study, paired enrolment and delivery plasma samples from 681 women were assayed for antibodies against recombinant antigens and for IgG and opsonising antibodies to antigens found on infected erythrocytes (IEs). At delivery, antibody responses did not differ between study arms. Between enrolment and delivery, antibodies to recombinant antigens decreased, whereas antibodies to IEs including opsonising antibodies remained stable. Overall, changes in antibody responses over pregnancy did not differ by treatment arm. Stratifying by gravidity, antibody to schizont extract decreased more in multigravidae receiving IST-DP than IPT-SP. There was minimal impact of treatment arm on the development and maintenance of malaria immunity. While antibodies to recombinant antigens declined between enrolment and delivery, antibodies directed against IEs tended to be more stable, suggesting longer-lasting protection.Clinical trial registration: Pa n African Clinical Trials Registry (PACTR201103000280319) 14/03/2011. URL: http://www.isrctn.com/ISRCTN69800930 .

This chapter presents nine case studies in which school students engage in challenging mathematics outside their immediate classroom environment. In each case, students are encouraged to collaborate in investigations that go beyond the standard curriculum and creatively use the ingredients of the particular context. In Italy, students visit a mathematical laboratory to understand and utilize mathematical machines. Morning assembly at an Indian school brings students from many classes together in the solution of mathematical problems. Four of the projects are from France: students analyze the configuration of a heap of sand, pursue astronomical investigations with software, obtain a flavor of research by having secondary school teams investigate interesting problems, and are presented at all levels with open-ended research problems. There are three programs from the United States, the first, an advanced geometry sequence for secondary students completing the regular syllabus early, the second, activities arising from exhibits in an art museum, and the third, using the school lawn to deepen student understanding of geometric constructions. All such activities need to be evaluated for their effectiveness, so that they move from just being initiatives of dynamic individuals to serve as the foundation for systemic improvements in the way in which students learn, understand and use mathematics. In the early part of this chapter, we briefly mention how research into such activities might be approached.