Worms, Magnets and Diagnostics: Exploring new methods to diagnose egg-patent schistosomiasis

News article 2 May 2017
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Photo from Left to right: Prof. Russell Stothard, Dr. Renata Candido and Prof. Tim St Pierre

The RCDD seminars aim to provide the group with new ideas and advances in diagnostics as control of many diseases requires better methods of parasite detection and treatment. the former is especially true when interventions haven driven down the intensity of infection to low levels. In these cases, the sensitivity of available diagnostics used to identify infected patients is no longer sensitive enough and new methods are sought to bolster. In the case of schistosomiasis the most common diagnostic methods are urine filtration for Schistosoma haematobium infections or Kato-Katz faecal slides for S. mansoni and S. japonicum infections. In comparison to more advanced, molecular methods, the traditional microscopy-based methods have been shown to be significantly less sensitive, however unlike PCR or qPCR they are often more pragmatic in resource poor settings.  Currently, there is a lack of studies describing the use of molecular methods in low endemic settings.

To bridge this gap in diagnostics, Professor Carlos Graeff-Teixeira, from the Pontifical Catholic University of Rio Grande do Sul in Brazil, developed the Helmintex method to screen for S. mansoni eggs. This method utilises 30g of faeces and is 100% sensitive down to 1.3 eggs per gram of faeces whereas a single Kato-Katz is only able to detect 24 eggs per gram of faeces. When developing this method the original intention was to use paramagnetic beads coupled with specific ligands to attach to and then extract the Schistosoma spp. eggs. This method used the same technology previously used to purify and extract DNA, proteins and other targets including whole cells. As part of the experiment a control was set up in which magnetic beads were added without any ligands attached to their surface. The results of this experiment showed that not only did it successfully work with the ligand bound beads but that the beads without ligands performed better in adhering to and then isolating the S. mansoni eggs; leading to the novel insight of para-magnetism.

This un-expected but exciting result spurred further investigations which found that embedded within the pores, in the shells of S. mansoni and S. japonicum eggs, were inclusions of iron phosphate, which had previously not been described. These developments also resulted in Carlos’ former PhD student, now Dr. Renata Candido, continuing the work at the University of Queensland with Professor Malcolm Jones, and in the School of Physics at the University of Western Australia, in Perth in collaboration with Professor Tim St Pierre. It was in the laboratories at Perth that a further twist was produced in this wormy story, despite only working with magnetic beads the forces involved that cause the beads to adhere to the helminth eggs are not in themselves magnetic but instead are mostly likely due to electrostatic forces.

The latest development of this new technology has resulted in the patent of a new device that uses a high field gradient magnetic probe composed of a special metal alloy. The shape and properties of the metal alloy allows for the magnetic field to be concentrated at the tip, making the tip an attractor of eggs in the presence of magnetic particles. This has the advantage of concentrating the capture of eggs at one point increasing the sensitivity of the method. The use of this special metal means that when the magnetic field is removed there remains no residual magnetization which may cause any eggs to remain attached to the probe when it is washed for microscopical analysis.

This new advance in schistosome diagnostics provides a fascinating potential solution to bridge the gap between current diagnostic tools and the need to identify low prevalence infections in near-elimination settings and newly emerging endemic zones. It is also a clear example for the value of pursuing unusual results and collaboration between different scientific fields. Since the magnetic probe is reusable and very low cost of consumables associated with this protocol, this method could be sufficiently low-cost and used at scale to augment, perhaps even replace, existing approaches.