Awarded Amount$3,733,973DiseaseNTD (Schistosomiasis)InterventionDiagnosticDevelopment StageProduct DevelopmentCollaboration PartnersInstitute of Tropical Medicine (NEKKEN) Nagasaki University , Leiden University Medical Center , Merck KGaA , Foundation for Innovative New Diagnostics (FIND)
Introduction and Background of the Project
Schistosomiasis (SCH) is a major neglected tropical disease impacting the health of the lowest income populations. More than 220 million people are affected by this disease, with ~90% of the burden found in sub-Saharan Africa. Current WHO guidelines for the diagnosis of SCH recommend examination of stool and/or urine samples by microscopy, for the presence of schistosome eggs. Whilst these tests are useful in settings with moderate to high intensity infections, they become futile in settings where prevalence and intensity are low, due to their poor sensitivity. To account for this, sampling is repeated on multiple days and several slides are examined by trained microscopists, rendering the methods time-consuming and challenging to deploy. To address this, the Foundation for Innovative New Diagnostics of Geneva, Switzerland (FIND), together with Leiden University Medical Center of Leiden, Netherlands (LUMC), Merck KGaA of Darmstadt, Germany and Nagasaki University Institute of Tropical Medicine of Nagasaki, Japan (NUITIM) are developing an easy-to-use, accurate and affordable SCH rapid diagnostic test (RDT) with a sensitivity comparable to repeated microscopy that detects circulating anodic antigen (CAA), an antigen that is secreted continuously by living schistosomes. The results of the test will be obtained within 20 minutes. The RDT is being developed and optimized by Mologic Ltd under a sub-contract to FIND, including incorporation of engineered antibodies, novel detection nanoparticles and materials to enable detection of CAA in finger-stick whole-blood.
The goal of this project is to develop and carry out clinical validation of an RDT that is simple to use, instrument free and affordable, to support SCH control programmes in monitoring the impact of treatment as well as for re-assessment mapping, that is effective on all schistosome species that are of public health importance.
The partners in this project will (a) conduct field evaluations on semi-quantitative prototype SCH RDT, (b) optimize the RDT, design-lock and transfer to manufacturing, (c) validate the performance of the RDT in the detection of the major schistosome species, and determine its suitability as a replacement of current microscopy-based diagnostic tests, and (d) develop an access strategy for the SCH RDT.
How can your partnership (project) address global health challenges?
The WHO 2021-2030 roadmap calls for the elimination of SCH as a public health problem by 2030. In order to reach this target, the report highlights several critical actions to be undertaken, notably i) the implementation of effective interventions, including expanding mass drug administration campaigns to all populations in need and ensuring access to necessary drugs, ii) implementation of targeted vector control, and iii) continued micro-mapping. To achieve i) and iii), the report explicitly highlights the importance of developing necessary diagnostic tests, including standardized point-of-care diagnostics. The availability of the SCH CAA RDT would represent part of the solution, as well as provide leverage to expanding treatment to all at-risk populations. “Without diagnostics, medicine is blind” – Alain Mérieux. It is therefore essential that these are packaged together. In addition, the SCH community has a unique opportunity to make optimal use of the Merck KGaA praziquantel donation programme, where drugs can be re-directed to the areas of need through micro-mapping. Current diagnostic methods are not fit for purpose and will not get us to where we need to go. Targeting treatment to the areas of need and thereby “freeing up” stocks of available drugs to extend to all the at-risk populations would have the greatest impact in reducing or even stopping disease transmission.
The SCH CAA RDT could potentially be a powerful tool to enable policy change to revise monitoring & evaluation and treatment guidelines in SCH endemic countries.
What sort of innovation are you bringing in your project?
To date there are no other commercially available RDTs that can detect all SCH species of public health importance from a single finger-prick sample. The novel assay uses a set of unique and specific, high affinity monoclonal antibodies that results in superior diagnostic accuracy, without the need for sample preparation or a reader for detection.
Role and Responsibility of Each Partner
NUITM will oversee the field evaluations and clinical validation studies in two SCH endemic countries. Together with FIND, they will develop the study protocol, conduct training at the sites, and ensure that data are collected according to Good Clinical Practice.
LUMC will validate the performance of the RDT by testing samples using a highly sensitive lab-based assay, that requires sample preparation and a reader for detection. In addition, they will create CAA reference standards which are critical for quality assurance in manufacturing, as well as continue to contribute their expert knowledge on CAA and more broadly on SCH diagnostics, as the project progresses.
Merck KGaA will, together with FIND, develop the access strategy of the RDT as well as provide specific scientific input in the steps leading to a designed-locked product.
FIND will be the overall coordinator of the project, responsible for establishing project goals and project management, monitoring, manage sub-contractors, including Mologic Ltd, and reporting on progress. FIND will provide technical oversight and oversee logistics of the field evaluation and clinical validation studies, as well as coordinate the development of the access strategy.
A schistosomiasis rapid diagnostic test to support control programmes in monitoring treatment impact and reassessment mapping