Developing inclusive digital health diagnostic for schistosomiasis: a need for guidance via target product profiles

IntroductionThe INSPIRED project aims to develop inclusive Digital Optical Diagnostic Devices (DODDs) for schistosomiasis, to support disease management by enabling rapid diagnostic results, to improve efficient data management to guide decision-making and to provide healthcare workers with critical health information to facilitate follow-up action. Due to the non-availability of Target Product Profiles (TPPs) for guiding the development of digital diagnostics for schistosomiasis, we explored existing diagnostic TPPs.MethodsUsing a curated open access database (Notion database), we studied a selection of TPPs for diagnosing infectious diseases, focusing on specifications related to digital health products for Neglected Tropical Diseases (NTDs).ResultsEighteen TPPs originating from 12 documents, covering 13 specific diseases, were selected and their characteristics were labeled and entered into the database. Further exploration of the database revealed several gaps, including a lack of stakeholder input, sustainability, and TPP availability. Other significant gaps related to digital health platform interconnectivity and data stewardship specifically in relation to digital diagnostics, including DODDs.DiscussionThese findings reflect two possible scenarios: (1) there is currently no need for digital diagnostic devices for schistosomiasis and, by extension for other NTDs; or (2) those needs are not yet covered by TPPs. Therefore, we recommend that digital health diagnostics are included in the use cases for schistosomiasis control and elimination, at least in the ideal/desirable scenario, as this will guide research and incentivize investment in digital health diagnostics for schistosomiasis

Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS

Introduction: Malignant pleural mesothelioma (MPM) is a malignancy with a very poor prognosis for which new treatment options are urgently needed. We have previously shown that dendritic cell (DC) immunotherapy provides a clinically feasible treatment option. In the current study, we set out to assess the immunological changes induced by DC immunotherapy in peripheral blood of MPM patients.Methods: Peripheral blood was collected from nine patients enrolled in a phase I dose escalation study, before and after treatment with DCs that were pulsed with an allogeneic tumor lysate preparation consisting of a mixture of five cultured mesothelioma cell lines. We used immune profiling by multiplex flow cytometry to characterize different populations of immune cells. In particular, we determined frequencies of T cell subsets that showed single and combinatorial expression of multiple markers that signify T cell activation, maturation and inhibition. Therapy-induced T cell reactivity was assessed in peptide/MHC multimer stainings using mesothelin as a prototypic target antigen with confirmed expression in the clinical tumor lysate preparation. T cell receptor (TCR) diversity was evaluated by TCRB gene PCR assays.Results: We observed an increase in the numbers of B cells, CD4 and CD8 T cells, but not NK cells at 6 weeks post-treatment. The increases in B and T lymphocytes were not accompanied by major changes in T cell reactivity toward mesothelin nor in TCRB diversity. Notably, we did observe enhanced proportions of CD4 T cells expressing HLA-DR, PD-1 (at 2 weeks after onset of treatment) and ICOS (6 weeks) and a CD8 T cell population expressing LAG3 (2 weeks).Discussion: DC immunotherapy using allogeneic tumor lysate resulted in enhanced frequencies of B cells and T cells in blood. We did not detect a skewed antigen-reactivity of peripheral CD8 T cells. Interestingly, frequencies of CD4 T cells expressing activation markers and PD-1 were increased. These findings indicate a systemic activation of the adaptive immune response and may guide future immune monitoring studies of DC therapies

Nouvel examen des langues des Antilles. Errata.

de Goeje C. H. Nouvel examen des langues des Antilles. Errata.. In: Journal de la Société des Américanistes. Tome 32 n°2, 1940. pp. 296-297