Dengue in Finnish international travelers, 2016–2019:a retrospective analysis of places of exposure and the factors associated with the infection

Abstract. As an emerging infectious disease dengue is putting a constantly growing number of international tourists at risk of the infection. To have a more complete picture of the phenomena among the Finnish travelers, the backgrounds of infections were retrospectively examined to find out the place of exposure, type of traveler and the trip, risk perceptions and protective measures taken. The study period was from January 2016 to May 2019 and reported dengue infections from this period were obtained from the National Infectious Disease Register, which is maintained by the Finnish Institute for Health and Welfare (THL). The questionnaire both in Finnish and Swedish was sent to the participants. The response rate in this study was 61.3 %. Data was analyzed spatially with QGIS 3.4.8 Madeira and statistically by using R 3.6.0. Descriptive statistics were used to analyze the demographic variables as well as answers given to the questionnaire. In addition, two binary logistic models were fitted to find out statistically significant factors for risk perception and the use of protective measures. Crude attack rates were calculated for different destinations using UNWTO travel data. Further on, the results were compared to existing literature related to this research. Thailand and Indonesia were identified as destinations with the most abundant number of infections imported to Finland. However, Maldives had the highest crude attack rate per 100,000 travelers. The type of travel during which the infections were acquired was mainly pre-booked holiday of 14 days with time spent mostly on the beach. Most of the travelers were not aware of the dengue risk before the travel and did not seek pre-travel advice. Those who sought pre-travel advice were 34.9 times more likely to use protective measures than those who did not. Moreover, the majority applied some protective measures but not during the right time of the day, and thus the measures were chosen incorrectly. Based on these results the knowledge about dengue, day-active/urban mosquito and the correct use of protective measures needs increasing. Further on, the risk within touristic destinations requires highlighting and the distinction between malaria and other mosquito-borne diseases could be made clearer. In addition, there is a need to increase the knowledge of dengue among healthcare workers

Clinical-grade patches as a medium for enrichment of sweat-extracellular vesicles and facilitating their metabolic analysis

Abstract Cell-secreted extracellular vesicles (EVs), carrying components such as RNA, DNA, proteins, and metabolites, serve as candidates for developing non-invasive solutions for monitoring health and disease, owing to their capacity to cross various biological barriers and to become integrated into human sweat. However, the evidence for sweat-associated EVs providing clinically relevant information to use in disease diagnostics has not been reported. Developing cost-effective, easy, and reliable methodologies to investigate EVs’ molecular load and composition in the sweat may help to validate their relevance in clinical diagnosis. We used clinical-grade dressing patches, with the aim being to accumulate, purify and characterize sweat EVs from healthy participants exposed to transient heat. The skin patch-based protocol described in this paper enables the enrichment of sweat EVs that express EV markers, such as CD63. A targeted metabolomics study of the sweat EVs identified 24 components. These are associated with amino acids, glutamate, glutathione, fatty acids, TCA, and glycolysis pathways. Furthermore, as a proof-of-concept, when comparing the metabolites’ levels in sweat EVs isolated from healthy individuals with those of participants with Type 2 diabetes following heat exposure, our findings revealed that the metabolic patterns of sweat EVs may be linked with metabolic changes. Moreover, the concentration of these metabolites may reflect correlations with blood glucose and BMI. Together our data revealed that sweat EVs can be purified using routinely used clinical patches, setting the foundations for larger-scale clinical cohort work. Furthermore, the metabolites identified in sweat EVs also offer a realistic means to identify relevant disease biomarkers. This study thus provides a proof-of-concept towards a novel methodology that will focus on the use of the sweat EVs and their metabolites as a non-invasive approach, in order to monitor wellbeing and changes in diseases

Single-cell characterization of anti–LAG-3 and anti–PD-1 combination treatment in patients with melanoma

Abstract Background: Relatlimab plus nivolumab (anti–lymphocyte-activation gene 3 plus anti–programmed death 1 [anti–LAG-3+anti–PD-1]) has been approved by the FDA as a first-line therapy for stage III/IV melanoma, but its detailed effect on the immune system is unknown. Methods: We evaluated blood samples from 40 immunotherapy-naive or prior immunotherapy–refractory patients with metastatic melanoma treated with anti–LAG-3+anti–PD-1 in a phase I trial using single-cell RNA and T cell receptor sequencing (scRNA+TCRαβ-Seq) combined with other multiomics profiling. Results: The highest LAG3 expression was noted in NK cells, Tregs, and CD8⁺ T cells, and these cell populations underwent the most significant changes during the treatment. Adaptive NK cells were enriched in responders and underwent profound transcriptomic changes during the therapy, resulting in an active phenotype. LAG3⁺ Tregs expanded, but based on the transcriptome profile, became metabolically silent during the treatment. Last, higher baseline TCR clonality was observed in responding patients, and their expanding CD8⁺ T cell clones gained a more cytotoxic and NK-like phenotype. Conclusion: Anti–LAG-3+anti–PD-1 therapy has profound effects on NK cells and Tregs in addition to CD8⁺ T cells. Trial registration: ClinicalTrials.gov (NCT01968109) Funding : Cancer Foundation Finland, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, Relander Foundation, State funding for university-level health research in Finland, a Helsinki Institute of Life Sciences Fellow grant, Academy of Finland (grant numbers 314442, 311081, 335432, and 335436), and an investigator-initiated research grant from BMS