Project description:The frequent movement of population between countries brings an increasing number of travel-related infections. This study aims to define the spectrum and dynamics of imported infections observed from international travel in the Chinese mainland. Sick travellers were screened by inbound sentinel surveillance and post-travel clinic visits from 2014 to 18. The infections were classified as respiratory, gastrointestinal, vector-borne, blood/sexually transmitted and mucocutaneous. The analysed variables included the place of origin of the travellers (Chinese or foreign) and the time when travel-related infection was present (at the time of return, during travel and post-travel visits to the clinic). In total, 58 677 cases were identified amongst 1 409 265 253 travellers, with an incidence of 41.64/million, comprising during-travel incidence of 27.44/million and a post-travel incidence of 14.20/million. Respiratory infections constituted the highest proportion of illnesses during travel (81.19%, 31 393 of 38 667), which mainly came from Asian countries and tourists; with influenza virus and rhinovirus infections being mainly diagnosed. Vector-borne diseases constituted the highest proportion of post-travel illnesses (98.14%, 19 638 of 20 010), which were mainly diagnosed from African countries and labourers; with malaria and dengue fever being mainly diagnosed. The differential infection spectrum varied in terms of the traveller's demography, travel destination and travel purpose. As such, a higher proportion of foreign travellers had blood/sexually transmitted diseases (89.85%, 2832 of 3152), while Chinese citizens had a higher prevalence of vector-borne diseases (85.98%, 19 247 of 22 387) and gastrointestinal diseases (79.36%, 1115 of 1405). The highest incidence rate was observed amongst travellers arriving from Africa, while the lowest was observed amongst travellers arriving from Europe. The findings might help in preparing recommendations for travellers and also aid in primary care or other clinics that prepare travellers before trips abroad. The findings will also help to identify locations and the associated types of infections that might require attention.

Project description:Abstract Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. Our group has showed that the virus is safe and effective in preclinical models of pHGG and DIPG. Moreover, we showed that the virus is able to trigger an antitumor immune response. These results allowed us to propel a phase I clinical trial for newly diagnosed DIPGs (NCT03178032) where the patients received an intratumoral injection of DNX-2401 (N=12). Tumor biopsy is performed through the cerebellar peduncle, followed by virus injection using a cannula that prevents the reflux. The trial is uncontrolled, unicentric with a 3 + 3 design. The objective of this trial is to determine the safety, tolerability, and toxicity of DNX-2401 in subjects with DIPG. Secondary endpoints are overall survival at 12 months (OS12), percentage of responses and induced immune response against tumor. To date 9 patients have been treated within the trial. Three patients were treated with the D1=1x1010vp and because the lack of toxicity we escalated to the D2= 5x1010vp. The procedure was well tolerated and safe. Patients were home 3–4 days after the injection. All the patients displayed a reduced tumor volume after combined treatment. We performed molecular studies in 8 out of the 9 patients (RNAseq and a thermofisher pediatric panel). Subsequently we evaluated the immune cell composition in the tumor using multiplexed quantitative immunofluorescence on the biopsies pre-virus injection. T cells were hardly noticeable in these tumors while macrophages were abundant. Using a multiplexed TCR-sequencing mRNA-based assay to analyze 18 available paired pre- and post-treatment samples from the trial, we detected increased clonal T cell diversity following treatment with virus. In addition, we are assessing the existence of pre and post treatment neutralizing antibodies and its relationship with survival. Finally, we have performed functional studies using 2 cell lines isolated from patients included in this trials and confronting them with T-cells isolated from peripheral blood of the same patients before and after the treatment with the virus. Information acquired within this clinical study would aid to understand the response of DIPGs to viral therapies and therefore to better tailor this strategy to improve the survival of pediatric brain tumors.

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Ena-DATASET-VUMC-CCA-18-03-2014-10:56:17:163-599 - samples

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