Davide Marangoni

Background: The potential of schistosomiasis to spread across borders, coupled with the considerable delay by which infected travellers and migrants are diagnosed in Europe, calls for better surveillance of the distribution of this disease. This study explored the geographical origin and genetic profiles of Schistosoma infections imported into Europe and diagnosed in a network of 11 European centres specialized in traveller and migrant health. Methods: Genetic profiles were obtained from DNA extracted from concentrated Schistosoma eggs or Schistosoma -positive samples (faeces, urine, biopsy) collected during routine diagnostic procedures. The species-specific cytochrome oxidase sub-unit 1 ( cox1 ) diagnostic region and the standard complete internal transcribed spacer (ITS) 1 + ITS2 (ITS1 + 2) ribosomal DNA region were amplified and sequenced, together with a partial region of 18S ribosomal DNA in selected cases. Prevalences of the different genetic profiles within the whole patient cohort and by country/geographical area of possible infection were analysed. A phylogenetic analysis was performed using the larger cox1 (~ 956 base pairs) sequences dataset. Results: A total of 94 samples were available for analysis, 36 from patients with a diagnosis of intestinal schistosomiasis and 58 with urinary schistosomiasis, all acquired in a sub-Saharan African country. Mitochondrial (mt) cox1 , nuclear ITS1 + 2 and/or 18S (mt/nuclear) genotypes were successfully obtained from 51/94 (54%) samples; while for 43/94 (46%) samples, only a partial mt genotype was obtained. Infections with Schistosoma haematobium and Schistosoma mansoni were identified in the majority of cases (66/94; 70%), while mixed Schistosoma spp. genetic profiles, which were identified in 30% (28/94) of the samples, were almost exclusively (27/28; 96%) associated with cases of urinary schistosomiasis. Among the urinary infections, almost half (27/58; 47%) could be identified as having a mixed genetic profile. These mostly (26/28; 93%) included genetic traits of S. haematobium and Schistosoma bovis , and all were from patients probably infected in West Africa. Conclusions: Infections with S. haematobium and S. mansoni represent the majority of cases of schistosomiasis currently being diagnosed in Europe; however, mixed Schistosoma genetic profiles (mostly S. haematobium/S. bovis ) were identified in at least 30% of samples. Our results call for a coordinated effort encompassing prompt diagnosis and treatment of Schistosoma infections, together with monitoring of the possible introduction of species of Schistosoma and establishment of their autochthonous transmission under suitable conditions in Europe.

Background: Dengue virus infection is a significant challenge for global health, with 100 million symptomatic cases, 2.3 million DALYs and 20,000 deaths annually. Dengue vaccines must provide long-lasting immunity against all four virus serotypes, especially in dengue-naïve individuals, in order to avoid the severe manifestations of secondary infections. Methods: This scoping review summarizes current evidence on licensed dengue vaccines and vaccine candidates, focusing on immunogenicity, efficacy, and safety outcomes. To identify relevant trials, in October 2023 we queried ClinicalTrials.gov using the search term “dengue vaccines” to identify past and present vaccine candidates; the search was repeated in February 2025. Vaccines were categorized into licensed (CYD-TDV and TAK-003), late-stage (TV003/TV005), and early-stage candidates (TDEN, DPIV, V180, TVDV). Results: CYD-TDV (Dengvaxia^®) showed moderate efficacy in large trials, with higher efficacy in seropositive than in seronegative individuals. Following commercialization, an increased hospitalization risk was discovered in the latter group. Due to these findings and impossibility of screening for prior exposure in endemic settings newer vaccines are now preferred and CYD-TDV production has recently been discontinued due to declining demand. TAK-003 (Qdenga^®) demonstrated high efficacy against virologically confirmed dengue (VCD) and dengue-related hospitalization. This vaccine was generally well tolerated and is currently recommended by scientific societies and national authorities for travelers and by WHO for routine use in adults and children in endemic settings. TV003 and TV005, developed by NIAID, showed strong immunogenicity and efficacy in phase II trials and human challenge models. Preliminary results show that a single-dose of TV003 has an efficacy of 79.6% in seronegatives and 89.2% in seropositives against VCD at a 2-year follow-up. Both formulations elicited tetravalent responses with an acceptable safety profile. Other vaccine strategies, including TDEN (live-attenuated), DPIV (purified inactivated), V180 (subunit), and TVDV (DNA-based) are still in early-phase development and suffer from waning antibody titers and limited efficacy in naïve subjects. Conclusions: The development of a safe and effective vaccine remains complex due to immunologic challenges. Currently, TAK-003 is regarded as the best option for broad implementation, while TV003 and TV005 remain promising candidates due to their shorter schedule and robust immunogenicity. Further research is needed to optimize vaccine strategies in seronegative populations, immunocompromised subjects, older adults, and travelers.

Background: Currently, there are no standardized guidelines for the diagnosis or management of the complications of urogenital schistosomiasis (UGS). This systematic review of the literature aims to investigate the state of the art in reference to diagnostic approaches and the clinical management of this condition.Methods: A systematic review of literature published between January 1990 and January 2021 was conducted in the MEDLINE database, scoping for articles regarding diagnostic means or therapeutic options for the complications of UGS, namely obstructive uropathy, bladder cancer, abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures. Relevant data were then extracted from the articles deemed eligible according to the inclusion criteria.Main results: In total, 3052 articles were identified by the research query, of which 167 articles fulfilling inclusion criteria after title/abstract screening and full-text evaluation were included, 35% on both diagnostic and therapeutic aspects, and 51% on diagnosis and 14% on therapy. Ultrasound was the most frequently tool employed for the diagnosis of UGS complications showing a good performance. Concerning the management of hydronephrosis, the majority of available evidences came from community-based studies where universal treatment with praziquantel was used leading to decrease of prevalence of obstructive uropathy. Concerning studies on surgical procedures, laser endoureterotomy followed by stenting was mostly employed in adult patients leading to a crude cure rate of 60% (43 of 71 patients). In the case of severe hydronephrosis, surgery consisting of ureteral re-implantation showed excellent results with a crude cure rate of 98% (157 cured patients of 160 treated). Concerning bladder cancer, data on 93 patients with a clear diagnosis of UGS-related bladder were available reporting a variable and sometime combined approach based on disease stage. Available data on diagnosis and management of abortion, ectopic pregnancy, infertility, kidney failure, urolithiasis and the need for invasive procedures due to UGS are also presented.Conclusions: The review produced a complete picture of the diagnostic and therapeutic options currently available for complicated UGS. These results can be useful both for guiding clinicians towards correct management and for tracing the direction of future research.

Highlight: We report on six patients with suspected chronic schistosomiasis and negative microbiological findings at baseline. All patients were treated empirically with praziquantel and all seroconverted 20 days to two months after treatment. We suggest that seroconversion after praziquantel treatment may be used as a confirmatory diagnostic tool for chronic schistosomiasis.