Potential role of ticks as vectors of bluetongue virus

When the first outbreak of bluetongue virus serotype 8 (BTV8) was recorded in North-West Europe in August 2006 and renewed outbreaks occurred in the summer of 2007 and again in 2008, the question was raised how the virus survived the winter. Since most adult Culicoides vector midges are assumed not to survive the northern European winter, and transovarial transmission in Culicoides is not recorded, we examined the potential vector role of ixodid and argasid ticks for bluetongue virus. Four species of ixodid ticks (Ixodes ricinus, Ixodes hexagonus, Dermacentor reticulatus and Rhipicephalus bursa) and one soft tick species, Ornithodoros savignyi, ingested BTV8-containing blood either through capillary feeding or by feeding on artificial membranes. The virus was taken up by the ticks and was found to pass through the gut barrier and spread via the haemolymph into the salivary glands, ovaries and testes, as demonstrated by real-time reverse transcriptase PCR (PCR-test). BTV8 was detected in various tissues of ixodid ticks for up to 21 days post feeding and in Ornithodoros ticks for up to 26 days. It was found after moulting in adult Ixodes hexagonus and was also able to pass through the ovaries into the eggs of an Ornithodoros savignyi tick. This study demonstrates that ticks can become infected with bluetongue virus serotype 8. The transstadial passage in hard ticks and transovarial passage in soft ticks suggest that ticks have potential vectorial capacity for bluetongue virus. Further studies are required to investigate transmission from infected ticks to domestic livestock. This route of transmission could provide an additional clue in the unresolved mystery of the epidemiology of Bluetongue in Europe by considering ticks as a potential overwintering mechanism for bluetongue virus

A Systematic Literature Review of Data from 2012 to 2022

Funding Information: The authors also acknowledge Andrew Wilhelmsen, PhD, and Jessica Patel, PhD, from Costello Medical, UK, for medical writing and editorial assistance based on the authors’ input and direction. Third-party writing assistance was funded by Janssen EMEA. Funding Information: Albino J. Oliveira-Maia: Received grants from Schuhfried GmBH, Janssen and Compass Pathways, Ltd; received payment, honoraria, travel support or advisory board fees from MSD, Janssen, Angelini, Neurolite AG, and the European Monitoring Centre for Drugs and Drug Addiction; investigator-driven research funded by Fundação para Ciência e Tecnologia (PTDC/SAU-NUT/3507/2021; PTDC/MED-NEU/1552/2021; PTDC/MED-NEU/31331/2017), Fundação para Ciência e Tecnologia and FEDER (PTDC/MED-NEU/30845/2017_LISBOA-01–0145-FEDER-030845; FCT-PTDC/MEC-PSQ/30302/2017-IC&DTLISBOA-01-0145-FEDER), the European Commission Horizon 2020 program (H2020-SC1-2017-CNECT-2-777167-ΒΟUNCE; H2020-SC1-DTH-2019-875358-FAITH), the European Research Council (grant ERC-2020-STG-Grant agreement 950357) and the European Joint Programme in Rare Diseases (Joint Translational Call 2019) through Fundação para Ciência e Tecnologia (EJPRD/0001/2020); Vice-President of the Portuguese Society for Psychiatry and Mental Health; Head of the Psychiatry Working Group for the National Board of Medical Examination (GPNA) at the Portuguese Medical Association and Portuguese Ministry of Health. Eric Constant: Received honoraria, advisory board fees and travel support from AstraZeneca, BMS, Lilly, Wyeth, Servier, Janssen Cilag, Pfizer, Lundbeck, Viatris and Teva. Tetsuro Ito, Yerkebulan Kambarov, Siobhán Mulhern-Haughey, Christian von Holt: Employees of Janssen; hold Johnson & Johnson company stocks/stock options. Ania Bobrowska, Hannah Luedke: Employees of Costello Medical, UK. Publisher Copyright: © 2023, The Author(s).Objective: Real-world evidence in treatment-resistant depression (TRD; commonly defined as non-response to ≥ 2 consecutive treatments at adequate dosage and duration) is lacking. A systematic literature review was conducted to understand disease burden and treatment outcomes for patients with TRD, studied in a real-world setting over the last decade. Data Sources: A literature search was conducted in May 2022 in MEDLINE, Embase, The Cochrane Libraries and PsycINFO, comprising studies published from 2012 to 2022. Bibliographies of all relevant identified systematic reviews and relevant conference proceedings from 2020 to 2022 were manually hand-searched. Study Selection: Real-world studies, including cohort, cross-sectional, case–control, chart review and registry studies, published in English and reporting outcomes in adults with TRD, were included. Data Extraction: Extracted data included study and baseline disease characteristics, treatment type, treatment response, clinical outcomes and health-related quality of life. Results: Twenty studies were included. Criteria for TRD varied, but patients typically experienced long-lasting depression (range 1.4 to 16.5 years). Across studies, mean disease severity scores demonstrated moderate to severe depression, reflecting a high burden of disease at baseline. Remission rates were typically low but generally increased with longer follow-up durations. However, the heterogeneity of interventions, follow-up durations (range 2 weeks to 9.4 years) and assessment tools precluded their quantitative synthesis. Studies were frequently limited by low sample size (range 14 to 411 patients) and health-related quality of life was infrequently assessed. Conclusions: There is a lack of clinical consensus regarding the definition, assessment and monitoring of TRD in real-world practice. Nevertheless, TRD carries a high burden of illness and there is an unmet need for faster and more effective treatments. To better understand the personal burden of affected patients, future studies would benefit from standardisation of severity assessment and measures of treatment effectiveness, as well as greater consideration of health-related quality of life.publishersversionepub_ahead_of_prin