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Background:Risk of infection is increased in patients with autoimmune inflammatory rheumatic diseases (AIRD)1. Furthermore, disease-modifying antirheumatic drug (DMARD) treatment contributes to this risk2. To reduce the risk of serious infections, it is recommended that patients are vaccinated againstStreptococcus pneumoniae3. However, some AIRD patients do not develop or maintain an adequate antibody response after pneumococcal vaccination4.Objectives:The aim of the study was to examine the proportion of patients with low antibody levels, who achieved a protective level of pneumococcal antibodies after vaccination.Methods:Pneumococcal antibodies were measured by a serological assay in patients treated with biologics in a rheumatology outpatient clinic. Vaccination with 23-valent-pneumococcal polysaccarid vaccine was then offered to patients with a protective antibody level below the defined threshold and pneumococcal antibody level was measured at follow-up 2-3 months later. The patients continued their DMARD treatment without any changes.Demographic and clinical data were collected, including age, sex, AIRD diagnosis, duration and activity (high/low), in addition to treatment (biologics, prednisolone, methotrexate) and previous vaccination history.Results:A total of 248 patients with inadequate antibody level accepted vaccination and among those, 137 patients (55%) had previously been vaccinated, 98 patients had not previously been vaccinated and for 13 patients data on vaccination status could not be obtained.At follow-up, 84 patients (34%) achieved a protective level of antibodies. Use of methotrexate as part of the DMARD regimen was associated with an unprotected level of pneumococcal antibodies (Figure 1) (pFigure 1In the group of patients who had previously been vaccinated, time between vaccinations spanned from 20 to 111 months, median 49 months.There was an association between previous vaccination, and failure in achieving a protective antibody level (Figure 1) (p=0,02), as well as an association between less than 5 years (60 months) between vaccinations and not achieving a protective level.Conclusion:We found that only one-third of patients achieved a protective pneumococcal antibody level after vaccination. Methotrexate treatment was associated with a decreased antibody response, which was not the case for treatment with biologics or prednisolone.Among patients who had previously been vaccinated, significantly less achieved a protective level of antibodies, compared to patients who had not been vaccinated. All 248 patients had a low antibody level at baseline, despite 137 being previously vaccinated.Further studies are warranted to show whether or not a short discontinuation of methotrexate, will better the response to vaccination.References:[1]Wolfe, F. et al. The mortality of rheumatoid arthritis.Arthritis Rheum1994;37(4):481–494.[2]Ramiro, S. et al.). Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis.Ann Rheum Dis2017;76(6):1101–1136.[3]van Assen S. et al. (). EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.Ann Rheum Dis2011;70(3):414–422.[4]Hua, C. et al. Effect of methotrexate, anti-tumor necrosis factor alpha, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis.Arthritis Care Res 2014;66(7):1016–1026.Disclosure of Interests:None declared

IntroductionBy end of 2018, the European Union countries hosted approximately 2.5 million refugees and Lebanon alone hosted more than 1 million. The majority of refugees worldwide came from Syria. The prevailing study design in published studies on asylum seekers’ and refugees’ health leaves a number of fundamental research questions unanswerable. In the Asylum seekers’ and Refugees’ Changing Health (ARCH) study, we examine the health of a homogeneous group of refugees and asylum seekers in two very different host countries with very different migration histories. We aim to study the health impact of the migration process, living conditions, access to healthcare, gene–environment interactions and the health transition.Methods and analysisARCH is an international multisite study of the health of adult (>18 years old) Syrian refugees and asylum seekers in Lebanon and Denmark. Using a standardised framework, we collect information on mental and physical health using validated scales and biological samples. We aim to include 220 participants in Danish asylum centres and 1100 participants in Lebanese refugee camps and settlements. We will use propensity score weights to control for confounding and multiple imputation to handle missing data.Ethics and disseminationEthical approval has been obtained in Lebanon and Denmark. In the short term, we will present the cross-sectional association between long-distance migration and the results of the throat and wound swab, blood and faeces samples and mental health screenings. In the longer term, we are planning to follow the refugees in Denmark with collection of dried blood spots, mental health screenings and semistructured qualitative interviews on the participant’s health and access to healthcare in the time lived in Denmark. Here, we present an overview of the background for the ARCH study as well as a thorough description of the methodology.

OBJECTIVE: Clostridium difficile is a major cause of nosocomial infectious diarrhoea. Treatment of C. difficile infection (CDI) depends on disease severity. A combination of vancomycin and metronidazole is often recommended in severe cases. The aim of this study was to examine, in a murine model of CDI, if mice treated with a combination of vancomycin and metronidazole had a better clinical outcome than mice treated with vancomycin or metronidazole alone.DESIGN: C57BL/6J mice pretreated with an antimicrobial mixture were challenged with C. difficile VPI 10463 or phosphate-buffered saline by oral gavage. After the challenge, the mice were treated with placebo, vancomycin, metronidazole or a combination of vancomycin and metronidazole for 10 days. The mice were monitored for 20 days with weight and a clinical score. Stool samples were examined for C. difficile spore load and presence of C. difficile toxins.RESULTS: None of the mice in the vancomycin-treated group died during the treatment phase compared to a mortality of 17%, 33% and 55% in the combination, metronidazole and infected control group, respectively. Mice treated with vancomycin alone or in combination with metronidazole recovered from CDI faster than mice treated with metronidazole alone. However, after discontinuation of treatment, vancomycin-treated and combination-treated mice succumbed to clinical and bacteriological relapse.CONCLUSIONS: Mice treated with vancomycin alone had a better clinical outcome in the treatment phase of CDI than mice treated with metronidazole alone. A combination of vancomycin and metronidazole did not improve the clinical outcome when compared to treatment with vancomycin alone.TRIAL REGISTRATION NUMBER: The trial registration number from the Danish Experimental Animal Inspectorate is J number 2012-15-2934-00422.