PT430 Involvement of Th17 cytokines in acute rheumatic fever

PT430 Involvement of Th17 cytokines in acute rheumatic fever

POSTER ABSTRACTS Conclusion:  Parental consanguinity is a preventable risk factor for CHD.  Health education to avoid consanguineous marriages is ne...

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POSTER ABSTRACTS Conclusion:  Parental consanguinity is a preventable risk factor for CHD.  Health education to avoid consanguineous marriages is needed to reduce the burden of CHD. Disclosure of Interest: None Declared PT430 Involvement of Th17 cytokines in acute rheumatic fever William J. Martin*1, Gabriela Minigo2, Joanne Keeble1, Peta Tipping2, Melita McKinnon2, Ruijie Liu3, Gordon Smyth3, Jonathan Carapetis2,4, Ian Wicks5,6 1 Inflammation Division, Walter & Eliza Hall Institute of Medical Research, Melbourne, 2Menzies School of Health Research, Darwin, 3Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Melbourne, 4Telethon Institute for Child Health Research, Perth, 5 Inflammation Division, Walter & Eliza Hall Institute, 6Rheumatology Unit, Royal Melbourne Hospital, Melbourne, Australia Introduction: The immune mechanisms that begin with group A streptococcal (GAS) infection and result in acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain poorly understood. It is widely believed that the Th1 response is involved in the development of ARF and RHD. This is largely due to the detection of the Th1 cytokine, IFNg, in ARF patient sera and in surgically removed rheumatic heart valves. However, IFNg also features in Th17 responses, and Th17 responses have been identified as being pathogenic in a number of autoimmune diseases. We sought to determine whether there was any evidence of Th17 responses resulting from GAS stimulation of immune cells and in ARF patients undergoing an acute episode. Objectives: To determine whether Th17 responses are involved in responses to GAS and the development of ARF. Methods: Peripheral blood mononuclear cells (PBMC) were isolated by ficoll gradient. Transcriptional profiling was performed using Illumina HT-12 Bead Chips and genes were analysed using rotation gene set testing, ROAST. Flow cytometry was used to detect intracellular cytokines produced by CD4+ T-cells in culture. Cytokines in patient plasma and culture supernatants were measured using Milliplex MAP human Th17 bead kit and ELISA. Results: Microarray of PBMC stimulated with GAS in vitro revealed that genes related to the Th17 as well as the Th1 response were upregulated simultaneously following exposure to GAS. CD4+ T-cells cultured with autologous, monocyte-derived dendritic cells loaded with GAS produced IFNg and IL-17A and IL-17F, with an increased proportion of CD4+ T cells co-producing IFNg and IL-17A/F. A cohort of 18 Aboriginal and Torres Strait Islanders undergoing an active episode of ARF exhibited elevated levels of five Th17 cytokines at an average of 18.7 days following the onset of symptoms with levels of Th17 cytokines returning to those of healthy controls following treatment. Conclusion: These data indicate that the involvement of the Th1 response as the primary pathological response in ARF and RHD, as evidenced by the presence of IFNg, may be a red herring. Instead, ARF may be the result of an underlying Th17 response. This provides new avenues for investigation of ARF immunopathogenesis. Disclosure of Interest: None Declared

based therapy. Some of these challenges include both patient factors (young age, pregnancy, non-adherence to therapy, psycho-social factors) and system issues (lack of coordination, infrastructure and staffing issues). Objectives: We aim to discuss some of these recent challenging cases of RHD and discuss our co-ordinated and collaborative approach to improve patient care and the outcome. Methods: Royal Darwin Hospital is the only major hospital with onsite cardiac services in the Northern Territory. RDH has most cardiac diagnostic capabilities but does not have any onsite interventional or cardiac surgical facilities. RDH cardiology unit has established a long standing relationship with Flinders Medical Centre (Cardiology and Cardio-thoracic units). FMC provides the vast majority of the cardiac surgical support to patients from the Top End. In the past, many complex patients have been managed in an ad-hoc manner and some have been lost to follow up resulting in poor outcome. Results: Over the last two years, there have been improvement with establishment of indigenous cardiac nurse co-ordinator (ICNC) positions and weekly complex case conferencing (“Triple C”) with FMC. A weekly case conferencing session is dedicated between these two units to discuss complex patients with rheumatic heart disease. There is an open and transparent discussion among a variety of clinicians (both interventional cardiologists and cardiac surgeons). Discussions and consensus recommendations are documented and communicated through the “chair” to all the clinicians involved. Recommendations are followed through by the ICNC based at RDH. ICNC is involved in the communication with patients, primary care team, local cardiologists and FMC staff and ensure the patients are not lost in the system. There will also be an establishment of a NT Cardiovascular Information System (CVIS) which is a partnership between NT Cardiac Pty Ltd, NT Government and the Commonwealth). Conclusion: Despite the significant challenges faced by the NT remote indigenous patients with RHD, there is an opportunity to improve clinical outcome by a co-ordinated and collaborative approach by all the service providers and the health systems involved. Disclosure of Interest: None Declared

PT432 Promoting primary prevention of rheumatic heart disease in Uganda: a qualitative study of group A streptococcal pharyngitis awareness in urban and rural communities Babak Moini*1, Jan E. Hanson2, Allison Webel3, Haddy Nalubwama4, Robert Salata5, Chris Longenecker6 1 Internal Medicine, University Hospitals Of Cleveland, 2Graduate School of Public Health, 3 Bolton School of Nursing, Case Western University, Cleveland, United States, 4School of Public Health, Makerere University, Kampala, Uganda, 5Infectious Diseases, 6Cardiology, University Hospitals Of Cleveland, Cleveland, United States Introduction: Rheumatic heart disease (RHD) is the most common cause of cardiovascular morbidity and mortality among children and young adults in Uganda with an estimated prevalence of 1.4% among school aged children. Increased community awareness of the causes of RHD and the appropriate treatment of Group A streptococcus (GAS) pharyngitis may decrease the prevalence of RHD in Uganda. Objectives: The objective of this study was twofold. In the first phase of the study, we aimed to investigate the knowledge of Ugandan children and their caregivers regarding the potential complications of GAS pharyngitis and its management. Using this data, the second phase of the study aimed to increase community awareness of appropriate pharyngitis treatment. Methods: We conducted focus group discussions with conveniently selected caregivers (N¼28). Separately, we conducted focus groups with adolescents 10 to 17 years of age (N¼24). The subjects were recruited from rural and peri-urban locations in Wakiso District in south-central Uganda. We used these qualitative data to inform the design of posters and radio advertisements which were used in a 4-week community-education intervention in the same geographical areas. Door-to-door post intervention surveys were conducted to measure the efficacy of the intervention. Results: Overall, most children had experienced symptoms of pharyngitis (78%), but less frequently reported symptoms to caregivers (38%). Many caregivers reported using home remedies to treat sore throat (71%). Very few caregivers understood that pharyngitis may lead to heart disease (19%), and only one subject reported any knowledge of RHD. The post intervention survey findings are summarized in the Table. Twentyfive adults were randomly selected and interviewed. Overall, substantially more people heard the radio advertisement than saw the posters (16 vs 8). Significantly more people who were exposed to the interventions reported that they would change their practice to seek appropriate treatment of pharyngitis compared to those who were not exposed (82% vs 0%).

PT431 Role of care co-ordination and case conferencing in managing pre and post operative challenges in the NT remote indigenous patients with severe rheumatic heart disease Nadarajah Kangaharan*1, Marcus Ilton1, Pupalan Iyngkaran1, Colin Farquharson1 Cardiology, Royal Darwin Hospital, Darwin, Australia

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Introduction: Northern Territory has a high proportion of indigenous patients living remotely with high burden of rheumatic heart disease (RHD). There are significant management challenges faced by the local cardiac service in providing optimum and evidence

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Conclusion: There was a significant lack of knowledge among residents of Wakiso District, Uganda regarding causes and treatment of pharyngitis and the potential risk of rheumatic heart disease. A simple, cost-effective, community-awareness intervention appears to effectively increase residents’ intentions to seek medical treatment for future episodes of pharyngitis. Disclosure of Interest: None Declared

GHEART Vol 9/1S/2014

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March, 2014

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POSTER/2014 WCC Posters