The Role of ST2/IL-33 pathway in Ugandan Children with Severe Malaria 1,2Pontian Adogamhe, 2Elizabeth Fernander, 2Katrina Co, 2Dibyadyuti Datta, 3Robert O. Opoka, 2Chandy C. John 1Department of Chemistry, University of Wisconsin-Whitewater, Whitewater, WI, 2Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University, Indianapolis, IN, 3Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda MAKERERE UNIVERSITY INTRODUCTION In 2017, about 219 million cases of malaria were reported. 92% of the burden was borne by Sub Sahara Africa especially children under the age of 5. Due to the complicated life cycle of Plasmodium falciparum, malaria has been difficult to treat and eliminate. Untreated P. falciparum infection causes severe malaria which can result in long term cognitive impairments and deaths. Although studies on mouse models reveal that severe malaria is strongly associated with the ST2/IL-33 axis,3 they have been inconclusive on the function. Human studies are needed to determine ST2/IL-33 levels and its role in the overall cognitive ability of children. Rationale: Do sST2 levels differ in children with different forms of severe malaria and what effect does it have on overall cognitive outcomes? MATERIALS AND METHODS ST2 AND COGNITIVE OUTCOMES IN CHILDREN WITH CM Cognitive Outcome β Coefficient 95% (N); Unadjusted P value Age < 5years Overal Cognitive ability -0.151(-0.935-0.632)(103) 0.70 -0.024 (-1.06-1.01)(99) 0.96 Attention 0.254(-0.390-0.898) (104) 0.44 -0.177(-0.98-0.63)(100) 0.66 Associate Memory -0.325(-0.890-0.240)(103) 0.26 -0.413 (-1.16-0.34)(99) 0.28 Age ≥ 5years Overall cognitive ability -1.550(-2.535-0.564)(60) 0.003 -1.56(-2.72-0.39)(54) 0.01 -1.419(-2.403-0.4341)(60) 0.006 -1.17(-2.32-0.27)(54) 0.04 Working Memory -0.876 (-1.900-0.148)(60) 0.09 0.88(-2.03-0.27)(54) 0.13 Table 2: Associations between ST2/IL-33 and cognitive attributes. DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF STUDY PARTICIPANTS Table 1: Demographic and clinical characteristics of 415 Ugandan Children enrolled in CMR01 whose sST2 levels were measured. DISCUSSION AND CONCLUSION Although there were no significant differences between severe malaria groups, levels of ST2 in CM and SMA were significantly higher than CC. Findings confirms mouse studies which found associations between experimental cerebral malaria and ST2/IL-333 higher levels of ST2/IL-33 were noticed in children with complicated malaria1 Associations were noticed in the overall cognitive ability of children above the age of 5. We suspect that cognitive testing for children >5 years are more effective than children <5. The cognitive outcomes were not associated with ST2 levels in SMA children. ST2/IL-33 is a potential biomarker for malaria disease severity RESULTS ST2/IL-33 References And Acknowledgements Ayimba, et al. 2011. Clin. Exp. Immunol 166, 218. Besnard, et al. 2015. PLoS Pathog 11, e1004607 Palomo, et al 2015. Eur J Immunol 45, 1354 Fact sheet about Malaria. (2018). Retrieved February 14, 2019, from https://www.who.int/news-room/fact-sheets/detail/malaria We thanks to the patients and their families for participation in this study. We also thank our team at Indiana University, Indianapolis, USA; University of Wisconsin McNair program, Wisconsin Alliance for Minority Participation and Makerere University Kampala, Uganda. The parent study was funded by NINDS R01 NS055349 Contact: Pontian Adogamhe, Adogamhepe01@uww,edu Fig. 4 and Table 2. Plasma sST2 concentrations in children diagnosed with cerebral malaria vs. severe malaria anemia vs control group