Delayed Care Seeking and its Varied Effects Across Severe Malaria Subtypes in Uganda - ABSTRACT Globally, severe malaria (SM) continues to cause more than 400,000 deaths each year with young children in sub-Saharan Africa accounting for 95% of deaths. Despite progress, Uganda still experiences approximately 20,000 death each year and SM is the most common cause of childhood death. Delayed care seeking, defined as receiving treatment more than 24 hours after symptom onset, is an important contributor to disease progression, yet its role in the development of distinct SM subtypes . cerebral malaria (CM), SM anemia, and acidosis - remains poorly understood. CM, the most lethal form, is characterized by neurological manifestations, with mortality rates exceeding 15% even in well-equipped facilities. CM may develop rapidly in individuals with limited immunity, while non-cerebral SM (nCSM) sub-types, may result from repeated or untreated infections. With limited research on the impact of delayed care seeking with regard to each sub-type, we propose a matched case-control study that aims to investigate the relationship between delayed careseeking and SM subtypes to understand if there could be other factors driving the development of CM. Aim 1 will document differences in care-seeking behaviors among children .12 years diagnosed with SM versus uncomplicated malaria at health facilities in Uganda, with a focus on potential differences between CM and nCSM. Aim 2 will analyze spatial patterns of SM cases to identify geographic and environmental barriers to timely care, looking for differential spatial clustering of SM sub-types. Aim 3 will explore caregiver decisionmaking through semi-structured interviews to contextualize delays in seeking treatment to identify possible areas for intervention around the 24-hours threshold for delayed care. By identifying potentially modifiable factors influencing the progression to SM this study will provide critical insights for improving malaria care and reducing mortality. Thus, the aims of this study align with broader goals to reduce malaria mortality globally by 90% by 2030 as listed in the 2025 America First Global Health Strategy by informing targeted interventions and policy strategies to enhance timely diagnosis and treatment, ultimately contributing to malaria mortality reduction efforts in Uganda and beyond. The applicantfs ultimate goal is to establish themselves as an independent epidemiologist with expertise in spatial analysis, epidemiologic study design, and qualitative research, particularly focusing on access to care. This fellowship will provide mentored training in (1) evaluating human behavior through case-control survey design, data collection, and analysis, (2) creating Bayesian spatial-temporal models to assess regional risks of severe malaria, and (3) analyzing qualitative data to explore community members' lived experiences and identify potential intervention strategies. These skills are easily translatable and necessary for any future work studying other infectious diseases impacting Americans. The proposed training will include personalized mentoring, practical application of statistical techniques, involvement in conferences, and the publication of at least three first-authored manuscripts.
