UC Berkeley

Dengue virus is a flavivirus of worldwide importance, with approximately 4 billion people across 128 countries at risk of dengue virus infection. Most cases present as classic dengue fever, a debilitating, but self-limited illness that manifests with high fever, retro-orbital pain, severe myalgia or arthralgia, and rash. However, in some cases, illness progresses to life-threatening dengue hemorrhagic fever or dengue shock syndrome. The identification of distinguishing clinical and laboratory features that occur during the early febrile phase of illness is important for developing a clinical prediction algorithm to differentiate dengue from other febrile illnesses, and severe dengue from mild dengue. In addition, the success of community-based programs for preventing dengue indicates that identifying environments that could benefit from intervention at a community level is critical in order to have the greatest impact and to target limited resources.

This dissertation focuses on data from two ongoing studies in order to investigate the epidemiologic, clinical and laboratory features of pediatric dengue in Nicaragua. Chapter 1 reports on the clinical and laboratory features of dengue virus infection in Nicaraguan children. The aims of the study were to examine the frequency of clinical signs and symptoms by day of dengue illness and to analyze the association of signs and symptoms with dengue virus infection during the early febrile phase of illness and over the course of illness.

Chapter 2 reports on the association of lower low-density lipoprotein cholesterol levels with severe dengue outcome. The aim of the study was to delineate the trajectories of cholesterol levels over time by dengue virus infection status in order to understand the effect of dengue virus infection on cholesterol metabolism. We also sought to delineate their trajectories by dengue severity and to assess the effect of cholesterol level at presentation on development of severe dengue.

Chapter 3 reports on individual-, household- and neighborhood-level determinants of dengue virus seropositivity in a community-based cohort. The aim of the study was to identify risk factors for DENV infection among children living in urban neighborhoods in Managua, Nicaragua. We also sought to determine the seroprevalence of dengue virus infection and identify individual- and household-level risk factors for dengue virus infection in neighborhood groups categorized by similar socioeconomic, infrastructural and ecological characteristics.

Together, these studies present important findings on the natural history of pediatric dengue in Nicaragua and provide the basis for future research to develop clinical prediction algorithms to discriminate dengue from other febrile illnesses, and severe dengue from mild dengue. They also reveal the importance of understanding neighborhood-level factors in targeting community-based programs to prevent dengue.