Dengue virus (DENV) infections are an emerging problem, causing disease in tropical and subtropical countries, including the U.S, with recent outbreaks in Texas, Hawaii and Florida. An increase in the average age of DENV related hospitalizations has been globally recognized with adult disease more commonly recognized, but prospective clinical studies that characterize dengue illness in both children and adults are lacking. Dengue hemorrhagic fever (DHF), a more severe clinical manifestation of DENV infection, has been classified by the WHO into four grades of severity with minimal criteria of capillary leakage and thrombocytopenia. The WHO released revised guidelines for the diagnosis of """"""""dengue"""""""" and """"""""severe dengue"""""""" in 2009. Severe dengue comprises not only plasma leakage and bleeding, but also end organ failure, which is a relatively rare event. In addition, several 'warning signs', such as abdominal pain and nausea, are highly non-specific. A major dilemma in the management of dengue illness is the difficulty in early recognition of those individuals who will go on to severe dengue and/or shock. We have previously developed a classification and regression tree algorithm for identifying such individuals at risk for severe illness. Frequent blood tests (white blood cell counts, hematocrit, liver function studies) are needed to identify severe disease, which is not practical in resource poor settings. Non-invasive monitoring which might capture individuals with impending complications and would help to guide therapy would greatly enhance the current management of DENV illness. We propose to address these issues with the following Specific Aims: I.To determine the clinical features which characterize severe disease in hospitalized children and adults with suspected dengue - characterize early and late disease in adults vs. children, evaluate old and new WHO criteria, compare immunologic and virologic correlates to severe disease in adults vs. children II.To develop and validate an algorithm which will enable physicians to predict which children or adults will develop significant plasma leakage and/or shock and to define those who will not. We will utilize novel noninvasive monitoring (near infrared spectroscopy and arterial wave forms) to accomplish these goals.
Dengue virus (DENV) infections are an emerging problem world-wide with several recent introductions of disease into the US. DENV infection can cause severe illness and shock, but early identification of individuals who will develop severe disease is currently lacking. Better modalities for early identification and management guidance in children and adults with DENV infection would have a significant impact on global health.
|Kang, Jeon-Young; Aldstadt, Jared (2017) The Influence of Spatial Configuration of Residential Area and Vector Populations on Dengue Incidence Patterns in an Individual-Level Transmission Model. Int J Environ Res Public Health 14:|
|Rattanamahaphoom, Jittraporn; Leaungwutiwong, Pornsawan; Limkittikul, Kriengsak et al. (2017) Activation of dengue virus-specific T cells modulates vascular endothelial growth factor receptor 2 expression. Asian Pac J Allergy Immunol 35:171-178|
|Kalayanarooj, Siripen; Rothman, Alan L; Srikiatkhachorn, Anon (2017) Case Management of Dengue: Lessons Learned. J Infect Dis 215:S79-S88|
|Srikiatkhachorn, Anon; Mathew, Anuja; Rothman, Alan L (2017) Immune-mediated cytokine storm and its role in severe dengue. Semin Immunopathol 39:563-574|
|Moulton, Steven L; Mulligan, Jane; Srikiatkhachorn, Anon et al. (2016) State-of-the-art monitoring in treatment of dengue shock syndrome: a case series. J Med Case Rep 10:233|
|Srikiatkhachorn, Anon; Yoon, In-Kyu (2016) Immune correlates for dengue vaccine development. Expert Rev Vaccines 15:455-65|
|Rothman, Alan L; Ennis, Francis A (2016) Dengue Vaccine: The Need, the Challenges, and Progress. J Infect Dis 214:825-7|
|Townsley, E; O'Connor, G; Cosgrove, C et al. (2016) Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells. Clin Exp Immunol 183:419-30|
|Clapham, Hannah E; Rodriguez-Barraquer, Isabel; Azman, Andrew S et al. (2016) Dengue Virus (DENV) Neutralizing Antibody Kinetics in Children After Symptomatic Primary and Postprimary DENV Infection. J Infect Dis 213:1428-35|
|Nisalak, Ananda; Clapham, Hannah E; Kalayanarooj, Siripen et al. (2016) Forty Years of Dengue Surveillance at a Tertiary Pediatric Hospital in Bangkok, Thailand, 1973-2012. Am J Trop Med Hyg 94:1342-7|
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