Graduation Year

2011

Document Type

Thesis

Degree

M.S.P.H.

Degree Granting Department

Epidemiology and Biostatistics

Major Professor

Aurora Sanchez-Anguiano, M.D. Ph.D.

Co-Major Professor

Shamala Devi Sekaran, Ph.D.

Committee Member

Azliyati Azizan, Ph.D.

Committee Member

Yangxin Huang, Ph.D.

Keywords

viral disease, macrophage, dendritic cell, hemorrhage, vascular leakage, regression analysis

Abstract

Dengue, a group of four similar viruses transmitted through the bite of a mosquito, is estimated to infect upwards of 100 million annually in over 100 nations throughout the global equatorial belt. Distribution of global dengue is highly skewed as Southeast Asian and Western Pacific regions endure 75% of the global dengue burden. Similar to other regional countries, Malaysia has been rapidly urbanizing, which has supported a hyperendemic dengue state.

The biological pathway by which dengue infection causes a wide range of clinical manifestations, spanning asymptomatic to life-threatening severe complications, is not comprehensively understood. Historically, severe dengue complications have primarily occurred in children. Consequentially, the majority of the dengue biological pathway research has been conducted on children; however, extrapolation of research findings to adults may be inappropriate as dengue manifestations have differed between age groups. As developing countries undergo epidemiologic transitions and dengue continues to spread geographically to non-endemic regions, youth and adult populations have been subjected to more of the severe dengue burden.

Epidemiology and laboratory-based evidence has supported both memory T-cell and antibody independent enhancement hypotheses to explain the biological pathway of severe dengue. Both hypotheses employ the central idea that a primary infection alters immune components so that during a secondary heterotypic dengue infection, an individual is more at risk for severe complications.

Monocytes, immune cells that are pivotal in both hypotheses, have been highly examined through in vivo and in vitro experimentation; however, epidemiological evidence for monocyte involvement is incomplete. The primary objective of the study was to examine if a difference in absolute monocyte count, considering independent risk factors, is present in individuals with primary and secondary dengue infections.

A secondary dengue infection was found to raise absolute monocyte count during the defervescence phase of dengue illness in individuals aged 15 years and older 0.71 ± 0.15 (x10^9) compared to those experiencing primary dengue infection. Gender and distance of study participants' residences from Hospital Ampang were found to be risk factors for the relationship of interest; whereas, age and race were not found to be significant risk factors.

The study helps expand current knowledge of the severe dengue biological pathway with respect to immunological differences between primary and secondary dengue infections. Further research is needed to confirm and expand the findings of this initial study, specifically to include infecting dengue serotype, education, and socioeconomic status which are known dengue risk factors.

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