Current Status: Alumni
Graduate Department: Epidemiology
Other Degrees: BS with honors in Zoology & Biological Aspects of Conservation, University of Wisconsin - Madison; MSPH in Epidemiology, Rollins School of Public Health, Emory University ;
Advisor(s): Ruth Berkelman, MD;
Hometown: Bloomington, MN
I am interested in the epidemiology of vector-borne infectious diseases; specifically, I am interested in transmission, pathogenesis, and immunity. I have focused on the epidemiology of dengue viruses for several years - a field for which defining protective versus pathological immunity remains a central issue, and one that looms ever larger as dengue vaccines near introduction. My PhD research was conducted in collaboration with the Armed Forces Research Institute of Medical Sciences (AFRIMS) in Bangkok, Thailand and scientists at the University of Massachusetts. The abstract for my dissertation follows.
Abstract: Dengue fever (DF) and dengue hemorrhagic fever (DHF) are important causes of morbidity and mortality globally. The four dengue virus serotypes (DENV-1 - DENV-4) co-circulate and cause annual epidemics in endemic regions such as Southeast Asia. Cross-reactive DENV antibodies have been linked to DHF in multiple epidemiological and immunological studies. However, cross-reactive antibodies have also been associated with protection from illness. The complex factors involved in whether a non-primary infection with DENV will be subclinical, DF, or develop into DHF are poorly understood. This remains a central issue in DENV immunology, and one that looms large as DENV vaccines approach licensure and implementation. These studies sought to address important knowledge gaps regarding DENV immunity in three complementary ways. The first study assessed how immunity to Japanese encephalitis virus (JEV), a related flavivirus, may influence the clinical severity of DENV infections, using data from a prospective, school-based cohort for asymptomatic and symptomatic DENV infections in Thailand that was conducted from 1998-2002. The study found a positive association between preexisting JEV antibodies and symptomatic (versus asymptomatic) DENV infection. The second study considered whether time between DENV infections was a significant predictor of DENV severity, using time as a proxy for the decay of cross-reactive antibodies. The same prospective cohort data were used as in study one, in addition to a second phase conducted from 2004-2007. There was evidence of a temporal trend in disease risk with time between first and second infections, with asymptomatic infections occurring at shorter intervals and DHF at longer intervals. The final study evaluated the nature of serotype interactions in multivalent DENV vaccines, using data from a factorial design clinical trial that evaluated all combinations of high and low dose serotype strains in tetravalent formulations. Analyses considered how adjustments in the dose of a serotype affected seroconversion to that and other serotypes. Both immunological interference and facilitation were observed to occur between DENV serotypes with respect to seroconversion as well as the occurrence of adverse events. Together, these three studies provide novel insights into the complex nature of DENV immunity in the setting of multiple serotype exposures.
Graduation Year: 2012
Residency: Internal Medicine, University of Minnesota