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Delta Omega

2010 Poster Competition Winners

1st Place- Applied Science and Overall Winner: Jesse Berman, PhD Candidate

Title: Health Benefits from Large Scale Ozone Reduction in the United States

Tropospheric ozone is one of six “criteria” air pollutants for which the U.S. Environmental Protection Agency (EPA) sets a health-based National Ambient Air Quality Standard (NAAQS). The EPA monitors levels of ozone across the United States (US) through a network of air quality monitors. Increased levels of ozone have been correlated with increased risk of adverse health effects, including premature mortality and related cardiopulmonary and respiratory morbidity. In 2008, the United States Environmental Protection Agency (EPA) lowered the ozone NAAQS from 84 ppb to 75ppb, expressed as the maximum 8-hr average over a 24-hr period. Based on current monitoring data, ozone levels in numerous locations across the U.S. exceed this standard. The avoided potential adverse health impacts are quantified among the U.S. population associated with attaining the current and two alternative ozone NAAQS levels. We estimate the avoided health impacts occurring after “rolling back” ozone values to just attain three alternate 8-hr ozone NAAQS: 75, 70, and 60 ppb (a range under current consideration for a revised ozone standard). The two lower alternatives reflect the upper and lower-bound range of EPA Clean Air Scientific Advisory Committee recommended values. The EPA Environmental Benefits Mapping and Analysis Program (BenMAP) is used to project the number of avoided cases of premature mortality and morbidity for an analysis year of 2007. Using a suite of short-term ozone mortality studies (Bell et al. 2005 and Levy et al. 2005) the avoided incidences from current ozone-related all-cause premature mortality range from 290-410 at 75ppb, 580-820 at 70ppb, and 1,890-2,660 at 60ppb. We also find that attaining the 75ppb standard result in prevention of 290 emergency room visits (respiratory) and 250 hospital admissions (respiratory), with a reduction of 550,250 acute respiratory symptoms and 237,100 lost school days. Attainment of the 70 and 60 ppb 8-hr maximum levels yielded substantial additional health benefits, with about 1.1 and 3.5 million acute respiratory symptoms and 510 and 1,670 hospital admissions (respiratory) prevented at the 70 and 60ppb rollbacks, respectively. Mapping of all scenario results display regional variation in health benefits, and reporting by metropolitan statistical areas (MSAs) show the greatest health benefits to be in the New York, Los Angeles, Philadelphia, and Riverside, California MSAs.

2nd Place- Applied Science: Christen Fornadel, PhD Candidate

Title: Analysis of Anopheles arabiensis blood feeding behavior in southern Zambia during the two years following the introduction of insecticide treated bed nets

Anopheles arabiensis is the primary vector responsible for Plasmodium falciparum transmission in Macha, Zambia. Since insecticide treated bed nets (ITNs) have the potential to alter host feeding behavior, the extent of the vector’s zoophilic and exophagic tendencies was evaluated during the two rainy seasons following ITN introduction. Paired indoor/outdoor human landing catches (HLCs) and outdoor cattle-baited collections were used to assess potential changes in host preference. Results support the hypothesis that An. arabiensis in Macha remains highly anthropophilic despite high ITN use. Additionally, HLCs and Centers for Disease Control light traps were employed to determine if ITNs were having an effect on foraging behavior. Similar numbers of mosquitoes were caught in light traps hung next to treated and untreated bed nets, suggesting that ITNs have little effect on entering behavior. Although no repellant effect was observed, An. arabiensis in Macha appears to be relatively exophagic and has been caught biting outdoors both right after sunset and right before sunrise, potentially circumventing the protective effects of ITNs.

3rd Place- Applied Science: David Hanna, PhD Candidate

Title: Disparities in HIV-related mortality in persons with HIV infection by state, 34 US states, 2001-2006

Introduction: Geographic disparities in HIV-related mortality highlight areas that may require more resources. Published US HIV-related death rates by state have used general population denominators. We used HIV-infected population denominators to control for prevalence differences among states, better reflecting the quality of care.

Methods: We calculated HIV-related death rates per 1,000 HIV-infected person-years among persons age 15+ for 2001 through 2006 by state, age-adjusted to the 2000 US Standard Population. Numerators were HIV-related deaths (defined by ICD-10 codes B20-B24) by state of residence at death from the National Vital Statistics System, which records the underlying cause of all US deaths. Denominators were person-years based on yearly differences between cumulative HIV infection diagnoses and cumulative deaths among persons with those diagnoses, adjusted for reporting delays, by state of residence at diagnosis. Denominator data came from the national HIV/AIDS Reporting System, which documents all persons diagnosed with HIV infection and their deaths, as reported to state health departments. Negative binomial regression determined rate ratios (RRs) among states, adjusted for age, sex, race/ethnicity, and year. Analysis was limited to 34 states with confidential name-based HIV reporting for at least four years.

Results: Based on 2,437,274 HIV-infected person-years, the overall death rate due to HIV was 22.8/1,000 person-years (95% confidence interval [CI], 22.5-23.2). Rates by state ranged from 10.5 (95% CI 8.8-12.3) to 35.2 (95% CI 31.8-38.7), showing significant heterogeneity across states even after adjusting for race/ethnicity (p<0.0001). Rates increased by age (RR 1.36 per decade, 95% CI 1.35-1.38) and decreased by calendar year (RR 0.91, 95% CI 0.90-0.91). States with the 11 highest rates were all in the southern region.

Conclusions: Our findings suggest that, among US states, the need for more resources to prevent HIV-related mortality is concentrated disproportionately in the South. Policymakers should consider state or regional differences within a country when analyzing death rates.

1st Place- Basic/Lab Science: Jose Ramirez, PhD Candidate

Title: The Toll pathway is a conserved immune defense active against different dengue serotypes and present in multiple Aedes aegypti strains

The dengue virus has become one of the most important arboviral pathogens given the recent increase in incidence in the tropics and subtropics. It is transmitted among humans, primarily by the mosquito Aedes aegypti. Dengue transmission and disease dynamics are exacerbated by the existence of four closely related dengue serotypes. Mosquito vectors are able to limit infection with certain pathogens by mounting a range of immune responses. Although great advances have been made in understanding the mosquito responses to other pathogens such as Plasmodium, little is known about the mosquito antiviral immune responses.

Our previous studies have demonstrated the implication of the Toll Pathway as part of the anti-dengue defense repertoire at 7days post-infection. In this study we have assessed the anti-dengue effectiveness of this pathway at the early stage of infection and against different dengue virus serotypes and in field-derived mosquitoes. We observed that the Toll pathway is active at the early stages of infection (72h post-infection), at the time when new virions are released from the midgut for widespread dissemination. Furthermore, this immune defense is effective against other dengue virus serotypes and present in different strains of field-derived Aedes aegypti mosquitoes. This work adds important information to our understanding of mosquito-dengue virus interactions at the early stages of infection and key factors that modulate dengue transmission. The implication of the mosquito’s innate immune system in the defense against infection was investigated through reverse genetic RNAi methodology and viral plaque assays.

2nd Place- Basic/Lab Science: Shuzhen Sim

Title: Dengue virus inhibits immune signaling in Aedes aegypti cells

The ability of many viruses to manipulate the host antiviral immune response often results in complex host-pathogen interactions. In order to study the interaction of dengue virus (DENV) with the Aedes aegypti immune response, we have characterized the DENV infection-responsive transcriptome of the immune-competent A. aegypti cell line Aag2. As in mosquitoes, DENV infection transcriptionally activated the cell line Toll pathway and a variety of cellular physiological systems. Most notably, however, DENV infection down-regulated the expression levels of numerous immune signaling molecules and antimicrobial peptides (AMPs). Functional assays showed that transcriptional induction of AMPs from the Toll and IMD pathways in response to bacterial challenge is impaired in DENV-infected cells. In addition, Escherichia coli, a Gram-negative bacterial species, grew better when co-cultured with DENV-infected cells than with uninfected cells, suggesting a decreased production of AMPs from the IMD pathway in virus-infected cells. Pre-stimulation of the cell line with Gram-positive bacteria prior to DENV infection had no effect on DENV titers, while pre-stimulation with Gram-negative bacteria resulted in an increase in DENV titers. These results indicate that DENV is capable of actively suppressing immune responses in the cells it infects, a phenomenon that may have important consequences for virus transmission and insect physiology.

3rd Place- Basic/Lab Science: Talibah Metcalf, PhD Candidate

Title: Characteristics of trafficking and long-term maintenance of B-cells in the central nervous system in response to Sindbis virus infection

Alphaviruses are mosquito-borne message-sense RNA viruses that can cause encephalitis in a wide range of vertebrates including humans. Previous studies with Sindbis virus (SINV), the prototype alphavirus, have shown that infectious virus is cleared within 7-9 days, but that viral RNA persists. IFN-gamma plays a role in noncytolytic clearance of virus from neurons and anti-viral antibodies are important for both viral clearance and suppression of viral reactivation. After recovery, SINV-specific antibody secreting cells are present in the central nervous system (CNS) for the life of the animal. However, little is known about the changing functional characteristics of B-cells and important determinants of B-cell trafficking and long-term maintenance in the CNS. To characterize the B-cell subset populations in the periphery and CNS tissue, as well as to understand the role of chemokines, C57BL/6 mice were infected intracerebrally with SINV and tissue was assessed at various times after infection by flow cytometry and qRT-PCR.

Plasmablasts and memory B-cells (CD19+CD38+CD138-IgM-IgD-) were 70% of the B-cell population for at least 6 months, while plasma cells (CD19+/-CD38-CD138+) were less than 5% of the population. Staining for intracellular and surface IgG at day 60 identified 40% of the B cells as plasmablasts and 50% as memory cells. A small population of CD19+CD38-CD138- cells, characteristic of germinal center B-cells, was detected and this was confirmed by staining for the germinal center marker GL7. Levels of CXCL9/CXCL10/CCL3/CCL5 (leukocyte trafficking), CCL19/CXCL13 (follicle formation), and BAFF (B-cell survival) mRNAs peaked between days 5-7 after infection, followed by a gradual decreased and return close to baseline by 6 months, except for BAFF that was maintained at a low level. The expression of CXCR3 (receptor for CXCL9/10), CCR5 (receptor for CCL3/5), CCR7 (receptor for CCL19), and BAFF receptor was detected on CNS B-cells.

These results show that plasmablasts and memory B-cells are present for months after infectious virus has been cleared and could play a role in the long-term suppression of SINV replication. The detection of germinal center B-cells along with the early upregulation of chemokines involved in follicle formation suggest the formation of germinal centers in the brain in response to SINV infection. The low levels of BAFF mRNA coincide with the low number of B-cells present after 2 months suggesting the brain provides a microenvironment for differentiation and survival of these cells.