The inaugural data from the first systematic program of sea-ice observations in Kotzebue Sound, Alaska, in 2018 coincided with the first winter in living memory when the Sound was not choked with ice. The following winter of 2018–19 was even warmer and characterized by even less ice. Here we discuss the mass balance of landfast ice near Kotzebue (Qikiqtaġruk) during these two anomalously warm winters. We use in situ observations and a 1-D thermodynamic model to address three research questions developed in partnership with an Indigenous Advisory Council. In doing so, we improve our understanding of connections between landfast ice mass balance, marine mammals and subsistence hunting. Specifically, we show: (i) ice growth stopped unusually early due to strong vertical ocean heat flux, which also likely contributed to early start to bearded seal hunting; (ii) unusually thin ice contributed to widespread surface flooding. The associated snow ice formation partly offset the reduced ice growth, but the flooding likely had a negative impact on ringed seal habitat; (iii) sea ice near Kotzebue during the winters of 2017–18 and 2018–19 was likely the thinnest since at least 1945, driven by a combination of warm air temperatures and a persistent ocean heat flux.

ABSTRACT IMPACT: This study aims to provide insight into naturally acquired immunity against severe malaria, thereby laying the foundation for the design of novel vaccine candidates to prevent severe disease as well as monoclonal antibody therapies to treat severe malaria. OBJECTIVES/GOALS: Severe malaria is caused by parasite surface antigens that contain high sequence diversity. Nevertheless, P. falciparum-exposed individuals develop antibody responses against these antigens. Our goal is to isolate antibodies with broad reactivity to understand how disease protection is acquired. METHODS/STUDY POPULATION: Our study cohort consists of Ugandan adults living in a malaria-endemic region with high transmission intensity, who are protected against severe malaria. Using fluorescently labeled probes of parasite surface antigens, we have isolated antigen-specific B cells from these donors. We then expressed the corresponding monoclonal antibodies in vitro. These antibodies were screened against a library of variant surface antigens to determine antibody breadth and potential to inhibit interaction of the parasite surface antigen with host receptors, a critical step in pathogenesis. Additionally, using a panel of variant surface antigen mutants, we have predicted the epitopes targeted by the broadest monoclonal antibodies. RESULTS/ANTICIPATED RESULTS: We have identified three monoclonal antibodies with exceptionally broad reactivity and inhibitory activity against our panel of severe disease-inducing variant surface antigens. We have identified two major sites targeted by these broadly reactive antibodies. The first site was associated with the largest breadth, but limited inhibitory potential, while the second site showed high-affinity antibody binding and inhibition of receptor binding. Interestingly, two of these three antibodies were very similar in structure, even though they were isolated from different donors. Isolation of antigen-specific B cells from additional donors will enable us to identify how common such broadly reactive antibodies are and allow the identification of additional epitopes DISCUSSION/SIGNIFICANCE OF FINDINGS: This study is the first to isolate broadly reactive antibodies that are likely to protect against severe malaria in naturally immune individuals. Further characterization of antibody-antigen interactions will inform the development of this surface antigen as a vaccine candidate for malaria.

Background: The standardized infection ratio (SIR) is the nationally adopted metric used to track and compare catheter-associated urinary tract infections (CAUTIs) and central-line– associated bloodstream infections (CLABSIs). Despite its widespread use, the SIR may not be suitable for all settings and may not capture all catheter harm. Our objective was to look at the correlation between SIR and device use for CAUTIs and CLABSIs across community hospitals in a regional network. Methods: We compared SIR and SUR (standardized utilization ratio) for CAUTIs and CLABSIs across 43 hospitals in the Duke Infection Control Outreach Network (DICON) using a scatter plot and calculated an R2 value. Hospitals were stratified into large (>70,000 patient days), medium (30,000–70,000 patient days), and small hospitals (<30,000 patient days) based on DICON’s benchmarking for community hospitals. Results: We reviewed 24 small, 11 medium, and 8 large hospitals within DICON. Scatter plots for comparison of SIRs and SURs for CLABSIs and CAUTIs across our network hospitals are shown in Figs. 1 and 2. We detected a weak positive overall correlation between SIR and SUR for CLABSIs (0.33; R2 = 0.11), but no correlation between SIR and SUR for CAUTIs (−0.07; R2 = 0.00). Of 15 hospitals with SUR >1, 7 reported SIR <1 for CLABSIs, whereas 10 of 13 hospitals with SUR >1 reported SIR <1 for CAUTIs. Smaller hospitals showed a better correlation for CLABSI SIR and SUR (0.37) compared to medium and large hospitals (0.19 and 0.22, respectively). Conversely, smaller hospitals showed no correlation between CAUTI SIR and SUR, whereas medium and larger hospitals showed a negative correlation (−0.31 and −0.39, respectively). Conclusions: Our data reveal a weak positive correlation between SIR and SUR for CLABSIs, suggesting that central line use impacts CLABSI SIR to some extent. However, we detected no correlation between SIR and SUR for CAUTIs in smaller hospitals and a negative correlation for medium and large hospitals. Some hospitals with low CAUTI SIRs might actually have higher device use, and vice versa. Therefore, the SIR alone does not adequately reflect preventable harm related to urinary catheters. Public reporting of SIR may incentivize hospitals to focus more on urine culture stewardship rather than reducing device utilization.

Funding: None

Disclosures: None

Background: UV-C light reduces contamination of high-touch clinical surfaces. Few studies have tested the relative efficacy of UV-C devices in real-world clinical environments. Methods: We assessed the efficacy of the Tru-D (SmartUVC) and Moonbeam-3 UV-C (Diversey) devices at eradicating important clinical pathogens in 2 hyperbaric chambers at a tertiary-care hospital. Formica sheets were inoculated with 106–107 CFU of MRSA (USA300) or 104–105 CFU of C. difficile (NAP1). Sheets were placed in 6 predetermined locations throughout the chambers. Two Moonbeam-3 UV-C devices were positioned in the center of each chamber and were run for 3-minute (per manufacturer’s instructions) and 5-minute cycles. One Tru-D was positioned in the center of the chamber and was run on the vegetative cycle for MRSA and the spore cycle for C. difficile. UV-C dosage was measured for both machines. Quantitative cultures were collected using Rodac plates with DE neutralizing agar and were incubated at 37C for 48 hours. C. difficile was likewise plated onto sheep’s blood agar. Results: We ran each combination of chamber, microbe, and UV-C device in triplicate for In total, 108 samples per species.

For MRSA, the Tru-D vegetative cycle, the 5-minute Moonbeam cycle, and the 3-minute Moonbeam cycle resulted in average CFU log10 reductions of 7.02 (95% CI, 7.02–7.02), 6.99 (95% CI, 6.95–7.02), and 6.58 (95% CI, 6.37–6.79), respectively (Fig. 1). The Tru-D vegetative and 5-minute Moonbeam cycles were similarly effective (P > .99), and both were more effective than the 3-minute Moonbeam cycle (P < .001 and P < .001, respectively). MRSA samples receiving direct UV-C exposure had significantly greater log10 reductions (6.95; 95% CI, 6.89–7.01) than did indirect exposure (6.67; 95% CI, 6.46–6.87; P < .05) (Fig. 2). For C. difficile, the Tru-D sporicidal, the 5-, and 3-minute Moonbeam cycles resulted in average CFU log10 reductions of 1.78 (95% CI, 1.43–2.12), 0.57 (95% CI, 0.33–0.81) and 0.64 (95% CI, 0.42–0.86), respectively (Fig. 1). Tru-D was significantly more effective than either the 3- or 5-minute Moonbeam cycles (P < .00). C. difficile samples receiving direct UV-C exposure had higher dosage and significantly greater log10 reductions (1.34; 95% CI, 1.10–1.58) than did indirect exposure (0.58; 95% CI, 0.31–0.86; P < .01) (Fig. 2). Conclusions: Use of the Tru-D vegetative cycle and the Moonbeam 3- and 5-minute cycles resulted in similar reductions in MRSA; both resulted in significantly greater reductions than the manufacturer’s recommended 3-minute Moonbeam cycle. Therefore, healthcare facilities should carefully evaluate manufacturer-recommended run times in their specific clinical setting. For C. difficile, the Tru-D sporicidal cycle was significantly more effective than either of the Moonbeam cycles, likely due to higher irradiation levels. As such, direct UV-C exposure resulted in greater average reductions than indirect exposure.

Funding: None

Disclosures: None