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BACKGROUND: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. METHODOLOGY/PRINCIPAL FINDINGS: We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. CONCLUSIONS/SIGNIFICANCE: Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination.

Abstract 820 Introduction: Hydroxyurea therapy has proven laboratory and clinical efficacy for ameliorating the signs and symptoms of sickle cell anemia, primarily by increasing the level of fetal hemoglobin (HbF). Virtually all treated pediatric patients will have symptomatic benefit and improvement in laboratory parameters associated with disease severity, including increased HbF and decreased white blood cell (WBC) count and lactate dehydrogenase (LDH). However, significant inter-patient variability exists in the maximum tolerated dose (MTD) of hydroxyurea and some patients have exaggerated toxicity (excessive myelosuppression) at relatively low doses. Similarly, there is substantial variation in the degree of response for relevant laboratory parameters such as HbF and LDH. We hypothesized that genetic polymorphisms may play an important role in the observed inter-patient variability for both hydroxyurea response and toxicity. Methods: Pediatric patients enrolled in the prospective Hydroxyurea Study of Long-term Effects (HUSTLE, NCT00305175) were eligible for analysis, including 72 subjects who had reached hydroxyurea MTD based on standardized criteria with dose escalation to mild bone marrow suppression. Candidate genes were selected based on a presumed effect on hydroxyurea pharmacokinetics (PK) or pharmacodynamics (PD) such as putative HbF modifiers, ribonucleotide reductase, and urea transporters. For these candidate genes, sequencing was performed for single nucleotide polymorphism (SNP) discovery. In addition, published genetic modifiers were studied to validate the proposed effect on hydroxyurea responses. Each SNP was first tested for Hardy-Weinberg equilibrium and then tested for association with three variables: MTD HbF, MTD LDH, and MTD hydroxyurea dose (mg/kg/day) using Least Squares Regression in dominant, co-dominant, and recessive genetic models. Results: The average age (mean ± 1SD) at hydroxyurea treatment initiation was 8.4 ± 4.9 years, with 58% males. The average MTD dose was 25.8 ± 4.2 mg/kg/day (median 26.7, range 14.2 – 35.5 mg/kg/day). The average MTD laboratory values for this cohort included hemoglobin (Hb) = 9.7 ± 1.1 gm/dL, mean corpuscular volume (MCV) = 110 ± 12 fL, HbF = 24.5 ± 7.4%, and LDH 432 ± 158 U/L, all significantly different than baseline values (p Summary and Conclusion: In the prospective HUSTLE study that includes standardized hydroxyurea dose escalation to MTD, significant associations were identified between candidate gene variants and the MTD phenotype for HbF, LDH, and hydroxyurea dose. SNPs in candidate genes previously reported to be important in basal HbF regulation were significant for MTD dose and novel SNPs in the urea transporter UTB were also significantly associated with MTD HbF. These results support the hypothesis that genetic modifiers play an important role in the treatment and toxicity responses to hydroxyurea therapy for children with SCA. Disclosures: Off Label Use: Hydroxyurea for children with sickle cell anemia.