Reassessment of the cadmium toxicological reference value for use in human health assessments of foods.

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd). The development of the TRV leveraged the FDA's previously published research including (1) a systematic review for adverse health effects associated with oral Cd exposure and (2) a human physiological based pharmacokinetic (PBPK) model adapted from Kjellstrom and Nordberg (1978) for use in reverse dosimetry applied to the U.S. population. Adverse effects of Cd on the bone and kidney are associated with similar points of departure (PODs) of approximately 0.50 µg Cd/g creatinine for females aged 50-60 based on available epidemiologic data. We also used the upper bound estimate of the renal cortical concentration (50 µg/g Cd) occurring in the U.S. population at 50 years of age as a POD. Based on the output from our reverse dosimetry PBPK Model, a range of 0.21-0.36 µg/kg bw/day was developed for the TRV. The animal data used for the animal TRV derivation (0.63-1.8 µg/kg bw/day) confirms biological plausibility for both the bone and kidney endpoints.

Quantitative risk assessment-epidemic curve prediction model for leafy green outbreak investigation.

The objective of this study was to leverage quantitative risk assessment to investigate possible root cause(s) of foodborne illness outbreaks related to Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) infections in leafy greens in the United States. To this end, we developed the FDA leafy green quantitative risk assessment epidemic curve prediction model (FDA-LG QRA-EC) that simulated the lettuce supply chain. The model was used to predict the number of reported illnesses and the epidemic curve associated with lettuce contaminated with STEC O157 for a wide range of scenarios representing various contamination conditions and facility processing/sanitation practices. Model predictions were generated for fresh-cut and whole lettuce, quantifying the differing impacts of facility processing and home preparation on predicted illnesses. Our model revealed that the timespan (i.e., number of days with at least one reported illness) and the peak (i.e., day with the most predicted number of reported illnesses) of the epidemic curve of a STEC O157-lettuce outbreak were not strongly influenced by facility processing/sanitation practices and were indications of contamination pattern among incoming lettuce batches received by the facility or distribution center. Through comparisons with observed number of illnesses from recent STEC O157-lettuce outbreaks, the model identified contamination conditions on incoming lettuce heads that could result in an outbreak of similar size, which can be used to narrow down potential root cause hypotheses.

Leveraging risk assessment for foodborne outbreak investigations: The Quantitative Risk Assessment-Epidemic Curve Prediction Model.

Root cause analysis can be used in foodborne illness outbreak investigations to determine the underlying causes of an outbreak and to help identify actions that could be taken to prevent future outbreaks. We developed a new tool, the Quantitative Risk Assessment-Epidemic Curve Prediction Model (QRA-EC), to assist with these goals and applied it to a case study to investigate and illustrate the utility of leveraging quantitative risk assessment to provide unique insights for foodborne illness outbreak root cause analysis. We used a 2019 Salmonella outbreak linked to melons as a case study to demonstrate the utility of this model (Centers for Disease Control and Prevention [CDC], 2019). The model was used to evaluate the impact of various root cause hypotheses (representing different contamination sources and food safety system failures in the melon supply chain) on the predicted number and timeline of illnesses. The predicted number of illnesses varied by contamination source and was strongly impacted by the prevalence and level of Salmonella contamination on the surface/inside of whole melons and inside contamination niches on equipment surfaces. The timeline of illnesses was most strongly impacted by equipment sanitation efficacy for contamination niches. Evaluations of a wide range of scenarios representing various potential root causes enabled us to identify which hypotheses, were likely to result in an outbreak of similar size and illness timeline to the 2019 Salmonella melon outbreak. The QRA-EC framework can be adapted to accommodate any food-pathogen pairs to provide insights for foodborne outbreak investigations.

Modeling the risk of low bone mass and osteoporosis as a function of urinary cadmium in U.S adults aged 50-79 years.

We developed an association model to estimate the risk of femoral neck low bone mass and osteoporosis from exposure to cadmium for women and men aged 50-79 in the U.S, as a function of the urinary cadmium (U-Cd) levels. We analyzed data from the NHANES 2005-2014 surveys and evaluated the relationship between U-Cd and femoral neck bone mineral density (BMD) using univariate and multivariate regression models with a combination of NHANES cycle, gender, age, smoking, race/ethnicity, height, body weight, body mass index, lean body mass, diabetes, kidney disease, physical activity, menopausal status, hormone replacement therapy, urinary lead, and prednisone intake as confounding variables. The regression coefficient between U-Cd and femoral neck BMD obtained with the best multivariate regression was used to develop an association model that can estimate the additional risk of low bone mass or osteoporosis in the population given a certain level of U-Cd. Results showed a linear relationship between U-Cd and BMD, conditional to body weight, where individuals with higher U-Cd had decreased BMD values. Our results do not support the hypothesis of a threshold for the effect of Cd on bone. Our model estimates that exposure to Cd results in an increase of 0.51 percentage points (CI95% 0.00, 0.92) of the population diagnosed with osteoporosis, compared to a theoretical absence of exposure. We estimate that 16% (CI95%: 0.00, 40%) of osteoporosis cases in the U.S. 50-79 aged population are a result of Cd exposure. This study presents the first continuous model estimating low bone mass and osteoporosis risk in the U.S. population given actual or potential changes in U-Cd levels. Our model will provide information to inform FDA's Closer to Zero initiative goal to reduce exposure to toxic elements.

Evaluation of Potential Impacts of Free Chlorine during Washing of Fresh-Cut Leafy Greens on Escherichia coli O157:H7 Cross-Contamination and Risk of Illness.

Addition of chlorine-based antimicrobial substances to fresh-cut leafy green wash water is done to minimize microbial cross-contamination during processing. We developed the FDA Leafy Green Risk Assessment Model (FDA-LGRAM) to quantify the impact of free chlorine concentration in wash water during fresh-cut lettuce processing on the extent of water-mediated cross-contamination between shredded lettuce and the associated risk of illness due to exposure to Escherichia coli O157:H7. At different contamination prevalence and levels of E. coli O157:H7 on incoming lettuce heads, the model compared the predicted prevalence of contaminated fresh-cut lettuce packages and the risk of illness per serving between: (1) a scenario where fresh-cut lettuce was packaged without washing; and (2) scenarios involving washing fresh-cut lettuce with different levels of free chlorine (0 ppm, 5 ppm, 10 ppm, 15 ppm, and 20 ppm) prior to packaging. Our results indicate that the free chlorine level in wash water has a substantial impact on the predicted prevalence of contaminated fresh-cut lettuce packages and the risk of illness associated with E. coli O157:H7 in fresh-cut lettuce. Results showed that the required level of free chlorine that can minimize water-mediated cross-contamination and reduce the corresponding risk of illness depended on contamination prevalence and levels of E. coli O157:H7 on incoming lettuce heads. Our model also indicated that the pathogen inactivation rate in wash water via free chlorine was a key model parameter that had a significant impact on the extent of cross-contamination during washing and the predicted associated risk of illness.

Risk Assessment of Norovirus Illness from Consumption of Raw Oysters in the United States and in Canada.

Human norovirus (NoV) is the leading cause of foodborne illness in the United States and Canada. Bivalve molluscan shellfish is one commodity commonly identified as being a vector of NoV. Bivalve molluscan shellfish are grown in waters that may be affected by contamination events, tend to bioaccumulate viruses, and are frequently eaten raw. In an effort to better assess the elements that contribute to potential risk of NoV infection and illness from consumption of bivalve molluscan shellfish, the U.S. Department of Health and Human Services/Food and Drug Administration (FDA), Health Canada (HC), the Canadian Food Inspection Agency (CFIA), and Environment and Climate Change Canada (ECCC) collaborated to conduct a quantitative risk assessment for NoV in bivalve molluscan shellfish, notably oysters. This study describes the model and scenarios developed and results obtained to assess the risk of NoV infection and illness from consumption of raw oysters harvested from a quasi-steady-state situation. Among the many factors that influence the risk of NoV illness for raw oyster consumers, the concentrations of NoV in the influent (raw, untreated) and effluent (treated) of wastewater treatment plants (WWTP) were identified to be the most important. Thus, mitigation and control strategies that limit the influence from human waste (WWTP outfalls) in oyster growing areas have a major influence on the risk of illness from consumption of those oysters.

A Predictive Model for Survival of Escherichia coli O157:H7 and Generic E. coli in Soil Amended with Untreated Animal Manure.

This study aimed at developing a predictive model that captures the influences of a variety of agricultural and environmental variables and is able to predict the concentrations of enteric bacteria in soil amended with untreated Biological Soil Amendments of Animal Origin (BSAAO) under dynamic conditions. We developed and validated a Random Forest model using data from a longitudinal field study conducted in mid-Atlantic United States investigating the survival of Escherichia coli O157:H7 and generic E. coli in soils amended with untreated dairy manure, horse manure, or poultry litter. Amendment type, days of rain since the previous sampling day, and soil moisture content were identified as the most influential agricultural and environmental variables impacting concentrations of viable E. coli O157:H7 and generic E. coli recovered from amended soils. Our model results also indicated that E. coli O157:H7 and generic E. coli declined at similar rates in amended soils under dynamic field conditions.The Random Forest model accurately predicted changes in viable E. coli concentrations over time under different agricultural and environmental conditions. Our model also accurately characterized the variability of E. coli concentration in amended soil over time by providing upper and lower prediction bound estimates. Cross-validation results indicated that our model can be potentially generalized to other geographic regions and incorporated into a risk assessment for evaluating the risks associated with application of untreated BSAAO. Our model can be validated for other regions and predictive performance also can be enhanced when data sets from additional geographic regions become available.

An Agent-Based Model for Pathogen Persistence and Cross-Contamination Dynamics in a Food Facility.

We used an agent-based modeling (ABM) framework and developed a mathematical model to explain the complex dynamics of microbial persistence and spread within a food facility and to aid risk managers in identifying effective mitigation options. The model explicitly considered personal hygiene practices by food handlers as well as their activities and simulated a spatially explicit dynamic system representing complex interaction patterns among food handlers, facility environment, and foods. To demonstrate the utility of the model in a decision-making context, we created a hypothetical case study and used it to compare different risk mitigation strategies for reducing contamination and spread of Listeria monocytogenes in a food facility. Model results indicated that areas with no direct contact with foods (e.g., loading dock and restroom) can serve as contamination niches and recontaminate areas that have direct contact with food products. Furthermore, food handlers' behaviors, including, for example, hygiene and sanitation practices, can impact the persistence of microbial contamination in the facility environment and the spread of contamination to prepared foods. Using this case study, we also demonstrated benefits of an ABM framework for addressing food safety in a complex system in which emergent system-level responses are predicted using a bottom-up approach that observes individual agents (e.g., food handlers) and their behaviors. Our model can be applied to a wide variety of pathogens, food commodities, and activity patterns to evaluate efficacy of food-safety management practices and quantify contamination reductions associated with proposed mitigation strategies in food facilities.

Differences Among Incidence Rates of Invasive Listeriosis in the U.S. FoodNet Population by Age, Sex, Race/Ethnicity, and Pregnancy Status, 2008-2016.

Listeria monocytogenes is a foodborne pathogen that disproportionally affects pregnant females, older adults, and immunocompromised individuals. Using U.S. Foodborne Diseases Active Surveillance Network (FoodNet) surveillance data, we examined listeriosis incidence rates and rate ratios (RRs) by age, sex, race/ethnicity, and pregnancy status across three periods from 2008 to 2016, as recent incidence trends in U.S. subgroups had not been evaluated. The invasive listeriosis annual incidence rate per 100,000 for 2008-2016 was 0.28 cases among the general population (excluding pregnant females), and 3.73 cases among pregnant females. For adults ≥70 years, the annual incidence rate per 100,000 was 1.33 cases. No significant change in estimated listeriosis incidence was found over the 2008-2016 period, except for a small, but significantly lower pregnancy-associated rate in 2011-2013 when compared with 2008-2010. Among the nonpregnancy-associated cases, RRs increased with age from 0.43 (95% confidence interval: 0.25-0.73) for 0- to 14-year olds to 44.9 (33.5-60.0) for ≥85-year olds, compared with 15- to 44-year olds. Males had an incidence of 1.28 (1.12-1.45) times that of females. Compared with non-Hispanic whites, the incidence was 1.57 (1.18-1.20) times higher among non-Hispanic Asians, 1.49 (1.22-1.83) among non-Hispanic blacks, and 1.73 (1.15-2.62) among Hispanics. Among females of childbearing age, non-Hispanic Asian females had 2.72 (1.51-4.89) and Hispanic females 3.13 (2.12-4.89) times higher incidence than non-Hispanic whites. We observed a higher percentage of deaths among older patient groups compared with 15- to 44-year olds. This study is the first characterizing higher RRs for listeriosis in the United States among non-Hispanic blacks and Asians compared with non-Hispanic whites. This information for public health risk managers may spur further research to understand if differences in listeriosis rates relate to differences in consumption patterns of foods with higher contamination levels, food handling practices, comorbidities, immunodeficiencies, health care access, or other factors.

Risk Assessment of Salmonellosis from Consumption of Alfalfa Sprouts and Evaluation of the Public Health Impact of Sprout Seed Treatment and Spent Irrigation Water Testing.

We developed a risk assessment of human salmonellosis associated with consumption of alfalfa sprouts in the United States to evaluate the public health impact of applying treatments to seeds (0-5-log10 reduction in Salmonella) and testing spent irrigation water (SIW) during production. The risk model considered variability and uncertainty in Salmonella contamination in seeds, Salmonella growth and spread during sprout production, sprout consumption, and Salmonella dose response. Based on an estimated prevalence of 2.35% for 6.8 kg seed batches and without interventions, the model predicted 76,600 (95% confidence interval (CI) 15,400-248,000) cases/year. Risk reduction (by 5- to 7-fold) predicted from a 1-log10 seed treatment alone was comparable to SIW testing alone, and each additional 1-log10 seed treatment was predicted to provide a greater risk reduction than SIW testing. A 3-log10 or a 5-log10 seed treatment reduced the predicted cases/year to 139 (95% CI 33-448) or 1.4 (95% CI <1-4.5), respectively. Combined with SIW testing, a 3-log10 or 5-log10 seed treatment reduced the cases/year to 45 (95% CI 10-146) or <1 (95% CI <1-1.5), respectively. If the SIW coverage was less complete (i.e., less representative), a smaller risk reduction was predicted, e.g., a combined 3-log10 seed treatment and SIW testing with 20% coverage resulted in an estimated 92 (95% CI 22-298) cases/year. Analysis of alternative scenarios using different assumptions for key model inputs showed that the predicted relative risk reductions are robust. This risk assessment provides a comprehensive approach for evaluating the public health impact of various interventions in a sprout production system.

Evaluation of Chlorine Treatment Levels for Inactivation of Human Norovirus and MS2 Bacteriophage during Sewage Treatment.

This study examined the inactivation of human norovirus (HuNoV) GI.1 and GII.4 by chlorine under conditions mimicking sewage treatment. Using a porcine gastric mucin-magnetic bead (PGM-MB) assay, no statistically significant loss in HuNoV binding (inactivation) was observed for secondary effluent treatments of ≤25 ppm total chlorine; for both strains, 50 and 100 ppm treatments resulted in ≤0.8-log10 unit and ≥3.9-log10 unit reductions, respectively. Treatments of 10, 25, 50, and 100 ppm chlorine inactivated 0.31, 1.35, >5, and >5 log10 units, respectively, of the norovirus indicator MS2 bacteriophage. Evaluation of treatment time indicated that the vast majority of MS2 and HuNoV inactivation occurred in the first 5 min for 0.2-µm-filtered, prechlorinated secondary effluent. Free chlorine measurements of secondary effluent seeded with MS2 and HuNoV demonstrated substantial oxidative burdens. With 25, 50, and 100 ppm treatments, free chlorine levels after 5 min of exposure ranged from 0.21 to 0.58 ppm, from 0.28 to 16.7 ppm, and from 11.6 to 53 ppm, respectively. At chlorine treatment levels of >50 ppm, statistically significant differences were observed between reductions for PGM-MB-bound HuNoV (potentially infectious) particles and those for unbound (noninfectious) HuNoV particles or total norovirus particles. While results suggested that MS2 and HuNoV (measured as PGM-MB binding) behave similarly, although not identically, both have limited susceptibility to chlorine treatments of ≤25 ppm total chlorine. Since sewage treatment is performed at ≤25 ppm total chlorine, targeting free chlorine levels of 0.5 to 1.0 ppm, these results suggest that traditional chlorine-based sewage treatment does not inactivate HuNoV efficiently.IMPORTANCE HuNoV is ubiquitous in sewage. A receptor binding assay was used to assess inactivation of HuNoV by chlorine-based sewage treatment, given that the virus cannot be routinely propagated in vitro Results reported here indicate that chlorine treatment of sewage is not effective for inactivating HuNoV unless chlorine levels are above those routinely used for sewage treatment.

Quantitative Risk Assessment of Norovirus Transmission in Food Establishments: Evaluating the Impact of Intervention Strategies and Food Employee Behavior on the Risk Associated with Norovirus in Foods.

We developed a quantitative risk assessment model using a discrete event framework to quantify and study the risk associated with norovirus transmission to consumers through food contaminated by infected food employees in a retail food setting. This study focused on the impact of ill food workers experiencing symptoms of diarrhea and vomiting and potential control measures for the transmission of norovirus to foods. The model examined the behavior of food employees regarding exclusion from work while ill and after symptom resolution and preventive measures limiting food contamination during preparation. The mean numbers of infected customers estimated for 21 scenarios were compared to the estimate for a baseline scenario representing current practices. Results show that prevention strategies examined could not prevent norovirus transmission to food when a symptomatic employee was present in the food establishment. Compliance with exclusion from work of symptomatic food employees is thus critical, with an estimated range of 75-226% of the baseline mean for full to no compliance, respectively. Results also suggest that efficient handwashing, handwashing frequency associated with gloving compliance, and elimination of contact between hands, faucets, and door handles in restrooms reduced the mean number of infected customers to 58%, 62%, and 75% of the baseline, respectively. This study provides quantitative data to evaluate the relative efficacy of policy and practices at retail to reduce norovirus illnesses and provides new insights into the interactions and interplay of prevention strategies and compliance in reducing transmission of foodborne norovirus.

Changing US Population Demographics: What Does This Mean for Listeriosis Incidence and Exposure?

Listeria monocytogenes is an important cause of foodborne illness hospitalization, fetal loss, and death in the United States. Listeriosis incidence rate varies significantly among population subgroups with pregnant women, older persons, and the Hispanic population having increased relative risks compared with the other subpopulations. Using estimated rates of listeriosis per subpopulation based on FoodNet data from 2004 to 2009, we evaluate the expected number of cases and incidence rates of listeriosis in the US population and the pregnant women subpopulation as the demographic composition changes over time with respect to ethnicity, pregnancy status, and age distribution. If the incidence rate per subpopulation is held constant, the overall US population listeriosis incidence rate would increase from 0.25 per 100,000 (95% confidence interval [CI]: 0.19-0.34) in 2010 to 0.28 (95% CI: 0.22-0.38) in 2020 and 0.32 (95% CI: 0.25-0.43) in 2030, because of the changes in the population structure. Similarly, the pregnancy-associated incidence rate is expected to increase from 4.0 per 100,000 pregnant women (95% CI: 2.5-6.5) in 2010 to 4.1 (95% CI: 2.6-6.7) in 2020 and 4.4 (95% CI: 2.7-7.2) in 2030 as the proportion of Hispanic pregnant women increases. We further estimate that a reduction of 12% in the exposure of the US population to L. monocytogenes would be needed to maintain a constant incidence rate from 2010 to 2020 (current trend), assuming infectivity (strain virulence distribution and individual susceptibility) is unchanged. To reduce the overall US population incidence rate by one-third (Healthy People 2020 goal) would require a reduction in exposure (or infectivity) to L. monocytogenes of 48% over the same time period. Reduction/elimination in exposure of pregnant and Hispanic subpopulations alone could not meet this target. This information may be useful in setting public health targets, developing risk management options, and in interpreting trends in the public health burden of foodborne listeriosis in the United States.

Infectious Dose of Listeria monocytogenes in Outbreak Linked to Ice Cream, United States, 2015.

The relationship between the number of ingested Listeria monocytogenes cells in food and the likelihood of developing listeriosis is not well understood. Data from an outbreak of listeriosis linked to milkshakes made from ice cream produced in 1 factory showed that contaminated products were distributed widely to the public without any reported cases, except for 4 cases of severe illness in persons who were highly susceptible. The ingestion of high doses of L. monocytogenes by these patients infected through milkshakes was unlikely if possible additional contamination associated with the preparation of the milkshake is ruled out. This outbreak illustrated that the vast majority of the population did not become ill after ingesting a low level of L. monocytogenes but raises the question of listeriosis cases in highly susceptible persons after distribution of low-level contaminated products that did not support the growth of this pathogen.

Meta-Analysis of the Reduction of Norovirus and Male-Specific Coliphage Concentrations in Wastewater Treatment Plants.

Human norovirus (NoV) is the leading cause of foodborne illness in the United States and Canada. Wastewater treatment plant (WWTP) effluents impacting bivalve mollusk-growing areas are potential sources of NoV contamination. We have developed a meta-analysis that evaluates WWTP influent concentrations and log10 reductions of NoV genotype I (NoV GI; in numbers of genome copies per liter [gc/liter]), NoV genotype II (NoV GII; in gc/liter), and male-specific coliphage (MSC; in number of PFU per liter), a proposed viral surrogate for NoV. The meta-analysis included relevant data (2,943 measurements) reported in the scientific literature through September 2013 and previously unpublished surveillance data from the United States and Canada. Model results indicated that the mean WWTP influent concentration of NoV GII (3.9 log10 gc/liter; 95% credible interval [CI], 3.5, 4.3 log10 gc/liter) is larger than the value for NoV GI (1.5 log10 gc/liter; 95% CI, 0.4, 2.4 log10 gc/liter), with large variations occurring from one WWTP to another. For WWTPs with mechanical systems and chlorine disinfection, mean log10 reductions were -2.4 log10 gc/liter (95% CI, -3.9, -1.1 log10 gc/liter) for NoV GI, -2.7 log10 gc/liter (95% CI, -3.6, -1.9 log10 gc/liter) for NoV GII, and -2.9 log10 PFU per liter (95% CI, -3.4, -2.4 log10 PFU per liter) for MSCs. Comparable values for WWTPs with lagoon systems and chlorine disinfection were -1.4 log10 gc/liter (95% CI, -3.3, 0.5 log10 gc/liter) for NoV GI, -1.7 log10 gc/liter (95% CI, -3.1, -0.3 log10 gc/liter) for NoV GII, and -3.6 log10 PFU per liter (95% CI, -4.8, -2.4 PFU per liter) for MSCs. Within WWTPs, correlations exist between mean NoV GI and NoV GII influent concentrations and between the mean log10 reduction in NoV GII and the mean log10 reduction in MSCs.

Prevalence, serotype diversity, and antimicrobial resistance of Salmonella in imported shipments of spice offered for entry to the United States, FY2007-FY2009.

In response to increased concerns about spice safety, the U.S. FDA initiated research to characterize the prevalence of Salmonella in imported spices. Shipments of imported spices offered for entry to the United Sates were sampled during the fiscal years 2007-2009. The mean shipment prevalence for Salmonella was 0.066 (95% CI 0.057-0.076). A wide diversity of Salmonella serotypes was isolated from spices; no single serotype constituted more than 7% of the isolates. A small percentage of spice shipments were contaminated with antimicrobial-resistant Salmonella strains (8.3%). Trends in shipment prevalence for Salmonella associated with spice properties, extent of processing, and export country, were examined. A larger proportion of shipments of spices derived from fruit/seeds or leaves of plants were contaminated than those derived from the bark/flower of spice plants. Salmonella prevalence was larger for shipments of ground/cracked capsicum and coriander than for shipments of their whole spice counterparts. No difference in prevalence was observed between shipments of spice blends and non-blended spices. Some shipments reported to have been subjected to a pathogen reduction treatment prior to being offered for U.S. entry were found contaminated. Statistical differences in Salmonella shipment prevalence were also identified on the basis of export country.

Foodborne illness outbreaks from microbial contaminants in spices, 1973-2010.

This review identified fourteen reported illness outbreaks attributed to consumption of pathogen-contaminated spice during the period 1973-2010. Countries reporting outbreaks included Canada, Denmark, England and Wales, France, Germany, New Zealand, Norway, Serbia, and the United States. Together, these outbreaks resulted in 1946 reported human illnesses, 128 hospitalizations and two deaths. Infants/children were the primary population segments impacted by 36% (5/14) of spice-attributed outbreaks. Four outbreaks were associated with multiple organisms. Salmonella enterica subspecies enterica was identified as the causative agent in 71% (10/14) of outbreaks, accounting for 87% of reported illnesses. Bacillus spp. was identified as the causative agent in 29% (4/10) of outbreaks, accounting for 13% of illnesses. 71% (10/14) of outbreaks were associated with spices classified as fruits or seeds of the source plant. Consumption of ready-to-eat foods prepared with spices applied after the final food manufacturing pathogen reduction step accounted for 70% of illnesses. Pathogen growth in spiced food is suspected to have played a role in some outbreaks, but it was not likely a contributing factor in three of the larger Salmonella outbreaks, which involved low-moisture foods. Root causes of spice contamination included contributions from both early and late stages of the farm-to-table continuum.

Prevalence, level and distribution of Salmonella in shipments of imported capsicum and sesame seed spice offered for entry to the United States: observations and modeling results.

In response to increased concerns about spice safety, the United States Food and Drug Administration (FDA) initiated research to characterize the prevalence and levels of Salmonella in imported spices. 299 imported dried capsicum shipments and 233 imported sesame seed shipments offered for entry to the United States were sampled. Observed Salmonella shipment prevalence was 3.3% (1500 g examined; 95% CI 1.6-6.1%) for capsicum and 9.9% (1500 g; 95% Confidence Interval (CI) 6.3-14%) for sesame seed. Within shipment contamination was not inconsistent with a Poisson distribution. Shipment mean Salmonella level estimates among contaminated shipments ranged from 6 × 10(-4) to 0.09 (capsicum) or 6 × 10(-4) to 0.04 (sesame seed) MPN/g. A gamma-Poisson model provided the best fit to observed data for both imported shipments of capsicum and imported shipments of sesame seed sampled in this study among the six parametric models considered. Shipment mean levels of Salmonella vary widely between shipments; many contaminated shipments contain low levels of contamination. Examination of sampling plan efficacy for identifying contaminated spice shipments from these distributions indicates that sample size of spice examined is critical. Sampling protocols examining 25 g samples are predicted to be able to identify a small fraction of contaminated shipments of imported capsicum or sesame seeds.

Prevalence of Listeria monocytogenes, Salmonella spp., Shiga toxin-producing Escherichia coli, and Campylobacter spp. in raw milk in the United States between 2000 and 2019: A systematic review and meta-analysis.

Raw (unpasteurized) milk is available for sale and direct human consumption within some states in the United States (US); it cannot be sold or distributed in interstate commerce. Raw milk may contain pathogenic microorganisms that, when consumed, may cause illness and sometimes may result in death. No comprehensive review for prevalence and levels of the major bacterial pathogens in raw milk in the US exists. The objective of the present research was to systematically review the scientific literature published from 2000 to 2019 to estimate the prevalence and levels of Listeria monocytogenes, Salmonella spp., Shiga toxin-producing Escherichia coli (STEC), and Campylobacter spp. in raw milk in the US. Peer-reviewed studies were retrieved systematically from PubMed®, Embase®, and Web of ScienceTM. The unique complete nonduplicate references were uploaded into the Health Assessment Work Collaborative (HAWC). Based on the selection criteria, twenty studies were included in the systematic review and meta-analysis. Comprehensive Meta-Analysis (CMA) was used for statistical analyses, specifically, random effects meta-analyses were used to synthesize raw bulk tank milk (BTM) and milk filters (MF) data. Data from studies using culture and non-culture-based detection methods were included. Forest plots generated in CMA (Biostat, Englewood, NJ) were used to visualize the results. The average prevalence (event rate) of L. monocytogenes, Salmonella spp., STEC, and Campylobacter spp. in raw BTM in the US was estimated at 4.3% (95% confidence intervals [CIs], 2.8-6.5%), 3.6% (95% CIs, 2.0-6.2%), 4.3% (95% CIs, 2.4-7.4%), and 6.0% (95% CIs, 3.2-10.9%), respectively. Estimated prevalence was generally larger in MF than in BTM. There was not enough data to perform a meta-analysis for the prevalence or levels of pathogens in raw milk from retail establishments or other milk categories.

Cadmium physiologically based pharmacokinetic (PBPK) models for forward and reverse dosimetry: Review, evaluation, and adaptation to the U.S. population.

The goal of this study was to assess a cadmium (Cd) physiologically based pharmacokinetic (PBPK) model to evaluate Cd toxicological reference values (e.g. reference dose, tolerable intake, minimum risk level) adapted to the U.S. population. We reviewed and evaluated previously published Cd PBPK models and developed further adaptations to the 1978 Kjellström and Nordberg (KN) model. Specifically, we propose adaptations with updated U.S.-specific bodyweight, kidney weight and creatinine excretion models by using NHANES data as well as a stochastic PBPK model that provides credible intervals of uncertainty around mean populational estimates. We provide our model review and adaptations as well as present estimates from the newly adapted models using observed U.S. urinary Cd values as a function of gender and age and given dietary exposure as evaluated from NHANES/WWEIA and U.S. Total Diet Study data. Results show all newly adapted models provide acceptable mean estimates of urinary Cd in the U.S. The stochastic model provides credible intervals to further inform regulatory decision making. Validation of the estimated K-Cd concentration values was not possible as data for a representative population was not available. We developed a web-based tool implementing these models and other potential adaptations to facilitate PBPK model estimate comparisons.