Foodborne disease outbreaks in flour and flour-based food products from microbial pathogens in the United States, and their health economic burden.

The most comprehensive and inclusive estimates for the economic burden of foodborne illness yield values as high as $97.4 billion USD annually. However, broad incidence and cost estimates have limited use if they cannot be attributed to specific foods, for the purposes of food safety control. In this study, we estimated the economic burden of foodborne illnesses resulting from flour and flour-based food products in the United States from the years 2001 to 2021. The outbreak, illness burden, and health economic data are combined to generate these estimates. Our model combined outbreak data with published Centers for Disease Control and Prevention multipliers to estimate the annual number of illnesses associated with flour-borne pathogens. We then integrated illness severity data with an updated economic model that accounts for costs related to medical care, productivity loss, loss of life, along with the quality of life loss that entails pain and suffering. In total, 752 cases and 223 hospitalizations from flour-related illnesses were reported from 2001 to 2021, with an average of 37.6 cases of reported cases annually. However, the actual number of cases, accounting for underreporting and underdiagnosis, can be as high as 19,440 annually. Pathogens involved in these outbreaks are Salmonella, E. coli O157:H7, and E. coli O121. Our estimates suggest average annual economic losses, including healthy years of life lost, of $108 and $258 million using two alternative models.

Environmental and economic concerns surrounding restrictions on glyphosate use in corn.

Since the commercialization of transgenic glyphosate-tolerant (GT) crops in the mid-1990s, glyphosate has become the dominant herbicide to control weeds in corn, soybean, and other crops in the United States and elsewhere. However, recent public concerns over its potential carcinogenicity in humans have generated calls for glyphosate-restricting policies. Should a policy to restrict glyphosate use, such as a glyphosate tax, be implemented? The decision involves two types of tradeoffs: human health and environmental (HH-E) impacts versus market economic impacts, and the use of glyphosate versus alternative herbicides, where the alternatives potentially have more serious adverse HH-E effects. Accounting for farmers' weed management choices, we provide empirical evaluation of the HH-E welfare and market economic welfare effects of a glyphosate use restriction policy on US corn production. Under a glyphosate tax, farmers would substitute glyphosate for a combination of other herbicides. Should a 10% glyphosate tax be imposed, then the most conservative welfare estimate is a net HH-E welfare gain with a monetized value of US$6 million per annum but also a net market economic loss of US$98 million per annum in the United States, which translates into a net loss in social welfare. This result of overall welfare loss is robust to a wide range of tax rates considered, from 10 to 50%, and to multiple scenarios of glyphosate's HH-E effects, which are the primary sources of uncertainties about glyphosate's effects.

Cost-effectiveness of a wetting method intervention to reduce cassava cyanide-related cognitive impairment in children.

Cassava cyanide-related neurocognitive impairment may persist for years in Central African children who rely on cassava as a dietary staple. In the Democratic Republic of the Congo, a cassava processing method, the 'wetting method', reduced cyanide in cassava, prevented konzo, and proved a cost-effective intervention to improve children's cognitive development. Scaling up use of the wetting method may help prevent neurocognitive impairment in millions of at-risk children in sub-Saharan Africa.

Forty Years of Food Safety Risk Assessment: A History and Analysis.

Before the founding of the Society for Risk Analysis (SRA) in 1980, food safety in the United States had long been a concern, but there was a lack of systematic methods to assess food-related risks. In 1906, the U.S. Congress passed, and President Roosevelt signed, the Pure Food and Drug Act and the Meat Inspection Act to regulate food safety at the federal level. This Act followed the publication of multiple reports of food contamination, culminating in Upton Sinclair's novel The Jungle, which highlighted food and worker abuses in the meatpacking industry. Later in the 20th century, important developments in agricultural and food technology greatly increased food production. But chemical exposures from agricultural and other practices resulted in major amendments to federal food laws, including the Delaney Clause, aimed specifically at cancer-causing chemicals. Later in the 20th century, when quantitative risk assessment methods were given greater scientific status in a seminal National Research Council report, food safety risk assessment became more systematized. Additionally, in these last 40 years, food safety research has resulted in increased understanding of a range of health effects from foodborne chemicals, and technological developments have improved U.S. food safety from farm to fork by offering new ways to manage risks. We discuss the history of food safety and the role risk analysis has played in its evolution, starting from over a century ago, but focusing on the last 40 years. While we focus on chemical risk assessment in the U.S., we also discuss microbial risk assessment and international food safety.

The Impact of Bt Corn on Aflatoxin-Related Insurance Claims in the United States.

Previous field studies have reached no collective consensus on whether Bt corn, the most commonly planted transgenic crop worldwide, has significantly lower aflatoxin levels than non-Bt isolines. Aflatoxin, a mycotoxin contaminating corn and other commodities, causes liver cancer in humans and can pose severe economic losses to farmers. We found that from 2001-2016, a significant inverse correlation existed between Bt corn planting and aflatoxin-related insurance claims in the United States, when controlling for temperature and drought. Estimated benefits of aflatoxin reduction resulting from Bt corn planting are about $120 million to $167 million per year over 16 states on average. These results suggest that Bt corn use is an important strategy in reducing aflatoxin risk, with corresponding economic benefits. If the same principles hold true in other world regions, then Bt corn hybrids adapted to diverse agronomic regions may have a role in reducing aflatoxin in areas prone to high aflatoxin contamination, and where corn is a dietary staple.

Risk assessment of aflatoxin-related liver cancer in Bangladesh.

Aflatoxins are mycotoxins (fungal toxins) produced by Aspergillus species in variety of food commodities. Consumption of aflatoxin-contaminated food can cause adverse health effects, including liver cancer. Aflatoxin exposure is usually higher in hot and humid countries. Previous biomarker-based studies have indicated significant exposure to aflatoxins among the Bangladeshi population. Recently, high aflatoxin levels were reported in dates, which are consumed in large quantities during the month of Ramadan in Bangladesh and other Muslim countries. Bangladesh has recently enacted aflatoxin regulation in foods. In this study, we determined the risk of aflatoxin-related liver cancer among the Bangladeshi population based on the average dietary intakes of different aflatoxin contaminated foods, accounting for the synergistic impacts of aflatoxin with chronic hepatitis B viral infection in inducing cancer. We also determined whether the new aflatoxin regulations in Bangladesh could significantly reduce the risk of liver cancer. The mean number of cancer cases per year caused by dietary aflatoxin exposure in Bangladesh was estimated at about 1311, or 43.9% of the total annual liver cancer cases in Bangladesh. The new aflatoxin regulations do not appear likely to significantly reduce the risk of liver cancer in the country.

A risk assessment of dietary Ochratoxin a in the United States.

Ochratoxin A (OTA) is a mycotoxin (fungal toxin) found in multiple foodstuffs. Because OTA has been shown to cause kidney disease in multiple animal models, several governmental bodies around the world have set maximum allowable levels of OTA in different foods and beverages. In this study, we conducted the first exposure and risk assessment study of OTA for the United States' population. A variety of commodities from grocery stores across the US were sampled for OTA over a 2-year period. OTA exposure was calculated from the OTA concentrations in foodstuffs and consumption data for different age ranges. We calculated the margin of safety (MOS) for individual age groups across all commodities of interest. Most food and beverage samples were found to have non-detectable OTA; however, some samples of dried fruits, breakfast cereals, infant cereals, and cocoa had detectable OTA. The lifetime MOS in the US population within the upper 95% of consumers of all possible commodities was >1, indicating negligible risk. In the US, OTA exposure is highest in infants and young children who consume large amounts of oat-based cereals. Even without OTA standards in the US, exposures would not be associated with significant risk of adverse effects.

Potential economic losses to the US corn industry from aflatoxin contamination.

Mycotoxins, toxins produced by fungi that colonise food crops, can pose a heavy economic burden to the US corn industry. In terms of economic burden, aflatoxins are the most problematic mycotoxins in US agriculture. Estimates of their market impacts are important in determining the benefits of implementing mitigation strategies within the US corn industry, and the value of strategies to mitigate mycotoxin problems. Additionally, climate change may cause increases in aflatoxin contamination in corn, greatly affecting the economy of the US Midwest and all sectors in the United States and worldwide that rely upon its corn production. We propose two separate models for estimating the potential market loss to the corn industry from aflatoxin contamination, in the case of potential near-future climate scenarios (based on aflatoxin levels in Midwest corn in warm summers in the last decade). One model uses the probability of acceptance based on operating characteristic (OC) curves for aflatoxin sampling and testing, while the other employs partial equilibrium economic analysis, assuming no Type 1 or Type 2 errors, to estimate losses due to proportions of lots above the US Food and Drug Administration (USFDA) aflatoxin action levels. We estimate that aflatoxin contamination could cause losses to the corn industry ranging from US$52.1 million to US$1.68 billion annually in the United States, if climate change causes more regular aflatoxin contamination in the Corn Belt as was experienced in years such as 2012. The wide range represents the natural variability in aflatoxin contamination from year to year in US corn, with higher losses representative of warmer years.

Methodological Framework for World Health Organization Estimates of the Global Burden of Foodborne Disease.

BACKGROUND: The Foodborne Disease Burden Epidemiology Reference Group (FERG) was established in 2007 by the World Health Organization to estimate the global burden of foodborne diseases (FBDs). This paper describes the methodological framework developed by FERG's Computational Task Force to transform epidemiological information into FBD burden estimates. METHODS AND FINDINGS: The global and regional burden of 31 FBDs was quantified, along with limited estimates for 5 other FBDs, using Disability-Adjusted Life Years in a hazard- and incidence-based approach. To accomplish this task, the following workflow was defined: outline of disease models and collection of epidemiological data; design and completion of a database template; development of an imputation model; identification of disability weights; probabilistic burden assessment; and estimating the proportion of the disease burden by each hazard that is attributable to exposure by food (i.e., source attribution). All computations were performed in R and the different functions were compiled in the R package 'FERG'. Traceability and transparency were ensured by sharing results and methods in an interactive way with all FERG members throughout the process. CONCLUSIONS: We developed a comprehensive framework for estimating the global burden of FBDs, in which methodological simplicity and transparency were key elements. All the tools developed have been made available and can be translated into a user-friendly national toolkit for studying and monitoring food safety at the local level.

Data-driven methods for imputing national-level incidence in global burden of disease studies.

OBJECTIVE: To develop transparent and reproducible methods for imputing missing data on disease incidence at national-level for the year 2005. METHODS: We compared several models for imputing missing country-level incidence rates for two foodborne diseases - congenital toxoplasmosis and aflatoxin-related hepatocellular carcinoma. Missing values were assumed to be missing at random. Predictor variables were selected using least absolute shrinkage and selection operator regression. We compared the predictive performance of naive extrapolation approaches and Bayesian random and mixed-effects regression models. Leave-one-out cross-validation was used to evaluate model accuracy. FINDINGS: The predictive accuracy of the Bayesian mixed-effects models was significantly better than that of the naive extrapolation method for one of the two disease models. However, Bayesian mixed-effects models produced wider prediction intervals for both data sets. CONCLUSION: Several approaches are available for imputing missing data at national level. Strengths of a hierarchical regression approach for this type of task are the ability to derive estimates from other similar countries, transparency, computational efficiency and ease of interpretation. The inclusion of informative covariates may improve model performance, but results should be appraised carefully.

The global burden of disease for skin, lung, and bladder cancer caused by arsenic in food.

BACKGROUND: Arsenic is a ubiquitous, naturally occurring metalloid that poses a significant human cancer risk. While water consumption provides the majority of human exposure, millions of individuals worldwide are significantly exposed to arsenic through naturally occurring levels of arsenic in grains, vegetables, meats and fish, as well as through food processed with water containing arsenic. Thus, we estimated the global burdens of disease for bladder, lung, and skin cancers attributable to inorganic arsenic in food. METHODS: To determine foodborne inorganic arsenic exposures worldwide, we used World Health Organization estimates of food consumption in thirteen country clusters, in conjunction with reported measurements of total and inorganic arsenic in different foods. We estimated slope factors for arsenic-related bladder and lung cancers, and used the U.S. Environmental Protection Agency skin cancer slope factor, to calculate the annual risk of the cancer incidence in males and females within each country cluster. RESULTS: We estimated that each year 9,129 to 119,176 additional cases of bladder cancer, 11,844 to 121,442 of lung cancer, and 10,729 to 110,015 of skin cancer worldwide are attributable to inorganic arsenic in food. CONCLUSIONS: These estimates indicate that foodborne arsenic exposure causes a significant global burden of human disease. IMPACT: Estimating the global cancer burden caused by arsenic exposure in food will support policies that reduce exposure to disease-promoting environmental hazards.

Public health impacts of foodborne mycotoxins.

Mycotoxins are toxic and carcinogenic metabolites produced by fungi that colonize food crops. The most agriculturally important mycotoxins known today are aflatoxins, which cause liver cancer and have also been implicated in child growth impairment and acute toxicoses; fumonisins, which have been associated with esophageal cancer (EC) and neural tube defects (NTDs); deoxynivalenol (DON) and other trichothecenes, which are immunotoxic and cause gastroenteritis; and ochratoxin A (OTA), which has been associated with renal diseases. This review describes the adverse human health impacts associated with these major groups of mycotoxins. First, we provide background on the fungi that produce these different mycotoxins and on the food crops commonly infected. Then, we describe each group of mycotoxins in greater detail, as well as the adverse effects associated with each mycotoxin and the populations worldwide at risk. We conclude with a brief discussion on estimations of global burden of disease caused by dietary mycotoxin exposure.

Global risk assessment of aflatoxins in maize and peanuts: are regulatory standards adequately protective?

The aflatoxins are a group of fungal metabolites that contaminate a variety of staple crops, including maize and peanuts, and cause an array of acute and chronic human health effects. Aflatoxin B1 in particular is a potent liver carcinogen, and hepatocellular carcinoma (HCC) risk is multiplicatively higher for individuals exposed to both aflatoxin and chronic infection with hepatitis B virus (HBV). In this work, we sought to answer the question: do current aflatoxin regulatory standards around the world adequately protect human health? Depending upon the level of protection desired, the answer to this question varies. Currently, most nations have a maximum tolerable level of total aflatoxins in maize and peanuts ranging from 4 to 20ng/g. If the level of protection desired is that aflatoxin exposures would not increase lifetime HCC risk by more than 1 in 100,000 cases in the population, then most current regulatory standards are not adequately protective even if enforced, especially in low-income countries where large amounts of maize and peanuts are consumed and HBV prevalence is high. At the protection level of 1 in 10,000 lifetime HCC cases in the population, however, almost all aflatoxin regulations worldwide are adequately protective, with the exception of several nations in Africa and Latin America.

Risk assessment of upper tract urothelial carcinoma related to aristolochic acid.

BACKGROUND: Aristolochic acid is a toxin found in plants of the genus Aristolochia, to which humans can be exposed either through certain Chinese herbal medicines or through inadvertent commingling with food crops. Our objective was to estimate cumulative exposures of aristolochic acid associated with increased risk of end-stage renal disease (ESRD), and to conduct a systematic review and meta-analysis on aristolochic acid-induced upper tract urothelial carcinoma (UUC). METHODS: Using epidemiologic studies on aristolochic acid-related disease from multiple different regions of the world, a systematic review was conducted in which relative risks (RR), HRs, and ORs were derived or extracted directly, and a meta-analysis was conducted. One study was used to estimate a benchmark dose lower confidence limit (BMDL) for aristolochic acid-related ESRD. RESULTS: Mean values for risk ratios, ORs, RRs, or HRs, of UUC caused by aristolochic acid ranged from 1 to 49. A meta-analysis of these studies resulted in a pooled OR of 5.97 [95% confidence interval (CI), 2.78-12.84] for this aristolochic acid-related cancer. The obtained BMDL for aristolochic acid-related ESRD was 0.42 g cumulative aristolochic acid exposure. CONCLUSIONS: Aristolochic acid exposure is significantly associated with an increased risk of UUC, and there is a dose-dependent relationship between cumulative aristolochic acid exposure and ESRD risk. IMPACT: Individuals who use certain Chinese herbal medicines may significantly increase their risk of developing UUC and/or ESRD, as would individuals who are inadvertently exposed to aristolochic acid through commingling of Aristolochia plants with harvested food crops.

Aflatoxin regulations in a network of global maize trade.

Worldwide, food supplies often contain unavoidable contaminants, many of which adversely affect health and hence are subject to regulations of maximum tolerable levels in food. These regulations differ from nation to nation, and may affect patterns of food trade. We soughtto determine whether there is an association between nations' food safety regulations and global food trade patterns, with implications for public health and policymaking. We developed a network model of maize trade around the world. From maize import/export data for 217 nations from 2000-2009, we calculated basic statistics on volumes of trade; then examined how regulations of aflatoxin, a common contaminant of maize, are similar or different between pairs of nations engaging in significant amounts of maize trade. Globally, market segregation appears to occur among clusters of nations. The United States is at the center of one cluster; European countries make up another cluster with hardly any maize trade with the US; and Argentina, Brazil, and China export maize all over the world. Pairs of nations trading large amounts of maize have very similar aflatoxin regulations: nations with strict standards tend to trade maize with each other, while nations with more relaxed standards tend to trade maize with each other. Rarely among the top pairs of maize-trading nations do total aflatoxin standards (standards based on the sum of the levels of aflatoxins B(1), B(2), G(1), and G(2)) differ by more than 5 µg/kg. These results suggest that, globally, separate maize trading communities emerge; and nations tend to trade with other nations that have very similar food safety standards.

Evaluating the technical feasibility of aflatoxin risk reduction strategies in Africa.

Public health interventions must be readily accepted by their target populations to have any meaningful impact and must have financial and infrastructural support to be feasible in the parts of the world where they are most needed. At the same time, these interventions must be assessed for potential unintended consequences, either to the environment or to human health. In this paper, we evaluate the technical feasibility of interventions to control aflatoxin risk, to be potentially deployed in parts of Africa where aflatoxin exposure poses a significant public health concern. We have applied a conceptual framework for feasibility to four interventions, one associated with each of four different stages of aflatoxin risk: biocontrol (pre-harvest), a post-harvest intervention package (post-harvest), NovaSil clay (dietary), and hepatitis B vaccination (clinical). For each intervention, we have assessed the following four components of technical feasibility: (1) characteristics of the basic intervention, (2) characteristics of delivery, (3) requirements on government capacity, and (4) usage characteristics. We propose ways in which feasibility of each intervention is currently high or low from the perspective of adoption in Africa, how public education is crucial for each of these interventions to succeed, and how to align economic incentives to make the interventions more suitable for less developed countries.

Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment.

BACKGROUND: Hepatocellular carcinoma (HCC), or liver cancer, is the third leading cause of cancer deaths worldwide, with prevalence 16-32 times higher in developing countries than in developed countries. Aflatoxin, a contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus in maize and nuts, is a known human liver carcinogen. OBJECTIVES: We sought to determine the global burden of HCC attributable to aflatoxin exposure. METHODS: We conducted a quantitative cancer risk assessment, for which we collected global data on food-borne aflatoxin levels, consumption of aflatoxin-contaminated foods, and hepatitis B virus (HBV) prevalence. We calculated the cancer potency of aflatoxin for HBV-postive and HBV-negative individuals, as well as the uncertainty in all variables, to estimate the global burden of aflatoxin-related HCC. RESULTS: Of the 550,000-600,000 new HCC cases worldwide each year, about 25,200-155,000 may be attributable to aflatoxin exposure. Most cases occur in sub-Saharan Africa, Southeast Asia, and China where populations suffer from both high HBV prevalence and largely uncontrolled aflatoxin exposure in food. CONCLUSIONS: Aflatoxin may play a causative role in 4.6-28.2% of all global HCC cases.

Problem formulation in the environmental risk assessment for genetically modified plants.

Problem formulation is the first step in environmental risk assessment (ERA) where policy goals, scope, assessment endpoints, and methodology are distilled to an explicitly stated problem and approach for analysis. The consistency and utility of ERAs for genetically modified (GM) plants can be improved through rigorous problem formulation (PF), producing an analysis plan that describes relevant exposure scenarios and the potential consequences of these scenarios. A properly executed PF assures the relevance of ERA outcomes for decision-making. Adopting a harmonized approach to problem formulation should bring about greater uniformity in the ERA process for GM plants among regulatory regimes globally. This paper is the product of an international expert group convened by the International Life Sciences Institute (ILSI) Research Foundation.

Mycotoxins in ethanol co-products: modeling economic impacts on the livestock industry and management strategies.

The rapidly expanding U.S. ethanol industry is generating a growing supply of co-products, mostly in the form of dried distillers' grain and solubles (DDGS) or wet distillers' grains (WDG). In the United States, 90% of the co-products of maize-based ethanol are fed to livestock. An unintended consequence is that animals are likely to be fed higher levels of mycotoxins, which are concentrated up to three times in DDGS compared to grain. The model developed in this study estimates current losses to the swine industry from weight gain reduction due to fumonisins in added DDGS at $9 million ($2-18 million) annually. If there is complete market penetration of DDGS in swine feed with 20% DDGS inclusion in swine feed and fumonisins are not controlled, losses may increase to $147 million ($29-293 million) annually. These values represent only those losses attributable to one mycotoxin on one adverse outcome on one species. The total loss due to mycotoxins in DDGS could be significantly higher due to additive or multiplicative effects of multiple mycotoxins on animal health. If mycotoxin surveillance is implemented by ethanol producers, losses are shifted among multiple stakeholders. Solutions to this problem include methods to reduce mycotoxin contamination in both pre- and postharvest maize.