Considering the Risk of Infection by Cryptosporidium via Consumption of Municipally Treated Drinking Water from a Surface Water Source in a Southwestern Ontario Community

Through the use of case‐control analyses and quantitative microbial risk assessment (QMRA), relative risks of transmission of cryptosporidiosis have been evaluated (recreational water exposure vs. drinking water consumption) for a Canadian community with higher than national rates of cryptosporidiosis. A QMRA was developed to assess the risk of Cryptosporidium infection through the consumption of municipally treated drinking water. Simulations were based on site‐specific surface water contamination levels and drinking water treatment log₁₀ reduction capacity for Cryptosporidium. Results suggested that the risk of Cryptosporidium infection via drinking water in the study community, assuming routine operation of the water treatment plant, was negligible (6 infections per 10¹³ persons per day—5th percentile: 2 infections per 10¹⁵ persons per day; 95th percentile: 3 infections per 10¹² persons per day). The risk is essentially nonexistent during optimized, routine treatment operations. The study community achieves between 7 and 9 log₁₀Cryptosporidium oocyst reduction through routine water treatment processes. Although these results do not preclude the need for constant vigilance by both water treatment and public health professionals in this community, they suggest that the cause of higher rates of cryptosporidiosis are more likely due to recreational water contact, or perhaps direct animal contact. QMRA can be successfully applied at the community level to identify data gaps, rank relative public health risks, and forecast future risk scenarios. It is most useful when performed in a collaborative way with local stakeholders, from beginning to end of the risk analysis paradigm.     

A Quantitative Risk Assessment of Waterborne Cryptosporidiosis in France Using Second-Order Monte Carlo Simulation

A pragmatic quantitative risk assessment (QRA) of the risks of waterborne Cryptosporidium parvum infection and cryptosporidiosis in immunocompetent and immunodeficient French populations is proposed. The model takes into account French specificities such as the French technique for oocyst enumeration performance and tap water consumption. The proportion of infective oocysts is based on literature review and expert knowledge. The probability of infection for a given number of ingested viable oocysts is modeled using the exponential dose-response model applied on published data from experimental infections in immunocompetent human volunteers challenged with the IOWA strain. Second-order Monte Carlo simulations are used to characterize the uncertainty and variability of the risk estimates. Daily risk of infection and illness for the immunocompetent and the immunodeficient populations are estimated according to the number of oocysts observed in a single storage reservoir water sample. As an example, the mean daily risk of infection in the immunocompetent population is estimated to be 1.08 x 10(-4) (95% confidence interval: [0.20 x 10(-4); 6.83 x 10(-4)]) when five oocysts are observed in a 100 L storage reservoir water sample. Annual risks of infection and disease are estimated from a set of oocyst enumeration results from distributed water samples, assuming a negative binomial distribution of day-to-day contamination variation. The model and various assumptions used in the model are fully explained and discussed. While caveats of this model are well recognized, this pragmatic QRA could represent a useful tool for the French Food Safety Agency (AFSSA) to define recommendations in case of water resource contamination by C. parvum whose infectivity is comparable to the IOWA strain.     

Cryptosporidium and Dairy Cattle in the Catskill/Delaware Watershed: A Quantitative Risk Assessment

We carried out a study to estimate the public health risk posed by dairy cattle located in New York City's Catskill/Delaware watershed, as measured by daily C. parvum-like oocyst loading. A Monte Carlo simulation model that takes into account the nature of the dairy cattle population within the target area, age-specific incidence/prevalence rates, as well as differential fecal production and oocyst-shedding intensity rates was used to address the objectives. Additionally, the model was designed to distinguish between zoonotic and nonzoonotic species/genotypes of Cryptosporidium. Total estimated daily C. parvum-like oocyst shedding across all age/production categories was estimated at 4.15 x 10(10). The zoonotic C. parvum comprised 93.5% of this load. It was estimated that preweaned calves produce 99.5% of the total daily C. parvum ocyst burden. The recently described nonzoonotic C. bovis was estimated to have a daily load of 2.2 x 10(9) oocysts across all age/production strata. C. parvum deer-like genotype was estimated to have a total daily load of 1.3 x 10(9) oocysts. The results of this study support earlier assertions that strategies aimed at reducing the cryptosporidial risk posed by dairy cattle to public health will be most efficacious if aimed at preweaned calves.     

Quantitative Risk Estimation for a Legionella pneumophila Infection Due to Whirlpool Use

Quantitative microbiological risk assessment was used to quantify the risk associated with the exposure to Legionella pneumophila in a whirlpool. Conceptually, air bubbles ascend to the surface, intercepting Legionella from the traversed water. At the surface the bubble bursts into dominantly noninhalable jet drops and inhalable film drops. Assuming that film drops carry half of the intercepted Legionella, a total of four (95% interval: 1–9) and 4.5×10⁴ (4.4×10⁴ – 4.7×10⁴) cfu/min were estimated to be aerosolized for concentrations of 1 and 1,000 legionellas per liter, respectively. Using a dose‐response model for guinea pigs to represent humans, infection risks for active whirlpool use with 100 cfu/L water for 15 minutes were 0.29 (～0.11–0.48) for susceptible males and 0.22 (～0.06–0.42) for susceptible females. A L. pneumophila concentration of ≥1,000 cfu/L water was estimated to nearly always cause an infection (mean: 0.95; 95% interval: 0.9–～1). Estimated infection risks were time‐dependent, ranging from 0.02 (0–0.11) for 1‐minute exposures to 0.93 (0.86–0.97) for 2‐hour exposures when the L. pneumophila concentration was 100 cfu/L water. Pool water in Dutch bathing establishments should contain <100 cfu Legionella/L water. This study suggests that stricter provisions might be required to assure adequate public health protection.     

Cryptosporidiosis Susceptibility and Risk: A Case Study

Regional estimates of cryptosporidiosis risks from drinking water exposure were developed and validated, accounting for AIDS status and age. We constructed a model with probability distributions and point estimates representing Cryptosporidium in tap water, tap water consumed per day (exposure characterization); dose response, illness given infection, prolonged illness given illness; and three conditional probabilities describing the likelihood of case detection by active surveillance (health effects characterization). The model predictions were combined with population data to derive expected case numbers and incidence rates per 100,000 population, by age and AIDS status, borough specific and for New York City overall in 2000 (risk characterization). They were compared with same-year surveillance data to evaluate predictive ability, assumed to represent true incidence of waterborne cryptosporidiosis. The predicted mean risks, similar to previously published estimates for this region, overpredicted observed incidence-most extensively when accounting for AIDS status. The results suggest that overprediction may be due to conservative parameters applied to both non-AIDS and AIDS populations, and that biological differences for children need to be incorporated. Interpretations are limited by the unknown accuracy of available surveillance data, in addition to variability and uncertainty of model predictions. The model appears sensitive to geographical differences in AIDS prevalence. The use of surveillance data for validation and model parameters pertinent to susceptibility are discussed.     

Quantitative Assessment of Human MRSA Risks from Swine

The public health community, news media, and members of the general public have expressed significant concern that methicillin‐resistant Staphylococcus aureus (MRSA) transmitted from pigs to humans may harm human health. Studies of the prevalence and dynamics of swine‐associated (ST398) MRSA have sampled MRSA at discrete points in the presumed causative chain leading from swine to human patients, including sampling bacteria from live pigs, retail meats, farm workers, and hospital patients. Nonzero prevalence is generally interpreted as indicating a potential human health hazard from MRSA infections, but quantitative assessments of resulting risks are not usually provided. This article integrates available data from several sources to construct a conservative (plausible upper bound) probability estimate for the actual human health harm (MRSA infections and fatalities) arising from ST398‐MRSA from pigs. The model provides plausible upper bounds of approximately one excess human infection per year among all U.S. pig farm workers, and one human infection per 31 years among the remaining total population of the United States. These results assume the possibility of transmission events not yet observed, so additional data collection may reduce these estimates further.     

Estimation of the Likelihood of Fecal–Oral HEV Transmission Among Pigs

Sources for human hepatitis E virus (HEV) infections of genotype 3 are largely unknown. Pigs are potential animal reservoirs for HEV. Intervention at pig farms may be desired when pigs are confirmed as a source for human infections, requiring knowledge about transmission routes. These routes are currently understudied. The current study aims to quantify the likelihood of pig feces in causing new HEV infections in pigs due to oral ingestion. We estimated the daily infection risk for pigs by modeling the fate of HEV in the fecal–oral (F–O) pathway. Using parameter values deemed most plausible by the authors based on current knowledge the daily risk of infection was 0.85 (95% interval: 0.03–1). The associated expected number of new infections per day was ～4 (2.5% limit 0.1, the 97% limit tending to infinity) compared to 0.7 observed in a transmission experiment with pigs, and the likelihood of feces causing the transmission approached 1. In alternative scenarios, F–O transmission of HEV was also very likely to cause new infections. By reducing the total value of all explanatory variables by 2 orders of magnitude, the expected numbers of newly infected pigs approached the observed number. The likelihood of F–O transmission decreased by decreasing parameter values, allowing for at most 94% of infections being caused by additional transmission routes. Nevertheless, in all scenarios F–O transmission was estimated to contribute to HEV transmission. Thus, despite the difficulty in infecting pigs with HEV via oral inoculation, the F–O route is likely to cause HEV transmission among pigs.     

Effect of Climate Change on the Concentration and Associated Risks of Vibrio Spp. in Dutch Recreational Waters

Currently, the number of reported cases of recreational‐ water‐related Vibrio illness in the Netherlands is low. However, a notable higher incidence of Vibrio infections has been observed in warm summers. In the future, such warm summers are expected to occur more often, resulting in enhanced water temperatures favoring Vibrio growth. Quantitative information on the increase in concentration of Vibrio spp. in recreational water under climate change scenarios is lacking. In this study, data on occurrence of Vibrio spp. at six different bathing sites in the Netherlands (2009–2012) were used to derive an empirical formula to predict the Vibrio concentration as a function of temperature, salinity, and pH. This formula was used to predict the effects of increased temperatures in climate change scenarios on Vibrio concentrations. For Vibrio parahaemolyticus, changes in illness risks associated with the changed concentrations were calculated as well. For an average temperature increase of 3.7 °C, these illness risks were calculated to be two to three times higher than in the current situation. Current illness risks were, varying per location, on average between 10^?4 and 10^?2 per person for an entire summer. In situations where water temperatures reached maximum values, illness risks are estimated to be up to 10^?2 and 10^?1. If such extreme situations occur more often during future summers, increased numbers of ill bathers or bathing‐water‐related illness outbreaks may be expected.     

Intuitive Toxicology. II. Expert and Lay Judgments of Chemical Risks in Canada

This study is a replication and extension in Canada of a previous study in the United States in which toxicologists and members of the public were surveyed to determine their attitudes, beliefs, and perceptions regarding risks from chemicals. This study of "intuitive vs. scientific toxicology" was motivated by the premise that different assumptions, conceptions, and values underlie much of the discrepancy between expert and lay views of chemical risks. The results showed that Canadian toxicologists had far lower perceptions of risk and more favorable attitudes toward chemicals than did the Canadian public. The public's attitudes were quite negative and showed the same lack of dose-response sensitivity found in the earlier U.S. study. Both the public and the toxicologists lacked confidence in the value of animal studies for predicting human health risks. However, the public had great confidence in the validity of animal studies that found evidence of carcinogenicity, whereas such evidence was not considered highly predictive of human health risk by many toxicologists. Technical judgments of toxicologists were found to be associated with factors such as affiliation, gender, and worldviews. Implications of these data for risk communication are briefly discussed.     

A Stochastic Assessment of the Public Health Risks of the Use of Macrolide Antibiotics in Food Animals

Campylobacteriosis is an important food-borne illness with more than a million U.S. cases annually. Antibiotic treatment is usually not required. However, erythromycin, a macrolide antibiotic, is recommended for the treatment of severe cases. Therefore, it is considered a critically important antibiotic and given special attention as to the risk that food animal use will lead to resistant infections and compromised human treatment. To assess this risk, we used a retrospective approach; estimating the number of campylobacteriosis cases caused by specific meat consumption utilizing the preventable fraction. We then determined the number of cases with macrolide resistance Campylobacter spp. based on a linear model relating the resistance fraction to on-farm macrolide use. In this article, we considered the uncertainties in the parameter estimates, utilized a more elaborate model of resistance development and separated C. coli and C. jejuni . There are no published data for the probability of compromised treatment outcome due to macrolide resistance. Therefore, our estimates of compromised treatment outcome were based on data for fluoroquinolone-resistant infections. The conservative results show the human health risks are extremely low. For example, the predicted risk of suboptimal human treatment of infection with C. coli from swine is only 1 in 82 million; with a 95% chance it could be as high as 1 in 49 million. Risks from C. jejuni in poultry or beef are even less. Reduced antibiotic use can adversely impact animal health. These low human risks should be weighed against the alternative risks.     

Characterizing the Risk of Infection from Mycobacterium tuberculosis in Commercial Passenger Aircraft Using Quantitative Microbial Risk Assessment

Quantitative microbial risk assessment was used to predict the likelihood and spatial organization of Mycobacterium tuberculosis ( Mtb ) transmission in a commercial aircraft. Passenger exposure was predicted via a multizone Markov model in four scenarios: seated or moving infectious passengers and with or without filtration of recirculated cabin air. The traditional exponential ( k  = 1) and a new exponential ( k  = 0.0218) dose-response function were used to compute infection risk. Emission variability was included by Monte Carlo simulation. Infection risks were higher nearer and aft of the source; steady state airborne concentration levels were not attained. Expected incidence was low to moderate, with the central 95% ranging from 10⁻⁶ to 10⁻¹ per 169 passengers in the four scenarios. Emission rates used were low compared to measurements from active TB patients in wards, thus a "superspreader" emitting 44 quanta/h could produce 6.2 cases or more under these scenarios. Use of respiratory protection by the infectious source and/or susceptible passengers reduced infection incidence up to one order of magnitude.     

Judgments of Chemical Risks: Comparisons Among Senior Managers, Toxicologists, and the Public

Nineteen Senior Managers of a major chemical company in the United Kingdom participated in a survey to determine their attitudes, beliefs, and perceptions regarding risks from chemicals. Similar surveys had previously been conducted with toxicologists and members of the general public in the United States and Canada. In general, the Senior Managers tended to judge risks to be quite small for most chemicals. Moreover, they had lower risk perceptions than did members of the British Toxicological Society and even far lower perceptions of risk than a comparison group of members of the Canadian public. The managers held views that were similar to British toxicologists working in industry and government and dissimilar to the views of toxicologists working in academia. The observed differences between views of managers, toxicologists, and the public must be recognized and understood in order to facilitate communication and constructive efforts to manage chemical risks.     

Interventions Targeting Deep Tissue Lymph Nodes May Not Effectively Reduce the Risk of Salmonellosis from Ground Pork Consumption: A Quantitative Microbial Risk Assessment

The inclusion of deep tissue lymph nodes (DTLNs) or nonvisceral lymph nodes contaminated with Salmonella in wholesale fresh ground pork (WFGP) production may pose risks to public health. To assess the relative contribution of DTLNs to human salmonellosis occurrence associated with ground pork consumption and to investigate potential critical control points in the slaughter‐to‐table continuum for the control of human salmonellosis in the United States, a quantitative microbial risk assessment (QMRA) model was established. The model predicted an average of 45 cases of salmonellosis (95% CI = [19, 71]) per 100,000 Americans annually due to WFGP consumption. Sensitivity analysis of all stochastic input variables showed that cooking temperature was the most influential parameter for reducing salmonellosis cases associated with WFGP meals, followed by storage temperature and Salmonella concentration on contaminated carcass surface before fabrication. The input variables were grouped to represent three main factors along the slaughter‐to‐table chain influencing Salmonella doses ingested via WFGP meals: DTLN‐related factors, factors at processing other than DTLNs, and consumer‐related factors. The evaluation of the impact of each group of factors by second‐order Monte Carlo simulation showed that DTLN‐related factors had the lowest impact on the risk estimate among the three groups of factors. These findings indicate that interventions to reduce Salmonella contamination in DTLNs or to remove DTLNs from WFGP products may be less critical for reducing human infections attributable to ground pork than improving consumers’ cooking habits or interventions of carcass decontamination at processing.     

Comparison of Risk Predicted by Multiple Norovirus Dose–Response Models and Implications for Quantitative Microbial Risk Assessment

The application of quantitative microbial risk assessments (QMRAs) to understand and mitigate risks associated with norovirus is increasingly common as there is a high frequency of outbreaks worldwide. A key component of QMRA is the dose–response analysis, which is the mathematical characterization of the association between dose and outcome. For Norovirus, multiple dose–response models are available that assume either a disaggregated or an aggregated intake dose. This work reviewed the dose–response models currently used in QMRA, and compared predicted risks from waterborne exposures (recreational and drinking) using all available dose–response models. The results found that the majority of published QMRAs of norovirus use the ₁F₁ hypergeometric dose–response model with α = 0.04, β = 0.055. This dose–response model predicted relatively high risk estimates compared to other dose–response models for doses in the range of 1–1,000 genomic equivalent copies. The difference in predicted risk among dose–response models was largest for small doses, which has implications for drinking water QMRAs where the concentration of norovirus is low. Based on the review, a set of best practices was proposed to encourage the careful consideration and reporting of important assumptions in the selection and use of dose–response models in QMRA of norovirus. Finally, in the absence of one best norovirus dose–response model, multiple models should be used to provide a range of predicted outcomes for probability of infection.     

Hexavalent Chromium and Lung Cancer in the Chromate Industry: A Quantitative Risk Assessment

The purpose of this investigation was to estimate excess lifetime risk of lung cancer death resulting from occupational exposure to hexavalent-chromium-containing dusts and mists. The mortality experience in a previously studied cohort of 2,357 chromate chemical production workers with 122 lung cancer deaths was analyzed with Poisson regression methods. Extensive records of air samples evaluated for water-soluble total hexavalent chromium were available for the entire employment history of this cohort. Six different models of exposure-response for hexavalent chromium were evaluated by comparing deviances and inspection of cubic splines. Smoking (pack-years) imputed from cigarette use at hire was included in the model. Lifetime risks of lung cancer death from exposure to hexavalent chromium (assuming up to 45 years of exposure) were estimated using an actuarial calculation that accounts for competing causes of death. A linear relative rate model gave a good and readily interpretable fit to the data. The estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium (as CrO3), with a lag of five years, was RR=2.44 (95% CI=1.54-3.83). The excess lifetime risk of lung cancer death from exposure to hexavalent chromium at the current OSHA permissible exposure limit (PEL) (0.10 mg/m3) was estimated to be 255 per 1,000 (95% CI: 109-416). This estimate is comparable to previous estimates by U.S. EPA, California EPA, and OSHA using different occupational data. Our analysis predicts that current occupational standards for hexavalent chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in 10, which is consistent with previous risk assessments.     

Offenders’ Risk‐Taking Attitude Inside and Outside the Prison Walls

It has long been assumed that risk taking is closely associated with criminal behavior. One reason for placing criminals behind bars—aside from punishment and protecting the public—is to prevent them from engaging in further risky criminal activities. Limited attention has been paid to whether being inside or outside prison affects offenders’ risk‐taking behaviors and attitudes. We compared risk‐taking behaviors and attitudes in five risk domains (ethical, financial, health/safety, recreational, social) among 75 incarcerated offenders (i.e., offenders who are currently in prison) and 45 ex‐offenders (i.e., offenders who have just been released from prison). Ex‐offenders reported higher likelihood of engaging in risky behavior, driven largely by a willingness to take more risks in the recreational and ethical domains. Benefits attributed to risk taking as well as risk perception did not differ between incarcerated and ex‐offenders, indicating that the opportunity to take risks might underlie behavioral risk intentions. Our results also indicate that risk‐taking activities are better predicted by the expected benefits rather than by risk perception, aside from the health/safety domain. These results highlight the importance of studying the person and the environment and examining risk taking in a number of content domains.     

The Impact of Social Amplification and Attenuation of Risk and the Public Reaction to Mad Cow Disease in Canada

Following the detection of bovine spongiform encephalopathy (BSE) in Canada, and subsequently in the United States, confidence in the safety of beef products remained high. Consumers actually increased their consumption of beef slightly after the news of an increased risk from mad cow disease, which has been interpreted as public support for beef farmers and confidence in government regulators. The Canadian public showed a markedly different reaction to the news of domestic BSE than the furious and panicked responses observed in the United Kingdom, Germany, and Japan. Using the social amplification of risk framework, we show that, while other countries displayed social amplification of risk, Canada experienced a social attenuation of risk. The attenuated reaction in Canada toward mad cow disease and increased human health risks from variant Creutzfeldt-Jakob disease (vCJD) was due to the social context at the time when BSE was discovered domestically. Mortality, morbidity, and psychosocial impacts resulting from other major events such as severe acute respiratory syndrome (SARS), West Nile virus (WNV), and the U.S.-Iraq war made the theoretical risks of BSE and vCJD a lower priority, reducing its concern as a risk issue.     

Rate of Foot-and-Mouth Disease Virus Transmission by Carriers Quantified from Experimental Data

Upon infection with foot-and-mouth disease virus (FMDV) a considerable number of animals become carriers of the virus. These carriers are considered to be a risk for new outbreaks, but the rate at which these animals can transmit the infection has not been quantified. An analysis was carried out using data from previously published experiments in order to quantify the transmission rate parameter β of FMDV infection from carriers to susceptible animals. The parameter β was estimated at 0.0256 (likelihood-based confidence interval: 0.008–0.059) infections per carrier per month. Moreover, analysis of published experimental data indicates that the proportion of FMDV carriers decreases at a rate of 0.115 per month. Both parameters obtained from this study are useful for quantitative risk analyses of the trade of animals from FMDV-infected areas or the lifting of vaccination programs.     

Evaluating the Potential for a Helicobacter pylori Drinking Water Guideline

Helicobacter pylori is a microaerophilic, gram‐negative bacterium that is linked to adverse health effects including ulcers and gastrointestinal cancers. The goal of this analysis is to develop the necessary inputs for a quantitative microbial risk assessment (QMRA) needed to develop a potential guideline for drinking water at the point of ingestion (e.g., a maximum contaminant level, or MCL) that would be protective of human health to an acceptable level of risk while considering sources of uncertainty. Using infection and gastric cancer as two discrete endpoints, and calculating dose‐response relationships from experimental data on humans and monkeys, we perform both a forward and reverse risk assessment to determine the risk from current reported surface water concentrations of H. pylori and an acceptable concentration of H. pylori at the point of ingestion. This approach represents a synthesis of available information on human exposure to H. pylori via drinking water. A lifetime risk of cancer model suggests that a MCL be set at <1 organism/L given a 5‐log removal treatment because we cannot exclude the possibility that current levels of H. pylori in environmental source waters pose a potential public health risk. Research gaps include pathogen occurrence in source and finished water, treatment removal rates, and determination of H. pylori risks from other water sources such as groundwater and recreational water.     

Development of Dose‐Response Models to Predict the Relationship for Human Toxoplasma gondii Infection Associated with Meat Consumption

Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States. It is thought that a substantial portion of human T. gondii infections is acquired through the consumption of meats. The dose‐response relationship for human exposures to T. gondii‐infected meat is unknown because no human data are available. The goal of this study was to develop and validate dose‐response models based on animal studies, and to compute scaling factors so that animal‐derived models can predict T. gondii infection in humans. Relevant studies in literature were collected and appropriate studies were selected based on animal species, stage, genotype of T. gondii, and route of infection. Data were pooled and fitted to four sigmoidal‐shaped mathematical models, and model parameters were estimated using maximum likelihood estimation. Data from a mouse study were selected to develop the dose‐response relationship. Exponential and beta‐Poisson models, which predicted similar responses, were selected as reasonable dose‐response models based on their simplicity, biological plausibility, and goodness fit. A confidence interval of the parameter was determined by constructing 10,000 bootstrap samples. Scaling factors were computed by matching the predicted infection cases with the epidemiological data. Mouse‐derived models were validated against data for the dose‐infection relationship in rats. A human dose‐response model was developed as P (d) = 1–exp (–0.0015 × 0.005 × d) or P (d) = 1–(1 + d × 0.003 / 582.414)^?1.479. Both models predict the human response after consuming T. gondii‐infected meats, and provide an enhanced risk characterization in a quantitative microbial risk assessment model for this pathogen.