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1.
To inform source attribution efforts, a comparative exposure assessment was developed to estimate the relative exposure to Campylobacter, the leading bacterial gastrointestinal disease in Canada, for 13 different transmission routes within Ontario, Canada, during the summer. Exposure was quantified with stochastic models at the population level, which incorporated measures of frequency, quantity ingested, prevalence, and concentration, using data from FoodNet Canada surveillance, the peer‐reviewed and gray literature, other Ontario data, and data that were specifically collected for this study. Models were run with @Risk software using Monte Carlo simulations. The mean number of cells of Campylobacter ingested per Ontarian per day during the summer, ranked from highest to lowest is as follows: household pets, chicken, living on a farm, raw milk, visiting a farm, recreational water, beef, drinking water, pork, vegetables, seafood, petting zoos, and fruits. The study results identify knowledge gaps for some transmission routes, and indicate that some transmission routes for Campylobacter are underestimated in the current literature, such as household pets and raw milk. Many data gaps were identified for future data collection consideration, especially for the concentration of Campylobacter in all transmission routes.  相似文献   

2.
In quantitative microbiological risk assessment (QMRA), the consumer phase model (CPM) describes the part of the food chain between purchase of the food product at retail and exposure. Construction of a CPM is complicated by the large variation in consumer food handling practices and a limited availability of data. Therefore, several subjective (simplifying) assumptions have to be made when a CPM is constructed, but with a single CPM their impact on the QMRA results is unclear. We therefore compared the performance of eight published CPMs for Campylobacter in broiler meat in an example of a QMRA, where all the CPMs were analyzed using one single input distribution of concentrations at retail, and the same dose‐response relationship. It was found that, between CPMs, there may be a considerable difference in the estimated probability of illness per serving. However, the estimated relative risk reductions are less different for scenarios modeling the implementation of control measures. For control measures affecting the Campylobacter prevalence, the relative risk is proportional irrespective of the CPM used. However, for control measures affecting the concentration the CPMs show some difference in the estimated relative risk. This difference is largest for scenarios where the aim is to remove the highly contaminated portion from human exposure. Given these results, we conclude that for many purposes it is not necessary to develop a new detailed CPM for each new QMRA. However, more observational data on consumer food handling practices and their impact on microbial transfer and survival are needed to generalize this conclusion.  相似文献   

3.
The Monte Carlo (MC) simulation approach is traditionally used in food safety risk assessment to study quantitative microbial risk assessment (QMRA) models. When experimental data are available, performing Bayesian inference is a good alternative approach that allows backward calculation in a stochastic QMRA model to update the experts’ knowledge about the microbial dynamics of a given food‐borne pathogen. In this article, we propose a complex example where Bayesian inference is applied to a high‐dimensional second‐order QMRA model. The case study is a farm‐to‐fork QMRA model considering genetic diversity of Bacillus cereus in a cooked, pasteurized, and chilled courgette purée. Experimental data are Bacillus cereus concentrations measured in packages of courgette purées stored at different time‐temperature profiles after pasteurization. To perform a Bayesian inference, we first built an augmented Bayesian network by linking a second‐order QMRA model to the available contamination data. We then ran a Markov chain Monte Carlo (MCMC) algorithm to update all the unknown concentrations and unknown quantities of the augmented model. About 25% of the prior beliefs are strongly updated, leading to a reduction in uncertainty. Some updates interestingly question the QMRA model.  相似文献   

4.
Quantitative microbial risk assessment (QMRA) is a valuable tool that can be used to predict the risk associated with human exposure to specific microbial contaminants in water sources. The transparency inherent in the QMRA process benefits discussions between multidisciplinary teams because members of such teams have different expertise and their confidence in the risk assessment output will depend upon whether they regard the selected input data and assumptions as being suitable and/or plausible. Selection of input data requires knowledge of the availability of appropriate data sets, the limitations of using a particular data set, and the logic of using alternative approaches. In performing QMRA modeling and in the absence of directly relevant data, compromises must be made. One such compromise made is to use available Escherichia coli data and apply a ratio of enteric viruses to indicator E. coli in wastewater obtained from prior studies to estimate the concentration of enteric viruses in other wastewater types/sources. In this article, we have provided an argument for why we do not recommend the use of a pathogen to E. coli ratio to estimate virus concentrations in single household graywater and additionally suggested circumstances in which use of such a ratio may be justified.  相似文献   

5.
Tucker Burch 《Risk analysis》2019,39(3):599-615
The assumptions underlying quantitative microbial risk assessment (QMRA) are simple and biologically plausible, but QMRA predictions have never been validated for many pathogens. The objective of this study was to validate QMRA predictions against epidemiological measurements from outbreaks of waterborne gastrointestinal disease. I screened 2,000 papers and identified 12 outbreaks with the necessary data: disease rates measured using epidemiological methods and pathogen concentrations measured in the source water. Eight of the 12 outbreaks were caused by Cryptosporidium, three by Giardia, and one by norovirus. Disease rates varied from 5.5 × 10?6 to 1.1 × 10?2 cases/person‐day, and reported pathogen concentrations varied from 1.2 × 10?4 to 8.6 × 102 per liter. I used these concentrations with single‐hit dose–response models for all three pathogens to conduct QMRA, producing both point and interval predictions of disease rates for each outbreak. Comparison of QMRA predictions to epidemiological measurements showed good agreement; interval predictions contained measured disease rates for 9 of 12 outbreaks, with point predictions off by factors of 1.0–120 (median = 4.8). Furthermore, 11 outbreaks occurred at mean doses of less than 1 pathogen per exposure. Measured disease rates for these outbreaks were clearly consistent with a single‐hit model, and not with a “two‐hit” threshold model. These results demonstrate the validity of QMRA for predicting disease rates due to Cryptosporidium and Giardia.  相似文献   

6.
The disease burden of pathogens as estimated by QMRA (quantitative microbial risk assessment) and EA (epidemiological analysis) often differs considerably. This is an unsatisfactory situation for policymakers and scientists. We explored methods to obtain a unified estimate using campylobacteriosis in the Netherlands as an example, where previous work resulted in estimates of 4.9 million (QMRA) and 90,600 (EA) cases per year. Using the maximum likelihood approach and considering EA the gold standard, the QMRA model could produce the original EA estimate by adjusting mainly the dose‐infection relationship. Considering QMRA the gold standard, the EA model could produce the original QMRA estimate by adjusting mainly the probability that a gastroenteritis case is caused by Campylobacter. A joint analysis of QMRA and EA data and models assuming identical outcomes, using a frequentist or Bayesian approach (using vague priors), resulted in estimates of 102,000 or 123,000 campylobacteriosis cases per year, respectively. These were close to the original EA estimate, and this will be related to the dissimilarity in data availability. The Bayesian approach further showed that attenuating the condition of equal outcomes immediately resulted in very different estimates of the number of campylobacteriosis cases per year and that using more informative priors had little effect on the results. In conclusion, EA was dominant in estimating the burden of campylobacteriosis in the Netherlands. However, it must be noted that only statistical uncertainties were taken into account here. Taking all, usually difficult to quantify, uncertainties into account might lead to a different conclusion.  相似文献   

7.
The aim of this study was to develop a modified quantitative microbial risk assessment (QMRA) framework that could be applied as a decision support tool to choose between alternative drinking water interventions in the developing context. The impact of different household water treatment (HWT) interventions on the overall incidence of diarrheal disease and disability adjusted life years (DALYs) was estimated, without relying on source water pathogen concentration as the starting point for the analysis. A framework was developed and a software tool constructed and then implemented for an illustrative case study for Nepal based on published scientific data. Coagulation combined with free chlorine disinfection provided the greatest estimated health gains in the short term; however, when long‐term compliance was incorporated into the calculations, the preferred intervention was porous ceramic filtration. The model demonstrates how the QMRA framework can be used to integrate evidence from different studies to inform management decisions, and in particular to prioritize the next best intervention with respect to estimated reduction in diarrheal incidence. This study only considered HWT interventions; it is recognized that a systematic consideration of sanitation, recreation, and drinking water pathways is important for effective management of waterborne transmission of pathogens, and the approach could be expanded to consider the broader water‐related context.  相似文献   

8.
T. Walton 《Risk analysis》2012,32(7):1122-1138
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.  相似文献   

9.
The public health significance of transmission of ESBL‐producing Escherichia coli and Campylobacter from poultry farms to humans through flies was investigated using a worst‐case risk model. Human exposure was modeled by the fraction of contaminated flies, the number of specific bacteria per fly, the number of flies leaving the poultry farm, and the number of positive poultry houses in the Netherlands. Simplified risk calculations for transmission through consumption of chicken fillet were used for comparison, in terms of the number of human exposures, the total human exposure, and, for Campylobacter only, the number of human cases of illness. Comparing estimates of the worst‐case risk of transmission through flies with estimates of the real risk of chicken fillet consumption, the number of human exposures to ESBL‐producing E. coli was higher for chicken fillet as compared with flies, but the total level of exposure was higher for flies. For Campylobacter, risk values were nearly consistently higher for transmission through flies than for chicken fillet consumption. This indicates that the public health risk of transmission of both ESBL‐producing E. coli and Campylobacter to humans through flies might be of importance. It justifies further modeling of transmission through flies for which additional data (fly emigration, human exposure) are required. Similar analyses of other environmental transmission routes from poultry farms are suggested to precede further investigations into flies.  相似文献   

10.
Epidemiology and quantitative microbiological risk assessment are disciplines in which the same public health measures are estimated, but results differ frequently. If large, these differences can confuse public health policymakers. This article aims to identify uncertainty sources that explain apparent differences in estimates for Campylobacter spp. incidence and attribution in the Netherlands, based on four previous studies (two for each discipline). An uncertainty typology was used to identify uncertainty sources and the NUSAP method was applied to characterize the uncertainty and its influence on estimates. Model outcomes were subsequently calculated for alternative scenarios that simulated very different but realistic alternatives in parameter estimates, modeling, data handling, or analysis to obtain impressions of the total uncertainty. For the epidemiological assessment, 32 uncertainty sources were identified and for QMRA 67. Definitions (e.g., of a case) and study boundaries (e.g., of the studied pathogen) were identified as important drivers for the differences between the estimates of the original studies. The range in alternatively calculated estimates usually overlapped between disciplines, showing that proper appreciation of uncertainty can explain apparent differences between the initial estimates from both disciplines. Uncertainty was not estimated in the original QMRA studies and underestimated in the epidemiological studies. We advise to give appropriate attention to uncertainty in QMRA and epidemiological studies, even if only qualitatively, so that scientists and policymakers can interpret reported outcomes more correctly. Ideally, both disciplines are joined by merging their strong respective properties, leading to unified public health measures.  相似文献   

11.
Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic inflammation of the intestines in humans, ruminants, and other species. It is the causative agent of Johne's disease in cattle, and has been implicated as the causative agent of Crohn's disease in humans. To date, no quantitative microbial risk assessment (QMRA) for MAP utilizing a dose‐response function exists. The objective of this study is to develop a nested dose‐response model for infection from oral exposure to MAP utilizing data from the peer‐reviewed literature. Four studies amenable to dose‐response modeling were identified in the literature search and optimized to the one‐parameter exponential or two‐parameter beta‐Poisson dose‐response models. A nesting analysis was performed on all permutations of the candidate data sets to determine the acceptability of pooling data sets across host species. Three of four data sets exhibited goodness of fit to at least one model. All three data sets exhibited good fit to the beta‐Poisson model, and one data set exhibited goodness of fit, and best fit, to the exponential model. Two data sets were successfully nested using the beta‐Poisson model with parameters α = 0.0978 and N50 = 2.70 × 102 CFU. These data sets were derived from sheep and red deer host species, indicating successful interspecies nesting, and demonstrate the highly infective nature of MAP. The nested dose‐response model described should be used for future QMRA research regarding oral exposure to MAP.  相似文献   

12.
We develop a model for bacterial cross-contamination during food preparation in the domestic kitchen and apply this to the case of Campylobacter-contaminated chicken breast. Building blocks of the model are the routines performed during food preparation, with their associated probabilities of bacterial transfer between food items and kitchen utensils. The model is used in a quantitative microbiological risk assessment (QMRA) of Campylobacter in the Netherlands. Using parameter values from the literature and performing elementary sensitivity analyses, we show that cross-contamination can contribute significantly to the risk of Campylobacter infection and find that cleaning frequency of kitchen utensils and thoroughness of rinsing of raw food items after preparation has more impact on cross-contamination than previously emphasized. Furthermore, we argue that especially more behavioral data on hygiene during food preparation is needed for a comprehensive Campylobacter risk assessment.  相似文献   

13.
Foodborne disease caused by nontyphoidal Salmonella (NTS) is one of the most important food safety issues worldwide. The objectives of this study were to carry out microbial monitoring on the prevalence of NTS in commercial ground pork, investigate consumption patterns, and conduct a quantitative microbiological risk assessment (QMRA) that considers cross-contamination to determine the risk caused by consuming ground pork and ready-to-eat food contaminated during food handling in the kitchen in Chengdu, China. The food pathway of ground pork was simplified and assumed to be several units according to the actual situation and our survey data, which were collected from our research or references and substituted into the QMRA model for simulation. The results showed that the prevalence of NTS in ground pork purchased in Chengdu was 69.64% (95% confidence interval [CI], 60.2–78.0), with a mean contamination level of −0.164 log CFU/g. After general cooking, NTS in ground pork could be eliminated (contamination level of zero). The estimated probability of causing salmonellosis per day was 9.43E-06 (95% CI: 8.82E-06–1.00E-05), while the estimated salmonellosis cases per million people per year were 3442 (95% CI: 3218–3666). According to the sensitivity analysis, the occurrence of cross-contamination was the most important factor affecting the probability of salmonellosis. To reduce the risk of salmonellosis caused by NTS through ground pork consumption, reasonable hygiene prevention and control measures should be adopted during food preparation to reduce cross-contamination. This study provides valuable information for household cooking and food safety management in China.  相似文献   

14.
Elizabethkingia spp. are common environmental pathogens responsible for infections in more vulnerable populations. Although the exposure routes of concern are not well understood, some hospital-associated outbreaks have indicated possible waterborne transmission. In order to facilitate quantitative microbial risk assessment (QMRA) for Elizabethkingia spp., this study fit dose–response models to frog and mice datasets that evaluated intramuscular and intraperitoneal exposure to Elizabethkingia spp. The frog datasets could be pooled, and the exact beta-Poisson model was the best fitting model with optimized parameters α  = 0.52 and β = 86,351. Using the exact beta-Poisson model, the dose of Elizabethkingia miricola resulting in a 50% morbidity response (LD50) was estimated to be approximately 237,000 CFU. The model developed herein was used to estimate the probability of infection for a hospital patient under a modeled exposure scenario involving a contaminated medical device and reported Elizabethkingia spp. concentrations isolated from hospital sinks after an outbreak. The median exposure dose was approximately 3 CFU/insertion event, and the corresponding median risk of infection was 3.4E-05. The median risk estimated in this case study was lower than the 3% attack rate observed in a previous outbreak, however, there are noted gaps pertaining to the possible concentrations of Elizabethkingia spp. in tap water and the most likely exposure routes. This is the first dose–response model developed for Elizabethkingia spp. thus enabling future risk assessments to help determine levels of risk and potential effective risk management strategies.  相似文献   

15.
A quantitative microbiological risk assessment model describes the transmission of Campylobacter through the broiler meat production chain and at home, from entering the processing plant until consumption of a chicken breast fillet meal. The exposure model is linked to a dose-response model to allow estimation of the incidence of human campylobacteriosis. The ultimate objective of the model is to serve as a tool to assess the effects of interventions to reduce campylobacteriosis in the Netherlands. The model describes some basic mechanistics of processing, including the nonlinear effects of cross-contamination between carcasses and their leaking feces. Model input is based on the output of an accompanying farm model and Dutch count data of Campylobacters on the birds' exterior and in the feces. When processing data are lacking, expert judgment is used for model parameter estimation. The model shows that to accurately assess of the effects of interventions, numbers of Campylobacter have to be explicitly incorporated in the model in addition to the prevalence of contamination. Also, as count data usually vary by several orders of magnitude, variability in numbers within and especially between flocks has to be accounted for. Flocks with high concentrations of Campylobacter in the feces that leak from the carcasses during industrial processing seem to have a dominant impact on the human incidence. The uncertainty in the final risk estimate is large, due to a large uncertainty at several stages of the chain. Among others, more quantitative count data at several stages of the production chain are needed to decrease this uncertainty. However, this uncertainty is smaller when relative risks of interventions are calculated with the model. Hence, the model can be effectively used by risk management in deciding on strategies to reduce human campylobacteriosis.  相似文献   

16.
Many farmers in water‐scarce regions of developing countries use wastewater to irrigate vegetables and other agricultural crops, a practice that may expand with climate change. There are a number of health risks associated with wastewater irrigation for human food crops, particularly with surface irrigation techniques common in the developing world. The World Health Organization (WHO) recommends using quantitative microbial risk assessment (QMRA) to determine if the irrigation scheme meets health standards. However, only a few vegetables have been studied for wastewater risk and little information is known about the disease burden of wastewater‐irrigated vegetable consumption in China. To bridge this knowledge gap, an experiment was conducted to determine volume of water left on Asian vegetables and lettuce after irrigation. One hundred samples each of Chinese chard (Brassica rapa var. chinensis), Chinese broccoli (Brassica oleracea var. alboglabra), Chinese flowering cabbage (Brassica rapa var. parachinensis), and lettuce (Lactuca sativa) were harvested after overhead sprinkler irrigation. Chinese broccoli and flowering cabbage were found to capture the most water and lettuce the least. QMRAs were then constructed to estimate rotavirus disease burden from consumption of wastewater‐irrigated Asian vegetables in Beijing. Results indicate that estimated risks from these reuse scenarios exceed WHO guideline thresholds for acceptable disease burden for wastewater use, signifying that reduction of pathogen concentration or stricter risk management is necessary for safe reuse. Considering the widespread practice of wastewater irrigation for food production, particularly in developing countries, incorporation of water retention factors in QMRAs can reduce uncertainty regarding health risks for consumers worldwide.  相似文献   

17.
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.  相似文献   

18.
Giardia is a zoonotic gastrointestinal parasite responsible for a substantial global public health burden, and quantitative microbial risk assessment (QMRA) is often used to forecast and manage this burden. QMRA requires dose–response models to extrapolate available dose–response data, but the existing model for Giardia ignores valuable dose–response information, particularly data from several well-documented waterborne outbreaks of giardiasis. The current study updates Giardia dose–response modeling by synthesizing all available data from outbreaks and experimental studies using a Bayesian random effects dose–response model. For outbreaks, mean doses (D) and the degree of spatial and temporal aggregation among cysts were estimated using exposure assessment implemented via two-dimensional Monte Carlo simulation, while potential overreporting of outbreak cases was handled using published overreporting factors and censored binomial regression. Parameter estimation was by Markov chain Monte Carlo simulation and indicated that a typical exponential dose–response parameter for Giardia is r = 1.6 × 10−2 [3.7 × 10−3, 6.2 × 10−2] (posterior median [95% credible interval]), while a typical morbidity ratio is m = 3.8 × 10−1 [2.3 × 10−1, 5.5 × 10−1]. Corresponding (logistic-scale) variance components were σr = 5.2 × 10−1 [1.1 × 10−1, 9.6 × 10−1] and σm = 9.3 × 10−1 [7.0 × 10−2, 2.8 × 100], indicating substantial variation in the Giardia dose–response relationship. Compared to the existing Giardia dose–response model, the current study provides more representative estimation of uncertainty in r and novel quantification of its natural variability. Several options for incorporating variability in r (and m) into QMRA predictions are discussed, including incorporation via Monte Carlo simulation as well as evaluation of the current study's model using the approximate beta-Poisson.  相似文献   

19.
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.  相似文献   

20.
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.  相似文献   

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