A QMRA for the Transmission of ESBL‐Producing Escherichia coli and Campylobacter from Poultry Farms to Humans Through Flies

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.     

A Decision Support Tool to Compare Waterborne and Foodborne Infection and/or Illness Risks Associated with Climate Change

Climate change may impact waterborne and foodborne infectious disease, but to what extent is uncertain. Estimating climate‐change‐associated relative infection risks from exposure to viruses, bacteria, or parasites in water or food is critical for guiding adaptation measures. We present a computational tool for strategic decision making that describes the behavior of pathogens using location‐specific input data under current and projected climate conditions. Pathogen‐pathway combinations are available for exposure to norovirus, Campylobacter, Cryptosporidium, and noncholera Vibrio species via drinking water, bathing water, oysters, or chicken fillets. Infection risk outcomes generated by the tool under current climate conditions correspond with those published in the literature. The tool demonstrates that increasing temperatures lead to increasing risks for infection with Campylobacter from consuming raw/undercooked chicken fillet and for Vibrio from water exposure. Increasing frequencies of drought generally lead to an elevated infection risk of exposure to persistent pathogens such as norovirus and Cryptosporidium, but decreasing risk of exposure to rapidly inactivating pathogens, like Campylobacter. The opposite is the case with increasing annual precipitation; an upsurge of heavy rainfall events leads to more peaks in infection risks in all cases. The interdisciplinary tool presented here can be used to guide climate change adaptation strategies focused on infectious diseases.     

Animal and Human Dose‐Response Models for Brucella Species

Human Brucellosis is one of the most common zoonotic diseases worldwide. Disease transmission often occurs through the handling of domestic livestock, as well as ingestion of unpasteurized milk and cheese, but can have enhanced infectivity if aerosolized. Because there is no human vaccine available, rising concerns about the threat of Brucellosis to human health and its inclusion in the Center for Disease Control's Category B Bioterrorism/Select Agent List make a better understanding of the dose‐response relationship of this microbe necessary. Through an extensive peer‐reviewed literature search, candidate dose‐response data were appraised so as to surpass certain standards for quality. The statistical programming language, “R,” was used to compute the maximum likelihood estimation to fit two models, the exponential and the approximate beta‐Poisson (widely used for quantitative risk assessment) to dose‐response data. Dose‐response models were generated for prevalent species of Brucella: Br. suis, Br. melitensis, and Br. abortus. Dose‐response models were created for aerosolized Br. suis exposure to guinea pigs from pooled studies. A parallel model for guinea pigs inoculated through both aerosol and subcutaneous routes with Br. melitensis showed that the median infectious dose corresponded to a 30 colony‐forming units (CFU) dose of Br. suis, much less than the N₅₀ dose of about 94 CFU for Br. melitensis organisms. When Br. melitensis was tested subcutaneously on mice, the N₅₀ dose was higher, 1,840 CFU. A dose‐response model was constructed from pooled data for mice, rhesus macaques, and humans inoculated through three routes (subcutaneously/aerosol/intradermally) with Br. melitensis.     

Development and application of a dose–response model for Elizabethkingia spp

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.     

Risk Assessment of Human Listeriosis from Semisoft Cheeses Made from Raw Sheep's Milk in Lazio and Tuscany (Italy)

Semisoft cheese made from raw sheep's milk is traditionally and economically important in southern Europe. However, raw milk cheese is also a known vehicle of human listeriosis and contamination of sheep cheese with Listeria monocytogenes has been reported. In the present study, we have developed and applied a quantitative risk assessment model, based on available evidence and challenge testing, to estimate risk of invasive listeriosis due to consumption of an artisanal sheep cheese made with raw milk collected from a single flock in central Italy. In the model, contamination of milk may originate from the farm environment or from mastitic animals, with potential growth of the pathogen in bulk milk and during cheese ripening. Based on the 48‐day challenge test of a local semisoft raw sheep's milk cheese we found limited growth only during the initial phase of ripening (24 hours) and no growth or limited decline during the following ripening period. In our simulation, in the baseline scenario, 2.2% of cheese servings are estimated to have at least 1 colony forming unit (CFU) per gram. Of these, 15.1% would be above the current E.U. limit of 100 CFU/g (5.2% would exceed 1,000 CFU/g). Risk of invasive listeriosis per random serving is estimated in the 10^?12 range (mean) for healthy adults, and in the 10^?10 range (mean) for vulnerable populations. When small flocks (10–36 animals) are combined with the presence of a sheep with undetected subclinical mastitis, risk of listeriosis increases and such flocks may represent a public health risk.     

Multi‐Exposure Pathway Model to Compare Escherichia coli O157 Risks and Interventions

The relative contributions of exposure pathways associated with cattle‐manure‐borne Escherichia coli O157:H7 on public health have yet to be fully characterized. A stochastic, quantitative microbial risk assessment (QMRA) model was developed to describe a hypothetical cattle farm in order to compare the relative importance of five routes of exposure, including aquatic recreation downstream of the farm, consumption of contaminated ground beef processed with limited interventions, consumption of leafy greens, direct animal contact, and the recreational use of a cattle pasture. To accommodate diverse environmental and hydrological pathways, existing QMRAs were integrated with novel and simplistic climate and field‐level submodels. The model indicated that direct animal contact presents the greatest risk of illness per exposure event during the high pathogen shedding period. However, when accounting for the frequency of exposure, using a high‐risk exposure‐receptor profile, consumption of ground beef was associated with the greatest risk of illness. Additionally, the model was used to evaluate the efficacy of hypothetical interventions affecting one or more exposure routes; concurrent evaluation of multiple routes allowed for the assessment of the combined effect of preharvest interventions across exposure pathways—which may have been previously underestimated—as well as the assessment of the effect of additional downstream interventions. This analysis represents a step towards a full evaluation of the risks associated with multiple exposure pathways; future incorporation of variability associated with environmental parameters and human behaviors would allow for a comprehensive assessment of the relative contribution of exposure pathways at the population level.     

A Risk Assessment of Campylobacteriosis and Salmonellosis Linked to Chicken Meals Prepared in Households in Dakar,Senegal

We used a quantitative microbiological risk assessment model to describe the risk of Campylobacter and Salmonella infection linked to chicken meals prepared in households in Dakar, Senegal. The model uses data collected specifically for this study, such as the prevalence and level of bacteria on the neck skin of chickens bought in Dakar markets, time‐temperature profiles recorded from purchase to consumption, an observational survey of meal preparation in private kitchens, and detection and enumeration of pathogens on kitchenware and cooks’ hands. Thorough heating kills all bacteria present on chicken during cooking, but cross‐contamination of cooked chicken or ready‐to‐eat food prepared for the meal via kitchenware and cooks’ hands leads to a high expected frequency of pathogen ingestion. Additionally, significant growth of Salmonella is predicted during food storage at ambient temperature before and after meal preparation. These high exposures lead to a high estimated risk of campylobacteriosis and/or salmonellosis in Dakar households. The public health consequences could be amplified by the high level of antimicrobial resistance of Salmonella and Campylobacter observed in this setting. A significant decrease in the number of ingested bacteria and in the risk could be achieved through a reduction of the prevalence of chicken contamination at slaughter, and by the use of simple hygienic measures in the kitchen. There is an urgent need to reinforce the hygiene education of food handlers in Senegal.     

Updating Parameters of the Chicken Processing Line Model

A mathematical model of chicken processing that quantitatively describes the transmission of Campylobacter on chicken carcasses from slaughter to chicken meat product has been developed in Nauta et al. (2005). This model was quantified with expert judgment. Recent availability of data allows updating parameters of the model to better describe processes observed in slaughterhouses. We propose Bayesian updating as a suitable technique to update expert judgment with microbiological data. Berrang and Dickens's data are used to demonstrate performance of this method in updating parameters of the chicken processing line model.     

A Risk Assessment Model for Enterotoxigenic Staphylococcus aureus in Pasteurized Milk: A Potential Route to Source‐Level Inference

This article describes a probabilistic model that quantifies hazards that arise from Staphylococcus aureus in milk that is sold as pasteurized in the United Kingdom. The model is centered on coupled dynamics for S. aureus populations, staphylococcal enterotoxins, and the concentration of alkaline phosphatase throughout the milk chain. The chain includes farm collection and storage of pooled milk, further pooling for off‐farm processing, high temperature short time thermal processing, and possible postprocess contamination. The model is implemented as a Bayesian belief network. The results indicate that milk sold as pasteurized is relatively safe with respect to the hazards associated with S. aureus and that most risk is associated with small scale on‐farm processing. An additional analysis of likelihood ratios shows that alkaline phosphatase concentrations in filler tank milk are a good indicator of potential hazards and that these concentrations, in conjunction with other measurements, can be used effectively to discriminate over possible failure modes. The ability to discriminate over potential failure modes can support preemptive actions, such as maintenance or hygiene, which assist with milk chain management and, over extended periods, accumulate to drive improved safety, efficiency, and security.     

Farms,Families, and Markets: New Evidence on Completeness of Markets in Agricultural Settings

The farm household model has played a central role in improving the understanding of small‐scale agricultural households and non‐farm enterprises. Under the assumptions that all current and future markets exist and that farmers treat all prices as given, the model simplifies households' simultaneous production and consumption decisions into a recursive form in which production can be treated as independent of preferences of household members. These assumptions, which are the foundation of a large literature in labor and development, have been tested and not rejected in several important studies including Benjamin (1992). Using multiple waves of longitudinal survey data from Central Java, Indonesia, this paper tests a key prediction of the recursive model: demand for farm labor is unrelated to the demographic composition of the farm household. The prediction is unambiguously rejected. The rejection cannot be explained by contamination due to unobserved heterogeneity that is fixed at the farm level, local area shocks, or farm‐specific shocks that affect changes in household composition and farm labor demand. We conclude that the recursive form of the farm household model is not consistent with the data. Developing empirically tractable models of farm households when markets are incomplete remains an important challenge.     

The Impact of Consumer Phase Models in Microbial Risk Analysis

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.     

Exposure to Persistent Organochlorines in Canadian Breast Milk: A Probabilistic Assessment

Exposure to persistent organochlorines in breast milk was estimated probabilistically for Canadian infants. Noncancer health effects were evaluated by comparing the predicted exposure distributions to published guidance values. For chemicals identified as potential human carcinogens, cancer risks were evaluated using standard methodology typically applied in Canada, as well as an alternative method developed under the Canadian Environmental Protection Act. Potential health risks associated with exposure to persistent organochlorines were quantitatively and qualitatively weighed against the benefits of breast-feeding. Current levels of the majority of contaminants identified in Canadian breast milk do not pose unacceptable risks to infants. Benefits of breast-feeding are well documented and qualitatively appear to outweigh potential health concerns associated with organochlorine exposure. Furthermore, the risks of mortality from not breast-feeding estimated by Rogan and colleagues exceed the theoretical cancer risks estimated for infant exposure to potential carcinogens in Canadian breast milk. Although levels of persistent compounds have been declining in Canadian breast milk, potentially significant risks were estimated for exposure to polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans. Follow-up work is suggested that would involve the use of a physiologically based toxicokinetic model with probabilistic inputs to predict dioxin exposure to the infant. A more detailed risk analysis could be carried out by coupling the exposure estimates with a dose–response analysis that accounts for uncertainty.     

Quantitative Risk Assessment of FMD Virus Transmission via Water

Foot-and-mouth disease (FMD) is a viral disease of domesticated and wild cloven-hoofed animals. FMD virus is known to spread by direct contact between infected and susceptible animals, by animal products such as meat and milk, by the airborne route, and mechanical transfer on people, wild animals, birds, and by vehicles. During the outbreak of 2001 in the Netherlands, milk from dairy cattle was illegally discharged into the sewerage as a consequence of transport prohibition. This may lead to contaminated discharges of biologically treated and raw sewage in surface water that is given to cattle to drink. The objective of the present study was to assess the probability of infecting dairy cows that were drinking FMD virus contaminated surface water due to illegal discharges of contaminated milk. So, the following data were collected from literature: FMD virus inactivation in aqueous environments, FMD virus concentrations in milk, dilution in sewage water, virus removal by sewage treatment, dilution in surface water, water consumption of cows, size of a herd in a meadow, and dose-response data for ingested FMD virus by cattle. In the case of 1.6 x 10(2) FMD virus per milliliter in milk and discharge of treated sewage in surface water, the probability of infecting a herd of cows was estimated to be 3.3 x 10(-7) to 8.5 x 10(-5), dependent on dilution in the receiving surface water. In the case of discharge of raw sewage, all probabilities of infection were 100 times higher. In the case of little dilution in small rivers, the high level of 8.5 x 10(-3) is reached. For 10(4) times higher FMD virus concentrations in milk, the probabilities of infecting a herd of cows are high in the case of discharge of treated sewage (3.3 x 10(-3) to 5.7 x 10(-1)) and very high in the case of discharge of raw sewage (0.28-1.0). It can be concluded that illegal and uncontrolled discharges of contaminated milk into the sewerage system may lead to high risks to other cattle farms at 6-50 km distance of the location of discharge within one day. This clearly underlines current measures that prohibit such discharges, and also asks for strict control. This risk assessment clearly demonstrated the potential significance of FMD virus transmission via water, and the results will be useful on an international scale, and could also serve as a basis for other FMD risk-assessment models.     

Improving the Milk Supply Chain in Developing Countries: Analysis,Insights, and Recommendations

Quality issues in milk—arising primarily from deliberate adulteration by producers—have been reported in several developing countries. In the milk supply chain, a station buys raw milk from a number of producers, mixes the milk and sells it to a firm (that then sells the processed milk to end consumers). We study a non‐cooperative game between a station and a population of producers. Apart from penalties on proven low‐quality producers, two types of incentives are analyzed: confessor rewards for low‐quality producers who confess and quality rewards for producers of high‐quality milk. Contrary to our expectations, whereas (small) confessor rewards can help increase both the quality of milk and the station's profit, quality rewards can be detrimental. We examine two structures based on the ordering of individual and mixed testing of milk: pre‐mixed individual testing (first test a fraction of producers individually and then [possibly] perform a mixed test on the remaining producers) and post‐mixed individual testing (first test the mixed milk from all producers and then test a fraction of producers individually). Whereas pre‐mixed individual testing can be socially harmful, a combination of post‐mixed individual testing and other incentives achieves a desirable outcome: all producers supply high‐quality milk with only one mixed test and no further testing by the station.     

Ebola Virus Dose Response Model for Aerosolized Exposures: Insights from Primate Data

This study develops dose–response models for Ebolavirus using previously published data sets from the open literature. Two such articles were identified in which three different species of nonhuman primates were challenged by aerosolized Ebolavirus in order to study pathology and clinical disease progression. Dose groups were combined and pooled across each study in order to facilitate modeling. The endpoint of each experiment was death. The exponential and exact beta-Poisson models were fit to the data using maximum likelihood estimation. The exact beta-Poisson was deemed the recommended model because it more closely approximated the probability of response at low doses though both models provided a good fit. Although transmission is generally considered to be dominated by person-to-person contact, aerosolization is a possible route of exposure. If possible, this route of exposure could be particularly concerning for persons in occupational roles managing contaminated liquid wastes from patients being treated for Ebola infection and the wastewater community responsible for disinfection. Therefore, this study produces a necessary mathematical relationship between exposure dose and risk of death for the inhalation route of exposure that can support quantitative microbial risk assessment aimed at informing risk mitigation strategies including personal protection policies against occupational exposures.     

Modeling of interventions for reducing external Enterobacteriaceae contamination of broiler carcasses during processing

This article presents a mathematical model for the Enterobacteriaceae count on the surface of broiler chicken during slaughter and how it may be affected by different processing technologies. The model is based on a model originally developed for Campylobacter and has been adapted for Enterobacteriaceae using a Bayesian updating approach and hitherto unpublished data gathered from German abattoirs. The slaughter process in the model consists of five stages: input, scalding, defeathering, evisceration, washing, and chilling. The impact of various processing technologies along the broiler processing line on the Enterobacteriaceae count on the carcasses’ surface has been determined from literature data. The model is implemented in the software R and equipped with a graphical user interface which allows interactively to choose among different processing technologies for each stage along the processing line. Based on the choice of processing technologies the model estimates the Enterobacteriaceae count on the surface of each broiler chicken at each stage of processing. This result is then compared to a so-called baseline model which simulates a processing line with a fixed set of processing technologies. The model calculations showed how even very effective removal of bacteria on the exterior of the carcass in a previous step will be undone by the cross-contamination with leaked feces, if feces contain high concentrations of bacteria.     

Dose‐Response Model of Coxiella burnetii (Q Fever)

Q fever is a zoonotic disease caused by the intracellular gram‐negative bacterium Coxiella burnetii (C. burnetii), which only multiplies within the phagolysosomal vacuoles. Q fever may manifest as acute or chronic disease. The acute form is generally not fatal and manifestes as self‐controlled febrile illness. Chronic Q fever is usually characterized by endocarditis. Many animal models, including humans, have been studied for Q fever infection through various exposure routes. The studies considered different endpoints including death for animal models and clinical signs for human infection. In this article, animal experimental data available in the open literature were fit to suitable dose‐response models using maximum likelihood estimation. Research results for tests of severe combined immunodeficient mice inoculated intraperitoneally (i.p.) with C. burnetii were best estimated with the Beta‐Poisson dose‐response model. Similar inoculation (i.p.) trial outcomes conducted on C57BL/6J mice were best fit by an exponential model, whereas those tests run on C57BL/10ScN mice were optimally represented by a Beta‐Poisson dose‐response model.     

Risk Assessment of Listeriosis Linked to the Consumption of Two Soft Cheeses Made from Raw Milk: Camembert of Normandy and Brie of Meaux

This article reports a quantitative risk assessment of human listeriosis linked to the consumption of soft cheeses made from raw milk. Risk assessment was based on data purposefully acquired inclusively over the period 2000-2001 for two French cheeses, namely: Camembert of Normandy and Brie of Meaux. Estimated Listeria monocytogenes concentration in raw milk was on average 0.8 and 0.3 cells/L, respectively, in Normandy and Brie regions. A Monte Carlo simulation was used to account for the time-temperature history of the milk and cheeses from farm to table. It was assumed that cell progeny did not spread within the solid cheese matrix (as they would be free to do in liquid broth). Interaction between pH and temperature was accounted for in the growth model. The simulated proportion of servings with no L. monocytogenes cell was 88% for Brie and 82% for Camembert. The 99th percentile of L. monocytogenes cell numbers in servings of 27 g of cheese was 131 for Brie and 77 for Camembert at the time of consumption, corresponding respectively to three and five cells of L. monocytogenes per gram. The expected number of severe listeriosis cases would be < or =10(-3) and < or =2.5 x 10(-3) per year for 17 million servings of Brie of Meaux and 480 million servings of Camembert of Normandy, respectively.     

Improving Risk Assessment Calculations for Traditional Foods Through Collaborative Research with First Nations Communities

As industrial development is increasing near northern Canadian communities, human health risk assessments (HHRA) are conducted to assess the predicted magnitude of impacts of chemical emissions on human health. One exposure pathway assessed for First Nations communities is the consumption of traditional plants, such as muskeg tea (Labrador tea) (Ledum/Rhododendron groenlandicum) and mint (Mentha arvensis). These plants are used to make tea and are not typically consumed in their raw form. Traditional practices were used to harvest muskeg tea leaves and mint leaves by two First Nations communities in northern Alberta, Canada. Under the direction of community elders, community youth collected and dried plants to make tea. Soil, plant, and tea decoction samples were analyzed for inorganic elements using inductively coupled plasma‐mass spectrometry. Concentrations of inorganic elements in the tea decoctions were orders of magnitude lower than in the vegetation (e.g., manganese 0.107 mg/L in tea, 753 mg/kg in leaves). For barium, the practice of assessing ingestion of raw vegetation would have resulted in a hazard quotient (HQ) greater than the benchmark of 0.2. Using measured tea concentrations it was determined that exposure would result in risk estimates orders of magnitude below the HQ benchmark of 0.2 (HQ = 0.0049 and 0.017 for muskeg and mint tea, respectively). An HHRA calculating exposure to tea vegetation through direct ingestion of the leaves may overestimate risk. The results emphasize that food preparation methods must be considered when conducting an HHRA. This study illustrates how collaboration between Western scientists and First Nations communities can add greater clarity to risk assessments.     

Dose‐Response Model of Rocky Mountain Spotted Fever (RMSF) for Human

Rickettsia rickettsii is the causative agent of Rocky Mountain spotted fever (RMSF) and is the prototype bacterium in the spotted fever group of rickettsiae, which is found in North, Central, and South America. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through tick bites; however, some cases of aerosol transmission also have been reported. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment, it can be fatal. This article develops dose‐response models of different routes of exposure for RMSF in primates and humans. The beta‐Poisson model provided the best fit to the dose‐response data of aerosol‐exposed rhesus monkeys, and intradermally inoculated humans (morbidity as end point of response). The average 50% infectious dose among (ID₅₀) exposed human population, N₅₀, is 23 organisms with 95% confidence limits of 1 to 89 organisms. Similarly, ID₁₀ and ID₂₀ are 2.2 and 5.0, respectively. Moreover, the data of aerosol‐exposed rhesus monkeys and intradermally inoculated humans could be pooled. This indicates that the dose‐response models fitted to different data sets are not significantly different and can be described by the same relationship.