beta-Poisson Dose-response Model Research Articles

Concentration and risk assessment of Cryptosporidium infection associated with exposure to the Njoro River, Njoro Sub-County, Nakuru, Kenya

BackgroundCryptosporidium is a gastrointestinal pathogen. The oocysts are transmitted through the environment, and drinking contaminated water is one particular route. There is heavy pollution of Cryptosporidium in Njoro River, the main source of drinking water for humans and animals around the watershed. However, there is no information on the parasite concentration and estimated health risk exposed to these populations. This study determined the level of contamination and risk of infection by Cryptosporidium parasites in Njoro River. Water samples were collected monthly from three ecological sites along Njoro River for twelve months. Cryptosporidium oocysts were concentrated from these water samples using calcium carbonate flocculation method, examined and counted using epifluorescent microscopy. Quantitative microbial risk assessment was applied to estimate the health risk of Cryptosporidium infection in Njoro River using a beta-Poisson dose–response model.ResultsThe concentration of Cryptosporidium parasites in Njoro River is 0.936 ± 0.73 oocysts/litre. However, this concentration fluctuates with ecological site of the river; highest concentration occurs at downstream (1.325 ± 0.73), followed by midstream (0.917 ± 0.74) and least at upstream (0.567 ± 0.54). Concentration of Cryptosporidium in the river is higher during wet than dry seasons, with the difference in mean concentrations between the two seasons being significant (t(34) = − 6.101, p < 0.01). There was a negative correlation between Cryptosporidium concentration, temperature and pH, while a strong positive correlation existed between Cryptosporidium concentration and turbidity. The daily probability of infection by Cryptosporidium in Njoro River watershed is 0.25, while the annual risk is 0.99.ConclusionsNjoro River is heavily polluted with Cryptosporidium parasites. This exposes both the humans and animals that drink water from this river to a high risk of cryptosporidiosis, a potentially fatal infection particularly in immunocompromised individuals.

Assessing the Prevalence and Potential Risks of Salmonella Infection Associated with Fresh Salad Vegetable Consumption in the United Arab Emirates.

This study aimed to investigate the occurrence and characteristics of Salmonella isolates in salad vegetables in the United Arab Emirates (UAE). Out of 400 samples tested from retail, only 1.25% (95% confidence interval, 0.41-2.89) were found to be positive for Salmonella, all of which were from conventional local produce, presented at ambient temperature, and featured as loose items. The five Salmonella-positive samples were arugula (n = 3), dill (n = 1), and spinach (n = 1). The Salmonella isolates from the five samples were found to be pan-susceptible to a panel of 12 antimicrobials tested using a disc diffusion assay. Based on whole-genome sequencing (WGS) analysis, only two antimicrobial resistance genes were detected-one conferring resistance to aminoglycosides (aac(6')-Iaa) and the other to fosfomycin (fosA7). WGS enabled the analysis of virulence determinants of the recovered Salmonella isolates from salad vegetables, revealing a range from 152 to 165 genes, collectively grouped under five categories, including secretion system, fimbrial adherence determinants, macrophage-inducible genes, magnesium uptake, and non-fimbrial adherence determinants. All isolates were found to possess genes associated with the type III secretion system (TTSS), encoded by Salmonella pathogenicity island-1 (SPI-1), but various genes associated with the second type III secretion system (TTSS-2), encoded by SPI-2, were absent in all isolates. Combining the mean prevalence of Salmonella with information regarding consumption in the UAE, an exposure of 0.0131 salmonellae consumed per person per day through transmission via salad vegetables was calculated. This exposure was used as an input in a beta-Poisson dose-response model, which estimated that there would be 10,584 cases of the Salmonella infection annually for the entire UAE population. In conclusion, salad vegetables sold in the UAE are generally safe for consumption regarding Salmonella occurrence, but occasional contamination is possible. The results of this study may be used for the future development of risk-based food safety surveillance systems in the UAE and to elaborate on the importance for producers, retailers, and consumers to follow good hygiene practices, particularly for raw food items such as leafy salad greens.

Seasonal assessment of risks to canoeists' health in a Taiwanese recreational river.

Canoeing is the most favorite recreational activity in several Taiwanese rivers. However, river water frequently contains elevated levels of pathogenic Escherichia coli, which has adverse effects on human health. This study adopted a quantitative microbial risk assessment to analyze seasonal risks to canoeists' health in the Dongshan River, Taiwan. First, river E. coli concentrations were statistically analyzed to determine the seasonal distributions. The exposure duration (ED) was determined by field observations. To propagate the parametric uncertainty, Monte Carlo simulation was employed to model the probability distributions of seasonal pathogenic E. coli levels, ingestion rates, and ED for athletes. Finally, the beta-Poisson dose-response model was implemented to determine seasonal health risks for canoeists. The study results indicated that the health risks in infection probability ranged from 0.5×10-3 to 8.8×10-3 illnesses/person/day for tourists and 1.2×10-3 to 7.7×10-3 illnesses/person/day for athletes. The health risks in the Lizejian Bridge area for tourists exceeded an acceptable level suggested by the U.S. Environmental Protection Agency, 8×10-3 illnesses/person/day, in spring for an ED of 2h/day, and the health risks for tourists and athletes approached this level in spring and winter for an ED exceeding or equaling 1.5h/day. According to sensitivity analysis, the geometric standard deviation of river E. coli levels was the most sensitive parameter affecting seasonal risks to canoeists' health. To protect canoeists' health, effluent sewer systems, best management practices, and total maximum daily loads should be promptly implemented in this watershed.

Extension of probability models of the risk of infections by human enteric viruses.

This study presents a novel approach for obtaining reliable models and coefficients to estimate the probability of infection caused by common human enteric viruses. The aim is to provide guidance for public health policies in disease prevention and control, by reducing uncertainty and management costs in health risk assessments. Conventional dose-response (DR) models, based on the theory elaborated by Furumoto and Mickey [1], exhibit limitations stemming from the heterogeneity of individual host susceptibilities to infection resulting from ingesting aggregate viruses. Moreover, the scarcity of well-designed viral challenge experiments contributes to significant uncertainty in these DR models. To address these issues, we conducted a review of infection models used in health risk analysis, focusing on Norovirus (NoV) GI.1, pooled Enterovirus group (EV), Poliovirus 1/SM, and Echo-12 virus via contaminated water or food. Using a mechanistic approach, we reevaluated the known DR models and coefficients for the probability of individual host infection in the mentioned viruses based on dose-infection challenge experiments. Specifically, we sought to establish a relationship between the minimum infectious dose (ID) and the ID having a 50% probability of initiating host infection in the same challenge experiment. Furthermore, we developed a new formula to estimate the degree of aggregation of GI.1 NoV at the mean infectious dose. The proposed models, based on "exact" beta-Poisson DR models, effectively predicted infection probabilities from ingestion of both disaggregated and aggregate NoV GI.1. Through a numerical evaluation, we compared the results with the maximum likelihood estimation (MLE) probability obtained from a controlled challenge trial with the NoV GI.1 virus described in the literature, demonstrating the accuracy of our approach. By addressing the indetermination of the unmeasured degree of NoV aggregation in each single infectious dose, our models reduce overestimations and uncertainties in microbial risk assessments. This improvement enhances the management of health risks associated with enteric virus infections.

Quantitative Risk Assessment of Vibrio parahaemolyticus in Shellfish from Retail to Consumption in Coastal Cities of Eastern China

Vibrio parahaemolyticus is the main foodborne pathogen worldwide that causes acute gastroenteritis. A quantitative microbiological risk assessment (QMRA) was conducted to evaluate the health risk associated with V. parahaemolyticus in shellfish in the coastal cities in the eastern part of the People's Republic of China. The QMRA framework was established from shellfish at retail to cooking at home to consumption. The prevalence and level of V. parahaemolyticus in shellfish, cooking methods, storage temperature, time after purchase, shellfish consumption frequency, and consumption amount were analyzed in the exposure assessment. The results of the exposure assessment were introduced into the beta-Poisson dose-response model, and Monte Carlo analysis was used to calculate the risk of gastroenteritis from shellfish consumption. The probability of illness caused by V. parahaemolyticus from shellfish consumption per person per year (Pill,yr) was 3.49E-05. Seasonal differences were noted in the Pill/meal; the maximum was 4.81E-06 in summer and the minimum was 2.27E-07 in winter. The sensitivity analysis revealed that the level of V. parahaemolyticus in shellfish and the amount of shellfish consumed per meal were main factors contributing to illness. This QMRA provided valuable information such as the probability of illness associated with the consumption of shellfish and reference points for prevention strategies and control standards of V. parahaemolyticus in shellfish.

Preliminary quantitative risk assessment of the effect of Salmonella on human health in retail fresh pork

A quantitative microbiological risk assessment was conducted for Salmonella spp. in fresh pork from retail stores to consumers in China in order to provide evidence for adopting effective risk management measures. The national food safety and risk monitoring data was used to estimate the initial contamination level of Salmonella in the retail fresh pork. The growth model and the cross-contamination model of Salmonella were referenced from the ComBase data base and scientific literature, respectively. Then the human health risk was predicted by the consumption of Salmonella-contaminated fresh pork and the Beta-Poisson dose-response model. The number of Salmonellosis per year among 1 million residents due to fresh pork was estimated to be 4748.The sensitivity analysis showed that the risk of Salmonellosis was mainly and positively correlated with the preparation rate of ready to eat food, the consumption quantity of pork, the initial contamination level of Salmonella in fresh pork, and the proportion of improper cleaning of knives and chopping boards. When the contamination level of Salmonella in fresh pork is controlled below 1 CFU/g, the average probability of illness will be reduced by 59.39%; the average probability of illness will be reduced by 58.97% by increasing the ratio of complete cleaning of chopping boards or the separation ratio of chopping boards for raw and ready-to-eat food to 90%. The risk could be effectively reduced by controlling the concentration of Salmonella contamination in retail pork or improving hygiene practices.

Preliminary Quantitative Risk Assessment of Norovirus in Shellfish in the Yellow Sea and Bohai Sea of China

Norovirus (NoV) is a main foodborne pathogen of acute gastroenteritis in the world. A preliminary quantitative risk assessment (QRA) was conducted to evaluate the health risk caused by this virus in shellfish in the Yellow Sea and Bohai Sea of China. The QRA framework was established from the process of shellfish at retail through cooking at home to consumer consumption. The prevalence and quantity of NoVs in shellfish, cooking methods, internal temperature and time of shellfish in different cooking conditions, shellfish consumption frequency, and consumption amount were analyzed in the exposure assessment. The results of exposure assessment were introduced into the beta-Poisson dose-response model, and Monte Carlo analysis was used to calculate the risk of gastroenteritis caused by shellfish consumption in the cities around the Yellow Sea and Bohai Sea of China. The results showed that the probability of illness caused by NoVs due to shellfish consumption per year (Pill,yr) was 1.86 × 10-5. It was estimated that the annual number of patients with gastroenteritis per 1,000,000 general population (Nexp,mil) was 0.10, 1.23, 16.90, and 0.38 for population aged 0-4, 5-18, 19-64, and >65 years, respectively. This assessment provides valuable information such as the probability of illness associated with the consumption of shellfish and it also provides a reference for further in-depth QRA of NoVs in shellfish or other foods.

Quantitative microbial risk assessment for waterborne pathogens in a wastewater treatment plant and its receiving surface water body

BackgroundAccess to safe water for drinking and domestic activities remains a challenge in emerging economies like South Africa, forcing resource-limited communities to use microbiologically polluted river water for personal and household purposes, posing a public health risk. This study quantified bacterial contamination and the potential health hazards that wastewater treatment plant (WWTP) workers and communities may face after exposure to waterborne pathogenic bacteria in a WWTP and its associated surface water, respectively.ResultsEscherichia coli (Colilert®-18/ Quanti-Tray® 2000) and enterococci (Enterolert®/ Quanti-Tray® 2000) were quantified and definitively identified by real-time polymerase chain reaction targeting the uidA and tuf genes, respectively. An approximate beta-Poisson dose-response model was used to estimate the probability of infection (Pi) with pathogenic E. coli. Mean E. coli concentration ranged from 2.60E+ 02/100 mL to 4.84E+ 06/100 mL; enterococci ranged from 2.60E+ 02/100 mL to 3.19E+ 06/100 mL across all sampled sites. Of the 580 E. coli isolates obtained from this study, 89.1% were intestinal, and 7.6% were extraintestinal pathogenic E. coli. The 579 enterococci obtained were 50.4% E. faecalis (50.4%), 31.4% E. faecium, 3.5%, E. casseliflavus and 0.7% E. gallinarum. The community health risk stemming from the use of the water for recreational and domestic purposes revealed a greater health risk (Pi) from the ingestion of 1 mL of river water from upstream (range, 55.1–92.9%) than downstream (range, 26.8–65.3%) sites. The occupational risk of infection with pathogenic E. coli for workers resulting from a once-off unintentional consumption of 1 mL of water was 0% (effluent) and 23.8% (raw influent). Multiple weekly exposures of 1 mL over a year could result in a Pi of 1.2 and 100% for the effluent and influent, respectively.ConclusionOur findings reveal that there is a potentially high risk of infection for WWTP workers and communities that use river water upstream and downstream of the investigated WWTP.

Survey of Listeria monocytogenes contamination of various environmental samples and associated health risks

Listeria monocytogenes is the causative agent of listeriosis, one of the most important foodborne infections. Pre-harvest contamination of ready to eat crops constitutes a potential source of Listeria infections. The aim of this study was to investigate the presence of Listeria spp. and L. monocytogenes via molecular methods in wastewater effluent, sewage sludge (SS) and livestock manure as potential sources of Listeria. The presence of L. monocytogenes in wastewater-irrigated soil and crops was also investigated. Quantitative microbial risk assessment (QMRA) was performed for analysis of Listeria infections for SS workers and farmers. The results of survey showed no presence of L. monocytogenes in wastewater effluent and wastewater-irrigated soil and crop samples, whereas L. monocytogenes was detected in SS (50%) and manure (8%) samples. QMRA analysis using exponential model showed that the likelihood of Listeria infections from direct ingestion of SS to be very low. In contrast, Beta-Poisson dose-response model showed an annual risk of Listeria infections higher than the proposed value of 10−4 per person per year (pppy) by EPA, with the highest risk (4.41 × 10−1 pppy) for SS workers. Based on our results, the agricultural use of wastewater doesn't seem to present risk of Listeria infections for consumers of wastewater-irrigated crops. However, direct ingestion of SS may pose a risk for exposed individuals. The estimated risk values could be further improved by obtaining accurate insights into the prevalence of Listeria infections especially at national or regional level. Further studies are also needed to determine inactivation rate of Listeria in SS-amended soils in arid and semi-arid areas.

Modeling the Risk of Salmonellosis from Consumption of Peanuts in the United States

Peanut products were the target of the largest food recall in United States history from 2008 to 2009, with more than 3,200 products implicated, economic losses estimated at $1 billion, and more than 700 reported illnesses and 9 deaths. Predictive modeling tools such as quantitative microbial risk assessment can be used to aid processors in making risk management decisions that may reduce the chances of foodborne illness, but published risk assessment for peanuts is not currently available. A quantitative microbial risk assessment was performed to quantify salmonellosis risk from consumption of peanuts in the United States. Prevalence and concentration data for Salmonella on raw, shelled peanuts were used in combination with probability distributions of simulated log reductions achieved during production steps before consumption. Data for time-temperature combinations used in each step were obtained from published literature, industry surveys, or expert opinion, and survival data were obtained from the literature. A beta-Poisson dose-response model was used to predict probability of illness from ingestion of Salmonella cells. The model predicted 14.2 (arithmetic mean) or 0.0123 (geometric mean) illnesses per year. Sensitivity analysis showed that thermal inactivation log reductions applied had the biggest impact on predicted salmonellosis risk, followed by consumer storage time, Salmonella starting concentration, Salmonella starting prevalence, and number of originally contaminated 25-g servings per originally positive 375-g sample. Scenario analysis showed that increasing log reduction variability increased mean salmonellosis risk. Removing the effect of storage on Salmonella survival increased the arithmetic and geometric means to 153 and 0.598 illnesses per year, respectively. This study indicated that the risk of salmonellosis from consumption of peanuts can be lowered by reducing field contamination, control of storage steps, and monitoring of appropriate critical limits in peanut roasting.

Preliminary quantitative microbial risk assessment of pathogenic Vibrio parahaemolyticus in short mackerel in Malaysia

A preliminary quantitative microbial risk assessment of Vibrio parahaemolyticus in short mackerels was conducted from retail to consumption levels in a stochastic model. The key uncertainties included of growth during retail display, transportation duration, and microbial log reduction after the preparation and cooking steps were taken into consideration in the exposure assessment. Human health risk associated with the consumption of short mackerels contaminated with pathogenic V. parahaemolyticus was predicted by fitting the number of cells ingested into a Beta-Poisson dose-response model. Advanced sensitivity analysis was performed to determine the predictive factors most highly correlated with risk illness. The model evaluated through Monte Carlo simulation revealed an estimated number of illness ranged from 1.34 × 10−4 to 12.80 with an average incidence of 2.07 cases per annum. The rates per 100,000 population were predicted at 6.53 × 10−3 cases per year in Malaysia. In this study, the development of quantitative microbial risk assessment of V. parahaemolyticus in short mackerels provides valuable information such as the probability of illness associated with the consumption of short mackerels and the primary factor quantitatively important for risk illness.

Development of a dose-response model for Naegleria fowleri.

This study develops novel dose-response models for Naegleria fowleri from selected peer-reviewed experiments on the virulence based on the intranasal exposure pathway. One data set measured the response of mice intranasally inoculated with the amebae and the other study addressed the response of mice swimming in N. fowleri infected water. The measured response for both studies was death. All experimental data were best fit by the beta-Poisson dose-response model. The three swimming experiments could be pooled, and this is the final recommended model with an LD50 of 13,257 amebae. The results of this study provide a better estimate of the probability of the risk to N. fowleri exposure than the previous models developed based on an intravenous exposure. An accurate dose-response model is the first step in quantifying the risk of free-living amebae like N. fowleri, which pose risks in recreational environments and have been detected in drinking water and premise plumbing systems. A better understanding of this risk will allow for risk management that limits the ability for pathogen growth, proliferation, and exposure.

Dose-response models for eastern US, western US and Venezuelan equine encephalitis viruses in mice–Part II: Quantification of the effects of host age on the dose response

Many infectious disease hazards demonstrate higher susceptibility with regards to younger host ages. This trend of increased susceptibility with decreasing host age can also lead to an increased likelihood of mortality, and prolonged/chronic health effects. For quantitative microbial risk assessment (QMRA) modeling, the ability to quantify the effect of host age in the dose response model can allow modelers to account for these effects mechanistically. Additionally, QMRA modelers using age-dependent dose response models can model entire populations within the dose-response itself rather than modeling age ranges using susceptibility factors. This research developed host-age dependent exponential and beta Poisson dose response models for Eastern, Western and Venezuelan encephalitis viruses (EEV, WEV and VEV respectively) for two routes – intracranial and intraperitoneal. Improvement in fit was statistically tested as a means of assessing the benefit of including age dependency into the dose response models. EEV demonstrated improvement in fit using host-age dependency only for the exponential model except for intracranial exposure. EEV demonstrated an improvement in fit when using age dependency in the beta Poisson dose response model for both exposure routes. VEV demonstrated an improvement in fit using age dependency for both exposure routes. WEV demonstrated an improvement in fit for intracranial exposure, but neither of the age dependent dose-response models provided a good fit for WEV intraperitoneal exposure.

Authors' Response to Comment on "Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model" - Previously Published Guidelines Continue to Be Ignored.

Authors' Response to Comment on "Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model" - Previously Published Guidelines Continue to Be Ignored.

Quantitative microbial risk assessment (QMRA) shows increased public health risk associated with exposure to river water under conditions of riverbed sediment resuspension

Although higher microbial concentrations have been reported in sediments than in the overlying water column, most quantitative microbial risk assessment (QMRA) studies have not clearly indicated the contribution of sediment-borne pathogens to estimated risks. Thus, the present study aimed at determining the public health risk associated with exposure to pathogenic bacteria in polluted river water under undisturbed conditions and conditions of sediment resuspension in the Apies River, Gauteng, South Africa. Microbial pathogens were isolated and identified using culture and molecular methods. The beta-Poisson dose-response model was used to estimate the probability of infection (Pi) with the various pathogens, following accidental/intentional ingestion of 1mL or 100mL (or 50mL) of untreated river water. Mean wet season Escherichia coli counts ranged between 5.8E+01 and 8.8E+04MPN/100mL (water column) and between 2.40E+03 and 1.28E+05MPN/100mL (sediments). Mean dry season E. coli counts ranged between 5.11E+00 and 3.40E+03MPN/100mL (water column) and between 5.09E+00 and 6.30E+03MPN/100mL (sediments). Overall (water and sediments) Vibrio cholerae was the most detected pathogen (58.8%) followed by Salmonella spp. (23.9%) and Shigella (10.1%). Ingestion of 1mL of river water could lead to 0%–4% and 1%–74% Pi with E. coli during the dry and wet season, respectively. During the dry season, the Pi with V. cholerae, Salmonella spp. and Shigella spp. were 0%–1.39%, 0%–4.11% and 0%–0.16% respectively, depending on volume of water ingested. The risks of infections with all microorganisms increased during the wet season. A 2-log increase in water E. coli count following sediments disturbance led to approximately 10 times higher Pi with E. coli than when sediments were undisturbed. Therefore, the use of the untreated water from the Apies River for drinking, household purposes or recreational activities poses a potential health risk to the users of the river.

A Generalized QMRA Beta-Poisson Dose-Response Model.

Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|α,β,r*), is proposed in which the minimum number of organisms required for causing infection, Kmin , is not fixed, but a random variable following a geometric distribution with parameter 0<r*≤1. The single-hit beta-Poisson model, PI(d|α,β), is a special case of the generalized model with Kmin = 1 (which implies r*=1). The generalized beta-Poisson model is based on a conceptual model with greater detail in the dose-response mechanism. Since a maximum likelihood solution is not easily available, a likelihood-free approximate Bayesian computation (ABC) algorithm is employed for parameter estimation. By fitting the generalized model to four experimental data sets from the literature, this study reveals that the posterior median r* estimates produced fall short of meeting the required condition of r* = 1 for single-hit assumption. However, three out of four data sets fitted by the generalized models could not achieve an improvement in goodness of fit. These combined results imply that, at least in some cases, a single-hit assumption for characterizing the dose-response process may not be appropriate, but that the more complex models may be difficult to support especially if the sample size is small. The three-parameter generalized model provides a possibility to investigate the mechanism of a dose-response process in greater detail than is possible under a single-hit model.

Analysis of Vibrio vulnificus Infection Risk When Consuming Depurated Raw Oysters

A beta Poisson dose-response model for Vibrio vulnificus food poisoning cases leading to septicemia was used to evaluate the effect of depuration at 15°C on the estimated health risk associated with raw oyster consumption. Statistical variability sources included V. vulnificus level at harvest, time and temperature during harvest and transportation to processing plants, decimal reductions (SV) observed during experimental circulation depuration treatments, refrigerated storage time before consumption, oyster size, and number of oysters per consumption event. Although reaching nondetectable V. vulnificus levels (<30 most probable number per gram) throughout the year and a 3.52 SV were estimated not possible at the 95% confidence level, depuration for 1, 2, 3, and 4 days would reduce the warm season (June through September) risk from 2,669 cases to 558, 93, 38, and 47 cases per 100 million consumption events, respectively. At the 95% confidence level, 47 and 16 h of depuration would reduce the warm and transition season (April through May and October through November) risk, respectively, to 100 cases per 100 million consumption events, which is assumed to be an acceptable risk; 1 case per 100 million events would be the risk when consuming untreated raw oysters in the cold season (December through March).

Development of an Interspecies Nested Dose-Response Model for Mycobacterium avium subspecies paratuberculosis.

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 × 10(2) 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.

Development of dose-response models of Creutzfeldt-Jakob disease infection in nonhuman primates for assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease.

Estimates for the risk of transmitting variant Creutzfeldt-Jakob disease (vCJD) via blood transfusion have relied largely on data from rodent experiments, but the relationship between dose (amount of infected blood) and response (vCJD infection) has never been well quantified. The goal of this study was to develop a dose-response model based on nonhuman primate data to better estimate the likelihood of transfusion-transmitted vCJD (TTvCJD) in humans. Our model used dose-response data from nonhuman primates inoculated intracerebrally (i.c.) with brain tissues of patients with sporadic and familial CJD. We analyzed the data statistically by using a beta-Poisson dose-response model. We further adjusted model parameters to account for the differences in infectivity between blood and brain tissue and in transmission efficiency between intravenous (i.v.) and i.c. routes to estimate dose-dependent TTvCJD infection. The model estimates a mean infection rate of 76% among recipients who receive one unit of whole blood collected from an infected donor near the end of the incubation period. The nonhuman primate model provides estimates that are more consistent with those derived from a risk analysis of transfused nonleukoreduced red blood cells in the United Kingdom than prior estimates based on rodent models. TTvCJD was recently identified as one of three emerging infectious diseases posing the greatest immediate threat to the safety of the blood supply. Cases of TTvCJD were reported in recipients of nonleukoreduced red blood cells and coagulation factor VIII manufactured from blood of United Kingdom donors. As the quantity of abnormal prions (the causative agent of TTvCJD) varies significantly in different blood components and products, it is necessary to quantify the dose-response relationship for a wide range of doses for the vCJD agent in transfused blood and plasma derivatives. In this paper, we suggest the first mechanistic dose-response model for TTvCJD infection based on data from experiments with nonhuman primates. This new model may improve estimates of the possible risk to humans.

An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10), and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.