Implementing a New Dose-response Model for Estimating Infection Probability of Campylobacter Jejuni based on the Key Events Dose-response Framework

Abstract Understanding the dose-response relationship between ingested pathogenic bacteria and infection probability is a key factor for appropriate risk assessment of foodborne pathogens. The objectives of this study were to develop and validate a novel mechanistic dose-response model for Campylobacter jejuni and simulate the underlying mechanism of foodborne illness during digestion. Bacterial behavior in the human gastrointestinal environment, including gastric reductions, transition to intestines, and invasion to intestinal tissues, was described using a Bayesian statistical model based on the reported experimental results of each process while considering physical food types (liquid or solid) and host age (young or elderly). Combining the models in each process, the relationship between pathogen intake and the cell invasion probability of C. jejuni was estimated and compared with reported epidemiological dose-response relationships. Taking food types into account, estimations of the cell invasion probability of C. jejuni successfully described the reported dose-response relationships from substantial accidents. The developed calculation framework is thus potentially applicable to other pathogens to quantify the dose-response relationship from experimental data obtained from digestion.

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Implementing a new dose-response model for estimating infection probability of Campylobacter jejuni based on the key events dose-response framework

Applied and Environmental Microbiology ◽

10.1128/aem.01299-21 ◽

2021 ◽

Author(s):

Hiroki Abe ◽

Kohei Takeoka ◽

Yuto Fuchisawa ◽

Kento Koyama ◽

Shigenobu Koseki

Keyword(s):

Risk Assessment ◽

Campylobacter Jejuni ◽

Dose Response ◽

Food Type ◽

Response Model ◽

Host Age ◽

Response Relationship ◽

Dose Response Relationship ◽

Mechanistic Approach ◽

Key Events

Understanding the dose-response relationship between ingested pathogenic bacteria and infection probability is a key factor for appropriate risk assessment of foodborne pathogens. The objectives of this study were to develop and validate a novel mechanistic dose-response model for Campylobacter jejuni and simulate the underlying mechanism of foodborne illness during digestion. Bacterial behavior in the human gastrointestinal environment, including survival at low pH in the gastric environment after meals, transition to intestines, and invasion to intestinal tissues, was described using a Bayesian statistical model based on the reported experimental results of each process while considering physical food types (liquid or solid) and host age (young adult or elderly). Combining the models in each process, the relationship between pathogen intake and the infection probability of C. jejuni was estimated and compared with reported epidemiological dose-response relationships. Taking food types and host age into account, the prediction range of the infection probability of C. jejuni successfully covered the reported dose-response relationships from actual C. jejuni outbreaks. According to sensitivity analysis of predicted infection probabilities, the host age factor and the food type factor have relatively higher relevance than other factors. Thus, the developed Key Events Dose Response Framework can derive novel information for quantitative microbiological risk assessment in addition of dose-response relationship. The developed framework is potentially applicable to other pathogens to quantify the dose-response relationship from experimental data obtained from digestion. Importance Based on the mechanistic approach called Key Events Dose Response Framework alternative to previous non-mechanistic approach, the dose-response models for infection probability of C. jejuni were developed considering with age of people who take pathogen and food type. The developed predictive framework illustrated highly accurate prediction of dose (minimum difference 0.21 log CFU) for a certain infection probability compared with the previously reported dose-response relationship. In addition, the developed prediction procedure revealed that the dose-response relationship strongly depends on food type as well as host age. The implementation of Key Event Dose Response Framework will mechanistically and logically reveal the dose-response relationship and provide useful information with quantitative microbiological risk assessment of C. jejuni on foods.

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A generalized dose-response relationship for adenovirus infection and illness by exposure pathway

Epidemiology and Infection ◽

10.1017/s0950268816001862 ◽

2016 ◽

Vol 144 (16) ◽

pp. 3461-3473 ◽

Cited By ~ 19

Author(s):

P. TEUNIS ◽

J. SCHIJVEN ◽

S. RUTJES

Keyword(s):

Dose Response ◽

Respiratory Illness ◽

Response Model ◽

Response Relationship ◽

Limited Data ◽

Dose Response Relationship ◽

Oral Ingestion ◽

Exposure Pathway ◽

Inoculation Route ◽

Account Variation

SUMMARYAdenoviruses are found everywhere in the environment, and cause various health problems including symptoms of enteric illness, and respiratory illness. Despite their significance to public health, few studies have addressed the health risks associated with exposure to adenovirus. Human challenge studies have been published for a few adenoviruses, which involved exposure through oral ingestion, inhalation, intranasal and intraocular droplet inoculation. Nothwithstanding the different symptoms resulting from such exposures, infection can be defined as colonization of a corresponding mucosa. A two-level dose-response model was developed to describe the distributions of infectivity and pathogenicity in various challenge studies of adenovirus, incorporating differences in inoculation route as shift in average infectivity and pathogenicity. This dose-response model can be used to make predictions for the infectivity of adenovirus, specific to any of the four studied inoculation methods. The generalized adenovirus dose-response relationship for infection and acute illness takes into account variation in infectivity and/or pathogenicity across adenovirus types, as well as uncertainty due to limited data.

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Hierarchical dose response of E. coli O157:H7 from human outbreaks incorporating heterogeneity in exposure

Epidemiology and Infection ◽

10.1017/s0950268807008771 ◽

2007 ◽

Vol 136 (6) ◽

pp. 761-770 ◽

Cited By ~ 97

Author(s):

P. F. M. TEUNIS ◽

I. D. OGDEN ◽

N. J. C. STRACHAN

Keyword(s):

Dose Response ◽

Foodborne Pathogens ◽

Poisson Model ◽

Additional Parameter ◽

Response Model ◽

Susceptible Population ◽

E Coli ◽

Risk Assessment Models ◽

Human Volunteers ◽

Key Factor

SUMMARYThe infectivity of pathogenic microorganisms is a key factor in the transmission of an infectious disease in a susceptible population. Microbial infectivity is generally estimated from dose–response studies in human volunteers. This can only be done with mildly pathogenic organisms. Here a hierarchical Beta-Poisson dose–response model is developed utilizing data from human outbreaks. On the lowest level each outbreak is modelled separately and these are then combined at a second level to produce a group dose–response relation. The distribution of foodborne pathogens often shows strong heterogeneity and this is incorporated by introducing an additional parameter to the dose–response model, accounting for the degree of overdispersion relative to Poisson distribution. It was found that heterogeneity considerably influences the shape of the dose–response relationship and increases uncertainty in predicted risk. This uncertainty is greater than previously reported surrogate and outbreak models using a single level of analysis. Monte Carlo parameter samples (α, β of the Beta-Poisson model) can be readily incorporated in risk assessment models built using tools such as S-plus and @ Risk.

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Use of Epidemiologic and Food Survey Data To Estimate a Purposefully Conservative Dose-Response Relationship for Listeria monocytogenes Levels and Incidence of Listeriosis†

Journal of Food Protection ◽

10.4315/0362-028x-60.8.918 ◽

1997 ◽

Vol 60 (8) ◽

pp. 918-922 ◽

Cited By ~ 102

Author(s):

ROBERT L. BUCHANAN ◽

WILLIAM G. DAMERT ◽

RICHARD C. WHITING ◽

MICHAEL van SCHOTHORST

Keyword(s):

Listeria Monocytogenes ◽

Survey Data ◽

Dose Response ◽

Foodborne Pathogens ◽

Foodborne Pathogen ◽

Significant Risk ◽

Biological Agent ◽

Quantitative Microbial Risk Assessment ◽

Response Relationship ◽

Dose Response Relationship

The development of effective quantitative microbial risk-assessment models for foodborne pathogens depends on the availability of data on the consumers' exposure to a biological agent and the dose-response relationship that relates levels of the biological agent ingested with frequency of infection or disease. Information on the latter has historically been acquired from human volunteer feeding studies. However, such studies are not feasible for pathogens that either have a significant risk of being life threatening or for which morbidity is primarily associated with high-risk populations (i.e., immunocompromised persons). For these pathogens, it is proposed that purposefully conservative dose-response relationships can be estimated on the basis of combining available epidemiologic data with food-survey data for a ready-to-eat product. As an example, data on the incidence of listeriosis in Germany were combined with data on the levels of Listeria monocytogenes in smoked fish to generate a dose-response curve for this foodborne pathogen.

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Assessment of the dose-response relationship of Campylobacter jejuni

International Journal of Food Microbiology ◽

10.1016/0168-1605(96)00994-4 ◽

1996 ◽

Vol 30 (1-2) ◽

pp. 101-111 ◽

Cited By ~ 98

Author(s):

G.J. Medema ◽

P.F.M. Teunis ◽

A.H. Havelaar ◽

C.N. Haas

Keyword(s):

Campylobacter Jejuni ◽

Dose Response ◽

Response Relationship ◽

Dose Response Relationship ◽

Relationship Of

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A SUBCUTANEOUS INJECTION ASSAY FOR ANTI-ANDROGENS IN THE CHICK

Acta Endocrinologica ◽

10.1530/acta.0.0410268 ◽

1962 ◽

Vol 41 (2) ◽

pp. 268-273 ◽

Cited By ~ 9

Author(s):

Ralph I. Dorfman

Keyword(s):

Dose Response ◽

Subcutaneous Injection ◽

Response Relationship ◽

Dose Response Relationship

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.

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