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

Author(s):  
Hiroki Abe ◽  
Kohei Takeoka ◽  
Yuto Fuchisawa ◽  
Kento Koyama ◽  
Shigenobu Koseki

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.

2021 ◽  
Author(s):  
Hiroki Abe ◽  
Kohei Takeoka ◽  
Yuto Fuchisawa ◽  
Kento Koyama ◽  
Shigenobu Koseki

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.


2016 ◽  
Vol 144 (16) ◽  
pp. 3461-3473 ◽  
Author(s):  
P. TEUNIS ◽  
J. SCHIJVEN ◽  
S. RUTJES

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.


1996 ◽  
Vol 30 (1-2) ◽  
pp. 101-111 ◽  
Author(s):  
G.J. Medema ◽  
P.F.M. Teunis ◽  
A.H. Havelaar ◽  
C.N. Haas

1962 ◽  
Vol 41 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Ralph I. Dorfman

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.


2021 ◽  
Vol 34 (01) ◽  
pp. 003-016
Author(s):  
John Michel Warner

AbstractAccording to Hahnemann, homoeopathic medicines must be great immune responses inducers. In crude states, these medicines pose severe threats to the immune system. So, the immune-system of an organism backfires against the molecules of the medicinal substances. The complex immune response mechanism activated by the medicinal molecules can handle any threats which are similar to the threats posed by the medicinal molecules. The intersectional operation of the two sets, medicine-induced immune responses and immune responses necessary to cure diseases, shows that any effective homoeopathic medicine, which is effective against any disease, can induce immune responses which are necessary to cure the specific disease. In this article, this mechanism has been exemplified by the action of Silicea in human body. Also, a neuroimmunological assessment of the route of medicine administration shows that the oral cavity and the nasal cavity are two administration-routes where the smallest doses (sometimes even few molecules) of a particular homoeopathic medicine induce the most effective and sufficient (in amount) purgatory immune responses. Administering the smallest unitary doses of Silicea in the oral route can make significant changes in the vital force line on the dose–response relationship graph. The dose–response relationship graph further implicates that the most effective dose of a medicine must be below the lethality threshold. If multiple doses of any medicine are administered at same intervals, the immune-system primarily engages with the medicinal molecules; but along the passage of time, the engagement line splits into two: one engages with the medicinal molecules and another engages with diseases. The immune system's engagement with the diseases increases along the passage of time, though the engagement with the medicinal molecules gradually falls with the administration of descending doses. Necessarily, I have shown through mathematical logic that the descending doses, though they seem to be funny, can effectively induce the most effective immune responses.


Sign in / Sign up

Export Citation Format

Share Document