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This dose response assessment combines data from 6 human challenge studies and 44 outbreaks to determine infectivity and pathogenicity of several serotypes of nontyphoid Salmonella. Outcomes focus on the major serotypes Salmonella Enteritidis and Typhimurium, showing that Typhimurium is less infectious and has a lower probability of causing acute illness in infected subjects. The dose response relation of Salmonella Enteritidis is less steep than that of Typhimurium, indicating greater heterogeneity in infectivity and pathogenicity. This study revisits an older study with less flexible methods that could not combine the widely different outcomes of challenge studies and outbreaks, and had limited capability for dealing with missing information. Reported outcomes are in a format that allows use in calculations of uncertainty for quantitative risk assessment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Noroviruses are a major public health concern: their high infectivity and environmental persistence have been documented in several studies. Genetic sequencing shows that noroviruses are highly variable, and exhibit rapid evolution. A few human challenge studies have been performed with norovirus, leading to estimates of their infectivity. However, such incidental estimates do not provide insight into the biological variation of the virus and the interaction with its human host. To study the variation in infectivity and pathogenicity of norovirus, multiple challenge studies must be analysed jointly, to compare their differences and describe how virus infectivity and host susceptibility vary. Since challenge studies can only provide a small sample of the diversity in the natural norovirus population, outbreaks should be exploited as an additional source of information. The present study shows how challenge studies and 'natural experiments' can be combined in a multilevel dose response framework. Infectivity and pathogenicity are analysed by secretor status as a host factor, and genogroup as a pathogen factor. Infectivity, characterized as the estimated mean infection risk when exposed to 1 genomic copy (qPCR unit)is 0.28 for GI norovirus, and 0.076 for GII virus, both in Se + subjects. The corresponding risks of acute enteric illness are somewhat lower, about 0.2 (GI) and 0.035 (GII), in outbreaks. Se - subjects are protected, with substantially lower risks of infection (0.00007 and 0.015 at a dose of 1 GC of GI and GII virus, respectively). The present study shows there is considerable variability in risk of infection and especially risk of acute symptoms following infection with norovirus. These challenge and outbreak data consistently indicate high infectivity among secretor positives and protection in secretor negatives., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Data from a set of different studies on the infectivity and pathogenicity of Campylobacter jejuni were analyzed with a multilevel model, allowing for effects of host species (nonhuman primates and humans) and different strains of the pathogen. All challenge studies involved high doses of the pathogen, resulting in all exposed subjects to become infected. In only one study a dose response effect (increasing trend with dose) for infection was observed. High susceptibility to infection with C. jejuni was found in a joint analysis of outbreaks and challenge studies. For that reason four outbreaks, associated with raw milk consumption, were also included in the present study. The high doses used for inoculation did not cause all infected subjects to develop acute enteric symptoms. The observed outcomes are consistent with a dose response effect for acute symptoms among infected subjects: a conditional illness dose response relation. Nonhuman primates and human volunteers did not appear to have different susceptibilities for developing enteric symptoms, but exposure in outbreaks (raw milk) did lead to a higher probability of symptomatic campylobacteriosis., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As a major zoonotic pathogen, characterization of the infectivity and pathogenicity of Coxiella burnetii is essential to understand Q-fever epidemiology., Objectives: We want to extend a recently published human dose response model based on experimental challenge of young adult males to include other age groups and both genders. Additionally, we can estimate the spatial distribution of exposure based on observed outbreak data., Methods: Dose response assessment based on human challenge, is extended by including outbreak data, using location of cases as a proxy for exposure. This allows estimation of the influence of age and gender on the probability of developing symptoms of acute respiratory illness., Results: In an outbreak in Switzerland, in 1983, exposure to C. burnetii was shown to depend strongly on distance from the source. The susceptibility of males to develop Q-fever decreases with age, while in females, middle-aged women appear to have the lowest risk., Conclusions: The published dose response model for Q-fever, based on experimental challenge of a small group of human volunteers, has been updated with data from a well studied outbreak. Infectivity estimates remain high, and even low doses (of 10 or fewer organisms) cause a high risk of illness., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Noroviruses (NoVs) are the major cause of acute epidemic gastroenteritis in industrialized countries. Outbreak strains are predominantly genogroup II (GII) NoV, but genogroup I (GI) strains are regularly found in oyster related outbreaks. The prototype Norwalk virus (GI), has been shown to have high infectivity in a human challenge study. Whether other NoVs are equally infectious via natural exposure remains to be established. Human susceptibility to NoV is partly determined by the secretor status (Se+/-). Data from five published oyster related outbreaks were analyzed in a Bayesian framework. Infectivity estimates where high and consistent with NV(GI) infectivity, for both GII and GI strains. The median and CI95 probability of infection and illness, in Se+ subjects, associated with exposure to a mean of one single NoV genome copy were around 0.29[0.015-0.61] for GI and 0.4[0.04-0.61] for GII, and for illness 0.13[0.007-0.39] for GI and 0.18[0.017-0.42] for GII. Se- subjects were strongly protected against infection. The high infectivity estimates for Norwalk virus GI and GII, makes NoVs critical target for food safety regulations., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Influenza virus may be transmitted through the respiratory route by inhalation of an aerosol of non-sedimenting droplets, or by deposition of sedimenting droplets in the upper respiratory tract. Whichever of these is the predominant route for infection with influenza virus has been subject of continuing debate, resulting in detailed studies of aerosol versus droplet exposure. A decisive knowledge gap preventing a satisfying conclusion is absence of a well defined human dose response model for influenza virus. This study uses a hierarchical approach generalizing over twelve human challenge studies collected in a literature search. Distinction is made between aerosol and intranasal inoculation. The results indicate high infectivity via either route, but intranasal inoculation leads to about 20 times lower infectivity than when the virus is delivered in an inhalable aerosol. A scenario study characterizing exposure to airborne virus near a coughing infected person in a room with little ventilation demonstrates that with these dose response models the probabilities of infection by either aerosol or sedimenting droplets are approximately equal. Droplet transmission results in a slightly higher illness risk due to the higher doses involved. Establishing a dose response model for influenza provides a firm basis for studies of interventions reducing exposure to different classes of infectious particles. More studies are needed to clarify the role of different modes of transmission in other settings., (Copyright © 2010 Elsevier B.V. All rights reserved.)