Acute illness from Campylobacter jejuni may require high doses while infection occurs at low doses

•This study generalizes infection and illness dose response relations for Campylobacter jejuni, accounting for variation in pathogen (strain) and host (immunity, species) characteristics.•Susceptibility to infection likely is high, requiring small doses to colonize.•In outbreaks illness occurs at lo...

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Published inEpidemics Vol. 24; pp. 1 - 20
Main Authors Teunis, Peter F.M., Bonačić Marinović, Axel, Tribble, David R., Porter, Chad K., Swart, Arno
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.09.2018
Elsevier
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Abstract •This study generalizes infection and illness dose response relations for Campylobacter jejuni, accounting for variation in pathogen (strain) and host (immunity, species) characteristics.•Susceptibility to infection likely is high, requiring small doses to colonize.•In outbreaks illness occurs at low doses, while in challenge studies high doses may be required.•This can be explained by selection bias: outbreaks select for highly virulent strains, not propagated in culture, and hosts susceptible to developing detectable symptoms of acute illness.•Nonhuman primates cannot be shown to have higher susceptibility to campylobacteriosis than humans. 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.
AbstractList 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.
•This study generalizes infection and illness dose response relations for Campylobacter jejuni, accounting for variation in pathogen (strain) and host (immunity, species) characteristics.•Susceptibility to infection likely is high, requiring small doses to colonize.•In outbreaks illness occurs at low doses, while in challenge studies high doses may be required.•This can be explained by selection bias: outbreaks select for highly virulent strains, not propagated in culture, and hosts susceptible to developing detectable symptoms of acute illness.•Nonhuman primates cannot be shown to have higher susceptibility to campylobacteriosis than humans. 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.
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. Keywords: Campylobacter jejuni, Hierarchical dose response, Natural experiments, Challenge studies, Infectivity
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.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.
Author Porter, Chad K.
Teunis, Peter F.M.
Swart, Arno
Bonačić Marinović, Axel
Tribble, David R.
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Keywords Natural experiments
Hierarchical dose response
Infectivity
Challenge studies
Campylobacter jejuni
Language English
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Snippet •This study generalizes infection and illness dose response relations for Campylobacter jejuni, accounting for variation in pathogen (strain) and host...
Data from a set of different studies on the infectivity and pathogenicity of Campylobacter jejuni were analyzed with a multilevel model, allowing for effects...
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SubjectTerms Acute Disease
Animals
Campylobacter Infections - epidemiology
Campylobacter Infections - pathology
Campylobacter jejuni
Campylobacter jejuni - pathogenicity
Challenge studies
Disease Outbreaks - statistics & numerical data
Hierarchical dose response
Humans
Infectivity
Natural experiments
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Title Acute illness from Campylobacter jejuni may require high doses while infection occurs at low doses
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https://dx.doi.org/10.1016/j.epidem.2018.02.001
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