View source for Campylobacter jejuni and Campylobacter coli: Dose Response Models

==<center>'''Campylobacter jejuni and Campylobacter colii'''''</center>==

<center><big>'''Author: Kyle S. Enger'''</big></center>

==='''Overview'''===

''Campylobacter'' are microaerophilic gram-negative curved or spiral rods with a polar flagellum. ''C. jejuni'' and ''C. coli'' are common causes of gastroenteritis  <ref name="Havelaar et al. 2009">Havelaar AH, Pelt W, Ang CW, Wagenaar JA, Putten JP, Gross U and Newell DG (2009) Immunity to ''Campylobacter'': its role in risk assessment and epidemiology. ''Critical Reviews in Microbiology''. 35 (1), 1-22. [http://informahealthcare.com/doi/abs/10.1080/10408410802636017?select23=Choose Full Text] </ref>. It can cause acute self-limiting diarrhea in healthy humans with an incubation period of 2-3 days, and appears very common worldwide. It is mainly a zoonosis, being primarily associated with birds (especially poultry). They do not grow in water and (like ''Escherichia coli'') are an indicator of post-treatment contamination in water distribution systems.

According to feeding studies with chickens, strains of ''C. jejuni'' that have been passaged many times in the laboratory tend to have a lower ID<sub>50</sub> than strains that are isolated from infected hosts and then used to infect new hosts, with minimal passage <ref name="Chen et al 2006">Chen L, Geys H, Cawthraw S, Havelaar A and Teunis P (2006) Dose response for infectivity of several strains of ''Campylobacter jejuni'' in chickens. ''Risk Analysis''. 26 (6), 1613-1621.[http://onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2006.00850.x/pdf Full Text]</ref>. Minimally passaged strains also had more variation in ID<sub>50</sub> <ref name="Chen et al 2006"></ref>. Given safety concerns, strains used for human studies may be passaged and studied more, possibly underestimating infectiousness in actual human exposure scenarios <ref name="Chen et al 2006"></ref>.

''Campylobacter'' epidemiology varies greatly between the developed and developing world, probably due to development of immunity early in life. Illness is rare after about 5 years of age (or earlier) in developing countries, but occurs among adults in industrialized countries, probably because they avoided exposure (and therefore immunity) in childhood <ref name="Havelaar et al. 2009"></ref>. However, immunity appears to protect against disease rather than infection, and asymptomatic shedding is common <ref name="Havelaar et al. 2009"></ref>. In a comparison of Mexican children <4 years of age and Swedish patients (ages not given), Swedish patients tended to carry only 1 ''Campylobacter'' serotype, while mixed serotypes were common among Mexican children (42%)<ref name = "Sjögren et al. 1989">Sjögren E, Ruiz-Palacios G and Kaijser B (1989) ''Campylobacter jejuni'' isolations from Mexican and Swedish patients, with repeated symptomatic and/or asymptomatic diarrhoea episodes. ''Epidemiology and Infection''. 102 (1), 47-57.[http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=4698732 Full Text]</ref>

http://www.cdc.gov/nczved/divisions/dfbmd/diseases/campylobacter/

==='''Summary of data'''===

Blaser et al. (1983)<ref name="Blaser et al 1983"></ref> experimentally infected adult female HA-ICR mice intragastrically with 3 different serotypes of ''C. jejuni'' (strains T1, T2, and T3). 

Chen et al. (2006)<ref name="Chen et al 2006">Chen L, Geys H, Cawthraw S, Havelaar A and Teunis P (2006) Dose response for infectivity of several strains of Campylobacter jejuni in chickens. Risk Analysis: An Official Publication of the Society for Risk Analysis. 26 (6), 1613-1621.</ref> described dose response models fitted to data from feeding studies in chickens with 19 different strains (18 ''C. jejuni'', 1 ''C. coli''). They found that isolates that had been passaged multiple times in the laboratory were more infectious than isolates taken from infected animals and reused with minimal passaging. Also, one passaged strain (11168) was substantially less infectious than the other passaged strains, which all had very similar dose response curves. 

Black et al. (1988)<ref name="Black et al 1988"></ref> fed human volunteers 2 different strains (81-176 and A3249) of ''C. jejuni'' suspended in 150 mL nonfat milk. Neither strain showed an increasing trend of illness with dose. The A3249 strain showed an increasing trend of infection with dose; however, all volunteers became infected with the 81-176 strain regardless of dose. The data describing infection with the A3249 strain were fit by Medema et al. (1996).<ref name="Medema et al. 1996">Medema GJ, Teunis PF, Havelaar AH and Haas CN (1996) Assessment of the Dose-Response Relationship of Campylobacter jejuni. International Journal of Food Microbiology. 1 (2), 101-111.</ref> Teunis et al. (1999) pooled all illness data from Black et al. (1988)<ref name="Black et al 1988"></ref> to fit a model for strains 81-176 and A3249, which remained similar to Medema et al. (1996). This model was later elaborated by Teunis et al. (2005) by including information from 2 outbreaks of ''C. jejuni'' in contaminated milk. 

Tribble et al. (2009)<ref name="Tribble et al 2009">Tribble DR, Baqar S, Carmolli MP, Porter C, Pierce KK, Sadigh K, Guerry P, Larsson CJ, Rockabrand D, Ventone CH et al (2009) Campylobacter jejuni strain CG8421: a refined model for the study of Campylobacteriosis and evaluation of Campylobacter vaccines in human subjects. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 49 (10), 1512-1519. [http://cat.inist.fr/?aModele=afficheN&cpsidt=22121873 Full Text]</ref> fed healthy adult human volunteers with the CG8421 strain of ''C. jejuni'', along with bicarbonate.  However, only 2 doses were used, and all but 1 volunteer became ill.

Tribble et al. (2010)<ref name="Tribble et al 2010"></ref> experimentally infected humans with strain 81-176 of ''C. jejuni'', one of the strains used by Black et al. (1988)<ref name="Black et al 1988"></ref>. Although Black et al. (1988) administered the dose in milk, Tribble et al. (2010) administered the dose in a solution containing 2g of bicarbonate. All volunteers were infected, but a dose response trend was seen in the development of disease.


{{DRSummaryTableStart|agent=''Campylobacter jejuni'' and ''Campylobacter coli''}}
{{DRSummaryTablePreferredModel|expID=106|refer=Black et al 1988|reference=Black RE, Levine MM, Clements ML, Hughes TP and Blaser MJ (1988) Experimental Campylobacter jejuni infection in humans. The Journal of Infectious Diseases. 157 (3), 472-479. [http://www.jstor.org/stable/30136650 Full Text]|host= human |agentStrain= strain A3249 |route= oral (in milk) |nDoses= 6 |doseUnits= CFU |response= infection |bestFitModel=beta-Poisson|parameters=&alpha;= 1.44E-01 , N<sub>50</sub> =  8.9E+02 |N50= 8.9E+02 }}
{{DRSummaryNonpreferredModel|expID= 184 |refer = Blaser et al 1983|reference=Blaser MJ, Duncan DJ, Warren GH and Wang WL (1983) Experimental Campylobacter jejuni infection of adult mice. Infection and Immunity. 39 (2), 908-916. [http://iai.asm.org/cgi/content/abstract/39/2/908 Full Text]|host= mice|agentStrain= type strain for serotype PEN 1 |route= intragastric |nDoses= 5 |doseUnits= CFU |response= infection |bestFitModel=exponential|parameters=k =  9.01E-07 |N50= 7.69E+05 }}
{{DRSummaryTableNonpreferredModel|expID= 185 |refer =Blaser et al 1983|reference=Blaser MJ et al. (1983) Experimental Campylobacter jejuni infection of adult mice. Infection and Immunity. 39(2), pp.908-916 [http://iai.asm.org/cgi/content/abstract/39/2/908 Full Text]|host= mice|agentStrain= type strain for serotype PEN 2 |route= intragastric |nDoses= 5 |doseUnits= CFU |response= infection |bestFitModel=beta-Poisson|parameters=α =  3.19E-01 , N<sub>50</sub> =  6.68E+04 |N50= 6.68E+04 }}
{{DRSummaryTableNonpreferredModel|expID= 186 |refer = Blaser et al 1983|reference=Blaser MJ et al. (1983) Experimental Campylobacter jejuni infection of adult mice. Infection and Immunity. 39(2), pp.908-916 [http://iai.asm.org/cgi/content/abstract/39/2/908 Full Text]|host= mice|agentStrain= type strain for serotype PEN 3 |route= intragastric |nDoses= 5 |doseUnits= CFU |response= infection |bestFitModel=beta-Poisson|parameters=α =  1.17E-01 , N<sub>50</sub> =  3.14E+04 |N50= 3.14E+04 }}
{{DRSummaryTableNonpreferredModel|expID= 188 |refer = Tribble et al 2010|reference=Tribble, DR, Baqar S, Scott DA et al (2010) Assessment of the duration of protection in Campylobacter jejuni experimental infection in humans. Infection and Immunity. 78 (4), 1750-1759. [http://iai.asm.org/cgi/content/abstract/78/4/1750 Full Text] |host= human |agentStrain= strain 81-176 |route= oral (w. 2g NaHCO3) |nDoses= 3 |doseUnits= CFU |response= campylobacteriosis |bestFitModel=beta-Poisson|parameters=α =  1.66E-01 , N<sub>50</sub> =  1.23E+05 |N50= 1.23E+05 }}
{{DRSummaryTableEnd}}

[[File:Exponential and betapoisson model.jpg|thumb|none|550px]]

=Experiment 106=

{{DRExperimentDataTable6|title=Strain A3249 model data|refer= Black et al 1988|reference=Black RE et al. (1988) Experimental Campylobacter jejuni infection in humans. The Journal of Infectious Diseases. 157(3), pp.472-479. [http://www.jstor.org/stable/30136650 Full Text] |pos=Infected|neg=Non-infected|d1=810|p1=5|n1=5|t1=10|d2=8100|p2=6|n2=4|t2=10|d3=91000|p3=11|n3=2|t3=13|d4=810000|p4=8|n4=3|t4=11|d5=1.1E+06|p5=15|n5=4|t5=19|d6=1.1E+08|p6=5|n6=0|t6=5}}


{{DRFit|title=Goodness of fit and model selection|devE=110|devB=2.43|delta=108|DFE=5|DFB=4|X2bPbetter=3.84|pbPbetter=0|X2GOFe=11.1|pGOFe=0|X2GOFb=9.49|pGOFb=0.658|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}


{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations|MLEa=1.44E-01|p5a=2.05E-02|p25a=3.61E-02|p50a=4.99E-02|p950a=2.66E-01|p975a=2.98E-01|p995a=3.71E-01|MLEN=8.9E+02|p5N=6.54E-10|p25N=1.47E-04|p50N=8.11E-02|p950N=6.69E+03|p975N=8.97E+03|p995N=1.53E+04}}


[[File:BPscatter ID106.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID106.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>


=Experiment 184=

{{DRExperimentDataTable5|title=T1 strain for serotype PEN 1 data|refer = Blaser et al 1983|reference=Blaser MJ et al. (1983) Experimental Campylobacter jejuni infection of adult mice. Infection and Immunity. 39(2), pp.908-916 [http://iai.asm.org/cgi/content/abstract/39/2/908 Full Text]|pos=Infected|neg=Non-infected|d1=1|p1=0|n1=5|t1=5|d2=100|p2=0|n2=5|t2=5|d3=1E+04|p3=0|n3=5|t3=5|d4=1E+06|p4=3|n4=2|t4=5|d5=1E+08|p5=5|n5=0|t5=5}}


{{DRFit|title=Goodness of fit and model selection|devE=0.0918|devB=0.0924|delta=-0.000599|DFE=4|DFB=3|X2bPbetter=3.84|pbPbetter=1|X2GOFe=9.49|pGOFe=0.999|X2GOFb=7.81|pGOFb=0.993|interpretation=Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.}}


{{DRConfidenceExponential|title=Optimized k parameter for the exponential model, from 10000 bootstrap iterations|MLEk=9.01E-07|p5k=4.61E-08|p25k=2.21E-07|p50k=2.21E-07|p950k=4.61E-06|p975k=4.61E-06|p995k=4.61E-06|N50type=ID50/LD50/ETC|MLEN=7.69E+05|p5N=1.51E+05|p25N=1.51E+05|p50N=1.51E+05|p950N=3.14E+06|p975N=3.14E+06|p995N=1.51E+07}}


[[File:ExpHisto ID184.png|thumb|left|500px|'''Parameter histogram for exponential model (uncertainty of the parameter)''']][[File:ExpModel ID184.png|thumb|none|500px|'''Exponential model plot, with confidence bounds around optimized model''']]<br>


=Experiment 185=

{{DRExperimentDataTable5|title=T2 Strain for serotype PEN 2 model data|refer =Blaser et al 1983|reference=Blaser MJ et al. (1983) Experimental Campylobacter jejuni infection of adult mice. Infection and Immunity. 39(2), pp.908-916 [http://iai.asm.org/cgi/content/abstract/39/2/908 Full Text]|pos=Infected|neg=Non-infected|d1=1E+04|p1=1|n1=4|t1=5|d2=1E+05|p2=3|n2=2|t2=5|d3=1E+06|p3=4|n3=1|t3=5|d4=1E+07|p4=4|n4=1|t4=5|d5=1E+08|p5=5|n5=0|t5=5}}


{{DRFit|title=Goodness of fit and model selection|devE=25.4|devB=0.969|delta=24.5|DFE=4|DFB=3|X2bPbetter=3.84|pbPbetter=7.59e-07|X2GOFe=9.49|pGOFe=4.13e-05|X2GOFb=7.81|pGOFb=0.809|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}


{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations|MLEa=3.19E-01|p5a=8.29E-02|p25a=1.26E-01|p50a=1.49E-01|p950a=1.05E+01|p975a=5.53E+02|p995a=1.52E+03|MLEN=6.68E+04|p5N=4.06E+02|p25N=5.55E+03|p50N=1.04E+04|p950N=3.58E+05|p975N=4.65E+05|p995N=8.48E+05}}


[[File:BPscatter ID185.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID185.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>


=Experiment 186=

{{DRExperimentDataTable5|title=T3 strain for serotype PEN 3 data|refer = Blaser et al 1983|reference=Blaser MJ et al. (1983) Experimental Campylobacter jejuni infection of adult mice. Infection and Immunity. 39(2), pp.908-916 [http://iai.asm.org/cgi/content/abstract/39/2/908 Full Text]|pos=Infected|neg=Non-infected|d1=1E+04|p1=2|n1=3|t1=5|d2=1E+05|p2=4|n2=1|t2=5|d3=1E+06|p3=2|n3=3|t3=5|d4=1E+07|p4=3|n4=2|t4=5|d5=1E+08|p5=5|n5=0|t5=5}}


{{DRFit|title=Goodness of fit and model selection|devE=45.6|devB=5.41|delta=40.2|DFE=4|DFB=3|X2bPbetter=3.84|pbPbetter=2.25e-10|X2GOFe=9.49|pGOFe=2.92e-09|X2GOFb=7.81|pGOFb=0.144|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}


{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations|MLEa=1.17E-01|p5a=1.06E-02|p25a=1.79E-02|p50a=2.48E-02|p950a=2.79E-01|p975a=3.29E-01|p995a=4.72E-01|MLEN=3.14E+04|p5N=3.29E-09|p25N=2.55E-05|p50N=2.53E-02|p950N=4.21E+05|p975N=9.69E+05|p995N=3.68E+06}}


[[File:BPscatter ID186.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID186.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>


=Experiment 188=

{{DRExperimentDataTable3|title=Strain 81-176 model data|refer = Tribble et al 2010|reference=Tribble, DR et al. (2010)  Assessment of the duration of protection in Campylobacter jejuni experimental infection in humans. Infection and Immunity. 78(4), pp.1750-1759 [http://iai.asm.org/cgi/content/abstract/78/4/1750 Full Text] |pos=Campylobacteriosis|neg=Non-campylobacteriosis|d1=1E+05|p1=3|n1=2|t1=5|d2=1E+07|p2=2|n2=3|t2=5|d3=1E+09|p3=33|n3=3|t3=36}}


{{DRFit|title=Goodness of fit and model selection|devE=50.1|devB=3.51|delta=46.6|DFE=2|DFB=1|X2bPbetter=3.84|pbPbetter=8.56e-12|X2GOFe=5.99|pGOFe=1.29e-11|X2GOFb=3.84|pGOFb=0.061|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}


{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations|MLEa=1.66E-01|p5a=2.92E-02|p25a=4.29E-02|p50a=6.44E-02|p950a=3.32E-01|p975a=4.07E-01|p995a=1.16E+00|MLEN=1.23E+05|p5N=6.24E-10|p25N=4.60E-05|p50N=9.04E-01|p950N=2.00E+06|p975N=6.12E+06|p995N=3.96E+07}}


[[File:BPscatter ID188.png|thumb|left|500px|'''Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.''']][[File:BPmodel ID188.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>


<headertabs />


===References===
<references />


[[Category:Completed Dose Response Models: Bacteria]][[Category:Campylobacter]]