Difference between revisions of "Burkholderia pseudomallei: Dose Response Models"

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==<center>'''''Burkholderia mallei and pseudomallei'''''</center>==
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==<center>'''Burkholderia pseudomallei'''''</center>==
 +
<center><big>'''Author: Mark H. Weir'''</big></center>
 +
 
 +
==='''Overview'''===
 +
The bacterium ''Bukholderia pseudomallei ''(''B. pseudomallei'') is a gram negative bacterium and is present in numerous tropical regions such as Central and South America and Southeast Asia causes Melioidosis, typically infects horses, mules and donkeys but can also present a potentially life threatening disease in humans as well. ''Burkholderia mallei ''(''B. mallei'') is a close relative of ''B. pseudomallei'' both of which have been categorized as a B level bioterror agent by the CDC. No dose response models are currently available for ''B. mallei''.
 +
 
 +
http://www.cdc.gov/melioidosis/
 +
 
 +
Liu et al. in 2002 examined infection through intranasal route to mimic infection through inhalation. C57BL/6 mice and BALB/c mice were inoculated intranasally to ''B. pseudomallei'' KHW strain and mortality was recorded as response (Liu, Koo et al. 2002). Miller et al.(1948) explored infection in guinea pigs via intraperitoneal route(Miller, Pannell et al. 1948). Similarly, Brett and Woods(1996) experimented infection in diabetic rats with ''B. pseuomallei'' 316c strain (Brett and Woods 1996.
 +
 
 +
 
 +
{{DRSummaryTableStart|agent=''Burkholderia pseudomallei''}}
 +
{{DRSummaryTablePreferredModel|expID= 18,23 |refer=Liu, Koo et al. 2002 and Brett and Woods 1996|reference=Brett PJ and Woods DE (1996) Structural and immunological characterization of ''Burkholderia pseudomallei'' O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828 and Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal ''Burkholderia pseudomallei'' Infection. Infection and Immunity 70(2), 504-511. |host=C57BL/6 mice and diabetic rat |agentStrain= KHW,316c |route= intranasal,intraperitoneal |nDoses= 10 |doseUnits= CFU |response= death |bestFitModel=beta-Poisson|parameters=&alpha; =  3.28E-01 , N<sub>50</sub> =  5.43E+03 |N50= 5.43E+03 }}
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{{DRSummaryTableNonpreferredModel|expID= 21,23 |refer=Miller, Pannell et al. 1948 and Brett and Woods 1996 |reference=Miller WR, Pannell L, Cravitz L, Tanner WA and Rosebury T (1948) Studies on Certain Biological Characteristics of ''Malleomyces mallei'' and ''Malleomyces pseudomallei'': II. Virulence and Infectivity for Animals. Journal of Bacteriology 55(1), 127-135. and Brett PJ and Woods DE (1996) Structural and immunological characterization of ''Burkholderia pseudomallei'' O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828|host= guinea pig and diabetic rat |agentStrain= W294, 316c |route= intraperitoneal |nDoses= 11 |doseUnits= CFU |response= death |bestFitModel=beta-Poisson|parameters=&alpha; =  2.13E-01 , N<sub>50</sub> =  4.77E+02 |N50= 4.77E+02 }}
 +
{{DRSummaryTableNonpreferredModel|expID=18|refer = Liu, Koo et al. 2002|reference=Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal ''Burkholderia pseudomallei'' Infection. Infection and Immunity 70(2), 504-511.|host=C57BL/6 mice|agentStrain= KHW |route= intranasal |nDoses= 5 |doseUnits= CFU |response= infection  |bestFitModel=exponential|parameters=k =  1.00E-04 |N50= 6.92E+03 }}
 +
{{DRSummaryNonpreferredModel|expID= 17 |refer = Liu, Koo et al. 2002|reference=Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal ''Burkholderia pseudomallei'' Infection. Infection and Immunity 70(2), 504-511.|host= BALB/c mice|agentStrain= KHW |route= intranasal |nDoses= 5 |doseUnits= CFU |response= infection  |bestFitModel=exponential|parameters=k =  1.04E-02 |N50= 6.63E+01 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 21 |refer = Miller 1947|reference=Miller WR, Pannel I, Cravitz I, Tanner WA and Rosebury T (1947) Studies on Certain Biological Characteristics of ''Melleomyces mallei'' and ''Malleomyces pseudomallei'' II. Virulence and Infectivity for Animals Journal of Bacteriology 55: 127-135 |host= guinea pig |agentStrain= W294 |route= intraperitoneal |nDoses= 6 |doseUnits= CFU |response= death |bestFitModel=beta-Poisson|parameters=&alpha; =  2.67E-01 , N<sub>50</sub> =  2.55E+02 |N50= 2.55E+02 }}
 +
{{DRSummaryTableNonpreferredModel|expID= 23 |refer=Brett and Woods 1996|reference=Brett PJ and Woods DE (1996) Structural and immunological characterization of ''Burkholderia pseudomallei'' O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828|host= diabetic rat |agentStrain= 316c |route= intraperitoneal |nDoses= 5 |doseUnits= CFU |response= death  |bestFitModel=beta-Poisson|parameters=&alpha; =  2.65E-01 , N<sub>50</sub> =  2.27E+03 |N50= 2.27E+03 }}
 +
{{DRSummaryTableEnd}}
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 +
=== '''Recommended Model''' ===
 +
 
 +
Since the  data of C57BL/6 mice and diabetic rat could be pooled and intranasal exposure is closer to inhalation which is the likeliest exposure route for humans, the pooled data sets and resulting models  is preferred. 
 +
 
 +
[[File:Exponential and betapoisson model.jpg|thumb|none|550px]]
 +
 
 +
=Experiment 18 and 23=
 +
 
 +
==='''Optimization Output for experiment 18 and 23 pooled (''B. pseudomallei'')'''===
 +
 
 +
{{DRExperimentDataTable10|title=Pooled data of C57BL/6 mice and diabetic rat|reference=Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal ''Burkholderia pseudomallei'' Infection. ''Infection and Immunity'' 70(2), 504-511. and Brett PJ and Woods DE (1996) Structural and immunological characterization of ''Burkholderia pseudomallei'' O-polysaccharide-flagellin protein conjugates. ''Infection and Immunity'' 64(7), 2824-2828. |pos=DEATH|neg=NOT DEATH|d1=150|p1=0|n1=6|t1=6|d2=450|p2=1|n2=5|t2=6|d3=1350|p3=1|n3=5|t3=6|d4=3000|p4=6|n4=4|t4=10|d5=4050|p5=3|n5=3|t5=6|d6=12200|p6=3|n6=3|t6=6|d7=3E+04|p7=7|n7=3|t7=10|d8=3E+05|p8=7|n8=3|t8=10|d9=3E+06|p9=10|n9=0|t9=10|d10=3E+07|p10=10|n10=0|t10=10}}
 +
 
 +
 
 +
{{DRFit|title=Goodness of fit and model selection|devE=63.3|devB=6.68|delta=56.6|DFE=9|DFB=8|X2bPbetter=3.84|pbPbetter=5.42e-14|X2GOFe=16.9|pGOFe=3.15e-10|X2GOFb=15.5|pGOFb=0.571|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=3.28E-01|p5a=1.94E-01|p25a=2.16E-01|p50a=2.31E-01|p950a=5.15E-01|p975a=5.86E-01|p995a=8.32E-01|MLEN=5.43E+03|p5N=1.82E+03|p25N=2.37E+03|p50N=2.64E+03|p950N=1.23E+04|p975N=1.39E+04|p995N=1.68E+04}}
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 +
 
 +
 
 +
 
 +
 
 +
[[File:BPscatter ID18 23.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 ID18 23.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
  
<center><big>'''Author: Mark H. Weir'''</big></center>
 
<center>'''If you want to download this chapter in pdf format, please click [http://wiki.camra.msu.edu/images/7/76/Burkholderia_Section_v1.pdf here]''' </center>
 
  
 +
=Experiment 21 and 23=
  
==='''Overview: ''Burkholderia and meliodosis''===
+
==='''Optimization Output for experiment 21 and 23 pooled (''B. pseudomallei'')'''===
  
Melioidosis, which typically infects horses, mules and donkeys but can also present a potentially life threatening disease in humans as well, is caused by the bacterium ''Bukholderia pseudomallei ''(''B. pseudimallei''). The bacterium is present in numerous tropical regions such as Central and South America and Southeast Asia. ''Burkholderia mallei ''(''B. mallei'') is a close relative of ''B. pseudomallei'' both of which have been categorized as a B level bioterror agent by the CDC.
+
{{DRExperimentDataTable11|title=Pooled data of guinea pig and diabetic rat|reference=Miller WR, Pannell L, Cravitz L, Tanner WA and Rosebury T (1948) Studies on Certain Biological Characteristics of ''Malleomyces mallei'' and ''Malleomyces pseudomallei'': II. Virulence and Infectivity for Animals. ''Journal of Bacteriology'' 55(1), 127-135. and Brett PJ and Woods DE (1996) Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828.|pos=DEATH|neg=NOT DEATH|d1=44|p1=1|n1=4|t1=5|d2=440|p2=3|n2=2|t2=5|d3=3000|p3=6|n3=4|t3=10|d4=4400|p4=4|n4=1|t4=5|d5=3E+04|p5=7|n5=3|t5=10|d6=44000|p6=5|n6=0|t6=5|d7=3E+05|p7=7|n7=3|t7=10|d8=440000|p8=5|n8=0|t8=5|d9=3E+06|p9=10|n9=0|t9=10|d10=4.4E+06|p10=4|n10=1|t10=5|d11=3E+07|p11=10|n11=0|t11=10}}
  
----
 
  
 +
{{DRFit|title=Goodness of fit and model selection|devE=163|devB=10.1|delta=152|DFE=10|DFB=9|X2bPbetter=3.84|pbPbetter=0|X2GOFe=18.3|pGOFe=0|X2GOFb=16.9|pGOFb=0.343|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
  
==='''Summary Data'''===
 
  
Brett, P.J. and Woods, D.E.(2000) Pathogenesis of and Immunity to Melioidosis ''Acta Tropica'' '''74''': 201-210
+
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations|MLEa=2.13E-01|p5a=9.14E-02|p25a=1.26E-01|p50a=1.39E-01|p950a=3.38E-01|p975a=3.76E-01|p995a=5.60E-01|MLEN=4.77E+02|p5N=3.04E+00|p25N=1.63E+01|p50N=7.19E+01|p950N=2.16E+03|p975N=2.75E+03|p995N=4.44E+03}}
  
Miller, W.R., Pannel, I., Cravitz, I., Tanner, W.A., Rosebury, T. (1947) Studies on Certain Biological Characteristics of ''Melleomyces mallei'' and ''Malleomyces pseudomallei'' II. Virulence and Infectivity for Animals ''Journal of Bacteriology'' '''55''': 127-135
 
  
{|
 
| STYLE="vertical-align: top; text-align: center"|
 
{| border = "1"
 
|+ '''Table 2.1.  Summary of data for ''Burkholderia'''''
 
|'''Experiment Number''' ||'''Reference'''||'''Host Type/Pathogen Strain'''||'''Route/# of Doses'''||'''Dose Units'''||'''Response'''||'''Best Fit Model<sup>a</sup>'''||'''Optimized Parameter(s)'''||'''ID<sub>50</sub>'''
 
|-
 
| 1 || Brett and Woods (2000) || BALBc mice/KHW || Intranasal – 5 || CFU || Infection || Exponential || 0.0104 || 66.34
 
|- style="background-color:#cccccc;border-top:none;border-bottom:none;border-left:none;border-right:none;padding:0.0201in;"
 
| 2<sup>*</sup>  || Brett and Woods (2000) || C57BL6 mice/KHW || Intranasal – 5 || CFU || Infection || Exponential || 1.0E-04 || 6,919
 
|-
 
| 3 || Miller et al. (1947) || Guinea Pigs/W294 || Intraperitoneal – 6 || CFU || Death || Beta Poisson || α = 0.27, N<sub>50</sub> = 254.56 || 254.56
 
|}
 
|}
 
  
=== '''<sup>*</sup> Recommended Model''' ===
 
  
Since intranasal exposure is closer to inhalation which is the likeliest exposure route for humans, especially compared to intraperitoneal, the data sets and resulting models from the Brett and Woods (2000) article is preferred. Also given the improved fit between the two data sets experiment 2 is chosen as the recommended model.
+
[[File:BPscatter ID21 23.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 ID21 23.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
  
a:[[File:Exponential and betapoisson model.jpg|thumb|none|550px]]
 
  
----
 
  
 +
=Experiment 18=
  
===Optimization Output for experiment 1===
+
==='''Optimization Output for experiment 18 (''B. pseudomallei'')'''===
  
{{DRexperimentDataTable5|title=C57BL/6 Mice KHW Strain Data|refer = Brett and Woods 2000|reference=Brett, P.J. and Woods, D.E.(2000) [http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271036&_user=1111158&_pii=S0001706X99000716&_check=y&_origin=&_coverDate=05-Feb-2000&view=c&wchp=dGLzVBA-zSkWA&md5=1de3999eee66ca154743edbc00367cc3/1-s2.0-S0001706X99000716-main.pdf Pathogenesis of and Immunity to Melioidosis] ''Acta Tropica'' '''74''': 201-210|pos=Infected|neg=Non-infected |d1=150|p1=0|n1=6|t1=6|d2=450|p2=1|n2=5|t2=6|d3=1350|p3=1|n3=5|t3=6|d4=4050|p4=3|n4=3|t4=6|d5=12200|p5=3|n5=3|t5=6}}
+
{{DRExperimentDataTable5|title=C57BL/6 Mice KHW Strain Data|refer = Liu, Koo et al. 2002|reference=Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal ''Burkholderia pseudomallei'' Infection. ''Infection and Immunity'' 70(2), 504-511.|pos=Infected|neg=Non-infected |d1=150|p1=0|n1=6|t1=6|d2=450|p2=1|n2=5|t2=6|d3=1350|p3=1|n3=5|t3=6|d4=4050|p4=3|n4=3|t4=6|d5=12200|p5=3|n5=3|t5=6}}
  
  
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=Experiment 17=
  
===Optimization Output for experiment 2===
+
==='''Optimization Output for experiment 17(''B. pseudomallei'')'''===
  
{{DRexperimentDataTable5|title=BALB/c Mice KHW Strain Data|refer = Brett and Woods 2000|reference=Brett, P.J. and Woods, D.E.(2000) [http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271036&_user=1111158&_pii=S0001706X99000716&_check=y&_origin=&_coverDate=05-Feb-2000&view=c&wchp=dGLzVBA-zSkWA&md5=1de3999eee66ca154743edbc00367cc3/1-s2.0-S0001706X99000716-main.pdf Pathogenesis of and Immunity to Melioidosis] ''Acta Tropica'' '''74''': 201-210 |pos=Infected|neg=Non-infected |d1=5|p1=0|n1=6|t1=6|d2=15|p2=0|n2=6|t2=6|d3=45|p3=3|n3=1|t3=4|d4=135|p4=4|n4=2|t4=6|d5=405|p5=6|n5=0|t5=6}}
+
{{DRExperimentDataTable5|title=BALB/c Mice KHW Strain Data|refer = Liu, Koo et al. 2002|reference=Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal ''Burkholderia pseudomallei'' Infection. ''Infection and Immunity'' 70(2), 504-511.|pos=Infected|neg=Non-infected |d1=5|p1=0|n1=6|t1=6|d2=15|p2=0|n2=6|t2=6|d3=45|p3=3|n3=1|t3=4|d4=135|p4=4|n4=2|t4=6|d5=405|p5=6|n5=0|t5=6}}
  
  
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[[File:ExpHisto ID17.png|thumb|left|500px|'''Parameter histogram for exponential model (uncertainty of the parameter)''']][[File:ExpModel ID17.png|thumb|none|500px|'''Exponential model plot, with confidence bounds around optimized model''']]<br>
 
[[File:ExpHisto ID17.png|thumb|left|500px|'''Parameter histogram for exponential model (uncertainty of the parameter)''']][[File:ExpModel ID17.png|thumb|none|500px|'''Exponential model plot, with confidence bounds around optimized model''']]<br>
 
<br style="clear:both" />
 
  
  
 +
=Experiment 21=
  
===Optimization Output for experiment 3===
+
==='''Optimization Output for experiment 21(''B. pseudomallei'')'''===
  
{{DRexperimentDataTable6|title=Guinea Pigs W294 Strain Data|refer = Miller 1947|reference=Miller, W.R., Pannel, I., Cravitz, I., Tanner, W.A., Rosebury, T. (1947) Studies on Certain Biological Characteristics of ''Melleomyces mallei'' and ''Malleomyces pseudomallei'' II. Virulence and Infectivity for Animals ''Journal of Bacteriology'' '''55''': 127-135
+
{{DRExperimentDataTable6|title=Guinea Pigs W294 Strain Data|refer = Miller 1947|reference=Miller WR, Pannel I, Cravitz I, Tanner WA, Rosebury T (1947) Studies on Certain Biological Characteristics of ''Melleomyces mallei'' and ''Malleomyces pseudomallei'' II. Virulence and Infectivity for Animals. ''Journal of Bacteriology'' 55: 127-135
 
|pos=Dead|neg=Survived|d1=44|p1=1|n1=4|t1=5|d2=440|p2=3|n2=2|t2=5|d3=4400|p3=4|n3=1|t3=5|d4=44000|p4=5|n4=0|t4=5|d5=440000|p5=5|n5=0|t5=5|d6=4.4E+06|p6=4|n6=1|t6=5}}
 
|pos=Dead|neg=Survived|d1=44|p1=1|n1=4|t1=5|d2=440|p2=3|n2=2|t2=5|d3=4400|p3=4|n3=1|t3=5|d4=44000|p4=5|n4=0|t4=5|d5=440000|p5=5|n5=0|t5=5|d6=4.4E+06|p6=4|n6=1|t6=5}}
  
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 +
=Experiment 23=
 +
 +
==='''Optimization Output for experiment 23 (''B. pseudomallei'')'''===
 +
 +
{{DRExperimentDataTable5|title=diabetic rat and  316c strain|reference=Brett PJ and Woods DE (1996) Structural and immunological characterization of ''Burkholderia pseudomallei'' O-polysaccharide-flagellin protein conjugates. ''Infection and Immunity'' 64(7), 2824-2828.|pos=DEATH |neg=NOT DEATH |d1=3000|p1=6|n1=4|t1=10|d2=3E+04|p2=7|n2=3|t2=10|d3=3E+05|p3=7|n3=3|t3=10|d4=3E+06|p4=10|n4=0|t4=10|d5=3E+07|p5=10|n5=0|t5=10}}
 +
 +
 +
 +
{{DRFit|title=Goodness of fit and model selection|devE=43.4|devB=4.39|delta=39|DFE=4|DFB=3|X2bPbetter=3.84|pbPbetter=4.25e-10|X2GOFe=9.49|pGOFe=8.61e-09|X2GOFb=7.81|pGOFb=0.222|interpretation=Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.}}
 +
 +
 +
{{DRConfidenceBetaPoisson|title=Optimized parameters for the beta-Poisson model, from 500 bootstrap iterations|MLEa=2.65E-01|p5a=7.56E-02|p25a=1.30E-01|p50a=1.54E-01|p950a=4.94E-01|p975a=5.69E-01|p995a=8.88E-01|MLEN=2.27E+03|p5N=7.58E-02|p25N=1.50E+01|p50N=5.32E+01|p950N=8.62E+03|p975N=1.11E+04|p995N=1.74E+04}}
 +
 +
 +
[[File:BPscatter ID23.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 ID23.png|thumb|none|500px|'''beta Poisson model plot, with confidence bounds around optimized model''']]<br>
 +
 +
<headertabs />
  
 
=== References ===
 
=== References ===
 
<references />
 
<references />
  
[[Category:Dose Response Model]]
+
[[Category:Completed Dose Response Models: Bacteria]][[Category:Dose Response Model]][[Category:Burkholderia]]
 +
<br>
 +
<br>

Latest revision as of 21:17, 7 June 2013

Burkholderia pseudomallei

Author: Mark H. Weir

Overview

The bacterium Bukholderia pseudomallei (B. pseudomallei) is a gram negative bacterium and is present in numerous tropical regions such as Central and South America and Southeast Asia causes Melioidosis, typically infects horses, mules and donkeys but can also present a potentially life threatening disease in humans as well. Burkholderia mallei (B. mallei) is a close relative of B. pseudomallei both of which have been categorized as a B level bioterror agent by the CDC. No dose response models are currently available for B. mallei.

http://www.cdc.gov/melioidosis/

Liu et al. in 2002 examined infection through intranasal route to mimic infection through inhalation. C57BL/6 mice and BALB/c mice were inoculated intranasally to B. pseudomallei KHW strain and mortality was recorded as response (Liu, Koo et al. 2002). Miller et al.(1948) explored infection in guinea pigs via intraperitoneal route(Miller, Pannell et al. 1948). Similarly, Brett and Woods(1996) experimented infection in diabetic rats with B. pseuomallei 316c strain (Brett and Woods 1996.


Experiment serial number Reference Host type Agent strain Route # of doses Dose units Response Best fit model Optimized parameter(s) LD50/ID50
18,23* [1] C57BL/6 mice and diabetic rat KHW,316c intranasal,intraperitoneal 10 CFU death beta-Poisson α = 3.28E-01 , N50 = 5.43E+03 5.43E+03
21,23 [2] guinea pig and diabetic rat W294, 316c intraperitoneal 11 CFU death beta-Poisson α = 2.13E-01 , N50 = 4.77E+02 4.77E+02
18 [3] C57BL/6 mice KHW intranasal 5 CFU infection exponential k = 1.00E-04 6.92E+03
17 [3] BALB/c mice KHW intranasal 5 CFU infection exponential k = 1.04E-02 6.63E+01
21 [4] guinea pig W294 intraperitoneal 6 CFU death beta-Poisson α = 2.67E-01 , N50 = 2.55E+02 2.55E+02
23 [5] diabetic rat 316c intraperitoneal 5 CFU death beta-Poisson α = 2.65E-01 , N50 = 2.27E+03 2.27E+03
*This model is preferred in most circumstances. However, consider all available models to decide which one is most appropriate for your analysis.

Recommended Model

Since the data of C57BL/6 mice and diabetic rat could be pooled and intranasal exposure is closer to inhalation which is the likeliest exposure route for humans, the pooled data sets and resulting models is preferred.

Exponential and betapoisson model.jpg
[edit]

Optimization Output for experiment 18 and 23 pooled (B. pseudomallei)

Pooled data of C57BL/6 mice and diabetic rat [6]
Dose DEATH NOT DEATH Total
150 0 6 6
450 1 5 6
1350 1 5 6
3000 6 4 10
4050 3 3 6
12200 3 3 6
3E+04 7 3 10
3E+05 7 3 10
3E+06 10 0 10
3E+07 10 0 10


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 63.3 56.6 9 3.84
5.42e-14
16.9
3.15e-10
Beta Poisson 6.68 8 15.5
0.571
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.


Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 3.28E-01 1.94E-01 2.16E-01 2.31E-01 5.15E-01 5.86E-01 8.32E-01
N50 5.43E+03 1.82E+03 2.37E+03 2.64E+03 1.23E+04 1.39E+04 1.68E+04



Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model


Optimization Output for experiment 21 and 23 pooled (B. pseudomallei)

Pooled data of guinea pig and diabetic rat [6]
Dose DEATH NOT DEATH Total
44 1 4 5
440 3 2 5
3000 6 4 10
4400 4 1 5
3E+04 7 3 10
44000 5 0 5
3E+05 7 3 10
440000 5 0 5
3E+06 10 0 10
4.4E+06 4 1 5
3E+07 10 0 10


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 163 152 10 3.84
0
18.3
0
Beta Poisson 10.1 9 16.9
0.343
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.


Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 2.13E-01 9.14E-02 1.26E-01 1.39E-01 3.38E-01 3.76E-01 5.60E-01
N50 4.77E+02 3.04E+00 1.63E+01 7.19E+01 2.16E+03 2.75E+03 4.44E+03



Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model


Optimization Output for experiment 18 (B. pseudomallei)

C57BL/6 Mice KHW Strain Data [3]
Dose Infected Non-infected Total
150 0 6 6
450 1 5 6
1350 1 5 6
4050 3 3 6
12200 3 3 6


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 3.36 2.17 4 3.84
0.141
9.49
0.499
Beta Poisson 1.19 3 7.81
0.755
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.


Optimized parameters for the exponential model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 1E-04 2.87E-05 4.15E-05 4.99E-05 1.89E-04 2.13E-04 2.70E-04
ID50/LD50/ETC* 6.92E+03 2.57E+03 3.26E+03 3.68E+03 1.39E+04 1.67E+04 2.41E+04
*Not a parameter of the exponential model; however, it facilitates comparison with other models.


Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model


Optimization Output for experiment 17(B. pseudomallei)

BALB/c Mice KHW Strain Data [3]
Dose Infected Non-infected Total
5 0 6 6
15 0 6 6
45 3 1 4
135 4 2 6
405 6 0 6


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 5.25 -0.000362 4 3.84
1
9.49
0.263
Beta Poisson 5.25 3 7.81
0.154
Exponential is preferred to beta-Poisson; cannot reject good fit for exponential.


Optimized parameters for the exponential model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
k 1.04E-02 4.94E-03 5.96E-03 6.60E-03 1.92E-02 2.45E-02 2.45E-02
ID50/LD50/ETC* 6.63E+01 2.82E+01 2.82E+01 3.61E+01 1.05E+02 1.16E+02 1.40E+02
*Not a parameter of the exponential model; however, it facilitates comparison with other models.


Parameter histogram for exponential model (uncertainty of the parameter)
Exponential model plot, with confidence bounds around optimized model


Optimization Output for experiment 21(B. pseudomallei)

Guinea Pigs W294 Strain Data [4]
Dose Dead Survived Total
44 1 4 5
440 3 2 5
4400 4 1 5
44000 5 0 5
440000 5 0 5
4.4E+06 4 1 5


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 70.3 66.1 5 3.84
4.44e-16
11.1
8.93e-14
Beta Poisson 4.14 4 9.49
0.387
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.


Optimized parameters for the beta-Poisson model, from 10000 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 2.67E-01 3.36E-02 8.80E-02 1.16E-01 1.05E+01 3.45E+02 3.55E+03
N50 2.55E+02 4.80E-07 2.49E+00 1.48E+01 1.35E+03 1.80E+03 3.22E+03


Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model


Optimization Output for experiment 23 (B. pseudomallei)

diabetic rat and 316c strain [6]
Dose DEATH NOT DEATH Total
3000 6 4 10
3E+04 7 3 10
3E+05 7 3 10
3E+06 10 0 10
3E+07 10 0 10


Goodness of fit and model selection
Model Deviance Δ Degrees
of freedom
χ20.95,1
p-value
χ20.95,m-k
p-value
Exponential 43.4 39 4 3.84
4.25e-10
9.49
8.61e-09
Beta Poisson 4.39 3 7.81
0.222
Beta-Poisson fits better than exponential; cannot reject good fit for beta-Poisson.


Optimized parameters for the beta-Poisson model, from 500 bootstrap iterations
Parameter MLE estimate Percentiles
0.5% 2.5% 5% 95% 97.5% 99.5%
α 2.65E-01 7.56E-02 1.30E-01 1.54E-01 4.94E-01 5.69E-01 8.88E-01
N50 2.27E+03 7.58E-02 1.50E+01 5.32E+01 8.62E+03 1.11E+04 1.74E+04


Parameter scatter plot for beta Poisson model ellipses signify the 0.9, 0.95 and 0.99 confidence of the parameters.
beta Poisson model plot, with confidence bounds around optimized model

References

  1. Brett PJ and Woods DE (1996) Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828 and Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal Burkholderia pseudomallei Infection. Infection and Immunity 70(2), 504-511.
  2. Miller WR, Pannell L, Cravitz L, Tanner WA and Rosebury T (1948) Studies on Certain Biological Characteristics of Malleomyces mallei and Malleomyces pseudomallei: II. Virulence and Infectivity for Animals. Journal of Bacteriology 55(1), 127-135. and Brett PJ and Woods DE (1996) Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828
  3. 3.0 3.1 3.2 3.3 Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal Burkholderia pseudomallei Infection. Infection and Immunity 70(2), 504-511. Cite error: Invalid <ref> tag; name "Liu.2C_Koo_et_al._2002" defined multiple times with different content Cite error: Invalid <ref> tag; name "Liu.2C_Koo_et_al._2002" defined multiple times with different content
  4. 4.0 4.1 Miller WR, Pannel I, Cravitz I, Tanner WA and Rosebury T (1947) Studies on Certain Biological Characteristics of Melleomyces mallei and Malleomyces pseudomallei II. Virulence and Infectivity for Animals Journal of Bacteriology 55: 127-135 Cite error: Invalid <ref> tag; name "Miller_1947" defined multiple times with different content
  5. Brett PJ and Woods DE (1996) Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828
  6. 6.0 6.1 6.2 Liu B, Koo GC, Yap EH, Chua KL and Gan Y-H (2002) Model of Differential Susceptibility to Mucosal Burkholderia pseudomallei Infection. Infection and Immunity 70(2), 504-511. and Brett PJ and Woods DE (1996) Structural and immunological characterization of Burkholderia pseudomallei O-polysaccharide-flagellin protein conjugates. Infection and Immunity 64(7), 2824-2828. Cite error: Invalid <ref> tag; name ".7B.7B.7Brefer.7D.7D.7D" defined multiple times with different content Cite error: Invalid <ref> tag; name ".7B.7B.7Brefer.7D.7D.7D" defined multiple times with different content