Difference between revisions of "Yersinia pestis: Dose Response Models"
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''Yersinia pestis'', the causative agent of plague, is a Gram-negative facultative anaerobic bipolar-staining bacillus bacterium belonging to the family Enterobacteriaceae. It has been classified as a Category A bioterrorism agent for public health preparedness by U.S. Centers for Disease Control and Prevention. | ''Yersinia pestis'', the causative agent of plague, is a Gram-negative facultative anaerobic bipolar-staining bacillus bacterium belonging to the family Enterobacteriaceae. It has been classified as a Category A bioterrorism agent for public health preparedness by U.S. Centers for Disease Control and Prevention. | ||
| − | Plague is a dreadful disease of long standing. It has been the cause of three pandemics, and has led to the deaths of millions of people, the devastation of cities and villages, and the collapse of governments and civilizations. Small outbreaks of plague continue to occur throughout the world, and at least 2000 cases of plague are reported annually. At the present time, plague remains a serious problem for international public health, and its risk has been assessed using quantitative modeling approaches.Plague may be manifested in one of three forms: bubonic, pneumonic and septicemic | + | Plague is a dreadful disease of long standing. It has been the cause of three pandemics, and has led to the deaths of millions of people, the devastation of cities and villages, and the collapse of governments and civilizations. Small outbreaks of plague continue to occur throughout the world, and at least 2000 cases of plague are reported annually. At the present time, plague remains a serious problem for international public health, and its risk has been assessed using quantitative modeling approaches.Plague may be manifested in one of three forms: bubonic, pneumonic and septicemic.<ref name="Lathem et al. 2005"></ref> Among the three forms of plague, pneumonic plague is particularly dangerous, with incubation period of 3 to 5 days and mortality rate approaching 100% unless antibiotic treatment is initiated within 24 hours of the onset of symptoms. |
| − | Plague is transmitted to humans from infected flees and rodents are reservoirs of the disease. While over 200 mammalian species have been reported to be naturally infected with ''Y. pestis'', rodents are the most important hosts for plague | + | Plague is transmitted to humans from infected flees and rodents are reservoirs of the disease. While over 200 mammalian species have been reported to be naturally infected with ''Y. pestis'', rodents are the most important hosts for plague.<ref name="Perry and Fetherston 1997"> |
| + | Perry RD, Fetherston JD (1997) [http://cmr.asm.org/cgi/content/abstract/10/1/35 Yersinia pestis-Etiologic Agent of Plague.] Clinical Microbiology Reviews 10(1): 35-66. | ||
| + | </ref> Currently, most human plague cases in the world are classified as sylvatic plague, namely infection from rural wild animals such as mice, chipmunks, squirrels, gerbils, marmots, voles and rabbits.<ref name="Christie 1982">Christie AB, (1982) [http://www.ncbi.nlm.nih.gov/pubmed/6765301 Plague: review of ecology.] Ecol. Dis. 1: 111-115.</ref> Transmission between rodents is achieved by their associated fleas from the infected blood of the host. The organism is not transovarially transmitted from flea-to-flea, and artificially infected larvae clear the organism within 24 hours. Therefore, maintenance of plague in environment is dependent upon cyclic transmission between fleas and mammals.<ref name="Perry and Fetherston 1997"></ref> | ||
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==='''Summary Data '''=== | ==='''Summary Data '''=== | ||
| − | Lathem et al. (2005) and Parent et al. (2005) respectively inoculated C57BL/6 mice intranasally with the ''Y. pestis'' virulent wild-type CO92 strain and with the KIM D27 strain. Rogers et al. (2007) administered the ''Y. pestis'' CO92 strain to BALB/c mice via intraperitoneal route. | + | Lathem et al. (2005)<ref name="Lathem et al. 2005"></ref> and Parent et al. (2005)<ref name="Parent et al. 2005"></ref> respectively inoculated C57BL/6 mice intranasally with the ''Y. pestis'' virulent wild-type CO92 strain and with the KIM D27 strain. Rogers et al. (2007)<ref name="Rogers et al. 2007"></ref> administered the ''Y. pestis'' CO92 strain to BALB/c mice via intraperitoneal route. |
{{DRSummaryTableStart|agent=''Yersinia pestis''}} | {{DRSummaryTableStart|agent=''Yersinia pestis''}} | ||
| − | {{DRSummaryTablePreferredModel|expID= [http://wiki.camra.msu.edu/index.php?title=File:Lathern2005_YersiniaPestis_datafitconf.xls '''1'''] |refer =Lathem et al | + | {{DRSummaryTablePreferredModel|expID= [http://wiki.camra.msu.edu/index.php?title=File:Lathern2005_YersiniaPestis_datafitconf.xls '''1'''] |refer =Lathem et al. 2005| reference=Lathem WW, et al. (2005) [http://www.pnas.org/content/102/49/17786.full Progression of Primary Pneumonic Plague: A Mouse Model of Infection, Pathology, and Bacterial Transcriptional Activity.] Proceedings of the National Academy of Sciences of the United States of America 102(49): 17786-17791. |
| − | {{DRSummaryNonpreferredModel|expID= 2 |refer = Parent et al | + | |host= mice|agentStrain= CO92 |route= intranasal |nDoses= 4 |doseUnits= CFU |response= death |bestFitModel=exponential|parameters=k = 1.63E-03 |N50= 4.26E+02 }} |
| − | {{DRSummaryNonpreferredModel|expID= 3 |refer =Rogers et al | + | {{DRSummaryNonpreferredModel|expID= 2 |refer = Parent et al. 2005|reference=Parent MA, et al. (2005) [http://iai.asm.org/cgi/content/abstract/73/11/7304 Cell-Mediated Protection against Pulmonary Yersinia pestis Infection.] Infection and Immunity 73(11): 7304-7310.|host= mice|agentStrain= KIM D27 |route= intranasal |nDoses= 4 |doseUnits= CFU |response= death |bestFitModel=exponential|parameters=k = 1.07E-04 |N50= 6.47E+03 }} |
| + | {{DRSummaryNonpreferredModel|expID= 3 |refer =Rogers et al. 2007 |reference=Rogers JV, et al. (2007) [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WN6-4NJ209K-2&_user=1111158&_coverDate=09%2F30%2F2007&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1619542941&_rerunOrigin=scholar.google&_acct=C000051676&_version=1&_urlVersion=0&_userid=1111158&md5=1326a5bac28cff82b4ca06a14cd7e533&searchtype=a Transcriptional Responses in Spleens from Mice Exposed to Yersinia pestis CO92.] Microbial Pathogenesis 43: 67-77. | ||
| + | |host= mice|agentStrain= CO92 |route= intraperitoneal |nDoses= 5 |doseUnits= CFU |response= death |bestFitModel=exponential|parameters=k = 3.45E-02 |N50= 2.01E+01 }} | ||
{{DRSummaryTableEnd}} | {{DRSummaryTableEnd}} | ||
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==='''Optimization Output for experiment 1'''=== | ==='''Optimization Output for experiment 1'''=== | ||
| − | {{DRExperimentDataTable4|title=Mouse/ CO92 model data|refer =Lathem et al | + | {{DRExperimentDataTable4|title=Mouse/ CO92 model data|refer =Lathem et al. 2005| reference=Lathem WW, et al. (2005) [http://www.pnas.org/content/102/49/17786.full Progression of Primary Pneumonic Plague: A Mouse Model of Infection, Pathology, and Bacterial Transcriptional Activity.] Proceedings of the National Academy of Sciences of the United States of America 102(49): 17786-17791. |
| + | |||
|pos=Dead|neg=Survived|d1=100|p1=1|n1=3|t1=4|d2=1000|p2=3|n2=1|t2=4|d3=1E+04|p3=4|n3=0|t3=4|d4=1E+05|p4=4|n4=0|t4=4}} | |pos=Dead|neg=Survived|d1=100|p1=1|n1=3|t1=4|d2=1000|p2=3|n2=1|t2=4|d3=1E+04|p3=4|n3=0|t3=4|d4=1E+05|p4=4|n4=0|t4=4}} | ||
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==='''Optimization Output for experiment 2'''=== | ==='''Optimization Output for experiment 2'''=== | ||
| − | {{DRExperimentDataTable4|title=Mouse/ KIM D27 model data|refer = Parent et al | + | {{DRExperimentDataTable4|title=Mouse/ KIM D27 model data|refer = Parent et al. 2005|reference=Parent MA, et al. (2005) [http://iai.asm.org/cgi/content/abstract/73/11/7304 Cell-Mediated Protection against Pulmonary Yersinia pestis Infection.] Infection and Immunity 73(11): 7304-7310.|pos=Dead|neg=Survived|d1=100|p1=0|n1=10|t1=10|d2=1000|p2=2|n2=8|t2=10|d3=1E+04|p3=6|n3=4|t3=10|d4=1E+05|p4=10|n4=0|t4=10}} |
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==='''Optimization Output for experiment 3'''=== | ==='''Optimization Output for experiment 3'''=== | ||
| − | {{DRExperimentDataTable5|title=Mouse/ CO92 model data|refer =Rogers et al | + | {{DRExperimentDataTable5|title=Mouse/ CO92 model data|refer =Rogers et al. 2007 |reference=Rogers JV, et al. (2007) [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WN6-4NJ209K-2&_user=1111158&_coverDate=09%2F30%2F2007&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1619542941&_rerunOrigin=scholar.google&_acct=C000051676&_version=1&_urlVersion=0&_userid=1111158&md5=1326a5bac28cff82b4ca06a14cd7e533&searchtype=a Transcriptional Responses in Spleens from Mice Exposed to Yersinia pestis CO92.] Microbial Pathogenesis 43: 67-77. |
|pos=Dead|neg=Survived|d1=2|p1=0|n1=20|t1=20|d2=8|p2=5|n2=15|t2=20|d3=26|p3=13|n3=7|t3=20|d4=74|p4=9|n4=1|t4=10|d5=257|p5=10|n5=0|t5=10}} | |pos=Dead|neg=Survived|d1=2|p1=0|n1=20|t1=20|d2=8|p2=5|n2=15|t2=20|d3=26|p3=13|n3=7|t3=20|d4=74|p4=9|n4=1|t4=10|d5=257|p5=10|n5=0|t5=10}} | ||
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[[Category:Completed Dose Response Models: Bacteria]][[Category:Dose Response Model]][[Category:Yersinia pestis]] | [[Category:Completed Dose Response Models: Bacteria]][[Category:Dose Response Model]][[Category:Yersinia pestis]] | ||
Revision as of 15:29, 18 September 2012
Contents
Yersinia pestis
General overview of Yersinia pestis and plague
Yersinia pestis, the causative agent of plague, is a Gram-negative facultative anaerobic bipolar-staining bacillus bacterium belonging to the family Enterobacteriaceae. It has been classified as a Category A bioterrorism agent for public health preparedness by U.S. Centers for Disease Control and Prevention.
Plague is a dreadful disease of long standing. It has been the cause of three pandemics, and has led to the deaths of millions of people, the devastation of cities and villages, and the collapse of governments and civilizations. Small outbreaks of plague continue to occur throughout the world, and at least 2000 cases of plague are reported annually. At the present time, plague remains a serious problem for international public health, and its risk has been assessed using quantitative modeling approaches.Plague may be manifested in one of three forms: bubonic, pneumonic and septicemic.[1] Among the three forms of plague, pneumonic plague is particularly dangerous, with incubation period of 3 to 5 days and mortality rate approaching 100% unless antibiotic treatment is initiated within 24 hours of the onset of symptoms.
Plague is transmitted to humans from infected flees and rodents are reservoirs of the disease. While over 200 mammalian species have been reported to be naturally infected with Y. pestis, rodents are the most important hosts for plague.[2] Currently, most human plague cases in the world are classified as sylvatic plague, namely infection from rural wild animals such as mice, chipmunks, squirrels, gerbils, marmots, voles and rabbits.[3] Transmission between rodents is achieved by their associated fleas from the infected blood of the host. The organism is not transovarially transmitted from flea-to-flea, and artificially infected larvae clear the organism within 24 hours. Therefore, maintenance of plague in environment is dependent upon cyclic transmission between fleas and mammals.[2]
Summary Data
Lathem et al. (2005)[1] and Parent et al. (2005)[4] respectively inoculated C57BL/6 mice intranasally with the Y. pestis virulent wild-type CO92 strain and with the KIM D27 strain. Rogers et al. (2007)[5] administered the Y. pestis CO92 strain to BALB/c mice via intraperitoneal route.
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*Recommended Model
It is recommended that experiment 1 should be used as the best dose-response model. Compared to experiment 2, a more virulent strain in experiment 1 can be more meaningful for emergency preparedness and public health intervention. Also, the exposure route was intranasal which is a better representation of an actual release scenario over the Intraperitoneal.
Optimization Output for experiment 1
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Optimization Output for experiment 2
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Optimization Output for experiment 3
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Advanced Dose Response Model
Incorporating the time postinoculation into the classical dose-response models for microbial infection generates a class of time-dose-response (TDR) models. The parameter k in the exponential dose-response model (equation 1) and the parameter N50 in the beta-Poisson model (equation 2) were set equal to functions of time that represent in vivo bacterial kinetics. Equations 1-2 with candidate G(t; θ,…) were fit to the time-dependent dose response data from experiment 1-3. The exponential TDR model (equation 1) incorporating the inverse-Weibull distribution (equation 3) provided the best fit to the data. In Fig. 17.4, the best TDR models are plotted to compare with the observed mortalities. As shown, the clear difference between the different times postinoculation gives a visible representation to the quantified results that the modification added to the classical models has a substantial effect on the dose response.
Summary
Noting a significant difference of LD50 between the inhalation (1.4x104 pfu) and subcutaneous (0.2 pfu) routes has been identified, which suggests a substantial variation of virulence with infection site. This could also attribute to the difference between out-bred and in-bred origins.
References
- ↑ 1.0 1.1 1.2 1.3 Lathem WW, et al. (2005) Progression of Primary Pneumonic Plague: A Mouse Model of Infection, Pathology, and Bacterial Transcriptional Activity. Proceedings of the National Academy of Sciences of the United States of America 102(49): 17786-17791.
- ↑ 2.0 2.1 Perry RD, Fetherston JD (1997) Yersinia pestis-Etiologic Agent of Plague. Clinical Microbiology Reviews 10(1): 35-66.
- ↑ Christie AB, (1982) Plague: review of ecology. Ecol. Dis. 1: 111-115.
- ↑ 4.0 4.1 4.2 Parent MA, et al. (2005) Cell-Mediated Protection against Pulmonary Yersinia pestis Infection. Infection and Immunity 73(11): 7304-7310.
- ↑ 5.0 5.1 5.2 Rogers JV, et al. (2007) Transcriptional Responses in Spleens from Mice Exposed to Yersinia pestis CO92. Microbial Pathogenesis 43: 67-77.
