A mathematical simulation of the inflammatory response to anthrax infection
Bacillus anthracis (anthrax) can trigger an acute inflammatory response that results in multisystem organ failure and death. Previously, we developed a mathematical model of acute inflammation after gram-negative infection that had been matched qualitatively to literature data. We modified the prope...
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Veröffentlicht in: | Shock (Augusta, Ga.) Ga.), 2008-01, Vol.29 (1), p.104-111 |
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creator | Kumar, Rukmini Chow, Carson C Bartels, John D Clermont, Gilles Vodovotz, Yoram |
description | Bacillus anthracis (anthrax) can trigger an acute inflammatory response that results in multisystem organ failure and death. Previously, we developed a mathematical model of acute inflammation after gram-negative infection that had been matched qualitatively to literature data. We modified the properties of the invading bacteria in that model to those specific to B. anthracis and simulated the host response to anthrax infection. We simulated treatment strategies against anthrax in a genetically diverse population including the following: (1) antibiotic treatment initiated at various time points, (2) antiprotective antigen vaccine, and (3) a combination of antibiotics and vaccine. In agreement with studies in mice, our simulations showed that antibiotics only improve survival if administered early in the course of anthrax infection. Vaccination that leads to the formation of antibodies to protective antigen is anti-inflammatory and beneficial in averting shock and improving survival. However, antibodies to protective antigen alone are predicted not to be universally protective against anthrax infection. Rather, our simulations suggest that an optimal strategy would require both vaccination and antibiotic administration. |
doi_str_mv | 10.1097/SHK.0b013e318067dcfe |
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Previously, we developed a mathematical model of acute inflammation after gram-negative infection that had been matched qualitatively to literature data. We modified the properties of the invading bacteria in that model to those specific to B. anthracis and simulated the host response to anthrax infection. We simulated treatment strategies against anthrax in a genetically diverse population including the following: (1) antibiotic treatment initiated at various time points, (2) antiprotective antigen vaccine, and (3) a combination of antibiotics and vaccine. In agreement with studies in mice, our simulations showed that antibiotics only improve survival if administered early in the course of anthrax infection. Vaccination that leads to the formation of antibodies to protective antigen is anti-inflammatory and beneficial in averting shock and improving survival. However, antibodies to protective antigen alone are predicted not to be universally protective against anthrax infection. 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Rather, our simulations suggest that an optimal strategy would require both vaccination and antibiotic administration.</description><subject>Anthrax - complications</subject><subject>Anthrax - drug therapy</subject><subject>Anthrax - therapy</subject><subject>Anthrax Vaccines - therapeutic use</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Bioterrorism</subject><subject>Humans</subject><subject>Inflammation - etiology</subject><subject>Mathematics</subject><subject>Models, Biological</subject><subject>Multiple Organ Failure - etiology</subject><issn>1073-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkM9LwzAUx3NQ3Jz-ByI5eet8SZqmPY6hTjbwoJ5Lmr6wStvMpAX335uygeDlvQffHzw-hNwxWDIo1OP7ZruECphAwXLIVG0sXpA5AyUSLjifkesQvgB4Kgp1RWYsZ1JBVszJdkU7PewxjsboloamG9t4u546S6NAm962uou680fqMRxcH5AOjup-2Hv9MxnQTIkbcml1G_D2vBfk8_npY71Jdm8vr-vVLjGCKUzygklrlUpTxousLipm8lRwjE9DjYZzW-WKS4VKSSEyLlldpwYU2FrKHLlYkIdT78G77xHDUHZNMNi2ukc3hlIByyRwiMb0ZDTeheDRlgffdNofSwblBK6M4Mr_4GLs_tw_Vh3Wf6EzNfELVGptdg</recordid><startdate>200801</startdate><enddate>200801</enddate><creator>Kumar, Rukmini</creator><creator>Chow, Carson C</creator><creator>Bartels, John D</creator><creator>Clermont, Gilles</creator><creator>Vodovotz, Yoram</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200801</creationdate><title>A mathematical simulation of the inflammatory response to anthrax infection</title><author>Kumar, Rukmini ; Chow, Carson C ; Bartels, John D ; Clermont, Gilles ; Vodovotz, Yoram</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c317e-8915ff77441296d9b1c8432edcf0dec22fb87257e775336251dd4c070fd558e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Anthrax - complications</topic><topic>Anthrax - drug therapy</topic><topic>Anthrax - therapy</topic><topic>Anthrax Vaccines - therapeutic use</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Bioterrorism</topic><topic>Humans</topic><topic>Inflammation - etiology</topic><topic>Mathematics</topic><topic>Models, Biological</topic><topic>Multiple Organ Failure - etiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumar, Rukmini</creatorcontrib><creatorcontrib>Chow, Carson C</creatorcontrib><creatorcontrib>Bartels, John D</creatorcontrib><creatorcontrib>Clermont, Gilles</creatorcontrib><creatorcontrib>Vodovotz, Yoram</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Shock (Augusta, Ga.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumar, Rukmini</au><au>Chow, Carson C</au><au>Bartels, John D</au><au>Clermont, Gilles</au><au>Vodovotz, Yoram</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A mathematical simulation of the inflammatory response to anthrax infection</atitle><jtitle>Shock (Augusta, Ga.)</jtitle><addtitle>Shock</addtitle><date>2008-01</date><risdate>2008</risdate><volume>29</volume><issue>1</issue><spage>104</spage><epage>111</epage><pages>104-111</pages><issn>1073-2322</issn><abstract>Bacillus anthracis (anthrax) can trigger an acute inflammatory response that results in multisystem organ failure and death. Previously, we developed a mathematical model of acute inflammation after gram-negative infection that had been matched qualitatively to literature data. We modified the properties of the invading bacteria in that model to those specific to B. anthracis and simulated the host response to anthrax infection. We simulated treatment strategies against anthrax in a genetically diverse population including the following: (1) antibiotic treatment initiated at various time points, (2) antiprotective antigen vaccine, and (3) a combination of antibiotics and vaccine. In agreement with studies in mice, our simulations showed that antibiotics only improve survival if administered early in the course of anthrax infection. Vaccination that leads to the formation of antibodies to protective antigen is anti-inflammatory and beneficial in averting shock and improving survival. However, antibodies to protective antigen alone are predicted not to be universally protective against anthrax infection. 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subjects | Anthrax - complications Anthrax - drug therapy Anthrax - therapy Anthrax Vaccines - therapeutic use Anti-Bacterial Agents - therapeutic use Bioterrorism Humans Inflammation - etiology Mathematics Models, Biological Multiple Organ Failure - etiology |
title | A mathematical simulation of the inflammatory response to anthrax infection |
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