Endotoxaemia is common in children with Plasmodium falciparummalaria
Children presenting to hospital with recent or current Plasmodium falciparum malaria are at increased the risk of invasive bacterial disease, largely enteric gram-negative organisms (ENGO), which is associated with increased mortality and recurrent morbidity. Although incompletely understood, the mo...
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| Veröffentlicht in: | BMC infectious diseases 2013-03, Vol.13 (1), Article 117 |
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| creator | Olupot-Olupot, Peter Urban, Britta C Jemutai, Julie Nteziyaremye, Julius Fanjo, Harry M Karanja, Henry Karisa, Japhet Ongodia, Paul Bwonyo, Patrick Gitau, Evelyn N Talbert, Alison Akech, Samuel Maitland, Kathryn |
| description | Children presenting to hospital with recent or current Plasmodium falciparum malaria are at increased the risk of invasive bacterial disease, largely enteric gram-negative organisms (ENGO), which is associated with increased mortality and recurrent morbidity. Although incompletely understood, the most likely source of EGNO is the bowel. We hypothesised that as a result of impaired gut-barrier function endotoxin (lipopolysaccharide), present in the cell-wall of EGNO and in substantial quantities in the gut, is translocated into the bloodstream, and contributes to the pathophysiology of children with severe malaria. We conducted a prospective study in 257 children presenting with malaria to two hospitals in Kenya and Uganda. We analysed the clinical presentation, endotoxin and cytokine concentration. Endotoxaemia (endotoxin activity [greater than or equai to]0.4 EAA Units) was observed in 71 (27.6%) children but its presence was independent of both disease severity and outcome. Endotoxaemia was more frequent in children with severe anaemia but not specifically associated with other complications of malaria. Endotoxaemia was associated with a depressed inflammatory and anti-inflammatory cytokine response. Plasma endotoxin levels in severe malaria negatively correlated with IL6, IL10 and TGF[beta] (Spearman rho: TNF[alpha]: r=-0.122, p=0.121; IL6: r=-0.330, p |
| doi_str_mv | 10.1186/1471-2334-13-117 |
| format | Article |
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Although incompletely understood, the most likely source of EGNO is the bowel. We hypothesised that as a result of impaired gut-barrier function endotoxin (lipopolysaccharide), present in the cell-wall of EGNO and in substantial quantities in the gut, is translocated into the bloodstream, and contributes to the pathophysiology of children with severe malaria. We conducted a prospective study in 257 children presenting with malaria to two hospitals in Kenya and Uganda. We analysed the clinical presentation, endotoxin and cytokine concentration. Endotoxaemia (endotoxin activity [greater than or equai to]0.4 EAA Units) was observed in 71 (27.6%) children but its presence was independent of both disease severity and outcome. Endotoxaemia was more frequent in children with severe anaemia but not specifically associated with other complications of malaria. Endotoxaemia was associated with a depressed inflammatory and anti-inflammatory cytokine response. Plasma endotoxin levels in severe malaria negatively correlated with IL6, IL10 and TGF[beta] (Spearman rho: TNF[alpha]: r=-0.122, p=0.121; IL6: r=-0.330, p<0.0001; IL10: r=-0.461, p<0.0001; TGF[beta]: r=-0.173, p<0.027). Endotoxaemia is common in malaria and results in temporary immune paralysis, similar to that observed in patients with sepsis and experimentally-induced endotoxaemia. Intense sequestration of P. falciparum-infected erythrocytes within the endothelial bed of the gut has been observed in pathological studies and may lead to gut-barrier dysfuction. The association of endotoxaemia with the anaemia phenotype implies that it may contribute to the dyserythropoesis accompanying malaria through inflammation. Both of these factors feasibly underpin the susceptibility to EGNO co-infection. Further research is required to investigate this initial finding, with a view to future treatment trials targeting mechanism and appropriate antimicrobial treatment.</description><identifier>ISSN: 1471-2334</identifier><identifier>EISSN: 1471-2334</identifier><identifier>DOI: 10.1186/1471-2334-13-117</identifier><language>eng</language><publisher>BioMed Central Ltd</publisher><subject>Anemia ; Bacteremia ; Bacterial infections ; Children ; Development and progression ; Disease susceptibility ; Endotoxins ; Health aspects ; Hospitals ; Kenya ; Malaria ; Measurement ; Medical research ; Medicine, Experimental ; Mitogens ; Mortality ; Plasmodium falciparum ; Transforming growth factors ; Uganda</subject><ispartof>BMC infectious diseases, 2013-03, Vol.13 (1), Article 117</ispartof><rights>COPYRIGHT 2013 BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2267-50154dd35147bb90258fcb5f5ae1f8fe17ca68b916cdabac8f25e57f69e7f37e3</citedby><cites>FETCH-LOGICAL-c2267-50154dd35147bb90258fcb5f5ae1f8fe17ca68b916cdabac8f25e57f69e7f37e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>Olupot-Olupot, Peter</creatorcontrib><creatorcontrib>Urban, Britta C</creatorcontrib><creatorcontrib>Jemutai, Julie</creatorcontrib><creatorcontrib>Nteziyaremye, Julius</creatorcontrib><creatorcontrib>Fanjo, Harry M</creatorcontrib><creatorcontrib>Karanja, Henry</creatorcontrib><creatorcontrib>Karisa, Japhet</creatorcontrib><creatorcontrib>Ongodia, Paul</creatorcontrib><creatorcontrib>Bwonyo, Patrick</creatorcontrib><creatorcontrib>Gitau, Evelyn N</creatorcontrib><creatorcontrib>Talbert, Alison</creatorcontrib><creatorcontrib>Akech, Samuel</creatorcontrib><creatorcontrib>Maitland, Kathryn</creatorcontrib><title>Endotoxaemia is common in children with Plasmodium falciparummalaria</title><title>BMC infectious diseases</title><description>Children presenting to hospital with recent or current Plasmodium falciparum malaria are at increased the risk of invasive bacterial disease, largely enteric gram-negative organisms (ENGO), which is associated with increased mortality and recurrent morbidity. Although incompletely understood, the most likely source of EGNO is the bowel. We hypothesised that as a result of impaired gut-barrier function endotoxin (lipopolysaccharide), present in the cell-wall of EGNO and in substantial quantities in the gut, is translocated into the bloodstream, and contributes to the pathophysiology of children with severe malaria. We conducted a prospective study in 257 children presenting with malaria to two hospitals in Kenya and Uganda. We analysed the clinical presentation, endotoxin and cytokine concentration. Endotoxaemia (endotoxin activity [greater than or equai to]0.4 EAA Units) was observed in 71 (27.6%) children but its presence was independent of both disease severity and outcome. Endotoxaemia was more frequent in children with severe anaemia but not specifically associated with other complications of malaria. Endotoxaemia was associated with a depressed inflammatory and anti-inflammatory cytokine response. Plasma endotoxin levels in severe malaria negatively correlated with IL6, IL10 and TGF[beta] (Spearman rho: TNF[alpha]: r=-0.122, p=0.121; IL6: r=-0.330, p<0.0001; IL10: r=-0.461, p<0.0001; TGF[beta]: r=-0.173, p<0.027). Endotoxaemia is common in malaria and results in temporary immune paralysis, similar to that observed in patients with sepsis and experimentally-induced endotoxaemia. Intense sequestration of P. falciparum-infected erythrocytes within the endothelial bed of the gut has been observed in pathological studies and may lead to gut-barrier dysfuction. The association of endotoxaemia with the anaemia phenotype implies that it may contribute to the dyserythropoesis accompanying malaria through inflammation. Both of these factors feasibly underpin the susceptibility to EGNO co-infection. Further research is required to investigate this initial finding, with a view to future treatment trials targeting mechanism and appropriate antimicrobial treatment.</description><subject>Anemia</subject><subject>Bacteremia</subject><subject>Bacterial infections</subject><subject>Children</subject><subject>Development and progression</subject><subject>Disease susceptibility</subject><subject>Endotoxins</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Kenya</subject><subject>Malaria</subject><subject>Measurement</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Mitogens</subject><subject>Mortality</subject><subject>Plasmodium falciparum</subject><subject>Transforming growth factors</subject><subject>Uganda</subject><issn>1471-2334</issn><issn>1471-2334</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqNkU1LAzEQhoMoWKt3jwuePKxmNpvN9lhq1UKh4tc1zGaTNrLZlGSL9d-7pSL25mmGh4dheF9CLoHeAJTFLeQC0oyxPAWWAogjMvhFx3_2U3IW4welIMpsNCB307b2nd-idhYTGxPlnfNtYttErWxTB90mn7ZbJU8NRudru3GJwUbZNYaNc9hgsHhOTnoW9cXPHJK3--nr5DGdLx5mk_E8VVlWiJRT4HldM94_U1UjmvHSqIobjhpMaTQIhUVZjaBQNVaoSpNxzYUpRloYJjQbkqv93SU2WtrW-C6gcjYqOeYsL6jgrOyt6wNL-bbT226Jmxjl7OX5_-7i_dCle1cFH2PQRq6DdRi-JFC560DuQpa7kCWwngj2DUnjd4w</recordid><startdate>20130305</startdate><enddate>20130305</enddate><creator>Olupot-Olupot, Peter</creator><creator>Urban, Britta C</creator><creator>Jemutai, Julie</creator><creator>Nteziyaremye, Julius</creator><creator>Fanjo, Harry M</creator><creator>Karanja, Henry</creator><creator>Karisa, Japhet</creator><creator>Ongodia, Paul</creator><creator>Bwonyo, Patrick</creator><creator>Gitau, Evelyn N</creator><creator>Talbert, Alison</creator><creator>Akech, Samuel</creator><creator>Maitland, Kathryn</creator><general>BioMed Central Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20130305</creationdate><title>Endotoxaemia is common in children with Plasmodium falciparummalaria</title><author>Olupot-Olupot, Peter ; Urban, Britta C ; Jemutai, Julie ; Nteziyaremye, Julius ; Fanjo, Harry M ; Karanja, Henry ; Karisa, Japhet ; Ongodia, Paul ; Bwonyo, Patrick ; Gitau, Evelyn N ; Talbert, Alison ; Akech, Samuel ; Maitland, Kathryn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2267-50154dd35147bb90258fcb5f5ae1f8fe17ca68b916cdabac8f25e57f69e7f37e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Anemia</topic><topic>Bacteremia</topic><topic>Bacterial infections</topic><topic>Children</topic><topic>Development and progression</topic><topic>Disease susceptibility</topic><topic>Endotoxins</topic><topic>Health aspects</topic><topic>Hospitals</topic><topic>Kenya</topic><topic>Malaria</topic><topic>Measurement</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Mitogens</topic><topic>Mortality</topic><topic>Plasmodium falciparum</topic><topic>Transforming growth factors</topic><topic>Uganda</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olupot-Olupot, Peter</creatorcontrib><creatorcontrib>Urban, Britta C</creatorcontrib><creatorcontrib>Jemutai, Julie</creatorcontrib><creatorcontrib>Nteziyaremye, Julius</creatorcontrib><creatorcontrib>Fanjo, Harry M</creatorcontrib><creatorcontrib>Karanja, Henry</creatorcontrib><creatorcontrib>Karisa, Japhet</creatorcontrib><creatorcontrib>Ongodia, Paul</creatorcontrib><creatorcontrib>Bwonyo, Patrick</creatorcontrib><creatorcontrib>Gitau, Evelyn N</creatorcontrib><creatorcontrib>Talbert, Alison</creatorcontrib><creatorcontrib>Akech, Samuel</creatorcontrib><creatorcontrib>Maitland, Kathryn</creatorcontrib><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>BMC infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olupot-Olupot, Peter</au><au>Urban, Britta C</au><au>Jemutai, Julie</au><au>Nteziyaremye, Julius</au><au>Fanjo, Harry M</au><au>Karanja, Henry</au><au>Karisa, Japhet</au><au>Ongodia, Paul</au><au>Bwonyo, Patrick</au><au>Gitau, Evelyn N</au><au>Talbert, Alison</au><au>Akech, Samuel</au><au>Maitland, Kathryn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endotoxaemia is common in children with Plasmodium falciparummalaria</atitle><jtitle>BMC infectious diseases</jtitle><date>2013-03-05</date><risdate>2013</risdate><volume>13</volume><issue>1</issue><artnum>117</artnum><issn>1471-2334</issn><eissn>1471-2334</eissn><abstract>Children presenting to hospital with recent or current Plasmodium falciparum malaria are at increased the risk of invasive bacterial disease, largely enteric gram-negative organisms (ENGO), which is associated with increased mortality and recurrent morbidity. Although incompletely understood, the most likely source of EGNO is the bowel. We hypothesised that as a result of impaired gut-barrier function endotoxin (lipopolysaccharide), present in the cell-wall of EGNO and in substantial quantities in the gut, is translocated into the bloodstream, and contributes to the pathophysiology of children with severe malaria. We conducted a prospective study in 257 children presenting with malaria to two hospitals in Kenya and Uganda. We analysed the clinical presentation, endotoxin and cytokine concentration. Endotoxaemia (endotoxin activity [greater than or equai to]0.4 EAA Units) was observed in 71 (27.6%) children but its presence was independent of both disease severity and outcome. Endotoxaemia was more frequent in children with severe anaemia but not specifically associated with other complications of malaria. Endotoxaemia was associated with a depressed inflammatory and anti-inflammatory cytokine response. Plasma endotoxin levels in severe malaria negatively correlated with IL6, IL10 and TGF[beta] (Spearman rho: TNF[alpha]: r=-0.122, p=0.121; IL6: r=-0.330, p<0.0001; IL10: r=-0.461, p<0.0001; TGF[beta]: r=-0.173, p<0.027). Endotoxaemia is common in malaria and results in temporary immune paralysis, similar to that observed in patients with sepsis and experimentally-induced endotoxaemia. Intense sequestration of P. falciparum-infected erythrocytes within the endothelial bed of the gut has been observed in pathological studies and may lead to gut-barrier dysfuction. The association of endotoxaemia with the anaemia phenotype implies that it may contribute to the dyserythropoesis accompanying malaria through inflammation. Both of these factors feasibly underpin the susceptibility to EGNO co-infection. Further research is required to investigate this initial finding, with a view to future treatment trials targeting mechanism and appropriate antimicrobial treatment.</abstract><pub>BioMed Central Ltd</pub><doi>10.1186/1471-2334-13-117</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Anemia Bacteremia Bacterial infections Children Development and progression Disease susceptibility Endotoxins Health aspects Hospitals Kenya Malaria Measurement Medical research Medicine, Experimental Mitogens Mortality Plasmodium falciparum Transforming growth factors Uganda |
| title | Endotoxaemia is common in children with Plasmodium falciparummalaria |
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