Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria
Identifieur interne : 000786 ( Istex/Corpus ); précédent : 000785; suivant : 000787Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria
Auteurs : Philip E. Thuma ; George F. Mabeza ; Godfrey Biemba ; G. J. Bhat ; Christine E. Mclaren ; Victor M. Moyo ; Stenford Zulu ; Hlosukwazi Khumalo ; Patricia Mabeza ; Abraham M'Hango ; Dean Parry ; Anton A. Poltera ; Gary M. Brittenham ; Victor R. GordeukSource :
- Transactions of The Royal Society of Tropical Medicine and Hygiene [ 0035-9203 ] ; 1998-04.
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- KwdEn :
Abstract
To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age <6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18·3% (32/175) in the deferoxamine group and 10·7% (19/177) in the placebo group (adjusted odds ratio 1·8; 95% confidence interval 0·9–3·6; P = 0·074). At the rural study site, mortality was 15·4% (18/117) with deferoxamine compared to 12·7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24·1% (14/58) with deferoxamine and 6·8% (4/59) with placebo (P = 0·061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1·2; 95% confidence interval 0·97–1·6; P = 0·089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.
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DOI: 10.1016/S0035-9203(98)90753-2
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Thuma</name><affiliation><mods:affiliation>The Pennsylvania State University, Hershey Medical Center, Hershey, Pennsylvania, USA</mods:affiliation></affiliation></author><author><name sortKey="Mabeza, George F" sort="Mabeza, George F" uniqKey="Mabeza G" first="George F." last="Mabeza">George F. Mabeza</name><affiliation><mods:affiliation>Macha Mission Hospital, Choma, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Biemba, Godfrey" sort="Biemba, Godfrey" uniqKey="Biemba G" first="Godfrey" last="Biemba">Godfrey Biemba</name><affiliation><mods:affiliation>Macha Mission Hospital, Choma, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Bhat, G J" sort="Bhat, G J" uniqKey="Bhat G" first="G. J." last="Bhat">G. J. Bhat</name><affiliation><mods:affiliation>University Teaching Hospital, The University of Zambia, Lusaka, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Mclaren, Christine E" sort="Mclaren, Christine E" uniqKey="Mclaren C" first="Christine E." last="Mclaren">Christine E. Mclaren</name><affiliation><mods:affiliation>Moorhead State University, Moorhead, Minnesota, USA</mods:affiliation></affiliation></author><author><name sortKey="Moyo, Victor M" sort="Moyo, Victor M" uniqKey="Moyo V" first="Victor M." last="Moyo">Victor M. Moyo</name><affiliation><mods:affiliation>The George Washington University Medical Center, Washington, DC, USA</mods:affiliation></affiliation></author><author><name sortKey="Zulu, Stenford" sort="Zulu, Stenford" uniqKey="Zulu S" first="Stenford" last="Zulu">Stenford Zulu</name><affiliation><mods:affiliation>Macha Mission Hospital, Choma, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Khumalo, Hlosukwazi" sort="Khumalo, Hlosukwazi" uniqKey="Khumalo H" first="Hlosukwazi" last="Khumalo">Hlosukwazi Khumalo</name><affiliation><mods:affiliation>Macha Mission Hospital, Choma, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Mabeza, Patricia" sort="Mabeza, Patricia" uniqKey="Mabeza P" first="Patricia" last="Mabeza">Patricia Mabeza</name><affiliation><mods:affiliation>Macha Mission Hospital, Choma, Zambia</mods:affiliation></affiliation></author><author><name sortKey="M Hango, Abraham" sort="M Hango, Abraham" uniqKey="M Hango A" first="Abraham" last="M'Hango">Abraham M'Hango</name><affiliation><mods:affiliation>Macha Mission Hospital, Choma, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Parry, Dean" sort="Parry, Dean" uniqKey="Parry D" first="Dean" last="Parry">Dean Parry</name><affiliation><mods:affiliation>Macha Mission Hospital, Choma, Zambia</mods:affiliation></affiliation></author><author><name sortKey="Poltera, Anton A" sort="Poltera, Anton A" uniqKey="Poltera A" first="Anton A." last="Poltera">Anton A. Poltera</name><affiliation><mods:affiliation>Swiss Serum and Vaccine Institute, Berne, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Brittenham, Gary M" sort="Brittenham, Gary M" uniqKey="Brittenham G" first="Gary M." last="Brittenham">Gary M. Brittenham</name><affiliation><mods:affiliation>Case Western Reserve University, Cleveland, Ohio, USA</mods:affiliation></affiliation></author><author><name sortKey="Gordeuk, Victor R" sort="Gordeuk, Victor R" uniqKey="Gordeuk V" first="Victor R." last="Gordeuk">Victor R. Gordeuk</name><affiliation><mods:affiliation>The George Washington University Medical Center, Washington, DC, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Address for correspondence: Victor R. Gordeuk, MD, Division of Hematology and Oncology, Department of Medicine, The George Washington University Medical Center, Suite 3-428, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA; phone +1 202 994 3556, fax +1 202 994 4524.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Transactions of The Royal Society of Tropical Medicine and Hygiene</title><title level="j" type="abbrev">Trans R Soc Trop Med Hyg</title><idno type="ISSN">0035-9203</idno><idno type="eISSN">1878-3503</idno><imprint><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><date type="published" when="1998-04">1998-04</date><biblScope unit="volume">92</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="214">214</biblScope><biblScope unit="page" to="218">218</biblScope></imprint><idno type="ISSN">0035-9203</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0035-9203</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>chemotherapy</term><term>deferoxamine</term><term>iron chelation</term><term>malaria</term><term>quinine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age <6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18·3% (32/175) in the deferoxamine group and 10·7% (19/177) in the placebo group (adjusted odds ratio 1·8; 95% confidence interval 0·9–3·6; P = 0·074). At the rural study site, mortality was 15·4% (18/117) with deferoxamine compared to 12·7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24·1% (14/58) with deferoxamine and 6·8% (4/59) with placebo (P = 0·061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1·2; 95% confidence interval 0·97–1·6; P = 0·089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Philip E. Thuma</name><affiliations><json:string>The Pennsylvania State University, Hershey Medical Center, Hershey, Pennsylvania, USA</json:string></affiliations></json:item><json:item><name>George F. Mabeza</name><affiliations><json:string>Macha Mission Hospital, Choma, Zambia</json:string></affiliations></json:item><json:item><name>Godfrey Biemba</name><affiliations><json:string>Macha Mission Hospital, Choma, Zambia</json:string></affiliations></json:item><json:item><name>G.J. Bhat</name><affiliations><json:string>University Teaching Hospital, The University of Zambia, Lusaka, Zambia</json:string></affiliations></json:item><json:item><name>Christine E. McLaren</name><affiliations><json:string>Moorhead State University, Moorhead, Minnesota, USA</json:string></affiliations></json:item><json:item><name>Victor M. Moyo</name><affiliations><json:string>The George Washington University Medical Center, Washington, DC, USA</json:string></affiliations></json:item><json:item><name>Stenford Zulu</name><affiliations><json:string>Macha Mission Hospital, Choma, Zambia</json:string></affiliations></json:item><json:item><name>Hlosukwazi Khumalo</name><affiliations><json:string>Macha Mission Hospital, Choma, Zambia</json:string></affiliations></json:item><json:item><name>Patricia Mabeza</name><affiliations><json:string>Macha Mission Hospital, Choma, Zambia</json:string></affiliations></json:item><json:item><name>Abraham M'Hango</name><affiliations><json:string>Macha Mission Hospital, Choma, Zambia</json:string></affiliations></json:item><json:item><name>Dean Parry</name><affiliations><json:string>Macha Mission Hospital, Choma, Zambia</json:string></affiliations></json:item><json:item><name>Anton A. Poltera</name><affiliations><json:string>Swiss Serum and Vaccine Institute, Berne, Switzerland</json:string></affiliations></json:item><json:item><name>Gary M. Brittenham</name><affiliations><json:string>Case Western Reserve University, Cleveland, Ohio, USA</json:string></affiliations></json:item><json:item><name>Victor R. Gordeuk</name><affiliations><json:string>The George Washington University Medical Center, Washington, DC, USA</json:string><json:string>Address for correspondence: Victor R. Gordeuk, MD, Division of Hematology and Oncology, Department of Medicine, The George Washington University Medical Center, Suite 3-428, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA; phone +1 202 994 3556, fax +1 202 994 4524.</json:string></affiliations></json:item></author><subject><json:item><value>malaria</value></json:item><json:item><value>chemotherapy</value></json:item><json:item><value>iron chelation</value></json:item><json:item><value>deferoxamine</value></json:item><json:item><value>quinine</value></json:item></subject><arkIstex>ark:/67375/HXZ-MZ5B58B2-5</arkIstex><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age >6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18·3% (32/175) in the deferoxamine group and 10·7% (19/177) in the placebo group (adjusted odds ratio 1·8; 95% confidence interval 0·9–3·6; P = 0·074). At the rural study site, mortality was 15·4% (18/117) with deferoxamine compared to 12·7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24·1% (14/58) with deferoxamine and 6·8% (4/59) with placebo (P = 0·061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1·2; 95% confidence interval 0·97–1·6; P = 0·089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.</abstract><qualityIndicators><score>9.148</score><pdfWordCount>4472</pdfWordCount><pdfCharCount>28549</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>5</pdfPageCount><pdfPageSize>576 x 828 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>223</abstractWordCount><abstractCharCount>1426</abstractCharCount><keywordCount>5</keywordCount></qualityIndicators><title>Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria</title><pmid><json:string>9764337</json:string></pmid><genre><json:string>research-article</json:string></genre><host><title>Transactions of The Royal Society of Tropical Medicine and Hygiene</title><language><json:string>unknown</json:string></language><issn><json:string>0035-9203</json:string></issn><eissn><json:string>1878-3503</json:string></eissn><publisherId><json:string>trstmh</json:string></publisherId><volume>92</volume><issue>2</issue><pages><first>214</first><last>218</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>1998</json:string></date><geogName></geogName><orgName><json:string>Ethical and Research Committee of the University of Zambia</json:string><json:string>Macha Mission Hospital, Choma, Zambia</json:string><json:string>The George Washington University</json:string><json:string>Moorhead State University</json:string><json:string>Jniversity Teaching Hospital, The University of Zambia, Lusaka, Zambia</json:string><json:string>Ciba-Geigy, Ltd, Basel, Switzerland</json:string><json:string>Hershey Medical Center</json:string><json:string>Boehringer-Mannheim Diagnostics</json:string><json:string>US National Institutes of Health International Collaboration for Infectious Disease Research</json:string><json:string>Division of Hematology</json:string><json:string>US Food and Drug</json:string><json:string>Western Reserve University</json:string><json:string>Committee on Human Investigation of the Hershey Medical Center, Pennsylvania State University</json:string><json:string>Department of Medicine, The George Washington University Medical Center, Suite</json:string><json:string>Medical Center, Washington</json:string><json:string>Vaccine Institute, Berne, Switzerland</json:string><json:string>Ciba-Geigy Ltd</json:string><json:string>Basel</json:string><json:string>Switzerland</json:string></orgName><orgName_funder><json:string>Ciba-Geigy Ltd</json:string><json:string>Basel</json:string><json:string>Switzerland</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Christine E. McLaren</json:string><json:string>Anton A. Poltera</json:string><json:string>Abraham M’Hang</json:string><json:string>Nancy F. Olivieri</json:string><json:string>Victor R. Gordeuk</json:string><json:string>R. Gordeuk</json:string><json:string>George F. Mabeza</json:string><json:string>Macha Hospital</json:string><json:string>G. J. Bhat</json:string><json:string>Except</json:string><json:string>Patricia Mabeza</json:string><json:string>Terrie E. Taylor</json:string><json:string>Dean Parry</json:string><json:string>Raymond Bergeron</json:string><json:string>Victor M. Moyo</json:string><json:string>David Wypij</json:string></persName><placeName><json:string>Washington</json:string><json:string>Lusaka</json:string><json:string>DC</json:string><json:string>Glasgow</json:string><json:string>Zambia</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>!iNONYMOUS, 1996</json:string><json:string>COX, 1972</json:string><json:string>WHO, 1974</json:string><json:string>AIKAWA, 1988</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/HXZ-MZ5B58B2-5</json:string></ark><categories><wos><json:string>social science</json:string><json:string>public, environmental & occupational health</json:string><json:string>science</json:string><json:string>tropical medicine</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>tropical medicine</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Infectious Diseases</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Public Health, Environmental and Occupational Health</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - General Medicine</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Parasitology</json:string></scopus></categories><publicationDate>1998</publicationDate><copyrightDate>1998</copyrightDate><doi><json:string>10.1016/S0035-9203(98)90753-2</json:string></doi><id>FD61516A26CD648CAAA807941E856DE36A81237A</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/FD61516A26CD648CAAA807941E856DE36A81237A/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/FD61516A26CD648CAAA807941E856DE36A81237A/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/FD61516A26CD648CAAA807941E856DE36A81237A/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://publisher-list.data.istex.fr">Royal Society of Tropical Medicine and Hygiene</publisher><availability><licence><p>oup</p></licence></availability><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M"></p><date>1998</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note>Address for correspondence: Victor R. Gordeuk, MD, Division of Hematology and Oncology, Department of Medicine, The George Washington University Medical Center, Suite 3-428, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA; phone +1 202 994 3556, fax +1 202 994 4524.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria</title><author xml:id="author-0000"><persName><forename type="first">Philip E.</forename><surname>Thuma</surname></persName><affiliation>The Pennsylvania State University, Hershey Medical Center, Hershey, Pennsylvania, USA</affiliation></author><author xml:id="author-0001"><persName><forename type="first">George F.</forename><surname>Mabeza</surname></persName><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Godfrey</forename><surname>Biemba</surname></persName><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation></author><author xml:id="author-0003"><persName><forename type="first">G.J.</forename><surname>Bhat</surname></persName><affiliation>University Teaching Hospital, The University of Zambia, Lusaka, Zambia</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Christine E.</forename><surname>McLaren</surname></persName><affiliation>Moorhead State University, Moorhead, Minnesota, USA</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Victor M.</forename><surname>Moyo</surname></persName><affiliation>The George Washington University Medical Center, Washington, DC, USA</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Stenford</forename><surname>Zulu</surname></persName><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Hlosukwazi</forename><surname>Khumalo</surname></persName><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Patricia</forename><surname>Mabeza</surname></persName><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation></author><author xml:id="author-0009"><persName><forename type="first">Abraham</forename><surname>M'Hango</surname></persName><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation></author><author xml:id="author-0010"><persName><forename type="first">Dean</forename><surname>Parry</surname></persName><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation></author><author xml:id="author-0011"><persName><forename type="first">Anton A.</forename><surname>Poltera</surname></persName><affiliation>Swiss Serum and Vaccine Institute, Berne, Switzerland</affiliation></author><author xml:id="author-0012"><persName><forename type="first">Gary M.</forename><surname>Brittenham</surname></persName><affiliation>Case Western Reserve University, Cleveland, Ohio, USA</affiliation></author><author xml:id="author-0013" corresp="yes"><persName><forename type="first">Victor R.</forename><surname>Gordeuk</surname></persName><affiliation>The George Washington University Medical Center, Washington, DC, USA</affiliation><affiliation>Address for correspondence: Victor R. Gordeuk, MD, Division of Hematology and Oncology, Department of Medicine, The George Washington University Medical Center, Suite 3-428, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA; phone +1 202 994 3556, fax +1 202 994 4524.</affiliation></author><idno type="istex">FD61516A26CD648CAAA807941E856DE36A81237A</idno><idno type="ark">ark:/67375/HXZ-MZ5B58B2-5</idno><idno type="DOI">10.1016/S0035-9203(98)90753-2</idno></analytic><monogr><title level="j">Transactions of The Royal Society of Tropical Medicine and Hygiene</title><title level="j" type="abbrev">Trans R Soc Trop Med Hyg</title><idno type="pISSN">0035-9203</idno><idno type="eISSN">1878-3503</idno><idno type="publisher-id">trstmh</idno><idno type="PublisherID-hwp">trstmh</idno><imprint><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><date type="published" when="1998-04"></date><biblScope unit="volume">92</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="214">214</biblScope><biblScope unit="page" to="218">218</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1998</date></creation><abstract><p>To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age <6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18·3% (32/175) in the deferoxamine group and 10·7% (19/177) in the placebo group (adjusted odds ratio 1·8; 95% confidence interval 0·9–3·6; P = 0·074). At the rural study site, mortality was 15·4% (18/117) with deferoxamine compared to 12·7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24·1% (14/58) with deferoxamine and 6·8% (4/59) with placebo (P = 0·061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1·2; 95% confidence interval 0·97–1·6; P = 0·089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>malaria</term></item><item><term>chemotherapy</term></item><item><term>iron chelation</term></item><item><term>deferoxamine</term></item><item><term>quinine</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1998-04">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/FD61516A26CD648CAAA807941E856DE36A81237A/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup, element #text not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article">
<front>
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<journal-id journal-id-type="publisher-id">trstmh</journal-id>
<journal-title>Transactions of The Royal Society of Tropical Medicine and Hygiene</journal-title>
<abbrev-journal-title>Trans R Soc Trop Med Hyg</abbrev-journal-title>
<issn pub-type="ppub">0035-9203</issn>
<issn pub-type="epub">1878-3503</issn>
<publisher>
<publisher-name>Royal Society of Tropical Medicine and Hygiene</publisher-name>
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<article-categories>
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<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Thuma</surname><given-names>Philip E.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Mabeza</surname><given-names>George F.</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Biemba</surname><given-names>Godfrey</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Bhat</surname><given-names>G.J.</given-names></name><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>McLaren</surname><given-names>Christine E.</given-names></name><xref ref-type="aff" rid="AFF4"><sup>4</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Moyo</surname><given-names>Victor M.</given-names></name><xref ref-type="aff" rid="AFF7"><sup>7</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Zulu</surname><given-names>Stenford</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Khumalo</surname><given-names>Hlosukwazi</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Mabeza</surname><given-names>Patricia</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>M'Hango</surname><given-names>Abraham</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Parry</surname><given-names>Dean</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Poltera</surname><given-names>Anton A.</given-names></name><xref ref-type="aff" rid="AFF5"><sup>5</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Brittenham</surname><given-names>Gary M.</given-names></name><xref ref-type="aff" rid="AFF6"><sup>6</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Gordeuk</surname><given-names>Victor R.</given-names></name><xref ref-type="corresp" rid="COR1"></xref><xref ref-type="aff" rid="AFF7"><sup>7</sup></xref>
</contrib>
<aff id="AFF1">
<label>1</label>The Pennsylvania State University, Hershey Medical Center, Hershey, Pennsylvania, USA</aff>
<aff id="AFF2">
<label>2</label>Macha Mission Hospital, Choma, Zambia</aff>
<aff id="AFF3">
<label>3</label>University Teaching Hospital, The University of Zambia, Lusaka, Zambia</aff>
<aff id="AFF4">
<label>4</label>Moorhead State University, Moorhead, Minnesota, USA</aff>
<aff id="AFF5">
<label>5</label>Swiss Serum and Vaccine Institute, Berne, Switzerland</aff>
<aff id="AFF6">
<label>6</label>Case Western Reserve University, Cleveland, Ohio, USA</aff>
<aff id="AFF7">
<label>7</label>The George Washington University Medical Center, Washington, DC, USA</aff>
</contrib-group>
<author-notes>
<corresp id="COR1">Address for correspondence: Victor R. Gordeuk, MD, Division of Hematology and Oncology, Department of Medicine, The George Washington University Medical Center, Suite 3-428, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA; phone +1 202 994 3556, fax +1 202 994 4524.</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>4</month>
<year>1998</year>
</pub-date>
<volume>92</volume>
<issue>2</issue>
<fpage>214</fpage>
<lpage>218</lpage>
<history>
<date date-type="received">
<day>4</day>
<month>8</month>
<year>1997</year></date>
<date date-type="rev-recd">
<day>30</day>
<month>10</month>
<year>1997</year></date>
<date date-type="accepted">
<day>30</day>
<month>10</month>
<year>1997</year></date>
</history>
<permissions>
<copyright-year>1998</copyright-year>
</permissions>
<abstract>
<p>To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age <6 years, <italic>Plasmodium falciparum</italic> parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18·3% (32/175) in the deferoxamine group and 10·7% (19/177) in the placebo group (adjusted odds ratio 1·8; 95% confidence interval 0·9–3·6; <italic>P</italic> = 0·074). At the rural study site, mortality was 15·4% (18/117) with deferoxamine compared to 12·7% (15/118) with placebo (<italic>P</italic> = 0.78, adjusted for covariates). At the urban site, mortality was 24·1% (14/58) with deferoxamine and 6·8% (4/59) with placebo (<italic>P</italic> = 0·061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1·2; 95% confidence interval 0·97–1·6; <italic>P</italic> = 0·089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.</p>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>malaria</kwd>
<kwd><italic>Plasmodium falciparum</italic></kwd>
<kwd>chemotherapy</kwd>
<kwd>iron chelation</kwd>
<kwd>deferoxamine</kwd>
<kwd>quinine</kwd>
</kwd-group>
<custom-meta-wrap>
<custom-meta>
<meta-name>cover-date</meta-name>
<meta-value>March-April 1998</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<back>
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</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria</title></titleInfo><name type="personal"><namePart type="given">Philip E.</namePart><namePart type="family">Thuma</namePart><affiliation>The Pennsylvania State University, Hershey Medical Center, Hershey, Pennsylvania, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">George F.</namePart><namePart type="family">Mabeza</namePart><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Godfrey</namePart><namePart type="family">Biemba</namePart><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.J.</namePart><namePart type="family">Bhat</namePart><affiliation>University Teaching Hospital, The University of Zambia, Lusaka, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine E.</namePart><namePart type="family">McLaren</namePart><affiliation>Moorhead State University, Moorhead, Minnesota, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Victor M.</namePart><namePart type="family">Moyo</namePart><affiliation>The George Washington University Medical Center, Washington, DC, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stenford</namePart><namePart type="family">Zulu</namePart><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hlosukwazi</namePart><namePart type="family">Khumalo</namePart><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patricia</namePart><namePart type="family">Mabeza</namePart><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Abraham</namePart><namePart type="family">M'Hango</namePart><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dean</namePart><namePart type="family">Parry</namePart><affiliation>Macha Mission Hospital, Choma, Zambia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anton A.</namePart><namePart type="family">Poltera</namePart><affiliation>Swiss Serum and Vaccine Institute, Berne, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Gary M.</namePart><namePart type="family">Brittenham</namePart><affiliation>Case Western Reserve University, Cleveland, Ohio, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Victor R.</namePart><namePart type="family">Gordeuk</namePart><affiliation>The George Washington University Medical Center, Washington, DC, USA</affiliation><affiliation>Address for correspondence: Victor R. Gordeuk, MD, Division of Hematology and Oncology, Department of Medicine, The George Washington University Medical Center, Suite 3-428, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA; phone +1 202 994 3556, fax +1 202 994 4524.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><dateIssued encoding="w3cdtf">1998-04</dateIssued><copyrightDate encoding="w3cdtf">1998</copyrightDate></originInfo><abstract>To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age <6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose. Mortality overall was 18·3% (32/175) in the deferoxamine group and 10·7% (19/177) in the placebo group (adjusted odds ratio 1·8; 95% confidence interval 0·9–3·6; P = 0·074). At the rural study site, mortality was 15·4% (18/117) with deferoxamine compared to 12·7% (15/118) with placebo (P = 0.78, adjusted for covariates). At the urban site, mortality was 24·1% (14/58) with deferoxamine and 6·8% (4/59) with placebo (P = 0·061, adjusted for covariates). Among survivors, there was a non-significant trend to faster recovery from coma in the deferoxamine group (adjusted odds ratio 1·2; 95% confidence interval 0·97–1·6; P = 0·089). Hepatomegaly was significantly associated with higher mortality, while splenomegaly was associated with lower mortality. This study did not provide evidence for a beneficial effect on mortality in children with cerebral malaria when deferoxamine was added to quinine, given in a regimen that included a loading dose.</abstract><note type="author-notes">Address for correspondence: Victor R. Gordeuk, MD, Division of Hematology and Oncology, Department of Medicine, The George Washington University Medical Center, Suite 3-428, 2150 Pennsylvania Avenue NW, Washington, DC 20037, USA; phone +1 202 994 3556, fax +1 202 994 4524.</note><subject lang="en"><genre>Keywords</genre><topic>malaria</topic><topic>chemotherapy</topic><topic>iron chelation</topic><topic>deferoxamine</topic><topic>quinine</topic></subject><relatedItem type="host"><titleInfo><title>Transactions of The Royal Society of Tropical Medicine and Hygiene</title></titleInfo><titleInfo type="abbreviated"><title>Trans R Soc Trop Med Hyg</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0035-9203</identifier><identifier type="eISSN">1878-3503</identifier><identifier type="PublisherID">trstmh</identifier><identifier type="PublisherID-hwp">trstmh</identifier><part><date>1998</date><detail type="volume"><caption>vol.</caption><number>92</number></detail><detail type="issue"><caption>no.</caption><number>2</number></detail><extent unit="pages"><start>214</start><end>218</end></extent></part></relatedItem><identifier type="istex">FD61516A26CD648CAAA807941E856DE36A81237A</identifier><identifier type="DOI">10.1016/S0035-9203(98)90753-2</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</recordContentSource></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/FD61516A26CD648CAAA807941E856DE36A81237A/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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