Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women
Identifieur interne : 003928 ( Istex/Corpus ); précédent : 003927; suivant : 003929Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women
Auteurs : C. J. Gill ; W. B. Macleod ; V. Mwanakasale ; V. Chalwe ; L. Mwananyanda ; D. Champo ; D. Mukwamataba ; R. Chilengi ; D. M. Thea ; D. H. HamerSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2007-12-01.
Abstract
Background. The World Health Organization advocates 2–3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear. Methods. Data were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to ⩾4 doses). Results. Of 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0–68.3]). Conclusions. Single-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.
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DOI: 10.1086/522137
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Gill</name><affiliation><mods:affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: cgill@bu.edu</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Dr. Christopher J. Gill Center for International Health and Development Dept. of International Health Boston University School of Public Health 85 E. 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Mwanakasale</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Chalwe, V" sort="Chalwe, V" uniqKey="Chalwe V" first="V." last="Chalwe">V. Chalwe</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Mwananyanda, L" sort="Mwananyanda, L" uniqKey="Mwananyanda L" first="L." last="Mwananyanda">L. Mwananyanda</name><affiliation><mods:affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Champo, D" sort="Champo, D" uniqKey="Champo D" first="D." last="Champo">D. Champo</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Mukwamataba, D" sort="Mukwamataba, D" uniqKey="Mukwamataba D" first="D." last="Mukwamataba">D. Mukwamataba</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Chilengi, R" sort="Chilengi, R" uniqKey="Chilengi R" first="R." last="Chilengi">R. Chilengi</name><affiliation><mods:affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Thea, D M" sort="Thea, D M" uniqKey="Thea D" first="D. M." last="Thea">D. M. Thea</name><affiliation><mods:affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Hamer, D H" sort="Hamer, D H" uniqKey="Hamer D" first="D. H." last="Hamer">D. H. Hamer</name><affiliation><mods:affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:AEFC50316197D9951E16D9B1B97457110772A4F6</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1086/522137</idno><idno type="url">https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">003928</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">003928</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women</title><author><name sortKey="Gill, C J" sort="Gill, C J" uniqKey="Gill C" first="C. J." last="Gill">C. J. Gill</name><affiliation><mods:affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: cgill@bu.edu</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Dr. Christopher J. Gill Center for International Health and Development Dept. of International Health Boston University School of Public Health 85 E. Concord St. Boston MA 02118</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: cgill@bu.edu</mods:affiliation></affiliation></author><author><name sortKey="Macleod, W B" sort="Macleod, W B" uniqKey="Macleod W" first="W. B." last="Macleod">W. B. Macleod</name><affiliation><mods:affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Mwanakasale, V" sort="Mwanakasale, V" uniqKey="Mwanakasale V" first="V." last="Mwanakasale">V. Mwanakasale</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Chalwe, V" sort="Chalwe, V" uniqKey="Chalwe V" first="V." last="Chalwe">V. Chalwe</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Mwananyanda, L" sort="Mwananyanda, L" uniqKey="Mwananyanda L" first="L." last="Mwananyanda">L. Mwananyanda</name><affiliation><mods:affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Champo, D" sort="Champo, D" uniqKey="Champo D" first="D." last="Champo">D. Champo</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Mukwamataba, D" sort="Mukwamataba, D" uniqKey="Mukwamataba D" first="D." last="Mukwamataba">D. Mukwamataba</name><affiliation><mods:affiliation>Tropical Diseases Research Centre, Ndola, Zambia</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Chilengi, R" sort="Chilengi, R" uniqKey="Chilengi R" first="R." last="Chilengi">R. Chilengi</name><affiliation><mods:affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Thea, D M" sort="Thea, D M" uniqKey="Thea D" first="D. M." last="Thea">D. M. Thea</name><affiliation><mods:affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author><author><name sortKey="Hamer, D H" sort="Hamer, D H" uniqKey="Hamer D" first="D. H." last="Hamer">D. H. Hamer</name><affiliation><mods:affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</mods:affiliation></affiliation><affiliation><mods:affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published" when="2007-12-01">2007-12-01</date><biblScope unit="volume">196</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1577">1577</biblScope><biblScope unit="page" to="1584">1584</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background. The World Health Organization advocates 2–3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear. Methods. Data were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to ⩾4 doses). Results. Of 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0–68.3]). Conclusions. Single-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Dr. C. J. Gill</name><affiliations><json:string>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</json:string><json:string>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string><json:string>E-mail: cgill@bu.edu</json:string></affiliations></json:item><json:item><name>W. B. MacLeod</name><affiliations><json:string>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>V. Mwanakasale</name><affiliations><json:string>Tropical Diseases Research Centre, Ndola, Zambia</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>V. Chalwe</name><affiliations><json:string>Tropical Diseases Research Centre, Ndola, Zambia</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>L. Mwananyanda</name><affiliations><json:string>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>D. Champo</name><affiliations><json:string>Tropical Diseases Research Centre, Ndola, Zambia</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>D. Mukwamataba</name><affiliations><json:string>Tropical Diseases Research Centre, Ndola, Zambia</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>R. Chilengi</name><affiliations><json:string>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>D. M. Thea</name><affiliations><json:string>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item><json:item><name>D. H. Hamer</name><affiliations><json:string>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</json:string><json:string>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</json:string><json:string>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</json:string></affiliations></json:item></author><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Background. The World Health Organization advocates 2–3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear. Methods. Data were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to ⩾4 doses). Results. Of 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0–68.3]). Conclusions. Single-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.</abstract><qualityIndicators><score>9.109</score><pdfWordCount>4709</pdfWordCount><pdfCharCount>29350</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>8</pdfPageCount><pdfPageSize>594 x 783 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>200</abstractWordCount><abstractCharCount>1347</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women</title><genre><json:string>research-article</json:string></genre><host><title>The Journal of Infectious Diseases</title><language><json:string>unknown</json:string></language><issn><json:string>0022-1899</json:string></issn><eissn><json:string>1537-6613</json:string></eissn><publisherId><json:string>jid</json:string></publisherId><volume>196</volume><issue>11</issue><pages><first>1577</first><last>1584</last></pages><genre><json:string>journal</json:string></genre></host><categories><wos><json:string>science</json:string><json:string>microbiology</json:string><json:string>infectious diseases</json:string><json:string>immunology</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>biomedical research</json:string><json:string>microbiology</json:string></scienceMetrix></categories><publicationDate>2007</publicationDate><copyrightDate>2007</copyrightDate><doi><json:string>10.1086/522137</json:string></doi><id>AEFC50316197D9951E16D9B1B97457110772A4F6</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://publisher-list.data.istex.fr">The University of Chicago Press</publisher><availability><licence><p>© 2007 by the Infectious Diseases Society of America</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</p></availability><date>2007</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></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women</title><author xml:id="author-0000" corresp="yes"><persName><forename type="first">C. J.</forename><surname>Gill</surname></persName><roleName type="degree">Dr.</roleName><email>cgill@bu.edu</email><email>cgill@bu.edu</email><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><affiliation>Reprints or correspondence: Dr. Christopher J. Gill Center for International Health and Development Dept. of International Health Boston University School of Public Health 85 E. Concord St. Boston MA 02118</affiliation></author><author xml:id="author-0001"><persName><forename type="first">W. B.</forename><surname>MacLeod</surname></persName><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0002"><persName><forename type="first">V.</forename><surname>Mwanakasale</surname></persName><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0003"><persName><forename type="first">V.</forename><surname>Chalwe</surname></persName><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0004"><persName><forename type="first">L.</forename><surname>Mwananyanda</surname></persName><affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0005"><persName><forename type="first">D.</forename><surname>Champo</surname></persName><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0006"><persName><forename type="first">D.</forename><surname>Mukwamataba</surname></persName><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0007"><persName><forename type="first">R.</forename><surname>Chilengi</surname></persName><affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0008"><persName><forename type="first">D. M.</forename><surname>Thea</surname></persName><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><author xml:id="author-0009"><persName><forename type="first">D. H.</forename><surname>Hamer</surname></persName><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation></author><idno type="istex">AEFC50316197D9951E16D9B1B97457110772A4F6</idno><idno type="ark">ark:/67375/HXZ-ZRFR863L-P</idno><idno type="DOI">10.1086/522137</idno></analytic><monogr><title level="j">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="pISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><idno type="publisher-id">jid</idno><idno type="PublisherID-hwp">jinfdis</idno><imprint><publisher>The University of Chicago Press</publisher><date type="published" when="2007-12-01"></date><biblScope unit="volume">196</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="1577">1577</biblScope><biblScope unit="page" to="1584">1584</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007</date></creation><abstract><p>Background. The World Health Organization advocates 2–3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear. Methods. Data were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to ⩾4 doses). Results. Of 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0–68.3]). Conclusions. Single-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.</p></abstract><textClass><keywords scheme="Journal Subject"><list><head></head><item><term>Parasites</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head></head><item><term>Major Article</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head></head><item><term>Global Theme Issue: Poverty and Human Development</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2007-12-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/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>
<journal-meta>
<journal-id journal-id-type="hwp">jinfdis</journal-id>
<journal-id journal-id-type="publisher-id">jid</journal-id>
<journal-title>The Journal of Infectious Diseases</journal-title>
<abbrev-journal-title>The Journal of Infectious Diseases</abbrev-journal-title>
<issn pub-type="ppub">0022-1899</issn>
<issn pub-type="epub">1537-6613</issn>
<publisher>
<publisher-name>The University of Chicago Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1086/522137</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Major Articles and Brief Reports</subject>
<subj-group>
<subject>Parasites</subject>
<subj-group>
<subject>Major Article</subject>
<subj-group>
<subject>Global Theme Issue: Poverty and Human Development</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Gill</surname>
<given-names>C. J.</given-names>
<prefix>Dr.</prefix>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A5"></xref>
<xref ref-type="corresp" rid="cor1"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>MacLeod</surname>
<given-names>W. B.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mwanakasale</surname>
<given-names>V.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chalwe</surname>
<given-names>V.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mwananyanda</surname>
<given-names>L.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Champo</surname>
<given-names>D.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Mukwamataba</surname>
<given-names>D.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chilengi</surname>
<given-names>R.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Thea</surname>
<given-names>D. M.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hamer</surname>
<given-names>D. H.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A5"></xref>
</contrib>
<aff id="A1">
<label>1</label>
<institution>Center for International Health and Development, Department of International Health, Boston University School of Public Health</institution>, <addr-line>Boston, Massachusetts</addr-line>
</aff>
<aff id="A2">
<label>2</label>
<institution>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine</institution>, <addr-line>Boston, Massachusetts</addr-line>
</aff>
<aff id="A3">
<label>3</label>
<institution>Tropical Diseases Research Centre</institution>, <addr-line>Ndola, Zambia</addr-line>
</aff>
<aff id="A4">
<label>4</label>
<institution>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private</institution>, <addr-line>Gaborone, Botswana</addr-line>
</aff>
<aff id="A5">
<label>5</label>
<institution>The Africa Malaria Network Trust</institution>, <addr-line>Dar es Salaam, Tanzania</addr-line>
</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Reprints or correspondence: Dr. Christopher J. Gill Center for International Health and Development Dept. of International Health Boston University School of Public Health 85 E. Concord St. Boston MA 02118 (<email>cgill@bu.edu</email>).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>1</day>
<month>12</month>
<year>2007</year>
</pub-date>
<volume>196</volume>
<issue>11</issue>
<fpage>1577</fpage>
<lpage>1584</lpage>
<history>
<date date-type="received">
<day>20</day>
<month>12</month>
<year>2006</year>
</date>
<date date-type="accepted">
<day>25</day>
<month>6</month>
<year>2007</year>
</date>
</history>
<permissions>
<copyright-statement>© 2007 by the Infectious Diseases Society of America</copyright-statement>
<copyright-year>2007</copyright-year>
</permissions>
<abstract>
<p><bold><italic>Background.</italic></bold> The World Health Organization advocates 2–3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear.</p>
<p><bold><italic>Methods.</italic></bold> Data were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to ⩾4 doses).</p>
<p><bold><italic>Results.</italic></bold> Of 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0–68.3]).</p>
<p><bold><italic>Conclusions.</italic></bold> Single-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.</p>
</abstract>
</article-meta>
</front>
<body>
<p>To mitigate the adverse health effects of malaria during pregnancy on mothers and their unborn infants [<xref ref-type="bibr" rid="R1">1</xref>–<xref ref-type="bibr" rid="R4">4</xref>], the World Health Organization (WHO) advocates intermittent preventive therapy during pregnancy (IPTp), most commonly using sulfadoxine-pyrimethamine (SP) [<xref ref-type="bibr" rid="R5">5</xref>]. Maternal HIV infection potentiates many of the adverse effects of malaria during pregnancy [<xref ref-type="bibr" rid="R6">6</xref>–<xref ref-type="bibr" rid="R9">9</xref>]. Despite the WHO's recommendation for at least 2 preventive doses of SP during the second and third trimesters of pregnancy [<xref ref-type="bibr" rid="R5">5</xref>], in practice, poor access, intermittent supplies ofmedications, irregular antenatal clinic attendance, inadequate clinic staff training, and other factors may result in vulnerable women receiving fewer doses of SP than recommended—or even no treatment. If so, the consequences might be particularly severe among the HIV-positive pregnant population [<xref ref-type="bibr" rid="R10">10</xref>].</p>
<p>In a subgroup analysis from a Kenyan IPTp study, Parise et al. [<xref ref-type="bibr" rid="R11">11</xref>] concluded that monthly IPT was superior to standard 2-dose IPT for reducing malaria-associated birth complications among HIV-positive women. Given the important policy implications of thispost hoc finding, 2 independently conducted randomized, controlled trials were completed in Malawi (US Centers for Disease Control and Prevention) and Zambia (Boston University School of Public Health) to explicitly test the hypothesis that monthly IPT would be superior to standard-dose IPT among HIV-positive women [<xref ref-type="bibr" rid="R12">12</xref>, <xref ref-type="bibr" rid="R13">13</xref>].</p>
<p>In the intention-to-treat analysis of our trial data from Zambia [<xref ref-type="bibr" rid="R13">13</xref>], we found no significant differences in any primary or secondary outcomes between monthly and standard-dose SP IPTp among HIV-infected pregnant women, possibly due to lower malaria transmission rates in our study area than in the Kenya or Malawi IPTp studies [<xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R12">12</xref>]. We now present results from a second, dose-response analysis, in which we evaluated the effectiveness of SP as a function of the actual, rather than planned, number of doses of SP that each subject received. Although mothers randomized to the control arm should have received 2 doses by study end and mothers randomized to the intervention arm ∼4 doses, in reality, mothers received between 1 and 6 doses. Contrasting maternal and birth outcomes by dose allowed us to address additional questions beyond those of the primary analysis, including: (1) What is the relative efficacy of single-dose SP? (2) Is there evidence of dose-dependent efficacy of SP for IPTp? (3) Is there evidence of a threshold effect above which additional doses confer no further benefit against malaria during pregnancy?</p>
<sec sec-type="methods">
<title>Methods</title>
<p><bold><italic>Study design.</italic></bold> The original data for this secondary analysis came from a randomized, double-blind, placebo-controlled clinical trial comparing the standard 2-dose SP IPTp (S-IPTp) regimen versus intensive monthly IPTp (I-IPTp) among a cohort of HIV-positive Zambian women in their second or third trimesters of pregnancy. See Hamer et al. [<xref ref-type="bibr" rid="R13">13</xref>] for full details of study objectives and definitions, study design, sample collection, and sample processing.</p>
<p><bold><italic>Statistical analyses.</italic></bold> Because eligibility screening, enrollment, and the first visit all occurred at the baseline visit date, all mothers received at least 1 dose of SP. Necessarily, if a mother received only 1 dose, this must have occurred at baseline—by definition. Our primary analysis contrasted mothers who received a single dose versus those who received 2, 3, or ⩾4 doses of SP. We examined the association between dosing frequency and our outcomes using the χ<sup>2</sup> , Fisher's exact, and <italic>t</italic> tests. Where appropriate, we conducted trend analyses for continuous variables using analysis of variance (with the Scheffé correction for multiple comparisons) and the Mantel-Haenszel χ<sup>2</sup> test for dichotomous outcomes [<xref ref-type="bibr" rid="R14">14</xref>]. We calculated crude and adjusted relative risks (RRs) associated with single-dose SP IPT using the contrast between 1 dose and ⩾2 doses of SP. Because the assumption of rare outcomes with logistic regression was inapplicable in our study, we used log-linear models to better approximate RRs in the multivariate analyses [<xref ref-type="bibr" rid="R14">14</xref>]. Potential confounding explanatory variables were selected through a process of forward stepwise entry. Variables tested for possible inclusion included infant gestational age at enrollment, maternal age, gravidity, insecticide-treated bed net (ITN) use, baseline maternal weight, and other baseline demographic features that differed significantly between the comparison groups. We derived a new variable, visit adherence score, to see whether mothers who received 1 dose were more or less likely to miss scheduled study visits than were mothers who received multiple doses. This assumed ∼ 1 visit per month, with the denominator being the number of days from enrollment to delivery divided by 30 days. Variables were included in a model as covariates if they exerted a 10% or greater change in the β coefficient or RR.</p>
<p>By design, mothers in the monthly dosing arm who received ⩾2 doses usually received each dose 1 month apart, whereas mothers in the standard arm who received 2 doses received the doses ∼ 1 trimester apart. This raised the question of whether dose density (defined as the spacing between sequential doses), as well as the absolute number ofdoses, could be associated with our study outcomes. We attempted to address this issue in 2 ways. First, we stratified the data set and explored our outcomes within each randomization group separately. Similarly, in our risk estimates using the entire data set, we tested for the effect of dose density by including an interaction term (defined as allocation arm by number of doses) in the regression models . All analyses were conducted using SAS (version 8.2).</p>
</sec>
<sec sec-type="results">
<title>Results</title>
<p>From 456 HIV-positive women (224 [49.9%] in the I-IPTp group and 232 [51.1%] in the S-IPTp group) enrolled in the study, 387 deliveries occurred. Placental biopsy samples were obtained for 89.8% (354) of the deliveries, or 77.6% of those initially randomized. As described in the main-effects article (see Hamer et al. [<xref ref-type="bibr" rid="R13">13</xref>]), there were no significant differences in baseline characteristics between the study participants assigned to the I-IPTp versus S-IPTp arms. Baseline characteristics were similar between women who completed the final study visit at 6 weeks post partum and those who were lost to follow-up between delivery and this visit (data not shown), except that non-completers (<italic>n</italic>= 101) were more likely to rent their homes (61.4% vs. 48.2%;<italic>P =</italic> .02) and had slightly higher mean baseline hemoglobin (Hb) levels (10.7 vs. 10.2 g/dL; <italic>P</italic>= .01) than did completers (<italic>n</italic> = 355).</p>
<p><xref ref-type="fig" rid="T1">table 1</xref> summarizes the baseline demographic and reproductive characteristics of the mothers at enrollment who completed the trial grouped by the actual number of doses of SP they ultimately received, rather than by their allocation through randomization. There were no significant differences in baseline characteristics as a function of the number of SP doses received except for mean gestational age, for which mothers who ulti mately received ⩾4 doses had earlier mean gestational ages than did those receiving <4 doses. Additionally, there was a trend toward lower proportions of primigravidae and slightly lower mean Hb levels among the mothers who received 3 doses of SP, although these variables did not differ significantly among mothers who received 1, 2, or ⩾4 doses.</p>
<p>Of women who received only 1 dose, 23 (21 from the S-IPTp arm and 2 from the I-IPTp arm) did so because they delivered prior to when the second dose was scheduled. Of the remaining 11 single-dose recipients, 1 (1 in the S-IPTp arm and 0 in the I-IPTp arm) had the dose withheld by the study team because it would have occurred beyond the 36-week limit, after which sulfonamides are not recommended because of increased risks of neonatal kernicterus [<xref ref-type="bibr" rid="R15">15</xref>]. We were unable determine why the remaining 8 women received only 1 dose.</p>
<p><xref ref-type="fig" rid="F1">figure 1</xref> summarizes the number of doses of SP actually taken by participants in each randomization arm before delivery. The median number of doses taken was 2 for S-IPTp and 4 for I-IPTp. Thirty-four women received only 1 dose, nearly all of whom (32/34 [94%]) had been randomized to the S-IPTp arm. Women randomized to the S-IPTp arm were much more likely to have received only 1 dose than were women randomized to the I-IPTp arm (RR, 15.9 [95% confidence interval, 3.9–69.2]).</p>
<p><xref ref-type="fig" rid="T2">table 2</xref> contrasts study outcomes for women receiving 1 dose of SP versus 2, 3, or ⩾4 doses of SP, regardless of their original randomized allocation. Single-dose SP was associated with significantly higher maternal anemia rates, lower mean Hb levels, and higher rates of placental parasitemia, and infants born to mothers receiving single-dose SP were significantly more likely to have cord blood parasitemia, to be born with low birth weight (LBW), and had lower mean birth weights.</p>
<p>We recognized that receipt of a single dose of SP could be the result of early delivery (and, hence, of there being no opportunity for future doses) or, conversely, could be a causal factor leading to an early delivery. Notably, the mean gestational age for mothers who received 1 dose was shorter than that for those receiving ⩾2 doses (33.8 vs. 38.6 weeks; <italic>P</italic>< .001). The mean interval between the first and second dose for the S-IPTp arm was 86.5 days (SD, 18.5 days) with the second dose occurring on average at 33.4 weeks of gestation (SD, 2.6 weeks), while the interval between the first and second dose in the I-IPTp arm was 32.0 days (SD, 5.3 days) and occurred at an average of 26.2 weeks (SD, 3.2 weeks). Although this was precisely as expected given the study procedures (trimesterly vs. monthly dosing of SP), it prompted consideration of whether the interval between the doses (dose density) might also explain the observed differences in outcomes between 1 versus ⩾2 doses, rather than just the absolute number of doses.</p>
<p><xref ref-type="fig" rid="T3">table 3</xref> summarizes the results for just the mothers randomized to the I-IPTp arm of the study. Mothers who received only 1 dose had lower mean Hb levels and higher rates of peripheral parasitemia at delivery, and their infants had significantly lower mean birth weights and were more likely to be classified as being of LBW.</p>
<p>In trend analyses, there appeared to be a threshold effect, with little incremental benefit beyond ⩾;2 doses of SP. There was a significant association between lower rates of maternal anemia (<italic>P</italic> = .03) and infant prematurity (<italic>P</italic> = .04); internal comparisons by doses of SP versus average maternal Hb levels were significant (<italic>P</italic> ⩽ .05) for 1 versus 2 and for 1 versus 4 doses of SP but were not significant for 1 versus 3, 2 versus 3, and 3 versus 4 doses of SP. Similarly, there was a significant association (<italic>P</italic> ⩽ .05) between increased mean birth weights and increasing numbers of doses for 1 versus 2,1 versus 3, and 1 versus 4 doses of SP, but there was not a significant association for 2 versus 3, 2 versus 4, or 3 versus 4 doses. Maternal peripheral parasitemia was more common in those who received 2 doses than in those who received 3 doses (<italic>P</italic> = .05) and in those who received 2 does than in those who received 4 doses (<italic>P</italic> = .06) but did not differ significantly between 3 and 4 doses. By contrast, there was no discernible effect of the number of doses administered on acute/recent (stage C1 or C2) or past (stage C3) placental infection by histology (data not shown).</p>
<p><xref ref-type="fig" rid="T4">table 4</xref> summarizes the outcomes for mothers originally randomized to the standard arm. Compared with mothers who received 2 doses, mothers who received a single dose had significantly higher rates of anemia and lower mean Hb levels at delivery, and their infants were significantly more likely to be born prematurely, were significantly more likely to be classified as being of LBW, and had lower mean birth weights. There was a nonsignificant trend toward higher rates of peripheral parasitemia, acute/recent placental infection, placental parasitemia by smear, and infant cord blood parasitemia associated with single-dose SP-IPTp.</p>
<p><xref ref-type="fig" rid="T5">table 5</xref> summarizes the crude and adjusted RRs associated with single-dose SP, compared with ⩾2 doses of SP. Gestational age <37 weeks at delivery, maternal anemia, maternal parasitemia at delivery, and infant LBW all showed a significantly increased risk if mothers had only received only 1 dose. The RRs remained virtually unchanged after adjustments for potential confounding. With the same intent as our stratification, we attempted to explore the effect of dose density in the multivariate analyses. To do this, we included an interaction term (defined as allocation arm by number of doses) in our multivariate model, with allocation arm serving as a proxy for dose density. However, there was no significant interaction, suggesting that the differences in these outcomes were better explained by the number of doses administered rather than by the dosing interval.</p>
<p>The mean adherence-to-visits scores were nearly identical between mothers who received a single dose of SP and those who received ⩾2 doses (0.98 visits/30 days vs. 1.01 visit/30 days; <italic>P</italic>= .76, pooled <italic>t</italic> test with Satterthwaite method), arguing that the observed differences in clinical outcomes were not a consequence of differential adherence to study visits.</p>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>The present dose-response analysis of SP IPTp for pregnant HIV-positive Zambian women led us to 2 policy-relevant conclusions. First, single-dose SP-IPTp was significantly associated with multiple adverse maternal and newborn outcomes and, therefore, appeared to be inferior to all other dosing regimens. Second, among those who received single-dose SP, nearly all had originally been randomized to receive the standard once-per-trimester 2-dose regimen currently advocated by the WHO. Approximately 15% of mothers assigned to receive the standard regimen received only a single dose of SP, compared with <1% of mothers assigned to receive I-IPTp. This point has important policy implications regarding future recommendations about IPTp dosing and is to be contrasted with the lack of incremental benefit conferred by I-IPTp versus S-IPTp in our intent-to-treat analysis [<xref ref-type="bibr" rid="R13">13</xref>]. Our primary analysis was designed to contrast the efficacy of 2 dosing regimens in the context of a tightly controlled clinical efficacy trial [<xref ref-type="bibr" rid="R13">13</xref>]. By contrast, the present analysis is more analogous to an effectiveness study insofar as the reasons for mothers receiving different numbers of doses of SP cannot be assumed to have occurred at random. At a programmatic level, the comparable efficacy of the 2 regimens in our main-effects article could convey a false sense of security about the adequacy of the standard regimen. In reality, the intention to give the standard 2-dose regimen frequently resulted in mothers inadvertently receiving only 1 dose, something that rarely occurred among mothers for whom the intention was to give monthly doses of SP. Therefore, a simple interpretation of our results is that monthly SP is preferable to standard IPTp because it virtually eliminates the risk of inadvertently underdosing pregnant women.</p>
<p>In addition to supporting a small dose-dependent benefit to SP IPTp, our analysis also suggested a threshold effect above 2 doses, with further doses conferring relatively clinically and statistically insignificant marginal benefits. However, we urge caution in generalizing this finding, given the unexpectedly mild malaria transmission that characterized the study period. Although it is probably safe to infer that a single dose of SP would be inadequate prophylaxis under conditions of more intense malaria transmission, it cannot be assumed that a similar threshold effect at 2 doses of SP would remain sufficient in more malarious settings. Because our analysis focused only on HIV-positive mothers, whether the same associations between single-dose SP IPTp and adverse outcomes exists for HIV-negative women cannot be inferred from our study.</p>
<p>Although these observations emerged in an analysis for which the original assumptions of randomization were no longer applicable, the adverse outcomes associated with single-dose SP IPTp persisted after statistical adjustments for dose density, differential adherence to study procedures, differences in gestational ages for the single-dose-recipient mother, and use of ITNs or other baseline maternal or demographic factors. That said, we recognize that statistical adjustments per se do not indicate the direction of causality in the association between 2 variables. In the present example, an early delivery (and, hence, low infant birth weights) could explain why a mother received fewer doses of SP but could also be the result of fewer doses of SP. That gestational ages for recipients of single-dose SP were significantly lower than those for recipients of ⩾2 doses supports this interpretation. In contrast, the associations between maternal anemia rates and single-dose SP are difficult to explain as anything other than a consequence of inadequate prophylaxis with SP. Because SP is a folic-acid antagonist and suppresses hematopoiesis, it would be expected to increase anemia rates in the absence of a compensatory benefit from SP IPTp, such as reduction of malaria-induced anemia. Similarly, the association between single-dose SP and increased rates of placental parasitemia and infant cord blood parasitemia is most likely a consequence of inadequate prophylaxis.</p>
<p>We emphasize that the enrollment procedures of our study ensured that all of our study participants received at least 1 dose of SP. This would not necessarily be the case in the setting of an antenatal SP IPTp program. Furthermore, the inadequacy of single-dose SP was evident despite the unexpectedly low rates of malaria transmission during the study period. Therefore, it is logical to assume that single-dose SP IPTp (or no IPTp at all) could be more common in nonstudy settings. Similarly, it is reasonable to infer that the adverse effects of single dosing could be far more serious in settings with more intense malaria transmission.</p>
<p>Limited information exists regarding the proportion of women overall who receive recommended levels of IPTp in sub-Saharan Africa. In a Kenyan study of 1800 women across 4 districts, Guyatt et al. [<xref ref-type="bibr" rid="R16">16</xref>] found that only 5% of interviewed women attending antenatal clinics had received 2 or more doses of SP and that 14% had received only a single dose of SP, leaving the majority untreated. In a study conducted after the implementation of a national IPTp program in Kenya several years later, van Eijk et al. [<xref ref-type="bibr" rid="R17">17</xref>] noted that still only 23.7% of mothers received 2 or more doses of SP, 43.4% only 1 dose, and 33% no doses. IPT rates were somewhat higher in a 2005 survey of 10 districts in Zambia in which, overall, 75% of women received some IPTp. However, this left 25% receiving no doses and between 8% and 28% of women receiving a single dose of SP, with significant variability in IPTp uptake rates between the districts [<xref ref-type="bibr" rid="R18">18</xref>]. It seems likely, therefore, that underutilization of IPTp and underdosing of SP is a common occurrence in the context of IPTp programs.</p>
<p>In conclusion, our data imply a programmatic advantage to monthly dosing of SP-IPT starting in the second trimester, at least in the case of HIV-infected women. This is relevant given that uptake rates for IPTp are likely far from ideal across various settings, countries, and programs in sub-Saharan Africa. Consequently, we suggest that the relative simplicity of monthly dosing, combined with the ability to compensate for missed doses at the next antenatal clinic visit, may offer a safer—and ultimately more effective—approach to preventing malaria during pregnancy than that advocated in the current WHO guidelines. Our findings should prompt a review of existing IPTp programs throughout sub-Saharan Africa to determine the proportion of women who are underdosed and what strategies could be introduced to reduce underdosing rates, including potentially adopting a monthly dose SP IPTp strategy.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgments</title>
<p>We thank Dr. Carlos Abramowsky of Emory University for performing quality control on the histological samples and the National Malaria Control Center parasitologists in Lusaka for performing quality control on the malaria blood smears. We also thank Ms. Christine Ayash for her assistance throughout the study with logistics.</p>
</ack>
<ref-list>
<title>References</title>
<ref id="R1">
<label>1.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Steketee</surname><given-names>RW</given-names></name>
<name><surname>Nahlen</surname><given-names>BL</given-names></name>
<name><surname>Parise</surname><given-names>ME</given-names></name>
<name><surname>Menendez</surname><given-names>C</given-names></name>
</person-group>
<article-title>The burden of malaria in pregnancy in malaria-endemic areas</article-title>
<source>Am J Trop Med Hyg</source>
<year>2001</year>
<volume>64</volume>
<fpage>28</fpage>
<lpage>35</lpage>
</nlm-citation>
</ref>
<ref id="R2">
<label>2.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>McDermott</surname><given-names>JM</given-names></name>
<name><surname>Wirima</surname><given-names>JJ</given-names></name>
<name><surname>Steketee</surname><given-names>RW</given-names></name>
<name><surname>Breman</surname><given-names>JG</given-names></name>
<name><surname>Heymann</surname><given-names>DL</given-names></name>
</person-group>
<article-title>The effect of placental malaria infection on perinatal mortality in rural Malawi</article-title>
<source>Am J Trop Med Hyg</source>
<year>1996</year>
<volume>55</volume>
<fpage>61</fpage>
<lpage>5</lpage>
</nlm-citation>
</ref>
<ref id="R3">
<label>3.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Guyatt</surname><given-names>HL</given-names></name>
<name><surname>Snow</surname><given-names>RW</given-names></name>
</person-group>
<article-title>Impact of malaria during pregnancy on low birth weight in sub-Saharan Africa</article-title>
<source>Clin Microbiol Rev</source>
<year>2004</year>
<volume>17</volume>
<fpage>760</fpage>
<lpage>9</lpage>
</nlm-citation>
</ref>
<ref id="R4">
<label>4.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Guyatt</surname><given-names>HL</given-names></name>
<name><surname>Snow</surname><given-names>RW</given-names></name>
</person-group>
<article-title>Malaria in pregnancy as an indirect cause of infant mortality in sub-Saharan Africa</article-title>
<source>Trans R Soc Trop Med Hyg</source>
<year>2001</year>
<volume>95</volume>
<fpage>569</fpage>
<lpage>76</lpage>
</nlm-citation>
</ref>
<ref id="R5">
<label>5.</label>
<nlm-citation citation-type="book">
<collab>World Health Organization (WHO)</collab>
<source>A strategic framework for malaria prevention and control during pregnancy in the African region</source>
<year>2004</year>
<publisher-loc>Brazzaville</publisher-loc>
<publisher-name>WHO Regional Office for Africa</publisher-name>
</nlm-citation>
</ref>
<ref id="R6">
<label>6.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>van Eijk</surname><given-names>AM</given-names></name>
<name><surname>De Cock</surname><given-names>KM</given-names></name>
<name><surname>Ayisi</surname><given-names>JG</given-names></name>
<etal></etal>
</person-group>
<article-title>Pregnancy interval and delivery outcome among HIV-seropositive and HIV-seronegative women in Kisumu, Kenya</article-title>
<source>Trop Med Int Health</source>
<year>2004</year>
<volume>9</volume>
<fpage>15</fpage>
<lpage>24</lpage>
</nlm-citation>
</ref>
<ref id="R7">
<label>7.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>van Eijk</surname><given-names>AM</given-names></name>
<name><surname>Ayisi</surname><given-names>JG</given-names></name>
<name><surname>Ter Kuile</surname><given-names>FO</given-names></name>
<etal></etal>
</person-group>
<article-title>Malaria and human immunodeficiency virus infection as risk factors for anemia in infants in Kisumu, western Kenya</article-title>
<source>Am J Trop Med Hyg</source>
<year>2002</year>
<volume>67</volume>
<fpage>44</fpage>
<lpage>53</lpage>
</nlm-citation>
</ref>
<ref id="R8">
<label>8.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>van Eijk</surname><given-names>AM</given-names></name>
<name><surname>Ayisi</surname><given-names>JG</given-names></name>
<name><surname>ter Kuile</surname><given-names>FO</given-names></name>
<etal></etal>
</person-group>
<article-title>Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya</article-title>
<source>Am J Trop Med Hyg</source>
<year>2001</year>
<volume>65</volume>
<fpage>623</fpage>
<lpage>30</lpage>
</nlm-citation>
</ref>
<ref id="R9">
<label>9.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>ter Kuile</surname><given-names>FO</given-names></name>
<name><surname>Parise</surname><given-names>ME</given-names></name>
<name><surname>Verhoeff</surname><given-names>FH</given-names></name>
<etal></etal>
</person-group>
<article-title>The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-saharan Africa</article-title>
<source>Am J Trop Med Hyg</source>
<year>2004</year>
<volume>71</volume>
<fpage>41</fpage>
<lpage>54</lpage>
</nlm-citation>
</ref>
<ref id="R10">
<label>10.</label>
<nlm-citation citation-type="book">
<collab>Joint United Nations Programme on HIV/AIDS (UNAIDS)</collab>
<source>2006 Report on the global AIDS epidemic</source>
<year>2006</year>
<publisher-loc>Geneva</publisher-loc>
<publisher-name>UNAIDS</publisher-name>
</nlm-citation>
</ref>
<ref id="R11">
<label>11.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Parise</surname><given-names>ME</given-names></name>
<name><surname>Ayisi</surname><given-names>JG</given-names></name>
<name><surname>Nahlen</surname><given-names>BL</given-names></name>
<etal></etal>
</person-group>
<article-title>Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection</article-title>
<source>Am J Trop Med Hyg</source>
<year>1998</year>
<volume>59</volume>
<fpage>813</fpage>
<lpage>22</lpage>
</nlm-citation>
</ref>
<ref id="R12">
<label>12.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Filler</surname><given-names>S</given-names></name>
<name><surname>Kazembe</surname><given-names>P</given-names></name>
<name><surname>Thigpen</surname><given-names>M</given-names></name>
<etal></etal>
</person-group>
<article-title>Randomized trial of2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-postive and HIV-negative pregnant women in Malawi</article-title>
<source>J Infect Dis</source>
<year>2006</year>
<volume>194</volume>
<fpage>286</fpage>
<lpage>93</lpage>
</nlm-citation>
</ref>
<ref id="R13">
<label>13.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Hamer</surname><given-names>DH</given-names></name>
<name><surname>Mwanakasale</surname><given-names>V</given-names></name>
<name><surname>MacLeod</surname><given-names>WB</given-names></name>
<etal></etal>
</person-group>
<article-title>Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women</article-title>
<source>J Infect Dis</source>
<year>2007</year>
<volume>196</volume>
<fpage>1585</fpage>
<lpage>94</lpage>
<comment>(in this issue)</comment>
</nlm-citation>
</ref>
<ref id="R14">
<label>14.</label>
<nlm-citation citation-type="book">
<person-group person-group-type="author">
<name><surname>Ramsey</surname><given-names>FL</given-names></name>
<name><surname>Schafer</surname><given-names>DW</given-names></name>
</person-group>
<source>The statistical sleuth—a course in methods of data analysis</source>
<year>1997</year>
<publisher-loc>Belmont, CA</publisher-loc>
<publisher-name>Duxbury Press</publisher-name>
</nlm-citation>
</ref>
<ref id="R15">
<label>15.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Forna</surname><given-names>F</given-names></name>
<name><surname>McConnell</surname><given-names>M</given-names></name>
<name><surname>Kitabire</surname><given-names>FN</given-names></name>
<etal></etal>
</person-group>
<article-title>Systematic review of the safety of trimethoprim-sulfamethoxazole for prophylaxis in HIV-infected pregnant women: implications for resource-limited settings</article-title>
<source>AIDS Rev</source>
<year>2006</year>
<volume>8</volume>
<fpage>24</fpage>
<lpage>36</lpage>
</nlm-citation>
</ref>
<ref id="R16">
<label>16.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Guyatt</surname><given-names>HL</given-names></name>
<name><surname>Noor</surname><given-names>AM</given-names></name>
<name><surname>Ochola</surname><given-names>SA</given-names></name>
<name><surname>Snow</surname><given-names>RW</given-names></name>
</person-group>
<article-title>Use of intermittent presumptive treatment and insecticide treated bed nets by pregnant women in four Kenyan districts</article-title>
<source>Trop Med Int Health</source>
<year>2004</year>
<volume>9</volume>
<fpage>255</fpage>
<lpage>61</lpage>
</nlm-citation>
</ref>
<ref id="R17">
<label>17.</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>van Eijk</surname><given-names>AM</given-names></name>
<name><surname>Ayisi</surname><given-names>JG</given-names></name>
<name><surname>ter Kuile</surname><given-names>FO</given-names></name>
<etal></etal>
</person-group>
<article-title>Effectiveness of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in western Kenya: a hospital-based study</article-title>
<source>Trop Med Int Health</source>
<year>2004</year>
<volume>9</volume>
<fpage>351</fpage>
<lpage>60</lpage>
</nlm-citation>
</ref>
<ref id="R18">
<label>18.</label>
<nlm-citation citation-type="book">
<person-group person-group-type="author">
<name><surname>Manyane</surname><given-names>B</given-names></name>
<name><surname>Mbata</surname><given-names>KB</given-names></name>
<name><surname>Ngwengwe</surname><given-names>AM</given-names></name>
</person-group>
<source>2004 Follow-up roll back malaria (RBM) baseline survey in 10 sentinel districts in Zambia</source>
<year>2005</year>
<publisher-loc>Lusaka</publisher-loc>
<publisher-name>Zambia RBM National Secretariat</publisher-name>
</nlm-citation>
</ref>
</ref-list>
<sec sec-type="display-objects">
<title>Figures and Tables</title>
<fig id="F1" position="float">
<label>Figure 1.</label>
<caption><p>No. of doses of sulfadoxine-pyrimethamine (SP) received by mothers at study end, by dosing regimen</p></caption>
<graphic mimetype="image" xlink:href="196-11-1577-fig001.tif"></graphic>
</fig>
<fig id="T1" position="float">
<label>Table 1.</label>
<caption><p>Baseline characteristics of study participants, by final no. of sulfadoxine-pyrimethamine (SP) doses received (<italic>n</italic>= 387).</p></caption>
<graphic mimetype="image" xlink:href="196-11-1577-tbl001.tif"></graphic>
</fig>
<fig id="T2" position="float">
<label>Table 2.</label>
<caption><p>Maternal and infant birth outcomes for all study participants, by no. of doses of sulfadoxine-pyrimethamine (SP) received during pregnancy (<italic>n</italic>= 387).</p></caption>
<graphic mimetype="image" xlink:href="196-11-1577-tbl002.tif"></graphic>
</fig>
<fig id="T3" position="float">
<label>Table 3.</label>
<caption><p>Maternal and infant birth outcomes for participants receiving intensive monthly sulfadoxine-pyrimethamine (SP) preventive treatment for malaria, by no. of doses of SP received during pregnancy (<italic>n</italic> = 187).</p></caption>
<graphic mimetype="image" xlink:href="196-11-1577-tbl003.tif"></graphic>
</fig>
<fig id="T4" position="float">
<label>Table 4.</label>
<caption><p>Maternal and infant birth outcomes for participants receiving standard sulfadoxine-pyrimethamine (SP) preventive treatment for malaria, by no. of doses of SP received during pregnancy (<italic>n</italic> = 200).</p></caption>
<graphic mimetype="image" xlink:href="196-11-1577-tbl004.tif"></graphic>
</fig>
<fig id="T5" position="float">
<label>Table 5.</label>
<caption><p>Crude and adjusted relative risks (RRs) of 1-dose sulfadoxine-pyrimethamine (SP) intermittent preventive treatment of malaria (IPTp) vs. ⩾2-dose SP IPTp.</p></caption>
<graphic mimetype="image" xlink:href="196-11-1577-tbl005.tif"></graphic>
</fig>
</sec>
<fn-group>
<fn fn-type="other">
<p>Potential conflicts of interest: none reported.</p>
</fn>
<fn fn-type="financial-disclosure">
<p>Financial support: Cooperative agreement S1954-21/21 between the Association of Schools of Public Health and the Centers for Disease Control and Prevention (Zambia Boston University Malaria Project); National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant K23-AI062208-03 to C.J.G.).</p>
</fn>
<fn fn-type="presented-at">
<p>Presented in part: 55th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Atlanta, 12–16 November 2006 (abstract 432).</p>
</fn>
</fn-group>
</back>
</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Inferiority of Single-Dose Sulfadoxine-Pyrimethamine Intermittent Preventive Therapy for Malaria during Pregnancy among HIV-Positive Zambian Women</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="termsOfAddress">Dr.</namePart><namePart type="given">C. J.</namePart><namePart type="family">Gill</namePart><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><affiliation>E-mail: cgill@bu.edu</affiliation><affiliation>Reprints or correspondence: Dr. Christopher J. Gill Center for International Health and Development Dept. of International Health Boston University School of Public Health 85 E. Concord St. Boston MA 02118</affiliation><affiliation>E-mail: cgill@bu.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">W. B.</namePart><namePart type="family">MacLeod</namePart><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V.</namePart><namePart type="family">Mwanakasale</namePart><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">V.</namePart><namePart type="family">Chalwe</namePart><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L.</namePart><namePart type="family">Mwananyanda</namePart><affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.</namePart><namePart type="family">Champo</namePart><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.</namePart><namePart type="family">Mukwamataba</namePart><affiliation>Tropical Diseases Research Centre, Ndola, Zambia</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.</namePart><namePart type="family">Chilengi</namePart><affiliation>HIV Vaccine Initiative, Botswana/Harvard School of Public Health AIDS Initiative Partnership for HIV Research and Education Private, Gaborone, Botswana</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D. M.</namePart><namePart type="family">Thea</namePart><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D. H.</namePart><namePart type="family">Hamer</namePart><affiliation>Center for International Health and Development, Department of International Health, Boston University School of Public Health, Boston, Massachusetts</affiliation><affiliation>Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts</affiliation><affiliation>The Africa Malaria Network Trust, Dar es Salaam, Tanzania</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>The University of Chicago Press</publisher><dateIssued encoding="w3cdtf">2007-12-01</dateIssued><copyrightDate encoding="w3cdtf">2007</copyrightDate></originInfo><abstract>Background. The World Health Organization advocates 2–3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear. Methods. Data were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to ⩾4 doses). Results. Of 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0–68.3]). Conclusions. Single-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.</abstract><relatedItem type="host"><titleInfo><title>The Journal of Infectious Diseases</title></titleInfo><titleInfo type="abbreviated"><title>The Journal of Infectious Diseases</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><subject><topic>Parasites</topic></subject><subject><topic>Major Article</topic></subject><subject><topic>Global Theme Issue: Poverty and Human Development</topic></subject><identifier type="ISSN">0022-1899</identifier><identifier type="eISSN">1537-6613</identifier><identifier type="PublisherID">jid</identifier><identifier type="PublisherID-hwp">jinfdis</identifier><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>196</number></detail><detail type="issue"><caption>no.</caption><number>11</number></detail><extent unit="pages"><start>1577</start><end>1584</end></extent></part></relatedItem><identifier type="istex">AEFC50316197D9951E16D9B1B97457110772A4F6</identifier><identifier type="DOI">10.1086/522137</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2007 by the Infectious Diseases Society of America</accessCondition><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><recordOrigin>© 2007 by the Infectious Diseases Society of America</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/metadata/json</uri></json:item></metadata><covers><json:item><extension>tiff</extension><original>true</original><mimetype>image/tiff</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/covers/tiff</uri></json:item><json:item><extension>html</extension><original>true</original><mimetype>text/html</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/covers/html</uri></json:item></covers><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/annexes/jpeg</uri></json:item><json:item><extension>gif</extension><original>true</original><mimetype>image/gif</mimetype><uri>https://api.istex.fr/document/AEFC50316197D9951E16D9B1B97457110772A4F6/annexes/gif</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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